Indexed in MEDLINE, PubMed, and PubMed Central National Library of Medicine

Summer 2020 Volume 24 No. 4

A peer-reviewed journal of medical science, social science in medicine, and medical humanities

ORIGINAL RESEARCH & CONTRIBUTIONS 1 A Pharmacist-Led Program to Taper Opioid Use at Kaiser Permanente Northwest: Rationale, Design, and Evaluation 12 An Evaluation of the SCORE Program: A Novel Re- search and Mentoring Program for Medical Students in Obstetrics/Gynecology and Otolaryngology 19 Sequential Changes Advancing from Exercise-In- duced Psychological Improvements to Controlled Eating and Sustained Weight Loss: A Treatment- Focused Causal Chain Model 28 On the Use of Sampling Weights for Retrospective Medical Record Reviews 37 Utilization of Secure Messaging to Primary Care Departments CLINICAL PRACTICE 67 Variation in Colorectal Cancer Stage and Mortality across Large Community-Based Populations: PORTAL Colorectal Cancer Cohort CLINICAL MEDICINE 101 Endocrine Tumor Board: Ten Years’ Experience of a Multidisciplinary Clinical Working Conference CASE REPORTS 110 Pertussis Infection in a Naturopathic Primary Care Setting: Reflection on a Case 114 Hemolytic Anemia in a Glucose-6-Phosphate Dehy- drogenase-Deficient Patient Receiving Hydroxychlo- roquine for COVID-19: A Case Report IMAGE DIAGNOSIS 131 Neodymium Magnetic Bead Ingestion in a Toddler COMMENTARY 133 Addressing Vaccine Hesitancy 135 CARE for COVID-19: A Checklist for Documentation of Coronavirus Disease 2019 Case Reports and Case Series 141 A Day in the Life during COVID-19: Long-term Care Providers in Durham, North Carolina 143 More Than Words: Reflections to Build Resilience during the COVID-19 Pandemic EDITORIAL 150 The South Asian Paradox NURSING 153 Collins Complex Wound Guide Template

Find us online at www.thepermanentejournal.org TABLE OF CONTENTS

Summer 2020/Volume 24 No. 4 ORIGINAL RESEARCH 28 On the Use of Sampling Weights for Retrospec- & CONTRIBUTIONS tive Medical Record Reviews. Ernest Shen, PhD Sponsored by the 8 Permanente Medical Groups A recent review of articles that used the retro- 1 A Pharmacist-Led Program to Taper Opioid Use spective medical record review method listed 10 at Kaiser Permanente Northwest: Rationale, best practices that ought to be followed. However, Mission: The Permanente Journal advances Design, and Evaluation. Jennifer L Kuntz, PhD; an issue that is not listed is the use of sampling knowledge in scientific research, clinical medicine, Jennifer L Schneider, MPH; Alison J Firemark, MA; weights, which are important when one can only and innovative health care delivery. John F Dickerson, PhD; Dea Papajorgji-Taylor, conduct retrospective medical record review for MPH; Katherine R Reese, PharmD; Traci A Hamer, a sample of the target population. Although that PharmD; Darlene Marsh, PharmD; Lou Ann Circulation: 2 million page views of TPJ articles review acknowledged the importance of carefully Thorsness, RPh; Mark D Sullivan, MD, PhD; Lynn selecting a sampling strategy for such a scenario in PubMed from a broad international readership L Debar, PhD; David H Smith, PhD, RPh and indeed had outlined 3 commonly used sam- Primary care practitioners (PCPs) are concerned pling methods (convenience, simple random, and about adverse effects and poor outcomes of opioid systematic), the authors say nothing of the use of use but may find opioid tapering difficult because sampling information at the data analysis stage. of a lack of pain management training or time This article aims to fill that gap and to demonstrate constraints limiting patient counseling. In 2010, why the use of sample weights ought to be another Kaiser Permanente Northwest implemented a best practice to add to the list by reviewing well- pharmacist-led opioid tapering program—Support known theoretical details and some published data Team Onsite Resource for Management of Pain analysis examples. (STORM)—to address high rates of opioid use, 32 Influence of Psychosocial Factors and alleviate PCPs’ workload demands, and improve Parafunctional Habits in Temporomandibular patient outcomes. Disorders: A Cross-Sectional Study. Utkarsh 12 An Evaluation of the SCORE Program: A Yadav, MDS; Junaid Ahmed, MDS; Ravikiran Novel Research and Mentoring Program for Ongole, MDS; Nandita Shenoy, MDS; Nanditha Medical Students in Obstetrics/Gynecology Sujir, MDS; Srikant Natarajan, MDS and Otolaryngology. Kellie Corcoran, MD, MPH; Temporomandibular disorders (TMDs) are abnor- Miranda Ritterman Weintraub, PhD, MPH; Isabel- malities affecting the temporomandibular joint, jaw la Silvestre; Reshma Varghese; Jonathan Liang, muscles, or both. An intrinsic relationship reportedly MD; Eve Zaritsky, MD exists between TMDs and psychosocial factors, in- There has been a steady decrease in the number cluding stress. Parafunctional habits such as brux- Chrysler Trylons of physician-scientists and a lack of diversity and ism and clenching are also known to be responsible photograph inclusion of underrepresented minorities (URMs) for TMDs. Patients included in the study reported, Manfred Hauben, MD, MPH in medicine. To assess the research productivity, as their chief concern, pain lasting for more than a interest, and experience of medical students, week in the temporomandibular joint area and/or In the heart of New York City, adjacent to the Chrysler Building including URMs, and resident and faculty masticatory muscles. The patients were divided into (left), the famed architect Philip Johnson designed the Trylons mentors of the Kaiser Permanente Oakland age groups as follows: Younger than 20 years, 21 “as a monument for 42nd Street… to give you the top of the Medical Center’s 8-week, intensive, mentored to 30 years, 31 to 40 years, 41 to 50 years, 51 to Chrysler building at street level” via visual analogy with the Summer Clinical Otolaryngology and Obstetrics/ 60 years, and above 60 years. Patients were ex- chevron-ornamented spire of its namesake. It’s one of many Gynecology Research (SCORE) Program for amined clinically and were asked to complete an visual reminders that the epicenter of the COVID-19 pandemic in second-year medical students. A database of anamnestic questionnaire (modified version of Hel- the US is still a bejeweled city. SCORE Program research projects was generat- kimo Anamnestic Index) and the Hospital Anxiety ed from 2016, when the program was launched, and Depression Scale (HADS). Dr Hauben is a Senior Director at Worldwide Medical & Safety, through 2018. SCORE Program students and 37 Utilization of Secure Messaging to Primary Pfizer, Inc and a Clinical Assistant Professor in the Department of faculty completed a brief, mixed-methods, anon- Care Departments. Jose Yakushi, MD; Mose Medicine at NYU Langone Health. ymous exit survey that captured respondents’ Wintner, PhD; Naomi Yau; Lina Borgo, MPH; experiences, perceived program strengths, and Edwin Solorzano, MD opportunities for improvement. Photograph and caption by Manfred Hauben, MD, MPH Secure messaging is a platform for email commu- 19 Sequential Changes Advancing from Exer- nication between patients and their physicians. cise-Induced Psychological Improvements to Although patient-generated emails are associated Controlled Eating and Sustained Weight Loss: with increased use of clinical services, greater A Treatment-Focused Causal Chain Model. member retention, and improved quality of care, EDITORIAL & PUBLISHING OFFICE James J Annesi, PhD, FAAHB, FTOS, FAPA secure messaging has a marked impact on prima- The Permanente Journal Behavioral (nonsurgical/nonpharmacologic) weight ry care physicians’ workload. To understand how c/o Laura Fegraus 1 Kaiser Plaza, 27th Floor loss treatments have been overwhelmingly unsuc- the email topic and volume vary by demographics Oakland, CA 94612 cessful beyond the short term. Rather than incor- and clinical factors among members of a managed Email: [email protected] porating accepted behavioral change theory, most care organization, we analyzed all secure mes- INSTRUCTIONS FOR SUBMISSION have inadequately relied on providing exercise and sages sent to primary care departments by adult Instructions for Authors are available along with a link to our manuscript nutrition information. Although adherence is a chal- members of Kaiser Permanente Southern Califor- submission center at www.thepermanentejournal.org/authors.html lenge, exercise has emerged as the most robust nia (KPSC) in 2017. PERMISSIONS AND REPRINTS predictor of sustained weight reduction. However, Reprint Permission Form available at: exercise might be more associated with long-term www.thepermanentejournal.org/about-us/5818-reprint-permissions.html weight loss through the relationship of its associated The Editorial Staff have disclosed that they have no personal, professional, psychological changes with improved nutrition than or financial involvement in any of the manuscripts they might judge. Should a through direct effects of energy expenditures, which conflict arise in the future, the Editorial Staff have agreed to recuse themselves are typically minimal in deconditioned individuals. regarding any specific manuscripts. The Editorial Staff also will not use the information attained through working with manuscripts for private gain.

The Permanente Journal (ISSN 1552-5775) is a quarterly publication of articles from the online journal of record, which is available at: Contents continued on next page www.thepermanentejournal.org. Copyright © 2020 The Permanente Journal The Permanente Journal • Summer 2020 46 Psychometric Properties of the Problem-Orient- 76 Treatment of Intertrochanteric Femur Fractures 105 Redressing Underrecognition of “Cold Drink ed Patient Experience—Primary Care (POPE-PC) with Long versus Short Cephalomedullary Nails. Heart”: Patients Teaching Physicians about Survey. Ali Rafik Shukor, M Biotech, MSc Cameron Sadeghi, MD; Heather A Prentice, PhD; Atrial Fibrillation Triggered by Cold Drink and Kanu M Okike, MD; Elizabeth W Paxton, PhD Food. David R Vinson, MD Measuring the experiences of patients regarding delivery and receipt of person-oriented primary care Prior studies regarding indications for long vs short In this essay I tell the story of insightful patients from is of increasing policy and research interest and is cephalomedullary nails in the treatment of intertro- around the world with cold-drink atrial arrhythmias, a core component of the Institute for Healthcare Im- chanteric fractures had limited sample sizes and particularly atrial fibrillation (AF). This common condi- provement’s Quadruple Aim. Psychometric testing follow-up, suggesting a need for further investigation. tion has received little research attention and remains was performed using data from a Canadian urgent Cohort study using Kaiser Permanente’s Hip Fracture unknown to many physicians. The underrepresenta- primary care center, derived from March 2019 to Registry. A total of 5526 patients who underwent sur- tion of “cold drink heart” in the literature led me and a September 2019. Patients automatically received gical treatment with cephalomedullary nails for an in- colleague a few years ago to publish a case report on the 9-question survey by email after leaving the tertrochanteric femur fracture (2009-2014) were iden- this topic in an open-access journal. Sixteen individ- clinic. Exploratory factor analysis (EFA) on all ques- tified: 3108 (56.2%) with long nails and 2418 (43.8%) uals have since written me to express their gratitude tions and the entire dataset was performed using with short nails. Cox proportional hazards model for having received medical validation of the causal parallel analysis and scree plot for factor extraction. regression was used to evaluate risks of all-cause connection they had made between swallowing cold Internal consistency was assessed by calculating revision and revision for periprosthetic fracture. Lin- drink or food and their episodes of paroxysmal AF. The Cronbach α. A split-half cross-validation of the en- ear regression was used to evaluate operative time, validation was all the more important because of their suing factor structure was conducted. A correlation estimated blood loss, and length of stay. Propensity physicians’ prevalent disregard of the link, making analysis helped explore associations between the score weights were used in all models to balance nail them miss out on the opportunity to partner with their survey’s questions. groups on patient and device characteristics. patients in AF management by trigger avoidance. SPECIAL REPORT 81 My Introduction to Mission Surgery: A Diary. Andrew Wexler, MD, MA, FACS CASE REPORTS 53 Breast Cancer: Lifestyle, the Human Gut Microbi- ota/Microbiome, and Survivorship. Balazs I Bodai, I experienced my first international surgical mission 110 Pertussis Infection in a Naturopathic Primary MD, FACS; Therese E Nakata, STAR Provider, trip in 1993. It was a turning point in my surgical ca- Care Setting: Reflection on a Case. Luciano CWFPBN reer and has been followed by many missions in many Garofalo, ND; Joshua Corn, ND, MS; Meghan countries over 25 years. Often I am asked by young Sperandeo, ND Since the early 2000s, the role of the human gut mi- surgeons what is it like to work on an international crobiota and its relation to breast cancer has become mission and what one should expect. Although each Pertussis is a vaccine-preventable disease that has a major area of interest in the scientific and medical mission is different, the sense of accomplishment is made a global resurgence in the 21st century. Vaccine community. We live and survive owing to the symbiot- always the same and the emotional high one gets from hesitancy remains a persistent barrier to achieving ic relationship with the microorganisms within us: the performing the work is always present. Different orga- protective vaccination rates. Vaccine-hesitant individ- human microbiota. Scientific advances have identified nizations have different team models. The description uals may be more likely to seek counsel with a na- a subset of the gut microbiota: the estrobolome, those here is based on my first mission with Operation turopathic doctor. Seven more state legislatures have bacteria that have the genetic capability to metabo- Smile, a global nonprofit medical service organization. voted to license and/or regulate naturopathic doctors lize estrogen, which plays a key role in most breast in the last decade, illustrating the growing popularity cancers. Recent research provides evidence that the 84 Assessing Perception of Patients and Physi- of naturopathic medicine in the present health care gut microbiome plays a substantial role in estrogen cians Regarding Spirituality in Karachi, Pakistan: landscape. Still, the growth of naturopathic medicine, regulation. Gut microbiota diversity appears to be an A Pilot Study. Hena Jawaid, MBBS, FCPS and its potential relationship to vaccine hesitancy, is essential component of overall health, including breast Spirituality plays an important part in coping with life worrisome. Naturopathic doctors can be advocates health. Future research attention should include a problems, health concerns, and well-being issues for immunization to vaccine-hesitant individuals, but more extensive focus on the role of the human gut at individual and collective levels. In Pakistan, few ambivalence toward vaccines within the profession microbiota in breast cancer. studies have looked at the role of religion in patients’ remains a public health concern. illnesses. To assess patients’ and health care pro- 114 Hemolytic Anemia in a Glucose-6-Phosphate CLINICAL PRACTICE fessionals’ beliefs concerning spirituality and illness Dehydrogenase-Deficient Patient Receiving Hy- to understand the role of spirituality and religion in droxychloroquine for COVID-19: A Case Report. 67 Variation in Colorectal Cancer Stage and Mortal- clinics. A total of 52 patients and 50 health care pro- Jorge Aguilar, MD, PhD; Yelena Averbukh, MD ity across Large Community-Based Populations: fessionals from different specialties were interviewed. PORTAL Colorectal Cancer Cohort. Jennifer L A self-devised tool was used to gain information from The growing coronavirus disease 2019 (COVID-19) Schneider, MPH; Heather Spencer Feigelson, PhD, patients. For health care professionals a 17-item pandemic initially led to widespread use of hydroxy- MPH; Virginia P Quinn, PhD; Carmit McMullen, questionnaire was used. chloroquine sulfate as an off-label experimental PhD; Pamela A Pawloski, PharmD, BCOP, FCCP; treatment of this disease. Acute hemolytic ane- John D Powers, MS; Andrew T Sterrett, PhD; David mia developed in an African American man with Arterburn, MD, MPH; Douglas A Corley, MD, PhD CLINICAL MEDICINE COVID-19-related pneumonia and glucose-6-phos- phate dehydrogenase (G6PD) deficiency who com- 101 Endocrine Tumor Board: Ten Years’ Experience of Colorectal cancer (CRC) incidence and mortality can pleted the standard 5-day experimental course of a Multidisciplinary Clinical Working Conference. be reduced by effective screening and/or treatment. hydroxychloroquine. Although the trigger leading to Alison Savitz, MD; Bryan Fong, MD; Aaron Hoch- However, the influence of health care systems on dis- our patient’s hemolytic sequelae will never be known berg, MD; Gregory Rumore, MD; Cui Chen, MD; parities among insured patients is largely unexplored. with certainty, his clinical course suggests that hy- Juanita Yun, MD; Craig Sadur, MD To evaluate insured patients with CRC diagnosed droxychloroquine use and/or COVID-19 infection may between 2010 and 2014 across 6 diverse US health Advances in specialized medical areas and updated trigger hemolysis in susceptible patients with G6PD care systems in the Patient-Centered Outcomes clinical guidelines show a need for a focused ap- deficiency. This case confirms recent findings that Research Institute (PCORI) Patient Outcomes Re- proach for patients with specific disorders. We es- the potential risks of hydroxychloroquine therapy for search To Advance Learning (PORTAL) CRC cohort, tablished an endocrine tumor board at a large health COVID-19 may outweigh the benefits. we contrasted CRC stage; CRC mortality; all-cause maintenance organization and studied cases pre- mortality; and influences of demographics, stage, co- sented between September 2007 and August 2017. morbidities, and treatment between health systems. To resolve diagnostic and/or therapeutic questions, a multidisciplinary team of specialists discussed patients’ clinical presentations. Cases were broken down into diagnostic categories, demographic char- acteristics (age, sex), and need for repeated presen- tations to the board. Contents continued on next page

The Permanente Journal • Summer 2020 117 Bilateral Quadriceps Tendon Repair with Suture 129 Image Diagnosis: Takotsubo Cardiomyopathy 141 A Day in the Life during COVID-19: Long-term Anchors: Case Series. Jason E Tucker II; Christo- Mimicking an Acute ST Elevation Myocardial Care Providers in Durham, North Carolina. pher R Jones, MD Infarction in the Setting of Anti-Depressant Nathan A Boucher, DrPH, PA, MS, MPA, CPHQ; Therapy Withdrawal. Suha Na Javeed; Seema Courtney H Van Houtven, PhD, MSPH Bilateral and simultaneous quadriceps tendon rup- Pursnani, MD, MPH ture is rarely observed. This case series evaluates The following day-in-the-life amalgam is based on 3 patients with bilateral ruptures of the quadriceps A 77-year-old woman with a history of bipolar disor- the recently reported experiences of 6 health care tendon. The purpose of this case series is to dis- der, hypertension, hyperlipidemia, and previous to- providers working in LTC who responded to an online play the effectiveness of the suture anchor surgical bacco use presented to the Emergency Department question and answer session; we coupled this with ev- repair technique in these patients. These quad- (ED) with acute shortness of breath and diaphoresis. idence from news sources and reports in March and riceps tendon ruptures occurred in patients with The patient was initially anxious and tearful upon pre- April 2020. All responding care providers are currently a predisposition to injury as a result of excessive sentation to the ED. While she denied acute emotion- dealing with COVID-19 in LTC settings in Durham, NC. weight bearing. When addressing bilateral quadri- al or social stressors, she did note abruptly stopping Notably absent from this day-in-the-life scenario are ceps tendon ruptures in this patient population, we her venlafaxine (brand name Effexor) approximately the family and friend caregivers who have not been found that a suture anchor-based construct allows 3 weeks before. able to visit the facilities because of policies restrict- for a secure repair, early initiation of physical thera- ing visitors. This narrative is a breakdown of life inside 131 Neodymium Magnetic Bead Ingestion in a Toddler. py, and a noted improvement in pain scores on the some of the most emotionally and physically perilous Kenneth J Hui; Vignesh A Arasu, MD; David R Visual Analog Scale. places to be in America right now. Vinson, MD; Dale M. Cotton, MD 122 Surgical Reconstruction of Cocaine-Induced 143 More Than Words: Reflections to Build Resilience An 18-month-old girl presented to the Emergency Cleft Lip: A Case Report. David W Chou, MD; during the COVID-19 Pandemic. David R Lee, MD, Department with 36 hours of nonbloody, nonbilious Charles Shih, MD MBA; Karina Chavez, MD emesis. She last had a bowel movement 2 days ear- Cocaine is known to cause necrosis of the soft tissues lier, and it was normal. She had been intermittently Physicians often forget to reflect or take time to secondary to its vasoconstrictive effects, which has placing her hands on her abdomen as if in pain. She process challenging patient encounters, which can negative functional and cosmetic outcomes of the had no fevers. The parents said that until this time she ultimately contribute to burnout. This is even more rel- midface and adjacent structures. To our knowledge, had been generally well without sick contacts or prior evant given the increased stressors on patients, fami- cleft lip caused by cocaine use has not been de- similar episodes. lies, and health care providers during the coronavirus scribed in the literature. A 52-year-old man presented disease 2019 (COVID-19) pandemic. Two resident with a deformity of the lip and nasal sill, septal perfo- physicians wrote this commentary to process a diffi- ration, and hard palate fistula secondary to long-term COMMENTARY cult experience in the hospital. It touches on the rami- cocaine use. The patient underwent lip reconstruction 133 Addressing Vaccine Hesitancy. Ryan Bradley, ND, fications of health care institutions’ COVID-19 policies using a modified Millard technique and had a lasting MPH; Charles Elder, MD, MPH in relation to key geriatric syndromes including loneli- favorable cosmetic outcome more than 5 years after ness, mental health in older adults, and processing of surgery. We report a case of cocaine abuse causing As vaccines against the severe acute respiratory our own emotions and feelings through narrative medi- cleft lip, and successful reconstruction with a modified syndrome-coronavirus 2 (SARS-CoV-2) become cine. As part of the future health care workforce, we are Millard technique. available, vaccine hesitancy may become a critical motivated and optimistic about our future contributions, public health issue. The Permanente Journal pub- all the while practicing compassion and empathy. lished a case report by Garofalo et al reporting on IMAGE DIAGNOSIS naturopathic counseling of a family toward appropri- 145 Is the Psychiatric History Losing Its Relevance? ate vaccinations for their children through vaccine Richard J Moldawsky, MD 125 Roth’s Spots, a clinical diagnostic clue for Infec- education. Their case illustration is important for tive Endocarditis. Navneet Arora MD; Deba Prasad One of the axioms of medical practice is that obtaining several reasons, but perhaps most importantly it Dhibar MD; Byanjana Bashyal MBBS; Aniruddha a good history is key to making a correct diagnosis counters a prevalent belief that naturopathic phy- Agarwal MS and developing a treatment plan. Any factor that com- sicians and other complementary and integrative promises a history may compromise care. This area of A 24-year male was admitted to the emergency ward health (CIH) practitioners are “anti-vaccination”. All practice has not been formally studied, although it is with a history of high-grade fever (103⁰ F) with fatigue accredited naturopathic colleges and universities widely believed to be true. In mental health settings, and palpitations for 3 months. He had a significant educate medical students on prevention of vac- there are many factors that affect obtaining the history. history of congenital heart disease in the form of a cine-preventable diseases and the current vacci- Some suggestions are offered to support clinicians’ ventricular septal defect. He had no history of alco- nation schedule recommended by the Centers for and organizations’ struggles to keep a comprehensive hol consumption or intravenous drug abuse. Cardiac Disease Control and Prevention. history at the forefront of care. auscultation revealed a harsh holosystolic murmur 135 CARE for COVID-19: A Checklist for Documenta- of grade 3 intensity over the entire precordium. The 148 Furin Protease: From SARS CoV-2 to Anthrax, tion of Coronavirus Disease 2019 Case Reports fundus examination revealed multiple pale-centered Diabetes, and Hypertension. Kara Fitzgerald, ND and Case Series. Paul G Werthmann, MD; David retinal hemorrhages suggestive of Roth’s spots. Riley, MD; Gunver Sophia Kienle, MD Furin is a protease that is ubiquitous in mammalian 127 Image Diagnosis: Eccentric Target Sign of Focal metabolism. One of the innovations that make sudden Coronavirus disease 2019 (COVID-19) is a new, rap- Toxoplasma Encephalitis. Samman Verma, MBBS; acute respiratory syndrome-coronavirus 2 (SARS- idly spreading pandemic that can lead to a life-threat- Vidhi Singla, MD; Aditya Singh, MBBS; Arghadip CoV-2) more infectious than its ancestor viruses is the ening disease. Accurate and transparent COVID-19 Bose, MBBS; Ashok Kumar Pannu, MD addition of a furin cleavage site. Conditions associated case reports provide systematic clinical observations with elevated furin levels, including diabetes, obesity, A 60-year-old woman was admitted to the hospital supporting researchers designing clinical trials and and hypertension, overlap greatly with vulnerabili- because of low-grade fever and altered mental sta- clinicians delivering health care. The checklist de- ty to the severe form of coronavirus disease 2019 tus of 1-month duration. The altered sensorium was scribed here is designed to systematically and accu- (COVID-19). We suggest that diet and lifestyle modifi- gradual in onset, in the form of confusion, decreased rately capture data from case reports and case series cations that reduce the associated comorbidities may verbal output, and progressively worsening level of for documentation on COVID-19. It is aligned with prevent the development of severe COVID-19 by, in consciousness. She recently had been repeating the CARE guidelines, available from the EQUATOR part, lowering circulating furin levels. Likewise, natural the words said to her and was not responding to the (Enhancing the QUAlity and Transparency Of health and pharmaceutical inhibitors of furin may be candi- family members. Research) Network. date prophylactic interventions or, if used early in the COVID-19, may prevent the development of critical symptoms.

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The Permanente Journal • Summer 2020 EDITORIAL 158 From Cultural Competency to Cultural Immer- sion: Lessons from A Community Advocate in 150 The South Asian Paradox. Arthur L Klatsky, MD; Guatemala. Yolande M Pengetnze, MD and Zoila H Nicole Tran, MD, PhD Gonzalez, RN, NP For several decades we have studied health out- The article introduces the novel concept of “Cultur- comes in identified Asian American (ASAM) ethnic al Immersion”, going beyond cultural competency to groups, comparing ASAM subgroups to whites and immerse oneself into the local culture for sustainable to each other. The most striking disparities we found community impact. involved South Asians (SAs). The SA individuals had higher coronary artery disease (CAD) risk and 160 Narrating The Cycle of Life. Tatiana Valverde da lower cancer risk than whites or any other ASAM Conceição, MD, PhD; Gabriel Graça de Oliveira, group. The SA individuals also did not share the low- MD, PhD er venous thromboembolism risk of all other ASAM Narrative medicine (NM) is an approach that values groups. The relatively low prevalence of CAD risk the patient’s narrative about his/her disease as cen- traits in SAs with high CAD incidence defines a para- tral to the clinical encounter and helps doctors to be dox. Exploration of these data might help the search more attentive to their patients’ perspectives in the di- for therapeutic and preventive medical benefits. agnostic and therapeutic process. A curricular change enabled a greater insertion of the humanities in the NURSING RESEARCH & PRACTICE curriculum of the Faculty of Medicine of the University of Brasília in Brasília, Brazil. In the present article, the 153 Collins Complex Wound Guide Template. Kelly authors describe the educational experience of the Collins BSN, RN, CWOCN and Erika Yazdanbakhsh insertion of NM in the medical curriculum and share MSN, CNL, RN, CWON personal impressions about the multiple possibilities The Collins Complex Wound Guide Template was of this approach. developed by a board certified wound, ostomy and 162 The Insomnia Plague in Fictional Macondo. continence nurse of many years’ experience, in con- Alejandro Velásquez-Torres, MD, MSc; Andrés sultation with other CWOCN nurses and hospitalists Díaz-Forero; Claudia Talero-Gutiérrez, MD who see patients with complex wounds. The goals set for this Complex Wound Guide Template were Disease and medicine are found throughout Gabriel to develop a guide template that could: - Address García Márquez’s work. This article examines the in- complex wounds as these seem to be the most in- somnia plague described in the novel One Hundred timidating types of wounds staff encounter. -Lead the Years of Solitude and performs a differential diag- clinician to a safe treatment recommendation every nosis exercise with conditions that affect both sleep time. -Be simple enough that anyone, (a layperson) and memory. The main finding is that the insomnia could technically use the guide template and select a plague narrated by García Márquez, with its clinical safe treatment recommendation.) manifestations, the sequence of symptoms, and its resolution, cannot be associated with any specific di- agnosis. However, similarities to and differences from HEALTH CARE COMMUNICATION several clinical conditions are discussed, as well as the relation between the neurophysiologic phenome- 156 Narrations In Psychiatry Training. Hena Jawaid, na of sleep and memory. MBBS, FCPS (Psychiatry) 168 Our Guest. Leonidas Nye Walthall, MD Narrations should be given significance in the pro- cess of psychiatric training in the form of story-tell- An atypical encounter with a homeless man affects a ing, art, music, poems, essays, and novel writing. It physician’s practice. enriches the trainee to be acquainted with different 170 Death by the Numbers. Wesley Chou perspectives of life. It widens the horizons of mental acuity to think in broad lines and in diverse ways. It “Your patient is trying to die on us,” the nurse prac- CORRECTION titioner chimed in through the doorway. As I sprang offers patience and deepens the information process Yakushi J, Wintner M, Yau N, Borgo L, Solorzano E. up to follow her already receding figure, I wondered to understand events and reactions at different levels. Utilization of secure messaging to primary care de- about this choice of phrase, one that made death partments. Perm J 2020;24:19.177. DOI: https://doi. sound like a tantrum put on by a sullen toddler. It lent org/10.7812/TPP/19.177 NARRATIVE MEDICINE an air of petulance to the patients who more often 157 The Rekindled Flame. Julio C Ramirez, MD than not hovered in a strange purgatory between con- In the above-listed article, an error was originally sciousness and oblivion. published in Figure 2 as the findings were interpreted I describe an impactful patient experience from my incorrectly when submitted. In the 3 bar graphs, the early medical career that has had a lasting impres- women’s orange bar lines needed to extend fully to sion on me not only as a clinician but also as a human STORIES AND POETRY the bottom of the graph to represent the full amount and, importantly, as a father. The experience is that 171 Shorelines. Kacper Niburski of women utilization. It did not do so in the previous of a patient who had undergone heart surgery and version and warranted a correction to accurately rep- subsequently died; I identified with the patient on a she just died and the room is dark and i can hear resent the findings. personal level. The challenge was not in providing her family pleading with the stars during their night’s medical care, but in providing medical care that did embrace and just before i stood like a solemn sun The corrected Figure now appears in the article online: not result in his survival. Encountering death is a atop of her and i compressed and i compressed and http://www.thepermanentejournal.org/issues/2020/ difficult reminder of why we practice medicine –to i compressed and her lips were still glossed with summer/7496-utilization-of-secure-messaging-to-pri- help others. Yet even healers, at times, need words beat-red lipstick and they were still still no matter mary-care-departments.html of encouragement. what i did... We apologize for this error.

The Permanente Journal • Summer 2020 EDITOR-IN-CHIEF: Stephen L. Tarnoff, MD

SENIOR EDITORS

James J. Annesi, PhD, FAAHB, FTOS, FAPA Gus M. Garmel, MD, FACEP, FAAEM Professor, School of Health Professions Clinical Professor of EM (Affiliate) University of Alabama at Birmingham Stanford University Senior Emergency Physician Philip I. Haigh, MD, MSc, FRCSC, FACS Kaiser Permanente Santa Clara Medical Center Assistant Chief, Department of Surgery Santa Clara, CA Kaiser Permanente Los Angeles Medical Center Los Angeles, CA Eric Macy, MD, MS, FAAAAI Department of Allergy David Riley, MD Kaiser Permanente San Diego Medical Center Founder, Scientific Writing in Health and Medicine Southern California Permanente Medical Group Adjunct Instructor San Diego, CA National University of Natural Medicine Portland, OR H. Nicole Tran, MD, PhD Internal Medicine Physician, Department of Adult and Family Medicine Director for Quality Improvement and Patient Safety, Internal Medicine Residency Kaiser Permanente Oakland Medical Center Oakland, CA

ASSOCIATE EDITORS

Carrie Davino-Ramaya, MD Wynnyee Tom, MD Practice Leader and Methodologist of Guidelines Department of Pediatrics and Evidence-Based Medicine San Jose Medical Center Department of Quality Management and Systems San Jose, CA Northwest Permanente, P.C. Portland, OR Calvin Weisberger, MD, FACC, FACP Cardiologist Lisa J. Herrinton, PhD Partner Emeritus Research Scientist, Division of Research Southern California Permanente Medical Group Kaiser Permanente Northern California Pasadena, CA Oakland, CA Chairman, Southern California Regional Product Council Los Angeles, CA Tom M. Judd, MS, CPHIMS, CPHQ, CCE, FACCE, FHIMSS, FAIMBE Information Technology and Quality Scott S. Young, MD Former National Project Director Associate Executive Director, Clinical Care and Innovation Kaiser Permanente Clinical Technology Senior Quality Director Marietta, GA The Permanente Federation Health Technology Advisor Oakland, CA World Health Organization Senior Medical Director and Executive Director, Care Management Institute Washington, DC Oakland, CA Board Chair, Global Clinical Engineering Federation Pat Zrelak, RN, PhD, FAHA, NEA-bc, CNRN, SCRN Ashok Krishnaswami, MD, MAS Clinical Practice Consultant Cardiologist Clinical Education, Practice, & Informatics Kaiser Permanente San Jose Medical Center Kaiser Permanente San Jose, CA Sacramento, CA

EDITORIAL & PUBLISHING OFFICE The Permanente Press Monica Leigh: Managing Editor The Permanente Journal is published Sheridan Composition services by The Permanente Press Patrick Versteeg: Web Developer

The Permanente Journal • Summer 2020 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Led Program to Taper Opioid Use at Kaiser Permanente Northwest: Rationale, Design, and Evaluation

Jennifer L Kuntz, PhD1; Jennifer L Schneider, MPH1; Alison J Firemark, MA1; John F Dickerson, PhD1; Dea Papajorgji-Taylor, MPH1; Katherine R Reese, PharmD2; Traci A Hamer, PharmD2; Darlene Marsh, PharmD2; Lou Ann Thorsness, RPh2; Mark D Sullivan, MD, PhD3; Lynn L Debar, PhD4; David H Smith, PhD, RPh1 Perm J 2020;24:19.216 E-pub: 04/21/2020 https://doi.org/10.7812/TPP/19.216

ABSTRACT cardiovascular events; and poor outcomes related to their opioid Introduction: Primary care practitioners (PCPs) are concerned use, such as central nervous system depression, misuse, opioid about adverse effects and poor outcomes of opioid use but may use disorder, or opioid-related death.3-14 These risks appear to find opioid tapering difficult because of a lack of pain manage- be related to both the dose and duration of use. 15,16 ment training or time constraints limiting patient counseling. In Opioid prescribing guidelines released by the Centers for 2010, Kaiser Permanente Northwest implemented a pharmacist- Disease Control and Prevention in 2016 address the initiation led opioid tapering program—Support Team Onsite Resource for of opioid therapy and the ongoing monitoring of that therapy, Management of Pain (STORM)—to address high rates of opioid including the need to reduce the opioid dose—or taper—when use, alleviate PCPs’ workload demands, and improve patient treatment goals are not being met or when the risks of therapy outcomes. begin to outweigh the benefits.3 To accomplish this, clinicians Objective: To describe the rationale, structure, and delivery of are relied on to identify unsafe opioid use, develop tapering goals this unique pharmacist-led program, which partners with PCPs and and plans with patients, monitor the tapering process, identify provides individualized care to help patients reduce opioid use, and potential opioid diversion, and coordinate care with mental the Facilitating Lower Opioid Amounts through Tapering study, health and pain specialists when needed.3 However, primary care which examines the program’s effectiveness, cost-effectiveness, clinicians often cite insufficient training in pain management and implementation. and time constraints as factors that make the substantial effort Results: The STORM program includes a pain medicine physi- associated with tapering difficult.17 Prior research has shown cian, a social worker or nurse, and pharmacists who have received that approaches that off-load work from primary care to other specialized clinical and communications training. The program has health care practitioners can reduce clinician stress and may a 2-fold role: 1) to provide PCP education about pain management lead to better patient outcomes.18 In particular, pharmacist-led and opioid use and 2) to offer clinician and patient support with interventions have shown promise in attainment of therapeu- opioid tapering and pain management. After program training, tic goals and improvement of quality of care, including in the PCPs are equipped to discuss the need for tapering with a patient management of opioid use for reduction of chronic pain. 19-27 and to refer to the program. Program pharmacists provide a range The Support Team Onsite Resource for Management of Pain of services, including opioid taper plans, nonopioid pain manage- (STORM) program is a novel, pharmacist-led, referral-based, ment recommendations, and taper-support outreach to patients. opioid tapering program implemented by Kaiser Permanente Discussion: The STORM program provides individualized care (KP) Northwest (KPNW) to address high rates of prescrip- to assist patients with opioid tapering while reducing the burden tion opioid use and primary care workload demands and to on PCPs. improve patient experience and outcomes related to opioid use Conclusion: The STORM program may be a valuable addition to and tapering. The objectives of this manuscript are to describe health care systems and settings seeking options to address their 1) the rationale, structure, and delivery of the pharmacist-led patients’ opioid tapering needs. STORM program that partners with primary care practitioners (PCPs) and provides individualized care to help patients reduce INTRODUCTION their opioid use; and 2) the National Institutes of Health- Opioid analgesic prescribing in the US increased consistently funded Facilitating Lower Opioid Amounts through Taper- from 1999 until reaching a peak in 2012.1 Despite decreases in ing (FLOAT) study, which seeks to examine the effectiveness, prescribing, 17% of Americans still had at least 1 opioid pre- cost-effectiveness, and implementation of this novel program. scription filled in 2017 and prescription opioid amounts were, on average, 3 times higher than in 1999.2 Although it is more common for patients to use opioids for short periods, a sub- Author Affiliations stantial number of patients continue opioid therapy for much 1 Kaiser Permanente Northwest Center for Health Research, Portland, OR longer periods. Long-term opioid use, defined by the Centers for 2 Kaiser Permanente Northwest Clinical Pharmacy Services, Portland, OR Disease Control and Prevention as the use of opioids on most 3 Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA days for more than 3 months, puts patients at increased risk of 4 Kaiser Permanente Washington Health Research Institute, Seattle, WA serious adverse effects that include reduced function and quality of life; increased risk of fractures, motor vehicle accidents, and Corresponding Author Jennifer L Kuntz, PhD ([email protected])

iKeywords: opioid tapering, chronic pain, opioids, pharmacy, primary care

The Permanente Journal • https://doi.org/10.7812/TPP/19.216 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 1 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Led Program to Taper Opioid Use at Kaiser Permanente Northwest: Rationale, Design, and Evaluation

METHODS and opioid use and 2) to offer direct clinician and patient sup- Our descriptions of the program were primarily gathered port with opioid tapering and pain management optimization. through meetings with Health Plan staff integral to the con- Program Staffing and Training ceptualization, design, and implementation of the STORM program and reviews of historical program documentation. To The STORM program is delivered by a multidisciplinary complement our descriptions, we have included data gathered team comprising pain management pharmacists, a pain medicine through qualitative interviews with current and former phar- physician lead, a clinical social worker, and a registered nurse. macy and clinical program staff (15 total interviews with 12 All STORM team members possess basic practice credentials: pharmacists, 1 social worker, 1 nurse case manager, and 1 pain Doctor of pharmacy for pain management pharmacists, licensed management physician). Staff trained in qualitative methods clinical social worker and master of social work for social work- ( JS, AF, and DPT) conducted the interviews in-person or over ers, and bachelor of science in nursing for nurses. the telephone, which lasted approximately 60 minutes and were All STORM pharmacists undergo clinical training and audiorecorded for transcription. Interview questions explored continuing medical education (CME) directly relevant to the topical areas such as the purpose, history, and structure of the management of chronic pain and opioid tapering. The clinical program; training of program staff and delivery of the program curriculum accounts for 25 hours of CME training completed in the health care system; and descriptions of the referral and over several months and provides intensive education in pain taper approach. This study was approved by the KPNW insti- medication pharmacology, pain treatment philosophy, and tutional review board. clinical applications of pain management. The curriculum also provides practical skills related to opioid management, includ- PROGRAM OVERVIEW ing chronic pain assessment, calculating morphine milligram KPNW is an integrated health system that provides care equivalents, opioid safety monitoring strategies (eg, use of urine for approximately 600,000 members in northwest Oregon and drug screens and pill counts), and calculating the average opioid southwest Washington. Each KPNW patient is managed by use relative to the prescribed dose to monitor opioid use. The a PCP who coordinates care, including the prescribing and STORM pharmacists also receive education about medical use of medications, such as opioids. The Health Plan employs or recreational cannabis use and local regulations related to about 500 PCPs—inclusive of physicians, physician assistants, opioid use. and nurse practitioners—who are supported by an integrated The STORM team has compiled a compendium of pain man- system of medical specialties, including pain management and agement resources that supplement the team’s own training of pharmacy services. Care is delivered in 34 KP medical offices new STORM pharmacists and other clinicians. These resources and 2 KP hospitals, as well as virtually through telephone and include practical clinical tools such as opioid equivalency and video appointments. Data for all care delivered are entered into conversion charts, pain assessment tools and instructions for and available to a patient’s entire care team via HealthConnect, their use (eg, Brief Pain Inventory), and patient education ma- a fully electronic medical record (EMR). terial. Additional online resources include reference materials related to threat management, unexpected results of pill counts Rationale or urine drug screens, cannabis use, and Health Plan guidelines In 2010, KPNW faced a large patient population receiving for opioid therapy planning. high-dose opioid prescriptions and PCPs who were over - All STORM practitioners undergo 8 hours of CME train- whelmed with patients who needed to have their opioid doses ing that focuses on advanced communication, motivational lowered. (Table 1). At the time, usual care involved chronic pain interviewing, and patient engagement skills in the context of management and opioid tapering delivered by PCPs, whose opioid use management. Training for STORM pharmacists also schedules often did not allow for the level of frequent follow- includes shadowing pain and addiction medicine physicians and up needed to educate patients about chronic pain management experienced STORM pharmacists. The pharmacists also attend and self-management or coping skills, to discuss and plan opioid KPNW pain management group classes, which are delivered tapering, or to manage withdrawal during tapering. As a result, by multidisciplinary teams and are aimed at educating patients opioid tapering would often not occur or would start but cease about pain-related self-management skills. By attending these in the absence of adequate support for patients and PCPs. groups, the pharmacists learn more about the self-care strategies In response, KPNW created the STORM program. This that they teach to their patients during the tapering process. pharmacist-led program provides patient education for those This practical training, including shadowing, continues until the taking high-dose opioid therapy and works with patients and STORM Pain Medicine Physician Lead believes the STORM their PCP to taper opioid doses to safer levels while also striving pharmacist is ready to directly interact with and provide care to improve patient function and pain control with alternative for patients undergoing opioid tapering. pharmacologic or nonpharmacologic treatment. This program In qualitative interviews, the STORM pharmacists empha- provides individualized tapering plans that address pain needs sized the importance of this baseline training, because it serves while lowering the opioid dosage. as the foundation for their understanding of the complexity of To accomplish its goals, the program serves 2 roles at KPNW: chronic pain management and the importance of a multifac- 1) to provide PCP education about chronic pain management eted approach to managing pain (Table 1). Pharmacists also

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Table 1. Qualitative feedback regarding STORM program and its processes Program component Qualitative interview quotes from former and current program staff Rationale and need for It [was] 2009, and for years what we were doing was exactly what everybody in the nation was doing—getting people on opioids for program chronic pain … . I specifically noticed with OxyContin [oxycodone] that patients were … craving it, and it was making me nervous. … I said I think the only way for primary care to have a chance of getting patients off of these high doses of OxyContin is if we do education with them [patients], one-on-one, and with the doc[tor]—maybe give them the services of a pharmacist. I said, we need some kind of group that could help the primary care doctor, help the patients get off of [the opioid] with regular contact and phone calls because primary care just did not have those resources.—STORM pain medicine physician Focus on patient-centered I start with where the patient is … and I’ll also look and see what [the] clinician’s goal is. So, is the clinician’s goal to taper off? Is care their goal to taper down? Or is it to taper off all the long-acting [opioids] and just go to short-acting? So, I take a look and see what’s been discussed and what the clinician wants, and from there it’s pretty individual … but again, giving them an option of where they want to start. And then I check in with them at every step of the way. … So, it could be anywhere from if we were tapering 9 tablets of oxycodone and the goal is off, we might be reducing by a tablet a week until they’re off. Or it might be if they’re really struggling, maybe it’s a half a tablet a week. Or maybe it’s even faster. Maybe it’s a couple of tablets. If they’re really tolerating it and the goal is to be off, and the patient is ready, then we can be off in just a couple of weeks. The taper process can range anywhere from a couple of weeks to a couple of months, and even quite longer when we’ve got a high-dose patient that we’re tapering down.— STORM pharmacist STORM pharmacist [O]ur baseline training is really understanding the complexity of chronic pain management neuroplasticity and the importance of a training multifaceted approach to managing pain—and that baseline training has been really crucial. As the years have gone by and new information has come out … about other medications, other successes of different pain treatments, then certainly we’ve added in new things … and then we’ve had the motivational interviewing training, or the communication intensive. And we all go to different continuing education seminars, and as we learn things that are new being done out there, we report back to the group. But that baseline [training] was very strategic.—STORM pharmacist Primary care practitioner We were creating something fresh, there was not a model out there. … I remember what my thought was at the time: that the only training way we were going to get these doctors’ attention is if they had time in clinic dedicated to the training, number 1. And number 2, we were talking about their patients, not just a generic patient out there having a problem, so the training was very real.—STORM pain medicine physician It’s our goal well before that first provider training session to stop by, introduce ourselves—spend time talking to them about who we are, what we can do, how we can support them. … We will show them how to set the stage if they have a new patient coming to them on an opioid regimen that they are not comfortable with, either with basic scripting or a basic approach of what to do at that first visit—so we do that within the first few weeks of when a provider is [new] here. And then … they have their STORM session. We intentionally plan that about 3 months after they’ve started [with KPNW] because they are more familiar with [the KPNW electronic health record] and they have more patients; they’ve had some situations come up where they can apply this.—STORM pharmacist Primary care referral for The referral process is really driven by the clinician. After the PCP has had the discussion with a patient, hopefully at that point, inclusion in program they’ve asked if they would like to be helped by STORM. And if so, then they refer to us at that point. … And they’ll take a look and make sure that the documentation is in the chart [medical record], that the clinician has actually talked with the patient, that they’ve discussed the STORM outreach. … We need to have patients onboard. … So, whenever we get a referral into the pool, they’ll take a look at it and make sure it’s something that is appropriate for STORM and that the documentation is in the chart.—STORM pharmacist Role of social worker in People are petrified. They don’t want to taper. They’re angry about it. They’re scared about it. And I’m the first person to reach out. STORM … [W]hat I’m doing for a 60-minute telephone call is I am building trust and confidence and rapport in this buy-in, so that when the pharmacist comes along behind me and calls the patient—there’s a second call—then the patient is now, basically, willing to try to taper.—STORM social worker Initial patient outreach [I]nitially when I outreach to the patient, I guess the number 1 thing I do before I call, I … look at the chart to get a sense of what’s going on and kind of get a sense what the [taper] change is supposed to be—if the change was discussed between the patient and the provider—and also try to get a sense of whether this is the patient’s request, or is it the provider’s request. [I] just kind of prepare myself for what kind of call it may be.—STORM pharmacist I think during the initial conversation, it’s really key to establishing that relationship with the patient. I think that’s where … motivational interviewing comes in: Opening it to the questions. I find when the patient feels heard, and even though they might not agree with the plan, that we’re there to help them and make this successful, I think even those patients who have some resistance initially, [with] that kind of approach … they tend to work with us. [It] opens the door to that relationship.—STORM pharmacist Role of STORM My daily work mostly is reaching out to patients. … And we’re checking in with them routinely, usually monthly, finding out how they pharmacist did with whatever changes we made the preceding month, particularly withdrawal symptoms. … We do ask about pain levels, but I feel we try to put more of an emphasis on how was your function affected? Assessing and offering help with withdrawal symptoms, if they’ve had that experience. And making sure that they’re staying involved in nondrug modalities that we’ve recommended to them. Encouraging [participation in] the pain [management] class. You know, primarily just letting them know they’ve got support through this, and they have someone to call, even when I’m not calling routinely. There’re some people I just might give a 1-time follow-up or a 1-time consult and kind of tell them what to expect of the taper. We’re still providing them our contact information for them to call us and let us know if they’re having difficulties.—STORM pharmacist KPNW = Kaiser Permanente Northwest; PCP = primary care practitioner; STORM = Support Team Onsite Resource for Management of Pain.

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Table 2. Overview of primary care practitioner training sessions Topic Concepts Program overview STORM Pain Medicine Physician Lead sets the stage, describes standards of care and new regulatory issues, helps clinicians become and introduction of more competent and comfortable, and recognizes challenges to managing pain and opioid tapering in primary care. STORM team STORM pharmacist discusses ongoing progress in the reduction of opioids, reviews how the STORM team can assist in conversions/ tapers, and says how to contact the STORM team for help. Introduction to Description of the STORM team STORM services Services offered: Pharmacist-led opioid tapering, medical record reviews, advice STORM referral procedures and setting expectations around time until STORM outreach How practitioners can have a conversation with the patient: You could say: We are learning new things about chronic pain management and the effects of long-term opioid use. We are finding that people who have been on these medications for a long time feel better on either less medication or a different kind of medication. I’d like you to work with a pain pharmacist to make changes to your medication therapy. Description of additional available services Early refill/pill count protocols through pharmacy Short- and long-acting opioids Other medication refill/discontinuation issues Clinical tools related Opioid therapy plan operational criteria, basic vs complex; use of opioid therapy plan as a tool about agreement and expectations to opioid use surrounding the use of opioids (early refills, lost/stolen medication, urine drug screen, etc) Prescription Drug Monitoring Program and how it can help Patient reviews STORM pharmacist case review (before training session): Pain-related diagnoses Location and quality of pain Level of function Current and historical opioid use Observed safety concerns that might influence treatment options, adequate therapeutic use of nonopioid medications Follow-through with other recommended health care services: pain management classes, use of supportive devices, care from specialty departments such as the pain clinic Other relevant observations: past adherence to recommended nonopioid treatments, use of medications not recommended when taking opioids such as benzodiazepines, contribution of comorbidities that may make chronic pain management more difficult (eg, anxiety) or that may be contributing to chronic pain (eg, obesity) Discussion of the PCP’s perspective of this patient Discussion of potential barriers to change in this particular patient STORM Pain Medicine Physician Lead reviews variety of talking points: How to set realistic expectations of opioids (only up to 30% reduction of pain in 50% of patients), benefits of multimodal pain management with nonopioid and nonpharmacologic therapies Use of pain scale Description of tolerance to analgesia vs tolerance to euphoria Success of opioid therapy defined by decreased pain and increased function, and when to change course with an opioid trial and taper instead Using the issue of safety to address concerning behaviors Examples of how the pharmacists can help with each case (pill count, urinalysis, staging opioid prescriptions, how to send referral, etc) Information about Pain management group class information and script for PCP to discuss attendance with patients available pain What is covered in the session and the message that we give the patients attending the sessions management Online resources resources Formulary and nonformulary nonopioid medication options Nonpharmacologic strategies and referral options: physical therapy, acupuncture, chiropractic, etc Clinical resources When to refer to pain clinic, STORM, or Addiction Medicine department related to STORM Script of discussion with patient about referral program and opioid Online resources management “STORM notebook” with compendium of references provided to each clinician at the meeting Electronic medical record charting tools Use of urine drug screen and interpretation of results Review/questions/ Review of clinician issues, questions, concerns, what they hope to gain, specific problem areas they encounter wrap-up PCP = primary care practitioner; STORM = Support Team Onsite Resource for Management of Pain.

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emphasized the importance of communications training and a patient’s pain management plan. They have learned how to continuing education as new guidelines and approaches to pain recognize the need for an assisted taper; how to discuss opioid management become available (Table 1). tapering with their patients; and, if agreed on mutually with patients, how to refer their patients to the STORM program. PROGRAM DELIVERY: PRIMARY CARE After PCPs meet with their patients and set the stage for taper- PRACTITIONER EDUCATION AND TRAINING ing, they contact the STORM program for assistance. This step The STORM team provides detailed CME sessions on brings us to the second principal role of the STORM program: chronic pain management for every clinician who delivers pri- Team-supported opioid tapering (Figure 1). mary care at KPNW (Table 2). The 2-hour training sessions assist PCPs in developing skills that will help them to assess and Program Delivery: Opioid Tapering Activities safely manage chronic pain in their patients while also educating Supported Or Led By Storm them about STORM services available to them. During these Support from the STORM program comes in many forms trainings, the STORM pain medicine physician and pharmacist depending on patient and PCP needs. All STORM program work in tandem to provide PCPs with current evidence and activities are initiated by communication from the PCP. After practice recommendations about the role of opioids for chronic this contact, the STORM team assesses patient needs and pain management, use of short-acting vs long-acting opioids, appropriateness of the taper and its timing through review of nonpharmacologic approaches to pain management, opioid patient medical history, current opioid dose (morphine milli- therapy plans, and prescription drug monitoring programs. gram equivalents), past taper trials, and active care from other (Training materials are available on request.) clinical departments or specialties. During the review, it may The training session includes a review and discussion of be determined that tapering should be deferred. Reasons for a particular patient cases that the PCP has selected before the deferred taper include, for example, acute illness, unexpected meeting. According to the STORM Pain Medicine Physician social situations (eg, death in the family), or a patient currently Lead, the review of the PCP’s own patients, rather than ge- having another medication tapered (eg, benzodiazepine taper- neric patient cases, is integral to engaging PCPs in the training ing). Patients with acute or postoperative pain, patients who are (Table 1). In preparation for the meeting, the pharmacist reviews actively being seen by the pain specialty clinic, patients with the medical history of the PCP’s real-world cases and focuses cancer-related pain, pregnant women, patients receiving pal- on helping the PCP understand how the patients reached their liative or hospice care, and those with unstable mental illness current level of opioid use and how the PCP can help patients are typically excluded. diversify their pain management repertoire to decrease their If tapering is determined to be the appropriate course of opioid dose, if appropriate. action on the basis of this review, the STORM team provides The STORM session provides the PCP with a forum for either a direct consultation for PCP-led opioid tapering or discussing next steps and possible approaches to what could be a proceeds to pharmacist-led opioid tapering (Figure 1). The challenging conversation about tapering or addressing concern- STORM team may also determine that a patient may benefit ing behaviors. Then the PCPs can practice communication using from health care services in addition to or instead of opioid ta- a script that was developed by STORM to provide examples pering. At this point, the STORM pharmacist may advise the of difficult patient conversations. The script provides clinicians PCP to refer the patient to additional health care services such with examples of dialogue that not only seek to validate the as specialty pain management, mental health services, addiction patient’s experience with chronic pain but also provide the medicine, or surgery. patient with a clinical rationale and evidence that supports the Pretapering Support for PCPs decision to taper opioids (Table 2). The script provides additional At times, PCPs request that the STORM program facilitate approaches that the PCP can use to introduce the patient to collection and interpretation of background information that the tapering process and engage the patient in shared decision will support their clinical actions regarding opioid use and po- making related to opioid tapering. tential tapering. Examples include interpretation of urine drug The STORM team also uses the session as an opportunity screen results, a review of past medication trials, a summary to express KPNW leadership’s encouragement for PCPs to of observed safety concerns, or comprehensive medical record actively discuss opioid changes with their patients; engage in review in anticipation of an appointment to discuss changes to shared decision making around the opioid tapering process; and, the pain management plan and opioid tapering. A STORM if needed, pursue an opioid taper when it is the safest course of pharmacist will review the patient’s record and communicate action, even if the patient is not in agreement. Clinicians are with the PCP to address questions or concerns, provide context encouraged to offer patients the STORM multidisciplinary sup- for the information presented, and recommend next steps. In port during the taper and are informed on how to refer patients the event of an unexpected result of a urine drug screen, for ex- for STORM intervention. ample, the pharmacist will highlight if this is a single event vs a Although there is no formal evaluation related to the train- pattern of behavior, identify what substances may have yielded ing, it is assumed that, on completion of the training, PCPs are the result, outline suggested next steps with safety monitoring armed with a comprehensive overview about chronic pain man- or if taper is indicated, and promote further clinician-patient agement. They are aware of the resources available to diversify discussion about changes to the treatment plan.

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Primary Care Practitioner-Led Tapering is achieved. Although the STORM process is the same as for PCPs may elect to use the STORM program to receive opi- a voluntary taper, there is less flexibility about if or how the oid tapering advice or assistance for the creation of an opioid taper will proceed. If the patient declines active participation tapering plan. As part of this process, the pharmacist performs in the STORM program, STORM pharmacists still support a medical record review and provides observations and recom- the PCP to keep the taper on track by staging prescriptions in mendations that may be helpful to the PCP during the tapering the EMR for clinician review and approval. Before staging the process. The pharmacist also develops a plan that provides the prescription for each step of the taper, the pharmacist reviews PCP with future prescription orders that will taper opioid use at the EMR for updated medical information that might influence a specific rate (eg 10% decrease in dosage per month) individu- how the taper should proceed (eg, ED visit for illicit substance alized to the patient’s opioid regimen, comorbidities, and risk toxicity or acute postsurgical pain). factors. During this process, pharmacists are readily available to consult with PCPs about the tapering plan and process or Pharmacist-Led Tapering the potential need for plan modifications. The STORM phar- When a PCP makes a referral for a STORM-led opioid macists also offer to “stage” opioid prescriptions (ie, preparing taper, a STORM team pharmacist performs a critical review future prescriptions in the EMR that will achieve a set taper of the patient’s medical record, including comorbidities, pain rate) to match a tapering plan for PCPs to review and approve. source, and other medical needs, in an effort to triage patients This helps the taper proceed in a timely and accurate fashion, on the basis of individual needs (Table 3). Attention is given with each prescription updated with the change in medication to safety concerns that may suggest that expedited interven- strength, quantity, and directions. tion is needed, such as recent hospitalization for respiratory Nonvoluntary Opioid Tapering depression, central nervous system impairment or use of illicit At times, an opioid taper must occur because of safety con- substances. The triaging pharmacist ensures that STORM is the cerns even if the patient is not in agreement. In these cases, the right resource for the patient and the patient’s clinical picture PCP may still offer STORM program support. If the patient and seeks to identify other helpful interventions that can be agrees to work with the STORM program, ongoing follow-up brought to the PCP’s attention for implementation before or in and withdrawal support will occur until the opioid taper goal tandem with opioid tapering through STORM. If the patient

Primary care provider (PCP) undergoes STORM program training (now eligible to refer patients)

PCP has an encounter with a patient who is a candidate for opioid tapering PCP may elect to do one of the following:

No opioid Opioid use is tapered PCP determines that opioid tapering is appropriate and discusses the tapering for patient by PCP STORM program and referral with patient

Referral to STORM Program (upon mutual agreement between patient and PCP)

STORM pharmacist determines patient needs and appropriateness for services

STORM Pharmacist-led Opioid Tapering Program Direct Provider Consultation Referral to other Steps in program include: Related to PCP-led Tapering support services 1. Intake: STORM Nurse/Social Worker obtain patient background and STORM pharmacist provides: (e.g., Pain Clinic, introduce patient to STORM intervention while setting expectations • Pre-tapering clinician support Addiction Medicine, 2. STORM pharmacist chart review and initial contact: Patient, • Advice about opioid conversion Mental Health) pharmacist, and PCP agree upon opioid tapering plan and tapering; or,

3. STORM pharmacist support for opioid tapering: Continued contact • An opioid tapering prescription to support patient and achieve goals set forth by tapering plan (contact plan for PCP-led tapering frequency and duration based on patient preference and need)

4. Patient discharge: Patient returns to clinical management by PCP once opioid tapering goal is met

Figure 1. Overview of Support Team Onsite Resource for Management of Pain (STORM) program.

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Table 3. Overview of STORM pharmacist-led tapering process Tapering process step Description of step and information exchanged Review of clinical picture to Review patient history to ascertain: determine appropriateness of Physical and emotional health comorbidities STORM tapering (pharmacist) Acute vs chronic vs malignant sources of pain Need to address mental health or other aspects of their medical care before tapering Safety concerns: recent hospitalization for respiratory depression, central nervous system impairment, use of illicit substances Initial intake telephone call Introduce STORM program (social worker or nurse) Prepare patient and set expectations Review background related to pain: pain location, Brief Pain Inventory (BPI), perception of what makes the pain better or worse Review history of patient use of nonpharmacologic strategies for pain control: using heat and/or ice, use of breathing and/or relaxation techniques Conduct depression screening: administer PHQ-9 Preoutreach medical record Review: review (pharmacist) Patient’s clinical history History of pain History of opioid use Potential related safety concerns: unexpected results of urine drug screening, history of early refills, respiratory compromise Use of nonopioid prescription medications History of referral and adherence to/follow-through with pain-related health care services Initial call (pharmacist and Introduce self and program patient) Outline the tapering process Obtain patient input that informs development of opioid tapering plan: Pain diagnoses and patient descriptions of their pain, administration of the BPI Current use of opioids, including details about how many pills they are taking and when they take them Use of other medications and how they use them (eg, over-the-counter pain medications, antidepressants, benzodiazepines, herbal supplements) Potential side effects of pain or opioid use, including impact on function or sleep, current or historical substance use disorder, and nonmedication and self-care strategies used by the patient for pain management Opioid safety concerns including results of recent urine drug screening and Prescription Drug Monitoring Program (PDMP) data for the patient Discuss patient’s pain management goals Ask if patient has concerns or questions Engage in shared decision making to develop opioid tapering plan, including planned reductions and frequency of reductions Reach agreement about plan among patient, pharmacist, and PCP Discuss what to expect during taper: potential withdrawal symptoms, including withdrawal hyperalgesia, and tips for self-care Schedule ongoing communication Documentation of plan Document the call in the EHR, with summary of encounter (pharmacist) Update patient’s opioid prescriptions in EHR to reflect the tapering plan Send plan to the PCP for review and approval Pharmacist-patient contact Review and update information provided by the patient in the initial call with focus on changes in opioid use, other (ongoing, frequency agreed on medication use, pain, and function with patient) Assess for and address withdrawal symptoms: self-care; withdrawal medications; or nonopioid, adjuvant pain medications Screen for and ensure that safety monitoring continues (as appropriate): urine drug screens and pill counts, check PDMP Allow patients to express any concerns or ask questions Adjust opioid tapering plan and contact frequency, as need arises Provide recommendations for coordination of care as needed with complementary medicine (eg, acupuncture, chiropractic), sleep medicine, mental health, and addiction medicine specialists and/or pain management group classes Discharge from STORM program Return management of patient’s pain care to PCP. EHR = electronic health record; PCP = primary care practitioner; PHQ-9 = Patient Health Questionnaire-9; STORM = Support Team Onsite Resource for Management of Pain.

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is an appropriate candidate for tapering, the triaging pharma- begins to experience difficulties with anxiety or depression as cist confirms receipt of the PCP referral, provides a timeline the taper progresses. for initial STORM outreach, communicates the pharmacist’s After the intake call, a patient is paired with a STORM phar- recommendations for pretapering intervention, and adds the macist who will guide the patient through the opioid tapering patient to an electronic queue in the EMR that indicates the process (Table 3). Before direct outreach to the patient, the need for team outreach. pharmacist performs a comprehensive medical record review to Pharmacist-led opioid tapering begins with a patient intake ascertain an initial understanding of the patient’s clinical history process delivered via a telephone call (Table 3). All patients are and experiences with pain management strategies and opioid contacted within 2 weeks of referral. During this initial call, use. This review also allows the pharmacist to understand the the STORM social worker or nurse introduces the patient to basis for the referral, including whether the tapering process the tapering program and provides counseling to prepare the was initiated by the PCP or by the patient (Table 1). After this patient and set expectations for opioid medication changes. The review, the pharmacist calls the patient to introduce himself/ social worker or nurse obtains the patient’s clinical data such as herself, outline the tapering process, and engage the patient in pain location, level of pain, and perceptions of what makes the initial shared decision making around an opioid tapering plan. pain better or worse. The nurse or social worker also discusses According to STORM pharmacists, their initial outreach serves nonpharmacologic strategies for pain and screens patients for as the basis for their ongoing relationship with the patient depression by administering the Patient Health Question - (Table 1). During this call, the pharmacist seeks the patient’s naire-9.28 Results of the Patient Health Questionnaire-9 are input about information that factors into the development of entered into the EMR and are also used to prompt additional the tapering plan: pain diagnoses and descriptions of his/her follow-up with the PCP, mental or behavioral health services, pain, details about current opioid use, the use of other medi- or the STORM program social worker before initiation of the cations and how s/he uses them, potential side effects of pain taper. Although the intake call serves as an introduction to the or opioid use, current or historical substance use disorder, and program and as an opportunity to gather additional clinical nonmedication and self-care strategies for pain management. information, STORM social workers emphasize that the call The call also includes a review of any opioid safety concerns, also provides a valuable opportunity to build patient trust and including results of recent urine drug screening and Prescrip- confidence in the program and its process (Table 1). In addi- tion Drug Monitoring Program data for the patient. Finally, tion to the introductory contact, the STORM social worker or the pharmacist ascertains the patient’s pain management goals nurse may continue to have regular telephone follow-up with and addresses concerns or questions. patients throughout the tapering process. Continued contact Using shared decision making, the patient and pharmacist most often occurs for complex patients who may have substantial develop an opioid tapering plan. The opioid tapering plan it- anxiety or depression, other comorbid health conditions, or a self outlines the patient’s overall goal (eg, complete cessation, need for additional support. Pharmacists may also request that tapering to an agreed-on dosage) and provides a framework for the social worker or nurse resume active follow-up if a patient how that goal will be attained, including planned reductions in

Table 4. Sample script for opioid tapering scenarios Example of patient statement Potential pharmacist response My pain is so bad, it makes no You’re scared making these changes will leave you unable to care for your family. sense for me to take less. I won’t Would it be OK to share some of the concerns I have about your current pain regimen, and what options I think will be more be able to work or take care helpful for you? of my family without my pain In my experience, we have overestimated how helpful opioids are and underestimated how sometimes they make people feel medications. worse. People frequently are able to lower their dose and end up having their pain improve, and they tell me they feel a lot better. I have always used my You have been doing this for a long time. You feel your current regimen is working for you and are really worried what will medications safely with no happen if we make any changes. problems. I just want to keep We now have a better understanding of how opioids work and how they change your body’s response to pain. I am worried taking what I know works. that the medication may be doing you more harm than good. May I share some information about these risks? Would you be open to discussing some of the other options we have now to manage your pain more safely? I ran out of my medication early, You feel that increasing your opioid medication was your only option. but with this taper, my pain Opioids can be a helpful tool to manage pain, but people who have chronic pain have better results when they also use a has increased, and what was I combination of nonmedication strategies. Opioids are one angle of many and have some of the biggest risks and setbacks. supposed to do? My hope for you is to improve your pain control by expanding your horizons with other treatment options. I like to think of it as coming at the problem of pain from as many angles as possible While we are making changes, it is important that we stay on track with the plan. It is normal for your pain to worsen temporarily when we decrease the dose. You already know a lot of ways to manage your pain. You are resourceful. I also hear you when you say you are not satisfied with your current pain management. May we take some time today to discuss other ways to manage your pain during the taper?

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dosage and the frequency of dosage reductions. Ultimately, this Presentation, intervention, and outcome for a patient who tapering plan will be pursued only on agreement by the patient, underwent STORM pharmacist-led opioid tapering the STORM pharmacist, and the patient’s PCP. On reaching this agreement, the pharmacist communicates with the patient Patient presentation at start of opioid tapering what to expect during his/her opioid taper, including potential • A 62-year-old woman was treated for complex regional pain syndrome, low withdrawal symptoms, and tips for self-care should symptoms, back pain, right foot pain, and osteoarthritis of both hands and left knee. including withdrawal hyperalgesia, occur. Her clinical presentation was complicated by concurrent PTSD, generalized A follow-up pharmacist outreach is proactively scheduled anxiety disorder, panic disorder, major recurrent depressive disorder, a body before conclusion of this initial assessment call, so the patient mass index (BMI) of 37 kg/m2, type 2 diabetes mellitus, and hypertension. always knows what to expect regarding the next steps. It is made • Her starting medication regimen included methadone at a dosage of 50 mg clear to the patient from the outset that the whole care team every 8 hours, oxycodone at 30 mg every 6 hours, lorazepam at 1 mg 3 times is communicating and working together to provide support daily, and doxepin, 250 mg at bedtime. Her starting daily opioid dose was and meet the patient’s health needs throughout the taper. The approximately 2000 morphine milligram equivalents (MME). pharmacist completes a note in the EMR that summarizes the STORM opioid-tapering intervention encounter, updates the patient’s opioid prescriptions to reflect • Starting in January 2014, the patient worked with the STORM pharmacist the tapering plan, and routes the plan to the PCP for review to taper to a lower daily opioid dose and facilitate finding other ways to and approval. help manage her pain. She resumed aquatic physical therapy and her home The patient and STORM pharmacist continue their tele- exercise program and worked on stress management. phone contact at the agreed-on frequency, which varies among • One year later, she was discharged from STORM after achieving the initial patients and depends on patient preferences and need. For tapering goal dosage of methadone, 10 mg every 8 hours, and discontinu- example, the frequency of contact can vary from 2 telephone ing her use of oxycodone. visits to more than 20 per year. The ongoing nature of these • Later that year, she was referred to the STORM program again because of communications is reflective of the STORM pharmacist guiding concurrent opioid and benzodiazepine use, and she decided to try tapering and supporting the patient during the opioid tapering process. her lorazepam first. She nearly tapered off lorazepam but struggled with According to STORM pharmacists, ongoing communications worsening PTSD symptoms and, in 2016, decided that she preferred to stay allow the pharmacist to talk with the patient about changes at the lower benzodiazepine dose and instead try tapering methadone since their last conversation, with an emphasis placed on func- further with STORM support. tion as well as withdrawal symptoms, pain levels, and the use • Because of her struggles with depression and PTSD symptoms, the metha- of nondrug therapies (Table 1). The pharmacist will also review done taper proceeded more slowly than the first phase of her taper. In so changes in the use of opioids and other medications as well as doing, she was able to improve self-care, lose weight, and follow through assess for and address withdrawal symptoms and their manage- with various specialty referrals to further optimize her health. ment. Finally, during follow-up calls, the pharmacist will screen for and ensure that safety monitoring continues as appropriate. Follow-up and outcomes Follow-up calls also provide time for patients to express any • As of the beginning of 2019, she was completely opioid-free. Her lorazepam concerns or to ask questions that have come up since the start of dose has been reduced to 0.5 mg twice daily. Her mood has stabilized, and the taper. Depending on information shared during these calls, she is feeling empowered. She has discontinued doxepin use. She started the opioid tapering plan and contact frequency may change, and exercising more and eating healthfully and was able to reduce her BMI to 2 as the need arises, the STORM pharmacist may recommend 25 kg/m . She improved her back pain by participating in physical therapy. coordination of care with other clinical departments, comple- She pursued an integrative medicine referral and has further reduced her hemoglobin A to 5.7%, which allowed her to discontinue metformin use. mentary medicine specialists (eg, acupuncture, chiropractic), 1C or pain management group classes. These communications also Patient perspective allow the pharmacists to emphasize the availability and diver- • In her final phone call with a STORM pharmacist in January 2019, the patient sity of support throughout the tapering process (Table 1). As reflected on the 5 years since her original referral to the STORM program. such, patients are given the direct telephone numbers for the She said, “At first I wondered, ‘Why me? What did I do to deserve this punish- STORM pharmacist in case sudden needs should arise, even if ment [of tapering]?’ But you know, I’m so grateful. I was in such a fog and so that need occurs outside normal business hours or on weekends. numb, but I didn’t realize it until my dose lowered. I still have pain—this is a This direct contact option is perceived to be a critical aspect of fact of my life—but this process made me realize that I have control over my the program because it fosters trust and assures the patients that pain. It doesn’t have to define me. I don’t need to be the victim anymore— they have ready access to support during their tapering process. about pain or other facets of my life. Tapering forced me to find other ways During all contacts with patients, STORM pharmacists to manage my pain, and I am ultimately so much healthier than I would engage in active listening and apply motivational interview- have been otherwise.” She expressed gratitude for the support with this ing techniques to support the patient during the opioid taper, change in her life. She graciously offered, should the opportunity ever arise, and they encourage the use of self-care strategies to manage to share her story. “People can learn from my experiences, that you can rise pain. The communication approach used during the telephone above, come out on top, and be joyful, in a good place.” interactions emphasizes that the pharmacist listens and reflects patient concerns in a nonjudgmental way and asks questions PTSD = posttraumatic stress disorder; STORM = Support Team Onsite Resource for Management of Pain.

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Table 5. Research questions and measurement of RE-AIM implementation evaluation framework dimensions RE-AIM framework Data collection and dimension Research question(s) Study measures analytic approach Reach To what extent did STORM reach the target population Characterization of PCP training over time, including Quantitative and what was the representativeness of participants? percentage of eligible PCPs who were trained Effectiveness What is the success of the intervention? What is the Changes in opioid prescribing patterns, use of Quantitative impact of the STORM program on primary and broader nonopioid medications, and patient outcomes related outcomes, overall and by subgroups? to STORM program implementation Adoption What was extent of STORM program uptake by PCPs? Description of aspects of implementing the program Qualitative into usual care Implementation What were the barriers and facilitators to System-, provider-, and patient-level barriers and Qualitative implementation? facilitators to implementation of the program What was the consistency of the implementation of the Patient-level predictors of the rate of opioid tapering Quantitative and STORM program? qualitative What was the cost and budget impact of delivering the Cost and cost-effectiveness Quantitative and intervention? qualitative Maintenance What were the long-term effects of the STORM program Patient-, PCP-, and system-level outcomes Quantitative and at the patient and provider levels? (eg, opioid use, health care utilization, health qualitative Was the intervention maintained over time? outcomes) over time PCP = primary care practitioner; STORM = Support Team Onsite Resource for Management of Pain.

that encourage patients to be active in their own care, encour- will be completed in 2020, employs quantitative and qualita- age freedom of choice, and emphasize the positive in what the tive research methods to address dimensions of the RE-AIM patient brings to the conversation. As an example, a prompt for framework (reach, efficacy, adoption, implementation, and a patient who is reticent about continued opioid tapering may maintenance).29,30 Specifically, the RE-AIM implementation be: “It sounds like you’re really sitting on the fence as to whether or science framework evaluates the reach of an intervention to its not you can decrease. What challenges do you feel keep you from de- target population; effectiveness of the intervention on specific creasing? What would be the benefits to tapering?” An example of outcomes; intervention adoption in a specified setting; and the a prompt to encourage continued progress in tapering may be: implementation of the intervention and its maintenance over “Decreasing your opioid dose can be concerning and difficult. It sounds time (Table 5).29,30 The study will examine the effectiveness like you’re not quite ready to take the next step at this point. What of the STORM program through time-series analyses that would need to change in order for you to consider further decreas- compare dispensing patterns of opioid medications in periods ing your opioid?” Table 4 provides examples of several scenarios before and after STORM training of PCPs. Additionally, the and the use of a script and motivational interviewing during study controls for practitioner and patient characteristics in the an interaction between a STORM pharmacist and a patient. context of local and national trends in opioid use and interven- The patient is discharged from the STORM program to be tions concurrently taking place in the KPNW Health Plan. clinically managed by his/her PCP, either when the mutually Examples of co-interventions include the development of agreed-on tapering goal is met or if, at any point, the patient state prescription drug monitoring programs, clinical guidelines chooses to end involvement with STORM. A patient’s opioid around the prescribing of opioids and opioid dosing thresholds tapering process may be discontinued or suspended because of (eg, Centers for Disease Control and Prevention prescribing new developments such as impending surgery or other clinical guidelines), and changes in KPNW EMR-based alerts tied to issues that require prioritization. Patients are eligible for ad- opioid prescribing. Given the positive impacts of the program, ditional STORM services if the need should arise in the future. our research will also provide additional guidance regarding the The clinical presentation, tapering process, outcome, and per- dissemination and implementation of similar opioid tapering spective of a patient who underwent STORM pharmacist-led programs in different health care settings. opioid tapering is provided in Sidebar: Presentation, Interven- tion, and Outcome for a Patient Who Underwent STORM CONCLUSION Pharmacist-led Opioid Tapering. Additional STORM staff The risks of chronic opioid use for the management of perspectives on the impetus for STORM and reflections on chronic noncancer pain, especially when taken at high daily the various components of the program are included in Table 1. doses, are well established. The STORM program is a unique, pharmacy-led resource that seeks to support patients in safely EVALUATION OF STORM PROGRAM tapering their opioid use. The STORM program provides in- The KPNW Center for Health Research is undertaking dividualized patient care while reducing the burden on PCPs. the National Institute on Drug Abuse-funded FLOAT study Thus, the program may be a valuable addition to health care to examine the impact, effectiveness, cost-effectiveness, and systems and settings seeking options to address their patients’ v implementation of the STORM program. The study, which opioid tapering needs.

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Disclosure Statement 13. Ballantyne JC, LaForge KS. Opioid dependence and addiction during opioid The author(s) have no conflicts of interest to disclose. treatment of chronic pain. Pain 2007 Jun;129(3):235-55. DOI: https://doi. org/10.1016/j.pain.2007.03.028 PMID:17482363 Erratum in: Pain 2007 Oct;131(3):350 Acknowledgments 14. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and This work was supported by the National Institute on Drug Abuse of the overdose: A cohort study. Ann Intern Med 2010 Jan 19;152(2):85-92. DOI: https://doi. National Institutes of Health (Award Number R01DA042124), Bethesda, org/10.7326/0003-4819-152-2-201001190-00006 PMID:20083827 MD. The study sponsor had no role in the data collection, preparation of this 15. Mack KA, Zhang K, Paulozzi L, Jones C. Prescription practices involving opioid analgesics among Americans with Medicaid, 2010. 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Opioids impact of health promotion programs: Using the RE-AIM framework to form summary for chronic noncancer pain: Prediction and identification of aberrant drug-related measures for decision making involving complex issues. Health Educ Res 2006 behaviors: A review of the evidence for an American Pain Society and American Oct;21(5):688-94. DOI: https://doi.org/10.1093/her/cyl081 PMID:16945984 Academy of Pain Medicine clinical practice guideline. J Pain 2009 Feb;10(2):131-46. DOI: https://doi.org/10.1016/j.pain.2008.10.009 PMID:19187890

The Permanente Journal • https://doi.org/10.7812/TPP/19.216 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.11 11 ORIGINAL RESEARCH & CONTRIBUTIONS An Evaluation of the SCORE Program: A Novel Research and Mentoring Program for Medical Students in Obstetrics/Gynecology and Otolaryngology Kellie Corcoran, MD, MPH1; Miranda Ritterman Weintraub, PhD, MPH2; Isabella Silvestre1; Reshma Varghese1; Jonathan Liang, MD3; Eve Zaritsky, MD1 Perm J 2020;24:19.153 E-pub: 04/16/2020 https://doi.org/10.7812/TPP/19.153

ABSTRACT US identify as an underrepresented minority (URM).2 Train- Background: There has been a steady decrease in the number ing in research and clinical care to a racially and ethnically and of physician-scientists and a lack of diversity and inclusion of socioeconomically diverse trainee population will not only help underrepresented minorities (URMs) in medicine. physician-scientists deliver evidence-based, data-driven care to Objective: To assess the research productivity, interest, and patients,3 helping to produce a population of physician-scientists experience of medical students, including URMs, and resident and capable of identifying a diversity of areas in need of further in- faculty mentors of the Kaiser Permanente Oakland Medical Center’s vestigation, but also build a physician-scientist population that 8-week, intensive, mentored Summer Clinical Otolaryngology and better reflects the increasingly diverse patient population.4 Obstetrics/Gynecology Research (SCORE) Program for second-year In response to the decreasing number of physician-scientists medical students. and given the small number of participants in medical and doc- Methods: A database of SCORE Program research projects was toral programs, the medical education system is unable to meet generated from 2016, when the program was launched, through the physician-scientist pool demand.5 There has been a push to 2018. SCORE Program students and faculty completed a brief, incorporate research opportunities into residency training set- mixed-methods, anonymous exit survey that captured respon- tings. Although these programs train participants in research dents’ experiences, perceived program strengths, and opportuni- skills and critical thinking, they are often underfunded and occur ties for improvement. The number of peer-reviewed manuscripts too late in training to influence physicians to further pursue re- produced were counted. search.6,7 In addition, although efforts have been made to improve Results: A total of 16 SCORE Program students (50% female diversity in academic medicine, including the establishment of and 38% URMs) between 2016 and 2018 and 8 residents and mentorship programs and the targeting of undergraduate (and 8 faculty members in 2018 completed a brief, mixed-methods, high school) students, these research programs do not take into anonymous exit survey that captured respondents’ experiences, consideration the diversity of their trainees.8-10 perceived program strengths, and opportunities for improvement. In an effort to reach physicians earlier in their careers, several The medical students coauthored 12 published peer-reviewed research programs now exist specifically to train medical students. articles, 25 abstracts or national posters, and 1 opinion editorial. Medical schools that have implemented mandatory research in According to the program’s annual exit survey, 87% of students the students’ third year found that a greater number of graduating reported an increased interest in pursuing research, 93% had an students were interested in research if they had positive experi- increased interest in their respective specialties, and 93% believed ences with mentors or success in publication.11-13 There are also they had positive mentorship experiences. Similarly, faculty and several research programs geared toward medical students in the residents enjoyed mentoring students, thought that students summer between their first and second years of school. Students positively contributed to their projects, and would support the participating in these highly structured and supportive programs SCORE Program in the future. reported greater interest in research and were more likely to con- Conclusion: Structured research and mentoring experiences, duct research after medical school.12-14 such as the SCORE Program, may encourage students, including Kaiser Permanente Oakland Medical Center initiated the URMs, to pursue research throughout their careers in addition 8-week Summer Clinical Otolaryngology and Obstetrics/Gy- to adding research to their curriculum vitae to strengthen their necology Research (SCORE) Program in 2016 to provide early residency applications. clinical exposure and research training to second-year medical INTRODUCTION The number of physician-scientists has been steadily decreasing Author Affiliations for decades, with more physicians opting to pursue purely clinical 1 1 Department of Obstetrics and Gynecology, Kaiser Permanente, Oakland, CA careers. Physician-scientists, through their direct patient interac- 2 Department of Graduate Medical Education, Kaiser Permanente, Oakland, CA tions and experience in clinical settings, are ideally positioned to 3 Department of Head and Neck Surgery, Kaiser Permanente, Oakland, CA identify clinically driven research topics and translate research findings into direct patient care. In addition, despite efforts to Corresponding Author Eve Zaritsky, MD ([email protected]) improve representation of minority persons in medicine, only 7% of full-time academic faculty within medical schools based in the Keywords: medical education, medical student, mentor, physician-scientist, research, underrepresented in medicine

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students. The SCORE Program is unique in that it attempts completed a brief mixed-methods anonymous exit survey to provide early clinical research exposure as well as serve as a before program departure (2016-2018, see Supplementary pipeline for URMs in medicine. The Association of American Material Sidebar: Kaiser Permanente SCORE Exit Survey for Medical Colleges defines URMs as “racial and ethnic minorities Students— Anonymous Survey, available at: www.theperman- in a designated health profession discipline relative to the per- entejournal.org/files/2020/19.153-Supp). In 2018, a survey was centage of that racial or ethnic group in the total population.”15 also created for key faculty and residents (see Supplementary The aim of this initial evaluation of the SCORE Program Material Sidebar: Kaiser Permanente SCORE Exit Survey for students and resident and faculty mentors was to identify the Residents and Faculty, available at: www.thepermanentejournal. scholarly activity productivity of the program, assess the program’s org/files/2020/19.153-Supp). The surveys contained a combina- impact on student interest in pursuing residencies and research tion of multiple choice and open-ended questions that evaluated in otolaryngology as well as obstetrics/gynecology (OB/GYN), the SCORE Program experience and the program’s strengths identify areas for improvement, and track the number of appli- and opportunities for improvement. cants to the program. In addition, perceived resident and faculty This research project was deemed exempt by the Kaiser Per- benefits were assessed. manente Northern California Research Determination Office. Data analyses were conducted using Microsoft Excel (Microsoft METHODS Corp, Redmond, WA), or Stata software (StataCorp, College The SCORE Program is an 8-week, intensive summer pro- Station, TX). Quantitative data were aggregated and analyzed gram at the Kaiser Permanente Oakland Medical Facility for using descriptive statistics. 6 second-year medical students. In its first year (2016), the SCORE Program accepted 4 second-year medical students RESULTS to participate in research in otolaryngology. In 2017, SCORE From 2016 to 2018, 16 students participated in the SCORE expanded to include 2 students in OB/GYN research. The pro- Program. In 2016, fewer than 20 students applied for 4 slots, gram continued with 6 students in 2018. Invitations to apply more than 70 applied for 6 positions in 2017, and nearly 90 online were sent to medical schools across the US in the winter applied for 6 positions in 2018. More than half of the students via graduate medical offices, and participants were selected in selected were women (50%), and more than one-third were the spring. URMs (37.5%) (Table 1). Most students were from out-of-state During the program, students were matched with faculty and medical schools (75%). resident mentors on the basis of student research interest. The The SCORE Program students have thus far been coauthors students assisted with ongoing research projects at various stag- on a total of 25 posters or presentations at national conferences, es, supporting resident and faculty scholarly activity efforts via 12 publications in peer-reviewed journals, and 1 opinion edito- literature searches, data collection, data analysis, medical record rial (Table 2). Thus far, 63% of past SCORE Program students review, abstract and manuscript writing, and/or oral or poster have published articles (2016 cohort: 100%, 2017: 83%, and presentation development and delivery. To provide a diverse 2018: 16%) and 75% have been involved in presentations or range of experiences, students in OB/GYN were encouraged abstracts. Of those who have published articles, 75% were first to participate in multiple projects. In otolaryngology, students were assigned to 1 research project and mentor. Throughout the program, approximately 75% of student Table 1. SCORE Program student demographics time was dedicated to participation in research, whereas the URMs, No. (%) remainder was devoted to clinical observation and didactic Year Otolaryngology Obstetrics and gynecology learning. Students observed a variety of clinics and operations 2016 1 (25) NA within their department to better understand different career 2017 1 (25) 2 (100) paths available within the specialty. In addition, students at- 2018 1 (25) 1 (50) tended resident didactics, grand rounds, and morbidity and NA = not applicable; SCORE = Summer Clinical Otolaryngology and Obstetrics/ mortality conferences. Faculty and resident mentors provided Gynecology Research; URM = underrepresented minority. weekly guidance and feedback, and students attended a weekly lunchtime lecture series on research methods and professional Table 2. SCORE Program student productivity development. Guest speakers covered research-related topics, including library database searching, patient safety and quality Otolaryngology Obstetrics and gynecology improvement, research methods, biostatistics, and epidemiol- Presentations Presentations ogy, as well as topics focused on professional development, Year Publications and abstracts Publications and abstracts including health disparities, introduction to integrated health 2016 4 4 NA NA care, and a resident panel designed to answer student questions 2017 5 (2 pending) 6 2 4 about life as a resident. 2018 1 3 0 8 At the end of the 8-week program, students gave an oral Total 10 13 2 12 presentation to the key SCORE Program faculty, residents, NA = not applicable; SCORE = Summer Clinical Otolaryngology and Obstetrics/ and students on their primary research project. The students Gynecology Research.

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authors. The impact factors of the 12 publications ranged from manager respondents enjoyed supporting the SCORE Program 1.13 to 2.55 (median, 2.442). and agreed that they had a good understanding of mentorship Fifteen of the students completed the exit survey between expectations and were able to effectively engage with students 2016 and 2018, and all 15 reported that they were more likely during their clinical and research experiences. Interestingly, to pursue clinical research in the future because of participa- 81% of respondents strongly believed that SCORE Program tion in the program, believed that the SCORE Program had students were able to contribute to their research in a meaning- increased their interest in a particular specialty, and reported that ful and productive way; the remaining 19% agreed or somewhat their faculty mentor was available and provided good direction, agreed with this statement. All residents and attending faculty teaching, and mentorship (Table 3). On the basis of open-ended who responded were interested in being involved in the pro- questions, the students reported on the program’s strengths, in- gram in the future and provided supportive comments for the cluding the diverse range of research and clinical experiences and program (see Sidebar: Faculty and resident feedback regarding the training it provided, opportunities to interact closely with SCORE Program). residents, and valuable mentorship. Overwhelmingly, students reported on the excellent mentorship, shadowing opportunities CONCLUSION in their respective specialty, and engaging research experiences The SCORE Program exposed second-year medical students, (see Sidebar: SCORE Program student comments representing including URMs, to a structured clinical research program, the range of responses summarizing their research experience providing medical students with clinical and research skills and providing feedback from the exit survey). training and mentorship, while providing residents and attend- In 2018, an exit survey was administered to the attending fac- ing faculty with support to advance their research endeavors. ulty and residents. Eight of the 16 residents (50%), 6 of the 16 This dual support of student mentees and resident and faculty attending faculty members (37.5%), and both program managers mentors resulted in numerous scholarly products. These find- completed the exit survey (Table 4). All faculty, resident, and ings complement the increasing body of research indicating that early exposure to mentored clinical research during medical Table 3. Likert scale student evaluation of the SCORE Program Response Mean (SD)a SCORE Program student comments representing the The program improved my understanding of clinical 4.6 (0.91) range of responses summarizing their research experience research and providing feedback from the exit survey I was able to participate in clinical research project(s) in a 4.5 (0.92) meaningful and productive way Student responses regarding what worked well (survey question: The program increased my interest in the specialty 4.6 (0.63) “describe 3 strengths of the program”): I am more likely to pursue a residency in the specialty 4.3 (0.62) • Ability to work on different projects at different stages of completion I am more likely to pursue clinical research in the future 4.1 (0.8) gave me a diverse range of research experiences.” because of my participation in the program • Dr X was an amazing mentor who took the time to get to know me and I had good understanding, expectations, and ownership of 4.1 (1.2) guide me along our projects. She was attentive to my desire to learn… my research project She also allowed me to have a level of independence and ownership of My faculty mentor was available and provided good 4.7 (1.1) my projects. direction, teaching, and mentorship • It [the SCORE Program] balanced clinical experience with clinical The weekly didactic lectures were informative and helpful 3.9 (0.67) research better than any other program I have seen I would recommend this program to other medical students 4.7 (0.71) • Everyone I shadowed was accommodating and I got to see a huge a A score of 1 indicates strongly disagree; 5, strongly agree. diversity of Ob/Gyn practices and experiences SCORE = Summer Clinical Otolaryngology and Obstetrics/Gynecology Research. • I loved the balance between research and shadowing. My schedule allowed me to get significant work done for my project and great expe- Table 4. SCORE Program faculty and resident Likert scale rience in clinic and the OR! evaluation of the program Response Mean (SD)* Student responses providing feedback and areas for growth (survey I had a good understanding of the purpose, structure and 4.3 (0.79) question: “describe 3 improvements that can be made to the program”): mentorship expectations • Increase hospital-wide knowledge of the SCORE program. I felt that I was able to effectively engage with the SCORE 4.6 (0.63) • I would have liked a little more information prior to beginning the students during their clinical, lecture and/or research program. Maybe a list of projects that are available or clinics to shadow experiences would have been nice to orient myself better prior to getting here.” SCORE students were able to contribute to my research 4.7 (0.70) • I think a little more communication amongst staff would make the project(s) in a meaningful and productive way program more efficient. I enjoyed supporting the SCORE Program 4.9 (0.34) • I thought the bonding especially between the ENT and Ob-Gyn students I would like to be involved with the SCORE Program 4.9 (0.34) wasn’t as strong as it could have been. *A score of 1 indicates strongly disagree; 5, strongly agree. SCORE = Summer Clinical Otolaryngology and Obstetrics/Gynecology Research. SCORE = Summer Clinical Otolaryngology and Obstetrics/Gynecology Research.

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school increases interest in, knowledge of, and exposure to The Kaiser Permanente SCORE Program is still in its specialty-specific research.12-14 Furthermore, the program’s fo- nascent state; therefore, there has not been the opportunity cus on recruiting and mentoring URMs is in alignment with for long-term student follow-up. Future evaluations of this the nationwide goal of improving diversity and inclusion in program could investigate the long-term impact it has on medicine. Lastly, the curriculum vitae of the SCORE Program prior participants’ careers and interest in research during and students was more robust on their completion of the program, beyond residency. In addition, because prior work11 suggests which could strengthen their residency applications. that interest in research is the biggest indicator of engaging in Throughout the first 3 years of the SCORE Program, students future research efforts, there may be a bias in who applies to have reported having positive experiences. All student partici- the program, which may be something measurable using a pre- pants responded that they were more likely to pursue clinical SCORE Program survey designed to gauge students’ interest research in the future. In addition, all students ended the 8-week in research at baseline. program with an increased interest in their specialty as well as a Although the long-term impact of the Kaiser Permanente greater understanding of clinical clerkships and residency. These SCORE Program has not been examined, past studies of findings corroborate those of prior studies,16,17 which have found similar programs have found that early research experiences, that early specialty exposure, including through mentorship strong mentorship, and publication success are all indicators of and experience with patients, increases interest in a particular participation in future research, especially if individuals have specialty as well as clinical competence. a preexisting interest in research.11-13 In addition, mentorship The applicant pool increased from fewer than 20 applicants for URMs alone increases their competitiveness when apply- in 2016 for 4 positions to nearly 90 applicants in 2018 for 6 ing to residency programs.17 On the basis of the follow-up positions as the program became more well known. SCORE surveys, each SCORE student expressed an increased interest Program students in the first 3 years of the program came from in incorporating research into their future careers. We believe across the US, with most being outside of California. This find- that the Kaiser Permanente SCORE Program and similar ex- ing indicates a desire for structured summer research programs periences that expose medical students to research early in their from medical students across the country. Furthermore, interest careers may help reverse the downward trend in the number of has been expressed by other departments for program expansion physician-scientists. Furthermore, this strategy to increase the but is limited at this time by funding. proportion of URMs in medicine and research may contribute Although the SCORE Program has received positive feed- to improvements not only in diversity and inclusion efforts in back from students, residents, and faculty, areas for improvement medical practice but also in better serving our patient com- v were documented. Although the attending faculty and residents munity. enjoyed hosting students overall, some found it challenging to incorporate the students into a clinical setting. Many physicians Disclosure Statement and hospital staff not directly mentoring the students were The author(s) have no conflicts of interest to disclose. unfamiliar with the SCORE Program despite programmatic emails that were sent. Acknowledgments Thank you to all the SCORE Program students who participated in the program, Kaiser Permanente Graduate Medical Education for financially supporting the program, and Antoinette Niblett, our administrator of the program. Faculty and resident feedback Laura King, ELS, performed a primary copy edit. regarding SCORE Program Authors’ Contributions • It was incredible to have the SCORE students involved in my Kellie Corcoran, MD, MPH, participated in the acquisition and analysis of project. They were able to take it to the next level by having the data, drafting, and submitting of the final manuscript. Miranda Weintraub, PhD, time to put into literature review, organization and manuscript participated in drafting and submitting of the final manuscript. Isabella Silvestre writing. participated in drafting and submission of the final manuscript. Reshma • They were invaluable in moving resident research forward. Varghese participated in drafting of the final manuscript. Eve Zaritsky, MD, and • Providing students with early exposure to clinical and research Jonathan Liang, MD, participated in study design, acquisition and analysis of experiences and providing residents and faculty with op- data, and drafting of the final manuscript. All authors have given final approval to this manuscript. portunities for support and personnel to help move their own research projects forward. It is a win-win-win! How to Cite this Article • I truly hope we can continue to keep this program going and Corcoran K, Weintraub MR, Silvestre I, Varghese R, Liang J, Zaritsky E. An potentially expand it to other departments. Other faculty have evaluation of the SCORE Program: A novel research and mentoring program expressed an interest in having score students in their subspe- for medical students in obstetrics/gynecology and otolaryngology. Perm J cialties. 2020;24:19.153. DOI: https://doi.org/10.7812/TPP/19.153 • Fabulous program. I hope it continues to be funded. References SCORE = Summer Clinical Otolaryngology and Obstetrics/Gynecology Research. 1. Schafer AI. The vanishing physician-scientist? Transl Res 2010 Jan;155(1):1-2. DOI: https://doi.org/10.1016/j.trsl.2009.09.006 PMID:20004354

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2. Diversity in medical education: Facts & figures 2016. Washington, DC: Association of 10. Wells RG. Building a better pipeline: The case for undergraduates in gastrointestinal American Medical Colleges; 2016 research. Gastroenterology 2007 Sep;133(3):740-1. DOI: https://doi.org/10.1053/j. 3. Harding CV, Akabas MH, Andersen OS. History and outcomes of 50 years of gastro.2007.07.036 PMID:17854586 physician-scientist training in medical scientist training programs. Acad Med 11. Weaver AN, McCaw TR, Fifolt M, Hites L, Lorenz RG. Impact of elective versus 2017 Oct;92(10):1390-8. DOI: https://doi.org/10.1097/ACM.0000000000001779 required medical school research experiences on career outcomes. J Investig Med PMID:28658019 2017 Jun;65(5):942-8. DOI: https://doi.org/10.1136/jim-2016-000352 PMID:28270407 4. Palepu A, Carr PL, Friedman RH, Ash AS, Moskowitz MA. Specialty choices, 12. Zier K, Wyatt C, Muller D. An innovative portfolio of research training programs compensation, and career satisfaction of underrepresented minority faculty for medical students. Immunol Res 2012 Dec;54(1-3):286-91. DOI: https://doi. in academic medicine. Acad Med 2000 Feb;75(2):157-60. DOI: https://doi. org/10.1007/s12026-012-8310-x PMID:22418729 org/10.1097/00001888-200002000-00014 PMID:10693848 13. Chang Y, Ramnanan CJ. A review of literature on medical students and scholarly 5. Feldman AM. The National Institutes of Health Physician-Scientist Workforce Working research: Experiences, attitudes, and outcomes. Acad Med 2015 Aug;90(8):1162-73. Group report: A roadmap for preserving the physician-scientist. Clin Transl Sci 2014 DOI: https://doi.org/10.1097/ACM.0000000000000702 PMID:25853690 Aug;7(4):289-90. DOI: https://doi.org/10.1111/cts.12209 PMID:25123835 14. Solomon SS, Tom SC, Pichert J, Wasserman D, Powers AC. Impact of medical 6. Ercan-Fang NG, Rockey DC, Dine CJ, Chaudhry S, Arayssi T. Resident research student research in the development of physician-scientists. J Investig Med 2003 experiences in internal medicine residency programs—A nationwide survey. May;51(3):149-56. DOI: https://doi.org/10.1136/jim-51-03-17 PMID:12769197 Am J Med 2017 Dec;130(12):1470-1476.e3. DOI: https://doi.org/10.1016/j. 15. Frequently asked questions and answers about the new underrepresented in amjmed.2017.08.033 PMID:28919025 medicine definition. Washington, DC: Association of American Medical Colleges; 7. Villwock JA, Hamill CS, Nicholas BD, Ryan JT. Otolaryngology residency program 2003. p. 1 research resources and scholarly productivity. Otolaryngol Head Neck Surg 16. Compton MT, Frank E, Elon L, Carrera J. Changes in U.S. medical students’ specialty 2017 Jun;156(6):1119-23. DOI: https://doi.org/10.1177/0194599817704396 interests over the course of medical school. J Gen Intern Med 2008 Jul;23(7):1095- PMID:28419807 100. DOI: https://doi.org/10.1007/s11606-008-0579-z PMID:18612751 8. Mahoney MR, Wilson E, Odom KL, Flowers L, Adler SR. Minority faculty voices 17. Yang Y, Li J, Wu X, et al. Factors influencing subspecialty choice among on diversity in academic medicine: Perspectives from one school. Acad Med medical students: A systematic review and meta-analysis. BMJ Open 2019 Mar 2008 Aug;83(8):781-6. DOI: https://doi.org/10.1097/ACM.0b013e31817ec002 7;9(3):e022097. DOI: https://doi.org/10.1136/bmjopen-2018-022097 PMID:30850399 PMID:18667896 18. Ramanan RA, Taylor WC, Davis RB, Phillips RS. Mentoring matters. Mentoring 9. Merchant JL, Omary MB. Underrepresentation of underrepresented minorities in and career preparation in internal medicine residency training. J Gen Intern Med academic medicine: The need to enhance the pipeline and the pipe. Gastroenterology 2006 Apr;21(4):340-5. DOI: https://doi.org/10.1111/j.1525-1497.2006.00346.x 2010 Jan;138(1):19-26.e1. DOI: https://doi.org/10.1053/j.gastro.2009.11.017 PMID:16686809 PMID:19944787

The Permanente Journal • https://doi.org/10.7812/TPP/19.153 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 16 Kaiser Permanente SCORE Exit Survey for Students—Anonymous Thank you in advance for taking a few moments to reflect on the SCORE Program. Your responses to these questions will be filed and reviewed anonymously and may inform how to make improvements to the program.

1. Program (select one) 8. My faculty mentor was available and provided good a. SCORE-Oto (Otolaryngology–Head & Neck Surgery) direction, teaching, and mentorship (select one answer). b. SCORE-Ob (Obstetrics and Gynecology) a. Strongly agree b. Agree 2. The SCORE Program improved my understanding of clinical c. Neutral research (select one answer). d. Disagree a. Strongly agree e. Strongly disagree b. Agree c. Neutral 9. The amount of time dedicated to clinical activities (OR, d. Disagree clinic) was (select one answer): e. Strongly disagree a. Just right b. Not enough 3. I was able to participate in clinical research project(s) in a c. Too much meaningful and productive way (select one answer). a. Strongly agree 10. The weekly didactic lectures were informative (select one b. Agree answer). c. Neutral a. Strongly agree d. Disagree b. Agree e. Strongly disagree c. Neutral d. Disagree 4. The SCORE Program increased my interest in the specialty e. Strongly disagree (Otolaryngology–Head & Neck Surgery or OB/GYN) (select one answer). 11. How likely are you to recommend the SCORE Program to a. Strongly agree other medical students (select one answer)? b. Agree a. Very likely c. Neutral b. Likely d. Disagree c. Neutral e. Strongly disagree d. Unlikely e. Very unlikely 5. I am more likely to pursue a residency in the specialty (Otolaryngology–Head & Neck Surgery or OB/GYN) because of 12. Please rank the following factors in your decision to my participation in the program (select one answer). participate in the SCORE Program. (1 = most important, 5 = a. Strongly agree least important): b. Agree a. Location c. Neutral b. Monetary stipend d. Disagree c. Interest in pursuing the specialty (Otolaryngology–Head & Neck e. Strongly disagree Surgery, OB/GYN)

6. I am more likely to pursue clinical research in the future d. Interest in pursuing clinical research because of my participation in the program (select one e. Interest in career at Kaiser Permanente answer). a. Strongly agree 13. Didactic/Lecture Series b. Agree a. Which was your favorite topic/lecture? c. Neutral b. Which was your least favorite topic/lecture? d. Disagree c. List a topic you would have liked to have included in your e. Strongly disagree didactics.

7. I had good understanding of my role in the research 14. Describe 3 strengths of the SCORE Program. project(s) (select one answer). a. Strongly agree 15. Describe 3 improvements that can be made to the SCORE b. Agree Program. c. Neutral d. Disagree 16. Any other comments/suggestions regarding the SCORE e. Strongly disagree Program?

Thank you.

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1. Please check which box describes you Resident Faculty/Attending Other

2. Please select your specialty Head and Neck Surgery Obstetrics and Gynecology Other

FOR THE FOLLOWING QUESTIONS, PLEASE SELECT ONE ANSWER.

During the course of the SCORE Program,

3. I had a good understanding of the purpose, structure and mentorship expectations. Strongly Disagree Somewhat Somewhat Agree Strongly Agree Disagree Disagree Agree

4. I felt that I was able to effectively engage with the SCORE students during their clinical, lecture and/or research experiences. Strongly Disagree Somewhat Slightly Agree Agree Strongly Agree Disagree Disagree

5. SCORE students were able to contribute to my research project(s) in a meaningful and productive way. Strongly Disagree Somewhat Slightly Agree Agree Strongly Agree Disagree Disagree

6. I enjoyed supporting the SCORE Program. Strongly Disagree Somewhat Somewhat Agree Strongly Agree Disagree Disagree Agree

7. I would like to be involved with the SCORE Program in the future. Yes No

8. What do you think is most valuable about the SCORE Program?

9. Please provide any additional comments you would like to share.

The Permanente Journal • https://doi.org/10.7812/TPP/19.153 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.7 18 ORIGINAL RESEARCH & CONTRIBUTIONS Sequential Changes Advancing from Exercise-Induced Psychological Improvements to Controlled Eating and Sustained Weight Loss: A Treatment-Focused Causal Chain Model

James J Annesi, PhD, FAAHB, FTOS, FAPA1 Perm J 2020;24:19.235 E-pub: 04/10/2020 https://doi.org/10.7812/TPP/19.235

ABSTRACT A near-complete weight regain then be- Introduction: Behavioral (nonsurgical/nonpharmacologic) weight loss treatments have gins and persists.2,3,11-13 Senior behavioral been overwhelmingly unsuccessful beyond the short term. Rather than incorporating ac- scientists cite even their own carefully pre- cepted behavioral change theory, most have inadequately relied on providing exercise and pared2,14 but failed treatments as evidence of nutrition information. Although adherence is a challenge, exercise has emerged as the most the futility of attempting sustained weight robust predictor of sustained weight reduction. However, exercise might be more associ- loss.15,16 Because of an unmistakable inabil- ated with long-term weight loss through the relationship of its associated psychological ity to alter weight management behaviors changes with improved nutrition than through direct effects of energy expenditures, which over the long term,2,3,11-13 some researchers are typically minimal in deconditioned individuals. professed that further efforts toward de- Objective: To facilitate improved helping methods through a proposed theory-based velopment of behavioral interventions are causal chain model in which supported exercise predicts sustained weight loss through useless and thus should be terminated.15 successive changes in exercise-related, then eating-related, self-regulation, self-efficacy, Other researchers, along with this and mood. article’s author, disagree with the sug- Results: Segments of the model predict that 1) exercise and eating behaviors will be gestion to end applied research activities sequentially improved through increased self-regulatory skill use and self-efficacy and in the behavioral weight management 2) exercise-induced mood improvements will foster greater self-regulation and reduced treatment arena. Yet, it cannot be refuted emotional eating. Short-term psychosocial changes can be leveraged to carry over to that sustained weight reduction has been longer-term changes and maintained weight reductions. Suggested interventions emerging “a problem that simply does not yield to from the model and supporting research include using self-regulation to enable a habit of treatment”,17p717 and “most obesity pre- regular moderate exercise, facilitating a transfer of self-regulatory skills from an exercise to vention interventions have attained only eating context, and leveraging mood improvements associated with manageable volumes limited or no behavioral changes … and of exercise to improve eating behaviors. have rarely impacted targeted physiological Conclusion: The model presents an evidence-based explanation of the exercise-weight or anthropomorphic health outcomes.”18p1 loss association through psychosocial mechanisms. It also informs the development of Most researchers concur that considerable practical methods to facilitate sustainable reductions in weight and health risks in adults innovation would be required for any future with obesity. chance at success.2,3,12 Possibilities for the use of behavioral methods as an adjunct INTRODUCTION health,9 and approximately 72% of Ameri- to bariatric surgery19 and pharmacothera- The persistent inability to reduce excess cans are at a higher-than-healthy weight.10 pies2,11 were posited. However, the prospect weight is associated with health risks, in- Examination of the association between of exercise holding importance well beyond cluding the cardiovascular disease-related the considerable amount of information its relatively minor direct function in weight conditions of type 2 diabetes, hypertension, already provided and the present levels of loss (because energy expenditures are mini- and hypercholesterolemia; various cancers; exercise and overweight/obesity in the US mal in deconditioned individuals20,21) was and musculoskeletal disorders.1 Compli- supports the need for the development of also advanced as a possible cost-effective ance with behavioral changes required to a viable but practical explanatory model basis for large-scale intervention.13 It was manage weight has been extremely prob- capable of better shaping helping meth- acknowledged, however, that adherence to lematic.2,3 However, most nonsurgical and ods. Preferably these techniques would be regular exercise regimens was problematic, nonpharmacologic treatment methods for able to be applied in an efficient and cost- obesity have been atheoretical.2,3 These effective manner. methods are related to the spurious assump- Adding to that challenge is the realiza- Author Affiliations tion that informing individuals about the tion that even state-of-the-art cognitive- 1 YMCA of Metropolitan Atlanta, GA need to be more physically active and to eat behavioral methods have been deficient in a healthier manner will improve those at facilitating sustained changes in weight Corresponding Author weight management behaviors.4-8 However, loss behaviors for decades.2,3,11-13 After James J Annesi PhD, FAAHB, FTOS, FAPA ([email protected]) less than 4% of US adults complete the treatment is initiated, weight loss con- Keywords: adherence, behavioral medicine, evidence-based, health minimum amount of exercise required for sistently plateaus within 6 to 9 months. education, integrative medicine, Lifestyle Medicine, nutrition, obesity, preventive, weight

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requiring an inventive solution,2 and uses self-efficacy were identified.26,27 Results be affected by a treatment.42 Hardeman of exercise as the sole treatment element of subsequent investigation indicated that and colleagues43p767 suggested that causal for weight loss lacked positive results.13 the changes in self-regulation, self-efficacy, modeling presents a fresh opportunity Recent research has sporadically as- and mood that explained large portions of for the development and testing of health sessed theoretically driven psychosocial the variances in exercise and healthy eat- behavior-change interventions, which they correlates of weight loss,22-25 and roles for ing behaviors over 6 months will, under assert, “remain at an early stage.” In the exercise beyond its typically minor function the correct conditions, also be associated proposed causal chain model, key tenets from energy expenditures have occasionally with maintained changes.32,33 Such self- of social cognitive theory,44,45 self-efficacy been suggested.26-28 Despite this, a com- regulatory skills included methods such theory,46 and self-regulation theory47,48 prehensive predictive model applicable for as managing negative self-talk, preparing are incorporated. Accordingly, there is treatment development and utilization has for inevitable behavioral lapses, and set- an expectation that increased self-regu- been absent. Given the substantial scope of ting interim goals. Research findings also lation will predict perseverance through the obesity problem, some researchers with supported propositions that exercise-as- lifestyle barriers, improved self-efficacy a translational behavioral medicine outlook sociated psychosocial improvements carry will foster persistent goal striving, and asserted that emergent methods require over, or generalize, to parallel psychosocial enhanced mood will generate a positive large-scale application potentials.13,29 Pres- predictors of eating changes in the pres- and reinforcing psychological climate that ently, however, the fragmented assortment ence of behavioral treatments focused on facilitates behavioral progress.28 Research of pretest/posttest, correlational, mediation, self-regulation.34-38 Additionally, eating is also incorporated on the generalization and moderation analyses falls far short of changes (as opposed to energy expendi- of self-regulation and self-efficacy across providing a map sufficient for effective- in tures) explain the preponderance of the health-related tasks35,38,49 (here, exercise tervention architectures. Beyond acknowl- variance in weight loss.26,39 to healthier eating). In addition to pro- edging that there are many personal barriers It should be noted, however, that when viding an overall “shape” to the model, to sustained change to overcome and that a treatment does not purposefully develop this theory-based emphasis additionally obesity is a chronic disorder requiring its participants’ self-regulatory skills (ie, restricts the plethora of relationships pos- lengthy attention, there is little consensus instead use only their existing skills), their sible among those and other variables.50 It on how to revise failed processes.2,3 As a usage might diminish for use in controlling furthermore limits probative analyses and result, many physicians and other health eating because they have been “depleted” statistically capitalizing on chance that are, care professionals simply provide basic by their focus on maintaining regular ex- unfortunately, common in applications of encouragements to eat healthier and to ercise.34,40 Moreover, other research find- structural equation modeling.51 Although get more physical activity while realizing ings indicated that also accounting for often of minimal concern to the practi- there is little chance of success through emotional eating would be productive,41 tioner, resolution of these methodologic such advice alone. and various theory- and research-based issues is of considerable import for the relationships (eg, between exercise-induced validity of an emergent model. FOUNDATIONS OF A PREDICTIVE mood change and emotional eating; effects In the present synthesis of research, MODEL FOR BEHAVIORAL CHANGE of mood change on self-regulatory skills although the inevitability of idiosyncratic Before development of a theory-based use) required better accounting for longer- differences across individuals with obe- causal chain model, a review of the related term changes in behaviors. Various other sity is acknowledged, a somewhat deter- research was conducted considering the tested psychosocial predictors of behavioral ministic view is incorporated that might mediation/moderation framework for changes (eg, body satisfaction, self-moti- ultimately enable numerous individuals to analyses of behavioral obesity reduction vation, self-concept) were excluded from finally be helped through standardization processes suggested by Baranowski and consideration for a next-generation pre- of methods arising from relationships in a colleagues.18 This review was influenced dictive model because of either covariance sound predictive model. Because the use of by the following factors: 1) research issues demonstrated with other predictors multiple experiments to explain aspects of indicating that exercise is the stron - or trivial additional impacts on the essen- a causal chain has been viewed as optimal42 gest predictor of success with sustained tial behavioral changes and weight loss. and identified as effective within a context weight loss20,30,31; 2) a previously proposed of dietary change,52 those processes formed model suggesting a path from exercise to Use of the Causal Chain the basis of the present model’s systematic weight loss that included improvements As an extension of the research, a re- development. This was a unique advantage. in mood, well-being, body image, self- vised model is proposed in this article Far from being an intellectual exercise that efficacy (ie, feelings of ability/compe- using a causal chain design.42 A causal is common in research-orientated abstrac- tence), self-esteem, and coping leading to chain is an explanatory process in which tions, the overall goal of the model being increased commitment, more psychologi- behaviors and psychosocial factors are proposed is clear: To create a structure in cal resources, and improved adherence to posited to exist in ordered schemas. Such which evidence-based methods facilitate diet and exercise28; and 3) a path where schemas should be congruent with ac- meaningful improvements in both exercise interrelations between exercise-related cepted theory, and both predictor and and healthy eating behaviors that are reli- and eating-related self-regulation and mediator variables might be expected to ably sustained.

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Focus on Real-World Applicability Although some research posits match- ing treatments to causal models, 53 the present concern was the development of a causal chain model in the presence of field- based treatments. This course of action allowed generalization to the real world to be maximized. Here, a fundamental aim was to seek an understanding of “active ingredients” of treatment effects54 so that processes might be accordingly developed, prioritized, and timed. This practical use of theory and the extant research has been cited as a gap in weight management in- tervention research concerned with long- term effects.13 Additionally, considering that a further aim of this research was to support effects that have sometimes been defined as separate (ie, initial weight loss vs sustaining lost weight), the model discussed here reflects this. The extensive research literature on the transtheoretical model55 supports the approach of account- ing for psychosocial effects on behaviors that are based on distinct stages (eg, de- velopment of a behavior vs maintenance of that behavior). Because what might be the most important aspect, that is, main- tenance of behavioral change, has typi- cally been omitted in related research,2,13 that matter received equal attention to the essential task of establishing initial changes.56 Given this, marked attention was devoted to accounting for the transfer of the psychosocial conditions enabling short-term weight loss to those facilitat- ing maintained loss (and accompanying reductions in health risks).57 MODEL DESCRIPTION A newly developed causal chain model is outlined that takes into account the fol- lowing: 1) the need for an innovative treat- Figure 1. Causal chain from exercise-induced psychosocial changes, to eating-related psychosocial a ment direction, 2) research demonstrating changes, to sustained weight loss. that exercise is the strongest predictor of a The weight loss phase is baseline to months 6 to 9, and the weight loss maintenance phase is beyond months 6 to 9. Treatment components targeting exercise and eating changes, separately, are denoted in boxes in the top-left side. sustained weight loss, 3) demonstrated Numbers 1 through 7 refer to the 7 proposed sequential segments in the model. Triangles in the model’s segments relationships between psychosocial corre- denote the classic mediation relationship, where the prediction of an outcome variable by a predictor variable is lates of exercise and eating improvements, expressed through a mediator. and 4) the need to address weight loss and a = path a (predictor→mediator); arrows = directionality of paths; b = path b (mediator→outcome); c′ = path c′ (predictor→outcome, controlling for the mediator [Path a × Path b]); dashed lines = relationships that might be redundant weight loss maintenance as distinct issues. (eg, Δmood→Δeating is possibly redundant with emotional eating), which are considered tentative in the model; The model is conveyed in 2 interrelated Δ (delta) = changes in the noted variables that account for dynamic relationships across the weight loss process, with parts: A weight loss phase (initial 6-9 a change in the predictor variables (eg, baseline to month 3) preceding changes in outcome variables (eg, month 3 to month 6); Em Eat, emotional eating; exercise = all types of physical activity (eg, walking); mood = overall emotional state months after treatment initiation) and a (aggregation of constructs such as depression, anxiety, fatigue); positive eating = healthy eating (eg, fruit and vegetable weight loss maintenance phase (beyond intake); SEeat = eating-related self-efficacy; SEex = exercise-related self-efficacy; solid dots = predictor variable in 6-9 months after treatment start). For a segment of the model; SReat = eating-related self-regulation; SRex = exercise-related self-regulation; unfavorable ease of interpretation, components of the eating = unhealthy eating (eg, intake of sweets, unhealthy fats).

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chain are denoted as “segments,” which are improvements in exercise self-efficacy.36 a reduction in unfavorable eating.75 This primarily delineated through their predic- As suggested by Gendolla and Brinkman67 portion of the model is supported by re- tor variables. As mentioned previously, the and supported by treatment research in search suggesting that the positive eating model is derived from research completed the present realm,68 one’s initial mood is behavior of increased fruit and vegetable in the presence of behavioral treatments. predicted to moderate the exercise self- consumption affects the diet as a whole,76 More specifically, those treatments had 2 regulation→physical activity relationship. including reducing unfavorable eating components. One component was based In segment 2, change in exercise be- behaviors such as the intake of sweets,61,77 on our 23-year program of research that havior serves as the predictor variable. Its and its effects on weight39,78 in a behavioral has focused on cognitive-behavioral exer- association with improved mood is posited treatment context. cise adherence methods.26,58 The compo- to be through improved exercise self-effi- Supported by recent findings,57 in seg- nent focused on eating behavior change cacy. 69 This is supported by research sug- ment 6, the increases in eating-related had various versions during the last 12 gesting that most exercise-induced change self-regulation over the weight loss phase years. In all cases, a pairing of exercise and in mood is induced via improvements in are purported to increase eating-related eating behavior change support transpired, feelings of accomplishment (ie, self-effica- self-regulation into the weight loss main- and emphases were placed on developing cy) rather than often-posited biochemical tenance phase through eating-related self- domain-specific self-regulatory skills and changes.70,71 Leading into segment 3, exer- efficacy changes attained in the weight loss self-efficacy while leveraging changes in cise self-regulation change is proposed to phase.62,79 Research findings also suggest mood. Associated improvements in those carry over to eating-related self-regulation, that the transfer of early increases in eat- psychosocial variables were supported change in exercise self-efficacy is posited ing-related self-regulation to their longer- across adult sample types,26,27,29,32-36,41,59-64 to carry over to eating-related self-efficacy term improvements is associated with the and in children65 and adolescents with change,34,35,72 and change in mood is a pro- degree of treatment attention provided to obesity.66 Figure 1 shows the model, and posed moderator of the change in eating self-regulatory skills development (vs more the next section presents a rationale for the self-regulation→positive eating behavior customary activities related to nutritional model’s component relationships. change relationship.67,73 advice).62,64 The association of increased In segment 3, the relationship between self-efficacy developed through feelings Relationships Embedded in the Model changes in eating-related self-regulation of ability derived from self-regulating At its basic level, the new causal chain and positive eating behaviors is proposed through barriers was addressed earlier, in model proposes that under behavioral to be mediated by change in eating-related segments 1 and 3. treatment conditions, psychosocial predic- self-efficacy.36 In the related research, the In segment 7, the prediction of weight tors of increased exercise will be associated decision to enter positive vs unfavorable loss sustained over the weight loss main- with parallel psychosocial changes related eating behaviors in segment 3 was influ- tenance phase by the eating-related self- to eating behaviors during the weight enced by the stronger relationships of self- regulation changes during that period is loss phase. These are associated with re- regulation with positive eating behaviors proposed to be moderated by the degree ductions in unfavorable eating behaviors previously identified.74 However, this was of negative mood present in the weight and weight during that period. The tar- somewhat arbitrary, and the significant loss maintenance phase. The research on geted psychosocial improvements from interrelationship is addressed in the ac- mood’s effect on self-regulation 67 was the weight loss phase will then transfer to count of segment 5. again the basis of that proposition, which maintained weight loss during the weight Part of segment 4 is represented with was also adequately supported in the pres- loss maintenance phase. The proposed dashed lines where change in emotional ent context.39,68 Also supported was that mediation-based segments, relationships eating enters the model. This is because the effect of the aforementioned mod- bridging those segments (eg, carryover of a lack of clarity on whether the ef- eration by mood during the weight loss of psychosocial changes from exercise to fect of mood change on eating behavior maintenance phase is, in turn, affected by eating contexts), and moderators of rela- encompasses the construct of “emotional exercise amounts completed during that tionships are described here, supported eating” or not. The reader is left to judge phase.39 Because it remains unclear what by a pointed representation of their as- this nuance in terminology. However, as- volume of exercise is required to sustain sociated research findings through pro- suming that it is a distinct construct, the exercise-induced improvements in mood, vided references. At a fundamental level, prediction of negative mood change’s ef- both its mean value and change during model-based predictions are supported by fect on change in positive eating behavior the weight loss phase is presently being both Bandurian44-46 and self-regulation47,48 is proposed to be mediated by emotional investigated. With formerly sedentary theory, with additional confirmation from eating change.61,68 adults, our preliminary findings suggest the many cited studies. Leading into segment 5, it is contended that 3 moderate exercise sessions per week In segment 1 of the model (top left in that increased emotional eating will are adequate. Figure 1) during the weight loss phase, predict increases in unfavorable eating increased exercise is predicted by in - behaviors.75 In this segment, the effect Model-Based Treatment Directives creased exercise-related self-regulation of increased positive eating behaviors on Success or failure with weight loss through (ie, mediated by) associated weight loss is proposed to be mediated by can often be synopsized via the constant

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“battle” of immediate gratification from present scope to propose interrelationships • Although the basis of the causal chain unhealthy eating and avoiding physical between behavioral and physiologic factors design emanates from seminal prin- exertion vs longer-term (already known) regarding weight change. Hence, although ciples of mediation analysis,85 recent health benefits from regular exercise and controlled eating will be associated with extensions of those tenets that do not controlled eating. Put in behavioral terms, reduced body weight because of an overall require a predictor and outcome vari- the management of one’s environment reduction in energy intake,39,76 analyses of able to initially demonstrate a signifi- to minimize challenges and of personal possible relationships such as the effect of cant bivariate relationship86 were also capabilities/perceptions to counter per- increased exercise on body composition incorporated in the guiding research. sistent barriers is where theory meets ef- and resting metabolic rate, and increases fective treatment application.80 With that in consumption of fruits and vegetables on CONCLUSION in mind and remaining in this article’s lean body mass, should be attended to in Predictive models on the effects of ex- intended parameters, treatment facets are future research. ercise on weight loss through psychosocial proposed on the basis of the causal chain Strengths of the model, including some processes have been scarce. Exceptions are model and its supporting data as well as based on methodologic aspects, include Baker and Brownell,28 who proposed that the field-based treatment context in which the following: exercise affects the relations of psychologi- those data were acquired (Table 1). • Findings that used a lagged variable ap- cal mechanisms (eg, body image, coping) proach, in which gains observed over an and physiologic mechanisms (eg, resting Assessing Generalizability earlier temporal period predicted longer- metabolic rate, appetite) that foster weight Assessment of outcomes and additional term changes in outcome variables,81,82 control, and our own earlier research decomposition of effects requires further were prioritized. That condition ad- positing interactions between physical testing across sample types (eg, ages, sexes, dresses possible reciprocal relationships activity-related and eating-related self- ethnicities, medical disorders beyond (and directionality opposite from expec- regulation and self-efficacy, and mood.26,27 excess weight, pre/post bariatric surgery, tations) among incorporated factors. Rather, what has been available in the area degrees of overweight/obesity, degrees • Where mediators and moderators are are studies limited by 1) cross-sectional of physical mobility, using pharmaco- included in the causal chain, actual analyses, 2) post hoc interpretations of therapies, with psychiatric/psychological determinants of targeted gains were relationships among variables, 3) a lack disorders), and treatment administration clarified and could also be accordingly of decomposition of treatment effects, formats (eg, group, individual, face-to-face, addressed in treatment applications. 4) an irrelevance of short-term findings, electronically supported, manual based). That could beneficially drive both the and 5) a lack of generalizability of results Although an aim of the predictive model timing and prioritization of interven- to applied settings. Even the emerging is large-scale applicability across individu- tion components. Also, such sequencing research on the phenomenon of coaction als with excess weight, it is also possible allowed an outcome variable in one area (ie, taking action on one treated behavior that, after further study, adjustments by of the causal chain to serve as a predictor increasing the probability of taking action subgroups will be indicated. However, in a subsequent section. on a second behavior) related to weight any such treatment alterations should • Variables selected for inclusion in the management has not yet proposed a causal be evaluated against the advantages (eg, model were reasonably malleable. For framework.87 Also, the few investigations logistical, cost) of a single standardized example, although factors such as edu- testing sequential applications of exercise protocol applicable across venues capable cational level and socioeconomic status and nutrition intervention components of supporting its widespread dissemination might predict (covary with) behaviors have been limited by a lack of decomposi- (eg, community health centers, YMCAs, associated with reduced weight, if emer- tion of effects through potential mediators, health maintenance organizations). gent interventions are to be pertinent failure to assess impacts on overweight across demographic groups, account- and obesity, and an absence of intention- Limitations and Strengths ing for such in the model would not be to-treat formats (ie, having self-select The clear advantage in the develop- practically useful. biases).88,89 Given their design limita- ment of the proposed model was our • Following from a goal of applicabil- tions, some studies simply presumed that nearly continuous compilation of relevant ity, the dynamic processes in inter- effects carry over from exercise to eating data since 1997. This was made possible ventions were represented by change improvements, without identifying pos- because the associated treatment com- (gain) scores. Although cross-sectional sible mechanisms.38,90 ponents were operationally embedded in research is (too) common in the area The model proposed in this article ad- a large community-based organization of health behavior change,83 data that dresses many of those limitations while concerned with changing health behaviors characterize change best reflect both also being the first explanatory paradigm and improving health risks. This provided a dynamic intervention effects and their found to focus on weight loss and weight unique opportunity for our sustained and impacts in a sequence of associations, loss maintenance as separate issues, as is systematic program of field-based inquiry. ultimately leading to improvements in suggested by much of the pertinent scien- However, given the behavioral nature of exercise and eating, their maintenance, tific literature.2,3,11-13,25,31 Its well-defined the proposed causal chain, it is beyond the and associated changes in weight.84 annotation of relevant variables and their

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Table 1. Practice suggestions based on proposed model Practice suggestion Rationale Use strong cognitive-behavioral methods that have demonstrated consistent Without regular exercise, the probability of sustained weight loss is negligible. support of adherence to exercise.1-3 Address self-regulation of exercise several weeks or months before initiating Help participants carry over the self-regulatory skills learned for maintaining exercise eating-behavior changes. to maintain improved eating. Focus on increasing present volumes of exercise rather than the attainment Exercise session durations and intensities should be adjusted so that they are “paired” of a “gold standard” (eg, 150 min/wk; expending 500 kcal per session). with positive (eg, rejuvenated) vs aversive (eg, exhausted) feelings.4 Adherence to even 2.5 to 3 moderate exercise sessions per week has been associated with the psychosocial predictors of healthier eating and weight loss.1,5-7 Help establish behavioral goal measures for exercise (eg, minutes of Realize that even manageable amounts of exercise are associated with increases cardiovascular exercise per wk), eating (eg, portions of fruits and vegetables in the psychosocial predictors of eating changes (where most weight loss will be per d), and weight loss (eg, caloric, or energy, intake per d) as clearly as derived).1,8 Realize that fruit and vegetable intake is associated with the health of the possible. diet as a whole.9 Regular self-weighing should be suggested.10 Attainment of a short-term goal, or upholding a behavioral contract, should Rewarding one’s self should be used to mark progress periodically. However, greater be distinctly indicated to help increase self-efficacy. than expected exercise volumes should not be rewarded by unhealthy foods. Require progress in behavioral and mood states to be diligently tracked to Mood improvements reliably associated with as few as 2 or 3 sessions of moderate help facilitate increased exercise-related and eating-related self-efficacy. exercise per week should help reduce emotional eating.7 Add anxiety-regulating activities such as deep breathing and abbreviated Even though moderate to large effects on mood can be expected through exercise progressive relaxation, which will be useful for situation-specific (stress- alone in formerly sedentary individuals,11 this is an adjunctive suggestion. oriented) prompts to inappropriate eating. Treat weight loss and maintaining weight loss as separate aims. Help participants denote weight loss goals that are sensitive to expected plateaus around the 6- to 9-month point so they are not perceived as a failure. Improve self-regulation by spending the preponderance of treatment time As such instruction progresses, provide more detail and training on how the skills in the instruction and rehearsal of self-regulatory skills such as cognitive learned in an exercise context can be adapted for ongoing use in controlling eating. restructuring, relapse prevention, and proximal goal setting with ongoing tracking of behavioral changes. Within the realm of increasing self-regulatory skills, address prompts to poor Realize that challenging stimuli such as high presence of fast foods can, at best, be behaviors (eg, social pressures to eat), controlling problematic stimuli (eg, high only minimized. Establishing feelings of hunger vs satiety (eg, on a 1-10 scale) helps food availabilities; fast foods), and understanding productive vs unproductive control unhelpful prompts to eating. cues to eating (eg, through regularly self-rating satiety levels). Increase self-efficacy by helping participants acknowledge all forms of Mastery experiences12 can be facilitated by underscoring when a newly learned self- progress. regulatory skill enables a lifestyle barrier to be overcome. This can also increase other group participants’ sense of ability to accomplish the same (ie, vicarious learning12). Limit detailed discussion on nuances of the diet (eg, macronutrient proportions; Realize that fruit and vegetable intake is alone a proxy for the overall adequacy of the supplements) because of the lack of evidence of their effects on weight loss diet.14 When there is high interest, an individual can be directed to reputable, freely and weight loss maintenance13 and because the treatment time required limits available sources for detailed nutrition information (eg, www.choosemyplate.gov). more productive activities (eg, rehearsal of self-regulatory skills). References 1. Annesi JJ. Supported exercise improves controlled eating and weight through its effects on psychosocial factors: Extending a systematic research program toward treatment development. Perm J 2012 Winter;16(1):7-18. DOI: https://doi.org/10.7812/TPP/11-136 2. Annesi JJ. Effects of a group protocol on physical activity and associated changes in mood and health locus of control in adults with Parkinson disease and reduced mobility. Perm J 2019;23:18-128. DOI: https://doi.org/10.7812/TPP/18-128 PMID:30624196 3. Annesi JJ, Unruh JL. Effects of The Coach Approach intervention on drop-out rates among adults initiating exercise programs at nine YMCAs over three years. Percept Mot Skills 2007 Apr;104(2):459-66. DOI: https://doi.org/10.2466/pms.104.2.459-466 PMID:17566435 4. Annesi JJ. Relationship between before-to-after-exercise feeling state changes and exercise session attendance over 14 weeks: Testing principles of operant conditioning. Eur J Sport Sci 2005;5(4):159-63. DOI: https://doi.org/10.1080/17461390500387056 5. Annesi JJ, Porter KJ, Johnson PH. Carry-over of self-regulation for physical activity to self-regulating eating in women with morbid obesity. Women Health 2015;55(3):314-33. DOI: https://doi.org/10.1080/03630242.2014.996727 6. Annesi JJ. Moderation of mood in the transfer of self-regulation from an exercise to an eating context: Short- and long-term effects on dietary change and obesity in women. Int J Behav Med 2019 Jun;26(3):323-8. DOI: https://doi.org/10.1007/s12529-019-09772-9 7. Annesi JJ, Vaughn LL. Relationship of exercise volume with change in depression and its association with self-efficacy to control emotional eating in severely obese women. Adv Prev Med 2011;article 514271. DOI: https://doi.org/10.4061/2011/514271 8. Annesi JJ, Unruh-Rewkowski JL, Mareno N. Replication and extension of the Weight Loss For Life community-based treatment protocol. Behav Med 2018 Jan-Mar;44(1):54-61. DOI: https://doi.org/10.1080/08964289.2016.1232241 9. Annesi JJ. Moderation of psychological factors in the relationship of increased fruit and vegetable intake with reductions in other food groups and weight in women with obesity. Minerva Psichiatr 2018 March;59(1):1-9. DOI: https://doi.org/10.23736/S0391-1772.17.01951-3 10. Annesi JJ, Johnson PH, Tennant GA, Porter KJ, McEwen KL. Weight loss and the prevention of weight regain: Evaluation of a treatment model of exercise self-regulation generalizing to controlled eating. Perm J 2016;20(3). DOI: https://doi.org/10.7812/TPP/15-146 11. Landers DM, Arent SM. Physical activity and mental health. In: Tennenbaum G, Eklund RC, editors. Handbook of sport psychology. 3rd edition. New York, NY: Wiley; 2007. pp. 469-91 12. Bandura A. Social foundations of thought and action: A social cognitive theory. Englewood Cliffs, NJ: Prentice Hall; 1986 13. Pagoto SL, Appelhans BM. A call for an end to the diet debates. JAMA 2013 Aug 21;310(7):687-8. DOI: https://doi.org/10.1001/jama.2013.8601 PMID:23989081 14. Aljadani HM, Patterson A, Sibbritt, D, et al. Diet quality, measured by fruit and vegetable intake, predicts weight change in young women. J Obes 2013;article 525161 DOI: https://doi. org/10.1155/2013/525161

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2. MacLean PS, Wing RR, Davidson T, et al. NIH 17. Brownell KD. The humbling experience of treating interrelationships addresses summary working group report: Innovative research to improve obesity: Should we persist or desist? Behav Res Ther suggestions from the recent National In- maintenance of weight loss. Obesity (Silver Spring) 2010 Aug;48(8):717-9. DOI: https://doi.org/10.1016/j. stitutes of Health working group charged 2015 Jan;23(1):7-15. DOI: https://doi.org/10.1002/ brat.2010.05.018 PMID:20691330 oby.20967 PMID:25469998 18. Baranowski T, Cerin E, Baranowski J. Steps in the with providing suggestions for future 3. Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels design, development and formative evaluation of research on improving maintenance of B, Chatman J. Medicare’s search for effective obesity prevention-related behavior change trials. weight loss such as, “Clear constructs with obesity treatments: Diets are not the answer. 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Morrow JR Jr, Krzewinski-Malone JA, Jackson Rankin JW, Smith BK; American College of Sports AW, Bungum TJ, FitzGerald SJ. American adults’ Medicine. American College of Sports Medicine to through the model’s ability to inform knowledge of exercise recommendations. Res Q Position Stand. Appropriate physical activity intervention. Ultimately, if physicians Exerc Sport 2004 Sep;75(3):231-7. DOI: https:// intervention strategies for weight loss and prevention doi.org/10.1080/02701367.2004.10609156 of weight regain for adults. Med Sci Sports Exerc and other health care professionals can PMID:15487287 2009 Feb;41(2):459-71. DOI: https://doi.org/10.1249/ be armed with targeted health behav- 6. Ruchlin HS, Lachs MS. Prevalence and MSS.0b013e3181949333 PMID:19127177 ioral change methods emerging from the correlates of exercise among older adults. J Appl 21. Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Gerontol 1999;18(3):341-57. DOI: https://doi. Church TS. The role of exercise and physical activity proposed model, and they are supported org/10.1177/073346489901800305 in weight loss and maintenance. Prog Cardiovasc through alliances with other professionals 7. Shepherd R, Towler G. Nutrition knowledge, attitudes Dis 2014 Jan-Feb;56(4):441-7. DOI: https://doi. that are tailored to addressing sustained and fat intake: Application of the theory of reasoned org/10.1016/j.pcad.2013.09.012 PMID:24438736 action. J Hum Nutr Diet 2007 Jun;20(3):159-69. DOI: 22. Greaves CJ, Sheppard KE, Abraham C, et al.; change in the same theoretically sound https://doi.org/10.1111/j.1365-277X.2007.00781.x IMAGE Study Group. Systematic review of reviews manner, chances for gaining control over PMID:17539865 of intervention components associated with obesity-related behaviors and outcomes 8. Stafleu A, Van Staveren WA, De Graaf C, Burema increased effectiveness in dietary and physical J, Hautvast JG. Nutrition knowledge and attitudes activity interventions. BMC Public Health 2011 Feb are likely to increase exponentially. Many towards high-fat foods and low-fat alternatives in 18;11(1):119. DOI: https://doi.org/10.1186/1471-2458- will agree that the realization of such a three generations of women. Eur J Clin Nutr 1996 11-119 PMID:21333011 partnership between the behavioral sci- Jan;50(1):33-41. PMID:8617189 23. Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention: ence, medical professional, and wellness 9. Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert v T, McDowell M. Physical activity in the United States The Look AHEAD study. Obesity (Silver Spring) communities is considerably past due. measured by accelerometer. Med Sci Sports Exerc 2014 Jan;22(1):5-13. DOI: https://doi.org/10.1002/ 2008 Jan;40(1):181-8. DOI: https://doi.org/10.1249/ oby.20662 PMID:24307184 Disclosure Statement mss.0b013e31815a51b3 PMID:18091006 24. Teixeira PJ, Carraça EV, Marques MM, et al. 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women with obesity. Int Q Community Health 79. Annesi JJ. Self-regulation foci and mood affect Conceptual, strategic, and statistical considerations. Educ 2018 Jan;38(2):107-14. DOI: https://doi. healthy and unhealthy eating behaviours differently J Pers Soc Psychol 1986 Dec;51(6):1173-82. org/10.1177/0272684X17749575 PMID:29298632 in successful weight-loss treatment participants. Int DOI: https://doi.org/10.1037/0022-3514.51.6.1173 74. Anderson ES, Winett RA, Wojcik JR. Self- J Psychol 2019 May 27 [Epub ahead of print]. DOI: PMID:3806354 regulation, self-efficacy, outcome expectations, https://doi.org/10.1002/ijop.12593 PMID:31134618 86. Hayes AF. An index and test of linear moderated and social support: Social cognitive theory and 80. Baranowski T, Perry CL, Parcel G. How individuals, mediation. Multivariate Behav Res 2015;50(1):1-22. nutrition behavior. Ann Behav Med 2007 Nov- environments, and health behaviors interact: Social DOI: https://doi.org/10.1080/00273171.2014.962683 Dec;34(3):304-12. DOI: https://doi.org/10.1007/ cognitive theory. In: Health behavior and health PMID:26609740 BF02874555 PMID:18020940 education: Theory, research and practice. Glanz K, 87. Johnson SS, Paiva AL, Mauriello L, Prochaska 75. Annesi JJ. Moderation of psychological factors in Lewis FM, Rimer B, editors. 3rd ed. San Francisco, JO, Redding C, Velicer WF. Coaction in multiple the relationship of increased fruit and vegetable CA: Jossey‐Bass; 2002. pp. 246-79 behavior change interventions: Consistency across intake with reductions in other food groups and 81. Cromwell JB, Hannan MJ, Labys WC, Terraza multiple studies on weight management and obesity weight in women with obesity. Minerva Psichiatr 2018 M. Multivariate tests for time series models. prevention. Health Psychol 2014 May;33(5):475- Mar;59(1):1-9. DOI: https://doi.org/10.23736/S0391- Thousand Oaks, CA: Sage; 1994. DOI: https://doi. 80. DOI: https://doi.org/10.1037/a0034215 1772.17.01951-3 org/10.4135/9781412985239 PMID:24274806 76. Aljadani HM, Patterson A, Sibbritt D, Hutchesson 82. Annesi JJ. Psychosocial correlates of emotional 88. Campbell MK, Tessaro I, DeVellis B, et al. Effects MJ, Jensen ME, Collins CE. Diet quality, measured eating and their interrelations: Implications for obesity of a tailored health promotion program for female by fruit and vegetable intake, predicts weight change treatment research and development. J Prim Prev blue-collar workers: Health works for women. Prev in young women. J Obes 2013;2013:525161. DOI: 2020 Jan 13 [Epub ahead of print]. DOI: https://doi. Med 2002;34(3):313-23. DOI: https://doi.org/10.1006/ https://doi.org/10.1155/2013/525161 PMID:24062946 org/DOI: https://doi.org/10.1007/s10935-020-00580-6 pmed.2001.0988 PMID:11902848 77. Annesi JJ. Effects of mood change on self-regulatory PMID:31933059 89. Vandelanotte C, De Bourdeaudhuij I, Sallis skill usage and subsequent impacts on physical 83. Buchan DS, Ollis S, Thomas NE, Baker JS. JF, Spittaels H, Brug J. Efficacy of sequential activity and eating changes within the weight-loss Physical activity behaviour: An overview of or simultaneous interactive computer-tailored phase of differing behavioral obesity treatment current and emergent theoretical practices. interventions for increasing physical activity and types: A retrospective cohort study. Eur J Integr J Obes 2012;2012:546459. DOI: https://doi. decreasing fat intake. Ann Behav Med 2005 Med 2017;16:75-81. DOI: https://doi.org/10.1016/j. org/10.1155/2012/546459 PMID:22778918 Apr;29(2):138-46. DOI: https://doi.org/10.1207/ eujim.2017.09.007 84. Fairchild AJ, MacKinnon DP. A general model for s15324796abm2902_8 PMID:15823787 78. Annesi JJ. Effects of treatment-associated increases testing mediation and moderation effects. Prev Sci 90. Hajat C, Kotzen D, Stein E, Yach D. Physical activity in fruit and vegetable intake on the consumption of 2009 Jun;10(2):87-99. DOI: https://doi.org/10.1007/ is associated with improvements in other lifestyle other food groups and weight through self-regulatory s11121-008-0109-6 PMID:19003535 behaviours. BMJ Open Sport Exerc Med 2019 processes. Perm J 2018;22:17-143. DOI: https://doi. 85. Baron RM, Kenny DA. The moderator-mediator Nov 28;5(1):e000500. DOI: https://doi.org/10.1136/ org/10.7812/TPP/17-143 PMID:29616916 variable distinction in social psychological research: bmjsem-2018-000500 PMID:31803493

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ABSTRACT explicit RMRR best practices, such as the a pulmonologist) may have led to more Retrospective medical record review is use of standardized data abstraction forms generalizable results. This finding reflects often used to answer the “why” questions and assessment of interrater reliability the suggestion of Worster and Haines8 that statistical modeling cannot. In addi- when multiple reviewers are involved.3 that data arising from RMRR “are more tion to its utility as an explanatory tool, These RMRR guidelines also acknowledge likely to yield less valid and reliable study it can be used to generate hypotheses the importance of considering sampling results than those based on relatively using available retrospective data and so issues a priori as well as conducting a objective data sources,” but appropriate is a convenient guide for developing fu- power analysis in the design of a sampling incorporation of sampling weights into ture prospective studies. A recent review strategy. Unfortunately, no recommenda- one’s analysis can allow for valid popula- of articles that used the retrospective tions are available to guide the use of the tion estimates and further describe the medical record review method listed 10 sampling information at the data analysis uncertainty in the sample statistics. The best practices that ought to be followed. stage of a RMRR study. We focus on ad- importance of sampling weights has been However, an issue that is not listed is dressing this gap, demonstrating why the long recognized in other areas of medical the use of sampling weights, which are use of sample weights should be added to research, such as national survey research, important when one can only conduct the list of best practices. as recommended for the Centers for Dis- retrospective medical record review Many studies have performed sampling ease Control and Prevention’s annual Na- for a sample of the target population. from well-defined target populations for tional Health and Nutrition Examination Although that review acknowledged RMRR; many of these studies report Survey (NHANES).9 Although the goals the importance of carefully selecting a sample statistics and tests to compare of national surveys may differ from those sampling strategy for such a scenario and subgroups of the population while ignor- of RMRR, we posit that it is similarly indeed had outlined 3 commonly used ing the sampling strategy in the analy- important to account for sampling design sampling methods (convenience, simple sis.4-7 Of the commonly used sampling when analyzing RMRR data as well. random, and systematic), the authors say methods, the most obvious choice is for The basic idea is that one should already nothing of the use of sampling informa- RMRR studies to conduct a simple ran- know the appropriate weights on the basis tion at the data analysis stage. This article dom sample (SRS) to select records for of the sampling design and then apply aims to fill that gap and to demonstrate review. However, summary data are often them as weights in whatever the data why the use of sample weights ought to not presented with measures of sampling analysis might be, for example, calculating be another best practice to add to the variability to report the uncertainty in the a weighted mean for each of several strata list by reviewing well-known theoretical sample statistics. Moreover, not applying in a stratified random sample. A general details and some published data analysis the sampling weights in even a descriptive approach to constructing such weights is examples. analysis can lead to misleading findings, the well-known Horvitz-Thompson esti- especially when sampling is performed in mator,10 which has been extended to the INTRODUCTION a stratified manner or clinically relevant analysis of health survey data in cancer re- In the current era of electronic health strata exist within a population from which search.11 This article provides 2 pragmatic records and big data analytics, there is still an SRS was drawn. examples of how to account for the sam- a place for retrospective medical record This issue was explicitly acknowledged pling strategy in the analysis stage, using review (RMRR).1 RMRR is often used to in the article by Belletti et al,4 who used long-standing methods from the survey answer the “why” questions that structured RMRR to ascertain adherence to primary sampling literature,12 and demonstrates data and statistical modeling usually can- care guidelines in treatment of patients the potential consequences of report- not. RMRR can also be used to capture ill- with chronic obstructive pulmonary dis- ing sample statistics without accounting defined or nondiscrete variables, validate ease. They found that “37% [of partici- for the sampling weights. Although the structured data, and generate hypotheses pants] had documentation of some level based on qualitative data. It is also used of pulmonologist care,” and thus their to validate phenotypes and outcomes that sample statistics on guideline adherence Author Affiliations have been ascertained via International may have not accurately reflected the rates 1 Kaiser Permanente Department of Research and Evaluation, Pasadena, CA Classification of Diseases codes using in primary care settings, and so a sampling administrative databases or from natural design that somehow incorporated other Corresponding Author language processing methods.2 There are care settings (ie, specialty care visits with Ernest Shen, PhD ([email protected]) Keywords: big data analytics, electronic medical record, retrospective medical record review, sampling methods

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methods presented in this article are spe- vetted the target population and incor- sample with c = 1, and equations 1 and 3

cific to estimating population frequencies porated the known sampling weights in become redundant because poverall = p. Such and proportions, analogous methods exist descriptive analyses. a strategy would be relevant, for example, that apply to means, ratios, regression, and had the AS study only been interested in differences.11,12 CALCULATING WEIGHTS FOR A the primary care setting. STRATIFIED RANDOM SAMPLE PRAGMATIC EXAMPLES AND We demonstrate the basic principle here RESULTS THE BASIC PRINCIPLE by using the above AS example, and all Table 1 gives the raw sample propor- Example 1 calculations can be performed by hand or tions that ignore the sampling weights Our first example deals explicitly with in any spreadsheet program (we used Mi- in the AS study, where the j from the sampling weights of clinical encounters crosoft Excel, Microsoft Corp, Redmond, above equations index the 3 care settings.

for acute sinusitis (AS). RMRR was used WA), and the following notation illustrates The sampling fractions (Nj/nj) are 6.7 to assess the rates of guideline-concordant how simple it can be to incorporate sam- for Emergency Department, 390.4 for care for patients treated in 3 different pling weights. Primary Care Department, and 93.9 for care settings: Emergency Department, Urgent Care. This means, for example, Primary Care Department, and Urgent (1) that each patient selected from primary Care.13 For this study, the investigators care represents approximately 391 other used a stratified random sampling ap- (2) Primary Care patients and contributes proach by which they randomly selected approximately 4 times more weight (or, 100 medical records to review from each (3) alternatively, information) to the popula- of the 3 care settings to ascertain whether tion proportion than one seen in urgent recommended care had been delivered for (4) care. To obtain the weighted population specific “AS encounters … which resulted proportion of LOS of 7 days or less, for ex-

in antibiotics filled, the performance of Starting with equation 1, let nj denote ample, one divides the sum of the product CT [computed tomography] imaging or the sample size for population stratum j of the care-specific totals and their weights

both.” It was important to estimate the and xij be an indicator of the outcome of by the total population size: 74×(601/90)

proportions of length of symptoms (LOS) interest for person i in stratum j (eg, xij=1 if + 37×(32,400/83) + 64×(9114/97) =

in the patients presenting at the 3 care set- LOS ≤ 7 and 0 otherwise). If we let j index 20,924/42,115 = 0.49. Repeating this for

tings because that was a key variable that the different care settings, pj denotes the the other categories gives the weighted indicated a recommendation for antibiotic sample proportion of the outcome in care proportions (and 95% CIs) of LOS for

treatment (ie, LOS ≤ 7 days). The study setting j. Variances of the pj are estimated randomly selected patients with AS 3 followed best practice recommendations using equation 2, where Nj and nj are the treated in different care settings, shown in for RMRR and showed excellent interrater population and sample sizes for group j, Table 2. Comparing those proportions be- reliability (93.3% agreement) with both respectively. The 95% confidence intervals tween Tables 1 and 2 clearly illustrates that raters using the same protocol and data (CIs) can then be computed for each care the overall proportion of LOS of 7 days abstraction forms. In addition, the study setting using the normal approximation or more should be closer to the Primary team knew the sampling weights based on to the Binomial distribution given by Care Department proportion, despite the 1/2 the design and incorporated them when pj 1.96*[V(pj)] , where 1.96 is the 97.5th Emergency Department proportion being conducting descriptive analyses. percentile of a standard normal distribu- nearly double, because of the underlying ∓ tion (ie, with a mean of 0 and a variance distribution of visits across settings. Example 2 of 1), and the stratum-specific variances We see a similar story in the breast can- 14 A second example involved the as - are weighted by a ratio of Nj and nj. The cer example. In the breast cancer exam- sessment of guideline-concordant use weighted overall sample proportions and ple, sampling fractions correspond to the of imaging for staging of early-stage variances for the population strata are different sets of imaging types that defined breast cancer in patients at low risk for estimated using equations 3 and 4, respec- the strata in the sample, which were 15.6 metastasis14 as recommended by the tively. Estimates of population parameters for CT, 13.6 for positron emission tomog- American Society of Cancer Oncology.15 are accented with carets (ie, ^). raphy or bone scan, and 15.8 for multiple The authors also used stratified random Although the same formulas apply to imaging techniques. Similarly, for example, sampling, but this time the population SRS, in either case the weights are de- each medical record reviewed from the set stratum corresponded to 3 different types termined by the sampling fractions of a of records from all patients who underwent of imaging, with different numbers of properly conducted sampling scheme as CT represented approximately 16 other medical records randomly sampled from discussed elsewhere.2 Instead of sampling patients. Unlike the AS example, however, each group of imaging within each study from different population strata j = 1… c, the patient medical records sampled from site: CT only and radionuclide bone scan one simply modifies equations 1 to 4 by each imaging type are all roughly equally or positron emission tomography. As with dropping the index j. Thus, the weights weighted and informative. Following the the study above, the authors carefully are the same as for a stratified random same procedure as in equations 1 to 4

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Table 1. Raw counts and unweighted proportions (95% CIs) of LOS for randomly target population or properly account for selected patients with acute sinusitis treated in different care settings, determined underlying population strata. from medical record review, Kaiser Permanente Southern California, 2012 (N = 100 per However, a few important limitations setting) are worth stating. An important caveat is that we are working with the assump- LOS, d ED (n = 601) PC (n = 32,400) UC (n = 9114) Sample proportion (95% CI) ≤ 7 74 (0.82) 37 (0.45) 64 (0.66) 0.65 (0.59-0.71) tion that a binomial random variable (eg, 8-13 6 (0.07) 14 (0.17) 9 (0.09) 0.11 (0.07-0.14) number of patients with AS presenting ≥ 14 10 (0.11) 32 (0.38) 24 (0.25) 0.25 (0.19-0.30) with LOS ≤ 7 days) can be approximated Total 90 83 97 270 using the normal distribution, although one could circumvent this assumption by CI = confidence interval; ED = Emergency Department; LOS = length of symptoms; PC = Primary Care; UC = Urgent Care. computing exact binomial CIs. A related issue is that the stratum-specific variances depend explicitly on their proportions, and Table 2. Weighted proportions (and 95% CIs) of LOS for randomly selected patients so if one performs SRS and then tries to with acute sinusitis treated in different care settings, determined from medical record construct postsampling stratified weights review, Kaiser Permanente Southern California, 2012 (n = 100 per setting) on the basis of underlying population Weighted proportion (95% CI) strata, one must take care to use the cor- LOS, d ED PC UC Total rect variance formulas (ie, equations 2 and ≤ 7 0.82 (0.75-0.89) 0.45 (0.34-0.55) 0.66 (0.56-0.76) 0.49 (0.41-0.58) 4) to obtain an unbiased estimate of the 8-13 0.07 (0.02-0.12) 0.17 (0.09-0.25) 0.09 (0.03-0.15) 0.15 (0.09-0.226) population parameter. Lastly, the sampling ≥ 14 0.11 (0.05-0.17) 0.38 (0.28-0.49) 0.25 (0.16-0.34) 0.35 (0.27-0.446) method used may be constrained by the CI = confidence interval; ED = Emergency Department; LOS = length of symptoms; PC = available resources or assume that the cost Primary Care; UC = Urgent Care. (in time and effort) of performing medical record reviews is the same for all popula- tion strata. In the AS case, this assumption described above, the unweighted propor- analysis stage of a study. We argue that would not be true if reviewing medical tion of inappropriate imaging works out this is a necessary step in RMRR studies records for the Emergency Department to 9% vs 16% when weighted. that use some form of random sampling, setting was more complicated and required For the AS example, had the unweight- which we have highlighted with practical more time than for Primary Care Depart- ed proportions with LOS of 7 days or less examples. First, a simple method can use ment, and the costs would therefore vary. been reported and the overrepresentation estimates of population parameters along In that instance, the different costs across of Emergency Department and Urgent with measures of variability for RMRR the 3 settings could be accounted for in Care visits in the sample vs Primary Care sample data to appropriately account for the determination of sample size for each been ignored, the population propor- sampling design using sample weights. group so as to minimize the cost for a fixed tion would have been overestimated by Second, the use of sample weights can level of variability or to minimize the vari- 12 roughly 32%. Notably, the 95% CIs for the offer more valid estimates of population ability for a fixed cost. weighted and unweighted proportions of parameters and variances. Third, strati- In addition to applying sample weights patients with LOS of 7 days or less do not fied random sampling can afford certain to the analysis of RMRR data arising from overlap, providing further evidence of the efficiency advantages over SRS because a given random sampling procedure, ar- danger of ignoring the sampling design in more information can be obtained per ticles reporting results from such studies the data analysis. In the breast cancer ex- unit sampled when there are important should also report complete information ample, the unweighted sample proportion subgroups in the target population. For on the sampling frame, such as the total of all imaging performed for surveillance example, use of SRS may miss patients number of eligible participants. This in- in the cohort appears to underestimate the from clinically meaningful subgroups of formation would allow others to assess population proportion by nearly half (9% the target population, resulting in find- the degree to which biases or impreci- unweighted vs 16% weighted). In both ings that may not generalize to the target sions in sample statistics or measures of cases, assuming SRS and then reporting population as in the study by Belletti et association and lack of generalizability to 4 the unweighted sample proportions could al. However, even then one could still the target population may be attributable be misleading because of ignoring the un- use the sampling fractions in the random to sampling design. For example, exist- derlying distribution of the outcome across sample in the data analysis assuming one ing methods from the survey sampling those population strata. had such information available (eg, in literature could allow one to make such Table 1 of the AS study). In such situa- assessments, such as the standardization DISCUSSION tions, one can be easily misled by sample methods used for the NHANES9 or for 11 This work demonstrates how estab- statistics that do not appropriately ac- health surveys in general. The same could lished survey sampling methods can count for sampling design because they be done to compare the study and target be incorporated into a RMRR at the may not always reflect quantities of the populations by applying sample weights as

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Sep;65(3):517-24. DOI: https://doi.org/10.1016/j. we described or by comparing the sampled the earliest of which provided the impetus for this article. Adam Sharp, MD, MS; and Erin Hahn, PhD, jaad.2010.06.040 PMID:21632153 population to the target population as in MPH, led the studies and authored the publications 6. Stracciolini A, Casciano R, Levey Friedman H, Stein 1 study that reported all details of the from which the example data originated. Corrine CJ, Meehan WP 3rd, Micheli LJ. Pediatric sports 16 injuries: A comparison of males versus females. Am J sampling frame. Munoz-Plaza, MPH, conducted all the medical Sports Med 2014 Apr;42(4):965-72. DOI: https://doi. This study has demonstrated that rela- record reviews for both example data sources, org/10.1177/0363546514522393 PMID:24567251 tively straightforward applications of exist- and Janet Shinn, MS, extracted all relevant 7. Vreeman RC, Scanlon ML, Mwangi A, et al. A cross- sectional study of disclosure of HIV status to children ing survey sampling methods can improve structured data from the Kaiser Permanente Southern California electronic medical record and adolescents in western Kenya. PLoS One 2014 the quality of reporting for RMRR studies system. Michael Gould, MD, contributed to the Jan 27;9(1):e86616. DOI: https://doi.org/10.1371/ by providing more representative estimates journal.pone.0086616 PMID:24475159 conception and design of both example studies. 8. Worster A, Haines T. Advanced statistics: Understanding of population parameters, along with corre- All the aforementioned people also provided medical record review (MRR) studies. Acad sponding estimates of variability. Our study valuable feedback on an early draft. Finally, Emerg Med 2004 Feb;11(2):187-92. DOI: https:// also demonstrates how using such methods thanks to the editors and especially 4 anonymous doi.org/10.1111/j.1553-2712.2004.tb01433.x PMID:14759964 can help ensure that underlying population reviewers whose comments and questions led to a considerably improved article. 9. Curtin LR, Mohadjer LK, Dohrmann SM, et al. National Health and Nutrition Examination Survey: Sample subgroups that may have been overrepre- Laura King, ELS, performed a primary copy edit. sented or underrepresented in a SRS do design, 2007-2010. Vital Health Stat 2 2013 Aug;(160):1-23. PMID:25090039 not bias the parameter estimates, both in How to Cite this Article 10. Horvitz DG, Thompson DJ. A generalization of sampling one’s own study and in the evaluation of Shen E. On the use of sampling weights for without replacement from a finite universe. J Am Stat others’ studies. As discussed earlier, such retrospective medical record reviews. Perm J Assoc 1952 Apr;47(260):663-85. DOI: https://doi.org/ 2020;24:18.308. DOI: https://doi.org/10.7812/ 10.1080/01621459.1952.10483446. sampling information can even be used 11. Graubard BI, Korn EL. Analyzing health surveys for TPP/18.308 after data collection has already been com- cancer-related objectives. J Natl Cancer Inst 1999 pleted to correct for having oversampled or Jun 16;91(12):1005-16. DOI: https://doi.org/10.1093/ jnci/91.12.1005 PMID:10379963 undersampled from some population strata References 12. Scheaffer RL, Mendenhall W 3rd, Ott L. Elementary using SRS. It is especially helpful when one 1. Raghupathi W, Raghupathi V. Big data analytics in survey sampling. Pacific Grove, CA: Duxbury Press; healthcare: Promise and potential. Health Inf Sci Syst is only able to review a limited number of 1996. 2014 Feb 7;2(1):3. DOI: https://doi.org/10.1186/2047- 13. Sharp AL, Klau MH, Keschner D, et al. Low-value medical records because of resource or time 2501-2-3 PMID:25825667 care for acute sinusitis encounters: Who’s choosing limitations because one can use strategic 2. Danforth KN, Early MI, Ngan S, Kosco AE, Zheng C, wisely? Am J Manag Care 2015 Jul;21(7):479-85. Gould MK. Automated identification of patients sampling choices along with the corre- PMID:26247738 with pulmonary nodules in an integrated health 14. Hahn EE, Tang T, Lee JS, et al. Use of posttreatment sponding weights to obtain as much pos- system using administrative health plan data, imaging and biomarkers in survivors of early- sible information from a limited sample. radiology reports, and natural language processing. stage breast cancer: Inappropriate surveillance or J Thorac Oncol 2012 Aug;7(8):1257-62. DOI: necessary care? Cancer 2016 Mar 15;122(6):908- CONCLUSION https://doi.org/10.1097/JTO.0b013e31825bd9f5 16. DOI: https://doi.org/10.1002/cncr.29811 PMID:22627647 PMID:26650715 We recommend that future RMRR 3. Vassar M, Holzmann M. The retrospective chart review: 15. Schnipper LE, Smith TJ, Raghavan D, et al. American Important methodological considerations. J Educ studies apply established survey sampling Society of Clinical Oncology identifies five key Eval Health Prof 2013 Nov 30;10:12. DOI: https://doi. opportunities to improve care and reduce costs: methods in the data analysis stage to im- org/10.3352/jeehp.2013.10.12 PMID:24324853 The top five list for oncology. J Clin Oncol 2012 May prove the quality of their methods and the 4. Belletti D, Liu J, Zacker C, Wogen J. Results of the 10;30(14):1715-24. DOI: https://doi.org/10.1200/ v CAPPS: COPD—assessment of practice in primary accuracy of their results. JCO.2012.42.8375 PMID:22493340 care study. Curr Med Res Opin 2013 Aug;29(8):957- 16. Turnbull K, Nguyen LN, Jamieson MA, Palerme S. 66. DOI: https://doi.org/10.1185/03007995.2013.8039 Seasonal trends in adolescent pregnancy conception Acknowledgments 57 PMID:23663130 rates. J Pediatr Adolesc Gynecol 2011 Oct;24(5):291- The following people are acknowledged for 5. Hodgkiss-Harlow CJ, Eichenfield LF, Dohil MA. Effective 3. DOI: https://doi.org/10.1016/j.jpag.2011.04.005 their many past and ongoing collaborations on monitoring of isotretinoin safety in a pediatric PMID:21715196 such retrospective medical record review studies, dermatology population: A novel “patient symptom survey” approach. J Am Acad Dermatol 2011

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/18.308 31 ORIGINAL RESEARCH & CONTRIBUTIONS Influence of Psychosocial Factors and Parafunctional Habits in Temporomandibular Disorders: A Cross-Sectional Study

Utkarsh Yadav, MDS1,2; Junaid Ahmed, MDS1,2; Ravikiran Ongole, MDS1,2; Nandita Shenoy, MDS1,2; Nanditha Sujir, MDS1,2; Srikant Natarajan, MDS2,3 Perm J 2020;24:19.144 E-pub: 04/22/2020 https://doi.org/10.7812/TPP/19.144

ABSTRACT of anxiety, depression, and bruxism with Introduction: Temporomandibular disorders (TMDs) are abnormalities affecting the TMD symptoms and their correlation temporomandibular joint, jaw muscles, or both. An intrinsic relationship reportedly exists with age and sex. between TMDs and psychosocial factors, including stress. Parafunctional habits such as bruxism and clenching are also known to be responsible for TMDs. METHODS Objective: To determine the association of anxiety, depression, and bruxism with TMD Patients symptoms and their relationship with age and sex. This cross-sectional study was conduct- Methods: Patients included in the study reported, as their chief concern, pain lasting for ed in patients reporting to the Department more than a week in the temporomandibular joint area and/or masticatory muscles. The of Oral Medicine and Radiology, Manipal patients were divided into age groups as follows: Younger than 20 years, 21 to 30 years, College of Dental Sciences, Mangalore, 31 to 40 years, 41 to 50 years, 51 to 60 years, and above 60 years. Patients were examined India. Ethical clearance was obtained clinically and were asked to complete an anamnestic questionnaire (modified version of from the institutional ethical committee Helkimo Anamnestic Index) and the Hospital Anxiety and Depression Scale (HADS). (MCODSMLR/2017.1414). Results: Seventy-five patients (55 women, 20 men) were included in the study. The Patients with pain lasting for 1 week or prevalence of TMDs was higher in female patients, of whom 33 (60%) had moderate to more in the TMJ region and/or the masti- severe TMDs. Of the 20 male patients, 12 (60%) had signs and symptoms of moderate TMDs. catory muscle and absence of any systemic Anxiety and depression scores were higher in female patients. No significant correlation conditions were included in the study. The was found between degree of malocclusion and TMDs. exclusion criteria were as follows: Discussion: We found correlations between the degree of TMD with age, sex, parafunc- 1. History of trauma or congenital abnor- tional habits, and psychosocial factors. Symptoms of TMD seemed to increase in patients malities to the TMJ with parafunctional habits, from younger to older age groups, and with increased anxiety 2. Odontogenic infections or any other and depression scores. pathologic swellings in relation to the Conclusion: The degree of TMDs is higher in women, and TMDs are associated with TMJ higher anxiety and depression scores. Correlation between these factors paves the way for 3. Metastatic tumors, cysts, or carcinomas preventive actions aimed at those with moderate and severe signs of TMDs. of the oral cavity affecting the TMJ 4. Regular intake of medicines such as INTRODUCTION in women than in men, TMDs are most analgesics or antianxiety drugs. Temporomandibular disorders (TMDs) prevalent in the 20- to 40-year age group With a 95% confidence level and 80% are a group of abnormalities affecting the and are least common in children and power, the sample size was estimated to temporomandibular joint (TMJ), jaw mus- elderly individuals. be 75.a cles, or both. Pain, malocclusion, deviated Various studies have provided an irre- mouth opening, limited jaw function, and futable evidence of a significantly appre- Procedures headache are some of the most commonly ciable relationship between bruxism and The study participants were asked to fill noticed signs and symptoms of TMDs. A TMDs.6-8 A clear and decisive relationship out an anamnestic questionnaire contain- multifactorial etiology of pain and dys- was found between TMDs and bruxism in ing 10 questions (a modified version of function resulting from biopsychosocial a case-control study conducted by Molina factors has been proposed.1-3 Alteration et al.6 In a study done by Michelotti et al,7 of form can cause changes in the sto- a habit such as sustained contact between matognathic system, eventually leading the teeth was seen to be an important Author Affiliations 1 Department of Oral Medicine & Radiology, Manipal College of Dental to malocclusion, which is recognized risk factor in triggering myofascial pain. 8 Sciences, Mangalore, Manipal Academy of Higher Education (MAHE), as one of the primary causes of TMDs. Kanehira et al concluded that stress is an Manipal Karnataka, India Several authors have studied the different important factor and is intimately con- 2 Manipal Academy of Higher Education (MAHE), Karnataka, India types of malocclusion, including posterior nected with parafunctional habits such 3 Department of Oral Pathology, Manipal College of Dental Sciences, crossbite, anterior open bite, and horizon- as bruxism during sleep and daytime Mangalore, India tal and vertical overlap. The authors have clenching. Considering the complexity Corresponding Author concluded that these changes can cause of TMDs involving psychosocial factors Junaid Ahmed, MDS ([email protected]) various degrees of TMD symptoms.4,5 Ap- and parafunctional habits, our study was proximately 1.5 to 2 times more common undertaken to determine the association Keywords: Hospital Anxiety and Depression Scale, parafunctional habits, psychosocial factors, temporomandibular disorder

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the Helkimo Anamnestic Index) consist- Two investigators participated in the RESULTS ing of TMD symptom-related questions study. The first investigator (UY) performed A total of 75 patients who reported (see Sidebar: Anamnestic Questionnaire), the clinical examination of patients and with a chief complaint of pain in the which was validated by a professor in the evaluation of the modified anamnestic TMJ region were included in the study; Department of Community Medicine, questionnaires, and the second investigator 55 patients (80%) were women and 20 Kasturba Medical College, Mangalore. ( JA) evaluated anxiety and depression using (20%) were men. Of these 75 patients, 63 The participants were later asked to com- the HADS questionnaire in the Depart- (84%) had Angle class 1 malocclusion and plete the Hospital Anxiety and Depression ment of Psychiatry, KMC Hospital, At- the remaining 12 (16%) had Angle class 2 Scale (HADS) questionnaire (developed tavar, Mangalore. Both investigators were malocclusion (Table 1). 9 by Zigmond and Snaith in 1983), consist- unaware of each other’s findings. The patients were divided into 6 groups ing of 14 questions, equally distributed for Data Analysis by age as follows: 1) 20 years and younger, anxiety and depression. 2) 21 to 30 years, 3) 31 to 40 years, 4) 41 The patients were then examined clini- Association of the role of bruxism with to 50 years, 5) 51 to 60 years, and 6) more cally and the findings, especially the hard- the severity of TMD cases was performed than 60 years. χ2 tissue findings (for parafunctional habits), using test. According to the DC/TMD criteria,10 were recorded in a case history pro forma. Simple linear regression analysis to patients were categorized into these 4 Palpation of the muscles of mastication predict the TMD score with the variables subgroups: was done using the 2014 Diagnostic Cri- of age, sex, bruxism, anxiety and depres- 1. Mild TMD: Mild myofascial pain, re- teria for Temporomandibular Disorders sion was conducted to derive the equation. curring in nature 10 (DC/TMD), followed by a thorough 2. Moderate TMD: An intra-articular examination of the TMJ. mechanical disturbance that interfered with a joint’s smooth action 3. Severe TMD: Signs and symptoms of arthralgia and arthritis (clinically Table 1. Distribution of participants with temporomandibular disorder (TMD) by age, evident joint pain with inflammation sex, Malocclusion, bruxism, and anxiety and depression scores or swelling) TMD free, Mild TMD, Moderate TMD, Severe TMD, Chi square 4. TMD free: Only occasional pain with Variable no. (%) no. (%) no. (%) no. (%) value p valuea a duration of less than 1 year. Age, y Bruxism was most prevalent among ≤ 20 1 (33.3) 4 (14.8) 8 (23.5) 1 (9.1) 16.3 0.365 women aged 21 to 30 years and 31 to 21-30 1 (33.3) 15 (55.6) 13 (38.2) 2 (18.2) 40 years (Table 1). Of 11 patients who 31-40 0 (0) 4 (14.8) 6 (17.6) 2 (18.2) had a diagnosis of severe TMD, 10 had 41-50 0 (0) 1 (3.7) 3 (8.8) 3 (27.3) bruxism, a significant finding (p = 0.001; 51-60 1 (33.3) 1 (3.7) 4 (11.8) 2 (18.2) Table 1). Our study findings revealed that > 60 0 (0) 2 (7.4) 0 (0) 1 (9.1) the degree of TMDs increased from the Sex youngest group to the oldest group and Female 2 (66.7) 21 (77.8) 22 (64.7) 10 (90.9) 3.3 0.338 was significant (p = 0.04; Table 2). Male 1 (33.3) 6 (22.2) 12 (35.3) 1 (9.1) In the present study, female participants Occlusion had an increased degree of TMDs com- Class 1 2 (66.7) 23 (85.2) 29 (85.3) 11 (100) 2.8 0.417 pared with male participants (Table 1). Class 2 1 (33.3) 4 (14.8) 5 (14.7) 0 (0) Results for the anxiety and depression Bruxism score revealed higher scores among the 21- Absent 0 (0) 19 (70.4) 12 (35.3) 1 (9.1) 16.5 0.001 to 30-year age group vs other age groups Present 3 (100) 8 (29.6) 22 (64.7) 10 (90.9) and an increased rate of prevalence among female patients compared with male pa- Anxiety score tients (Table 1). Normal 2 (66.7) 17 (63) 13 (38.2) 3 (27.3) 9.9 0.354 In our study, patients with TMDs Mild 0 (0) 2 (7.4) 11 (32.4) 4 (36.4) showed moderate depression scores, nota- Moderate 1 (33.3) 7 (25.9) 9 (26.5) 3 (27.3) bly seen among women in the age group of Severe 0 (0) 1 (3.7) 1 (2.9) 1 (9.1) 31 to 40 years. In the severe TMD group, Depression score 12 patients had raised HADS scores and Normal 1 (33.3) 21 (77.8) 22 (64.7) 7 (63.6) 8.2 0.221 10 had normal HADS scores, which was Mild 2 (66.7) 5 (18.5) 11 (32.4) 2 (18.2) a clinically significant finding but not sta- Moderate 0 (0) 1 (3.7) 1 (2.9) 2 (18.2) tistically significant (Figure 1). Severe 0 (0) 0 (0) 0 (0) 0 (0) Linear regression analysis was con- a Boldface indicates significant. ducted to derive a formula to calculate the TMD score as follows:

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Table 2. Correlation of degree of temporomandibular disorder (TMDs) with age, sex, concluded that TMD primarily affects bruxism, anxiety, and depression women, because more than 84% of those 16 Unstandardized 95% Confidence affected were women. Bonjardim et al coefficientsa Standardized interval for B conducted a study in 217 patients and B Standard coefficients,a Lower Upper found that women were more commonly Model 1 error β t p valueb bound bound affected by TMDs. In the present study, we (Constant) 7.482 1.869 4.003 <0.001 3.754 11.211 found that 73.3% of patients having signs Age 0.747 0.357 0.256 2.093 0.040 0.035 1.459 and symptoms of TMDs were women. Ac- 17 Sex -0.608 1.039 -0.067 -0.585 0.561 -2.680 1.465 cording to a study by Syed et al in 2012, Bruxism 2.335 0.927 0.286 2.519 0.014 0.486 4.184 women were seen to have higher degree Anxiety 0.086 0.144 0.081 0.595 0.554 -0.202 0.373 of TMDs, attributed to higher anxiety Depression -0.116 0.172 -0.094 -0.672 0.504 -0.460 0.228 and depression scores with the habit of bruxism. The authors state that because a Dependent variable: TMD Score = 7.482 + 0.747 (Age) - 0.608 (Sex [male 2, female 1]) + 2.335 (Bruxism 1, 0) + 0.086 (Anxiety) - 0.116 (Depression) bruxism results in overuse of masticatory b Boldface indicates significant. muscles, it can eventually lead to a higher possibility of developing TMDs.17 In the our study, with an increase in anxiety score, TMD score = 7.482 + 0.747(Age) - clinical criteria used among various stud- it was noticed that the degree of TMDs 0.608{Sex [Female(1)] [Male(2)} + 2.335 ies, there appears to be an irregularity in also increased. {Bruxism [Absent(1)], Present(0)} + the literature regarding the prevalence of The results of our study reinforce the 0.086(Anxiety) - 0.116(Depression) clinical signs and symptoms. Studies have assumption that there is an association where the score for male sex = 2 and for suggested that between 1% and 75% of between TMD and bruxism. Although the female sex = 1, and the score for having the population showed at least 1 objec- association between psychological factors bruxism = 0, and no bruxism = 1. tive TMD sign, and 5% to 33% reported and TMD is inconsistent in the literature, subjective symptoms.12 there is biological plausibility for this as- DISCUSSION sociation in our study. A peak incidence for TMD symptoms 18 TMDs are distinctively identified as was recorded between age 20 and 40 years, Bonjardim et al conducted a study a triad of clinically apparent signs and with a lower incidence seen in younger or in 196 young adults in which 101 were symptoms that include muscle and/or elderly patients.13 Graff-Radford et al,14 women and 95 were men. They noted that TMJ pain, TMJ sounds, and restriction in a 1989 study, found that patients had participants who had moderate or severe TMD exhibited class 1 malocclusion, and deviation of the mouth in its open- TMDs prevalent at ages 21 to 30 years 18 ing path.11 followed by above 50 years. In the present which was seen to be nonsignificant. The prevalence of TMD is debatable, study, among 75 patients aged between 0 Similar findings were observed in our owing to the lack of uniformity in the and 70 years, it was noted that 80% of the study, wherein the patients with class diagnostic criteria adapted by various in- patients had TMDs, and most of these 1 malocclusion had moderate to severe vestigators. Evidence toward an increasing patients were in the 21- to 30-year group TMD symptoms but the results were nonsignificant. prevalence of TMD signs and symptoms followed by 20 years of age or younger. 19 in the general population has been noted Esposito et al15 reviewed records of 425 Wieckiewicz et al conducted a study in in several studies. Because of the dissimilar consecutive patients having TMDs. They 456 Polish university students to assess the

Anxiety score Depression score 100% 100% 90% 0% 0% 0% 60% 60% 50% 40% 40% 30% 20% 20% 0% 10% TD REE ILD TD ODERTE TD SEERE TD 0% TD REE ILD TD ODERTE TD SEERE TD NORL ILD ODERTE SEERE

NORL ILD ODERTE SEERE

Figure 1. Correlation of degree of temporomandibular disorders with anxiety and depression score.

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occurrence of TMDs and parafunctional habit of bruxism among patients with in women, increases with the increase in habits and their correlation with psycho- such parafunctional habits and the start anxiety and depression scores. The existing logical and emotional factors. Symptoms of relaxation therapy. It is important to correlation between these factors paves the of TMDs were noticed in 246 students. A explain to the patient the background of way for preventive actions aimed at those total of 164 female students were found to the disorders, especially the role of one’s with moderate and severe signs of TMD. have TMDs, anxiety, and depression. The emotional stress, and to prescribe coun- An interdisciplinary approach should be authors observed a significant correlation seling and behavioral therapy to reduce created for this population to reduce para- 20 v between TMD and psychological prob- anxiety. functional habits and TMDs. a 2 2 lems. The incidence of TMD symptoms As explained in the Results section, we Using the formula n = Zα p q/E , where Zα = 95% was seen to be higher in women, and emo- performed linear regression analysis to confidence level, p = Proportion from reference, q = 100 – p, and E = 20/100 × p. tional issues appeared to be an important derive a formula to calculate the TMD predisposing factor for the occurrence of score using the variables age, sex, brux- 19 Disclosure Statement muscular disorders. ism, anxiety, and depression. Association The author(s) have no conflicts of interest to In our study, we found that 73.3% of of the prediction of the TMD score with disclose. patients with TMD diagnosis were female. the variables showed a significant asso- Bruxism was more common in female pa- ciation with age (p = 0.040) and bruxism Acknowledgments tients than in male patients. Hence, female (p = 0.014) with anxiety and depression Kathleen Louden, ELS, of Louden Health patients appeared to have higher chances .However sex did not appear to play a Communications performed a primary copy edit. of TMDs compared with male patients. significant role. In a study by Montero- Anxiety and depression scores were seen Martín et al,21 clinical variables of pain References to be higher in women with signs and duration and pain interference with ac- 1. LeResche L. Epidemiology of temporomandibular disorders: Implications for the investigation symptoms of TMDs. Hence, the degree tivities of daily living, as well as the bio- of etiologic factors. Crit Rev Oral Biol Med of TMDs appeared to be higher in female psychosocial variables of depression and 1997;8(3):291-305. DOI: https://doi.org/10.1177/1045 patients with a bruxism habit and high jaw disability were used to calculate the 4411970080030401 PMID:9260045 2. Weinberg LA. Temporomandibular dysfunctional anxiety and depression scores. TMD score. All the variables they used to profile: A patient-oriented approach. J Prosthet In our study we found a correlation calculate the TMD score were significant Dent 1974 Sep;32(3):312-25. DOI: https://doi. between the degree of TMD with age, in their regression model. org/10.1016/0022-3913(74)90036-5 PMID:4530847 3. Oral K, Bal Küçük B, Ebeoğlu B, Dinçer S. Etiology sex, bruxism, anxiety, and depression. The of temporomandibular disorder pain. Agri 2009 degree of TMD increases from younger CONCLUSION Jul;21(3):89-94. PMID:19779999 to older age groups and is significant. The present study revealed that the 4. Bonjardim LR, Lopes-Filho RJ, Amado G, Albuquerque RL Jr, Goncalves SR. Association Additionally, women have increased in- degree of TMDs is higher in the female between symptoms of temporomandibular tensity of TMDs, and the degree of TMD population and increases from younger to disorders and gender, morphological occlusion, and psychological factors in a group of significantly increases in patients with the older age groups. The correlation between university students. Indian J Dent Res 2009 Apr- habit of bruxism. Finally, patients having malocclusion and degree of TMD is not Jun;20(2):190-4. DOI: https://doi.org/10.4103/0970- increased anxiety and depression scores significant, but the parafunctional habit of 9290.52901 PMID:19553721 5. Valle-Corotti K, Pinzan A, do Valle CV, Nahás AC, appear to be more susceptible to an in- bruxism is significantly associated with a Corotti MV. Assessment of temporomandibular creased degree of TMD. higher degree of TMD symptoms. Anxiety disorder and occlusion in treated class III The most important stage of a treatment and depression scores are higher in wom- malocclusion patients. J Appl Oral Sci 2007 Apr;15(2):110-4. DOI: https://doi.org/10.1590/S1678- protocol in TMD is education about the en, and the degree of TMDs, especially 77572007000200007 PMID:19089112 6. Molina OF, dos Santos J Jr, Nelson SJ, Grossman E. Prevalence of modalities of headaches and bruxism among patients with craniomandibular disorder. 1 Cranio 1997 Oct;15(4):314-25. DOI: https://doi.org/10 Anamnestic Questionnaire .1080/08869634.1997.11746026 PMID:9481994 7. Michelotti A, Cioffi I, Festa P, Scala G, Farella Q1) Do you have difficulty in opening your mouth? Yes/no M. Oral parafunctions as risk factors for Q2) Do you have difficulty in moving or using your jaw? Yes/no diagnostic TMD subgroups. J Oral Rehabil 2010 Mar;37(3):157-62. DOI: https://doi.org/10.1111/j.1365- Q3) Do you have tenderness or muscular pain when chewing? Yes/no 2842.2009.02033.x PMID:20002533 Q4) Do you have frequent headaches? Yes/no 8. Kanehira H, Agariguchi A, Kato H, Yoshimine Q5) Do you have neck aches or shoulder pain? Yes/no S, Inoue H. Association between stress and temporomandibular disorder. Nippon Hotetsu Shika Q6) Do you have pain in or about the ears? Yes/no Gakkai Zasshi 2008 Jul;52(3):375-80. DOI: https:// Q7) Are you aware of noises in the jaw joints? Yes/no doi.org/10.2186/jjps.52.375 PMID:18678971 Q8) Do you consider your bite “normal”? Yes/no 9. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand Q9) Do you use only one side of your mouth when chewing? Yes/no 1983 Jun;67(6):361-70. DOI: https://doi. Q10) Do you have morning facial pain? Yes/no org/10.1111/j.1600-0447.1983.tb09716.x PMID:6880820 10. Schiffman E, Ohrbach R, Truelove E, et al; References International RDC/TMD Consortium Network, 1. Conti A, Freitas M, Conti P, Henriques J, Janson G. Relationship between signs and symptoms of temporomandibular International Association for Dental Research, disorders and orthodontic treatment: A cross-sectional study. Angle Orthod 2003 Aug;73(4):411–417. DOI: https://10.1043/0003-3219(2003)073<0411:RBSASO>2.0.CO;2 PMID:12940562

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Orofacial Pain Special Interest Group, International 23. DOI: https://doi.org/10.3109/00016357.2011.6348 between symptoms of temporomandibular Association for the Study of Pain. Diagnostic criteria 32 PMID:22126531 disorders and gender, morphological occlusion, for temporomandibular disorders (DC/TMD) for 14. Graff-Radford SB, Reeves JL, Baker RL, Chiu and psychological factors in a group of clinical and research applications: Recommendations D. Effects of transcutaneous electrical nerve university students. Indian J Dent Res 2009 Apr- of the International RDC/TMD Consortium Network* stimulation on myofascial pain and trigger point Jun;20(2):190-4. DOI: https://doi.org/10.4103/0970- and Orofacial Pain Special Interest Group†. J Oral sensitivity. Pain 1989 Apr;37(1):1-5. DOI: https://doi. 9290.52901 PMID:19553721 Facial Pain Headache 2014 Winter;28(1):6-27. DOI: org/10.1016/0304-3959(89)90146-2 PMID:2786179 19. Wieckiewicz M, Grychowska N, Wojciechowski K, https://doi.org/10.11607/jop.1151 PMID:24482784 15. Esposito CJ, Panucci PJ, Farman AG. Associations et al. Prevalence and correlation between TMD 11. Fricton JR, Schiffmann EL. Epidemiology of in 425 patients having temporomandibular based on RDC/TMD diagnoses, oral parafunctions temporomandibular disorders. In: Fricton JR, Dubner disorders. J Ky Med Assoc 2000 May;98(5):213-5. and psychoemotional stress in Polish university R, editors. Orofacial pain and temporomandibular PMID:10835837 students. Biomed Res Int 2014;2014:472346. DOI: disorders. New York, NY: Raven; 1995. p 295-303 16. Bonjardim LR, Garião MB, Pereira LJ, Castelo https://doi.org/10.1155/2014/472346 PMID:25121100 12. De Kanter RJ, Truin GJ, Burgersdijk RC, et al. PM. Anxiety and depression in adolescence and 20. Freesmeyer WB, Fussnegger MR, Ahlers MO. Prevalence in the Dutch adult population and their relationship with signs and symptoms of Diagnostic and therapeutic-restorative procedures a meta-analysis of signs and symptoms of temporomandibular disorders. Int J Prosthodont 2005 for masticatory dysfunctions. GMS Curr Top temporomandibular disorder. J Dent Res 1993 Jul-Aug;18(4):347-52. PMID:16052791 Otorhinolaryngol Head Neck Surg 2005;4:Doc19. Nov;72(11):1509-18. DOI: https://doi.org/10.1177/002 17. Syed RA, Syeda AR, Katti G, Arora V. Prevalence PMID:22073067 20345930720110901 PMID:8227702 of temporomandibular joint disorders in outpatients 21. Montero-Martín J, Bravo-Pérez M, Albaladejo- 13. Anastassaki Köhler A, Hugoson A, Magnusson at Al-Badar Dental College and Hospital and Martínez A, Hernández-Martín LA, Rosel-Gallardo T. Prevalence of symptoms indicative of its relationship to age, gender, occlusion and EM. Validation the Oral Health Impact Profile (OHIP- temporomandibular disorders in adults: Cross- psychological factors. J Indian Acad Oral Med Radiol 14sp) for adults in Spain. Med Oral Patol Oral Cir sectional epidemiological investigations covering two 2012 Oct-Dec;24(4):261-8. Bucal 2009 Jan 1;14(1):E44-50. PMID:19114956 decades. Acta Odontol Scand 2012 May;70(3):213- 18. Bonjardim LR, Lopes-Filho RJ, Amado G, Albuquerque RL Jr, Gonçalves SR. Association

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Jose Yakushi, MD1; Mose Wintner, PhD2; Naomi Yau2; Lina Borgo, MPH2; Edwin Solorzano, MD1 Perm J 2020;24:19.177 E-pub: 04/29/2020 https://doi.org/10.7812/TPP/19.177

ABSTRACT KP’s secure messaging system was implemented in 2005, first Introduction: Secure messaging is a platform for email com- beginning with the KP Hawaii Region. Secure messaging is fa- munication between patients and their physicians. Although cilitated through KP’s member portal (https://kp.org), which is patient-generated emails are associated with increased use of integrated with KP’s electronic health record, HealthConnect. clinical services, greater member retention, and improved quality HealthConnect represents KP’s implementation of the Epic of care, secure messaging has a marked impact on primary care suite of software (Epic Systems Corp, Verona, WI). To access physicians’ workload. the member portal, patients are required to register for a kp.org Objective: To understand how the email topic and volume account and be authenticated users.8 In the first quarter of 2017, vary by demographics and clinical factors among members of a more than 67% KP Southern California (KPSC) members were managed care organization. registered on the member portal, an 8.3% growth from the prior Methods: We analyzed all secure messages sent to primary care year. In the fourth quarter of that same year, 23.1% of all portal- departments by adult members of Kaiser Permanente Southern registered members in KPSC sent 1 or more secure email mes- California (KPSC) in 2017. sages to their physicians; an average of 1272 emails were sent per Results: Members with a higher volume of office visits and tele- 1000 registered members in a year. When the 3.6% membership phone appointment visits generated a higher volume of emails to increase from the previous year is factored in, 2017 saw an 11% primary care physician. Members with a Centers of Medicare and increase in secure messages from 2016, with a total of 5,807,833 Medicaid Services Hierarchical Condition Category diagnosis his- secure messages sent.8 Secure messaging is now a common form tory sent 3 times as many emails as those without such a diagnosis of physician-patient interaction through which care is provided history. Women accounted for nearly two-thirds of emails despite and common concerns are addressed by the care team. making up only half of the KPSC member population. Less than This study analyzed all adult-generated secure messages in the one-fourth (21.4%) of members sent 2.3 million total emails to KPSC Region. The purpose of this study was to better under- their physician. Medical advice was the most common reason for stand the usage of secure messaging between KPSC members sending secure messages (24.7%) in a sample studied (n = 2397). and primary care departments. This was accomplished by 1) Discussion: These findings confirm the need for additional comparing the use of secure messaging against the utilization of research to more accurately quantify the additional burden from office visits and telephone appointment visits (TAVs) in primary secure message utilization on primary care physicians. Knowing care, 2) examining the demographic characteristics of patients the factors associated with secure messaging usage and message who use KP’s secure messaging platform, and 3) investigating content could assist in building more efficient staffing models and the content of secure messages that KP members sent to their creating more efficient routing that matches the message content primary care physicians (PCPs). with a physician’s scope of practice. METHODS INTRODUCTION Study Design and Population Secure messaging is a protected electronic communication After obtaining KP institutional review board approval, we service between patients and physicians. Known for its ability to conducted a retrospective study analyzing patient demographic foster physician-patient relationships, secure email has become a data (eg, age, sex), clinical factors (eg, Health Plan type, time ubiquitous communication tool in health care settings.1 Studies between a sent message and nearest completed office visit), and have shown that patient satisfaction has generally increased since primary care utilization data (eg, encounter volume). adopting secure messaging in family medicine, with satisfaction All data examined in this study pertain to the utilization of scores higher on questions related to “ease of communicating with primary care services in Southern California, by adult KPSC the physician” and “understanding of diagnosis/treatment plan”.2 members from January 2017 to December 2017. Primary care Some organizations initially adopted secure messaging as a way included both family medicine and internal medicine specialties. to address low-acuity medical issues, assuming this might reduce unnecessary telephone or in-person office visits.3,4 Others have targeted young and healthy patients in an early attempt to increase use of secure messaging, assuming the millennial population is Author Affiliations 2,5 more likely to use this virtual service than the older population. 1 Department of Family Medicine, Downey Medical Center, CA The rapid adoption of secure messaging has furthered the focus 2 Department of Health Innovation, Southern California Permanente Medical Group, Tustin, CA on and improved the quality of patient-centered care6,7, a pillar of Kaiser Permanente’s (KP) care delivery system.8 Corresponding Author Jose Yakushi, MD ([email protected])

Keywords: family medicine, patient-generated emails, primary care email topics, physician-patient communication, physician-patient relationship, secure messaging

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Data from the Pediatrics and Obstetrics/Gynecology Depart- instances of the following primary care services for each individual 3. Secure messages (n = 2,316,309) from adult KPSC members RESULTS ments were not included in this study. who held a KPSC membership in 2017 (4.7 million KP members): to primary care departments in 2017 that were not replies Utilization of Primary Care Services At KP, members seeking care for primary care services have 1. Office visits in 2017 (n = 4,898,596) to primary care depart- to a previous message (ie, initiations of message threads by Main Drivers for Secure Message Utilization several options. For the purposes of this study, we focused on 3 ments by adult KPSC members members, not by physicians). As shown in Figure 1, the number of completed primary care main primary care services: Office visits, TAVs, and secure mes- 2. Telephone appointment visits (n = 1,185,590) with primary Furthermore, we performed random sampling of secure mes- office visits by a member was most strongly associated with a saging. To quantify the utilization of these modalities, we counted care departments by adult KPSC members in 2017 sages (n = 2397 of total 2,316,309) for email topic analysis. member sending a greater number of secure messages to the In this study, patients with a chronic condition were defined primary care department. The number of TAVs was the second Table 1. Primary topic categories as having a Centers for Medicare and Medicaid Services (CMS) strongest factor. Other factors associated with a member sending Category Description Example Hierarchical Condition Category (HCC) diagnosis history (used more secure messages included being a Medicare member, being 10 Medical advice Physical or mental health problem or concern not coded “My right shoulder has been extremely sore for more than a month. I can’t lift in the CMS risk-adjustment model ) listed in their medical re- a woman, and having a prior CMS HCC diagnosis. Because this as a medication issue or test issue my right arm up and to the side without great pain. This has been over a month cord. The CMS HCC was originally designed to estimate future regression looks at each variable independently, this study’s find- and is getting worse.” health care costs for patients and is now often used to commu- ings show that having an office visit was more indicative of send- New or change in Request for a new medication or a change of current “My current medication isn’t working for me anymore but my sister-in-law nicate patient complexity. ing a secure message than being a Medicare member or having a medication request medication recommended [medication name]. Can you prescribe me that?” Of the 2.3 million email messages sent in 2017, we analyzed chronic disease. Conversely, being a KP-Medicaid member and Medication renewal Request for refill or renewal of a medication or medical “Please renew my prescription to oxycodone HCL 5 mg tab. Please have the content and corresponding metadata of 2397 messages. Our self-identifying as black and/or Hispanic were factors associated or refill supply pharmacy mail [it] to me.” researchers tagged each email message with up to 3 primary with fewer secure messages sent. Medication issue/ Medication or supply issue that is not a refill/renew “I’m sending a list of vitamins and supplements I take. Please have the doctor message topic tags, using a detailed description of each message Average counts of office visit utilizations were similar between question request or a problem with receiving the medication in make sure they are okay to take and don’t counteract what I take for my topic. The detailed description and table were modified from the racial groups, but propensities for secure messaging varied widely mail (eg, questions about dose or side effects) Parkinson’s [disease].” 11 Veterans Affairs study by Shimada et al. Table 1 depicts the (Table 2). Though there was only a small difference between aver- Imaging request Request for imaging/test “I’ve been having terrible headaches and I want a CT scan to see what the various email topics. age numbers of office visits between black, Hispanic, and white problem is.” members, members who self-identified as black and/or Hispanic Imaging issue/ Patient questions about imaging, choosing among “Am I allowed to eat before my MRI tomorrow?” Statistical Analysis question imaging options, why a particular imaging procedure is important, preparing for a scan/imaging procedure We performed a negative binomial regression to assess the Table 2. Average encounter volume of utilization per patient number of messages sent by a patient. Independent variables Imaging result Request for or discussion of imaging results “Hello, I got the ultrasound [scan result] last week and I want to know what are by self-reported race/ethnicity included primary care utilization counts; geographic area of the next steps to take?” Telephone Lab/test request Request for lab test “I need some bloodwork done.” the patient’s medical center; and patient’s age, sex, number of Race/ethnicity No. of Office appointment Secure chronic illnesses, race/ethnicity, and Health Plan product type. Lab/test issue/ Patient questions about testing, choosing among testing “Did you want me to get lab work done before I see you?” members visits visits messages question options, why a test is important, preparing for a test The reference patient we compared all variables to was white, White 1,779,631 0.984 0.265 0.748 Lab/test results Request for or discussion of test results “Thanks for sending me the test results. I still have a question for the doctor male, age 52 years (median age in our dataset), had no chronic Native American/ 19,334 0.957 0.271 0.562 about the numbers that you gave me.” illnesses, and had a KP Health Plan in his home Region. This Inuit/Aleutian Surgery or Patient questions about a surgery or procedure “Good morning. I am still having a lot a lot of pain in my knees. The injections regression accounts for each variable independent of one an- Asian/Pacific 521,774 0.942 0.215 0.522 procedure issue/ did not seem to help. But I heard the second time around it usually helps a lot other. For example, although being a Medicare member and Islander question more. So, I was wondering if I can get another injection in my knees??” age may be related, this regression represents them as 2 separate Black/African 412,163 0.958 0.291 0.434 FYI informing Patient sharing information with no additional discussion “Just to keep you posted. EKG done yesterday. Bloodwork and urine done variables, independent of one another. Transformed versions of American that does not fit other category (eg, inform about non-VA this AM.” office visit counts and TAV counts were used in the regression, Other 75,775 0.795 0.196 0.417 care or test result) namely log(variable + 1). Hispanic/Latino 1,525,834 0.906 0.223 0.289 Scheduling Schedule an appointment, test, or procedure “I would like to set up an appointment for a physical.” Declined to state 489,833 0.392 0.094 0.189 Referral Request referral to a specialist “I would like to be referred to MOVE! to help me with some weight loss. I also need you to set up an appointment for [examination of] my knees and lower Black/ Chronic Office back. I’m having a great deal of pain in both, been injured in the past. Thank you.” Hispanic/ African Medicaid/ disease Member TAV visit Table 3. Average utilization counts per patient Latino American Medical count Women Medicare count* count* Note request Request doctor’s note “I’m supposed to go on vacation this week but I’m too sick to fly. Can you write Telephone

me a note for my travel insurance?” 0.6 Parameter Office appointment Secure Administrative Administrative issues other than appointment “I didn’t receive my medication in the mail.” visits visits (TAVs) messages 0.4 scheduling Members with at least 1 office 2.15 0.47 0.93 Life issue Any contextual issues that are not strictly biomedical “We’re having lots of changes with my mom. Hospice people are coming here 0.2 visita and are about the patient’s life context but now they’re talking about putting her in a nursing home. They say they can 0 Members with at least 1 TAVa 2.46 1.63 1.46 help her all the time.” -0.2 Members who sent at least 1 2.17 0.61 2.92 Clinical Factors Callback request Simple callback request “Please call me at xxx-xxx-xxxx when you get the chance.” secure messagea -0.4 Thanks Expressing appreciation “I do want to take a minute to thank you for your help. It is a different world Members with 0 office visitsb — 0.08 0.14 -0.6 going through a pain-free day. You have been kind and caring and I do really Members with 0 TAVsb 1.04 — 0.42 appreciate it!!!” -0.8 Members who sent 0 secure 1.09 0.24 — Complaint Complaining about care, services, KP, etc “First and foremost … and I would think you would be aware of this by now, -1 messagesb [patient first name] is NOT my Dad … he’s my husband.” Coefficient a Average counts of utilizations per patient compared against having at least 1 office Other Content not captured by the above categories “Both of my glucose] meters are reading E-9 when trying to get a reading. I Figure 1. Effect of clinical factors on secure messaging. Coefficients indicate visit, having 1 telephone appointment visit (TAV), or sending 1 secure message, think it’s the battery, but I don’t know how to fix it. Tell me how or what to do.” association of each factor on the reference patient (see text). respectively. b Average counts of utilizations per patient compared against having 0 office visits, 0 AM = morning; CT = computed tomography; EKG = electrocardiogram (ECG); FYI = for your information; HCL = hydrochloride; KP = Kaiser Permanente; lab = laboratory; a indicates regression coefficients of greatest magnitude. TAVs or sending 0 secure messages, respectively. MOVE! = Veterans Affair’s National Weight Management Program; MRI = magnetic resonance imaging; tab = tablet; VA = Veterans Affairs. TAV = telephone appointment visit.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 38 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Data from the Pediatrics and Obstetrics/Gynecology Depart- instances of the following primary care services for each individual 3. Secure messages (n = 2,316,309) from adult KPSC members RESULTS ments were not included in this study. who held a KPSC membership in 2017 (4.7 million KP members): to primary care departments in 2017 that were not replies Utilization of Primary Care Services At KP, members seeking care for primary care services have 1. Office visits in 2017 (n = 4,898,596) to primary care depart- to a previous message (ie, initiations of message threads by Main Drivers for Secure Message Utilization several options. For the purposes of this study, we focused on 3 ments by adult KPSC members members, not by physicians). As shown in Figure 1, the number of completed primary care main primary care services: Office visits, TAVs, and secure mes- 2. Telephone appointment visits (n = 1,185,590) with primary Furthermore, we performed random sampling of secure mes- office visits by a member was most strongly associated with a saging. To quantify the utilization of these modalities, we counted care departments by adult KPSC members in 2017 sages (n = 2397 of total 2,316,309) for email topic analysis. member sending a greater number of secure messages to the In this study, patients with a chronic condition were defined primary care department. The number of TAVs was the second Table 1. Primary topic categories as having a Centers for Medicare and Medicaid Services (CMS) strongest factor. Other factors associated with a member sending Category Description Example Hierarchical Condition Category (HCC) diagnosis history (used more secure messages included being a Medicare member, being 10 Medical advice Physical or mental health problem or concern not coded “My right shoulder has been extremely sore for more than a month. I can’t lift in the CMS risk-adjustment model ) listed in their medical re- a woman, and having a prior CMS HCC diagnosis. Because this as a medication issue or test issue my right arm up and to the side without great pain. This has been over a month cord. The CMS HCC was originally designed to estimate future regression looks at each variable independently, this study’s find- and is getting worse.” health care costs for patients and is now often used to commu- ings show that having an office visit was more indicative of send- New or change in Request for a new medication or a change of current “My current medication isn’t working for me anymore but my sister-in-law nicate patient complexity. ing a secure message than being a Medicare member or having a medication request medication recommended [medication name]. Can you prescribe me that?” Of the 2.3 million email messages sent in 2017, we analyzed chronic disease. Conversely, being a KP-Medicaid member and Medication renewal Request for refill or renewal of a medication or medical “Please renew my prescription to oxycodone HCL 5 mg tab. Please have the content and corresponding metadata of 2397 messages. Our self-identifying as black and/or Hispanic were factors associated or refill supply pharmacy mail [it] to me.” researchers tagged each email message with up to 3 primary with fewer secure messages sent. Medication issue/ Medication or supply issue that is not a refill/renew “I’m sending a list of vitamins and supplements I take. Please have the doctor message topic tags, using a detailed description of each message Average counts of office visit utilizations were similar between question request or a problem with receiving the medication in make sure they are okay to take and don’t counteract what I take for my topic. The detailed description and table were modified from the racial groups, but propensities for secure messaging varied widely mail (eg, questions about dose or side effects) Parkinson’s [disease].” 11 Veterans Affairs study by Shimada et al. Table 1 depicts the (Table 2). Though there was only a small difference between aver- Imaging request Request for imaging/test “I’ve been having terrible headaches and I want a CT scan to see what the various email topics. age numbers of office visits between black, Hispanic, and white problem is.” members, members who self-identified as black and/or Hispanic Imaging issue/ Patient questions about imaging, choosing among “Am I allowed to eat before my MRI tomorrow?” Statistical Analysis question imaging options, why a particular imaging procedure is important, preparing for a scan/imaging procedure We performed a negative binomial regression to assess the Table 2. Average encounter volume of utilization per patient number of messages sent by a patient. Independent variables Imaging result Request for or discussion of imaging results “Hello, I got the ultrasound [scan result] last week and I want to know what are by self-reported race/ethnicity included primary care utilization counts; geographic area of the next steps to take?” Telephone Lab/test request Request for lab test “I need some bloodwork done.” the patient’s medical center; and patient’s age, sex, number of Race/ethnicity No. of Office appointment Secure chronic illnesses, race/ethnicity, and Health Plan product type. Lab/test issue/ Patient questions about testing, choosing among testing “Did you want me to get lab work done before I see you?” members visits visits messages question options, why a test is important, preparing for a test The reference patient we compared all variables to was white, White 1,779,631 0.984 0.265 0.748 Lab/test results Request for or discussion of test results “Thanks for sending me the test results. I still have a question for the doctor male, age 52 years (median age in our dataset), had no chronic Native American/ 19,334 0.957 0.271 0.562 about the numbers that you gave me.” illnesses, and had a KP Health Plan in his home Region. This Inuit/Aleutian Surgery or Patient questions about a surgery or procedure “Good morning. I am still having a lot a lot of pain in my knees. The injections regression accounts for each variable independent of one an- Asian/Pacific 521,774 0.942 0.215 0.522 procedure issue/ did not seem to help. But I heard the second time around it usually helps a lot other. For example, although being a Medicare member and Islander question more. So, I was wondering if I can get another injection in my knees??” age may be related, this regression represents them as 2 separate Black/African 412,163 0.958 0.291 0.434 FYI informing Patient sharing information with no additional discussion “Just to keep you posted. EKG done yesterday. Bloodwork and urine done variables, independent of one another. Transformed versions of American that does not fit other category (eg, inform about non-VA this AM.” office visit counts and TAV counts were used in the regression, Other 75,775 0.795 0.196 0.417 care or test result) namely log(variable + 1). Hispanic/Latino 1,525,834 0.906 0.223 0.289 Scheduling Schedule an appointment, test, or procedure “I would like to set up an appointment for a physical.” Declined to state 489,833 0.392 0.094 0.189 Referral Request referral to a specialist “I would like to be referred to MOVE! to help me with some weight loss. I also need you to set up an appointment for [examination of] my knees and lower Black/ Chronic Office back. I’m having a great deal of pain in both, been injured in the past. Thank you.” Hispanic/ African Medicaid/ disease Member TAV visit Table 3. Average utilization counts per patient Latino American Medical count Women Medicare count* count* Note request Request doctor’s note “I’m supposed to go on vacation this week but I’m too sick to fly. Can you write Telephone me a note for my travel insurance?” 0.6 Parameter Office appointment Secure Administrative Administrative issues other than appointment “I didn’t receive my medication in the mail.” visits visits (TAVs) messages 0.4 scheduling Members with at least 1 office 2.15 0.47 0.93 Life issue Any contextual issues that are not strictly biomedical “We’re having lots of changes with my mom. Hospice people are coming here 0.2 visita and are about the patient’s life context but now they’re talking about putting her in a nursing home. They say they can 0 Members with at least 1 TAVa 2.46 1.63 1.46 help her all the time.” -0.2 Members who sent at least 1 2.17 0.61 2.92 Clinical Factors Callback request Simple callback request “Please call me at xxx-xxx-xxxx when you get the chance.” secure messagea -0.4 Thanks Expressing appreciation “I do want to take a minute to thank you for your help. It is a different world Members with 0 office visitsb — 0.08 0.14 -0.6 going through a pain-free day. You have been kind and caring and I do really Members with 0 TAVsb 1.04 — 0.42 appreciate it!!!” -0.8 Members who sent 0 secure 1.09 0.24 — Complaint Complaining about care, services, KP, etc “First and foremost … and I would think you would be aware of this by now, -1 messagesb [patient first name] is NOT my Dad … he’s my husband.” Coefficient a Average counts of utilizations per patient compared against having at least 1 office Other Content not captured by the above categories “Both of my glucose] meters are reading E-9 when trying to get a reading. I Figure 1. Effect of clinical factors on secure messaging. Coefficients indicate visit, having 1 telephone appointment visit (TAV), or sending 1 secure message, think it’s the battery, but I don’t know how to fix it. Tell me how or what to do.” association of each factor on the reference patient (see text). respectively. b Average counts of utilizations per patient compared against having 0 office visits, 0 AM = morning; CT = computed tomography; EKG = electrocardiogram (ECG); FYI = for your information; HCL = hydrochloride; KP = Kaiser Permanente; lab = laboratory; a indicates regression coefficients of greatest magnitude. TAVs or sending 0 secure messages, respectively. MOVE! = Veterans Affair’s National Weight Management Program; MRI = magnetic resonance imaging; tab = tablet; VA = Veterans Affairs. TAV = telephone appointment visit.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 39 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Age and Sex Percentage of messages sent by number of days between In Figure 3, the largest volume of messages is highlighted, 90000 a message and an office visit detailing that 7.69% of messages sent by adult members to pri- 3.00% 80000 mary care departments were sent within 1 day of a PCP office 2.50% visit. Another 14.85% of messages were sent within 3 days of 70000 2.00% a PCP office visit, and 37.5% of messages were sent within 7

60000 1.50% days of a PCP office visit.

office visit Utilization by Chronic Condition Diagnosis 50000 1.00% Of KPSC members, 42.5% had a chronic condition, yet this 40000 0.50% population accounted for two-thirds of primary care service 30000 0.00% Percentage of messages sent either before/after an -14 -13 -12 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0* 1 2 3 4 5 6 7 8 9 10 12 13 14 utilization. Those KP members with a chronic condition used Number of days between a secure message and an office visit with a PCP TAVs and secure messaging more than in-person office visits. In Number of office visits 20000 Table 4, patients with a chronic condition diagnosis history sent 10000 Figure 3. Percentage of messages sent either before (negative numbers) or after (positive numbers) an office visit compared with number of days between more than 3 times as many secure messages to their PCP and 0 a secure message and an office visit shown in 28-day span. Asterisk indicates had 2 times as many office visits compared with patients without 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 that 0 days is the day of visit. any chronic condition diagnosis. Age (years) Utilization by Sex Men Women Approximately half of KPSC members (51.7%) in 2017 were Table 4. Percentage of primary care service encounters in women (Table 4), but female members accounted for almost two- diagnosis history Age and Sex thirds of primary care utilization. On average, 5 of 8 messages Percentage with CMS Percentage with 25000 sent to a PCP were sent by women. In a comparison of the 3 Service encounter HCC diagnosis history female patient different primary care services, the biggest difference in utilization Office visits 62.6 60.4 between sexes was seen in TAVs, with female members account- 20000 Telephone appointment 68.5 65.0 ing for 65% of TAV encounters. visits Utilization of All Service Modalities 15000 Secure messages 67.2 62.4 Less than one-fourth of the member population was respon- CMS HCC = Centers for Medicare and Medicaid Services Hierarchical Condition sible for the sum of 2.3 million secure messages to PCPs in Category 10000 2017 (Table 5). According to Figure 4, younger men used primary care services Table 5. Percentage of members using primary care services the least. For example, less than 5% of 18-year-old men used Number of TAVs 5000 in 2017 secure messaging. Overall, women across all ages used primary Service encounter Percentage care office visits and TAVs more than men did. However, in -se 0 Office visits 61.6 cure messaging, after age 70 years, men consistently sent more 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 Telephone appointment visits 19.7 messages to their primary care department than did women. Age (years) Secure messages 21.4 Message Content Men Women Nearly 1 in 4 secure messages to the primary care office fell into the medical advice category. The top categories included Age and Sex sent fewer messages than other races with similar average number medication issues and questions, informing the physician (ie, 50000 of office visits. messages not requiring an action or reply), medication refills, 45000 As seen in Table 3, members who had at least 1 office visit had, and scheduling (Figure 5). Nearly 25% of all messages examined 40000 on average, more than 2 office visit in 2017. Members who had at were about medications. 35000 least 1 TAV had, on average, 1.63 TAVs. Members who initiated a secure message thread initiated nearly 3 messages on average. DISCUSSION 30000 Table 3 also shows the average counts for members who did not 25000 This study demonstrates the interdependency of patient have any office visits, TAVs, or secure messages sent. demographics and clinical factors on secure message utiliza- 20000 Correlation between Secure Messaging and Office Visits/TAVs tion. Studies have shown that secure messages and TAVs were 15000 Figure 2 illustrates how age and sex were associated with implemented to create more efficient primary care services.3,4,12

Number of Messages 10000 utilization of different primary care services. The spike in office Our study findings reveal that members with a higher utilization visit utilization correlates with a spike in utilization of TAVs 5000 of office visits and TAVs sent more secure messages than those and secure messages. The observed spike is likely related to the who did not use those clinical services. Through our variable- 0 free Medicare annual wellness office visit that members are 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 independent regression analysis, we found that having an office encouraged by KP to schedule once they become a Medicare Age (years) visit and having a TAV are more indicative of sending secure member. Additionally, KP PCPs often use TAVs to follow-up messages than being a Medicare member or having a chronic Men Women with Medicare members after a Medicare wellness visit and condition, by a factor of 6 and 13, respectively, although being often encourage members to use secure messaging to follow-up a Medicare member and having a chronic condition are still Figure 2. Counts of primary care utilizations by member age and sex. after their Medicare wellness visit. TAV = telephone appointment visit. significant in attributing to larger secure message volumes. At

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 40 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Age and Sex Percentage of messages sent by number of days between In Figure 3, the largest volume of messages is highlighted, 90000 a message and an office visit detailing that 7.69% of messages sent by adult members to pri- 3.00% 80000 mary care departments were sent within 1 day of a PCP office 2.50% visit. Another 14.85% of messages were sent within 3 days of 70000 2.00% a PCP office visit, and 37.5% of messages were sent within 7

60000 1.50% days of a PCP office visit.

office visit Utilization by Chronic Condition Diagnosis 50000 1.00% Of KPSC members, 42.5% had a chronic condition, yet this 40000 0.50% population accounted for two-thirds of primary care service 30000 0.00% Percentage of messages sent either before/after an -14 -13 -12 -11 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0* 1 2 3 4 5 6 7 8 9 10 12 13 14 utilization. Those KP members with a chronic condition used Number of days between a secure message and an office visit with a PCP TAVs and secure messaging more than in-person office visits. In Number of office visits 20000 Table 4, patients with a chronic condition diagnosis history sent 10000 Figure 3. Percentage of messages sent either before (negative numbers) or after (positive numbers) an office visit compared with number of days between more than 3 times as many secure messages to their PCP and 0 a secure message and an office visit shown in 28-day span. Asterisk indicates had 2 times as many office visits compared with patients without 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 that 0 days is the day of visit. any chronic condition diagnosis. Age (years) Utilization by Sex Men Women Approximately half of KPSC members (51.7%) in 2017 were Table 4. Percentage of primary care service encounters in women (Table 4), but female members accounted for almost two- diagnosis history Age and Sex thirds of primary care utilization. On average, 5 of 8 messages Percentage with CMS Percentage with 25000 sent to a PCP were sent by women. In a comparison of the 3 Service encounter HCC diagnosis history female patient different primary care services, the biggest difference in utilization Office visits 62.6 60.4 between sexes was seen in TAVs, with female members account- 20000 Telephone appointment 68.5 65.0 ing for 65% of TAV encounters. visits Utilization of All Service Modalities 15000 Secure messages 67.2 62.4 Less than one-fourth of the member population was respon- CMS HCC = Centers for Medicare and Medicaid Services Hierarchical Condition sible for the sum of 2.3 million secure messages to PCPs in Category 10000 2017 (Table 5). According to Figure 4, younger men used primary care services Table 5. Percentage of members using primary care services the least. For example, less than 5% of 18-year-old men used Number of TAVs 5000 in 2017 secure messaging. Overall, women across all ages used primary Service encounter Percentage care office visits and TAVs more than men did. However, in -se 0 Office visits 61.6 cure messaging, after age 70 years, men consistently sent more 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 Telephone appointment visits 19.7 messages to their primary care department than did women. Age (years) Secure messages 21.4 Message Content Men Women Nearly 1 in 4 secure messages to the primary care office fell into the medical advice category. The top categories included Age and Sex sent fewer messages than other races with similar average number medication issues and questions, informing the physician (ie, 50000 of office visits. messages not requiring an action or reply), medication refills, 45000 As seen in Table 3, members who had at least 1 office visit had, and scheduling (Figure 5). Nearly 25% of all messages examined 40000 on average, more than 2 office visit in 2017. Members who had at were about medications. 35000 least 1 TAV had, on average, 1.63 TAVs. Members who initiated a secure message thread initiated nearly 3 messages on average. DISCUSSION 30000 Table 3 also shows the average counts for members who did not 25000 This study demonstrates the interdependency of patient have any office visits, TAVs, or secure messages sent. demographics and clinical factors on secure message utiliza- 20000 Correlation between Secure Messaging and Office Visits/TAVs tion. Studies have shown that secure messages and TAVs were 15000 Figure 2 illustrates how age and sex were associated with implemented to create more efficient primary care services.3,4,12

Number of Messages 10000 utilization of different primary care services. The spike in office Our study findings reveal that members with a higher utilization visit utilization correlates with a spike in utilization of TAVs 5000 of office visits and TAVs sent more secure messages than those and secure messages. The observed spike is likely related to the who did not use those clinical services. Through our variable- 0 free Medicare annual wellness office visit that members are 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100 independent regression analysis, we found that having an office encouraged by KP to schedule once they become a Medicare Age (years) visit and having a TAV are more indicative of sending secure member. Additionally, KP PCPs often use TAVs to follow-up messages than being a Medicare member or having a chronic Men Women with Medicare members after a Medicare wellness visit and condition, by a factor of 6 and 13, respectively, although being often encourage members to use secure messaging to follow-up a Medicare member and having a chronic condition are still Figure 2. Counts of primary care utilizations by member age and sex. after their Medicare wellness visit. TAV = telephone appointment visit. significant in attributing to larger secure message volumes. At

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 41 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Proportion who had primary care office visit Figure 5. Percentage of messages by Volume 100% message topic indicating frequency in Medical advice message sample (n = 2397).a Medication issue/question 90% a FYI informing Message may have multiple topics. 80% Medication renew/refill FYI = for your information; lab = laboratory. Scheduling 70% Lab/test results Lab/test request 60% New/change medication request Referral 50% Note request Administrative 40% Lab/test issue/question 30% Imaging result Thanks 20% categories Message Surgery issue/question Imaging request 10% Other Life issue 0% 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 Complaint Imaging issue/question Age (years) Callback request Men Women 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0%

Proportion who had primary care TAVs 8,9 40% KPSC, our PCPs often prompt patients at the end of their office each year. The primary care team needs to be well positioned to visits to email them if they have any further questions. Whereas account for the increased general adoption of secure messaging. 35% our study results suggest an association between the volume of Our study adds to existing research by looking at message top- 30% secure messaging and office visits, other studies have shown ics to primary care departments. Consistent with other studies, that the relationship between secure messaging, office visits, and medical advice is ranked as one of the top message topics that 25% TAVs are complex. Some studies have shown that messaging members are inquiring about.22,24,25 The top 6 message topics

20% can replace the number of office visits or TAVs; other studies following medical advice are very similar to the message topic have suggested that secure messaging either increases or does study conducted at Veterans Affairs medical centers,11 with a 15% not alter the utilization of office visits or telephone calls. 4,12-20 slight difference in topic ranks. The variation could be caused

10% Further studies must be done to confirm these correlations. by the small sample size and difference in the service popula- Studies have found that patients with certain demographic tion. Knowing what types of messages patients are sending will 5% backgrounds used care services overall more than others did.21,22 help when building, prioritizing, or updating routing protocols. Our study findings confirm previous research by demonstrat- 0% 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ing that certain patient variables, such as being a woman, being Practical Applications Age (years) white, having a chronic condition, and being older, contribute Today, drivers of secure message utilization are not commonly Men Women to higher secure messaging utilization. Moreover, results of considered in certain aspects of the secure message management this study reveal the magnitude at which certain clinical and system in primary care settings. Knowing the factors associ- patient demographic factors affect secure message utilization. ated with secure messaging utilization and the message content Proportion who sent messages to primary care 35% A member having a CMS HCC diagnosis history may send 3 could assist in the following: 1) building more efficient staffing times as many emails to primary care than a member without models; 2) creating more efficient routing that matches the -se

30% an HCC diagnosis history. Women also account for almost cure message content with maximum scope of practice allowed two-thirds of secure messaging to primary care departments for nurses, pharmacists, and advanced practice physicians; and 25% excluding Obstetrics/Gynecology. Because of this exclusion, our 3) using message volume as a weighted factor that influences a results likely underestimate the message gap between sexes. In PCP’s panel ceiling, or cap. 20% a comparison of the 3 different primary care services, the big- Staffing Models gest difference in utilization between sexes was seen in virtual Our analysis suggests that certain populations tend to send a 15% services, with female members using 65% of TAV encounters larger number of secure messages and therefore produce addi-

10% and 62.4% of secure messaging encounters. tional virtual work for physicians. The factors in these populations Many studies have researched the heavy adoption of secure should be considered by health systems when developing staffing 5% messaging in outpatient medicine and obstetrics/gynecol - and resource allocation protocols to address this imbalance. For ogy. 4,12-22 Data shows that the adoption of the secure messag- example, if a physician is projected to have a heavier secure mes- 0% 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ing platform is not yet widespread. Nearly 25% of the KPSC sage workload based on his/her panel, nurses experienced with Age (years) member population used the secure messaging platform in 2017. handling secure messaging can be assigned to assist. This group sent approximately 2.3 million messages in 2017. Routing Secure Messages Men Women This finding can also be interpreted as more than 75% of KPSC Understanding what patients are messaging about can aid in Figure 4. Proportion of patients by age and sex who had an encounter with primary care (office visit, telephone appointment visit [TAV], secure messaging) in 2017. members have yet to adopt secure messaging. Past KP trends designing a more efficient secure messaging model to route and data suggest, however, that the use of secure messaging increases prioritize messages, stratifying them for the appropriate recipient.

The6 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 42 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.7 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Proportion who had primary care office visit Figure 5. Percentage of messages by Volume 100% message topic indicating frequency in Medical advice message sample (n = 2397).a Medication issue/question 90% a FYI informing Message may have multiple topics. 80% Medication renew/refill FYI = for your information; lab = laboratory. Scheduling 70% Lab/test results Lab/test request 60% New/change medication request Referral 50% Note request Administrative 40% Lab/test issue/question 30% Imaging result Thanks 20% categories Message Surgery issue/question Imaging request 10% Other Life issue 0% 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 Complaint Imaging issue/question Age (years) Callback request Men Women 0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0%

Proportion who had primary care TAVs 8,9 40% KPSC, our PCPs often prompt patients at the end of their office each year. The primary care team needs to be well positioned to visits to email them if they have any further questions. Whereas account for the increased general adoption of secure messaging. 35% our study results suggest an association between the volume of Our study adds to existing research by looking at message top- 30% secure messaging and office visits, other studies have shown ics to primary care departments. Consistent with other studies, that the relationship between secure messaging, office visits, and medical advice is ranked as one of the top message topics that 25% TAVs are complex. Some studies have shown that messaging members are inquiring about.22,24,25 The top 6 message topics

20% can replace the number of office visits or TAVs; other studies following medical advice are very similar to the message topic have suggested that secure messaging either increases or does study conducted at Veterans Affairs medical centers,11 with a 15% not alter the utilization of office visits or telephone calls. 4,12-20 slight difference in topic ranks. The variation could be caused

10% Further studies must be done to confirm these correlations. by the small sample size and difference in the service popula- Studies have found that patients with certain demographic tion. Knowing what types of messages patients are sending will 5% backgrounds used care services overall more than others did.21,22 help when building, prioritizing, or updating routing protocols. Our study findings confirm previous research by demonstrat- 0% 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ing that certain patient variables, such as being a woman, being Practical Applications Age (years) white, having a chronic condition, and being older, contribute Today, drivers of secure message utilization are not commonly Men Women to higher secure messaging utilization. Moreover, results of considered in certain aspects of the secure message management this study reveal the magnitude at which certain clinical and system in primary care settings. Knowing the factors associ- patient demographic factors affect secure message utilization. ated with secure messaging utilization and the message content Proportion who sent messages to primary care 35% A member having a CMS HCC diagnosis history may send 3 could assist in the following: 1) building more efficient staffing times as many emails to primary care than a member without models; 2) creating more efficient routing that matches the -se

30% an HCC diagnosis history. Women also account for almost cure message content with maximum scope of practice allowed two-thirds of secure messaging to primary care departments for nurses, pharmacists, and advanced practice physicians; and 25% excluding Obstetrics/Gynecology. Because of this exclusion, our 3) using message volume as a weighted factor that influences a results likely underestimate the message gap between sexes. In PCP’s panel ceiling, or cap. 20% a comparison of the 3 different primary care services, the big- Staffing Models gest difference in utilization between sexes was seen in virtual Our analysis suggests that certain populations tend to send a 15% services, with female members using 65% of TAV encounters larger number of secure messages and therefore produce addi-

10% and 62.4% of secure messaging encounters. tional virtual work for physicians. The factors in these populations Many studies have researched the heavy adoption of secure should be considered by health systems when developing staffing 5% messaging in outpatient medicine and obstetrics/gynecol - and resource allocation protocols to address this imbalance. For ogy. 4,12-22 Data shows that the adoption of the secure messag- example, if a physician is projected to have a heavier secure mes- 0% 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 ing platform is not yet widespread. Nearly 25% of the KPSC sage workload based on his/her panel, nurses experienced with Age (years) member population used the secure messaging platform in 2017. handling secure messaging can be assigned to assist. This group sent approximately 2.3 million messages in 2017. Routing Secure Messages Men Women This finding can also be interpreted as more than 75% of KPSC Understanding what patients are messaging about can aid in Figure 4. Proportion of patients by age and sex who had an encounter with primary care (office visit, telephone appointment visit [TAV], secure messaging) in 2017. members have yet to adopt secure messaging. Past KP trends designing a more efficient secure messaging model to route and data suggest, however, that the use of secure messaging increases prioritize messages, stratifying them for the appropriate recipient.

The6 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.7 43 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Acknowledgments 17. Palen TE, Ross C, Powers JD, Xu S. Association of online patient access to clinicians 2016 Sep-Oct;29(5):592-603. DOI: https://doi.org/10.3122/jabfm.2016.05.160046 For example, if messages about medications have a high volume, The authors thank the physicians and operational directors in the Kaiser and medical records with use of clinical services. JAMA 2012 Nov 21;308(19):2012-9. PMID:27613792 there may be value in routing messages about medication to Permanente Southern California Region, the Health Innovation team under the DOI: https://doi.org/10.1001/jama.2012.14126 PMID:23168824 22. Bertakis KD, Azari R, Helms LJ, Callahan EJ, Robbins JA. Gender differences 18. Katz SJ, Moyer CA, Cox DT, Stern DT. Effect of a triage-based E-mail system in the utilization of health care services. J Fam Pract 2000 Feb;49(2):147-52. pharmacists directly, bypassing the primary care team. Southern California Permanente Medical Group and Peter Jung from Kaiser Optimized Panel Calculation on clinic resource use and patient and physician satisfaction in primary care: A PMID:10718692 Permanente Business Systems and Reporting for their assistance. randomized controlled trial. J Gen Intern Med 2003 Sep;18(9):736-44. DOI: https:// 23. Cronin RM, Davis SE, Shenson JA, Chen Q, Rosenbloom ST, Jackson GP. Growth To account for workload owing to messaging volumes, our Kathleen Louden, ELS, of Louden Health Communications performed a doi.org/10.1046/j.1525-1497.2003.20756.x PMID:12950483 of Secure Messaging Through a Patient Portal as a Form of Outpatient Interaction research findings suggest that some patient variables should be primary copy edit. 19. Lin C-T, Wittevrongel L, Moore L, Beaty BL, Ross SE. An Internet-based patient- across Clinical Specialties. Appl Clin Inform 2015 Apr 29;6(2):288-304. DOI: https:// provider communication system: Randomized controlled trial. J Med Internet Res doi.org/10.4338/ACI-2014-12-RA-0117 PMID:26171076 considered when health systems calculate PCP panel sizes. PCPs How to Cite this article 2005 Aug 5;7(4):e47. DOI: https://doi.org/10.2196/jmir.7.4.e47 PMID:16236699 24. Stiles RA, Deppen SA, Figaro MK, et al. Behind-the-scenes of patient-centered whose panels contain white, Medicare-eligible women with a 20. Bavafa H, Hitt LM, Terwiesch C. The impact of e-visits on visit frequencies and patient care: Content analysis of electronic messaging among primary care clinic providers Yakushi J, Wintner M, Yau N, Borgo L, Solorzano E. Utilization of secure chronic condition likely have a heavier workload because of the health: Evidence from primary care. SSRN 2017 July 22. DOI: https://doi.org/10.2139/ and staff. Med Care 2007 Dec;45(12):1205-9. DOI: https://doi.org/10.1097/ messaging to primary care departments. Perm J 2020;24:19.177. DOI: https:// ssrn.2363705 MLR.0b013e318148490c PMID:18007171 increased volume of secure messages they receive from these doi.org/10.7812/TPP/19.177 21. Wallace LS, Angier H, Huguet N, et al. Patterns of Electronic Portal Use among 25. Sittig D. Results of a content analysis of electronic messages (email) sent between patient populations. Vulnerable Patients in a Nationwide Practice-based Research Network: From patients and their physicians. BMC Med Inform Decis Mak 2003 Oct 1:3:11. DOI: the OCHIN Practice-based Research Network (PBRN). J Am Board Fam Med https://doi.org/10.1186/1472-6247-3-11 PMID:14519206 Limitations References 1. Garrido T, Meng D, Wang JJ, Palen TE, Kanter MH. Secure e-mailing between This study has several limitations. First, our study included se- physicians and patients: Transformational change in ambulatory care. J cure messages through https://kp.org only to the Family Medicine Ambul Care Manage 2014 Jul-Sep;37(3):211-8. DOI: https://doi.org/10.1097/ JAC.0000000000000043 PMID:24887522 and Internal Medicine Departments, excluding the Pediatrics 2. Franklin R. Secure messaging: Myths, facts, and pitfalls. Fam Pract Manag 2013 and Obstetrics/Gynecology Departments. Our analysis did Jan-Feb;20(1):21-4. PMID:23418834 not include any messages to specialty departments. Second, we 3. Kane B, Sands DZ. Guidelines for the clinical use of electronic mail with patients. The AMIA Internet Working Group, Task Force on Guidelines for the Use of Clinic-Patient examined data from only a single KP Region, KPSC. Our study Electronic Mail. J Am Med Inform Assoc 1998 Jan-Feb;5(1):104-11. DOI: https://doi. does not include messaging, office visit, and TAV data trends org/10.1136/jamia.1998.0050104 PMID:9452989 from other KP Regions. 4. Chen C, Garrido T, Chock D, Okawa G, Liang L. The Kaiser Permanente Electronic Health Record: Transforming and streamlining modalities of care. Health Aff Studies have found that the relationship between secure (Millwood) 2009 Mar-Apr;28(2):323-33. DOI: https://doi.org/10.1377/hlthaff.28.2.323 messaging, office visits, and TAVs is complex. Some study PMID:19275987 findings have shown that messaging can replace the number of 5. Ralston JD, Rutter CM, Carrell D, Hecht J, Rubanowice D, Simon GE. Patient use of secure electronic messaging within a shared medical record: A cross-sectional study. office visits or TAVs; other studies have suggested that secure J Gen Intern Med 2009 Mar;24(3):349-55. DOI: https://doi.org/10.1007/s11606-008- messaging either increases or does not alter the utilization of 0899-z PMID:19137379 office visits or telephone calls.4,12-20 Therefore, our study, being 6. Ralston JD, Martin DP, Anderson ML, et al. Group health cooperative’s transformation toward patient-centered access. Med Care Res Rev 2009 Dec;66(6):703-24. DOI: an observational study, cannot claim whether messaging drives https://doi.org/10.1177/1077558709338486 PMID:19549993 other forms of care or vice versa. To make such a claim about 7. Anand SG, Feldman MJ, Geller DS, Bisbee A, Bauchner H. A content analysis of causality, we would need a randomized controlled trial. The e-mail communication between primary care providers and parents. Pediatrics 2005 results in this article speak only to associations. May;115(5):1283-8. DOI: https://doi.org/10.1542/peds.2004-1297 PMID:15867036 8. Zhou YY, Kanter MH, Wang JJ, Garrido T. Improved quality at Kaiser Permanente Last, it is important to note that the total number of secure through e-mail between physicians and patients. Health Aff (Millwood) 2010 messages sampled in this study reflects only the 21.4% of KPSC Jul;29(7):1370-5. DOI: https://doi.org/10.1377/hlthaff.2010.0048 PMID:20606190 members who used secure messaging and does not reflect the 9. Report Kaiser Permanente Digital Metrics. Southern California Region. 2017-2018 annual report. Portland, OR: Kaiser Permanente Digital Experience Center Analytics; population as a whole. As more and more members adopt the 2017 service, further studies are needed to determine if the observa- 10. 2017 Model software/ICD-10 mappings [Internet]. Atlanta, GA: Centers for Medicare tions found in this study stay consistent. & Medicaid Services; 2017 [cited 2019 Sep 29]. Available from: www.cms.gov/ Medicare/Health-Plans/MedicareAdvtgSpecRateStats/Risk-Adjustors-Items/ Risk2017.html?DLPage=1&DLEntries=10&DLSort=0&DLSortDir=descending CONCLUSION 11. Shimada SL, Petrakis BA, Rothendler JA, et al. An analysis of patient-provider This study examined several factors that were often associated secure messaging at two Veterans Health Administration medical centers: Message content and resolution through secure messaging. J Am Med Inform Assoc 2017 Sep with utilization of secure messaging, ranging from having an 1;24(5):942-9. DOI: https://doi.org/10.1093/jamia/ocx021 PMID:28371896 office visit to having a chronic condition. Factors most strongly 12. Liederman EM, Lee JC, Baquero VH, Seites PG. Patient-physician web associated with increased utilization of secure messaging were messaging. The impact on message volume and satisfaction. J Gen Intern Med 2005 Jan;20(1):52-7. DOI: https://doi.org/10.1111/j.1525-1497.2005.40009.x the numbers of primary care office visits and TAVs. Demo- PMID:15693928 graphic factors associated with secure message utilization in- 13. de Lusignan S, Mold F, Sheikh A, et al. Patients’ online access to their electronic cluded sex, age, HCC diagnosis history, and Health Plan type. health records and linked online services: A systematic interpretative review. BMJ Open 2014 Sep 8;4(9):e006021. DOI: https://doi.org/10.1136/bmjopen-2014-006021 Being white, female, and older and having a Medicare Health PMID:25200561 Plan type and a previous HCC diagnosis were associated with 14. Goldzweig CL, Towfigh AA, Paige NM, et al. Systematic review: Secure messaging higher utilization of secure messages. The findings of this study between providers and patients, and patients’ access to their own medical record: Evidence on health outcomes, satisfaction, efficiency and attitudes [Internet]. reveal the magnitude of these factors on secure message utiliza- Washington, DC: US Department of Veterans Affairs; 2012 Jul [cited 2019 Oct 23]. tion and challenge many existing assumptions around secure Available from: www.ncbi.nlm.nih.gov/books/NBK100359/ v messaging. 15. Roter DL, Larson S, Sands DZ, Ford DE, Houston T. Can e-mail messages between patients and physicians be patient-centered? Health Commun 2008;23(1):80-6. DOI: https://doi.org/10.1080/10410230701807295 PMID:18443995 Disclosure Statement 16. Zhou YY, Garrido T, Chin HL, Wiesenthal AM, Liang LL. Patient access to an The author(s) have no conflicts of interest to disclose. electronic health record with secure messaging: Impact on primary care utilization. Am J Manag Care 2007 Jul;13(7):418-24. PMID:17620037

The8 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 44 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.9 ORIGINAL RESEARCH & CONTRIBUTIONS ORIGINAL RESEARCH & CONTRIBUTIONS Utilization of Secure Messaging to Primary Care Departments Utilization of Secure Messaging to Primary Care Departments

Acknowledgments 17. Palen TE, Ross C, Powers JD, Xu S. Association of online patient access to clinicians 2016 Sep-Oct;29(5):592-603. DOI: https://doi.org/10.3122/jabfm.2016.05.160046 For example, if messages about medications have a high volume, The authors thank the physicians and operational directors in the Kaiser and medical records with use of clinical services. JAMA 2012 Nov 21;308(19):2012-9. PMID:27613792 there may be value in routing messages about medication to Permanente Southern California Region, the Health Innovation team under the DOI: https://doi.org/10.1001/jama.2012.14126 PMID:23168824 22. Bertakis KD, Azari R, Helms LJ, Callahan EJ, Robbins JA. Gender differences 18. Katz SJ, Moyer CA, Cox DT, Stern DT. Effect of a triage-based E-mail system in the utilization of health care services. J Fam Pract 2000 Feb;49(2):147-52. pharmacists directly, bypassing the primary care team. Southern California Permanente Medical Group and Peter Jung from Kaiser Optimized Panel Calculation on clinic resource use and patient and physician satisfaction in primary care: A PMID:10718692 Permanente Business Systems and Reporting for their assistance. randomized controlled trial. J Gen Intern Med 2003 Sep;18(9):736-44. DOI: https:// 23. Cronin RM, Davis SE, Shenson JA, Chen Q, Rosenbloom ST, Jackson GP. Growth To account for workload owing to messaging volumes, our Kathleen Louden, ELS, of Louden Health Communications performed a doi.org/10.1046/j.1525-1497.2003.20756.x PMID:12950483 of Secure Messaging Through a Patient Portal as a Form of Outpatient Interaction research findings suggest that some patient variables should be primary copy edit. 19. Lin C-T, Wittevrongel L, Moore L, Beaty BL, Ross SE. An Internet-based patient- across Clinical Specialties. Appl Clin Inform 2015 Apr 29;6(2):288-304. DOI: https:// provider communication system: Randomized controlled trial. J Med Internet Res doi.org/10.4338/ACI-2014-12-RA-0117 PMID:26171076 considered when health systems calculate PCP panel sizes. PCPs How to Cite this article 2005 Aug 5;7(4):e47. DOI: https://doi.org/10.2196/jmir.7.4.e47 PMID:16236699 24. Stiles RA, Deppen SA, Figaro MK, et al. Behind-the-scenes of patient-centered whose panels contain white, Medicare-eligible women with a 20. Bavafa H, Hitt LM, Terwiesch C. The impact of e-visits on visit frequencies and patient care: Content analysis of electronic messaging among primary care clinic providers Yakushi J, Wintner M, Yau N, Borgo L, Solorzano E. Utilization of secure chronic condition likely have a heavier workload because of the health: Evidence from primary care. SSRN 2017 July 22. DOI: https://doi.org/10.2139/ and staff. Med Care 2007 Dec;45(12):1205-9. DOI: https://doi.org/10.1097/ messaging to primary care departments. Perm J 2020;24:19.177. DOI: https:// ssrn.2363705 MLR.0b013e318148490c PMID:18007171 increased volume of secure messages they receive from these doi.org/10.7812/TPP/19.177 21. Wallace LS, Angier H, Huguet N, et al. Patterns of Electronic Portal Use among 25. Sittig D. Results of a content analysis of electronic messages (email) sent between patient populations. Vulnerable Patients in a Nationwide Practice-based Research Network: From patients and their physicians. BMC Med Inform Decis Mak 2003 Oct 1:3:11. DOI: the OCHIN Practice-based Research Network (PBRN). J Am Board Fam Med https://doi.org/10.1186/1472-6247-3-11 PMID:14519206 Limitations References 1. Garrido T, Meng D, Wang JJ, Palen TE, Kanter MH. Secure e-mailing between This study has several limitations. First, our study included se- physicians and patients: Transformational change in ambulatory care. J cure messages through https://kp.org only to the Family Medicine Ambul Care Manage 2014 Jul-Sep;37(3):211-8. DOI: https://doi.org/10.1097/ JAC.0000000000000043 PMID:24887522 and Internal Medicine Departments, excluding the Pediatrics 2. Franklin R. Secure messaging: Myths, facts, and pitfalls. Fam Pract Manag 2013 and Obstetrics/Gynecology Departments. Our analysis did Jan-Feb;20(1):21-4. PMID:23418834 not include any messages to specialty departments. Second, we 3. Kane B, Sands DZ. Guidelines for the clinical use of electronic mail with patients. The AMIA Internet Working Group, Task Force on Guidelines for the Use of Clinic-Patient examined data from only a single KP Region, KPSC. Our study Electronic Mail. J Am Med Inform Assoc 1998 Jan-Feb;5(1):104-11. DOI: https://doi. does not include messaging, office visit, and TAV data trends org/10.1136/jamia.1998.0050104 PMID:9452989 from other KP Regions. 4. Chen C, Garrido T, Chock D, Okawa G, Liang L. The Kaiser Permanente Electronic Health Record: Transforming and streamlining modalities of care. Health Aff Studies have found that the relationship between secure (Millwood) 2009 Mar-Apr;28(2):323-33. DOI: https://doi.org/10.1377/hlthaff.28.2.323 messaging, office visits, and TAVs is complex. Some study PMID:19275987 findings have shown that messaging can replace the number of 5. Ralston JD, Rutter CM, Carrell D, Hecht J, Rubanowice D, Simon GE. Patient use of secure electronic messaging within a shared medical record: A cross-sectional study. office visits or TAVs; other studies have suggested that secure J Gen Intern Med 2009 Mar;24(3):349-55. DOI: https://doi.org/10.1007/s11606-008- messaging either increases or does not alter the utilization of 0899-z PMID:19137379 office visits or telephone calls.4,12-20 Therefore, our study, being 6. Ralston JD, Martin DP, Anderson ML, et al. Group health cooperative’s transformation toward patient-centered access. Med Care Res Rev 2009 Dec;66(6):703-24. DOI: an observational study, cannot claim whether messaging drives https://doi.org/10.1177/1077558709338486 PMID:19549993 other forms of care or vice versa. To make such a claim about 7. Anand SG, Feldman MJ, Geller DS, Bisbee A, Bauchner H. A content analysis of causality, we would need a randomized controlled trial. The e-mail communication between primary care providers and parents. Pediatrics 2005 results in this article speak only to associations. May;115(5):1283-8. DOI: https://doi.org/10.1542/peds.2004-1297 PMID:15867036 8. Zhou YY, Kanter MH, Wang JJ, Garrido T. Improved quality at Kaiser Permanente Last, it is important to note that the total number of secure through e-mail between physicians and patients. Health Aff (Millwood) 2010 messages sampled in this study reflects only the 21.4% of KPSC Jul;29(7):1370-5. DOI: https://doi.org/10.1377/hlthaff.2010.0048 PMID:20606190 members who used secure messaging and does not reflect the 9. Report Kaiser Permanente Digital Metrics. Southern California Region. 2017-2018 annual report. Portland, OR: Kaiser Permanente Digital Experience Center Analytics; population as a whole. As more and more members adopt the 2017 service, further studies are needed to determine if the observa- 10. 2017 Model software/ICD-10 mappings [Internet]. Atlanta, GA: Centers for Medicare tions found in this study stay consistent. & Medicaid Services; 2017 [cited 2019 Sep 29]. Available from: www.cms.gov/ Medicare/Health-Plans/MedicareAdvtgSpecRateStats/Risk-Adjustors-Items/ Risk2017.html?DLPage=1&DLEntries=10&DLSort=0&DLSortDir=descending CONCLUSION 11. Shimada SL, Petrakis BA, Rothendler JA, et al. An analysis of patient-provider This study examined several factors that were often associated secure messaging at two Veterans Health Administration medical centers: Message content and resolution through secure messaging. J Am Med Inform Assoc 2017 Sep with utilization of secure messaging, ranging from having an 1;24(5):942-9. DOI: https://doi.org/10.1093/jamia/ocx021 PMID:28371896 office visit to having a chronic condition. Factors most strongly 12. Liederman EM, Lee JC, Baquero VH, Seites PG. Patient-physician web associated with increased utilization of secure messaging were messaging. The impact on message volume and satisfaction. J Gen Intern Med 2005 Jan;20(1):52-7. DOI: https://doi.org/10.1111/j.1525-1497.2005.40009.x the numbers of primary care office visits and TAVs. Demo- PMID:15693928 graphic factors associated with secure message utilization in- 13. de Lusignan S, Mold F, Sheikh A, et al. Patients’ online access to their electronic cluded sex, age, HCC diagnosis history, and Health Plan type. health records and linked online services: A systematic interpretative review. BMJ Open 2014 Sep 8;4(9):e006021. DOI: https://doi.org/10.1136/bmjopen-2014-006021 Being white, female, and older and having a Medicare Health PMID:25200561 Plan type and a previous HCC diagnosis were associated with 14. Goldzweig CL, Towfigh AA, Paige NM, et al. Systematic review: Secure messaging higher utilization of secure messages. The findings of this study between providers and patients, and patients’ access to their own medical record: Evidence on health outcomes, satisfaction, efficiency and attitudes [Internet]. reveal the magnitude of these factors on secure message utiliza- Washington, DC: US Department of Veterans Affairs; 2012 Jul [cited 2019 Oct 23]. tion and challenge many existing assumptions around secure Available from: www.ncbi.nlm.nih.gov/books/NBK100359/ v messaging. 15. Roter DL, Larson S, Sands DZ, Ford DE, Houston T. Can e-mail messages between patients and physicians be patient-centered? Health Commun 2008;23(1):80-6. DOI: https://doi.org/10.1080/10410230701807295 PMID:18443995 Disclosure Statement 16. Zhou YY, Garrido T, Chin HL, Wiesenthal AM, Liang LL. Patient access to an The author(s) have no conflicts of interest to disclose. electronic health record with secure messaging: Impact on primary care utilization. Am J Manag Care 2007 Jul;13(7):418-24. PMID:17620037

The8 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • https://doi.org/10.7812/TPP/19.177 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.9 45 ORIGINAL RESEARCH & CONTRIBUTIONS Psychometric Properties of the Problem-Oriented Patient Experience—Primary Care (POPE-PC) Survey

Ali Rafik Shukor, M Biotech, MSc1,2 Perm J 2020;24:19.191 E-pub: 04/21/2020 https://doi.org/10.7812/TPP/19.191

ABSTRACT validated for specific organizational settings, patient population Introduction: Measuring the experiences of patients regarding profiles, and purposes.8 delivery and receipt of person-oriented primary care is of increas- This study describes a novel instrument designed to measure ing policy and research interest and is a core component of the patient experiences relating to the care delivery and receipt Institute for Healthcare Improvement’s Quadruple Aim. functions of person-oriented primary care, and assesses the Objective: To describe the Problem-Oriented Patient Experi- instrument’s psychometric properties. The survey, named the ence—Primary Care (POPE-PC) survey, a novel instrument de- Problem-Oriented Patient Experience-Primary Care (POPE- signed to measure patients’ experiences of primary care, and to PC), was designed by a team of medical directors and senior assess the instrument’s psychometric properties. administrators at Vancouver Coastal Health Authority in Van- Methods: Psychometric testing was performed using data from couver, British Columbia, Canada. a Canadian urgent primary care center, derived from March 2019 to Before development of the survey, a scoping literature review September 2019. Patients automatically received the 9-question sur- was performed to identify potentially suitable English-language vey by email after leaving the clinic. Exploratory factor analysis (EFA) patient experience and satisfaction surveys for consideration. on all questions and the entire dataset was performed using parallel The following tools were identified and reviewed because most analysis and scree plot for factor extraction. Internal consistency was had undergone at least some processes of validation: The Johns assessed by calculating Cronbach α. A split-half cross-validation of Hopkins Primary Care Assessment Tool,4,6 the Canadian Insti- the ensuing factor structure was conducted. A correlation analysis tute for Health Information Measuring Patient Experiences in helped explore associations between the survey’s questions. Primary Health Care Survey,8 the General Practice Assessment Results: Results from the initial EFA indicate that the POPE-PC Questionnaire,9 the Relational Communication Scale,10 the has a conceptually sound 2-factor structure, with good internal CollaboRATE survey,11 the Primary Care Assessment Sur- consistency. A split-half validation yielded the same findings, vey, 12 the European Task Force on Patient Evaluation of Gen- reaffirming that the 2-factor model has good psychometric eral Practice Care (EUROPEP),13 the Components of Primary properties. The correlation analysis indicated that the concept Care Index,14 the Interpersonal Processes of Care Survey,15 the of respect is strongly associated with clinical functions related to Saanich Peninsula Patient Experience Survey,16 the Veterans problem recognition. Affairs National Outpatient Customer Satisfaction Survey,17 Discussion: Problem recognition, despite being the cornerstone the Consumer Assessment of Healthcare Providers and Systems of person-oriented primary care, remains largely overlooked in (CAHPS) Patient-Centered Medical Home survey,18 the Care health services research. The POPE-PC’s validity and problem ori- Coordination Quality Measure for Primary Care survey,19 and entation render it potentially useful in rigorously assessing patient the RAND Patient Satisfaction Questionnaire.20 experiences of problem-oriented primary care. Although these surveys have interesting and useful content for Conclusion: The survey’s conceptual underpinning and psy- primary care in various contexts, none were deemed to properly chometric properties, coupled with its simple and parsimonious fit the specific needs or context in this case. The main reasons design, enable application in primary care settings to provide pertained to factors such as the length of surveys, the perceived person-oriented care. complexity of wording, a lack of specific focus on experiences of clinical interactions at the interface of care delivery and receipt, INTRODUCTION and general perceptions of survey design and content not fitting Measuring the experiences of patients in relation to the delivery the needs of the particular organizational or regional context. and receipt of person-oriented primary care is of increasing policy Therefore, the survey development team decided to conceptual- and research interest and is a core component of the Institute for ize and develop a new survey (described in the Methods section) Healthcare Improvement’s (IHI’s) Quadruple Aim.1-3 Patient with a fit-for-purpose design using the following key criteria: experiences pertaining to the delivery and receipt of clinical primary care can be measured and assessed using systematic 4-6 and validated survey instruments. There has therefore been Author Affiliations increasing health services research attention and resources dedi- 1 Seymour Health Centre, Inc. Vancouver, British Columbia, Canada cated to the design and testing of survey instruments to measure 2 Department of Public Health, Amsterdam University Medical Center, The Netherlands primary care patients’ experiences.7,8 Existing instruments vary in design, content, and function and are underpinned by differ- Corresponding Author Ali Rafik Shukor, M Biotech, MSc ([email protected]) ent conceptual frameworks because they are often adapted and Keywords: patient experience, primary care, problem orientation, psychometric properties, quadruple aim, quality improvement, validation

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conceptual rigor, system orientation, problem orientation, Table 1. Problem-Oriented Patient Experience-Primary Care parsimony, simplicity, consistency, relevance, and practicality. (POPE-PC) survey The team decided to conceptually underpin the survey using Question 21,22 Dr. Starfield’s model for health services research, because its number Question content directly pertains to system-oriented functions of prob- 1 Were you given a chance to describe your problems or concerns? lem-oriented primary care delivery and receipt (specifically the 2 Did staff listen to what you had to say? performance domains related to Provision of care and Receipt of 3 Did you get useful help for your problems or concerns? care; Figure 1). The model’s key functions are defined and summa- 4 Did you get a chance to ask questions? 4 rized in Starfield’s seminal book titled Primary Care: Balancing 5 Did you get a chance to talk about decisions and plans Health Needs, Services, and Technology. The most poorly recognized regarding your care? and understood function by health services researchers is that of 6 Did you understand the advice you received? 4(p28) “problem recognition,” which Starfield defines as follows: 7 Were you given enough time to discuss your problems or The providers first must recognize the needs existing both in the concerns? community and in individual patients. This feature is known as 8 Were you treated with respect? problem (or needs) recognition and is a particularly important 9 Would you recommend this clinic to your friends, family, or consideration for primary care. The problem may be a symptom, a colleagues? sign, an abnormal laboratory test, a previous but relevant item in the history of the patient or of the community, or a need for an indicated preventive procedure. Problem recognition implies being Team members operationalized the model’s domains into a aware of the existence of situations requiring attention in a health series of 6 questions, with the first 2 regarding receipt-of-care context. After recognizing the problem, the health professional gen- functions related to problem recognition and the other 4 ques- tions about delivery-of-care functions related to acceptance and erally formulates a diagnosis or an understanding of the problem 4,21 when no diagnosis is possible. satisfaction, understanding, and concordance. Two additional cross-cutting questions were added: 1 relating to the temporal METHODS nature of the experience at the interface of care delivery and re- Survey Development and Implementation ceipt, and one relating to the theme of respect. A final question was added to measure patient satisfaction, using Reichheld’s The team worked collaboratively to operationalize the concep- 23 tual model into survey questions. The content of the POPE-PC Net Promoter Score (NPS) question. The ensuing 9-question survey was refined by the team using an iterative content valida- POPE-PC survey is found in Table 1. tion approach, whereby the list of drafted questions was reviewed Survey questions 1-8 (Q1-Q8) are answered on a 5-point several times for relevance, completeness, and essentiality until Likert scale (not at all; very little; somewhat; yes, for the most consensus was reached. The team members paid special attention part; yes, definitely). The NPS question (Q9) is answered on a to ensure that the survey content and design were simple and simple 3-point scale (not at all; maybe; yes, definitely) rather concise, considering that their public community health centers’ than the traditional 10-item NPS scale, which was perceived to patients present with differing levels of distress, limited literacy, be potentially confusing for patients. Furthermore, the 3-point high burdens of illness and disease, complex psychosocial needs, scale conceptually aligns with the 3 assessment categories used limited resources and abilities, and weak motivational profiles.3 by the NPS instrument (ie, “detractors,” “passives,” and “promot- ers”). The POPE-PC survey is free to use by anyone and requires no licensing or special permission for use. The finalized survey questions specifically pertain to experi- Provision of Care ences at the interface of care delivery and receipt, thereby provid- ing insights on the performance of functions that are directly in Problem recognition Diagnosis health care practitioners’ actual sphere of influence and that are Management amenable to change and improvement. This approach renders the Reassessment survey tool fit for purpose and useful for quality improvement efforts. The survey’s design explicitly focuses on the practitioner- People / Practitioner patient relationship and on patient engagement in the context of Interface problem-oriented care settings, both of which are critical aspects of person-oriented primary care.21,24,25 The POPE-PC survey’s Receipt of Care content and problem orientation therefore support assessment of the IHI’s and the National Patient Safety Foundation’s “Ask Utilization Acceptance & Satisfaction Me 3” guidance activities, which focus on enabling patients to Understanding ask the following 3 questions during care encounters: 1) “What Concordance is my main problem?,” 2) “What do I need to do?,” and 3) “Why is it important for me to do this?”26 Figure 1. Starfield’s19 model for health services research. The POPE-PC survey was implemented at a public communi- ty-based urgent primary care setting, and patients automatically

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Table 2. Descriptive statistics (N = 1118) Statistic Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Mean 4.872 4.846 4.600 4.739 4.553 4.795 4.768 4.908 2.925 Standard deviation 0.395 0.421 0.749 0.606 0.793 0.501 0.556 0.338 0.287 Minimum 2.000 2.000 1.000 1.000 1.000 1.000 1.000 2.000 1.000 Maximum 5.000 5.000 5.000 5.000 5.000 5.000 5.000 5.000 3.000 Q = question.

receive the survey by email on leaving the clinic. The survey has 0.08 considered acceptable. Internal consistency was assessed by enabled performance assessment, evaluation, multidisciplinary calculating a Cronbach α, with a score of 0.7 or higher being team-based quality improvement initiatives, and accountability to considered satisfactory.28 the regional Health Authority and provincial Ministry of Health. There is also substantial organizational and policy interest in po- Split-Half Cross-validation tentially leveraging the POPE-PC as a regional and provincial A split-half cross-validation of the ensuing factor structure standard. Validation of the instrument’s psychometric properties (from the aforementioned EFA of the entire dataset) was then is therefore essential and is the key purpose of this study. conducted, by randomly splitting the dataset in halves and run- ning EFA on each half.28 Parallel analysis and scree plot (Promax Data Processing and Preliminary Analysis oblique rotation, JASP Version 0.11.1) were used for factor extrac- Psychometric testing was performed using POPE-PC survey tion, with factor loadings of 0.4 or greater considered significant. data from City Centre Urgent Primary Care Centre, Vancou- Goodness of fit was tested using the NNFI, and values above ver Canada, derived from the 6-month period of March 2019 0.90 were considered acceptable. Residual statistics were tested to September 2019. The original dataset is not linked to any using the RMSEA, with values below 0.08 considered accept- patient identifiers and is completely anonymous. Research was able. Internal consistency was assessed by calculating a Cronbach conducted according to the ethical principles of the Declara- α, with a score of 0.7 or higher being considered satisfactory.28 tion of Helsinki. Cronbach α values were calculated for all factor models emerging Data were randomized using a spreadsheet’s random function from the respective EFA. (Microsoft Excel RAND function, Microsoft Corp, Redmond, WA). Outliers were identified by calculating z-scores (standard Exploratory Correlation Analysis scores) and were removed if found to be 2.99 standard deviations The correlation table (used to test assumptions relating to ad- from the mean. Assumptions (ie, additivity, normality, homogene- ditivity) was used to explore associations between questions that ity, homoscedasticity) were tested in Excel by running the correla- did not fit the factor structure and those that did. tion table, histogram, normal probability plot, and residual plot. Excel data were saved as a CSV (comma separated values) RESULTS file. The file was then imported into an open-source statistics Assumptions Testing and Descriptive Statistics program ( JASP v0.11, University of Amsterdam, Amsterdam, The dataset was composed of 1152 complete survey responses Netherlands) to conduct descriptive statistics (ie, means, stan- collected between March 2019 and September 2019. Of the total dard deviations, minimum/maximum ranges, frequency tables, dataset, 2.95% (34 responses) were deemed to be outliers (ie, z- distribution plots, and box plots). score = 2.99) and therefore excluded from further analysis. The ensuing dataset was tested and found to meet the assumptions Exploratory Factor Analysis and Internal Consistency relating to additivity, normality, homogeneity, and homoscedas- JASP software was used to conduct testing of psychometric ticity. Basic descriptive statistics were run on the ensuing dataset properties.27 Exploratory factor analysis (EFA) on the entire (N = 1118), as shown in Table 2. The descriptive statistics indi- dataset was used to assess the factor structure of the study data. cated a high level of clinic performance in relation to patient An EFA was performed on the entire dataset and all 9 questions experiences across all 9 survey questions. using parallel analysis and scree plot using the Promax oblique rotation ( JASP Team [2019], JASP Version 0.11.1, Amsterdam, Exploratory Factor Analysis The Netherlands) for factor extraction. Factor loadings of 0.4 EFA on the entire dataset (N = 1118) and all 9 questions or greater were considered significant, and any factor cross- was conducted using parallel analysis and scree plot (Promax loadings below 0.4 were considered acceptable.28 With use of oblique rotation, JASP Version 0.11.1) for factor extraction. these criteria, problematic items were gradually eliminated until Factor loadings equal to or greater than 0.4 were considered EFA resulted in a satisfactory factor structure. Goodness of fit significant; factor cross-loadings were not found. Because was tested using the Non-Normed Fit Index (NNFI, also called single-item factors and factors that had a loading less than the Tucker-Lewis Index), with values above 0.90 considered 0.4 were removed, questions 7 to 9 were removed, resulting acceptable. Residual statistics were tested using the root mean in a 2-factor model comprising 6 questions (Table 3). Factor square error of approximation (RMSEA), with values less than 2 (questions 1 and 2) conceptually aligns with the “Provision

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of Care” performance domain’s problem recognition function, As expected from the conceptual framework, questions 7 to 9 whereas factor 1 (questions 3-6) conceptually aligns with the did not fit the factor structure. The correlation matrix (Table 6) “Receipt of Care” performance domain. highlighted hypothetically plausible and interesting associations Goodness of fit was found to be satisfactory with an NNFI between the 3 questions and the questions that fit the 2-factor value of 0.993 and residual statistics with a RMSEA value of model, providing interesting insights for future potential assess- 0.033. Reliability analysis yielded a Cronbach α of 0.810 for ments of concurrent validity. Performance on Q7 (a temporal factor 1 and a Cronbach α of 0.760 for factor 2, indicating sat- question relating to patients being given enough time to discuss isfactory reliability. Split-Half Cross-validation of Two-Factor Structure Table 3. Factor loadingsa b A split-half cross-validation of the 6-question, 2-factor struc- Question Factor 1 Factor 2 Uniqueness ture was conducted by randomly splitting the dataset in halves 1 0.826 0.365 (set 1 and set 2, each consisting of 576 survey responses) and 2 0.747 0.403 running EFA on each half. Parallel analysis and scree plot (Pro- 3 0.662 0.502 max oblique rotation JASP Version 0.11.1) were used for factor 4 0.634 0.429 extraction. For both sets, single-item factors and factors that had 5 0.886 0.275 loadings less than 0.4 were removed, resulting in 2-factor models 6 0.659 0.619 composed of 6 questions (Tables 4 and 5). a Applied rotation method is Promax oblique (Promax oblique rotation, JASP Version 0.11.1). For set 1, goodness of fit was found to be satisfactory with b Uniqueness is the variance that is unique to the variable and not shared with other an NNFI value of 0.965, and residual statistics with a RMSEA variables. value of 0.075. Reliability analysis yielded a Cronbach α of 0.823 Table 4. Set 1 factor loadingsa for factor 1 and a Cronbach α of 0.784 for factor 2, indicating satisfactory reliability. Question Factor 1 Factor 2 Uniqueness For Set 2, goodness of fit was found to be satisfactory with 1 0.885 0.299 an NNFI value of 0.967 and residual statistics with a RMSEA 2 0.729 0.386 value of 0.065. Reliability analysis yielded a Cronbach α of 0.795 3 0.635 0.515 for factor 1 and a Cronbach α of 0.723 for factor 2, indicating 4 0.680 0.394 satisfactory reliability. 5 0.897 0.243 6 0.705 0.574 Exploratory Correlation Analysis a Applied rotation method is Promax oblique (Promax oblique rotation, JASP Version 0.11.1). The correlation matrix (Table 6) indicates that Q7 was most strongly associated with Q4 (r = 0.737), Q5 (r = 0.672), Q2 Table 5. Set 2 factor loadingsa (r = 0.665), and Q1 (r = 0.663). Q8 was most strongly associated Question Factor 1 Factor 2 Uniqueness with Q2 (r = 0.694), Q7 (r = 0.629), Q4 (r = 0.613), and Q1 1 0.696 0.489 (r = 0.613). Q9 was most strongly associated with Q8 (r = 0.665) 2 0.822 0.372 and Q3 (r = 0.609). 3 0.693 0.486 DISCUSSION 4 0.584 0.460 This study aimed to assess the psychometric properties of the 5 0.876 0.308 POPE-PC survey. Results from the initial EFA indicate that the 6 0.605 0.664 POPE-PC survey has a 2-factor structure, with good internal a Applied rotation method is Promax oblique (JASP v0.11, University of Amsterdam, Amsterdam, Netherlands). consistency. A split-half validation yielded the same findings, which reaffirms that the 2-factor model has good psychometric properties. Table 6. Correlation matrix The 2-factor structure aligns with the survey tool’s underpin- Q Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 ning conceptual framework, which reaffirms the value of the 1 expert input and their perceptions pertaining to the tool’s face 2 0.749 21,22 validity. Factor 2 (Q1 and Q2) operationalizes the “Provision 3 0.514 0.573 of Care” performance domain’s problem recognition function, 4 0.612 0.631 0.660 whereas factor 1 (Q3-Q6) operationalizes the “Receipt of Care” 5 0.524 0.562 0.685 0.711 performance domain’s functions related to acceptance and satis- 6 0.398 0.469 0.518 0.556 0.584 faction, understanding, and concordance.21 The study’s findings 7 0.663 0.665 0.602 0.737 0.672 0.592 therefore suggest that the survey is conceptually sound, which 8 0.613 0.694 0.523 0.613 0.508 0.484 0.630 has important implications regarding the instrument’s validity for 9 0.549 0.578 0.609 0.585 0.478 0.448 0.582 0.665 the measurement and assessment of patient experiences related to delivery and receipt of person-oriented primary care. Q = question.

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problems or concerns) is strongly associated with patients being team-led quality improvement activities. These performance given the opportunity to ask questions, patients being given the assessments and quality improvement activities are executed opportunity to discuss decisions regarding their care, whether with a spirit of enabling learning, continuous improvement, staff listened to what patients had to say, and whether patients and professional development, rather than being punitive. The were given the opportunity to describe their problems or con- clinic’s leadership, clinical, and administrative teams have been cerns. Performance on Q8 (respect) is most strongly associated reporting the patient survey to be of high value, particularly in with whether staff listened to what patients had to say, whether relation to quality improvement and enabling staff motivation. patients were given enough time to discuss their problems or The leadership team plans to design trending studies that enable concerns, whether patients were given the opportunity to ask assessment of the impact of aquality improvement activities on questions, and whether patients were given a chance to describe patient experience over time. The clinic also sends monthly pa- their problems or concerns. Performance on Q9 (NPS question) tient experience performance reports to the Vancouver Coastal is most strongly associated with whether patients were treated Health Authority and the British Columbia Ministry of Health, with respect and whether patients perceived that they received for accountability purposes. useful help for their problems or concerns. By enabling the measurement of patient experiences of The dynamics of the aforementioned associations warrant problem-oriented primary care, the POPE-PC survey aims further exploration by health services researchers to better un- to make a major contribution to health services research, with derstand the complex mechanisms by which different primary a focus on the field of primary care. Problem recognition, de- care functions affect patient perceptions relating to respect spite being a critical function and the cornerstone of person- and satisfaction. Specifically, the strength of the relationships oriented primary care, remains largely overlooked by health between respect (Q8) and factor 2’s questions (Q1 and Q2) services research.4,21,24,25 Survey instruments that incorporate relating to problem recognition are particularly interesting in elements of measuring performance relating to the function light of research findings indicating that respect is strongly a of problem recognition include The Johns Hopkins Primary function of recognition of problems and attention to needs. 29 Care Assessment Tool, the Relational Communication Scale, Such findings, along with this study’s correlation analysis results, and the CollaboRATE survey.6,11,31-33 The POPE-PC survey, by do indicate that Q8 (respect) can potentially be used as a proxy explicitly focusing on problem orientation in primary care, can to assess concurrent validity for factor 2’s questions. potentially help assess performance of organizations participat- It is important to also highlight the survey’s parsimonious ing in the IHI’s and National Patient Safety Foundation’s Ask design philosophy, which has likely enabled a high response Me 3 educational program.26 rate, which peaked at 42% for one of the study’s months. The Basic standards for problem recognition and problem orien- survey was created by a team of Health Authority Medical tation of care, originally developed in the 1960s by Lawrence Directors, senior administrators, and researchers working with L Weed, MD,34 father of the problem-oriented medical record, public community health centers and was therefore designed remain largely absent in contemporary primary care systems. to enable responses by patients presenting for care exhibiting Problem lists in contemporary electronic medical records often high levels of distress, relatively low literacy rates, weak motiva- contain diagnostic hypotheses rather than verifiable statements tional profiles, high burdens of illness and disease, and complex of the presenting problem or chief concern.35 Ensuing care plans biopsychosocial profiles. are therefore potentially formulated for the wrong diagnoses.36 The survey may be potentially well suited for application in The subsequent inappropriate care and outcomes are not ac- various primary care settings that strive to provide problem- curately captured, since the frame of reference (ie, the patient’s oriented care, regardless of the patient population profile. This actual problem) is effectively distorted. This compromises the is reaffirmed by the context and setting of the study’s clinical meaning of quality of care evaluations by health services re- site, an urgent primary care center with a multidisciplinary searchers. Without problem-oriented standards, primary care team providing care for patients from diverse demographic activities are often untethered from the realities of patients and and socioeconomic backgrounds, exhibiting various levels of are therefore of uncertain value.37,38 Starfield’s21 research there- urgency (of needs) and biopsychosocial complexity. It would fore strongly affirmed that the performance of primary care is be of value to test and to continue to validate the POPE-PC largely contingent on systems enabling problem recognition. survey at different health care settings (ie, different organization Trained both in clinical medicine (Pediatrics) and Public Health, contexts serving various patient population profiles) that strive I have devoted my entire professional career to improving the effec- to provide problem-oriented primary care, including virtual care tiveness and equity of health services. Early in my career, I developed or telehealth interactions. a conceptual scheme—published in the New England Journal of Accurate measurement of the core functions of primary care Medicine—that captured all the health systems [sic] characteristics enables meaningful performance assessment and the develop- related to providing health services. One key feature was identified ment of evaluation and quality improvement initiatives.3,30 At as “health needs and problem recognition” by health professionals, the study’s clinical site, monthly clinic and practitioner-level pa- a feature of care neglected by all approaches to measuring and as- tient experience reports are operationalized, the results of which suring quality of care. My subsequent work expanded on the notion are actively used by the clinic’s Medical Director and manage- that recognition of needs is a salient contributor to improvements in ment team to monitor performance and enable multidisciplinary individual and population health.

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How to Cite this Article It is therefore hypothetically plausible that the relatively high Shukor AR. Psychometric properties of the Problem-Oriented Patient level of performance of City Centre Urgent Primary Care Cen- Experience—Primary Care (POPE-PC) survey. Perm J 2020;24:19.191. DOI: tre on the POPE-PC survey can be attributed to the fact that https://doi.org/10.7812/TPP/19.191 its multidisciplinary team systematically elicits and documents patients’ presenting problems and concerns, which are coded References in the electronic medical record using Presenting Complaint 1. Bodenheimer T, Sinsky C. From triple to quadruple aim: Care of the patient requires codes derived from the Canadian Emergency Department care of the provider. Ann Fam Med 2014 Nov-Dec;12(6):573-6. DOI: https://doi. Information System Presenting Complaint List.39 It is likely org/10.1370/afm.1713 PMID:25384822 2. Gelmon S, Sandberg B, Merrthew N, Bally R. Refining reporting mechanisms in that most community-based primary care clinics in Canada, Oregon’s patient-centered primary care home program to improve performance. which solely use International Classification of Diseases, Ninth Perm J 2016 Sum;20(3):15-115. DOI: https://doi.org/10.7812/TPP/15-115 Revision electronic medical record classification systems and PMID:27213488 3. Shukor AR, Edelman S, Brown D, Rivard C. Developing community-based primary do not systematically elicit and code presenting problems or health care for complex and vulnerable populations in the Vancouver Coastal chief concerns, could manifest lower levels of performance on Health Region: HealthConnection Clinic. Perm J 2018;22:18-010. DOI: https://doi. the POPE-PC survey.35,40,41 Use of the POPE-PC tool across org/10.7812/TPP/18-010 PMID:30227907 4. Starfield B. Primary care: Balancing health needs, services, and technology. New primary care settings could reaffirm the importance of problem York, NY: Oxford University Press; 1998 recognition and promote positive changes to classification and 5. Malouin RA, Starfield B, Sepulveda MJ. Evaluating the tools used to assess the care standards, which ultimately contribute toward achievement medical home. Manag Care 2009 Jun;18(6):44-8. PMID:19569570 of the Quadruple Aim.1,4 6. Cassady CE, Starfield B, Hurtado MP, Berk RA, Nanda JP, Friedenberg LA. Measuring consumer experiences with primary care. Pediatrics 2000 Apr;105(4 Pt It is important to highlight that a formal assessment of concur- 2):998-1003. PMID:10742362 rent validity—although essential as part of the survey’s ongoing 7. Haggerty JL, Pineault R, Beaulieu M-D, et al. Practice features associated with validation process—was not performed within the scope of this patient-reported accessibility, continuity, and coordination of primary health care. Ann Fam Med 2008 Mar-Apr;6(2):116-23. DOI: https://doi.org/10.1370/afm.802 study. Concurrent validity will be the subject of future studies PMID:18332403 that will involve linkage of the POPE-PC survey dataset to 8. Wong ST, Haggerty JL. Measuring patient experiences in primary health care: a other datasets that are deemed to contain suitable variables that review and classification of items and scales used in publicly-available questionnaires [Internet]. Vancouver, BC: University of British Columbia Centre for Health Services enable analyses of concurrent validity. In the absence of a formal and Policy Research; 2013 May [cited 2019 Jan 7]. Available from: https:// assessment of concurrent validity, the study’s exploratory corre- open.library.ubc.ca/cIRcle/collections/facultyresearchandpublications/52383/ lation analysis (Table 6) provided interesting insights requiring items/1.0048528 9. Mead N, Bower P, Roland M. The General Practice Assessment Questionnaire further research, particularly in relation to potentially leveraging (GPAQ)—adevelopment and psychometric characteristics. BMC Fam Pract 2008 Feb questions outside the POPE-PC’s 2-factor structure (ie, Q7-Q9) 20;9(1):13. DOI: https://doi.org/10.1186/1471-2296-9-13 PMID:18289385 for assessment of concurrent validity. 10. Gallagher TJ, Hartung PJ, Gregory SW. Assessment of a measure of relational communication for doctor-patient interactions. Patient Educ Couns 2011 Dec 1;45(3):211-8. DOI: https://doi.org/10.1016/s0738-3991(01)00126-4 PMID:11722857 CONCLUSION 11. Forcino RC, Barr PJ, O’Malley AJ, et al. Using CollaboRATE, a brief patient-reported The POPE-PC survey was designed to enable the concep- measure of shared decision making: Results from three clinical settings in the United States. Health Expect 2018 Feb;21(1):82-9. DOI: https://doi.org/10.1111/hex.12588 tually sound measurement of patient experiences of problem- PMID:28678426 oriented primary care. This study indicates that the instrument 12. Safran DG, Kosinski M, Tarlov AR, et al. The Primary Care Assessment Survey: Tests has satisfactory psychometric properties and is unique in that it of data quality and measurement performance. Med Care 1998 May;36(5):728-39. DOI: https://doi.org/10.1097/00005650-199805000-00012 PMID:9596063 rigorously enables the assessment of initiatives promoting prob- 13. Wensing M, Mainz J, Grol R. A standardised instrument for patient evaluations of lem orientation in primary care, such as the IHI’s and National general practice care in Europe. Eur J Gen Pract 2000 Jan 1;6(3):82-7. DOI: https:// Patient Safety Foundation’s Ask Me 3 activities.26 The POPE- doi.org/10.3109/13814780009069953 21 14. Flocke SA. Measuring attributes of primary care: Development of a new instrument. J PC survey’s problem orientation reaffirms Starfield’s assertion Fam Pract 1997 Jul;45(1):64-74. PMID:9228916 that “recognition of needs is a salient contributor to improve- 15. Stewart AL, Nápoles-Springer AM, Gregorich SE, Santoyo-Olsson J. Interpersonal ments in individual and population health” and thereby aims to processes of care survey: Patient-reported measures for diverse groups. Health Serv Res 2007 Jun;42(3 Pt 1):1235-56. DOI: https://doi.org/10.1111/j.1475- make a positive contribution to operationalization of the IHI’s v 6773.2006.00637.x PMID:17489912 Quadruple Aim. 16. Saanich Peninsula Patient Experience Survey. Community Health and Care Evaluation Program. Victoria, British Columbia, Canada: Vancouver Island Health Disclosure Statement Authority. The author(s) have no conflicts of interest to disclose. 17. Borowsky SJ, Nelson DB, Fortney JC, Hedeen AN, Bradley JL, Chapko MK. VA community-based outpatient clinics: Performance measures based on patient perceptions of care. Med Care 2002 Jul;40(7):578-86. DOI: https://doi. Acknowledgments org/10.1097/00005650-200207000-00004 PMID:12142773 The author would like to acknowledge that the Problem-Oriented Patient 18. Hays RD, Berman LJ, Kanter MH, et al. Evaluating the psychometric properties of the Experience-Primary Care (POPE-PC) Survey was developed in collaboration CAHPS Patient-centered Medical Home survey. Clin Ther 2014 May;36(5):689-696. with the following team: Dean Brown, MD; Andrew Day, MSc; Rachael e1. DOI: https://doi.org/10.1016/j.clinthera.2014.04.004 PMID:24811752 McKendry, MA; Michael Norbury, MD; and Nardia Strydom, MD, ChB. The 19. Care Coordination Quality Measure for Primary Care (CCQM-PC) [Internet]. Rockville, MD: Agency for Healthcare Research and Quality; 2016 Jul [cited 2019 author notes that the content of the published article does not necessarily reflect Dec 11]. Available from: www.ahrq.gov/ncepcr/care/coordination/quality/index.html their respective individual views or perspectives. 20. Thayaparan AJ, Mahdi E. The Patient Satisfaction Questionnaire Short Form (PSQ- Kathleen Louden, ELS, of Louden Health Communications performed a 18) as an adaptable, reliable, and validated tool for use in various settings. Med primary copy edit. Educ Online 2013 Jul 23;18(1):21747. DOI: https://doi.org/10.3402/meo.v18i0.21747 PMID:23883565

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21. Starfield B. Primary care and equity in health: The importance to effectiveness and 32. Tai-Seale M, Elwyn G, Wilson CJ, et al. Enhancing shared decision making through equity of responsiveness to peoples’ needs. Humanity Soc 2009 Feb 1;33(1-2):56-73. carefully designed interventions that target patient and provider behavior. Health Aff DOI: https://doi.org/10.1177/016059760903300105 (Millwood) 2016 Apr;35(4):605-12. DOI: https://doi.org/10.1377/hlthaff.2015.1398 22. Starfield B. Health services research: A working model. N Engl J Med 1973 PMID:27044959 Jul 19;289(3):132-6. DOI: https://doi.org/10.1056/NEJM197307192890305 33. Barr PJ, Forcino RC, Thompson R, et al. Evaluating CollaboRATE in a clinical setting: PMID:4711342 Analysis of mode effects on scores, response rates and costs of data collection. BMJ 23. Krol MW, de Boer D, Delnoij DM, Rademakers JJ. The Net Promoter Score—An Open 2017 Mar 24;7(3):e014681. DOI: https://doi.org/10.1136/bmjopen-2016-014681 asset to patient experience surveys? Health Expect 2015 Dec;18(6):3099-109. DOI: PMID:28341691 https://doi.org/10.1111/hex.12297 PMID:25345554 34. Weed LL. Medical records that guide and teach. N Engl J Med 1968 Mar 24. Starfield B. Is patient-centered care the same as person-focused care? Perm J 2011 21;278(12):652-7. DOI: https://doi.org/10.1056/NEJM196803212781204 Spring;15(2):63-9. DOI: https://doi.org/10.7812/TPP/10-148 PMID:21841928 PMID:5637250 25. Shukor AR. An alternative paradigm for evidence-based medicine: Revisiting 35. Hofmans-Okkes IM, Lamberts H. The International Classification of Primary Care Lawrence Weed, MD’s system approach. Perm J 2017;21(16):16-147. DOI: https:// (ICPC): New applications in research and computer-based patient records in doi.org/10.7812/TPP/16-147 PMID:28488985 family practice. Fam Pract 1996 Jun;13(3):294-302. DOI: https://doi.org/10.1093/ 26. Ask Me 3: Good questions for your good health [Internet]. Boston, MA: Institute fampra/13.3.294 PMID:8671139 for Healthcare Improvement [cited 2019 Oct 21]. Available from: www.ihi.org:80/ 36. Weed LL, Weed L. Diagnosing diagnostic failure. Diagnosis (Berl) 2014 Jan resources/Pages/Tools/Ask-Me-3-Good-Questions-for-Your-Good-Health.aspx 1;1(1):13-7. DOI: https://doi.org/10.1515/dx-2013-0020 PMID:29539981 27. Quintana DS, Williams DR. Bayesian alternatives for common null-hypothesis 37. Weed LL, Weed L. Medicine in denial. Scotts Valley, CA: CreateSpace Independent significance tests in psychiatry: A non-technical guide using JASP. BMC Publishing Platform; 2011 Psychiatry 2018 Jun 7;18(1):178. DOI: https://doi.org/10.1186/s12888-018-1761-4 38. Weed LL, Weed L. Opening the black box of clinical judgment—an overview. PMID:29879931 Interview by Abi Berger. BMJ 1999 Nov 13;319(7220):1279. DOI: https://doi. 28. Gambashidze N, Hammer A, Brösterhaus M, Manser T; WorkSafeMed Consortium. org/10.1136/bmj.319.7220.1279 PMID:10559033 Evaluation of psychometric properties of the German Hospital Survey on Patient 39. Grafstein E, Bullard MJ, Warren D, Unger B; CTAS National Working Group. Safety Culture and its potential for cross-cultural comparisons: A cross-sectional Revision of the Canadian Emergency Department Information System (CEDIS) study. BMJ Open 2017 Nov 9;7(11):e018366. DOI: https://doi.org/10.1136/ Presenting Complaint List version 1.1. CJEM 2008 Mar;10(2):151-73. DOI: https://doi. bmjopen-2017-018366 PMID:29127231 org/10.1017/S1481803500009878 PMID:18371253 29. Dickert NW, Kass NE. Understanding respect: Learning from patients. J Med 40. Verbeke M, Schrans D, Deroose S, De Maeseneer J. The International Classification Ethics 2009 Jul;35(7):419-23. DOI: https://doi.org/10.1136/jme.2008.027235 of Primary Care (ICPC-2): An essential tool in the EPR of the GP. Stud Health PMID:19567690 Technol Inform 2006;124:809-14. PMID:17108613 30. Bodenheimer T, Ghorob A, Willard-Grace R, Grumbach K. The 10 building blocks of 41. Soler J-K, Okkes I, Wood M, Lamberts H. The coming of age of ICPC: Celebrating high-performing primary care. Ann Fam Med 2014 Mar-Apr;12(2):166-71. DOI: https:// the 21st birthday of the International Classification of Primary Care. Fam Pract 2008 doi.org/10.1370/afm.1616 PMID:24615313 Aug;25(4):312-7. DOI: https://doi.org/10.1093/fampra/cmn028 PMID:18562335 31. Tai-Seale M, Foo PK, Stults CD. Patients with mental health needs are engaged in asking questions, but physicians’ responses vary. Health Aff (Millwood) 2013 Feb;32(2):259-67. DOI: https://doi.org/10.1377/hlthaff.2012.0962 PMID:23381518

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Balazs I Bodai, MD, FACS; Therese E Nakata, STAR Provider, CWFPBN Perm J 2020;24:19.129 E-pub: 05/13/2020 https://doi.org/10.7812/TPP/19.129

ABSTRACT distinctive. The microbiome defines the collection of the genomes Patients with a current diagnosis of breast cancer are enjoying that the microbiota (the bacterial population) possess. The mi- dramatic cure rates and survivorship secondary to an increase crobiota are now considered an “essential organ” and have been in awareness, earlier detection, and more effective therapies. associated with overall health and chronic disease.5,8,9 Bacteria, Although strategies such as Breast Cancer Awareness Month in fungi, protozoa, yeast, and viruses comprise up to 90% of the October focus on early detection, lifestyle changes are seldom human cellular population.10 These organisms, until recently, discussed other than dietary concerns and physical activity. Life- were the unrecognized “organ system” responsible for most of style modifications centered on diet and exercise have been dem- our immunity. The microbiota rely on us, and in turn, we rely on onstrated to affect overall disease-free survival in breast cancer. them, representing a truly symbiotic relationship. An imbalance of Since the early 2000s, the role of the human gut microbiota and healthy and derogatory bacteria can lead to uncontrolled processes its relation to breast cancer has become a major area of interest in resulting in the development of chronic conditions, including the scientific and medical community. We live and survive owing to cancer.5,11,12 Results of recent investigations have suggested that the symbiotic relationship with the microorganisms within us: the specific hormones, particularly estrogen, and the gut microbiome human microbiota. Scientific advances have identified a subset of might act synergistically in the development of obesity, type 2 the gut microbiota: the estrobolome, those bacteria that have the diabetes mellitus (T2DM), and cancer.5,12 genetic capability to metabolize estrogen, which plays a key role Metabolic syndrome is characterized by central obesity, T2DM, in most breast cancers. Recent research provides evidence that the hypercholesterolemia, insulin resistance/hyperinsulinemia, and gut microbiome plays a substantial role in estrogen regulation. hypertension (Table 1). Metabolic syndrome is the result of life- Gut microbiota diversity appears to be an essential component of style choices that are modifiable by healthy changes.13-17 Recom- overall health, including breast health. Future research attention mendations addressing lifestyle adjustments that influence breast should include a more extensive focus on the role of the human cancer survivorship are evidence based.5,7 The underlying reasons gut microbiota in breast cancer. for their effectiveness are multifactorial, poorly understood, and often vague. In this report, we address potential factors that play INTRODUCTION a major role in breast cancer survival, particularly those that are In 2020, nearly 260,000 women in the US will receive a di- influenced by the gut microbiota. The potential ability to ma- agnosis of breast cancer, and more than 40,000 will die due to nipulate our gut microbiota through lifestyle recommendations the disease.1,2 Breast cancer is the most common malignancy may positively affect survival. among women, affecting 2.4 million women and responsible for more than 500,000 deaths worldwide.3 In 2015, there were an estimated 3.4 million breast cancer survivors in the US.4 This Table 1. Characteristics of the Metabolic Syndrome number increases yearly. Most breast cancer patients survive • Obesity (central) disease free for many years, making survivorship a major health issue. The American College of Surgeons has mandated that • Hypertension survivorship care plans become an integral component of their • T2DM (often related to obesity) accreditation. This has prompted the appearance of a plethora of articles addressing lifestyle issues that positively affect many • Hypercholesterolemia (HDL, Triglycerides) chronic comorbidities, a decrease in recurrence, and an increase in overall survival.4,5 Lifestyle recommendations, although inad- • Hyperinsulinemia (insulin resistance) equately addressed, also contribute to prolonged survival.5,7 Such recommendations are generally focused on diet and exercise, Table 1. Characteristics of metabolic syndrome but the developing awareness of the influence of the human gut microbiota on survival and overall health creates the need to ex- pand that focus to encompass diet, exercise, and the microbiome. Author Affiliations GUT MICROBIOTA AND HEALTH The Breast Cancer Survivorship Institute, Kaiser Permanente, Sacramento, CA The human microbiome is composed of trillions of microor- Corresponding Author ganisms living inside and outside the human body. Often used Balazs I. Bodai, MD, FACS ([email protected]) interchangeably, the terms microbiome and microbiota are, in fact, Keywords: breast cancer survivorship, estrobolome, human gut microbiota, inflammation, lifestyle, metabolic syndrome, microbiome, whole food plant-based diet

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Since 2010, the recognition of the gut microbiota on human puts one at risk of breast cancer. What has been referred to as health has been monumental, as demonstrated by the number of the standard American diet results in obesity, insulin resistance, medical publications in well-respected, peer-reviewed journals.18 dysbiosis, and inflammation.5 Insulin also stimulates the synthe- We are beginning to understand that a large portion of our im- sis of insulin growth factor-1 (IGF-1), linked to tumor growth munity resides in the human gut microbiota and that this ecologic and metastasis. Both estrogen and IGF-1-mediated signaling system, in and of itself, is a unique “organ.” The roughly 37 trillion are increased in obese postmenopausal women.27 “Cross-talk” cells in an average human are far surpassed by the nearly 100 tril- between such pathways represents an important link to tumor lion bacterial cells, which account for an estimated 2.25 to 2.7 kg progression. Obesity leads to a pathway of subclinical inflam- (5-6 lb) of an average human’s weight.19 Furthermore, a human’s mation; adipose tissues contribute to insulin resistance as well DNA is outnumbered by the DNA of these microbes by a factor as cancer development and progression. Activated macrophages of 100 to 800.20 The role of the gut microbiota and their effect on in adipose tissues in obese individuals produce proinflammatory dysbiosis (alterations in gut diversity) needs further investigation mediators. Obesity leads to insulin resistance, an increased level and may identify potential links in the development of cancer.21,22 of insulin, IGF-1, a decrease in adiponectin (the fat-burning The recently discovered estrobolome—those bacteria that are the hormone), and an increase in leptin (the satiety hormone).27,28 subset of the microbiota possessing genetic traits responsible for Leptin promotes angiogenesis, whereas adiponectin inhibits the estrogen metabolism and degradation—plays an important role same.28 Obesity has been associated with an increased risk of in the development and/or progression of breast cancer.23 postmenopausal breast cancer in addition to multiple metabolic There is little literature addressing the influence of the hu- disorders.5 Several biologic mechanisms may contribute to a man gut microbiota on long-term breast cancer survivorship. worsened prognosis of obese patients with breast cancer. This We address how lifestyle and the gut microbiota influence these is at least in part the result of the presence of comorbidities in concerns here and in Appendix 1. patients with breast cancer (Figure 1).17,29,30 Metabolic syndrome is a cluster of conditions that predict an DISCUSSION increased risk of cardiovascular disease and T2DM.30 Although Breast cancer survivorship is on the rise.24,25 Nearly 90% of major attention regarding this syndrome has focused on cardio- patients survive at least 5 years after diagnosis. Breast cancer is vascular disease risks, results of recent studies suggest that the no longer considered an acute disease; rather, it is now a chronic metabolic syndrome also plays an independent role in increas- condition.7,26 This creates an opportunity to improve the lives of ing the risk factors for breast cancer.31 Yet, the conditions that survivors through lifestyle choices. The Western lifestyle (a diet define this syndrome are modifiable by lifestyle changes. A well- high in sugar and fat, low in fiber, and minimal activity), however, recognized risk factor for breast cancer and recurrence, obesity

Figure 1. Impact of lifestyle on breast cancer. Although the diagram separates diet and inactivity, they are intimately connected, leading to an increase in obesity, T2DM, and ultimately an increase in inflammation. IGF1 = insulin growth factor 1; SHGB = steroid hormone-binding globulin; T2DM = type 2 diabetes mellitus.

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may also be substantially influenced by our gut microbiome.32 In in overall health.46-48 We believe the identification of the human addition to its capacity to store lipid, adipose tissue should be gut microbiome equals the importance of the discovery of aspirin, viewed as an active endocrine and metabolic organ. The human antibiotics, and vaccines. Our bodies are inhabited by trillions gut microbiome is intimately associated with obesity.19 of microorganisms that are vital to our survival, the majority of A major factor underlying the increased risk of hormone which reside in the gastrointestinal tract, particularly in the large receptor-positive breast cancers in obese women is an elevated intestine.18,49,50 The exact number/ratio of human cells vs gut estrogen level, which is related to increased adipose tissue mass microorganisms and the ratio of their DNA has been debated.51 and the production/storage of multiple inflammatory mediators.5 Further investigation is needed to resolve these figures. One fact Such proinflammatory molecules have been linked to tumor pro- is indisputable: the role of the gut microbiota is indeed important gression and the upregulation of aromatase (the enzyme respon- and regulates our well-being.52 sible for the conversion of testosterone to estrogenic compounds The human microbiota represent the constellation of micro- and unwanted byproducts of cholesterol metabolism).27 Obesity organisms that inhabit our bodies. The complex interactions of also leads to insulin resistance, hyperinsulinemia, and impaired the gut microbiota remain beyond our understanding, regardless glucose tolerance. High levels of fasting insulin in patients with of numerous advances in genomic profiling.53,54 More than 50% breast cancer have been associated with distant recurrence, me- of our gut microbiota refuses to be cultured or identified outside tastases, and increased mortality. Insulin has been implicated in the body using current technologies.8,53,55 cancer progression by virtue of its mitogenic, antiapoptotic, and Nearly 90% of our gut bacteria are composed of 2 major phyla: proangiogenic properties. Bacteroidetes and Firmicutes.46,53,56 These phyla and their ratios Physical inactivity promotes stress, inflammation, and psy- have been extensively studied; however, our understanding of chological issues such as depression, which are influenced by the them and their interactions remains elusive.32,47,57 Improper ra- gut microbiome. Obesity and self-image concerns may further tios of thousands of species have been linked to the development contribute to depression. Physical activity after breast cancer of multiple chronic conditions and account for more than 80% decreases cancer recurrence by 24%, decreases the risk of breast of all chronic maladies.5-7,44,53,58,59 When the ratios are optimal, cancer-related death by 34%, and decreases all-cause mortality these gut microbiota provide valuable services (energy produc- by 41%.33 Observational evidence suggests a primary reduction tion through the fermentation of foods, synthesis of vitamins, the in breast cancer between 30% to 50% with regular physical activ- building of amino acids, and a general oversight of the immune ity. 34 Even exercise such as walking for 30 minutes a day, 5 times system halting infections), keeping chronic conditions at bay and per week, may appreciably affect overall health. Physical activity preventing disease. guidelines for health in the US have recently been updated and Diet plays an integral role in the complex interrelationship have concluded that a sedentary lifestyle may be responsible for up between the human gut microbiota, estrogen metabolism, and to 10% of premature deaths.35-37 Although the “Physical Activity its influence on breast cancer recurrence as well as metastatic Guidelines for Americans” report is noteworthy and applauded, potential. The standard American diet results in the increased there was absolutely no mention of the role of lifestyle or its pro- propagation of unhealthy bacteria, which contain high levels of motion as an interventional strategy in the article by Giroir and β-glucuronidase. This enzyme is responsible for deconjugating Wright.35 The article did not specifically address cancer survivor- estrogen and returning it to the circulatory system, thus raising its ship or issues regarding the composition of the gut microbiota, availability to further fuel estrogen-responsive cancers. This diet which have been identified as playing a major role in fitness and results in a decrease in the production of short-chain fatty acids survival.38 However, it did note the importance of physical activity (SCFA; butyrate, propionate, and acetate), which play a major for overall health. Additional studies have demonstrated that the role in the prevention of “leaky gut syndrome.” This syndrome is adoption of a healthy lifestyle after a breast cancer diagnosis may responsible for the flow of harmful inflammatory products into decrease mortality rates by up to 50%. This can be accomplished the circulatory system, influencing the development and recur- if patients adhere to the adoption of a high fruit/vegetable diet rence of breast cancer. Inflammatory proteins promote insulin (4-5 servings per day) coupled with regular physical activity (30 resistance and support leptin, which influences carcinogenesis.60 minutes/5 times per week).39 Insulin binds steroid hormone-binding globulin (SHBG), in- Lifestyle medicine, as it relates to breast cancer survivorship, creasing estrogen availability, promoting higher estrogen levels, relies on 3 major pillars: diet, physical activity, and stress manage- and contributing to breast carcinogenesis.27,61 Adiponectin levels ment. Stress management is outside the scope of this article; it is are decreased, resulting in insulin resistance and increased levels extensively discussed elsewhere.5,7,40,41 There remains considerable of IGF-1, which promote cell proliferation.27 debate regarding the association of diet, physical activity, and can- In contrast, a whole-food, plant-based diet (especially one cer prevention.42 Medical advances in treating chronic conditions high in fiber) results in the promotion of “healthy” microbiota. have seen a revolution since the turn of the 21st century. Perhaps By decreasing the activity of β-glucuronidase, circulating estro- 2 of the most important advances have been 1) the identification gen levels are minimized, and SGBH is increased along with of epigenetics (turning genes on and off) and the modification the fecal excretion of estrogen. As SCFAs are increased, they of gene expression as opposed to the alteration of the genetic protect the colonic mucosa from developing leaky gut syndrome, code itself, which can be influenced by lifestyle,5,7,43-45 and 2) the decrease inflammation, and potentially lower the risk of breast recognition that the human gut microbiome plays a major role cancer.5,27,48,62-65 Estrogen is conjugated in the liver and excreted

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Figure 2. Dietary influence on gut microbiota/microbiome and estrogen metabolism. SHBG = steroid hormone-binding globulin.

into the gastrointestinal tract; estrogen is deconjugated by bac- consumption of a high-fiber diet, leading to the production of terial glucuronidase and is reabsorbed as free estrogen into the SCFAs and intestinal alkaline phosphatase.71 Intestinal alkaline bloodstream. Multiple bacteria are involved in this process; phosphatase is a protein of the intestinal epithelium that plays however, which bacteria are high producers of β-glucuronidase a major role in gut endothelial integrity. Along with SCFAs, in- remain controversial (Figure 2).66,67 testinal alkaline phosphatase strengthens the tight junctions of The current literature regarding the gut microbiota is confusing the colonic mucosa, decreasing the leakage of harmful pathogens and contradictory as a result of 2 factors. First, only recently have and their carcinogenic potential.5,20,72-74 Chronic inflammation we acquired technologies that effectively identify an important, may be promoted by the gut microbiota through its influence albeit small, portion of the microbiota. Second, there appears to be on self-proliferation and apoptosis.5,66,74-76 a disconnect that surrounds the interaction or interactions of these Nonalcoholic fatty liver disease (NAFLD) affects nearly one- bacteria. What is currently understood are the major bacteria and fourth of the global population.77,78 This presence of fat in the liver their phyla, which are summarized as follows. The phylum Fir- (hepatic steatosis) is a diagnosis based on exclusion of other causes micutes includes the genera Lactobacillus and Clostridium (various such as excessive alcohol consumption. Regardless of our poor subtypes), the phylum Bacteroidetes includes the genera Prevetella understanding of its etiology, NAFLD is of great importance and and Bacteroides, and the phylum Actinobacteria includes the genus a major cause of mortality, not only owing to the condition itself Bifidobacterium. These are believed to be the major producers of but also as a harbinger of malignancies, including breast cancer.77 SCFAs that result in a decreased breast cancer risk, recurrence, This association results from the fact that NAFLD is associated and mortality. There is evidence that 1 or another of the phyla with metabolic syndrome.79,80 Components of metabolic syn- in the gastrointestinal tract may be responsible for the majority drome and its association with breast cancer have been described of SCFA production. It appears that the primary producers of and documented in numerous publications.81-83 The influence of butyrate (the major colonic epithelial protector) are Firmicutes.68 NALFD on extrahepatic carcinogenesis and mortality has also Bacteroidetes may increase propionate, another beneficial SCFA, been noted.84 The association is poorly understood; however, although this has been less extensively studied.69 multiple hypotheses to explain a carcinogenic link have been put Firmicutes and Bacteroidetes are the major colonic phyla re- forth.85 The common link appears to be an inflammatory state, sponsible for the metabolism of fiber and polyphenols. Multiple fueled by hyperinsulinemia and resulting in tumor proliferation.60 studies have reached different conclusions on the impact of Inflammation, obesity, T2DM, and chronic conditions such these phyla, particularly as they relate to obesity (a major risk as cancer share common pathways, which are influenced by the factor for breast cancer).19,49,50,67,70 Leaky gut syndrome and the human gut microbiota.57,86-90 This complex and intricate system inflammation associated with it may well be minimized by the affects numerous distant organ systems.91 The idea that our

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microbial “friends” aid and participate in the promotion of our activity, both of which are modifiable. The gut microbiota are a health is hardly a new concept; in fact, such recognition dates major conduit in the inflammatory process. Our immune system to the 20th century.18 Similarly, the association of inflammation can only be challenged to a certain degree. When overcome by and cancer has long been recognized owing to the work of Vir- oxidative stressors and chronic inflammation, we may no longer chow.92-94 Inflammation plays a role in most chronic conditions be capable of responding to immunosuppressive conditions; the and, if uncontrolled, leads to chronic processes that promote development of malignancies is the result.99 tumorigenesis, from initiation to metastasis.95 Our sedentary lifestyle, the link between the gut microbiota In the diverse human gut microbiota exists a subset of bacteria and obesity, is well known.5,100 Overweight has now become a that possess the genetic capability to metabolize estrogen: the pandemic with serious psychosocial ramifications.101 Obesity is estrobolome. These microbes favor fiber as their primary source also an inflammatory state that promotes immune responses and of energy. When a high-fiber diet is consumed, the estrobolome carcinogenesis.5,102,103 Carcinogenesis is fueled by the development increases the metabolism of estrogen and thus its elimination of obesity because fatty tissues (particularly in the midsection) are from the body. Because nearly 70% of breast cancers are estrogen largely responsible for the promotion and storage of numerous fueled, a high-fiber diet contributes to estrogen elimination, rob- proteins that promote inflammation and estrogen production/ bing breast cancer cells of a major fuel source. The “commonsense” storage, fueling most breast cancers.5,52 recommendation to increase dietary fiber in the setting of breast Diabetes, now a pandemic, is recognized not just as a metabolic cancer decreases inflammation. The increased consumption of condition but an inflammatory process as well.91,104,105 The inter- fiber and polyphenols, readily available from a whole-food, plant- action of diabetes, obesity, and carcinogenesis is well known.91,92 based diet, contributes to an overall increase in breast cancer Understanding the role of the human gut microbiome in breast survival.5,7,96-98 The benefits of lifestyle recommendations in the cancer survival, obesity, and the comorbidity of diabetes should setting of breast cancer are summarized in Figure 3. be a focus of further research. Interventional strategies need to Our gut microbiota are not only subject to our dietary intake be identified starting with the promotion of a healthy lifestyle. but also are influenced by multiple prescription drugs and over- Emotional resilience (our response and recovery from a con- the-counter medications. The Western population seeks a cure siderable life-altering event) and the ability to deal with such for multiple conditions with a drug prescription. This has led to stressful issues (acute and chronic) are also influenced by the gut a nation that relies on a “pill for every ill,” and such an ideology microbiota. In particular, depression is an underaddressed con- may affect the gut microbiome (Appendix 2). cern in women with a diagnosis of breast cancer.106-110 The gut The Western world lives in a state of chronic inflammation microbiota play an important role in our ability to deal with emo- largely due to the standard American diet and low physical tional concerns because they are responsible for the production

Figure 3. Benefits of lifestyle recommendations for overall disease-free survival in breast cancer. CVD = cardiovascular disease; IAP = intestinal alkaline phosphatase; SCFA = short-chain fatty acids.

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of multiple neurotransmitters, including γ-aminobutyric acid, of our bacterial occupants is affected by dietary choices. Our gut norepinephrine, serotonin, and dopamine.111-113 The human gut microbiota represent an individual genetic “fingerprint” of each is responsible for the production of nearly 90% of the neurologic of us, as unique individuals, with no 2 being alike (Sidebar 1: The regulators of chemicals that affect our emotions. Lifecycle of the Gut Microbiota). A whole-food, plant-based diet contributes to the favorable ratio of Firmicutes/Bacteroidetes. Fat and dairy consumption CONCLUSION increases Bacteroidetes, whereas plant and fiber consumption in- Breast cancer is now a chronic condition and is no longer an creases Prevotella, Akkermansia, and other favorable bacteria.114-117 acute disease with the mediocre cure rates of decades ago. As such, Most research to date has addressed only the bacterial population there is time to intervene and provide healthy lifestyle recom- of the gut, and the investigation of the other microorganisms mendations that affect long-term, disease-free survival. Dietary has received little attention. The complex interactions of these recommendations are of major importance as they influence inhabitants have yet to be discovered but are certain to exist. The the gut microbiota, a major factor in increasing immunologic gut microbiota may be our most powerful endocrine regulator, strength. Additionally, management of breast cancer survivors because it affects nearly all distant organs and their appropriate is now recognized as a new subspecialty. More health care pro- functions.118,119 There exists a cross-talk between our immune grams are emerging that address long-term issues related to this system and the microbiota with the constant exchange of signals, ever-expanding population. Most individuals with breast cancer serving as an alarm for immune system activation. The population far exceed a 5-year disease-free survival. Dietary and lifestyle

Sidebar 1: The Lifecycle of the Gut Microbiota The gut microbiota is established at birth as the infant passes such we are ill-prepared to provide basic and much needed through the birth canal and becomes exposed to the vaginal nutritional advice for the prevention and reversal of chronic flora. In those born by cesarean section, such an early exposure conditions. Recent publications have called attention to this im- to the human microbiota is forfeited. Long-term consequences portant matter.7,10-12 Ultimately a healthy, high-fiber, whole food on the future health of such individuals is influenced by their plant-based diet, combined with an active lifestyle, reduces the microbiota habitants.1 Additionally, the breast-fed child is also risks of comorbidities, improves health, and improves breast exposed to additional bacteria, especially from colostrum, cancer survivorship. which is rich in bifidobacteria and further adds to the coloniza- tion of the newborn gut. Lack of early colonization of the young Sidebar References gut has been documented to result in a number of future 1. Odamaki T, Kato K, Sugahara H, et al. Age-related changes in gut microbiota chronic conditions.2 The inhabitants of the young gut microbio- composition from newborn to centenarian: a cross-sectional study. BMC Microbiology (2016)16:90DOI 10.1186/s12866-016-0708-5 ta appear to play a significant role in the establishment of early 2. Arboleya S, Watkins C, Stanton C, Ross RP. Gut Bifidobacteria Populations in onset immunity.3,4 As the impact of the gut microbiota becomes Human Health and Aging. Front Microbiol. 2016 Aug 19;7:1204. doi: 10.3389/ further unraveled, we are starting to realize that as we age our fmicb.2016.01204. microbiota “ages” as well; a concept not previously recognized. 3. Urbaniak C, Burton JP, Reid G. Breast , Milk and Microbes: A Complex Relationship that Does Not End with Lactation. 2012.doi.org/10.2217/WHE.12.23 Each human cell has a natural life cycle with apoptosis (cell 4. Toscano M, DeGrandi R, et al Role of the Human Breast Milk- Associated death) as their final destination. Currently, we hardly possess a Microbiota on the Newborns Immune System: A Mini Review. Front full understanding of the complete life cycle of the nearly 100 Microbiol.2017:8:2100 5. Boccardi V, Paolisso G, Mecocci P. Nutrition and lifestyle in healthy aging: the trillion gut microorganisms that occupy our gastrointestinal telomerase challenge. Aging 2016. 8(1):12-15.doi:10.18632/aging.100886 tract. Despite lack of such information, we do understand that 6. Werner CM, Hecksteden A, Morsch A, et al. Differential effects of endurance, the gut microbiota is also subject to an aging process.5,6 Telo- interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study. Eur Heart J. 2018;40(1):34–46. doi:10.1093/ mere length, which decreases with age, has been recognized as eurheartj/ehy585 a bio-marker of aging and its association with the development 7. Bodai BI, Nakata TE, Wong WT, et al. Lifestyle Medicine: A Brief Review of Its of malignancies has been noted.5-9 Bacterial DNA also possess Dramatic Impact on Health and Survival. The Permanente Journal. 2018;22:17- 025. doi:10.7812/TPP/17-025. telomeres, which decrease in length with aging, resulting in a 8. Bodai BI, Tuso P. Breast cancer survivorship: A comprehensive review of reduced lifespan. long-term medical issues and lifestyle recommendations. Perm J. 2015 Spring;19(2):48–79. DOI: https://doi.org/10.7812/TPP/14-241. Because of our newly acquired understanding of the impor- 9. Ornish D, Lin J, Chan JM, et al. Effect of comprehensive lifestyle changes on tance of the gut microbiota, recent attention has also been di- telemerase activity and telomere length in men with biopsy-proven low-risk rected to the importance of educating health care practitioners prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol. 2013 Oct;14(11):1112-1120.doi:10.1016/S1470-2045(13)70366-8. and patients regarding a healthy lifestyle. This must begin with 10. Abbasi J. Medical Students Around the World Poorly Trained in Nutrition. JAMA. a focus on nutrition education—the food sources that feed and Published online October 31, 2019. doi:https://doi.org/10.1001/jama.2019.17297 promote a healthy gut microbiota.7 As with all living organisms, 11. Devries S, Willett W, Bonow RO. Nutrition education in medical school, residency training, and practice. JAMA 2019 Mar 21; 321(14):1351-2. DOI:https:// the health of the microbiota is determined by the quality of the doi.org/10.1001/jama.2019.1581 nutrients consumed. There exists a significant lack of nutritional 12. Rahman V. Time to revamp nutrition education for physicians. Perm J education in medical schools and post-graduate training. As 2019;23:19.052.DOI:https://doi.org/10.1812/TPP/19.052

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98. Roopchard DE, Carmody RN, Kuhn P, et al. Dietary Polyphenols Promote Growth 109. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst of the Gut Bacterium Akkermansia muciniphila and attenuate High Fat diet-Induced Monogr. 2004;(32):57-71. DOI: https://doi.org/10.1093/jncimonographs/lgh014. metabolic Syndrome. Diabetes. 2015:64;2547-58 110. Dash S, Clarke G, Berk M, Jacka FN. The gut microbiome and diet in psychiatry: 99. Reuter S, Subash CG, Chaturuedi MM, et al. Oxidative Stress, inflammation, focus on depression. Curr Opin Psychiatry. 2015 Jan;28(1):1-6. doi:10.1097/ and cancer: How are they linked? Free Radic Biol Med. 201049(11):1603-16. YCO.0000000000000117. doi:10:1016/J.freeradbiomed.2010.09.006 111. Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota 100. Wolf KJ, Lorenz RG. Gut microbiota and obesity. Curr Obes Rep 2012 Mar 1;1(1):1-8. on brain and behavior. Nat Rev Neurosci. 2012;13:701-12 DOI: https://doi.org/10.1007/s13679-011-0001-8. 112. Gillard L. The Gut Microbiome and the Brain. J Med Food 2014;17(12):1261-72 101. Apovian CM. The obesity epidemic-understanding the disease and the treatment. N 113. Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human Engl J Med. 2016;374:177-9 gut microbiota in quality of life and depression. Nat Microbiol. 2019 Apr;4(4):623-632. 102. Cancello R, Clément K. Review article: Is obesity an inflammatory illness? Role 114. Dao MC, Everard A, Aron-Wisnewsky J. Akkermansia muciniphila and improved of low-grade inflammation and macrophage infiltration in human white adipose metabolic health during a dietary intervention in obesity: relationship with tissue. BJOG 2006 Oct;113(10):1141-7. DOI: https://doi.org/10.1111/j.1471- gut microbiome richness and ecology. Gut 2016;65:426-436.doi:10.1136/ 0528.2006.01004.x gutjnl-2014-308778 103. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Ann Rev Immunol. 115. Anhê FF, Pilon G, Roy D, et al. Triggering Akkermansia with dietary polyphenols: A 2011;29:415-45. DOI: https://doi.org/10.1146/annurev-immunol-031210-101322. new weapon to combat the metabolic syndrome? [published correction appears in 104. Klonoff DC. The increasing incidence of diabetes in the 21st century. J Diabetes Sci Gut Microbes. doi: 10.1136/gutjnl-2014-307142]. Gut Microbes 2016;7(2):146-153. do Technol. 2009 Jan;3(1):1-2. DOI: https://doi.org/10.1177/193229680900300101. i:10.1080/19490976.2016.1142036 105. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005 116. Cani PD, de Vos WM. Next-generation beneficial microbes: The case of May;115(5):1111-9. DOI: https://doi.org/10.1172/jci25102. Akkermanisa muciniphila. Front Microbiol 2018;8:1765. DOI: https://doi.org/10.3389/ 106. Mitchell AJ, Chan M, Bhatti H, et al. Prevalence of depression, anxiety, and fmicb.2017.01765. adjustment disorder in oncological, haematological, and palliative-care settings: a 117. Geerlings SY, Kostopoulos I, de Vos WM, Belzer C. Akkermansia muciniphila in the meta-analysis of 94 interview-based studies. Lancet Oncol. 2011 Feb;12(2):160-74. Human Gastrointestinal Tract: When, Where, and How? Microorganisms. 2018 Jul DOI: https://doi.org/10.1016/S1470-2045(11)70002-X. 23;6(3). pii: E75. doi: 10.3390/microorganisms6030075. 107. Fann JR, Berry DL, Wolpin S, et al. Depression screening using the Patient Health 118. Evans JM, Morris LS, Marchesi JR. The gut microbiome- the role of a virtual organ in Questionnaire-9 administered on a touch screen computer. Psychooncology. 2009 the endocrinology of the host. J Endocrinol. 2013; 218:R37-R47. Jan;18(1):14-22. DOI: https://doi.org/10.1002/pon.1368. 119. Clarke G, Stilling RM, Kennedy PJ, et al. Minireview: Gut microbiota: the neglected 108. Berk M, Jacka FN. Diet and Depression- From Confirmation to Implementation. JAMA endocrine organ. Mol Endocrinol. 2014Aug;28(8):1221-38. doi: 10.1210/me.2014- 2019:321(9);842-3. 1108.

Appendix 1: Adverse effects of currents treatments for breast cancer and the gut microbiome

Cardiovascular Concerns invasive radiotherapies years ago and, thus their cardiovascular Cardiovascular disease (CVD) is the current leading cause of adverse effects may only be peaking at 10-20 years post exposure. mortality in women in the United States.1-3 Although mortal- As such, cardiovascular adverse effects are more likely to occur ity rates for CVD have declined in recent years, this decline in this aging population.21-26 (Figure 1) has waned.4 Recent information appears conflicting regard- Cardiovascular health is influenced by the bacteria that reside ing long-term toxicities of current regimens employed to treat in our gastrointestinal tract.27 The Standard American Diet may breast cancer.5 Survival following breast cancer has increased in promote the development of CVD by influencing the growth the past decades, and as such, increase the risk of death from and altering the ratios of good/bad bacteria.28 A major concern cardiovascular events simply due to aging. Cardiac events exceed is the recognition that the consumption of red and processed the risk of death from breast cancer or its recurrence.1,2,6-8 Cur- meats results in an increase in all-cause mortality. Such foods rently employed chemotherapeutic agents may result in future chronic cardiovascular complications.3,9,10 Targeted biologic thera- Figure 1. pies have assumed a prominent role in the treatment of breast cancer portend short- and long-term cardiotoxic effects.11-13 Radiation therapy, as an adjunctive treatment in breast conserving therapy (BCT), has been proven equally effective compared with modified radical mastectomy, and results in reduced recurrence and mortality.14-20 As radiotherapy is undergoing a rapid evolution, (i.e. altera- tions in schedules of administration, radiation exposure, dosage, length of therapy, etc), we anticipate potential cardiovascular effects will diminish. However, many current survivors had been subjected to more intensive and

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are high in L-carnitine and lead to elevated serum levels of tri- cannot tolerate the adverse-effects nor adhere to such long-term methylamine which are hepatically converted to trimethylamine anti-estrogenic therapies. oxide (TMAO) through the action of the gut microbiota. Red The gut microbiome is intricately involved in the regulation meat intake reduction may decrease TMAO formation, inhibiting of estrogen levels. A dysbiotic environment plays a crucial role atherogenesis by the down-regulation of the macrophagic uptake in circulating estrogens. Within the nearly 100 trillion microbes of oxidized endothelial cells. Additionally, this may minimize that inhabit us, there exists a subset of these colonizers known to damage to the colonic endothelial barrier decreasing the develop- possess the genetic capability to influence estrogen metabolism, ment of the “leaky gut” syndrome.29,30 The association of TMAO the “estrobolome.”73,74 Although systemic estrogen modulation is production appears to be gut-microbiota dependent.27,31,32 beyond the scope of this article, the reader is directed to several comprehensive reviews of this issue.6,74,75 Bone Health Concerns Breast cancer survivors are at an increased risk of developing Thromboembolic Concerns osteoporosis, as an adverse effect of current therapies, as well as Cancer, regardless of tissue origin, is a prothrombotic state,76-79 increased longevity. As nearly 75% of breast cancers are estrogen well recognized since the German physician Virchow originally driven, the use of aromatase inhibitors (AIs; anastrozole, letrozole identified the association of cancer and inflammation in 1863.80-82 and aromasin) in estrogen receptor positive breast cancers have The second leading cause of death in patients diagnosed with a been markedly effective in decreasing recurrence,6,33 however malignancy is, in fact, a thromboembolic event.78,83 Patients with AIs can result in a substantial and often rapid decrease in bone a cancer diagnosis have a 4- to7-fold increased risk of a throm- mineral density and contribute to an increased risk of fracture.34,35 boembolic event compared with those without cancer.84,85 An Osteoporosis, the destruction of the bony matrix, is a condition important adverse effect of anti-estrogenic therapy is an increase often unrecognized until a fracture event. Risk factors for the in the risk of thromboembolic events. Tamoxifen, the earliest development of osteoporosis have been identified and aggressive and most frequently prescribed hormonal blocker increases the interventions for prevention are needed.36-41 Multiple prescription risk of such an episode by1% to 2%.86-90 The human gut micro- drugs, especially for minimal indications such as gastrointestinal biome directly increases the potential of a thromboembolic event symptoms related to acid reflux and psychotropic drugs for de- through its role in the generation of trimethylamine and in the pression also promote the development of osteoporosis. These, up-regulation of platelet production, increasing the risk of throm- among other frequently prescribed medications, account for more bosis. The association between TMAO (oxidized trimethylamine) than 100 million prescriptions annually.42-49 Recent studies have production and the consumption of foods high in L-carnitine established an association between the human gut microbiota and (red meat), and choline (poultry, fish and dairy) is well known. bone metabolism.50-52 The exact mechanism of bone metabolism TMAO production is easily influenced by modifying our diet regulation by the gut microbiota is unclear, however multiple decreasing thrombogenesis.6,30,33,91,92 pathways have been proposed. These include influencing the -im mune and endocrine systems as well as potential interference with Emotional Concerns the absorption of calcium.50,53-55 A healthier microbiota could be Depression and anxiety, so prevalent in the modern world, beneficial in maintaining bone health of breast cancer survivors. are major risk factors affecting health. Depression is projected to be the second-largest health care burden within the next Hormonal Blockade Concerns few years.93 Depression is particularly relevant in the setting of The majority of breast cancers are endogenous estrogen driv- breast cancer as it is often unrecognized, under addressed, and en,56-62 a favorable characteristic associated with less aggressive inadequately treated.6,30,94,95 Depression has also been associ- disease. More than 30 years of data demonstrate the effect of ated with an increase in CVD.96 Undiagnosed, depression can hormonal blockade in decreasing death rates.9,63,64 Strong evi- diminish treatment adherence, resulting in inferior outcomes.97 dence suggests overall disease-free survival in patients adhering Intensified screening, earlier interventions, and “cancer-specific to long-term hormonal blockade. Unfortunately, a substantial depression”counseling has become available.98,99 The role of the number of patients who would benefit from such therapeutic gut microbiome is now recognized as a contributor to depres- interventions do not avail themselves of this proven recommen- sion and to overall mental health.100 This is the result of the gut dation. Rates of compliance to a 5-year regimen only approach microbiota’s influences on the levels of circulating chemicals that 30% to 70%.65-67 Previous studies have demonstrated a higher directly influence mood and affect. The role of diet, as it affects recurrence rate and an increase in mortality in those discontinu- depression and anxiety is an area of intense research as current ing the recommended 5-year regimen.68,69 More recent studies evidence supports such an association.101-103 suggest that a 10-year protocol may result in a further increase in overall disease-free survival.70-72 Adherence to a five-year regimen References 1. 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Borger JH, Hooning MJ, Boersma LJ, et al. Cardiotoxic effects of tangential breast 47. Roux C, Briot K, Gossec L, et al. Increase in vertebral fracture risk in postmenopausal irradiation in early breast cancer patients: the role of irradiated heart volume. Int J women using omeprazole. Calcif Tissue Int. 2009 Jan;84(1):13–9. DOI: http://dx.doi. Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1131–8. DOI: http://dx.doi.org/10.1016/j. org/10.1007/s00223-008-9188-4. ijrobp.2007.04.042 48. Targownik LE, Leslie WD, Davison KS, et al. CaMos Research Group The 23. Doyle JJ, Neugut AI, Jacobson JS, et al. Radiation therapy, cardiac risk factors, and relationship between proton pump inhibitor use and longitudinal change in cardiac toxicity in early-stage breast cancer patients. Int J Radiat Oncol Biol Phys. bone mineral density: a population-based study from the Canadian Multicentre 2007 May 1;68(1):82–93. DOI: http://dx.doi.org/10.1016/j.ijrobp.2006.12.019. 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49. Rizzoli R, Cooper C, Reginster JY, et al. Antidepressant medications and 6953 women with early breast cancer [ASCP Annual Meeting Abstracts] J Clin Oncol. osteoporosis. Bone. 2012 Sep;51(3):606–13. DOI: http://dx.doi.org/10.1016/j. 2013;31(15_suppl May 20):5. bone.2012.05.018. 73. Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 50. Xu X, Jia X, Mo L, etal. Intestinal Microbiota: a potential target for the treatment 2011;10(4):324-35 of postmenopausal osteoporosis. Bone Research (2017): 5:17046;10.1038/ 74. Kwa M, Plottel CS, Blaser MJ et al The Intestinal Microbiome and Estrogen Receptor- boneres.2017..46 Positive Female Breast Cancer. 2016:JNCI108(8):djw029doi:10.1093/jnci/djw029 51. Yan J, Herzog JW, Tsang K et al. Gut microbiota induce IGF-1 and promote bone 75. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: formation and growth. Proc Natl Acad Sci USA 2016; 113: E7554–e7563. Physiological and clinical implications.maturitas.2017;103,45-53. 52. Guss JD, Horsfield MW, Fontenele FF et al. Alterations to the gut microbiome impair 76. Turken S, Siris E, Seldin D, Flaster E, Hyman G, Lindsay R. Effects of tamoxifen bone strength and tissue material properties. J Bone Miner Res 2017; 32: 1343– on spinal bone density in women with breast cancer. J Natl Cancer Inst. 1989 Jul 1353. 19;81(14):1086–8. DOI: http://dx.doi.org/10.1093/jnci/81.14.1086 53. Zupan J, Jeras M, Marc J. Osteoimmunology and the influence of pro-inflammatory 77. Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral cytokines on osteoclasts. Biochem Med (Zagreb) 2013; 23: 43–63. density in postmenopausal women with breast cancer. N Engl J Med. 1992 Mar 54. Geuking MB, Koller Y, Rupp S et al. The interplay between the gut microbiota and the 26;326(13):852–6. DOI: http://dx.doi.org/10.1056/NEJM199203263261302. immune system. Gut Microbes 2014; 5: 411–418. 78. Letai A, Kuter DJ. Cancer, coagulation, and anticoagulation. Oncologist. 55. Crotti TN, Dharmapatni AA, Alias E et al. Osteoimmunology: major and costimulatory 1999;4(6):443–9. pathway expression associated with chronic inflammatory induced bone loss. J 79. Vehmanen L, Elomaa I, Blomqvist C, Saarto T. Tamoxifen treatment after adjuvant Immunol Res 2015;2015: 281287. chemotherapy has opposite effects on bone mineral density in premenopausal 56. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998 Nov patients depending on menstrual status. J Clin Oncol. 2006 Feb 1;24(4):675–80. DOI: 26;339(22):1609–18. DOI: http://dx.doi.org/10.1056/NEJM199811263392207 http://dx.doi.org/10.1200/JCO.2005.02.3515. 57. Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by 80. Green KB, Silverstein RL. Hypercoagulability in cancer. Hematol Oncol Clin immunohistochemistry is superior to the ligand-binding assay for predicting response North Am. 1996 Apr;10(2):449–530. DOI: http://dx.doi.org/10.1016/S0889- to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999 May;17(5):1474– 8588(05)70349-X. [PubMed] 388. 81. 81. Rickles FR, Levine MN. Venous thromboembolism in malignancy and malignancy in 58. Fabian CJ, Kimler BF. Selective estrogen-receptor modulators for primary prevention venous thromboembolism. Haemostasis. 1998;28(Suppl 3):43–9. DOI: http://dx.doi. of breast cancer. J Clin Oncol. 2005 Mar 10;23(8):1644–55. DOI: http://dx.doi. org/10.1159/000022404. org/10.1200/JCO.2005.11.005 82. Kumar DR, Hanlin E, Glurich I, Mazza JJ, Yale SH. Virchow’s contribution to the 59. Kennecke HF, Ellard S, O’Reilly S, Gelmon KA. New guidelines for treatment of early understanding of thrombosis and cellular biology. Clin Med Res. 2010 Dec;8(3– hormone-positive breast cancer with tamoxifen and aromatase inhibitors. B C Med J. 4):168–72. DOI: http://dx.doi.org/10.3121/cmr.2009.866. 2006 Apr;48(3):121–6. 83. Donati MB. Cancer and thrombosis. 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DOI: http://dx.doi.org/10.1093/ to adjuvant hormonal therapy in a cohort of 8,679 early-stage breast cancer jnci/90.18.1371. patients. J Clin Oncol. 2010 Sep 20;28(27):4120–8. DOI: http://dx.doi.org/10.1200/ 88. Braithwaite RS, Chlebowski RT, Lau J, George S, Hess R, Col NF. Meta-analysis of JCO.2009.25.9655 vascular and neoplastic events associated with tamoxifen. J Gen Intern Med. 2003 65. Partridge AH, Wang PS, Winer EP, Avorn J. Nonadherence to adjuvant tamoxifen Nov;18(11):937–47. DOI: http://dx.doi.org/10.1046/j.1525-1497.2003.20724.x. therapy in women with primary breast cancer. J Clin Oncol. 2003 Feb 15;21(4):602–6. 89. Vogel VG, Costantino JP, Wickerham DL, et al. National Surgical Adjuvant Breast and DOI: http://dx.doi.org/10.1200/JCO.2003.07.071. Bowel Project (NSABP) Effects of tamoxifen vs raloxifene on the risk of developing 66. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen Adherence to adjuvant therapy among breast cancer survivors in clinical practice: and Raloxifene (STAR) P-2 trial. JAMA. 2006 Jun 21;295(23):2727–41. DOI: http:// a systematic review. Breast Cancer Res Treat. 2012 Jul;134(2):459–78. DOI: http:// dx.doi.org/10.1001/jama.295.23.joc60074. dx.doi.org/10.1007/s10549-012-2114-5. 90. Vogelvang TE, van der Mooren MJ, Mijatovic V, Kenemans P. Emerging selective 67. Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with estrogen receptor modulators: special focus on effects on coronary heart disease hormone receptor-positive breast cancer: American Society of Clinical Oncology in postmenopausal women. Drugs. 2006;66(2):191–221. DOI: http://dx.doi. clinical practice guideline focused update. J Clin Oncol. 2014 Jul 20;32(21):2255–69. org/10.2165/00003495-200666020-00005. DOI: http://dx.doi.org/10.1200/JCO.2013.54.2258. 91. Zhu W, Gregory JC, Org E, et al. Gut Microbial Metabolite TMAO Enhances 68. Geiger AM, Thwin SS, Lash TL, et al. Recurrences and second primary breast Platelet Hyperactivity and Thrombosis Risk. Cell 2017;165(1): 111-24.doi:10.1016/j. cancers in older women with initial early-stage disease. Cancer. 2007 Mar cell.2016.02.011 1;109(5):966–74. DOI: http://dx.doi.org/10.1002/cncr.22472. 92. Zhu W, Want Z, Tang WH, et al. Gut Microbe-Generated Trimethylamine N-Oxide 69. Yood MU, Owusu C, Buist DS, et al. Mortality impact on less-than-standard therapy From Dietary Choline is Prothrombotic in Subjects.Circulation 2017;135;1167-73. in older breast cancer patients. J Am Coll Surg. 2008 Jan;206(1):66–75. DOI: http:// doi:10;1161/CIRCUALTION ANA,116.025338. dx.doi.org/10.1016/j.jamcollsurg.2007.07.015. 93. Lopez AD, Murray CC. The global burden of disease, 1990–2020. Nat Med. 1990 70. Cuzick J, Sestak L, Baum M, et al. ATAC/LATTE Investigators Effect of anastrozole Nov;4(11):1241–3. DOI: https://doi.org/10.1038/3218. and tamoxifen as adjuvant treatment for early-stage breast cancer: 10 year analysis 94. Fann JR, Thomas-Rich AM, Katon WJ, et al. Major depression after breast of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135–41. DOI: http://dx.doi. cancer: a review of epidemiology and treatment. Gen Hosp Psychiatry. 2008 Mar- org/10.1016/S1470-2045(10)70257-6. Apr;30(2):112–26. DOI: http://dx.doi.org/10.1016/j.genhosppsych.2007.10.008. 71. Davies C, Pan H, Godwin J, et al. Adjuvant Tamoxifen: Longer Against Shorter 95. Mitchell AJ, Chan M, Bhatti H, et al. Prevalence of depression, anxiety, and (ATLAS) Collaborative Group Long-term effects of continuing adjuvant tamoxifen to adjustment disorder in oncological, haematological, and palliative-care settings: a 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive meta-analysis of 94 interview-based studies. Lancet Oncol. 2011 Feb;12(2):160–74. breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805–16. DOI: http://dx.doi.org/10.1016/S1470-2045(11)70002-X. DOI: http://dx.doi.org/10.1016/S0140-6736(12)61963-1. Erratum in: Lancet 2013 Mar 96. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular 9;381(9869):804. DOI: http://dx.doi.org/10.1016/S0140-6736(13)60252-4 disease: A clinical review. Eur Heart J. 2014 Jun 1;35(21):1365–72. DOI: https://doi. 72. Gray RG, Rea D, Handley K, et al. aTTOM Collaborative Group aTTom: long-term org/10.1093/eurheartj/eht462. effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in

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97. Reich M, Lesur A, Perdrizet-Chevallier C. Depression, quality of life and breast 1108. Epub 2014 Jun 3. Review. PubMed PMID: 24892638; PubMed Central PMCID: cancer: a review of the literature. Breast Cancer Res Treat. 2008 Jul;110(1):9–17. PMC5414803. DOI: http://dx.doi.org/10.1007/s10549-007-9706-5. 101. Jacka FN, Pasco JA, Mykldefun A, et al Association of Western and traditional diets 98. Strong V, Waters R, Hibberd C, et al. Management of depression for people with with depression and anxiety in women. AmJ psychiatry, 2010;169(3):305-11 cancer (SMaRT oncology 1): a randomised trial. Lancet. 2008 Jul 5;372(9632):40–8. 102. Lassale C, Batty GD, Baghdadli P, et al. Healthy dietary indices and risks of DOI: http://dx.doi.org/10.1016/S0140-6736(08)60991-5. depressive outcomes.Mol Psychiatry.2018.doi:10.1038/s41380-018-0237-8 99. Fann JR, Berry DL, Wolpin S, et al. Depression screening using the Patient Health 103. Berk M, Jacka FN. Diet and Depression-From Confirmation to Implementation. JAMA Questionnaire-9 administered on a touch screen computer. Psychooncology. 2009 2019:321(9);842-3. Jan;18(1):14–22. DOI: http://dx.doi.org/10.1002/pon.1368. 100. Clarke G, Stilling RM, Kennedy PJ, et al. Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014Aug;28(8):1221-38. doi: 10.1210/me.2014-

Appendix 2: The impact of common pharmacologic interventions on the gut microbiota and breast cancer

Antibiotics understanding of the gut microbiome expands, the influence of Recent concerns have been raised that the ongoing, indiscrimi- commonly prescribed medications and the role they play in the nate use of antibiotics may result in an increase in the incidence development of disease progression deserves attention.19,20 and fatality of breast cancer.1 Lifesaving antibiotics are one of the most effective therapeutics since their initial identification Antidepressants by Ehrlich and Fleming in the early 20th century.2 Undoubt- Antidepressants are yet another overprescribed medication in edly, saving countless lives, these drugs may also have become a the US. Nearly 10% of our population consume such drugs on significant threat to our future. Overprescribing, a common daily a regular basis.17,21,22 These prescriptions have increased nearly practice, disrupts the normal flora of the gut microbiota and may 65% since 2010 and women are twice as likely to be prescribed contribute to disease.1,3 In 2015 nearly 300 million antibiotic such medications.23 Each year millions of prescriptions are writ- prescriptions were dispensed in the US; nearly one-third lacked ten; more than one-third are inappropriately dispensed, without a proper indication.4,5 Antibiotics, by destroying pathogens also evidence of efficacy. Mental health issues, beyond depression, and disrupt healthy bacteria and contribute to a state of dysbiosis.6 their relationship to the gut microbiome, are receiving increased Furthermore, resistance to antibiotics develops as bacterial genes attention.24 Evidence is accumulating that the gut microbiota evolve and the growth of multidrug resistant pathogens emerge.7 communicates with the central nervous system influencing hu- In addition to overprescribing, antibiotics enter our diet through man behavior. The gut microbiota not only synthesizes, but also meat and dairy products that contain high levels of antibiot- respond to neurotransmitters that affect our mental health.25,26 ics used prophylactically in animals. In fact, most antibiotics produced in the US (18.4 million pounds) are utilized by the Polypharmacy agricultural industry.8 Antibiotics, given in early childhood, also Consideration must also be given to the issue of polyphar- have a profound influence on the development of future obesity.9 macy—the simultaneous prescription of multiple drugs which Antibiotics have a definitive impact on the gut microbiota, al- is increasing in the aging population.27 It has long been known though their exact interference requires further investigation.10,11 that as the number of drugs prescribed rises, so do potential in- Antibiotic use and its relation to breast cancer development has teractions, often negating or potentiating effects of one on the been postulated, as these drugs may disrupt the phytochemical other or even resulting in adverse events. Polypharmacy needs metabolic pathways that influence the development and progres- to be recognized as a growing problem as many malignancies sion of breast cancer.1 are also age related.27-29 As the gut microbiota becomes further characterized, newer targeted therapies may be developed that Proton-Pump Inhibitors affect overall disease-free breast cancer survival and long-term Nearly 150 million prescriptions for proton-pump inhibitors cure.30 Multiple other drugs affect the microbiotic ecology which are written annually in the US to treat gastrointestinal complaints, are beyond the scope of the current manuscript but are reviewed in particular, reflux.12,13 The majority of such prescriptions are in-depth and are available.31,32 proton pump inhibitors, which inhibit the gastric delivery of acids.14 Anti-reflux medications, first introduced in the 1980s, References 1. Velicer CM, Heckbert Sr, Lampe JW, et al Antibiotic Use in Relation to the Risk of contribute to decreasing the diversity of the gut microbiota. Breast Cancer. JAMA 2004 291(7);827-35 Many of these medications are “over the counter” and are used 2. Aminov R. A Brief History of the Antibiotic Era: Lessons Learned and Challenges for for prolonged periods, without demonstrable benefit, and beyond the Future. Front. Microbiol. 2010.doi.org/10.389/fmicb.2010.00134 13 3. Davies J, Davies J Origins and Evolution of Antibiotic Residence. Microbiota Mol Biol professional control. Bacteria originating in the oral cavity may Rev 2010;74(3):417-33 be altered by these medications and contribute to dysbiosis in 4. Centers for Disease Control and Prevention Outpatient Antibiotic Prescriptions – the distal gastrointestinal tract.14-16 Such drugs also interfere United States, 2014.cdc.gov/antibiotic-use/community/pdfs/annual report-2015.pdf 5. Fleming-Dutra K, et al Prevalence of Inappropriate Antibiotic Prescriptions Among US with breast cancer survival as they affect bone metabolism lead- Ambulatory Care Visits. JAMA 2018;315(17):1864-73 ing to the development of osteoporosis and fragility.17,18 As our

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6. Becuttini S, Taur Y, Pamer EG Antibiotic Induced Changes in the Intestinal Microbiota 20. Takanishi T, naito Y, Inoue R. The influence to long-term use of proton pump inhibitors and Disease Trends Molec Med: 2016:22(6),458-78. on the gut microbiota: an age-sex-matched-case-controlled study. J. Con.Biochem. 7. Perera M, Perera I. Fire in the Forest: Adverse Effects of Antibiotics on the Healthy Nutr. 2018;62(7):100-5 Human Gut Microbiome. Int J Med Rev 2018;5(1):19-26 21. Williams JW, Jr, Mulrow CD, Chiquette E, Noël PH, Aguilar C, Cornell J. A 8. Trends in U.S. Antibiotic Use, 2018.pewtrusts.org/antibiotic-resistance-project. systematic review of newer pharmacotherapies for depression in adults: evidence 9. Bailey LC, Forrest CB, Zhang P, et al Association of antibiotics in infancy with report summary. Ann Intern Med. 2000 May 2;132(9):743–56. DOI: http://dx.doi. early childhood obesity. JAMA Pediatr. 2014; 168(11);1063-9.doi:10.1001/jama org/10.7326/0003-4819-132-9-200005020-00011. pediatrics.2014.1539 22. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone 10. Francino MR. Antibiotics and the Human Gut Microbiome: Dysbiosis and loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun Accumulation of Resistance. Front. Microbiol.2015:1543.doi:10.3389/ 25;167(12):1240–5. fmicb.2015.01543 23. Winerman L. By the numbers: antidepressants use on the rise. Am Psych Assoc.2017 11. Ianiro G, Tilq H, Gasbarrini A. Antibiotics as deep modulators of gut microbiota: (45):10;120 between good and evil.Gut.2016;65:1906-15. 24. Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human 12. Targownik LE, Leslie WD, Davison KS, et al. CaMos Research Group The gut microbiota in quality of life and depression. Nat Microbiol. 2019 Apr;4(4):623-632. relationship between proton pump inhibitor use and longitudinal change in 25. Cryan JF, Dinan TG: Mind-altering microorganisms: the impact of the gut microbiota bone mineral density: a population-based study from the Canadian Multicentre on brain and behavior.Nat Rev Neurosci. 2012;13:701-12 Osteoporosis Study (CaMos) Am J Gastroenterol. 2012 Sep;107(9):1361–9. 26. Galland L. The gut Microbiome and the Brain. J med food. 2014.17(12),1261.72 13. Melgar S, Nieuwdorp M Are Proton Pump Inhibitors Affecting Intestinal Microbiota 27. Maher RL, Hanlon JT, Hajjar ER. Clinical consequences of polypharmacy in elderly. health? Gastroenterolgy.2015;149;848-63 Expert Opin Drug Saf. 2014:13(1):10.1517/14740338.2013.827660 14. Imhann F, Bonder MJ, Vila AV. Proton pump inhibitors affect the microbiome. Gut 28. Panebianco C, Andriulli A, Panzienza V Pharmacomicrobiomics: exploiting the drug- 2016;65:740-8.doi:10.1136/gutjni-2015-33310376 microbiota interactions in anticancer therapies. Microbiome. 2018;6:92doi:10.1186/ 15. Reveles KR, Ryan CN, Chan L, Cosimi RA, Haynes WL. Proton pump inhibitor use s40168-018-0483-7 associated with changes in gut microbiota composition. Gut. 2018 Jul;67(7):1369- 29. Rea D, Coppola G, Palma G, Barbieri A, Luciano A, Del Prete P, Rossetti S, Berretta 1370. doi: 10.1136/gutjnl-2017-315306. M, Facchini G, Perdonà S, Turco MC, Arra C. Microbiota effects on cancer: from 16. Takagi T, Naito Y, Inoue R, et al. The influence of long-term use of proton pump risks to therapies. Oncotarget. 2018 Apr 3;9(25):17915-17927. doi:10.18632/ inhibitors on the gut microbiota: an age-sex-matched case-controlled study. J. Clin. oncotarget.24681. Biochem.Nutr. 2018.62(1):100-5 30. Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: A 17. Bodai BI, Tuso P. Breast cancer survivorship: A comprehensive review of long-term new clinical frontier. Gut 2016 Feb;65(2):330-9. DOI: https://doi.org/10.1136/ medical issues and lifestyle recommendations. Perm J. 2015 Spring;19(2):48–79. gutjnl-2015-309990. DOI: https://doi.org/10.7812/TPP/14-241. 31. Bastard QL, AI-Ghalith GA, Gregorre M, et al. systematic review: human gut 18. Vaezi MF, yang XY, Howden CW. Complications of proton pump inhibitor therapy. dysbiosis induced by non-antibiotic prescription medication. Ailment Pharmacol Ther. Gastroenterology 2017;152:35-48 2018;47:332-45. Doi:10:111/apt.14451 19. Lynch SV, Pederson O. the human intestinal microbiome in health and in disease. N 32. Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on Engl J Med 2016;375:2369-79 human gut bacteria. Nature. 2018;555(7698):623-8.doi:10.1038/nature 25979.

The14 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.129 66 CLINICAL PRACTICE Variation in Colorectal Cancer Stage and Mortality across Large Community-Based Populations: PORTAL Colorectal Cancer Cohort

Jennifer L Schneider, MPH1; Heather Spencer Feigelson, PhD, MPH2; Virginia P Quinn, PhD3; Carmit McMullen, PhD4; Pamela A Pawloski, PharmD, BCOP, FCCP5; John D Powers, MS2; Andrew T Sterrett, PhD2; David Arterburn, MD, MPH6; Douglas A Corley, MD, PhD1 Perm J 2020;24:19.182 E-pub: 07/21/2020 https://doi.org/10.7812/TPP/19.182

ABSTRACT The lack of studies evaluating systems-level differences in Introduction: Colorectal cancer (CRC) incidence and mortality CRC outcomes has impeded addressing potentially modifiable can be reduced by effective screening and/or treatment. However, disparities between health care systems in CRC outcomes. A the influence of health care systems on disparities among insured few studies have suggested that access to care may diminish patients is largely unexplored. racial disparities in CRC outcomes, treatment, and recurrent Methods: To evaluate insured patients with CRC diagnosed cancers, although few studies have fully evaluated the entire between 2010 and 2014 across 6 diverse US health care systems in process of care, including diagnosis, treatment, and survival.14-16 the Patient-Centered Outcomes Research Institute (PCORI) Patient A challenge to studying variation in outcomes is a lack of studies Outcomes Research To Advance Learning (PORTAL) CRC cohort, comparing multiple health care systems with different under- we contrasted CRC stage; CRC mortality; all-cause mortality; and lying populations. Surveillance systems such as Surveillance, influences of demographics, stage, comorbidities, and treatment Epidemiology, and End Results (SEER) collect information between health systems. on endpoints but lack risk factors such as comorbidities that Results: Among 16,211 patients with CRC, there were sig- may influence screening and treatment decisions or linkages nificant differences between health care systems in CRC stage to health care systems. In contrast, single medical centers may at diagnosis, CRC-specific mortality, and all-cause mortality. The have rich data on a single population but lack variation in patient unadjusted risk of CRC mortality varied from 27% lower to 21% demographics, screening methods, or treatment patterns.17 To higher than the reference system (hazard ratio [HR] = 0.73, 95% overcome these limitations, the Patient-Centered Outcomes confidence interval = 0.66-0.80 to HR = 1.21, 95% confidence in- Research Institute (PCORI) developed a scientific community terval = 1.05-1.40; p < 0.01 across systems). Significant differences and data resource of US patients, clinicians, and health care persisted after adjustment for demographics and comorbidities delivery systems. The Kaiser Permanente (KP) and Strategic (p < 0.01); however, adjustment for stage eliminated significant Partners Patient Outcomes Research to Advance Learning differences (p = 0.24). All-cause mortality among patients with (PORTAL) network is one of the PCORI-funded initiatives CRC differed approximately 30% between health care systems (HR and includes a multisystem CRC cohort. In this study we le- = 0.89-1.17; p < 0.01). Adjustment for age eliminated significant verage this cohort’s size—more than 16,000 patients—and its differences (p = 0.48). demographic diversity to estimate intersystem differences in Discussion: Differences in CRC survival between health care postdiagnosis outcomes.18,19 systems were largely explained by stage at diagnosis, not demo- The aim of this study was to identify major, potentially modi- graphics, comorbidity, or treatment. Given that stage is strongly fiable factors related to CRC mortality. in the current study we related to early detection, these results suggest that variation in evaluated a large, diverse, multicenter cohort of patients with CRC screening systems represents a modifiable systems-level a diagnosis of CRC, and we contrasted CRC mortality and factor for reducing disparities in CRC survival. all-cause mortality across 6 distinct health care systems. Ad- ditionally, we evaluated whether patient-related factors (age, INTRODUCTION race/ethnicity, comorbidities) and health care system-related Colorectal cancer (CRC) is the second leading cause of cancer differences in stage-specific cancer treatments and in cancer death overall, but its incidence and mortality can be markedly reduced by effective screening, treatment, or both.1-3 The over- all incidence of CRC in the US has decreased in recent years, mostly due to increases in CRC screening rates for recommended Author Affiliations 4-6 groups. However, disparities in both incidence and survival 1 Division of Research, Kaiser Permanente Northern California, Oakland exist among certain races, age groups, and insurance types (ac- 2 Institute for Health Research, Kaiser Permanente Colorado, Denver cess to care) and by cancer type (histology, morphology, genetic 3 Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena 4 markers).7-10 For example, CRC incidence has actually increased Center for Health Research, Kaiser Permanente Northwest, Portland, OR 5 HealthPartners Institute, Bloomington, MN among some subgroups, including younger persons (< 50 years 6 Kaiser Permanente Washington Health Research Institute, Seattle old), and decreased more slowly among African Americans, Asians, and Hispanic whites than it has among non-Hispanic Corresponding Author whites.11-13 Jennifer Schneider, MPH ([email protected])

Keywords: Colorectal cancer, health care systems, mortality, patient outcomes research, variation

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stage (a surrogate for effective CRC screening) explained the The Cox proportional hazards assumption was evaluated by differences found. inspecting plots of the cumulative sums of Martingale residuals over follow-up times. All analyses were performed using statisti- METHODS cal analysis software (SAS version 9.4, SAS Institute Inc, Cary, NC). The study was approved by the institutional review boards Study Population at all participating health care systems, and oversight was ceded This observational cohort study was done in the PORTAL to KPCO; informed consent was not required. In all models, CRC cohort. Cohort development has been described else- patients were censored at the first of the following events: end of where20; briefly, the cohort includes all adults (≥ 18 years of age) health care system membership, death (non-CRC death in CRC with CRC diagnosed between 2010 and 2014 from 6 health death analyses), or end of the study period (December 31, 2014). Given strong known associations between screening, stage, care systems. Those systems are Health Partners in Minneapo- 2-6 lis, Minnesota; Kaiser Permanente Colorado (KPCO); Kaiser and CRC mortality , logistic regression was used to evaluate Permanente Northern California (KPNC); Group Health Co- risk factors, independent of health care system, for late-stage operative in Washington State; Kaiser Permanente Northwest (stages 3 and 4) vs early-stage disease (stages 1 and 2). These (KPNW); and Kaiser Permanente Southern California (KPSC). supplemental analyses allowed evaluation of whether between- All patients are insured, although different insurance coverage system differences were independent of variation in, for example, exists in and across systems. Each system is administratively age, race/ethnicity, or comorbidities between systems. 19 distinct in its practices for cancer screening and treatment. RESULTS Health care systems are randomly designated A-F, with health care system A selected as the referent throughout. Colorectal Cohort cancer was defined using International Classification of Dis- The CRC cohort characteristics have been previously de- eases O-3 codes C180, 182 to 189, C199, and C209. For this 20 analysis, we excluded cohort members with SEER stage 0 dis- scribed. A total of 16,211 persons with diagnosed CRC were ease, given inconsistent recording between cancer registries of identified. Exclusion of 1539 persons with stage 0 cancer pro- carcinoma in situ. vided 14,672 persons for the main analyses. The racial/ethnic distribution was 64% non-Hispanic white, 15% Hispanic, 11% Variables and Data Sources Asian/Pacific Islander, and 10% African American. Half were female (50%); most were greater than 65 years old (mean age at Harmonized common data elements were available for all diagnosis = 68 years); and most had commercial insurance alone PORTAL health care systems. These data elements included de- or in combination with another insurance type (66%; Table 1). mographics (age, race/ethnicity), comorbid conditions (Charlson The number of CRC diagnoses per year was similar over the comorbidity index), vital status (including cause of death, as ap- study period; 89% of cancers were nonmucinous adenocarci- propriate), and social history. Cancer registry data characterized nomas, and 64% had moderately differentiated histology. The cancer diagnosis, location, treatment (surgery, chemotherapy, most common initial treatments were surgery (85%), chemo- radiation therapy), tumor characteristics, additional patient therapy (39%), radiation therapy (11%), and palliative care (< demographic variables, and cause of death (supplemented by 21 1%); some patients received more than 1 initial treatment type. additional center-specific death registries). The mean follow-up after CRC diagnosis was 1.94 (SD = 1.42) years (range by site = 1.73-1.98 years). During follow-up, 1179 Statistical Analyses patients were censored at disenrollment from the health care Multivariable Cox proportional hazards regression models system, and 3624 patients died of any cause, among whom 2415 were used to calculate hazard ratios (HRs) as estimates of rela- had CRC-related deaths. tive risk and 95% confidence intervals (CIs) for CRC mortality and all-cause mortality across health care systems. Health care Colorectal Cancer-Specific Mortality system A served as the referent group. A sequential analytic The HRs for CRC-specific mortality varied substantially (> approach, adding in factors individually or in related groups to 45%) and significantly across health care systems in unadjusted evaluate their influence on model results, estimated the influence models (HR range referent to health care system A = 0.73-1.21, of demographics (age, sex, race/ethnicity, language preference, p < 0.01). Significant variation of approximately 40% remained socioeconomic status) and comorbidities (abnormal body mass after adjustment for potential differences in demographics (age 22-24 index [BMI], Charlson comorbidity index score) ; cancer group, race/ethnicity, sex) and health status (Charlson comor- stage (as a surrogate for system-specific factors such as screen- bidity index score and BMI) between health systems (p=.0002). ing that would influence early detection); tumor characteristics In contrast, adjustment for stage, which is a surrogate of screen- (morphology, grade); cancer treatments; and, as measures of op- ing/early detection, eliminated significant differences between portunity to screen, health care system membership duration, health care systems (p = 0.24, Figure 1). year of diagnosis, and insurance coverage type.

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Additional evaluations of the influences of tumor characteris- in integrated health systems, although these were not linked tics, insurance type, receipt of treatment, and year of diagnosis with outcomes data.25 did not further influence differences in CRC mortality. Race is one of the most commonly studied factors related to variation in CRC outcomes. Several races, in general, have All-Cause Mortality demonstrated poorer outcomes than whites in some settings, The HRs for all-cause mortality among patients with CRC although a small increased risk of advanced-stage disease in differed approximately 30% between health care systems (HR the current study was found only among African Americans range = 0.89-1.17, p < 0.01); however, adjustment for age alone (OR = 1.12, 95% CI = 1.00-1.26) and not among other race/ eliminated significant differences (p = 0.48). Adjustment for ethnicity groups compared with whites. The current findings both demographics and comorbidity provided even more com- are consistent with those of another recent study, which found parable estimates (Figure 2). The additional inclusion of BMI, disparities in CRC outcomes by race in nonintegrated health co-morbid conditions, and stage at diagnosis did not substan - care settings but not in integrated health care settings.26 The tially further influence variability across health care systems in current study now finds that even between integrated systems, all-cause mortality (p = 0.50). race does not explain disparities in CRC survival; rather, it is related to stage, independent of race. Early versus Late Stage at Diagnosis Although we were not able to directly assess variations in Given that cancer stage, as a surrogate of screening and early screening methods and proportions screened across systems, detection, is a primary driver of CRC mortality, we evaluated among persons with access to care, screening is the main known predictors of CRC stage at diagnosis among the 14,224 patients cause of early detection; thus stage of cancer at diagnosis serves with stages 1 to 4 disease (late stage [3/4] vs early stage [1/2] as a likely marker for penetrance of the screening program in a at diagnosis, Figure 3). Significant variation in late-stage vs health care system. Screening programs that are well accepted early-stage disease across systems was observed after adjust- and broadly implemented will detect cancers at earlier stages ment for demographic factors, health status, health care system than programs with less coverage and can directly and markedly membership duration, and insurance type (HR range = 0.77- reduce CRC mortality.27-30 In this study, health care system F 1.19, p = 0.03). had lower risks of both CRC-specific mortality and late-stage Factors associated with later-stage disease, independent of diagnosis (OR = 0.89, 95% CI = 0.83-0.96). These results are health care system, included African American race (odds ratio concordant with preexisting knowledge, from prior analyses, [OR] = 1.12, 95% CI = 1.00-1.26), age outside usual screen- of differences in screening rates and follow-up of abnormal ing intervals (ie, < 50 or > 80 years), and greater numbers of screening tests between some of the programs under evalua- comorbidities (eg, Charlson comorbidity index score 3: OR = tion.31-34 In addition, patients outside screening ages (50-75 years 1.36, 95% CI = 1.28-1.43; Table 2). for average risk), as expected, also were more likely to have a late-stage diagnosis. Screening differences between health care DISCUSSION systems can include variation in formal outreach and differences In this cohort study of 6 US health care systems, using the in use of the most effective tests, such as colonoscopy or fecal PORTAL CRC cohort, we found substantial and significant immunochemical testing, vs use of less effective tests, such as differences between health care systems in CRC-specific mor- sigmoidoscopy or fecal occult blood testing.35 tality, all-cause mortality, and stage of CRC at diagnosis. The Further exploration into the differences in screening practices between-system differences in all-cause mortality were largely of individuals across health systems would better inform modi- explained by differing age structures between populations. fiable differences between health care systems. Well-designed In contrast, the between-system differences in CRC-specific screening programs with high overall proportions of persons mortality were explained almost solely by differences in cancer who are up to date with screening can have variable uptake by stage, a surrogate for effective screening, and not by differences different patient populations. Even with relatively standardized in demographics, comorbidities, or cancer treatment. Combined screening offerings, the uptake, follow-up of patients with ab- with the observation that the CRC-associated mortality was normal test results, and the screening test choices can vary by higher among persons older or younger than recommended race, age, and comorbidity status.23,29 Access to care and insur- screening ages, these findings suggest that systems-level factors ance coverage are known to vary by demographic group and can in early detection (ie, CRC screening programs) likely explain affect severity of disease and eventually mortality; however, our the demonstrated disparities in CRC mortality between health study design adjusted for this by only evaluating persons with care systems. health care insurance coverage.36 Few studies have contrasted systems-level data on CRC There are several strengths to this study. The multicenter outcomes; thus, the current study informs the relative roles cohort is one of the largest, most diverse CRC cohorts with that demographics, stage/early detection, and treatments may individual-level data yet described. The demographic and geo- have in influencing CRC-specific and all-cause mortality graphic diversity (15% Hispanic, 10% African American, and among patients with a diagnosis of CRC. Prior studies dem- 11% Asian/Pacific Islander; almost 1500 persons who received onstrated substantial variation in screening completion, even a diagnosis under the age of 50 years) allow analyses of multiple factors that may influence CRC survival and all-cause mortality

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4. Austin, H., et al., Changes in colorectal cancer incidence rates in young and older across 6 distinct, large health care systems with different care adults in the United States: what does it tell us about screening. Cancer Causes delivery models. Limitations include cohort homogeneity re- Control, 2014. 25(2): p. 191-201 DOI: 10.1007/s10552-013-0321-y. garding access to care, although this can also be a strength, 5. Levin, T.R., et al., Effects of Organized Colorectal Cancer Screening on Cancer Incidence and Mortality in a Large Community-Based Population. because this homogeneity effectively “controlled” for health Gastroenterology, 2018. 155(5): p. 1383-1391 e5 DOI: 10.1053/j. care access, allowing less biased evaluations of other factors. As gastro.2018.07.017. noted, although the study assessed stage, it did not directly as- 6. Doubeni, C.A., et al., Modifiable Failures in the Colorectal Cancer Screening Process and Their Association with Risk of Death. Gastroenterology, 2018 DOI: sess screening completion. Thus, the analyses could not evaluate 10.1053/j.gastro.2018.09.040. how variations in screening rates influence stage independent 7. DeSantis, C.E., et al., Cancer statistics for African Americans, 2016: Progress and of race, sex, age, and other factors. opportunities in reducing racial disparities. CA Cancer J Clin, 2016. 66(4): p. 290- 308 DOI: 10.3322/caac.21340. CONCLUSION 8. Alexander, D.D., et al., African-American and Caucasian disparities in colorectal cancer mortality and survival by data source: an epidemiologic review. Cancer Among patients with a diagnosis of CRC cancer, there is Biomark, 2007. 3(6): p. 301-13. 9. Pardini, B., et al., Polymorphisms in microRNA genes as predictors of clinical substantial and significant variation in both CRC-related outcomes in colorectal cancer patients. Carcinogenesis, 2015. 36(1): p. 82-6 DOI: mortality and all-cause mortality across different health care 10.1093/carcin/bgu224. systems. Although the differences in all-cause mortality were 10. Phipps, A.I., et al., Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis. Carcinogenesis, 2016. 37(1): p. 87-95 DOI: largely explained by differences in age between the health care 10.1093/carcin/bgv161. systems, the differences in CRC-related mortality were largely 11. O’Connell, J.B., et al., Rates of colon and rectal cancers are increasing in young explained by differences in cancer stage, not by differences in adults. Am Surg, 2003. 69(10): p. 866-72. demographics or cancer treatment. Given that the main deter- 12. Ashktorab, H., et al., Colorectal Cancer in Young African Americans: Is It Time to Revisit Guidelines and Prevention? Dig Dis Sci, 2016. 61(10): p. 3026-30 DOI: minant of cancer stage is the use of effective CRC screening 10.1007/s10620-016-4207-1. tests for early detection, and the demonstrated prior differences 13. Siegel, R.L., et al., Colorectal Cancer Incidence Patterns in the United States, in screening and screening follow-up rates between some of the 1974-2013. J Natl Cancer Inst, 2017. 109(8) DOI: 10.1093/jnci/djw322. 14. Haider, A.H., et al., Racial disparities in surgical care and outcomes in the United centers evaluated, these results suggest that more consistent States: a comprehensive review of patient, provider, and systemic factors. J Am application of cancer screening across health care systems may Coll Surg, 2013. 216(3): p. 482-92.e12 DOI: 10.1016/j.jamcollsurg.2012.11.014. further reduce the current disparities in CRC mortality between 15. Laiyemo, A.O., et al., Race and colorectal cancer disparities: health-care utilization v vs different cancer susceptibilities. J Natl Cancer Inst, 2010. 102(8): p. 538-46 DOI: health care systems. 10.1093/jnci/djq068. 16. Rutter, M.D., et al., World Endoscopy Organization Consensus Statements on Disclosure Statement Post-Colonoscopy and Post-Imaging Colorectal Cancer. Gastroenterology, 2018 The author(s) have no conflicts of interest to disclose. DOI: 10.1053/j.gastro.2018.05.038. 17. Levin, T.R., et al., Effects of Organized Colorectal Cancer Screening on Cancer Incidence and Mortality in a Large, Community-based Population. Acknowledgments Gastroenterology, 2018 DOI: 10.1053/j.gastro.2018.07.017. This study used infrastructure developed by the PORTAL (Patient 18. Corley, D.A., et al., Building Data Infrastructure to Evaluate and Improve Quality: Outcomes Research to Advance Learning) Network, a consortium of 3 PCORnet. J Oncol Pract, 2015. 11(3): p. 204-6 DOI: 10.1200/jop.2014.003194. integrated delivery systems (Kaiser Permanente, HealthPartners, and Denver 19. McGlynn, E.A., et al., Developing a data infrastructure for a learning health system: Health) and their affiliated research centers. The PORTAL Network also the PORTAL network. J Am Med Inform Assoc, 2014. 21(4): p. 596-601 DOI: performed data collection. 10.1136/amiajnl-2014-002746. Research reported in this article was funded through Patient-Centered 20. Feigelson, H.S., et al., Optimizing patient-reported outcome and risk factor reporting from cancer survivors: a randomized trial of four different survey methods Outcomes Research Institute (PCORI) Award CDRN-1306-04681 Phase II. among colorectal cancer survivors. J Cancer Surviv, 2017. 11(3): p. 393-400 DOI: The statements in this article are solely the responsibility of the authors and 10.1007/s11764-017-0596-1. do not necessarily represent the views of the Patient-Centered Outcomes 21. North American Association of Central Cancer Registries. 2018 [cited 2018 Nov Research Institute (PCORI), its Board of Governors, or Methodology 29]. Available from: https://www.naaccr.org/cina-data-products-overview/. Committee. 22. Klabunde, C.N., et al., A refined comorbidity measurement algorithm for claims- Kathleen Louden, ELS, of Louden Health Communications performed a based studies of breast, prostate, colorectal, and lung cancer patients. Ann primary copyedit. Epidemiol, 2007. 17(8): p. 584-90 DOI: 10.1016/j.annepidem.2007.03.011. 23. Klabunde, C.N., et al., Influence of Age and Comorbidity on Colorectal Cancer Screening in the Elderly. Am J Prev Med, 2016. 51(3): p. e67-75 DOI: 10.1016/j. Authors’ Contributions amepre.2016.04.018. Heather Spencer Feigelson, PhD, MPH, and Douglas A. Corley, MD, 24. Cho, H., et al., Comorbidity-adjusted life expectancy: a new tool to inform PhD, assisted with study design and data analysis. John D. Powers, MS, recommendations for optimal screening strategies. Ann Intern Med, 2013. 159(10): participated in data analysis. Jennifer L. Schneider, MPH, drafted the p. 667-76 DOI: 10.7326/0003-4819-159-10-201311190-00005. 25. Green, B.B., et al., A centralized mailed program with stepped increases of support manuscript. All authors reviewed, edited, and approved the final manuscript. increases time in compliance with colorectal cancer screening guidelines over 5 years: A randomized trial. Cancer, 2017. 123(22): p. 4472-4480 DOI: 10.1002/ References cncr.30908. 1. Aran, V., et al., Colorectal Cancer: Epidemiology, Disease Mechanisms and 26. Rhoads, K.F., et al., How do integrated health care systems address racial and Interventions to Reduce Onset and Mortality. Clin Colorectal Cancer, 2016. 15(3): ethnic disparities in colon cancer? J Clin Oncol, 2015. 33(8): p. 854-60 DOI: p. 195-203 DOI: 10.1016/j.clcc.2016.02.008. 10.1200/jco.2014.56.8642. 2. Zauber, A.G., The impact of screening on colorectal cancer mortality and 27. Doubeni, C.A., et al., Effectiveness of screening colonoscopy in reducing the risk incidence: has it really made a difference? Dig Dis Sci, 2015. 60(3): p. 681-91 DOI: of death from right and left colon cancer: a large community-based study. Gut, 10.1007/s10620-015-3600-5. 2018. 67(2): p. 291-298 DOI: 10.1136/gutjnl-2016-312712. 3. Nishihara, R., et al., Long-term colorectal-cancer incidence and mortality after 28. Cole, S.R., et al., Shift to earlier stage at diagnosis as a consequence of the lower endoscopy. N Engl J Med, 2013. 369(12): p. 1095-105 DOI: 10.1056/ National Bowel Cancer Screening Program. Med J Aust, 2013. 198(6): p. 327-30. NEJMoa1301969.

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29. Fedewa, S.A., et al., Colorectal Cancer Screening Initiation After Age 50 Years in 33. Burnett-Hartman, A.N., et al., Racial/Ethnic Disparities in Colorectal Cancer an Organized Program. Am J Prev Med, 2017. 53(3): p. 335-344 DOI: 10.1016/j. Screening Across Healthcare Systems. Am J Prev Med, 2016. 51(4): p. e107-15 amepre.2017.02.018. DOI: 10.1016/j.amepre.2016.02.025. 30. Knudsen, A.B., et al., Estimation of Benefits, Burden, and Harms of Colorectal 34. Chubak, J., et al., Time to Colonoscopy after Positive Fecal Blood Test in Four U.S. Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Health Care Systems. Cancer Epidemiol Biomarkers Prev, 2016. 25(2): p. 344-50 Force. JAMA, 2016. 315(23): p. 2595-609 DOI: 10.1001/jama.2016.6828. DOI: 10.1158/1055-9965.EPI-15-0470. 31. Tosteson, A.N., et al., Variation in Screening Abnormality Rates and Follow- 35. Bibbins-Domingo, K., et al., Screening for Colorectal Cancer: US Preventive Up of Breast, Cervical and Colorectal Cancer Screening within the PROSPR Services Task Force Recommendation Statement. Jama, 2016. 315(23): p. 2564- Consortium. J Gen Intern Med, 2016. 31(4): p. 372-9 DOI: 10.1007/s11606-015- 2575 DOI: 10.1001/jama.2016.5989. 3552-7. 36. Grant, S.R., et al., Variation in insurance status by patient demographics and tumor 32. McCarthy, A.M., et al., Follow-Up of Abnormal Breast and Colorectal Cancer site among nonelderly adult patients with cancer. Cancer, 2015. 121(12): p. 2020-8 Screening by Race/Ethnicity. Am J Prev Med, 2016. 51(4): p. 507-12 DOI: 10.1016/j. DOI: 10.1002/cncr.29120. amepre.2016.03.017.

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Table 1. Descriptive characteristics of patients with colorectal cancer (CRC), treatment modalities, and cancer outcomes for PORTAL CRC cohort, by health care system (N = 14,672)a System A, System B, System C System D System E no. System F no. Total Characteristic no. (%) no. (%) no. (%) no. (%) (%) (%) no. (%) Number (%) 6073 (41.4) 1020 (7.0) 180 (1.2) 860 (5.9) 935 (6.4) 5604 (38.2) 14,672 (100.0) Sex Female 3070 (50.6) 540 (52.9) 98 (54.4) 462 (53.7) 462 (49.4) 2652 (47.3) 7284 (49.6) Male 3003 (49.4) 480 (47.1) 82 (45.6) 398 (46.3) 473 (50.6) 2952 (52.7) 7388 (50.4) Race/ethnicity African American 531 (8.7) 34 (3.3) 9 (5.0) 36 (4.2) 26 (2.8) 752 (13.4) 1388 (9.5) Asian/Pacific Islander 842 (13.9) 75 (7.4) 9 (5.0) 22 (2.6) 28 (3.0) 572 (10.2) 1548 (10.6) Hispanic 766 (12.6) 24 (2.4) 1 (0.6) 88 (10.2) 28 (3.0) 1323 (23.6) 2230 (15.2) White 3904 (64.3) 862 (84.5) 160 (88.9) 647 (75.2) 844 (90.3) 2923 (52.2) 9340 (63.7) Other/unknown 30 (0.5) 25 (2.5) 1 (0.6) 67 (7.8) 9 (1.0) 34 (0.6) 166 (1.1) Age, y, at CRC Dx < 40 146 (2.4) 17 (1.7) 2 (1.1) 16 (1.9) 14 (1.5) 163 (2.9) 358 (2.4) 40-49 473 (7.8) 57 (5.6) 16 (8.9) 60 (7.0) 55 (5.9) 465 (8.3) 1126 (7.7) 50-59 1183 (19.5) 176 (17.3) 32 (17.8) 165 (19.2) 166 (17.8) 1171 (20.9) 2893 (19.7) 60-69 1476 (24.3) 260 (25.5) 40 (22.2) 215 (25.0) 286 (30.6) 1491 (26.6) 3768 (25.7) 70-79 1433 (23.6) 231 (22.6) 38 (21.1) 205 (23.8) 217 (23.2) 1312 (23.4) 3436 (23.4) ≥ 80 1362 (22.4) 279 (27.4) 52 (28.9) 199 (23.1) 197 (21.1) 1002 (17.9) 3091 (21.1) Mean (SD) 67.83 (13.96) 69.77 (13.6) 69.33 (14.49) 68.32 (13.35) 68.28 (12.87) 66.52 (13.55) 67.54 (13.74) BMI, kg/m2, mean (SD) 27.67 (6.29) 28.49 (6.5) 28.6 (7.05) 27.84 (6.23) 29.65 (7.1) 28.1 (6.17) 28.03 (6.34) Charlson comorbidity index score 1 1122 (18.5) 65 (6.4) 7 (3.9) 125 (14.5) 61 (6.5) 1557 (27.8) 2937 (20.0) 2.1 578 (9.5) 46 (4.5) 5 (2.8) 50 (5.8) 32 (3.4) 703 (12.5) 1414 (9.6) 3.2 1195 (19.7) 260 (25.5) 54 (30.0) 213 (24.8) 309 (33.0) 1028 (18.3) 3059 (20.8) ≥ 4.3 3178 (52.3) 649 (63.6) 114 (63.3) 472 (54.9) 533 (57.0) 2316 (41.3) 7262 (49.5) Enrollment duration before Dx, y, 3.77 (1.74) 3.7 (0.02) 3.56 (0.02) 3.49 (0.02) 3.57 (1.8) 3.62 (1.9) 3.67 (1.82) mean (SD) Year of Dx 2010 1326 (21.8) 187 (18.3) 36 (20.0) 187 (21.7) 211 (22.6) 1128 (20.1) 3075 (21.0) 2011 1317 (21.7) 192 (18.8) 45 (25.0) 161 (18.7) 197 (21.1) 1081 (19.3) 2993 (20.4) 2012 1201 (19.8) 208 (20.4) 41 (22.8) 193 (22.4) 183 (19.6) 1134 (20.2) 2960 (20.2) 2013 1228 (20.2) 227 (22.3) 44 (24.4) 187 (21.7) 176 (18.8) 1145 (20.4) 3007 (20.5) 2014 1001 (16.5) 206 (20.2) 14 (7.8) 132 (15.3) 168 (18.0) 1116 (19.9) 2637 (18.0) Stage at Dx 1 1646 (27.1) 239 (23.4) 60 (33.3) 250 (29.1) 263 (28.1) 1702 (30.4) 4160 (28.4) 2 1555 (25.6) 266 (26.1) 48 (26.7) 202 (23.5) 242 (25.9) 1413 (25.2) 3726 (25.4) 3 1596 (26.3) 272 (26.7) 46 (25.6) 222 (25.8) 213 (22.8) 1417 (25.3) 3766 (25.7) 4 1117 (18.4) 194 (19.0) 21 (11.7) 159 (18.5) 144 (15.4) 937 (16.7) 2572 (17.5) Unknown 159 (2.6) 49 (4.8) 5 (2.8) 27 (3.1) 73 (7.8) 135 (2.4) 448 (3.1) Morphology Nonmucinous adenocarcinoma 5472 (90.1) 901 (88.3) 159 (88.3) 769 (89.4) 839 (89.7) 4934 (88.0) 13074 (89.1) Mucinous adenocarcinoma 389 (6.4) 71 (7.0) 15 (8.3) 61 (7.1) 69 (7.4) 495 (8.8) 1100 (7.5) Signet ring 64 (1.1) 10 (1.0) 2 (1.1) 7 (0.8) 9 (1.0) 91 (1.6) 183 (1.2) Other/NOS 148 (2.4) 38 (3.7) 4 (2.2) 23 (2.7) 18 (1.9) 84 (1.5) 315 (2.1) Histology Well differentiated 393 (6.5) 54 (5.3) 7 (3.9) 65 (7.6) 126 (13.5) 651 (11.6) 1296 (8.8) Moderately differentiated 4118 (67.8) 642 (62.9) 121 (67.2) 514 (59.8) 540 (57.8) 3511 (62.7) 9446 (64.4) Poorly differentiated 661 (10.9) 130 (12.7) 37 (20.6) 145 (16.9) 133 (14.2) 967 (17.3) 2073 (14.1) Undifferentiated 155 (2.6) 38 (3.7) 1 (0.6) 53 (6.2) 7 (0.7) 53 (0.9) 307 (2.1) Not determined 746 (12.3) 156 (15.3) 14 (7.8) 83 (9.7) 129 (13.8) 422 (7.5) 1550 (10.6)

Table 1 continues on next page

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Treatment Surgery 5092 (83.8) 868 (85.1) 154 (85.6) 726 (84.4) 796 (85.1) 4779 (85.3) 12415 (84.6) Chemotherapy 2312 (38.1) 395 (38.7) 65 (36.1) 329 (38.3) 318 (34.0) 2367 (42.2) 5786 (39.4) Radiation therapy 594 (9.8) 147 (14.4) 25 (13.9) 123 (14.3) 109 (11.7) 681 (12.2) 1679 (11.4) Palliative care 0 (0) 0 (0) 23 (12.8) 33 (3.8) 72 (7.7) 0 (0) 128 (0.9) Insurance type Medicaid 77 (1.3) 0 (0) 15 (8.3) 31 (3.6) 14 (1.5) 75 (1.3) 212 (1.4) Medicare and private pay 1845 (30.4) 391 (38.3) 0 (0) 187 (21.7) 0 (0) 1722 (30.7) 4145 (28.3) Medicare and commercial 1741 (28.7) 259 (25.4) 0 (0) 225 (26.2) 35 (3.7) 25 (0.5) 2285 (15.6) High-deductible 137 (2.3) 35 (3.4) 12 (6.7) 18 (2.1) 1 (0.1) 401 (7.2) 604 (4.1) Commercial 2273 (37.4) 335 (32.8) 153 (85) 399 (46.4) 885 (94.7) 3381 (60.3) 7426 (50.6) Died of any cause 1582 (25.1) 279 (27.4) 47 (26.1) 223 (25.9) 226 (24.2) 1267 (22.6) 3624 (24.7) CRC death 1141 (19.0) 212 (20.9) 24 (14.5) 159 (18.8) 167 (17.9) 712 (13.7) 2415 (17.0) Follow-up time, y, mean (SD) 1.98 (1.42) 1.73 (1.37) 1.96 (1.33) 1.94 (1.41) 1.93 (1.44) 1.93 (1.42) 1.94 (1.42)

a Some totals do not total to 100% because of rounding. BMI = body mass index; Dx = diagnosis; NOS = not otherwise specified; PORTAL = Patient Outcomes Research To Advance Learning; SD = standard deviation.

Table 2. Individual predictors of stage at diagnosis (N = 14,224) Predictor Hazard ratio (95% CI) Body mass index 0.98 (0.97-0.98) Race/ethnicity (referent = white non-Hispanic) African American 1.12 (1.00-1.26) Asian/Pacific Islander 0.97 (0.87-1.08) Hispanic 0.99 (0.89-1.09) Other/unknown 0.94 (0.72-1.21) Age group, y (referent = 50-59) < 40 2.02 (1.67-2.44) 40-49 1.59 (1.42-1.78) 50-59 1 (referent) 60-69 0.75 (0.70-0.80) 70-79 0.68 (0.62-0.74) ≥ 80 0.70 (0.64-0.77) Sex (referent = male) 1 (0.97-1.03) Years enrolled 0.97 (0.96-0.99) Charlson comorbidity index score (referent = 0) 1 0.95 (0.87-1.04) 2 0.89 (0.83-0.95) ≥ 3 1.36 (1.28-1.43) Insurance type (referent = commercial only) Medicaid 1.04 (0.82-1.30) Medicare and private pay 0.95 (0.86-1.04) Medicare and commercial 0.99 (0.89-1.11) High-deductible 1.04 (0.90-1.21) CI = confidence interval.

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Figure 1. Colorectal cancer-specific mortality hazard ratios (HR) adjusted for demographics, comorbidities, and stage at diagnosis, by health care system.a a Referent health care system is A. Error bars indicate 95% confidence intervals.

Figure 2. All-cause mortality hazard ratios (HR) adjusted for demographics and comorbidities among patients with colorec- tal cancer, by health care system.a a Referent health care system is A. Error bars indicate 95% confidence intervals.

The8 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.182 74 CLINICAL PRACTICE Variation in Colorectal Cancer Stage and Mortality across Large Community-Based Populations: PORTAL Colorectal Cancer Cohort

Figure 3. Distribution of colorectal cancer stage at diagnosis, by health care system (N = 14,672).

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Cameron Sadeghi, MD1; Heather A. Prentice, PhD2; Kanu M. Okike, MD3; Elizabeth W. Paxton, PhD2 Perm J 2020;24:19.229 E-pub: 06/10/2020 https://doi.org/10.7812/TPP/19.229

ABSTRACT studies have failed to identify differences in failure or periprosthetic Context: Prior studies regarding indications for long vs short fracture rates between long and short nails, but they demonstrated cephalomedullary nails in the treatment of intertrochanteric frac- a reduced surgical time and blood loss for short nails.4-9 However, tures had limited sample sizes and follow-up, suggesting a need these studies have been limited by small sample sizes and short for further investigation. postoperative follow-up, suggesting a need for further investigation. Objective: To evaluate the association between cephalomedul- Using data from a US hip fracture registry (HFR), we sought lary nail length and outcomes for the treatment of intertrochanteric to investigate the following questions: 1) Is there a difference in femur fractures. revision risk, either all-cause or for periprosthetic fracture, when Design: Cohort study using Kaiser Permanente’s Hip Fracture using long vs short cephalomedullary nails in the treatment of in- Registry. A total of 5526 patients who underwent surgical treat- tertrochanteric femur fractures? 2) Does operative time, estimated ment with cephalomedullary nails for an intertrochanteric femur blood loss, or inhospital length of stay (LOS) differ for patients fracture (2009-2014) were identified: 3108 (56.2%) with long nails who receive a long vs short cephalomedullary nail in the treatment and 2418 (43.8%) with short nails. Cox proportional hazards model of intertrochanteric femur fractures? regression was used to evaluate risks of all-cause revision and revision for periprosthetic fracture. Linear regression was used to METHODS evaluate operative time, estimated blood loss, and length of stay. Study Design, Setting, and Sample Propensity score weights were used in all models to balance nail groups on patient and device characteristics. We conducted a retrospective cohort study using data from an Main Outcome Measures: All-cause revision surgery. integrated health care system’s HFR, the Kaiser Permanente Hip Results: No association was found in risk of all-cause revision Fracture Registry. Kaiser Permanente covers more than 12.2 mil- (hazard ratio = 0.75, 95% confidence interval [CI] = 0.48-1.15) or lion members throughout 8 US geographical regions (ie, Colorado, revision for periprosthetic fracture (hazard ratio = 0.59, 95% CI = Georgia, Hawaii, Mid-Atlantic, Northern California, Northwest, 0.23-1.48) for long nails compared with short nails. Use of longer Southern California, and Washington). Members of the integrated health care system have been previously shown to be representative nails resulted in 18.80 more minutes of operative time (95% CI = 10,11 17.33-20.27 minutes), 41.10 mL more of estimated blood loss (95% of the regional population served, increasing generalizability CI = 31.71-50.48 mL), and a longer hospitalization (8.4 hours; β = of study results. 0.35, 95% CI = 0.12-0.58 hours). The study sample was selected using the HFR and consisted of Conclusion: These findings suggest that routine use of short patients with a closed femur-based fracture of the intertrochanteric cephalomedullary nails is safe and effective in the treatment of section who underwent primary fixation procedures from 2009 intertrochanteric fractures. through 2014. Intertrochanteric fractures were identified using International Classification of Diseases, Ninth Revision (ICD-9) INTRODUCTION code 820.21 and adjudicated through implant information. Only fractures fixed with the 2 highest volume implants in the HFR, Cephalomedullary nails are the most common fixation device 1 the Gamma3 Nailing System (Stryker Orthopaedics, Kalamazoo, used in the treatment of intertrochanteric femur fractures. Cepha- MI) and the trochanteric femoral nail (TFN, DePuy Synthes, lomedullary nails are commonly divided into long and short devices. West Chester, PA), were included. The study consisted of 5526 Little consensus exists regarding indications for long vs short nails hip fracture procedures: 3108 (56.2%) with long nails and 2418 in the treatment of intertrochanteric fractures. Early designs of (43.8%) with short nails. short cephalomedullary nails were associated with a higher risk of periprosthetic fracture, but with the newer generation of nails, this risk was reduced.2 Experts have recommended long nails for unstable and highly displaced fracture patterns because of the perceived protective effect of long nails in preventing refracture in this population of Author Affiliations 1 Department of Orthopaedic Surgery, Southern California Permanente Medical Group, San Diego, CA, USA patients, who commonly have osteoporotic bones and a higher 2 3 Surgical Outcomes and Analysis, Kaiser Permanente, San Diego, California, USA risk of falls. Historically, long nails were recommended to reduce 3 Department of Orthopaedic Surgery, Kaiser Moanalua Medical Center, Honolulu, HI, USA the risk of future periprosthetic femur fractures. Results of prior Corresponding Author Cameron Sadeghi, MD ([email protected])

Keywords: cephalomedullary nail, hip fracture, intertrochanteric fracture, revision surgery, registry

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Data Source outcomes,14 and treatment) was performed15 under a fully condi- 16 A detailed summary of data collection procedures for our HFR tional specification. Subsequently, inverse probability of treatment has been previously described.12 Started in 2009, this surveillance weights were calculated (ie, using a logistic regression model with tool for all surgically treated hip fractures performed in 4 regions the listed confounders as predictors of treatment assignment and of our health care system (Hawaii, Northern California, Northwest, a caliper restriction of 0.20 standard deviation [SD] of the logit 17,18 and Southern California) captures patient, procedure, implant, sur- propensity score ), and a treatment effect was estimated. geon, and hospital information using the electronic health record We used 500 bootstrap samples to calculate the treatment effect (EHR), administrative claims data, health care membership data, estimate (mean of the samples) and the variance of the estimate. β other institutional databases, and mortality records. From 2009 to Hazard ratios (HRs) for survival endpoints, estimates for con- 2014, the registry included 26,873 procedures. Coverage is 100% tinuous endpoints, 95% normal-theory confidence intervals (CIs), for all surgically treated hip fractures performed in Kaiser Per- and 2-sided p-values were reported. Analyses were performed α manente. Outcomes are longitudinally monitored after the index using R version 3.3.0 software, and = 0.05 was the statistical procedure using electronic screening algorithms and are validated significance threshold used for this study. by trained clinical content experts using the EHR. RESULTS Treatment Among the 5526 hip fracture procedures, there were 96 all- cause revisions (1.7%). Of the 96 revisions, 50 (1.6%) were among The treatment of interest was length of the cephalomedullary the 3108 cases using long nails and 46 (1.9%) were among the nail. For this study, long nails were defined as those extending 2418 with short nails. Twenty-seven (0.5%) revisions were for into the distal metadiaphysis and short nails as 170 to 180 mm periprosthetic fracture specifically: 13 (0.4%) among long nails in length. Nails that were not classified as long or short according and 14 (0.6%) among short nails. Operative times, estimated to these definitions were excluded from the analysis. Data for all blood loss, and LOS data were available from 5493 (99.4%), 4696 implants (including nails) were entered into the EHR at the time (85.0%), and 5504 (99.6%) of the 5526 hip fractures, respectively. of implantation via a barcode scan. This detailed implant informa- Mean (SD) operative time, estimated blood loss, and LOS for tion is extracted from the EHR to the registry and is reviewed by long vs short nail groups were as follows: 62.7 minutes (SD = clinical content experts, who classify each implant into its respec- 33.1) vs 47.4 minutes (SD = 22.8 minutes), 135.7 mL (SD = tive category. 151.7 mL) vs 99.8 mL (SD = 105.5 mL), and 5.57 days (SD = Outcome 4.43 days) vs 5.34 days (SD = 4.24 days). Member terminations during the follow-up period included The primary outcome of interest was all-cause revision surgery. 201 patients (3.6%), and there were 2027 deaths (36.7%). Revision was defined as any reoperation performed after the index procedure where an implant was exchanged. Secondary endpoints Cephalomedullary Nail Length and Revision Risk included revision for periprosthetic fracture, operative time (in min- Unadjusted cumulative incidence curves for time to all-cause re- utes), estimated blood loss (in milliliters), and in hospital LOS (in vision stratified by nail length are displayed in Figure 1. Propensity days). Revision outcomes were time-to-event with follow-up time score weights significantly reduced the imbalance of the devices defined as the time from the index procedure date until the date on the covariates (all standardized differences < 0.01; Table 1). of revision surgery, health care membership termination, death, or After the application of inverse probability of treatment weights, study end date (December 31, 2014), whichever came first. Date we failed to observe evidence of a difference in risk of all-cause of membership termination and death for survival endpoints were revision when long nails were compared with short nails (HR = treated as censored cases, with survival time based on the time those 0.75, 95% CI = 0.48-1.15, p = 0.186). A subgroup analysis based cases exited the study sample. on conditional (regression-adjusted) proportional hazards mod- Statistical Analysis els indicated a lack of evidence supporting a difference between Gamma3 and TFN (reference group) among long nails (HR = Several potential confounders of treatment were considered, 1.13, 95% CI = 0.63-2.04, p = 0.675) and short nails (HR = 0.79, including age, body mass index (BMI), American Society of An- 95% CI = 0.39-1.61, p = 0.521), with respect to all-cause revision. esthesiologists (ASA) classification, sex, race/ethnicity, and use of The use of interlocking screws was not associated with a higher risk interlocking screws. Average treatment effects were estimated by among long nails (HR = 0.90, 95% CI = 0.51-1.58, p = 0.703) or incorporating inverse probability of treatment weights in a Cox short nails (HR = 0.78, 95% CI = 0.35-1.76, p = 0.554; reference proportional hazards regression for survival endpoints (revision group = no interlocking screw). The primary reason for all-cause surgery) and a linear regression model for continuous endpoints revision was fixation failure/symptomatic implant for both long (operative time, estimated blood loss, LOS). The use of weights can and short nails, 56.0% and 52.2%, respectively (Table 2). A similar induce dependence in the data, and an effective option for variance conclusion was reached when we looked specifically at risk of revi- 13 estimation is a nonparametric bootstrap. Given the presence of sion for periprosthetic fracture for long vs short nails (HR = 0.59, missing data on some covariates, for each bootstrap sample a single 95% CI = 0.23-1.48, p = 0.258). imputation (imputation model included all potential confounders,

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.229 77 CLINICAL PRACTICE Treatment of Intertrochanteric Femur Fractures with Long versus Short Cephalomedullary Nails

Figure 1. Cumulative incidence of all-cause revision for long (black line) and short (gray line) cephalomedullary nails after surgical repair of intertrochanteric hip fracture.

Table 1. Descriptive statistics and covariate balance for 5526 Table 2. Reasons for revision by cephalomedullary nail lengtha patients undergoing intertrochanteric hip fracture surgery using Long nails Short nails Reason a cephalomedullary nail, by nail length (2009-2014) (n = 50) (n = 46) Preweight Postweight Fixation failure/symptomatic implant 28 (56.0) 24 (52.2) Long nail Short nail Characteristica standardized standardized (n = 3108) (n = 2418) Infection 0 (0) 1 (2.2) difference difference Osteonecrosis 1 (2.0) 2 (4.4) Continuous, mean (SD) Posttraumatic osteoarthritis 2 (4.0) 5 (10.9) Age, y 80.6 (11.0) 81.2 (10.8) 0.06 0 Periprosthetic fracture 13 (26.0) 14 (30.4) BMI, kg/m2 24.6 (5.4) 24.1 (5.1) 0.11 0.01 Malunion 1 (2.0) 1 (2.2) ASA 2.8 (0.6) 2.9 (0.6) 0.10 0 classification Nonunion 11 (22.0) 6 (13.0) Categorical, a Patients could have more than 1 revision reason. Data are number (%). no. (%) Female sex 2170 1698 0.01 0 (69.8) (70.3) Table 3. Risk of outcomes for long versus short Race/ethnicity 141 (4.5) 225 (9.3) 0.18 0 cephalomedullary nails in linear regression models fit with Asian inverse probability of treatment weights Hispanic 367 (11.9) 202 (8.4) 0.11 0.01 Outcome β (95% CI) p value White 2465 1870 0.04 0.01 Operative time,a min 18.80 (17.33-20.27) < 0.001 (79.6) (77.7) Estimated blood loss,b mL 41.10 (31.71-50.48) < 0.001 Other 124 (4.0) 111 (4.6) 0.02 0 c Interlocking 1937 2109 0.61 0.01 Inhospital length of stay, d 0.35 (0.12-0.58) 0.003 screws (62.3) (87.2) a n = 5493. a Missing data: BMI (n = 29), ASA (n = 74), sex (n = 1), race/ethnicity (n = 21). b n = 4696. c n = 5504. ASA = American Society of Anesthesiologists; BMI = body mass index; pre- CI = confidence interval. weight = before applying propensity score weights; postweight = after applying propensity score weights; SD = standard deviation.

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Secondary Outcomes of transfusion related to more blood loss have also been previously 5,21 In adjusted models, long nails were associated with 18.80 more reported in prior studies, which could also prolong LOS. Our minutes of operative time (95% CI = 17.33-20.27 minutes, p < registry lacks detail on transfusions; therefore, this could not be 0.001; Table 3). There was 41.1 mL more of estimated blood loss investigated in the present study. for long nails compared with short nails (95% CI = 31.71-50.48 Our study is not without limitations. This study is observa- mL, p < 0.001), and patients who received a long nail had a longer tional in nature, and causation cannot be inferred. To mitigate inhospital LOS (8.4 hours; β = 0.35, 95% CI = 0.12-0.58 hours, confounding due to differences across implant designs outside p = 0.003). of nail length, we restricted the study sample to the 2 highest volume designs in the HFR. Furthermore, although we at- DISCUSSION tempted to account for potential confounders in our analysis, Cephalomedullary nails are the most common method for residual confounding due to unmeasured variables is a possibil- stabilizing intertrochanteric femur fractures, but controversy ity. For example, we were unable to account for fracture type and exists regarding the indications for long vs short nails. Several surgeon decision making. A surgeon may judge a fracture, such studies have compared the use of long and short nails, but many as those with large posteromedial fragments or subtrochanteric of these have been limited by sample size and length of follow-up. extension, to be more unstable, and preferentially select a long Therefore, we evaluated the risk of all-cause revision for a large cephalomedullary nail in the treatment of these fractures. We cohort of patients treated with long vs short cephalomedullary also were unable to perform radiographic review for the entire nails using the Kaiser Permanente Hip Fracture Registry. Even study sample but relied instead on diagnostic coding to identify in our cohort of more than 5500 patients, we failed to observe a patients with intertrochanteric fractures. However, we do not difference between nail length and risk of revision, but long nails expect diagnosis coding of intertrochanteric fractures to depend did have a longer operative time, a greater estimated blood loss, on receipt of a long or short nail. and a longer LOS. Study strengths include use of our institution’s hip fracture In general, we found high union rates and a low incidence registry as the data source, which prospectively collects informa- of implant revision for intertrochanteric femur fractures with tion on a predefined set of variables. Outcomes are longitudinally cephalomedullary nails: 1.9% for all-cause revision and 0.5% tracked using algorithms and are validated through manual chart for revision due to periprosthetic fracture specifically. This is in review, which increases the internal validity of our study. line with results of recent studies that have reported the risk of CONCLUSION ipsilateral femur refracture in the range of 0.5% to 10%.4-6,8,19,20 In a larger study sample, after adjusting for a number of poten- In a cohort of more than 5500 patients with intertrochanteric tial confounders, our revision findings are consistent with results fractures who underwent hip fracture surgery using a cephalom- of prior studies with smaller sample sizes investigating long vs edullary nail, we failed to observe a difference in risk of all-cause short nails.5,8,9,21-23 Most of these prior studies had sample sizes revision and revision for periprosthetic fracture regardless of use of around 200 patients, with the exception of the study by Liu of long or short nails. Short cephalomedullary nails resulted in et al,9 which included 899 patients. There has been concern shorter operative times, with a lower estimated blood loss, and reported regarding heterogeneity across implant devices.5 How- a shorter LOS. These findings suggest that a surgeon’s routine use of short cephalomedullary nails may be appropriate in the ever, our results held even when stratifying the data by patients v treated with Gamma3 vs TFN nails. The most common reason treatment of intertrochanteric fractures. for revision surgery, regardless of nail length, was the presence Disclosure Statement of symptomatic implants. The registry lacked detail on whether The author(s) have no conflicts of interest to disclose. this was due to a cut-out or removal of a painful implant, and this is a study limitation. Acknowledgments Our findings on operative time and estimated blood loss are We acknowledge the Kaiser Permanente orthopedic surgeons who contribute 5 similar to those of a prior report. Our LOS findings are similar to the Kaiser Permanente Hip Fracture Registry as well as the Surgical to those of a prior study21 but contrast with another study that Outcomes and Analysis Department staff, which coordinates registry operations. reported no difference in LOS.5 One reason for this discrepancy The authors also acknowledge Brian H. Fasig, PhD, for his ongoing support of might be a longer procedure time for localizing and placing a the Kaiser Permanente Hip Fracture Registry and quality control management. Kathleen Louden, ELS, of Louden Health Communications performed a distal interlocking screw in long nails. Furthermore, our analysis primary copyedit. accounted for a number of patient and surgical factors through propensity score weighting before the evaluation of outcomes. References Although our findings for operative time, estimated blood loss, 1. Lugovskaya N, Vinson DR. Paroxysmal atrial fibrillation and brain freeze: A case and LOS are statistically significant, we acknowledge that the of Anglen JO, Weinstein JN. Nail or plate fixation of intertrochanteric hip fractures: changing pattern of practice. A review of the American Board of Orthopaedic Surgery differences observed in these outcomes by nail length may be of Database. J Bone Joint Surg Am 2008 Apr;90(4):700-7. limited clinical significance. An increase in LOS by 8 hours for 2. Bhandari M, Schemitsch E, Jonsson A, Zlowodzki M, Haidukewych GJ. Gamma patients treated with long nails may be related to an inherent nails revisited: gamma nails versus compression hip screws in the management of intertrochanteric fractures of the hip: a meta-analysis. J Orthop Trauma. 2009 selection bias in which patients with more severe fracture pat- Jul;23(6):460-4. terns are more likely to be treated with a long nail. Higher rates

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.229 79 CLINICAL PRACTICE Treatment of Intertrochanteric Femur Fractures with Long versus Short Cephalomedullary Nails

3. Haidukewych GJ. Intertrochanteric fractures: ten tips to improve results. J Bone Joint 13. Austin PC. Variance estimation when using inverse probability of treatment weighting Surg Am. 2009 Mar 1;91(3):712-9. (IPTW) with survival analysis. Stat Med. 2016 Dec 30;35(30):5642-55. 4. Hou Z, Bowen TR, Irgit KS, Matzko ME, Andreychik CM, Horwitz DS, et al. Treatment 14. White IR, Royston P. Imputing missing covariate values for the Cox model. Stat Med. of pertrochanteric fractures (OTA 31-A1 and A2): long versus short cephalomedullary 2009 Jul 10;28(15):1982-98. nailing. J Orthop Trauma. 2013 Jun;27(6):318-24. 15. Shao J, Sitter RR. Bootstrap for Imputed Survey Data. J Am Stat Assoc. 5. Boone C, Carlberg KN, Koueiter DM, Baker KC, Sadowski J, Wiater PJ, et al. Short 1996;91(435):1278-88. versus long intramedullary nails for treatment of intertrochanteric femur fractures 16. van Buuren S. Multiple imputation of discrete and continuous data by fully conditional (OTA 31-A1 and A2). J Orthop Trauma. 2014 May;28(5):e96-e100. specification. Stat Methods Med Res. 2007 Jun;16(3):219-42. 6. Kleweno C, Morgan J, Redshaw J, Harris M, Rodriguez E, Zurakowski D, et al. Short 17. Hong G. Marginal mean weighting through stratification: Adjustment for selection bias versus long cephalomedullary nails for the treatment of intertrochanteric hip fractures in multilevel data. J Educ Behav. 2010;35:499-531. in patients older than 65 years. J Orthop Trauma. 2014 Jul;28(7):391-7. 18. Hong G. Marginal mean weighting through stratification: A generalized method for 7. Kanakaris NK, Tosounidis TH, Giannoudis PV. Nailing intertrochanteric hip fractures: evaluating multivalued and multiple treatments with nonexperimental data. Psychol short versus long; locked versus nonlocked. J Orthop Trauma. 2015 Apr;29 Suppl Methods. 2012 Mar;17(1):44-60. 4:S10-6. 19. Okcu G, Ozkayin N, Okta C, Topcu I, Aktuglu K. Which implant is better for treating 8. Vaughn J, Cohen E, Vopat BG, Kane P, Abbood E, Born C. Complications of short reverse obliquity fractures of the proximal femur: a standard or long nail? Clin Orthop versus long cephalomedullary nail for intertrochanteric femur fractures, minimum 1 Relat Res. 2013 Sep;471(9):2768-75. year follow-up. Eur J Orthop Surg Traumatol. 2015 May;25(4):665-70. 20. Lindvall E, Ghaffar S, Martirosian A, Husak L. Short Versus Long Intramedullary Nails 9. Liu J, Frisch NB, Mehran N, Qatu M, Guthrie ST. Short-term Medical Complications in the Treatment of Pertrochanteric Hip Fractures: Incidence of Ipsilateral Fractures Following Short Versus Long Cephalomedullary Nails. Orthopedics. 2018 Sep and Costs Associated With Each Implant. J Orthop Trauma. 2016 Mar;30(3):119-24. 1;41(5):e636-e42. 21. Krigbaum H, Takemoto S, Kim HT, Kuo AC. Costs and Complications of Short Versus 10. Karter AJ, Ferrara A, Liu JY, Moffet HH, Ackerson LM, Selby JV. Ethnic disparities in Long Cephalomedullary Nailing of OTA 31-A2 Proximal Femur Fractures in U.S. diabetic complications in an insured population. JAMA. 2002 May 15;287(19):2519- Veterans. J Orthop Trauma. 2016 Mar;30(3):125-9. 27. 22. Hulet DA, Whale CS, Beebe MJ, Rothberg DL, Gililland JM, Zhang C, et al. Short 11. Koebnick C, Langer-Gould AM, Gould MK, Chao CR, Iyer RL, Smith N, Versus Long Cephalomedullary Nails for Fixation of Stable Versus Unstable et al. Sociodemographic characteristics of members of a large, integrated Intertrochanteric Femur Fractures at a Level 1 Trauma Center. Orthopedics. 2019 health care system: comparison with US Census Bureau data. Perm J. 2012 Mar 1;42(2):e202-e9. Summer;16(3):37-41. 23. Shannon SF, Yuan BJ, Cross WW 3rd, Barlow JD, Torchia ME, Holte PK, et al. 12. Inacio MC, Weiss JM, Miric A, Hunt JJ, Zohman GL, Paxton EW. A Community- Short Versus Long Cephalomedullary Nails for Pertrochanteric Hip Fractures: A Based Hip Fracture Registry: Population, Methods, and Outcomes. Perm J. 2015 Randomized Prospective Study. J Orthop Trauma. 2019 Oct;33(10):480-6. Summer;19(3):29-36.

The Permanente Journal • https://doi.org/10.7812/TPP/19.229 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 80 CLINICAL PRACTICE My Introduction to Mission Surgery: A Diary Andrew Wexler, MD, MA, FACS1 Perm J 2020;24:19.219 E-pub: 04/03/2020 https://doi.org/10.7812/TPP/19.219

ABSTRACT naked children stare disbelieving at the white faces in the bus. I experienced my first international surgical mission trip in 1993. “Mzungu,” they cry (“white people strangers”). It was a turning point in my surgical career and has been followed There are few cars, but the roadside teems with people walking, by many missions in many countries over 25 years. Often I am newspapers tucked under their arms or basketed burdens on their asked by young surgeons what is it like to work on an international heads. We pass small outdoor markets, where women sit in the dirt mission and what one should expect. Although each mission is behind colorful blankets covered with fruit, clothing, and multi- different, the sense of accomplishment is always the same and colored plastic containers. The day starts early in Africa. Ahead the emotional high one gets from performing the work is always we see a large 3-story concrete building, and an old sign above present. Different organizations have different team models. The the rusted iron gate proclaims that this is the provincial hospital. description here is based on my first mission with Operation Smile, The bus pulls up to the front of the hospital, where a large a global nonprofit medical service organization. banner welcomes our mission team. Medical Director Dr Otieno and the nurse matron, Sister Julia, greet us. Dr Otieno’s brow is INTRODUCTION covered with sweat, and he apologizes that he is not feeling well In 1993, I experienced my first international surgical mission. because of recurrent malaria. He guides us through the stark It was a turning point in my surgical career and has been followed concrete hospital lobby and out a back door to a yard, where hun- by many missions in many countries over 25 years. Often I am dreds of children and their families sit under corrugated-metal asked by young surgeons, “What is it like to work on an interna- shades in the morning sun. There are children with tumors and tional mission? What should one expect?” Although each mission with burns, but the overwhelming number are infants, children, is different, the sense of accomplishment is always the same and teens, and adults with unrepaired clefts. The infants are swaddled the emotional high one gets from performing the work is always in colorful African fabrics, and the older children and most of present. Different organizations have different team models. The the adults as well are shoeless. They look to us expectantly. We description here is based on my first mission, to Kenya, Africa, move back into the hospital, where large rooms with wooden with Operation Smile, a global nonprofit medical service orga- tables and dozens of plastic chairs and benches have been set up. nization focused on performing safe cleft surgery. This will be the designated screening area, where each child will be seen by a dentist, a pediatrician, an anesthesiologist, a plastic DIARY OF A FIRST MISSION surgeon, and a speech therapist. Medical records will be created The equatorial sun rises, and with first light the vibrations of and a photo taken of each child. During the next 2 days more insects and the unfamiliar calls of strange birds fill the room. than 300 children will be screened for surgery, with every parent Yesterday evening we arrived after 30 hours of travel through and child hoping that their name will be chosen for the surgical 10 time zones. At the primitive airport the luggage and equip- schedule. The team hurries to unpack the screening equipment ment was piled high into old trucks, which stirred the fine red and set up the examination tables. dust of the road into our hair and gritted it between our teeth. While we gather important patient information, we also gather Our clothes stuck to our bodies with the heat and humidity. We the stories of children and adults whose lives have been affected longed for a tepid shower in our old hotel. by facial deformity. Their stories are of travel and expectation and Before collapsing into our beds, we carefully taped the holes hope. There is Aaron, a 10-year-old boy, who has walked 100 in the screens and our bed nets and meticulously killed every miles across the African landscape with Gabriel, his 6-year-old mosquito in the room. In this part of Africa 1 in every 5 mos- brother who has a cleft. There is Chastity, the 12-year-old girl quitoes carries malaria, and they feed at night. In the daytime it with a bilateral cleft who was given by her family to a wealthy is the mosquitoes that carry dengue that one must worry about. woman to work as a servant. She is allowed to work only in the This morning I walk out on my balcony, the day already hot, back rooms of the house and not be seen by others. Her employer and the smell of burning braziers and garbage is in the air. In has dropped her off alone at the hospital. There is Grace, age 11 front of me glitters Lake Victoria, headwaters for the Nile. Large years, burned in a house fire, with her neck and chin fused to white egrets and blue-gray storks fill the trees along the lake bank. her chest, her lower lip contorted against the contracture, her An African eagle skims the waters looking for fish. Two impala nervously graze in the morning light. I am in Africa, and I am in shock, thousands of miles from those I love, and a stranger in Author Affiliations a difficult land. What am I doing here? This is nuts! 1 Emeritus, Plastic Surgery, West Los Angeles Medical Center, CA At 6:30 am we board the bus, with our knapsacks filled with water bottles, stethoscopes, flashlights, tongue depressors, and Corresponding Author Andrew Wexler, MD, MA, FACS ([email protected]) little toys for the children. We drive past mud and dung huts, where women prepare breakfast outside over charcoal fires and Keywords: Africa, career satisfaction, cleft palate, global health, international health, Kenya, Operation Smile, Operation Smile Mission Kenya, plastic surgery

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eyes dark and piercing under the shawl she wears to hide her Our trip binds us to the lives of our Kenyan hosts; their culture deformities. For 3 months she has lived in the courtyards and is warm, friendly, and accepting. They are both happy and grateful corridors of the hospital begging food, waiting for the promise that we have come and openly express their gratitude. of a team of physicians to come and release her from the social Sunday night I can’t sleep. There is the time difference, the and physical prison of her flesh. knowledge that I must get up very early, and the self-doubt of As a boy I was fascinated by a textbook of tropical diseases a young surgeon who hopes that his work will be good enough on the shelf of the public library. Before me in these lines of with so many watching over his shoulder. If I can just have the patients I see the lives affected by those diseases: Malaria, as- first case go smoothly and do well . … Am I good enough . … cariasis, elephantiasis, noma (cancrum oris), schistosomiasis, Do I know enough? Why can’t I sleep when I know I must? malnutrition, vitamin deficiency, and so much untreated HIV Day 5, Monday, I am up before 6, as the sunrise wakes the infection. There are so many clefts and burns that we can fix avian chorus. I quickly wash, dress, and make a final check of and so many others whose conditions we cannot change. Our my cheat sheet for bilateral cleft lip markings. I was confident selection process engenders incredible joy in the chosen and dis- of my cleft experience when I applied for the mission, but sud- appointment for those we cannot. I must accept the realization denly I am now not so sure it is enough. The clefts seemed so that we cannot cure the ills of Africa but only hope to change wide during screening. the life of 1 child at a time. We arrive at the hospital greeted by the expectant gazes of By the end of the second day of screening, we have seen 300 children and their parents. Hope and anxiety mix in their faces. patients, and the hospital has turned over 3 of their 4 operating As I wait for my first patient to be ready, I am impressed with rooms (ORs) to the visiting team. Through the doors of the OR the efficiency and professionalism of the team members. The are stark rooms, with concrete floors, and central drains still wet nurses, physicians, and support crew are people of extraordinary from the nightly hosing they receive as a cleaning. We don white talent bound by a common heart and sense of caring. Although rubber boots to go in while the local nurses walk barefooted most have never worked together before, the team operates with sloshing through the remnant standing water. The tables sit with military precision. torn cushions. Large cranks and gears control their movement, My first patient is Gabriel, the 6-year-old who has walked although most don’t move at all. Two rooms have an overhead 100 miles to be here. Aaron, his brother, holds his hand until we light, and the other OR has a standing metal lamp with a flexible take him through the OR doors. In the OR Gabriel climbs up neck. One room has air conditioning, and the other 2 have open on the OR table unassisted, holds the mask over his face, and windows with screens. falls asleep. He is intubated, and with a simple povidone-iodine In the OR corridor sit our large white plastic crates with all the preparation and a single drape with a hole cut in it, we are ready contents of a modern OR inside. What happens next is part magic to go. My scrub nurse is a local woman from the Luo tribe; Her and part military mission as the OR nurses, anesthesiologists, and name is Hope. biotechnician take charge of transforming these tile and concrete A young Kenyan surgeon, Joseph, is my first assistant and my enclosures into modern ORs. What is immediately evident is the student. My job during the next few days is to teach him how to expertise, skill, and dedication demonstrated by a group of true do a cleft repair by himself. The room is hot, too hot for me to professionals, most of whom who have never met before. wear a surgical gown, and there are additional physicians, nurses, By Saturday night on day 3 the full team has arrived. We sit and students who press behind me to look over my shoulder. Hey, together for the first time crowded into a room with a long table no pressure, I think and start the procedure, explaining my moves and a ceiling fan, which circulates the tropical air. We are 46 to Joseph while I reinforce them to myself. people from 7 different countries with 5 different religions and An hour later the operation is over, and I am drenched with 5 different native languages. I do not know most of the team perspiration, but Gabriel has a beautiful new lip. Outside the OR members, but what I will come to learn during the next week is doors I find Aaron just where we had left him. that these people are a collection of some of the finest gems in “Where is my brother?” he asks. His face looks much older the world of health care. The individuals in the room are bound than 10. together by a heartfelt desire to give of themselves for the pure “Your brother is fine,” I say. “He has a new lip, and you will joy of giving. During the next few hours we will be greeted by see him soon.” the local mayor; learn each other’s names; and review in detail Aaron bursts into a broad smile. the mission procedures, safety regulations, and expectations. We Throughout the day the postoperative ward fills with children. entered the room as individuals from around the world, and we Families crowd around the beds, cradle their children in their arms, leave the room as a team. and fan them, trying to keep them cool in the sweltering ward. On Sunday our local hosts have arranged a trip for us, a tour The ward nurses have the most difficult job of the mission. For by bus and boat to visit the villages that many of our Kenyan col- 15 hours a day they scurry between the tightly packed beds in leagues call home. The bus is packed with the Kenyan nurses and the heat of the ward, caring for the postoperative patients who physicians, who eagerly point out all the important sites, introduce are rolled in from the OR in a constant stream. us to their village chiefs, and laugh as we hesitantly try their local Between cases the surgeons drink tea and coffee, and eat rice foods. The villages are hot, dusty, and poor, but everywhere are and fried tilapia caught from Lake Victoria. My least favorite the sounds of laughter and children. food is ugali, a boiled root starch mashed into a pastelike mix.

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By the end of the day we have completed 33 operations. It is EPILOGUE 8 pm, and exhausted, we pile into the bus for the dusty ride back Operation Smile served Kenya for nearly 20 years (before be- to the hotel. Dinner is at the hotel bar, and we drink, Tusker, the coming its own nongovernmental organization, Operation Smile local beer. The nights are balmy, but we wear long sleeves to hide Mission in Kenya1). During that time, I returned to Kenya on 4 from the mosquitoes. separate occasions. Over 2 decades we witnessed and contributed For the next 4 days we will live in the ORs from 7 am to 8 pm, to the growth of the local surgical talent, training residents and performing as many surgical cases as we can fit into the sched- young surgeons, who are now the professors teaching others. ule. Grace will have her neck and elbows released and grafted. Kisumu, the city of my first mission in 1993, was a small poor Chastity will cry herself to sleep after her cleft repair, overcome city in a neglected western province. Today it is thriving as the with emotion. We find her asleep in the morning, clutching a third largest city in Kenya.2 Over a generation, Kenya’s health care mirror close to her face. system has developed the skill set self-sufficiency, and additional Throughout the week there is the intricate puzzle of schedule revenue streams, that has allowed Operation Smile Mission in manipulation. The nurse coordinator and chief surgeon match Kenya to function independently. Today there are Kenyan sur- surgeons’ strengths and speeds with the appropriate cases, sliding geons and nurses working on the international mission teams, v cases from one room to another to squeeze in another child or serving other countries where the need is also great. maybe 3 or 4 if possible. As surgeons, we learn from each other small technical points, tricks, and techniques, and we teach. Dur- Disclosure Statement ing the week I become a better surgeon, and Joseph, my Kenyan Dr Wexler is the founder and president of “Surgiwex” a 501c3 first assistant, can now close a cleft lip and a palate on his own. charitable organization that brings training in and instruments for maxillofacial surgery to low- and/or middle-income countries. He has no other conflicts of Our final day, with the last child operated on, there are high interest to disclose. fives in the OR and an exhalation of fatigue and relief that 175 children’s lives have been changed without a single complication. Acknowledgments The OR equipment is now folded back into the large white plas- Kathleen Louden, ELS, of Louden Health Communications performed a tic crates. We have so much help from so many local new friends. primary copy edit. That evening there is a party with our team and all those who participated in the mission, as well as the local sponsors, the How to Cite this Article Kenyan medical professionals, the mayor, and the district health Wexler A. My introduction to mission surgery: A diary. Perm J 2020;24:19.219. DOI: https://doi.org/10.7812/TPP/19.219 officer, the translators, and the students. The mayor thanks the city utilities manager for the outstanding job he has done in keeping the electricity and water flowing (most of the time) to the hospital. References The next day when we board our international flight, we instantly 1. Quick facts Smile [Internet]. Nairobi, Kenya: Operation Smile Mission in Kenya [cited 2019 Jan 3]. Available from: http://kenya.operationsmile.org/aboutus/facts/. move from the Third World to that of the First. The plane is new 2. Mwaniki A. The largest cities in Kenya [Internet]. WorldAtlas; updated 2018 March and clean, no red dust covers its seats, the air is cool and filtered, 14. Available from: www.worldatlas.com/articles/biggest-cities-in-kenya.html. and there is no smell of burning refuse and densely packed bodies sweating in the heat. We leave behind Africa, unchanged except for 175 children whose lives will now be different and so much better.

The Permanente Journal • https://doi.org/10.7812/TPP/19.219 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 83 CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

Hena Jawaid, MBBS, FCPS1 Perm J 2020;24:19.214 E-pub: 06/03/2020 https://doi.org/10.7812/TPP/19.214

ABSTRACT The State of Spirituality and Mental Health in Pakistan Introduction: Spirituality plays an important part in coping with life problems, health concerns, and well-being issues at Psychiatric problems carry a huge stigma in Pakistan, and individual and collective levels. In Pakistan, few studies have unfortunately Pakistani citizens are paying the price. The stigma looked at the role of religion in patients’ illnesses. against mental illness is rampant. It is sustained by spiritual Objective: To assess patients’ and health care professionals’ cures such as exorcising evil spirits, experimenting with herbal beliefs concerning spirituality and illness to understand the role cures, and tying taw’iz (amulets) around the neck or arms. In of spirituality and religion in clinics. addition, a lack of awareness about mental illness worsens the Methods: A total of 52 patients and 50 health care profession- whole scenario. Thus, the positive impact of religion is some- als from different specialties were interviewed. A self-devised times lost in Pakistan. In general, however, the majority believe tool was used to gain information from patients. For health care that faith in Allah (God) helps them overcome their problems. In Pakistan, few studies have looked at the role of religion professionals a 17-item questionnaire was used. 2 Results: The study results show that most patients view spiri- and spirituality in health. Rana and North found partial re- tuality positively and want their physicians to discuss spirituality mission of depression among study participants who listened with them. Most patients believed that having a strong belief in to Quranic verses in addition to their usual treatment. Results spirituality helped them cope with their condition better. Most of another study revealed a significant positive association of workplace spirituality and self-esteem with psychological well- health care professionals surveyed believed that spirituality plays 3 an important part in a patient’s illness and its prognosis, but only being among mental health professionals. a minority asked patients about spirituality. Most health care professionals quoted lack of time as one of the main reasons for Effects of Spirituality on Health: Global Evidence not discussing spirituality with patients, and some believed it Studies from different countries have shown that spirituality was a private matter. can be a source of comfort and coping for patients with a variety 4 Discussion: Many health care professionals are hesitant to of disorders. In the UK, patients including mental health service discuss spiritual issues with patients because of lack of time, users have expressed concern that they would like to be able to 5 insufficient training, or their own discomfort. There is a need to discuss spiritual matters with their doctor or psychiatrist. In incorporate training about spirituality in the medical curriculum, Germany, a study showed that 1700 inpatients believed their especially in religious societies such as in Pakistan. Further re- faith was a strong source of support in hard times and that search is needed in this area. their trust in a higher power and belief in God helped them in recovery.6 Authors of a study from England, in cancer patients INTRODUCTION (n = 189), showed 35%, 31%, and 18% described opportunities Spirituality is a broad concept with a capacity for various for personal prayer, support from people of their faith, and sup- port from a spiritual adviser, respectively, as an important part perspectives. In general, it includes a sense of connection to 7 8 something bigger than us, and it typically involves a search of their coping with their illnesses. In North America, a local for meaning in life. It is an intrinsic universal human experi- survey found that more than 80% of the population believed in ence—something that touches all of us. People may describe a God or a spiritual force, although they do not necessarily practice spiritual experience as sacred or transcendent or as simply a deep any specific religion. In Greece, an observational study indicated sense of connection with a higher entity. Some may find that that highly religious participants scored low on the depression their spiritual life is intricately linked with a church, temple, scale and, combined with high sense of coherence, religion buf- fers the negative effects of stress on numerous health issues.9 mosque, or synagogue. Others may pray or find comfort in a 10 personal relationship with God or a higher power. Still oth- In the US in 1990, Domar et al found “the relaxation ers seek meaning through their association with nature or art. response”—that 10 to 20 minutes of meditation twice a day Spirituality and religion are now topics of major interest in the world of health care, including mental health. Religiosity can be described by the external manifestations such as praying rituals, dress codes, and abstinence from things believed to be wrong. Author Affiliations 1 Department of Wellbeing, Minaret College, Officer campus, Victoria, Australia Both spirituality and religion play an important part in coping with life’s difficulties. Although research has shed light on the Corresponding Author role of spirituality in the management of patients with a variety Hena Jawaid, MBBS, FCPS ([email protected]) of illnesses, there is still a need for greater understanding of the role of spirituality to solve some of medicine’s greatest mysteries.1 Keywords: disease, health care professionals, positivity, religiosity, spirituality

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leads to a decreased metabolic, respiratory, and heart rates, and (95.8%) believed that prayers could heal, and 75.3% believed slower brain waves. The practice was beneficial for the treat- that prayers could curtail the duration of disease.18 ment of chronic pain, insomnia, anxiety, hostility, depression, premenstrual syndrome, and infertility and was a useful adjunct The Practice Gap 10 to treatment for patients with cancer or HIV. Doctors in Pakistan are mostly trained to deliver strict sci- In Hong Kong, a qualitative study included 18 patients with entific information to patients regarding their particular ill- schizophrenia and 19 mental health professionals; study par- nesses, with little or no emphasis on the spiritual aspect of one’s ticipants regarded spirituality as an inherent part of a patient’s life and disease. Hence, there remains a small but significant well-being, a client’s rehabilitation, and their lives in general.11 12 gap in effective doctor-patient communication and successful In Iran, positive religious coping methods were assessed to be therapeutic alliance. Therefore, the objective of this study was in more frequent use than negative strategies to cope with life’s to examine some reasons leading to this gap and to determine difficulties. In 2002, a prospective study from India reported whether spiritual matters would have any effect on the patients’ improvement in objective clinical psychopathology after a visit treatment and management. or stay at a religious temple, indicating the effect of religious belief on mental health.13 METHODS The proposal for the study was sent to the hospital’s Ethical Pakistan Society, Religion, and Culture Review Committee. After approval, the committee guidelines Pakistan is the sixth most populous country situated in were observed and applied. Consent was obtained from the re- Southeast Asia. Islam as a main religion holds an important spective department chairs. Separate written informed consent position in Pakistan’s social fabric. It is one of the chief sources forms were developed for the health care professionals (HCPs) of values, norms, and national symbols. Thus, religious beliefs group and the patient group. have great influence on institutions (family, education, govern- ment, politics, etc) and social behavior. Study Setting and Design Mazars and ziarats (shrines) are faith healing centers of Mus- The study was conducted in an outpatient setting. All the lims and belong to deceased spiritualists. Their followers visit patients were interviewed separately in outpatient clinics of them to pay their respect due to a deep impact left by their good neurology, psychiatry, oncology, internal medicine, and family deeds. Followers pray for the deceased pirs (saint, faith healer, medicine. Patients’ privacy and confidentiality were maintained. or spiritualist), believing that the faith healers are closer to God Interviews were conducted with follow-up patients with chronic than they themselves, and that showing faith in them will please illnesses who had an established rapport with a particular physi- God. This satisfies their faith and belief. People also visit shrines cian for at least 6 months. The inclusion criteria were confirmed hoping to get solutions to their multifarious problems, such as a through the medical records. cure from disease, request for a child, liberation from poverty, This pilot study used convenient sampling. Fifty-two clinic mental peace, higher crop yield, marriage with their beloved, 14 patients were recruited for the interview, and in the other arm, 50 or for any other social or medical problem. HCPs were taken onboard. None of them declined the interview. Despite all the marvelous advancements in modern medi- The prevalence of a regional study, based on patients’ percep- cine, traditional medicine has always been in practice. Alter- tions, which was done in Islamabad, Pakistan, in 2012,16 was native therapies are used by people in Pakistan who have faith considered. That study showed 93% perceived positive impact in spiritualists, clergy, hakeems (herbal physicians), or even in 15 of spirituality on health. Considering a 95% confidence interval many quacks. These are the first choice for dealing with health and a margin of error of 5%, a sample size of 100 subjects would problems such as infertility, epilepsy, psychosomatic troubles, be needed to achieve a statistical power. We divided the sample depression, and many other ailments. equally into 2 cohorts: patients (n = 52) and HCPs (n = 50).

Effects of Spirituality on Health: Local Evidence Study Criteria Three previous studies from Pakistan have looked at the role 16 The inclusion criteria consisted of 1) patients older than 18 of religion in patients’ illnesses. Ahmed et al conducted a study years of age with chronic illnesses following up on an outpatient on faith-based healing in 604 admitted patients from various basis for 6 months or more who had the capacity to give informed specialty units, including intensive care units, who were capable consent, and 2) HCPs (consultants, fellows, and residents) from of comprehending questions. Their results showed that 93% of Aga Khan University Hospital in Karachi, Pakistan. patients want their physician to express a prayer for them aloud The exclusion criteria included patients who 1) were medi- and 88% accepted that being in the care of “God-fearing physi- 16 cally unstable, 2) lacked the capacity to give informed consent, cians” would have a positive impact on their health. 3) could not understand Urdu or English, 4) could not com- A study in cancer patients showed that applying religious municate or comprehend, and 5) had a follow-up duration of coping in their lives reduced the psychological distress associ- less than 6 months. ated with illness.17 A similar study was conducted in 2008 (N = 400), in which interviews were carried out in patients in family medicine clinics and the patients’ caregiver.18 Most respondents

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Questionnaires rarely do, 20 (40%) indicated sometimes, 12 (24%) often, and 2 We used 2 types of questionnaires for interviews. The patient (4%) always (Table A6). cohort received a self-devised questionnaire based on the FICA Negative Influence of Religion (faith and belief, importance, community, address in care) ques- On considering how often religion can induce guilt, anxiety, 19 tionnaire developed by Puchalski. This questionnaire has 7 or other negative emotions, which can increase patient distress, items with 1 subsection in it. The questionnaire was available 6 (12%) of the HCPs marked never, 21 (42%), rarely; 15 (30%), in English and an Urdu translation. A 17-item questionnaire sometimes; and 8 (16%), often (Table A7). 20 described by Al-Yousefi was used for the HCPs with permis- On a question regarding how often religion influences a sion from the author. The questions were narrated before the patient to refuse, delay, or stop medically indicated therapy, 5 interviewee, and the answers were recorded by the interviewer. participants (10%) marked never, 20 (40%) indicated rarely, 21 The research data were analyzed by statistical analysis soft - (42%) replied sometimes, and 4 (8%) commented often (Table ware (SPSS version 24, IBM Corp, Armonk, NY) for both A8). patient data as well as for HCPs. Regarding HCPs’ perceptions of how often patients use RESULTS religion to avoid taking responsibility for their own health, 10 participants (20%) commented never; 15 (19%), rarely; 19 (38%), A sample of 102 participants was obtained for the study. Par- sometimes; and 6 (12%), often (Table A9). ticipants were divided into 2 groups: 52 patients and 50 HCPs. Communication with Patients about Religion Health Care Professionals’ Responses Health care professionals were asked in general whether they Demographic Characteristics thought it was appropriate to ask about a patient’s religiosity. Four HCPs (8%) indicated it was always appropriate; 19 (38%), Among 50 HCPs, 18 were male (36%), 29 were female (58%), usually appropriate; 12 (24%), rarely appropriate; and 15 (30%), and 3 subjects (6%) did not mention their sex. Other descriptive inappropriate (Table A10). Similarly, 37 (74%) of the HCPs said characteristics of the HCP participants are presented in Table 1. they do not actually inquire about patients’ religious issues, and Intrinsic Religiosity 13 (26%) said they did (Table A11). Even when a patient “suf- Among the 50 participants, 7 (14%) considered their intrinsic fers,” only 25 HCPs (50%) would often (n = 6, 12%) or sometimes religiosity low, 35 (70%) moderate, and 6 (12%) high. Two (4%) (n = 19, 38%) inquire about a patient’s religiosity (Table A12). of them did not comment on their intrinsic religiosity (Table A1 That number was slightly higher if the patient brought up a in online Appendix A (available at www.thepermanentejournal. religious matter. In that case, 29 HCPs (58%) always (n = 3, 6%) org/files/2020/19.214supp.pdf), Health Care Professionals’ or usually (n = 26, 52%) believed it was appropriate to discuss Replies to Questionnaire). the religious matter (Table A13). Patients’ Expression of Faith in Clinics On initiating a discussion with patients about their religious beliefs, 15 HCPs (30%) reported they would whenever they Among 50 HCPs, 18 (36%) mentioned that their patients felt the need, and 2 (4%) said they always would (Table A14). sometimes express their faith in clinical consultations, another Regarding encouraging patients’ adherence to religious ritu- 30 HCPs (60%) said this occurs often, and 1 (2%) HCP always als such as prayers (dua’a) and reading the Quran, only 3 HCPs finds this an active discussion in the clinic (online Table A2). (6%) each responded that they never or rarely do, with the largest Only 1 participant never had such experiences in clinic. proportion (46%, n = 23) replying they often do (Table A15). Positive Influence of Religion The question about sharing one’s own religious ideas and Forty-eight HCPs (96%) reported they consider the influence experiences with a patient evoked a variety of responses. Twen- of religion on health as positive, and 2 (4%) were uncertain about ty-one HCPs (42%) replied never; 8 (16%), rarely; 15 (30%), the influence of religion on health (Table A3). sometimes; 5 (10%), often; and 1 (2%), always (Table A16). Regarding whether religion helps patients to deal with his/ The participants also were split on whether they distract her illness, 13 HCPs (26%) believe religion sometimes helps patients from a religious discussion. Forty-six percent (n = 23) patients, 34 (68%) feel religion often helps, and 3 (6%) think said they never or rarely change the subject, and the remaining it always helps (Table A4). Eight HCPs (16%) consider that 54% (n = 27) replied they sometimes, often, or always change religion sometimes delivers hope, 34 (68%) reported it often the subject in this situation (Table A17). gives hope, and 8 participants (16%) reported it always does The most common factors that discourage a physician from (Table A5). discussing religion with patients were concern about patients’ Support from Religious Leaders discomfort (n = 22, 28.6%) and insufficient time (n = 16, 20.8%). When asked whether they believe patients receive emotional The other reported factors are listed in Table 2. support from their religious members in the community such as an imam (priest) or spiritual healer, only 2 HCPs (4%) re- Patients’ Responses sponded that they believe patients never receive such support The first question in the patient questionnaire was about their from religious members; 13 (26%) of the HCPs believe patients understanding of the term spirituality. Most of the patients de- fined it in terms of faith (trust in God), meaning “a connection

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between God and people,” whereas others described spirituality reciting verses of the holy book) and to the scientific cure of ill- as “an inner state of a person.” One of the patients also expressed nesses. A number of patients seek a spiritual healer in an attempt his disbelief of the concept of spirituality. to find a permanent cure for chronic illnesses before arriving The second question pertained to the importance of faith in at a hospital. Hence, spirituality plays an integral part of daily regard to one’s illness. Fifty of the 52 patients expressed that life of an average person in Pakistan. their beliefs had the utmost importance in their illnesses. One Spirituality in most cases is a belief in God. It is an aspect of patient was not sure about the role of faith in his illness, and life that typically is introduced in one’s childhood and stays until another commented that “its importance in terms of illness is the time of death. It is a conceptual framework to which people minimal.” The third question was about the importance of faith are personally attached or familiar with. Religion, on the other in God at other times in one’s life. Nearly all patients (n = 51) hand, is the external code of practices.1 Socioeconomic tumult said faith was important, but 1 patient said “it is not important and political injustices have unsettled the world’s stability. To in other parts of life.” understand this mayhem, people use various sources to derive The fourth question was about having someone in life to talk comfort, peace, and strength. Religion/spirituality is one of the with about spiritual matters. A total of 22 patients reported methods to deal with this chaos.21 People may place their trust that they have no one to talk to, and 5 patients did not specify in higher powers, which becomes a source of great comfort to whom they talk to about spirituality. Among the others, 4 pa- them in times of emotional and/or physical distress. This system tients mentioned their children, 2 participants mentioned their of belief differs from a scientific or medical knowledge of physi- spouses, 1 patient mentioned his father, 6 patients mentioned cal or mental illness, which is an alien concept to most patients family members, 2 mentioned that they can talk to random in Pakistani culture. The medical approach to illness is usually people about spirituality, 2 specified their spiritual leaders, introduced to them for the first time through HCPs in terms and 1 participant considered that “rituals are the sources to discuss of diagnosis and treatment. spiritual matters with the Higher Being.” Although nurses, paramedical staff, and physicians do con- The fifth question addressed whether their doctors discuss sider spiritual care important, they are usually hesitant to pro- spiritual matters with them. One patient indicated sometimes, ceed in this regard because of a lack of training.22 and 4 answered yes, whereas 47 patients replied no. All of the 47 stated different reasons for this, for instance, “it seems to be Importance of Pastoral Care in Clinics unprofessional,” “doctors have nothing to do with it,” “time con- According to the findings of this study, most of the participat- straints,” “doctors do not talk about it,” and “doctors perceive their ing HCPs regard their intrinsic religiosity at a moderate level, patients differently.” Some said the reason was unknown. A and a few of them think they are highly religious. The HCPs’ subsection of the fifth question was about how one feels when own intrinsic religiosity was not correlated with other key survey the doctor talks about spiritual matters. Eight patients com- parameters. The HCPs also consider that religion often helps mented “good” but gave different responses qualifying their patients to cope with their illnesses and achieve a hopeful state feeling, such as feeling relaxed and calm. The sixth question of mind. In Pakistan, culture embellishes and celebrates religion was about the patient’s preference that doctors should discuss fervently, and patients often discuss religious issues in clinical spiritual matters with their patients or not; 35 patients said yes, settings with their physicians. Interestingly, none of the HCPs 4 patients had no opinion about the matter, 6 patients said no, think that religion has a negative impact on health. Most of and 2 patients preferred a discussion only if patients get relief the HCPs think that patients sometimes seek practical support out of this dialogue. from religious members in the community to get relief and that The seventh question focused on the impact of spiritual religion rarely leads to increased “suffering” among patients. conversation on health. Twenty-seven patients answered yes, that spiritual conversation had an impact on health; 9 patients Other Side of Religious Context in Health Care answered no, and 10 patients had no idea about this. This last question was concerned about the influence of spiritual discus- On the other hand, a large number of HCPs think that reli- sion over one’s health; multiple free-text responses surfaced. gion sometimes leads patients to refuse or stop medicines when Patients commented that “it develops one’s understanding of his they are indicated and that sometimes patients use religion to or her illness and faith,” “it reminds one about the blessings of God,” avoid taking responsibility for their own health. “it is a source of relief,” and “when it is being said by the doctor, then The Need to Ask More it makes a difference.” This study’s findings support the need for HCPs to bring up DISCUSSION a patient’s spiritual beliefs in the clinical setting but to do so This study underpins the importance of spiritual care in clini- in a manner of curiosity and desire to understand the patient’s cal settings. Patients were asked their opinions about spirituality belief system. They need to be very careful not to impose their in conjunction with HCPs’ clinical practices. beliefs unless asked. Although HCPs believe that it is usually A large part of the Pakistani population holds the belief that appropriate to inquire about a patient’s religiosity, especially spiritual and medical cures go hand in hand. Equal power of when patients bring up the topic in clinics, most of the providers belief is given to religiosity (eg, healing power of prayers and do not go ahead to further explore the religious issues of their

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.214 87 CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

patients. At times, HCPs do inquire about a patient’s religios- to incorporate spirituality training in the medical curriculum, v ity when the patient experiences anxiety or depression, or when especially in Pakistan. the patient wants to discuss religiosity in a clinical setting. The HCPs often encourage patients to discuss their own religious Disclosure Statement The author(s) have no conflicts of interest to disclose. beliefs and practices. Most of the HCPs do share their own re- ligious ideas and experiences when they come across any kind of Acknowledgments religious issues in the discussion, but a few of them try to change Kathleen Louden, ELS, of Louden Health Communications performed a the subject tactfully. Patients’ discomfort is the most common primary copyedit. reason why HCPs avoid religious discussion in a clinical setting. Physicians and communities across the globe are now sug- References gesting spirituality-integrated care to boost recovery and to 1. Simpson JA, Weiner ES. The compact Oxford dictionary. Oxford, UK: Oxford make effective use of spiritual resources for physical benefit. 23 University Press; 1991. 2. Rana, S.A., & North, A.C. (2007). The Effect of Rhythmic Quranic Recitation on Some medical curriculums now require pastoral care training Depression. Journal of Behavioral Sciences, 17 (1-2); 37-53 to deal with spiritual matters effectively and diligently without 3. Awan, S., & Sitwat, A. (2014). Workplace spirituality, self-esteem, and making anyone uncomfortable.24 psychological well-being among mental health professionals. Pakistan Journal of Psychological Research, 29(1), 125. Patients do want to discuss spiritual issues in the clinics with 4. Anandarajah, G., & Hight, E. (2001). Spirituality and medical practice. American their physicians, but most of them are afraid that doctors might family physician, 63(1), 81-88. not have time to do so and may believe it is unprofessional to 5. McCord, G., Gilchrist, V. J., Grossman, S. D., King, B. D., McCormick, K. F., Oprandi, A. M., ... & Amorn, M. (2004). Discussing spirituality with patients: a hold such kinds of discussion in a professional setting. Most of rational and ethical approach. The Annals of Family Medicine, 2(4), 356-361. the patients in this study adhere to the concept of spirituality 6. Büssing, A., Michalsen, A., Balzat, H. J., Grünther, R. A., Ostermann, T., and emphasize its importance in various aspects of life other than Neugebauer, E. A., & Matthiessen, P. F. (2009). Are spirituality and religiosity disease. Patients believe that spiritual discussion will broaden resources for patients with chronic pain conditions? Pain medicine, 10(2), 327-339. 7. Soothill, K., Morris, S. M., Harman, J. C., Thomas, C., Francis, B., & McIllmurray, their understanding and meaning regarding their illnesses and M. B. (2002). Cancer and faith. Having faith–does it make a difference among provide them relief. It also connects them with God and reminds patients and their informal carers? Scandinavian Journal of Caring Sciences, 16(3), them about his blessings in their lives. 256-263. 8. Lukoff, D., Turner, R., & Lu, F. (1992). Transpersonal psychology research review: Psychoreligious dimensions of healing. The Journal of Transpersonal Psychology, Limitations 24(1), 41. 9. Anyfantakis, D., Symvoulakis, E. K., Linardakis, M., Shea, S., Panagiotakos, D., Although this study has drawn on patients’ and physicians’ & Lionis, C. (2015). Effect of religiosity/spirituality and sense of coherence on perspectives regarding spirituality in a clinical background, the depression within a rural population in Greece: the Spili III project. BMC psychiatry, study needs to have a greater sample size. This can help research- 15(1), 173. 10. Domar, A., Seibel, M., & Benson, H. (1990). The mind/body program for infertility: A ers, clinicians, and policy makers to incorporate patients and new behavioral treatment approach for women with infertility. Fertility and Sterility, HCPs’ preferences into a biopsychosocial-spiritual model. Most 53, 246-249. Pakistani physicians are trained outside the country in a secular 11. Ho, R. T. H., Sing, C. Y., Fong, T. C. T., Au-Yeung, F. S. W., Law, K. Y., Lee, L. F., & Ng, S. M. (2016). Underlying spirituality and mental health: the role of burnout. setting that alters their religious preferences. Data from different Journal of occupational health, 58(1), 66-71. governmental settings and from various other private hospitals 12. Aflakseir, A., & Coleman, P. G. (2011). Initial development of the Iranian religious would have given a broader and more diverse range of opinions. coping scale. Journal of Muslim Mental Health, 6(1). 13. Raguram, R., Venkateswaran, A., Ramakrishna, J., & Weiss, M. G. (2002). Despite these limitations, this study may prove to be a base Traditional community resources for mental health: a report of temple healing from for further studies that can help in the development of a bio- India. Bmj, 325(7354), 38-40. psychosocial-spiritual model to see patients in a holistic way. 14. Mohyuddin, A., & Ambreen, M. (2014). From faith healer to a medical doctor: creating biomedical hegemony. Open Journal of Applied Sciences, 4(2), 56. 15. Saeed, K., Gater, R., Hussain, A., & Mubbashar, M. (2000). The prevalence, CONCLUSION classification and treatment of mental disorders among attenders of native faith This study has revealed findings from both sides of the table; healers in rural Pakistan. Social psychiatry and psychiatric epidemiology, 35(10), 480-485. it includes the views of physicians and patients. Most of the 16. Ahmed, W., CHOUDHRY, A. M., ALAM, A. Y., & KAISAR, F. (2012). Muslim physicians regard themselves as moderately religious and find patients perceptions of faith-based healing and religious inclination of treating that religion is positively associated with health. However, they physicians. Pakistan Heart Journal, 40(3-4). 17. Khan, Z. H., Watson, P. J., Chen, Z., Iftikhar, A., & Jabeen, R. (2012). Pakistani want to bring this discussion to the clinical setting only when religious coping and the experience and behaviour of Ramadan. Mental Health, patients bring it up in conversation. Their major concern to avoid Religion & Culture, 15(4), 435-446. such discussions in the clinical setting is a patient’s discomfort. 18. Qidwai, W., Tabassum, R., Hanif, R., & Khan, F. H. (2009). Belief in prayers and its role in healing among family practice patients visiting a teaching hospital in Karachi, Pakistan. Pak J Med Sci, 25(2), 182-9. On the other side of the picture, most patients consider 19. Puchalski CM. The role of spirituality in health care. Proc Bayl Univ Med Cent 2001 faith and spirituality as important aspects of their lives and Oct;14(4):352-7. want their doctor to hold a spiritual conversation in the clinics 20. Al-Yousefi, N. A. (2012). Observations of Muslim physicians regarding the influence of religion on health and their clinical approach. Journal of religion and health, because it helps them understand their illnesses in a different 51(2), 269-280. context. Patients, however, think that physicians do not have 21. Hefti, R. (2011). Integrating religion and spirituality into mental health care, time to talk to their patients about spirituality. There is a need psychiatry and psychotherapy. Religions, 2(4), 611-627.

The Permanente Journal • https://doi.org/10.7812/TPP/19.214 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 88 CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

22. Balboni, M. J., Sullivan, A., Amobi, A., Phelps, A. C., Gorman, D. P., Zollfrank, 24. Van de Geer, J., Veeger, N., Groot, M., Zock, H., Leget, C., Prins, J., & Vissers, A., ... & Balboni, T. A. (2013). Why is spiritual care infrequent at the end of life? K. (2018). Multidisciplinary training on spiritual care for patients in palliative care Spiritual care perceptions among patients, nurses, and physicians and the role of trajectories improves the attitudes and competencies of hospital medical staff: training. Journal of Clinical Oncology, 31(4), 461. Results of a quasi-experimental study. American Journal of Hospice and Palliative 23. Yamada, A. M., Lukoff, D., Lim, C. S., & Mancuso, L. L. (2019). Integrating Medicine, 35(2), 218-228. spirituality and mental health: Perspectives of adults receiving public mental health services in California. Psychology of Religion and Spirituality.

Figure 1. Al-Yousefi, N. A. (2012). Observations of Muslim physicians regarding the influence of religion on health and their clinical approach. Journal of religion and health, 51(2), 269-280.

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Table 1. Health care professionals’ demographics Total no. Women, no. Demographic characteristic Men, no. (%) (% of all (%) respondents) Primary specialty Family practice (5.6) 6 (20.7) 7 (14.9) Internal medicine and its subspecialties 11 (61.1) 11 (37.9) 22 (46.8) Pediatrics 0 (0) 3 (10.3) 3 (6.4) Psychiatry 3 (16.7) 6 (20.7) 9 (19.1) Others 3 (16.7) 2 (6.9) 5 (10.6) Psychology 0 (0) 1 (3.4) 1 (2.1) Total 18 (100.0) 29 (100.0) 47 (100.0) Occupation Resident level 1 2 (11.8) 2 (7.1) 4 (8.9) Resident level 2 0 (0) 1 (3.6) 1 (2.2) Resident level 3 2 (11.8) 2 (7.1) 4 (8.9) Resident level 4 0 (0) 4 (14.3) 4 (8.9) Resident level 5 1 (5.9) 4 (14.3) 5 (11.1) Board certified 1 (5.9) 2 (7.1) 3 (6.7) Staff physician 0 (0) 1 (3.6) 1 (2.2) Assistant consultant 0 (0) 2 (7.1) 2 (4.4) Associate consultant 1 (5.9) 1 (3.6) 2 (4.4) Consultant 6 (35.3) 4 (14.3) 10 (22.2) Other 4 (23.5) 5 (17.9) 9 (20.0) Total 17 (100.0) 28 (100.0) 45 (100.0)

Table 2. Reasons why health care professionals do not discuss religion with patientsa Number (%) of Percentage of Reason for not discussing religion responses respondents (n = 77) (n = 50) Insufficient time 16 (20.8) 32.8 Concern about patient discomfort 22 (28.6) 47.8 Unsuitable environment 16 (20.8) 34.8 Insufficient knowledge and training 13 (16.9) 28.3 General discomfort 6 (7.8) 13.0 Concern that colleagues will disapprove 4 (5.2) 8.7 a Group frequencies. Respondents could choose more than 1 reason.

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Hena Jawaid, MBBS, FCPS1 Perm J 2020;24:19.214 E-pub: 06/03/2020 https://doi.org/10.7812/TPP/19.214

SUPPLEMENTARY TABLES A1-A18

Health Care Professionals’ Replies to Questionnaire

You consider your intrinsic religiosity as

Frequency Percent Valid Percent Cumulative Percent

Valid Low 7 14.0 14.6 14.6

Moderate 35 70.0 72.9 87.5

High 6 12.0 12.5 100.0

Total 48 96.0 100.0

Missing System 2 4.0

Total 50 100.0

Table A1 Amongst 50 subjects, 7 (14%) considered their intrinsic religiosity low, 35 (70%) moderate and 6 (12%) high, 2 (4%) of them did not comment on intrinsic religiosity.

In your experience, how often have your patients mentioned religion issues?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 1 2.0 2.0 2.0 Author Affiliations 1 Department of Wellbeing, Minaret College, Officer campus, Victoria, Australia Sometimes 18 36.0 36.0 38.0 Corresponding Author Hena Jawaid, MBBS, FCPS ([email protected]) Often 30 60.0 60.0 98.0 Keywords: disease, health care professionals, positivity, religiosity, spirituality

The Permanente Journal • https://doi.org/10.7812/TPP/19.214Always The Permanente1 Journal • For personal2.0 use only. No other uses without2.0 permission. Copyright © 2020100.0 The Permanente Press. All rights reserved.1 91

Total 50 100.0 100.0

Table A2 Amongst 50 HCPs, 18 (36%) HCPs mention that their patient do express their faith in clinical consultations. 30 (60%) HCPs say it’s often, 1 (2%) subject never found such experience in clinics while another 1 (2%) HCPs always find this as an active discussion in a clinic. Health Care Professionals’ Replies to Questionnaire

You consider your intrinsic religiosity as

Frequency Percent Valid Percent Cumulative Percent

Valid Low 7 14.0 14.6 14.6

Moderate 35 70.0 72.9 87.5

High 6 12.0 12.5 100.0

Total 48 96.0 100.0

Missing System 2 4.0

Total 50 100.0

Table A1 Amongst 50 subjects, 7 (14%) considered their intrinsic religiosity low, 35 (70%) moderate and CLINICAL PRACTICE6 (12%) high, 2 (4%) of them did not comment on intrinsic religiosity. Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

In your experience, how often have your patients mentioned religion issues?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 1 2.0 2.0 2.0

Sometimes 18 36.0 36.0 38.0

Often 30 60.0 60.0 98.0

Always 1 2.0 2.0 100.0

Total 50 100.0 100.0

Table A2 Amongst 50 HCPs, 18 (36%) HCPs mention that their patient do express their faith in clinical consultations. 30 (60%) HCPs say it’s often, 1 (2%) subject never found such experience in clinics while another 1 (2%) HCPs always find this as an active discussion in a clinic.

Is the influence of religion on health generally positive or negative?

Frequency Percent Valid Percent Cumulative Percent

48 96.0 96.0 96.0

2 4.0 4.0 100.0

50 100.0 100.0

Table A3

48 (96%) subjects consider the influence of religion on health as positive and 2 (4%) subjects do not know about the influence of religion on health.

Considering your experience, how often do you think, religion helps patient?

Frequency Percent Valid Percent Cumulative Percent

Valid Sometimes 13 26.0 26.0 26.0 The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.214 92 Often 34 68.0 68.0 94.0

Always 3 6.0 6.0 100.0

Total 50 100.0 100.0

Table A4

13 (26%) subjects feel religion sometimes helps patients to deal with one’s illness, 34 (68%) HCPs feel religion often helps and 3 (6%) HCPs feel it always helps. Is the influence of religion on health generally positive or negative?

Frequency Percent Valid Percent Cumulative Percent

48 96.0 96.0 96.0

2 4.0 4.0 100.0

50 100.0 100.0

Table A3

48 (96%) subjects consider the influence of religion on health as positive and 2 (4%) subjects do not know about the influence of religion on health. CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

Considering your experience, how often do you think, religion helps patient?

Frequency Percent Valid Percent Cumulative Percent

Valid Sometimes 13 26.0 26.0 26.0

Often 34 68.0 68.0 94.0

Always 3 6.0 6.0 100.0

Total 50 100.0 100.0

Table A4

13 (26%) subjects feel religion sometimes helps patients to deal with one’s illness, 34 (68%) HCPs feel religion often helps and 3 (6%) HCPs feel it always helps.

Considering your experience, how often do you think, religion gives patient hope?

Frequency Percent Valid Percent Cumulative Percent

Valid Sometimes 8 16.0 16.0 16.0

Often 34 68.0 68.0 84.0

Always 8 16.0 16.0 100.0

Total 50 100.0 100.0

Table A5

8 (16%) subjects feel religion sometimes delivers hope, 34 (68%) HCPs feel often and 8 participants feel always (16%).

In your experience, how often have your patients received emotional or practical support?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 2 4.0 4.1 4.1 The Permanente Journal • https://doi.org/10.7812/TPP/19.214 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 93

Rarely 13 26.0 26.5 30.6

Sometimes 20 40.0 40.8 71.4

Often 12 24.0 24.5 95.9

Always 2 4.0 4.1 100.0

Total 49 98.0 100.0

Missing System 1 2.0

Total 50 100.0

Table A6

2 (4%) subjects feel patients never receive emotional support from their religious members in community like Imam or spiritual healer, 13 (26%) of them feel they rarely do, 20 (40%) subjects marked sometimes, 12 (24%) participants marked often and 2 (4%) subjects marked always. Considering your experience, how often do you think, religion gives patient hope?

Frequency Percent Valid Percent Cumulative Percent

Valid Sometimes 8 16.0 16.0 16.0

Often 34 68.0 68.0 84.0

Always 8 16.0 16.0 100.0

Total 50 100.0 100.0

Table A5

8 (16%) subjects feel religion sometimes delivers hope, 34 (68%) HCPs feel often and 8 participants feel always (16%). CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

In your experience, how often have your patients received emotional or practical support?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 2 4.0 4.1 4.1

Rarely 13 26.0 26.5 30.6

Sometimes 20 40.0 40.8 71.4

Often 12 24.0 24.5 95.9

Always 2 4.0 4.1 100.0

Total 49 98.0 100.0

Missing System 1 2.0

Total 50 100.0

Table A6

2 (4%) subjects feel patients never receive emotional support from their religious members in community like Imam or spiritual healer, 13 (26%) of them feel they rarely do, 20 (40%) subjects marked sometimes, 12 (24%) participants marked often and 2 (4%) subjects marked always.

Considering your experience, how often do you think, religion causes guilt, anxiety, or other negative emotions?

Frequency Percent Valid Percent Cumulative Percent

6 12.0 12.0 12.0

21 42.0 42.0 54.0

15 30.0 30.0 84.0

8 16.0 16.0 100.0

50 100.0 100.0

Table A7

On considering how religion can induce guilt, anxiety, or other negative emotions which can increase patient suffering; 6(12%) subjects marked never, 21 (42%) rarely, 15 (30%) sometimes and 8 (16%) subjects marked often.

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.214 94

Considering your experience, how often do you think, religion leads patient to refuse, delay, or stop medically indicated therapy?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 5 10.0 10.0 10.0

Rarely 20 40.0 40.0 50.0

Sometimes 21 42.0 42.0 92.0

Often 4 8.0 8.0 100.0

Total 50 100.0 100.0

Table A8 On a question that either religion influences a patient to refuse, delay, or stop medically indicated therapy, 5 subjects (10%) marked never, 20 (40%) rarely, 21 (42%) sometimes and 4 subjects (8%) marked often. Considering your experience, how often do you think, religion causes guilt, anxiety, or other negative emotions?

Frequency Percent Valid Percent Cumulative Percent

6 12.0 12.0 12.0

21 42.0 42.0 54.0

15 30.0 30.0 84.0

8 16.0 16.0 100.0

50 100.0 100.0

Table A7

On considering how religion can induce guilt, anxiety, or other negative emotions which can increase patient suffering; 6(12%) subjects marked never, 21 (42%) rarely, 15 (30%) sometimes and 8 (16%) subjects marked often.

CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

Considering your experience, how often do you think, religion leads patient to refuse, delay, or stop medically indicated therapy?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 5 10.0 10.0 10.0

Rarely 20 40.0 40.0 50.0

Sometimes 21 42.0 42.0 92.0

Often 4 8.0 8.0 100.0

Total 50 100.0 100.0

Table A8 On a question that either religion influences a patient to refuse, delay, or stop medically indicated therapy, 5 subjects (10%) marked never, 20 (40%) rarely, 21 (42%) sometimes and 4 subjects (8%) marked often.

In your experience, how often have your patients used religion as a reason to avoid taking responsibility for their own health?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 10 20.0 20.0 20.0

Rarely 15 30.0 30.0 50.0

Sometimes 19 38.0 38.0 88.0

Often 6 12.0 12.0 100.0

Total 50 100.0 100.0

Table A9 On another stem about the used of religion by patients to avoid taking responsibility for their own health, 10 (20%) subjects commented never, 15 (19%) rarely, 19 (38%) sometimes and 6 (12%) subjects marked often.

The Permanente Journal • https://doi.org/10.7812/TPP/19.214 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 95

In general, do you think it is appropriate for a physician to inquire about a patient’s religiosity?

Frequency Percent Valid Percent Cumulative Percent

Valid Always appropriatie 4 8.0 8.0 8.0

Usaualy appropriate 19 38.0 38.0 46.0

Rarely appropriate 12 24.0 24.0 70.0

Inappropriate 15 30.0 30.0 100.0

Total 50 100.0 100.0

Table A10 On appropriateness for a physician to ask about a patient’s religiosity, 4 (8%) subjects marked always, 19 (38%) usually appropriate, 12 (24%) rarely and 15 subjects (30%) marked inapt. In your experience, how often have your patients used religion as a reason to avoid taking responsibility for their own health?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 10 20.0 20.0 20.0

Rarely 15 30.0 30.0 50.0

Sometimes 19 38.0 38.0 88.0

Often 6 12.0 12.0 100.0

Total 50 100.0 100.0

Table A9 On another stem about the used of religion by patients to avoid taking responsibility for their own health, 10 (20%) subjects commented never, 15 (19%) rarely, 19 (38%) sometimes and 6 (12%) subjects marked often.

CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

In general, do you think it is appropriate for a physician to inquire about a patient’s religiosity?

Frequency Percent Valid Percent Cumulative Percent

Valid Always appropriatie 4 8.0 8.0 8.0

Usaualy appropriate 19 38.0 38.0 46.0

Rarely appropriate 12 24.0 24.0 70.0

Inappropriate 15 30.0 30.0 100.0

Total 50 100.0 100.0

Table A10 On appropriateness for a physician to ask about a patient’s religiosity, 4 (8%) subjects marked always, 19 (38%) usually appropriate, 12 (24%) rarely and 15 subjects (30%) marked inapt.

Do you ever inquire about patients' religious issues?

Frequency Percent Valid Percent Cumulative Percent

Valid Yes 13 26.0 26.0 26.0

No 37 74.0 74.0 100.0

Total 50 100.0 100.0

Table A11

On inquiring about patients’ religiosity, 13 (26%) marked yes and 37 (74%) marked no.

How often do you inquire about patient's religiosity when a patient suffers?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 10 20.0 20.4 20.4

Rarely 14 28.0 28.6 49.0

The6 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.214 96 Sometimes 19 38.0 38.8 87.8

Often 6 12.0 12.2 100.0

Total 49 98.0 100.0

Missing System 1 2.0

Total 50 100.0

Table A12 The frequency of inquiry was marked never by 10 (20%), rarely by 14(28%), sometimes by 19 (38%) and often by 6 (12%). Do you ever inquire about patients' religious issues?

Frequency Percent Valid Percent Cumulative Percent

Valid Yes 13 26.0 26.0 26.0

No 37 74.0 74.0 100.0

Total 50 100.0 100.0

Table A11

On inquiring about patients’ religiosity, 13 (26%) marked yes and 37 (74%) marked no.

CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

How often do you inquire about patient's religiosity when a patient suffers?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 10 20.0 20.4 20.4

Rarely 14 28.0 28.6 49.0

Sometimes 19 38.0 38.8 87.8

Often 6 12.0 12.2 100.0

Total 49 98.0 100.0

Missing System 1 2.0

Total 50 100.0

Table A12 The frequency of inquiry was marked never by 10 (20%), rarely by 14(28%), sometimes by 19 (38%) and often by 6 (12%).

In general, is it appropriate for a physician to discuss religious issues when patient brings it up?

Frequency Percent Valid Percent Cumulative Percent

Valid Always appropriatie 3 6.0 6.0 6.0

Usaualy appropriate 26 52.0 52.0 58.0

Rarely appropriate 13 26.0 26.0 84.0

Inappropriate 8 16.0 16.0 100.0

Total 50 100.0 100.0

Table A13 Another stem on appropriateness of discussing religious matter in a case where patient brings it, 3 (6%) subjects marked always, 26 (52%) usually, rarely by 13 (26%) and inapt by 8 (16%).

The Permanente Journal • https://doi.org/10.7812/TPP/19.214 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.7 97

When, if ever, is it appropriate for a physician to initiate discussion with patients about their religious beliefs?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 8 16.0 16.0 16.0

Only when patient asks 25 50.0 50.0 66.0

Whenever the physician sense 15 30.0 30.0 96.0

Always 2 4.0 4.0 100.0

Total 50 100.0 100.0

Table A14

On initiating a discussion with patients about their religious beliefs; 8 (16%) marked never, 25 (50%) only when patients ask, 15 (30%) whenever physicians feel its need, always by 2 (4%). In general, is it appropriate for a physician to discuss religious issues when patient brings it up?

Frequency Percent Valid Percent Cumulative Percent

Valid Always appropriatie 3 6.0 6.0 6.0

Usaualy appropriate 26 52.0 52.0 58.0

Rarely appropriate 13 26.0 26.0 84.0

Inappropriate 8 16.0 16.0 100.0

Total 50 100.0 100.0

Table A13 Another stem on appropriateness of discussing religious matter in a case where patient brings it, 3 (6%) subjects marked always, 26 (52%) usually, rarely by 13 (26%) and inapt by 8 (16%).

CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

When, if ever, is it appropriate for a physician to initiate discussion with patients about their religious beliefs?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 8 16.0 16.0 16.0

Only when patient asks 25 50.0 50.0 66.0

Whenever the physician sense 15 30.0 30.0 96.0

Always 2 4.0 4.0 100.0

Total 50 100.0 100.0

Table A14

On initiating a discussion with patients about their religious beliefs; 8 (16%) marked never, 25 (50%) only when patients ask, 15 (30%) whenever physicians feel its need, always by 2 (4%).

When religious issues come up in discussions with patients, I encourage patients’ adherence to religious rituals?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 3 6.0 6.0 6.0

Rarely 3 6.0 6.0 12.0

Sometimes 12 24.0 24.0 36.0

Often 23 46.0 46.0 82.0

Always 9 18.0 18.0 100.0

Total 50 100.0 100.0

Table A15 On encouraging adherence to religious rituals like Prayers, Dua'a, Reading Quran, 3 subjects (6%) marked never, 3 (6%) rarely, 12 (24%) sometimes, 23 (46%) often and 9 (18%) marked always.

The8 Permanente Journal • For personal useI share only. No othermy uses own without when permission. religious Copyright ©issues 2020 The Permanentecome up Press. in All discussions rights reserved. with patientsThe Permanente Journal • https://doi.org/10.7812/TPP/19.214 98

Frequency Percent Valid Percent Cumulative Percent

Valid Never 21 42.0 42.0 42.0

Rarely 8 16.0 16.0 58.0

Sometimes 15 30.0 30.0 88.0

Often 5 10.0 10.0 98.0

Always 1 2.0 2.0 100.0

Total 50 100.0 100.0

Table A16

On sharing one’s own religious ideas and experiences with a patient, 21 subjects (42%) marked never, 8 (16%) rarely, 15 (30%) sometimes, 5 (10%) often and 1 (2%) marked always. When religious issues come up in discussions with patients, I encourage patients’ adherence to religious rituals?

Frequency Percent Valid Percent Cumulative Percent

Valid Never 3 6.0 6.0 6.0

Rarely 3 6.0 6.0 12.0

Sometimes 12 24.0 24.0 36.0

Often 23 46.0 46.0 82.0

Always 9 18.0 18.0 100.0

Total 50 100.0 100.0

Table A15 On encouraging adherence to religious rituals like Prayers, Dua'a, Reading Quran, 3 subjects (6%) marked never, 3 (6%) rarely, 12 (24%) sometimes, 23 (46%) often and 9 (18%) marked always. CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

I share my own when religious issues come up in discussions with patients

Frequency Percent Valid Percent Cumulative Percent

Valid Never 21 42.0 42.0 42.0

Rarely 8 16.0 16.0 58.0

Sometimes 15 30.0 30.0 88.0

Often 5 10.0 10.0 98.0

Always 1 2.0 2.0 100.0

Total 50 100.0 100.0

Table A16

On sharing one’s own religious ideas and experiences with a patient, 21 subjects (42%) marked never, 8 (16%) rarely, 15 (30%) sometimes, 5 (10%) often and 1 (2%) marked always.

When religious issues come up in discussions with patients, I try to change the subject

Frequency Percent Valid Percent Cumulative Percent

Valid Never 11 22.0 22.0 22.0

Rarely 12 24.0 24.0 46.0

Sometimes 17 34.0 34.0 80.0

Often 8 16.0 16.0 96.0

Always 2 4.0 4.0 100.0

Total 50 100.0 100.0

Table A17

On tactfully distracting patients from the religious discussion, 11 (22%) marked never, 12 (24%) rarely, 17 (34%) sometimes, 8 (16%) often and 2 (4%) marked always.

The Permanente Journal • https://doi.org/10.7812/TPP/19.214 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.9 99 CLINICAL PRACTICE Assessing Perception of Patients and Physicians Regarding Spirituality in Karachi, Pakistan: A Pilot Study

Table A18

Question Themes of responses

Spirituality definition “it’s about ones faith”

‘connection between God and man’

‘inner state of a person’ (variable responses)

Importance of faith in Yes (major No Don’t know Slightly illness response)

Importance of faith on Yes (major Negligible other matters of life response)

Presence of someone in Family member Spiritual Rituals No unspecified life to discuss spirituality (major response) leader one

Discussion with a doctor Yes No (major response) Sometimes on spirituality

Feeling of a patient if Feeling Feeling good Depth inside doctor discusses of (major response) spirituality relaxatio n

Preference of a patient Yes (major No Don’t know for spiritual discussion in response) clinic

Impact of spiritual Yes (major No Don’t know discussion on health response)

How spirituality can Strengthening faith impact one’s health Reminding God’s blessings

Developing understanding of illness

Relief

Doctor’s influence

The10 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.214 100 CLINICAL MEDICINE Endocrine Tumor Board: Ten Years’ Experience of a Multidisciplinary Clinical Working Conference Alison Savitz, MD1; Bryan Fong, MD2; Aaron Hochberg, MD3; Gregory Rumore, MD4; Cui Chen, MD4; Juanita Yun, MD5; Craig Sadur, MD6 Perm J 2020;24:19.140 E-pub: 06/17/2020 https://doi.org/10.7812/TPP/19.140

ABSTRACT guidelines. For that reason, separate specialty-specific tumor Introduction: Advances in specialized medical areas and up- boards developed.1,2 To our knowledge, there has not been a re- dated clinical guidelines show a need for a focused approach for port of a tumor board dedicated to all endocrine tumors. If such patients with specific disorders. a tumor board existed, it would be helpful to determine whether Objective: To describe a multidisciplinary tumor board for it reflected expected endocrine patients’ diversity and whether the patients with endocrine tumors. case discussions led to changes in evaluation and treatment plans. Methods: We established an endocrine tumor board at a large We present a 10-year experience of a multispecialty endocrine- health maintenance organization and studied cases presented specific tumor board serving a large patient population. between September 2007 and August 2017. To resolve diagnostic and/or therapeutic questions, a multidisciplinary team of specialists METHODS discussed patients’ clinical presentations. Cases were broken down The Kaiser Permanente Diablo Service Area (KPDSA) located into diagnostic categories, demographic characteristics (age, sex), in the San Francisco Bay Area provides health care to more than and need for repeated presentations to the board. 400,000 members. The affiliated facilities include 2 hospitals and Results: We included 608 patients: 401 female (66%) and 207 8 medical office buildings. Thyroid, parathyroid, adrenal, and male (34%). Ages ranged from teens to more than 90 years, with pancreatic surgeries were directed to few surgeons, ones who per- the peak decade 50 to 59 years (26%). Although most patients formed those procedures frequently and demonstrated expertise needed only 1 presentation to the board, 151 (25%) required in the fields. The KPDSA Endocrine Tumor Board (ETB) is a representation, for a total of 853 presentations. The diagnoses multispecialty board composed of endocrinologists, pathologists, reflected the workup status with tumor identification and localiza- radiologists, and nuclear medicine specialists in addition to sur- tion at the initial case presentation. Diagnoses included thyroid geons. When specific cases arose, neurosurgeons, gynecologists, cancer (234 patients, 38.4%), adrenal mass (165 patients, 27.1%), and urologists participated. primary hyperparathyroidism (120 patients, 19.7%), thyroid nodule The period studied was the 10-year span from August 2007 (95 patients, 15.6%), and extrathyroidal mass (23 patients, 3.8%). through September 2017. Before each scheduled meeting of Other diagnoses composed the remaining 14.6%. Tumor board the ETB, presenting physicians posted the cases onto a secure attendees overwhelmingly supported the meetings’ benefits, with electronic site, which was viewable by meeting attendees. The all clinicians reporting frequently changing patient management pattern of the conference was to select patients who presented because of the meetings. diagnostic and/or therapeutic questions for which clinical discus- Conclusion: Patients with endocrine tumors may benefit from sion could result in an agreement leading to a subsequent plan. a specialized approach to care. A multidisciplinary tumor board The clinical cases for some patients evolved and required repeated can focus discussions efficiently, provide a forum to advance care, presentations for further diagnostic and/or therapeutic questions apply endocrine-related clinical guidelines, and lead to recom- that arose. The radiologists, pathologists, and nuclear medicine mendations that clinicians often employed. physicians planning to discuss cases at the meeting reviewed the Keywords: endocrine tumor, tumor board, endocrine tumor data in advance. board, thyroid cancer, adrenal mass, primary hyperparathyroidism, Board members convened monthly at a central meeting loca- thyroid nodule, extra-thyroidal mass. tion, where there was large-screen visualization of the electronic INTRODUCTION General oncology tumor boards have been a mainstay of medi- cine for several years. The meetings typically call for a team of Author Affiliations 1 Department of General Surgery, Kaiser Permanente, Walnut Creek, CA specialists to provide diverse expertise in medical fields related 2 Department of Head and Neck Surgery, Kaiser Permanente, Walnut Creek, CA to the evaluation and treatment of patients with cancer. Review 3 Department of Radiology, Kaiser Permanente, Walnut Creek, CA of patient cases with discussion by the various experts can lead 4 Department of Pathology, Kaiser Permanente, Walnut Creek, CA to action plans to direct patient care and limit unnecessary tests 5 Department of Nuclear Medicine, Kaiser Permanente, Walnut Creek, CA and procedures.1-3 6 Department of Endocrinology, Kaiser Permanente, Pleasanton, CA (retired) However, one format does not fit the needs of all patients with Corresponding Author assorted medical issues. Specific physician talents are needed Alison Savitz, MD ([email protected]) with the ongoing medical research and updated field-specific Keywords: endocrine tumor board, tumor board, endocrine tumor, thyroid cancer, adrenal mass, primary hyperparathyroidism, thyroid nodule

The Permanente Journal • https://doi.org/10.7812/TPP/19.140 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 101 CLINICAL MEDICINE Endocrine Tumor Board: Ten Years’ Experience of a Multidisciplinary Clinical Working Conference

medical record (EMR) of each patient presented. The EMR distribution curve, which peaked in the sixth decade (23%) and afforded access to necessary clinical details, such as clinic ap- was skewed toward the older age ranges. The age brackets by pointment notes, medical problem lists, and available data from decade are shown in Figure 1. other medical centers as well as results of imaging, cytology, The diagnoses listed reflected how far along the workup was surgical pathology, and laboratory reports. Projections of medi- in terms of tumor identification and localization at the time of cal images provided the same details that were available to the the initial case presentation (Table 1). The most common diag- reading radiologists or nuclear medicine physicians. The attend- nosis was thyroid cancer, which affected 234 patients (38.4% ing pathologists provided electronic images of cytologic and of the total patient population). Included among them were surgical pathology specimens. Other doctors connected to the papillary, follicular, Hürthle cell, insular cell, medullary, anaplas- meeting via remote access with audio linkage and simultaneous tic, and metastatic carcinoma to the thyroid as well those who visualization of the same EMR elements viewed by attendees. had a history of thyroid carcinomas but for which the original Endocrinologists presented almost all the cases, with the patients’ pathologic diagnoses were unobtainable. The second most fre- surgeons almost always attending the meeting. Cases included quent diagnosis, which accounted for 165 patients (27.1%), was both initial presentations and follow-up reports, with a variable adrenal mass. Diagnoses that each made up to less than 3% of number of patients discussed during the 90-minute meeting. the total were pituitary mass, goiter (both neck and mediastinal), All members were encouraged to ask questions and voice their pancreatic mass, and pheochromocytoma/paraganglioma. A total assessments, leading to a consensus for further actions. Cultural of 51 patients (8.4%) cumulatively included the most sporadic diversity sensitivities4 were emphasized as part of the pertinent diagnoses that led to inclusion in the meeting agenda or were discussions to consider patient-centered concerns, with the goal adjunctive to the primary disorder. Those conditions included to provide high-quality medical care in the most optimal ways. adnexal masses, sphenoid mass, calcifying fibrous pseudotumor, Attendees filled out continuing medical education questionnaires gastric diverticulum mimicking an adrenal tumor, tertiary hyper- for educational credits. parathyroidism, normocalcemic hyperparathyroidism, carcinoid, A 10-question questionnaire was presented via email to the gastrinoma, Cushing syndrome, insulinoma, pancreatic mass, regularly participating ETB attendee clinicians to tabulate if and parathyroid carcinoma, and Rathke cleft cyst. how they found the ETB useful for the clinical needs of their The 10-question questionnaire was sent to clinicians with their patients with endocrine disorders. responses listed in Table 2. All 12 doctors polled completed the survey. Results showed that 11 (92%) came into the ETB meet- RESULTS ings to establish a treatment plan, and 12 (100%) came with goals A total of 608 cases were presented at least once. Of those 608 to establish a diagnostic plan as well as learn updates in fields patients, 151 (25%) were subsequently discussed at least 1 more related to the care of endocrine patients. Similarly, 100% of the time. Ninety-six (64%) of those 151 patients were discussed in respondents reported cultural diversity was addressed, no com- follow-up 1 time; 32 patients (21%), 2 more times; 15 patients mercial bias occurred, coordinating care with different specialties (10%), 3 more times; 4 patients (3%), 4 more times; 1 patient (< was facilitated, interacting with those different specialties was 1%), 5 more times; 2 patients (1%), 6 more times; and 1 patient (< educational, clinical practice guidelines were addressed when ap- 1%), 7 more times. Thus, there was a total of 245 times a patient propriate, continuing medical education hours were worthwhile, was reviewed in follow-up. Coupled with the initial presentations and the ETB overall was considered of value. The clinicians were of 608, there was a total of 853 times a case was discussed either asked what estimated percentage of cases they presented led to initially or in follow-up. changes in management. Six (50%) of the doctors responded that The distribution by sex was 401 female patients (66% of the the ETB led to management changes in 20% to 39% of their total) and 207 male patients (34%). Age distribution at the time presented cases; 2 (17%), 40% to 59% of cases; and 4 (33%), 60% of the initial case presentation followed somewhat of a normal to 79% of cases. Regarding whether the meeting outcomes led to improvement in patients’ quality of care, all respondents either Age Distribution strongly agreed or agreed (Table 2). DISCUSSION 180 158 160 138 Whereas a standard oncology tumor board works with patients 140 120 with known malignancies, an ETB could include patients with 96 100 89 benign, malignant, or at times coexisting benign and malignant 80 60 lesions. A tissue diagnosis was not needed for inclusion of a case in 60 the ETB’s meeting agenda because a clinical working conference 40 29 29 Number of Patients of Number 20 7 2 of endocrine patients can help greatly with diagnostic evaluations 0 that are in progress as well as treatment recommendations. Con- 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99 sensus opinions for diagnostic issues ranged from not pursuing Years any further testing to performing invasive procedures for more precise tumor characterization, including when to operate and Figure 1. Age distribution of patients (N = 608). how extensive a surgery should be performed. Treatment-centered

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.140 102 CLINICAL MEDICINE Endocrine Tumor Board: Ten Years’ Experience of a Multidisciplinary Clinical Working Conference

discussions included whether postoperative aggressive treatment with various endocrine disorders can benefit from tapping into the was indicated and specific postoperative steps. expertise of specialists in a tumor board setting, which often can The ETB illustrated different trends of patient populations lead to modifications of diagnostic and treatment plans. Because presented. Three-fourths of the patients required only 1 case of the complexities of evolution in the areas of endocrinology, conference discussion. Follow-up presentations often reflected endocrine surgery, neurosurgery, gynecology, urology, radiology, challenging aspects of the conditions and/or ongoing endocrine neuroradiology, nuclear medicine, and pathology, an endocrine- issues that lent themselves to reopening the case discussion. Of specific tumor board provides a forum for quick and practical v those cases discussed in follow-up presentations, 64% needed discussions in busy clinical settings. only 1 other time for seeking consensus opinions. The other 36% that lead to repeated follow-up presentations typically reflected Disclosure Statement The author(s) have no conflicts of interest to disclose. an increased complexity in those cases. Most patients whose cases were on the agenda were female, likely reflecting the female Acknowledgments predominance among patients with thyroid and hyperparathy- We sincerely thank Quincy McCrary, MA, MLIS, for assistance with roid disease. Another contributing factor could be that women manuscript preparation. are more likely than men to seek medical evaluation in a timely Kathleen Louden, ELS, of Louden Health Communications performed a manner.5 Although pediatric endocrinologists were not part of primary copy edit. the roster of physicians attending the ETB, 7 patients 19 years of age or younger were included in the case population. Most were References teenagers with thyroid cancers, patients not typically followed 1. Petty JK, Vetto JT. Beyond doughnuts: tumor board recommendations influence patient care. J Cancer Education: the official journal of the American Association for up by general pediatric endocrinologists. The peak decades for Cancer Education. 2002;17(2):97-100. patients discussed in conference were the ages of 40 through 59 2. O’Brien JC Jr. History of tumor site conferences at Baylor University Medical Center. years, likely reflecting times of increased thyroid and parathyroid Proc (Bayl Univ Med Cent). 2006 Apr;19(2):130-1. DOI: https://doi.org10.1080/08998 280.2006.11928145. disease detection. 3. Lamb BW, Sevdalis N, Arora S, Pinto A, Vincent C, Green JS. Teamwork and team A mainstay of clinical medicine in general and tumor boards decision-making at multidisciplinary cancer conferences: Barriers, facilitators, and more specifically is to apply updated evidence-based develop- opportunities for improvement. World Journal of Surgery. 2011;35(9):1970-1976. 4. Lipson JG, Dibble SL. Culture & clinical care. 2nd ed. San Francisco, CA: University ments for patient care. In 2017, new changes in classification of of California at San Francisco Nursing Press; 2005. 6 thyroid cytopathology were published. Guidelines published 5. Summary health statistics: National Health Interview Survey, 2018 [Internet]. from leading medical organizations provide frameworks for Hyattsville, MD: National Center for Healtlh Statistics; 2018:table A-18a [cited 2020 Feb 20]. Available from: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/ evaluation and treatment of various medical conditions. During SHS/2018_SHS_Table_A-18.pdf the 2007 through 2017 years of this study, updated guidelines 6. Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. on thyroid nodules and differentiated thyroid cancer emanated Thyroid : official journal of the American Thyroid Association. 2017;27(11):1341-1346. 7 7. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association from the American Thyroid Association. Also, during that period Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated the Endocrine Society announced new guidelines on Cushing Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid syndrome treatment,8 pheochromocytoma and paraganglioma,9 Nodules and Differentiated Thyroid Cancer. Thyroid : official journal of the American 10 11 Thyroid Association. 2016;26(1):1-133. acromegaly, and pituitary incidentaloma. In 2014, the Fourth 8. Nieman LK, Biller BM, Findling JW, et al. Treatment of Cushing’s syndrome: An International Workshop updated the recommendations on as- Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and ymptomatic primary hyperparathyroidism.12 Experts published an Metabolism. 2015;100(8):2807-2831. 13 9. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: update for primary aldosteronism in 2016. The ETB reviewed An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. the new recommendations in management as they were released 2014;99(6):1915-1942. by the governing bodies and quickly adapted these changes, using 10. Katznelson L, Laws ER, Jr., Melmed S, et al. Acromegaly: An Endocrine Society them to guide patient discussions and care plans. clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. 11. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: An Endocrine Polling the clinicians who brought their patients’ clinical cases Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(4):894-904. to the ETB showed overwhelmingly positive results. When en- 12. Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of tering the ETB, nearly all surveyed clinicians sought to establish asymptomatic primary hyperparathyroidism: Summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561-3569. diagnostic and treatment plans. After completing the meetings, 13. Funder JW, Carey RM, Mantero F, et al. The management of primary aldosteronism: each of the doctors reported subsequent changes in patient man- case detection, diagnosis, and treatment: An Endocrine Society clinical practice agement for a substantial percentage of the cases they presented. guideline. J Clin Endocrinol Metab. 2016;101(5):1889-1916. 14. Baum HBA. Clinical excellence in endocrinology. J Clin Endocrinol Metab. The meetings facilitated coordination of care with different spe- 2018;103(7):2430-2435. cialties in a simultaneously educational setting, making the time spent considered of value, particularly with a unanimous sense of improved patient quality of care. CONCLUSION As medical research advances in the various specialty fields, rec- ommendations require updating. Multidisciplinary teamwork can help promote clinical excellence.14 Clinicians caring for patients

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Table 1. Diagnosis distribution of patients at initial case Table 2. Clinician survey responses regarding presentation (N = 608) tumor board meetings Diagnosis Number (%) of patients Number (%) of Survey question Thyroid cancer 234 (38.4) respondents Adrenal mass 165 (27.1) Coming into the meeting, have your possible goals included Primary hyperparathyroidism 120 (19.7) the options below? (You can select ≥ 1 answer) Thyroid nodule 95 (15.6) Establishing a diagnostic plan 12 (100) Extrathyroidal mass 23 (3.8) Establishing a treatment plan 11 (92) Pituitary mass 16 (2.6) Learn updates in fields related to the care of endocrine 12 (100) Goiter 14 (2.3) patients Pancreatic mass 5 (0.8) In the meetings, was cultural diversity addressed? Pheochromocytoma/paraganglioma 3 (0.5) Yes 12 (100) Other endocrine tumorsa 51 (8.4) No 0 (0) a 608 patients had 726 diagnoses because some patients had more than one Was there commercial bias in the meetings? endocrine diagnosis; See the Results section for a breakdown of types. Yes 0 (0) No 12 (100) Were the meetings helpful in coordinating care with the different specialties? Yes 12 (100) No 0 (0) Were clinical practice guidelines discussed when appropriate? Yes 12 (100) No 0 (0) Was interacting with the different specialties in the meeting educational? Yes 12 (100) No 0 (0) Were the meetings worthy of continuing medical education hours? Yes 12 (100) No 0 (0) What estimated percentage of cases that you presented led to changes in management? < 20 0 (0) 20-39 6 (50) 40-59 2 (17) 60-79 4 (33) > 80 0 (0) As a result of the meeting, the quality of care improved for my patients. Strongly agree 11 (92) Agree 1 (8) Neither agree nor disagree 0 (0) Disagree 0 (0) Strongly disagree 0 (0) Did you see value in the meetings? Yes 12 (100) No 0 (0)

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.140 104 CLINICAL MEDICINE Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food

David R Vinson, MD1 Perm J 2020;24:19.238 E-pub: 05/20/2020 https://doi.org/10.7812/TPP/19.238

ABSTRACT reached its intended medical audience. But it did reach inquisitive In this essay I tell the story of insightful patients from around patients. Sixteen from around the world have written so far to ex- the world with cold-drink atrial arrhythmias, particularly atrial press their gratitude. One patient even sent me an email during his fibrillation (AF). This common condition has received little research Emergency Department (ED) visit: “This morning I had another attention and remains unknown to many physicians. The under- episode [of paroxysmal AF], also while drinking a cold smoothie, representation of “cold drink heart” in the literature led me and a and voila, here I am at the emergency room.” colleague a few years ago to publish a case report on this topic in an open-access journal. I included my email address so that EAGER TO UNDERSTAND WHAT CAUSED THEIR SYMPTOMS physicians and researchers could contact me. Although I sought These patients had strongly suspected a direct relationship be- a physician audience, the report struck a chord with patients. Six- tween their frozen drinks and desserts and their sudden-onset AF, teen individuals have since written me to express their gratitude especially when symptoms predictably recurred with subsequent for having received medical validation of the causal connection provocations by icy-cold ingestions. The patients were looking for they had made between swallowing cold drink or food and their professional confirmation: “Did a cold drink really land me in the episodes of paroxysmal AF. The validation was all the more impor- [ED]?” one asked. This inquiry drove them to search the Internet, tant because of their physicians’ prevalent disregard of the link, which directed them to our online case report.1 They were com- making them miss out on the opportunity to partner with their forted and reassured to learn that they were not the only person patients in AF management by trigger avoidance. I explain here with this seemingly unusual condition. how these patients have handled their cold-drink AF and con- The case report may have had better patient uptake than most nect their reports with the few published in the literature. These research articles because it opened with a story. Narratives are rich email exchanges illustrate how eager patients can be for an far more palatable to a wider audience than the drier details of explanation of their medical condition and for an opportunity to research methods and results. But this case report would never manage their symptoms. These communications also remind us have found its way into the hands of so many patients if it had about the important role patients play in physician education. not been published in an open-access journal, like this one. Most These email-writing patients have done us all a great service by patients do not have access to a hospital or university library that teaching about the precipitants, prevention, and underrecognition shares its paid subscriptions with its members. Reaching patients of cold-drink atrial arrhythmias. far and wide with our research findings is another reason to sup- port high-quality open-access publishing.2 INTRODUCTION One of the advantages of supplementing a medical career with THE CASE REPORT PATIENTS FOUND ONLINE clinical research is the quiet satisfaction of knowing that our work In the case report,1 Lugovskaya and I told the story of a young improves the care and lives of patients far beyond the limited scope healthy man, who was walking home after a long, hot day of of our own practices. But we never expect to hear from such pa- hard outdoor labor. He stopped at the local convenience store tients. This explains my surprise when the emails first arrived. Why to purchase an ice-cold slushy drink. As he rapidly gulped down would patients write to a physician researcher they had never met? the chilly beverage, he developed a sudden brain-freeze headache It had nothing to do with any of my hard-won research studies. and a concurrent episode of acute AF. The co-occurrence of “ice Our large pragmatic controlled trials and multicenter prospective cream headache” with “cold drink heart” directly implicated the observational studies never generated even 1 patient letter or email. rapid cold ingestion as the trigger for both conditions. When the What precipitated the response of emails was a simple case report in 2016, which my colleague, Lugovskaya, and I1 did not write for patients. We sought to educate physicians about the causal con- Author Affiliations nection between the rapid ingestion of ice-cold drinks or ice cream 1 Department of Emergency Medicine, Kaiser Permanente (KP) Sacramento Medical Center, Sacramento, and acute paroxysmal atrial fibrillation (AF). I had included my CA; The Permanente Medical Group, the CREST Network, and the KP Division of Research, Oakland, CA email address so that other physicians and researchers could easily contact me. None have, and so I do not know if the case report ever Corresponding Author David R Vinson, MD ([email protected])

Keywords: Atrial fibrillation, cold drink, continuing medical education, etiology, patient education, open- access publishing

The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 105 CLINICAL MEDICINE CLINICAL MEDICINE Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food

uncomfortable palpations failed to spontaneously resolve (unlike my many [ED] visits for AF, I don’t want to do anything that physicians warned him about the potential harms of drinking The cold-drink connection has helped some patients, in fact, the headache), he sought emergency medical attention, as many could possibly aggravate it.” For many, the resolve is firm, even caffeinated beverages but gave no advice about cold foods and reproduce their symptoms during medical evaluation. “My cardi- of my email correspondents have done. Under medical care, he in face of dietary sacrifices: “But if doing something as simple as beverages. Study findings suggest, however, that moderate levels ologist … asked if I could re-create the issue. I was certain I could, received an atrial arrhythmia diagnosis—paroxysmal AF (Figure avoiding cold stuff can keep me AF-free, then I’m all for trying of tea and coffee are safe for people with AF.5 A third patient even on the Tikosyn [dofetilide]. I grabbed an ice-cold drink and 1)—and restoration to a normal rhythm with the administration it, even if it means missing out on the ice cream.” articulated his impression that the relationship between AF and gulped it down. I instantly went into AF.” Another joked that of intravenous pharmacotherapy (ibutilide).3 Interestingly, he By not recognizing the triggering capacity of ingesting cold cold drinks may seem crazy, which helped him account for the a cold drink would have been a better “drug” for inducibility: “I landed in the ED for an identical episode 3 summers later, after stimuli, many physicians are missing the chance to collaborate incredulity of his physician. “In 4 of those 5 instances [of paroxys- underwent an ablation in January, and the surgeon was unable to having stopped at the same convenience store and having bought with their patients in symptom management.1 This deficit of mal AF] I had eaten ice pop, ice cream, or [a] slushy within about trigger AF with adrenaline. I think he needs to have me drink a the same slushy drink— after a long break from ice-cold drinks care, however, is open to correction. Studies are under way for 5 minutes of the episodes. I even mentioned this to the doctor slushy before putting me under.” and paroxysmal AF. patients with paroxysmal AF to help them identify their triggers after my third episode, and they dismissed it (probably because and reduce their exposure risk (eg, Clinicaltrials.gov identifier I sounded like a crazy person).” Another patient admitted that OFFERS TO HELP SIMPLE, TRANSFORMATIVE LIFESTYLE CHANGES NCT03323099). Research like this could help educate patients he didn’t mention the antecedent cold drink to his physician at The kindness and generosity of these email senders is moving. As described in the case report, the protagonist’s treating and their physicians about the importance of recognizing and the time because he “did not think it important.” I imagine that They were eager to reciprocate the help they received and offered physicians failed to attribute the genesis of AF to the icy bever- reducing AF triggers. Physician education of this sort is needed, patients often fail to mention the precipitating cold drink because me their stories in hopes these might advance my AF research. age.1 Overlooking the nexus, they failed to advise him to avoid as we learn from our informative patients. William Osler’s maxim they underestimate its importance, and when they do happen to “Just letting you know the patient in your case study is not the repeated exposure. The patient, however, had connected the dots is as fitting today as it was more than 100 years ago: “Listen to mention it, physicians often fail to appreciate the importance. only one.” Their magnanimity is expressed concisely here: “Please and afterward avoided rapid ingestion of frozen drinks, except your patient; he is telling you the diagnosis.” Given that patients and physicians both underrecognize the con- contact me if I can further your research.…” Another writer on the 1 fateful repeated occurrence 3 years later. In the report dition means that it is likely to be substantially underdocumented set the case report in the larger context of general AF research: my coauthor and I made it clear that a simple lifestyle change EAGER FOR VALIDATION in the health records.1 This explains why a retrospective study, “Thanks for your contribution to the field, and if you’d like any can have big implications: reduce exposure to ice-cold drinks and One emailing patient voiced the frustration common to many conditioned as it would be on the happenstance of discussion and further information, please let me know.” One patient sent me food and lessen the risk of arrhythmia recurrence. in the group when the health care team did not “get it”: “I men- documentation, would greatly underestimate the prevalence of a thoughtful follow-up on his case 2 years after our initial email My correspondents appreciated this point and wrote to tell tioned to the nurses, ED doctors, residents, and cardiologist that what I colloquially call cold drink heart. exchange: “I wanted to provide a brief update; perhaps it might me of their success with lifestyle changes, akin to many loose, this condition [the cold-drink AF] began seconds after experienc- It was the 2016 case report1 that gave these patients the valida- be useful.” Another correspondent offered to help me spread self-run single-subject trials.4 One email writer speaks for the ing a massive brain freeze, but no one mentioned a correlation tion they sought and needed. One email sender put it like this: the message, realizing that the topic needs broader dissemina- group: “I am very careful to drink cold drinks very slowly and there.” Another patient writes, “No one seemed to care about the “My attending cardiologist was unsure of the cause, but having tion among both patients and physicians: “Contact me if I can have not had a symptomatic episode in the past 3 years.” Others cold-drink link despite my indications this is the obvious only found your paper on PubMed, I’m now confident it was indeed be of assistance with your research and in getting the word out.” have gone further in their prevention efforts: “I have fully given trigger. [They were] more curious about whether I smoke or drink the drink.” For many medical conditions, we in the medical com- up on eating anything cold at all. It may seem extreme, but after alcohol or caffeine.” I saw this with our case report. The patient’s munity have no rational causal explanation and, lacking scientific EXPANDING WHAT THE LITERATURE TELLS US evidence, may implicate bad genes or bad luck. But when an My colleagues and I also sought to get the word out. It was this explanation is ready at hand, we should put it to good use. Life desire to educate physicians about cold-drink AF that initially can be chaotic for many of our patients, and much of it is unpre- drove us to publish our case report.1 We thought this important dictable, eluding explanation. But explanations can be invaluable. because so little had been published on the topic—mostly a few “When your life changes in a heartbeat (no pun intended),” one case reports, in fact. The first of these was reported in the literature email sender wrote, “It’s good to know why.” We should not miss in 1994.6 A healthy 43-year-old woman had experienced AF with this opportunity to explain the cause of our patient’s paroxysmal rapid ventricular response while eating frozen yogurt. The rela- AF when cold ingestion is the readily identifiable precipitant. tionship between her yogurt dessert and the tachydysrhythmia, however, may have been just coincidental and not causal, since this PATIENTS EDUCATING THEIR PHYSICIANS was a one-time experience and not replicated with similar cold- Many patients were eager to share what they had learned from food ingestions before she underwent treatment with ablation. our case report with their outpatient physicians. They printed Cold-drink ingestion is more likely the culprit when its precipi- the publication and hand delivered it in clinic. One patient even tation of AF is replicated with subsequent exposures. This was the wanted additional references to strengthen his case: “My claim nature of the symptoms in our own case report1 and in many of that the frozen smoothie triggered this [paroxysmal AF] has been the email-writing patients. In some patients with this condition, dismissed by relevant doctors…, but I know this was the proxi- episodes of paroxysmal AF develop independent of swallowing mate cause. Can you point me to any additional info[rmation] I cold beverages, whereas in other patients they develop only with might share with them to bolster my case and open their eyes?” ingestion of a cold drink or ice cream. One woman made it clear Physician education comes in all forms. Add this to the long list that her AF was brought about exclusively by cold drinks: “[H] of things we can learn from our patients. istorically every episode of AF has only been brought on by drink- Not all physicians were dismissive that swallowing a cold drink ing cold.” One of the earliest published reports to demonstrate was the cause of their patient’s paroxysmal AF. One cardiologist the exclusive reproducible nature of the condition was published now lightheartedly refers to this patient as “the drinker,” after in 1999.7 A 55-year-old man related a long history of paroxysmal the patient’s comical self-designation. The patient explains: “The AF. Each episode occurred when he “drank an ice-cold beverage name ‘drinker’ stuck when they asked how things were and I told quickly.” He was able to demonstrate the causal relation during them I was still having issues with drinking. The PA [physician electrocardiographic monitoring by drinking an ice-cold soft assistant] was all upset because she instantly thought I was refer- drink, which “immediately precipitated” AF. A similar pattern Figure 1. 12-lead electrocardiogram obtained from a young adult man who presented to the emergency department with recent-onset cold-drink atrial fibrillation with rapid ventricular response triggered by rapid ingestion of an ice-cold slushy drink1 ring to getting drunk. Anyway, it was good for a laugh.” of infrequent, but predictably recurrent, paroxysmal AF was

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.238 106 The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 CLINICAL MEDICINE CLINICAL MEDICINE Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food

uncomfortable palpations failed to spontaneously resolve (unlike my many [ED] visits for AF, I don’t want to do anything that physicians warned him about the potential harms of drinking The cold-drink connection has helped some patients, in fact, the headache), he sought emergency medical attention, as many could possibly aggravate it.” For many, the resolve is firm, even caffeinated beverages but gave no advice about cold foods and reproduce their symptoms during medical evaluation. “My cardi- of my email correspondents have done. Under medical care, he in face of dietary sacrifices: “But if doing something as simple as beverages. Study findings suggest, however, that moderate levels ologist … asked if I could re-create the issue. I was certain I could, received an atrial arrhythmia diagnosis—paroxysmal AF (Figure avoiding cold stuff can keep me AF-free, then I’m all for trying of tea and coffee are safe for people with AF.5 A third patient even on the Tikosyn [dofetilide]. I grabbed an ice-cold drink and 1)—and restoration to a normal rhythm with the administration it, even if it means missing out on the ice cream.” articulated his impression that the relationship between AF and gulped it down. I instantly went into AF.” Another joked that of intravenous pharmacotherapy (ibutilide).3 Interestingly, he By not recognizing the triggering capacity of ingesting cold cold drinks may seem crazy, which helped him account for the a cold drink would have been a better “drug” for inducibility: “I landed in the ED for an identical episode 3 summers later, after stimuli, many physicians are missing the chance to collaborate incredulity of his physician. “In 4 of those 5 instances [of paroxys- underwent an ablation in January, and the surgeon was unable to having stopped at the same convenience store and having bought with their patients in symptom management.1 This deficit of mal AF] I had eaten ice pop, ice cream, or [a] slushy within about trigger AF with adrenaline. I think he needs to have me drink a the same slushy drink— after a long break from ice-cold drinks care, however, is open to correction. Studies are under way for 5 minutes of the episodes. I even mentioned this to the doctor slushy before putting me under.” and paroxysmal AF. patients with paroxysmal AF to help them identify their triggers after my third episode, and they dismissed it (probably because and reduce their exposure risk (eg, Clinicaltrials.gov identifier I sounded like a crazy person).” Another patient admitted that OFFERS TO HELP SIMPLE, TRANSFORMATIVE LIFESTYLE CHANGES NCT03323099). Research like this could help educate patients he didn’t mention the antecedent cold drink to his physician at The kindness and generosity of these email senders is moving. As described in the case report, the protagonist’s treating and their physicians about the importance of recognizing and the time because he “did not think it important.” I imagine that They were eager to reciprocate the help they received and offered physicians failed to attribute the genesis of AF to the icy bever- reducing AF triggers. Physician education of this sort is needed, patients often fail to mention the precipitating cold drink because me their stories in hopes these might advance my AF research. age.1 Overlooking the nexus, they failed to advise him to avoid as we learn from our informative patients. William Osler’s maxim they underestimate its importance, and when they do happen to “Just letting you know the patient in your case study is not the repeated exposure. The patient, however, had connected the dots is as fitting today as it was more than 100 years ago: “Listen to mention it, physicians often fail to appreciate the importance. only one.” Their magnanimity is expressed concisely here: “Please and afterward avoided rapid ingestion of frozen drinks, except your patient; he is telling you the diagnosis.” Given that patients and physicians both underrecognize the con- contact me if I can further your research.…” Another writer on the 1 fateful repeated occurrence 3 years later. In the report dition means that it is likely to be substantially underdocumented set the case report in the larger context of general AF research: my coauthor and I made it clear that a simple lifestyle change EAGER FOR VALIDATION in the health records.1 This explains why a retrospective study, “Thanks for your contribution to the field, and if you’d like any can have big implications: reduce exposure to ice-cold drinks and One emailing patient voiced the frustration common to many conditioned as it would be on the happenstance of discussion and further information, please let me know.” One patient sent me food and lessen the risk of arrhythmia recurrence. in the group when the health care team did not “get it”: “I men- documentation, would greatly underestimate the prevalence of a thoughtful follow-up on his case 2 years after our initial email My correspondents appreciated this point and wrote to tell tioned to the nurses, ED doctors, residents, and cardiologist that what I colloquially call cold drink heart. exchange: “I wanted to provide a brief update; perhaps it might me of their success with lifestyle changes, akin to many loose, this condition [the cold-drink AF] began seconds after experienc- It was the 2016 case report1 that gave these patients the valida- be useful.” Another correspondent offered to help me spread self-run single-subject trials.4 One email writer speaks for the ing a massive brain freeze, but no one mentioned a correlation tion they sought and needed. One email sender put it like this: the message, realizing that the topic needs broader dissemina- group: “I am very careful to drink cold drinks very slowly and there.” Another patient writes, “No one seemed to care about the “My attending cardiologist was unsure of the cause, but having tion among both patients and physicians: “Contact me if I can have not had a symptomatic episode in the past 3 years.” Others cold-drink link despite my indications this is the obvious only found your paper on PubMed, I’m now confident it was indeed be of assistance with your research and in getting the word out.” have gone further in their prevention efforts: “I have fully given trigger. [They were] more curious about whether I smoke or drink the drink.” For many medical conditions, we in the medical com- up on eating anything cold at all. It may seem extreme, but after alcohol or caffeine.” I saw this with our case report. The patient’s munity have no rational causal explanation and, lacking scientific EXPANDING WHAT THE LITERATURE TELLS US evidence, may implicate bad genes or bad luck. But when an My colleagues and I also sought to get the word out. It was this explanation is ready at hand, we should put it to good use. Life desire to educate physicians about cold-drink AF that initially can be chaotic for many of our patients, and much of it is unpre- drove us to publish our case report.1 We thought this important dictable, eluding explanation. But explanations can be invaluable. because so little had been published on the topic—mostly a few “When your life changes in a heartbeat (no pun intended),” one case reports, in fact. The first of these was reported in the literature email sender wrote, “It’s good to know why.” We should not miss in 1994.6 A healthy 43-year-old woman had experienced AF with this opportunity to explain the cause of our patient’s paroxysmal rapid ventricular response while eating frozen yogurt. The rela- AF when cold ingestion is the readily identifiable precipitant. tionship between her yogurt dessert and the tachydysrhythmia, however, may have been just coincidental and not causal, since this PATIENTS EDUCATING THEIR PHYSICIANS was a one-time experience and not replicated with similar cold- Many patients were eager to share what they had learned from food ingestions before she underwent treatment with ablation. our case report with their outpatient physicians. They printed Cold-drink ingestion is more likely the culprit when its precipi- the publication and hand delivered it in clinic. One patient even tation of AF is replicated with subsequent exposures. This was the wanted additional references to strengthen his case: “My claim nature of the symptoms in our own case report1 and in many of that the frozen smoothie triggered this [paroxysmal AF] has been the email-writing patients. In some patients with this condition, dismissed by relevant doctors…, but I know this was the proxi- episodes of paroxysmal AF develop independent of swallowing mate cause. Can you point me to any additional info[rmation] I cold beverages, whereas in other patients they develop only with might share with them to bolster my case and open their eyes?” ingestion of a cold drink or ice cream. One woman made it clear Physician education comes in all forms. Add this to the long list that her AF was brought about exclusively by cold drinks: “[H] of things we can learn from our patients. istorically every episode of AF has only been brought on by drink- Not all physicians were dismissive that swallowing a cold drink ing cold.” One of the earliest published reports to demonstrate was the cause of their patient’s paroxysmal AF. One cardiologist the exclusive reproducible nature of the condition was published now lightheartedly refers to this patient as “the drinker,” after in 1999.7 A 55-year-old man related a long history of paroxysmal the patient’s comical self-designation. The patient explains: “The AF. Each episode occurred when he “drank an ice-cold beverage name ‘drinker’ stuck when they asked how things were and I told quickly.” He was able to demonstrate the causal relation during them I was still having issues with drinking. The PA [physician electrocardiographic monitoring by drinking an ice-cold soft assistant] was all upset because she instantly thought I was refer- drink, which “immediately precipitated” AF. A similar pattern Figure 1. 12-lead electrocardiogram obtained from a young adult man who presented to the emergency department with recent-onset cold-drink atrial fibrillation with rapid ventricular response triggered by rapid ingestion of an ice-cold slushy drink1 ring to getting drunk. Anyway, it was good for a laugh.” of infrequent, but predictably recurrent, paroxysmal AF was

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 107 CLINICAL MEDICINE CLINICAL MEDICINE Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food

Disclosure Statement 10. Al-Farsi Y, Tariq O, Siddiqui A, Sharef YW. Atrial fibrillation with a rare cause of described in 2000 in a young man without cardiac disease with were healthy and free of other cardiopulmonary diagnoses. These initiation. Case report. Med J Babylon. 2014;11(2):482-6. 8 The author(s) have no conflicts of interest to disclose. the swallowing of cold shakes and sundaes. patients also tell me how broad-ranging the cold stimuli can be, 11. Groh CA, Faulkner M, Getabecha S, et al. Patient-reported triggers of paroxysmal A published report from 2001 tells a similar story. A healthy including chilled water, ice-cold sodas, flavored ice-slushies (as atrial fibrillation. Heart Rhythm. 2019 Jul;16(7):996-1002. https://doi.org/10.1016/j. Acknowledgments hrthm.2019.01.027 42-year-old man had been experiencing transient palpitations in our initial case report1), frozen yogurt, and ice cream—what- 9 This work was supported by The Permanente Medical Group’s Delivery 12. Rosso R, Sparks PB, Morton JB, et al. Vagal paroxysmal atrial fibrillation: “after drinking cold beverages.” The dysrhythmia spells were ever the flavor. These were all nonalcoholic triggers, so physicians Science and Physician Researcher Programs, Oakland, California. prevalence and ablation outcome in patients without structural heart disease. J documented on several occasions to be AF. He figured out the can avoid confusing cold drink heart with holiday heart, which I am grateful to Nelya Lugovskaya Nemcek, BA, University of California Davis Cardiovasc Electrophysiol. 2010 May;21(5):489-493. https://doi.org/10.1111/j.1540- 8167.2009.01658.x 19,20 School of Medicine, Sacramento, California, for leading our efforts on the initial same prevention solution that my corresponding patients dis- is caused by excess alcohol ingestion. 13. Carpenter A, Frontera A, Bond R, Duncan E, Thomas G. Vagal atrial fibrillation: covered. The authors write: “Recently, his episodes of palpitation case report of this condition. I’m also indebted to Art Klatsky, MD, senior editor What is it and should we treat it? Int J Cardiol. 2015 Dec 15;201:415-421. https://doi. have been rare because he assiduously avoids swallowing anything NAMING THIS CONDITION at The Permanente Journal, and his bright team of reviewers, whose many org/10.1016/j.ijcard.2015.08.108 helpful suggestions greatly improved this essay. 14. Mandyam MC, Vedantham V, Scheinman MM, et al. Alcohol and vagal tone as cold.” A 2014 report followed a parallel pattern: ice-cold drinks Cold-drink AF lacks a conventional diagnostic name. It goes Kathleen Louden, ELS, of Louden Health Communications performed a triggers for paroxysmal atrial fibrillation. Am J Cardiol. 2012 Aug 1;110(3):364-368. induced AF again and again until “deliberate avoidance” led to a by several names in the case report literature, none of which is primary copy edit. https://doi.org/10.1016/j.amjcard.2012.03.033 long symptom-free interval.10 commonly used: cold-induced, swallow-related AF18; cold water 15. Efremidis M, Letsas KP, Lioni L, et al. The impact of vagotonic, adrenergic, and 21 random type of paroxysmal atrial fibrillation on left atrial ablation outcomes. Int J Unique to the 2001 case report is a family tendency to cold- swallowing-induced paroxysmal AF ; cold-induced AF; or cold- References 1 Cardiol. 2013 Oct 9;168(4):4015-4018. https://doi.org/10.1016/j.ijcard.2013.06.075 drink AF, which none of my email-writing patients had men- swallow-induced AF. Several case reports do not even name the 1. Lugovskaya N, Vinson DR. Paroxysmal atrial fibrillation and brain freeze: A case of 16. Lee SH, Park SJ, Byeon K, et al. Risk factors between patients with lone and tioned.9 The 79-year-old father of the 42-year-old man described condition itself but provide only the broader diagnostic category recurrent co-incident precipitation from a frozen beverage. Am J Case Rep 2016 Jan non-lone atrial fibrillation. J Korean Med Sci. 2013 Aug;28(8):1174-1180. https://doi. 8 13;17:23-6. DOI: https://doi.org/10.12659/ajcr.896035 org/10.3346/jkms.2013.28.8.1174 in the report was found to have his son’s condition after ingesting in which it sits, such as vagally mediated AF or swallowing- 2. Finch J, Bell S, Bellingan L, et al. Accessibility, sustainability, excellence: how to 22 17. Hansson A, Madsen-Hardig B, Olsson SB. Arrhythmia-provoking factors and a shaved-ice drink. No family members besides these 2 had this induced tachyarrhythmia. I prefer to describe this condition expand access to research publications. Executive summary. Int Microbiol. 2013 symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews particular condition (or AF in general).9 Cold-drink and ice as cold-drink AF. Like the term cough syncope, cold-drink AF Jun;16(2):125-132. https://doi.org/10.2436/20.1501.01.187 with 100 patients seeking hospital assistance. BMC Cardiovasc Disord. 2004 Aug 3. Vinson DR, Lugovskaya N, Warton EM, et al. Ibutilide Effectiveness and Safety 3;4:13. https://doi.org/10.1186/1471-2261-4-13 cream triggers of AF are thought to be vagally mediated (like communicates succinctly and explicitly both the most common in the Cardioversion of Atrial Fibrillation and Flutter in the Community Emergency 11,12 18. Robinson JA, Synder CS. Cold-Induced, Swallow-Related Atrial Fibrillation in sleep, post-prandial, and late post-exercise states). Some stud- trigger and the effect. The modifier “induced” is implied; for- in Department. Ann Emerg Med. 2018 Jan;71(1):96-108.e102. https://doi.org/10.1016/j. an Adolescent. J Innov Card Rhythm Manag. 2016;7(6):2391-2393. https://doi. ies have found that patients with vagally mediated triggers of AF stance, cough syncope means cough-induced syncope. In cold- annemergmed.2017.07.481 org/10.19102/icrm.2016.070604 4. Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: 19. Ettinger PO, Wu CF, De La Cruz C, Jr., Weisse AB, Ahmed SS, Regan TJ. are more likely to have a family history of AF than those with drink AF, a cold drink is understood to include non-beverages the ultimate strategy for individualizing medicine? Per Med. 2011 Mar;8(2):161-173. 13,14 Arrhythmias and the “Holiday Heart”: alcohol-associated cardiac rhythm disorders. adrenergic or random triggers, although a family tendency like ice cream and frozen yogurt. From what we know from the https://doi.org/10.2217/pme.11.7 Am Heart J. 1978 May;95(5):555-562. https://doi.org/10.1016/0002-8703(78)90296-x to cold-drink AF, in particular, has not been explored, except as literature today, AF is the prevalent atrial arrhythmia triggered by 5. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and Arrhythmias: Time to Grind the 20. Tonelo D, Providencia R, Goncalves L. Holiday heart syndrome revisited after 9 Data. JACC Clin Electrophysiol. 2018 Apr;4(4):425-432. https://doi.org/10.1016/j. 34 years. Arq Bras Cardiol. 2013 Aug;101(2):183-189. https://doi.org/10.5935/ described in the 2001 case report. swallowing cold drink and food, but other atrial arrythmias could jacep.2018.01.012 19,20 abc.20130153 These several case reports offer helpful patient-specific detail well be possible, as seen in holiday heart. “Cold-stimulus AF” 6. Brodsky MA, Orlov MV, Allen BJ, Selvan A. Frozen yogurt near deep-freeze. Am J 21. Yang PS, Park JG, Pak HN. Catheter ablation for cold water swallowing-induced on cold drink heart but are unable to provide an estimate of is a serviceable name, but the stimulus is not specific and could Cardiol. 1994 Mar 15;73(8):617-618. https://doi.org/10.1016/0002-9149(94)90349-2 paroxysmal atrial fibrillation: a case report. Heart Rhythm. 2014 Dec;11(12):2300- prevalence of this condition. Fortunately, researchers from the be misconstrued as exposure to cold weather or the application 7. Wilmshurst PT. Tachyarrhythmias triggered by swallowing and belching. Heart. 1999 2302. https://doi.org/10.1016/j.hrthm.2014.08.020 Mar;81(3):313-315. https://doi.org/10.1136/hrt.81.3.313 22. Tada H, Kaseno K, Kubota S, et al. Swallowing-induced atrial tachyarrhythmias: University of California, San Francisco begin to fill this gap with a of a cold ice pack to a swollen ankle. For colloquial use, I prefer 8. Ringdahl EN. Vagally mediated atrial fibrillation in a young man. Arch Fam Med. 2000 prevalence, characteristics, and the results of the radiofrequency catheter ablation. 11 23 recently published survey among patients with symptomatic AF. cold drink heart, which was inspired by ice cream headache Apr;9(4):389-390 Pacing Clin Electrophysiol. 2007 Oct;30(10):1224-1232. https://doi.org/10.1111/ The investigators invited 1295 patients from a separate AF study and holiday heart.19,20 9. Tan CW, Gerry JL, Glancy DL. Atrial fibrillation in father and son after ingestion j.1540-8159.2007.00844.x of cold substances. Am J Med Sci. 2001 May;321(5):355-357. https://doi. 23. Hulihan J. Ice cream headache. BMJ. 1997 May 10;314(7091):1364. and from a patient-centered AF advocacy organization to partici- org/10.1097/00000441-200105000-00010 pate in a questionnaire on common triggers of paroxysmal AF. The WHY OUR WORK MATTERS list of triggers was based on the literature, physician experience, These many considerate email senders have reminded me why and several patients with AF who served as study advisors. Un- clinical research matters. Our publications—case reports includ- like some studies of acute AF triggers,12,14-16 cold food and drink ed—are making a difference in the lives of patients, in our own were included. Among the 957 survey respondents, 122 (13%) medical centers and beyond. “Finding your paper changed my reported that swallowing cold food or drink sometimes or always life.… Can’t say thank you enough!” one writer kindly expressed. triggered paroxysmal AF episodes. The prevalence is roughly What an affirmation. similar to that of a much smaller Swedish study in which 8 (8%) I have written this essay for physicians, to take what I have of 100 adults seeking hospital care for paroxysmal AF reported learned from these generous patients—about the prevalence, cold drinks as an AF precipitant on a questionnaire about AF prevention, and underrecognition of cold-drink AF—and share triggers.17 Neither study reported characteristics of this subpopu- it with physicians. My goal is to help them better understand lation of patients. Authors of other studies, however, suggest that and care for their patients with cold-drink AF. But I hope this patients with vagally mediated AF are typically younger and less essay finds its way also into the hands of patients with cold drink likely to have structurally abnormal atria or cardiac comorbidities heart, as our case report did. than those with sympathetic or random AF.13,14 If some of my correspondents are reading, thank you for your Regarding the demographics of patients with cold-drink AF emails. I appreciate the inspiration that your correspondence from my email writers, one cannot infer much from such a small has provided. You have reminded me that research publications number of cases, but this is all I have to go on for now. Fifteen can have far-reaching beneficial effects, including direct patient of the 16 correspondents, to date, were male. They were generally education. You also have reminded me the role patients can young; among the 9 who mentioned their age, the median was 38 have in physician education. We will be better able to care for years (range = 27-57 years), although few reported at what age you—and others like you—when we learn to listen to what you v the condition began. One 54-year-old man said his first episode have to teach us. of cold-drink AF occurred when he was 16 years old. Cold drink heart has been reported in adolescents.18 Most of my email writers

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.238 108 The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 CLINICAL MEDICINE CLINICAL MEDICINE Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food Redressing Underrecognition of “Cold Drink Heart”: Patients Teaching Physicians about Atrial Fibrillation Triggered by Cold Drink and Food

Disclosure Statement 10. Al-Farsi Y, Tariq O, Siddiqui A, Sharef YW. Atrial fibrillation with a rare cause of described in 2000 in a young man without cardiac disease with were healthy and free of other cardiopulmonary diagnoses. These initiation. Case report. Med J Babylon. 2014;11(2):482-6. 8 The author(s) have no conflicts of interest to disclose. the swallowing of cold shakes and sundaes. patients also tell me how broad-ranging the cold stimuli can be, 11. Groh CA, Faulkner M, Getabecha S, et al. Patient-reported triggers of paroxysmal A published report from 2001 tells a similar story. A healthy including chilled water, ice-cold sodas, flavored ice-slushies (as atrial fibrillation. Heart Rhythm. 2019 Jul;16(7):996-1002. https://doi.org/10.1016/j. Acknowledgments hrthm.2019.01.027 42-year-old man had been experiencing transient palpitations in our initial case report1), frozen yogurt, and ice cream—what- 9 This work was supported by The Permanente Medical Group’s Delivery 12. Rosso R, Sparks PB, Morton JB, et al. Vagal paroxysmal atrial fibrillation: “after drinking cold beverages.” The dysrhythmia spells were ever the flavor. These were all nonalcoholic triggers, so physicians Science and Physician Researcher Programs, Oakland, California. prevalence and ablation outcome in patients without structural heart disease. J documented on several occasions to be AF. He figured out the can avoid confusing cold drink heart with holiday heart, which I am grateful to Nelya Lugovskaya Nemcek, BA, University of California Davis Cardiovasc Electrophysiol. 2010 May;21(5):489-493. https://doi.org/10.1111/j.1540- 8167.2009.01658.x 19,20 School of Medicine, Sacramento, California, for leading our efforts on the initial same prevention solution that my corresponding patients dis- is caused by excess alcohol ingestion. 13. Carpenter A, Frontera A, Bond R, Duncan E, Thomas G. Vagal atrial fibrillation: covered. The authors write: “Recently, his episodes of palpitation case report of this condition. I’m also indebted to Art Klatsky, MD, senior editor What is it and should we treat it? Int J Cardiol. 2015 Dec 15;201:415-421. https://doi. have been rare because he assiduously avoids swallowing anything NAMING THIS CONDITION at The Permanente Journal, and his bright team of reviewers, whose many org/10.1016/j.ijcard.2015.08.108 helpful suggestions greatly improved this essay. 14. Mandyam MC, Vedantham V, Scheinman MM, et al. Alcohol and vagal tone as cold.” A 2014 report followed a parallel pattern: ice-cold drinks Cold-drink AF lacks a conventional diagnostic name. It goes Kathleen Louden, ELS, of Louden Health Communications performed a triggers for paroxysmal atrial fibrillation. Am J Cardiol. 2012 Aug 1;110(3):364-368. induced AF again and again until “deliberate avoidance” led to a by several names in the case report literature, none of which is primary copy edit. https://doi.org/10.1016/j.amjcard.2012.03.033 long symptom-free interval.10 commonly used: cold-induced, swallow-related AF18; cold water 15. Efremidis M, Letsas KP, Lioni L, et al. The impact of vagotonic, adrenergic, and 21 random type of paroxysmal atrial fibrillation on left atrial ablation outcomes. Int J Unique to the 2001 case report is a family tendency to cold- swallowing-induced paroxysmal AF ; cold-induced AF; or cold- References 1 Cardiol. 2013 Oct 9;168(4):4015-4018. https://doi.org/10.1016/j.ijcard.2013.06.075 drink AF, which none of my email-writing patients had men- swallow-induced AF. Several case reports do not even name the 1. Lugovskaya N, Vinson DR. Paroxysmal atrial fibrillation and brain freeze: A case of 16. Lee SH, Park SJ, Byeon K, et al. Risk factors between patients with lone and tioned.9 The 79-year-old father of the 42-year-old man described condition itself but provide only the broader diagnostic category recurrent co-incident precipitation from a frozen beverage. Am J Case Rep 2016 Jan non-lone atrial fibrillation. J Korean Med Sci. 2013 Aug;28(8):1174-1180. https://doi. 8 13;17:23-6. DOI: https://doi.org/10.12659/ajcr.896035 org/10.3346/jkms.2013.28.8.1174 in the report was found to have his son’s condition after ingesting in which it sits, such as vagally mediated AF or swallowing- 2. Finch J, Bell S, Bellingan L, et al. Accessibility, sustainability, excellence: how to 22 17. Hansson A, Madsen-Hardig B, Olsson SB. Arrhythmia-provoking factors and a shaved-ice drink. No family members besides these 2 had this induced tachyarrhythmia. I prefer to describe this condition expand access to research publications. Executive summary. Int Microbiol. 2013 symptoms at the onset of paroxysmal atrial fibrillation: a study based on interviews particular condition (or AF in general).9 Cold-drink and ice as cold-drink AF. Like the term cough syncope, cold-drink AF Jun;16(2):125-132. https://doi.org/10.2436/20.1501.01.187 with 100 patients seeking hospital assistance. BMC Cardiovasc Disord. 2004 Aug 3. Vinson DR, Lugovskaya N, Warton EM, et al. Ibutilide Effectiveness and Safety 3;4:13. https://doi.org/10.1186/1471-2261-4-13 cream triggers of AF are thought to be vagally mediated (like communicates succinctly and explicitly both the most common in the Cardioversion of Atrial Fibrillation and Flutter in the Community Emergency 11,12 18. Robinson JA, Synder CS. Cold-Induced, Swallow-Related Atrial Fibrillation in sleep, post-prandial, and late post-exercise states). Some stud- trigger and the effect. The modifier “induced” is implied; for- in Department. Ann Emerg Med. 2018 Jan;71(1):96-108.e102. https://doi.org/10.1016/j. an Adolescent. J Innov Card Rhythm Manag. 2016;7(6):2391-2393. https://doi. ies have found that patients with vagally mediated triggers of AF stance, cough syncope means cough-induced syncope. In cold- annemergmed.2017.07.481 org/10.19102/icrm.2016.070604 4. Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: 19. Ettinger PO, Wu CF, De La Cruz C, Jr., Weisse AB, Ahmed SS, Regan TJ. are more likely to have a family history of AF than those with drink AF, a cold drink is understood to include non-beverages the ultimate strategy for individualizing medicine? Per Med. 2011 Mar;8(2):161-173. 13,14 Arrhythmias and the “Holiday Heart”: alcohol-associated cardiac rhythm disorders. adrenergic or random triggers, although a family tendency like ice cream and frozen yogurt. From what we know from the https://doi.org/10.2217/pme.11.7 Am Heart J. 1978 May;95(5):555-562. https://doi.org/10.1016/0002-8703(78)90296-x to cold-drink AF, in particular, has not been explored, except as literature today, AF is the prevalent atrial arrhythmia triggered by 5. Voskoboinik A, Kalman JM, Kistler PM. Caffeine and Arrhythmias: Time to Grind the 20. Tonelo D, Providencia R, Goncalves L. Holiday heart syndrome revisited after 9 Data. JACC Clin Electrophysiol. 2018 Apr;4(4):425-432. https://doi.org/10.1016/j. 34 years. Arq Bras Cardiol. 2013 Aug;101(2):183-189. https://doi.org/10.5935/ described in the 2001 case report. swallowing cold drink and food, but other atrial arrythmias could jacep.2018.01.012 19,20 abc.20130153 These several case reports offer helpful patient-specific detail well be possible, as seen in holiday heart. “Cold-stimulus AF” 6. Brodsky MA, Orlov MV, Allen BJ, Selvan A. Frozen yogurt near deep-freeze. Am J 21. Yang PS, Park JG, Pak HN. Catheter ablation for cold water swallowing-induced on cold drink heart but are unable to provide an estimate of is a serviceable name, but the stimulus is not specific and could Cardiol. 1994 Mar 15;73(8):617-618. https://doi.org/10.1016/0002-9149(94)90349-2 paroxysmal atrial fibrillation: a case report. Heart Rhythm. 2014 Dec;11(12):2300- prevalence of this condition. Fortunately, researchers from the be misconstrued as exposure to cold weather or the application 7. Wilmshurst PT. Tachyarrhythmias triggered by swallowing and belching. Heart. 1999 2302. https://doi.org/10.1016/j.hrthm.2014.08.020 Mar;81(3):313-315. https://doi.org/10.1136/hrt.81.3.313 22. Tada H, Kaseno K, Kubota S, et al. Swallowing-induced atrial tachyarrhythmias: University of California, San Francisco begin to fill this gap with a of a cold ice pack to a swollen ankle. For colloquial use, I prefer 8. Ringdahl EN. Vagally mediated atrial fibrillation in a young man. Arch Fam Med. 2000 prevalence, characteristics, and the results of the radiofrequency catheter ablation. 11 23 recently published survey among patients with symptomatic AF. cold drink heart, which was inspired by ice cream headache Apr;9(4):389-390 Pacing Clin Electrophysiol. 2007 Oct;30(10):1224-1232. https://doi.org/10.1111/ The investigators invited 1295 patients from a separate AF study and holiday heart.19,20 9. Tan CW, Gerry JL, Glancy DL. Atrial fibrillation in father and son after ingestion j.1540-8159.2007.00844.x of cold substances. Am J Med Sci. 2001 May;321(5):355-357. https://doi. 23. Hulihan J. Ice cream headache. BMJ. 1997 May 10;314(7091):1364. and from a patient-centered AF advocacy organization to partici- org/10.1097/00000441-200105000-00010 pate in a questionnaire on common triggers of paroxysmal AF. The WHY OUR WORK MATTERS list of triggers was based on the literature, physician experience, These many considerate email senders have reminded me why and several patients with AF who served as study advisors. Un- clinical research matters. Our publications—case reports includ- like some studies of acute AF triggers,12,14-16 cold food and drink ed—are making a difference in the lives of patients, in our own were included. Among the 957 survey respondents, 122 (13%) medical centers and beyond. “Finding your paper changed my reported that swallowing cold food or drink sometimes or always life.… Can’t say thank you enough!” one writer kindly expressed. triggered paroxysmal AF episodes. The prevalence is roughly What an affirmation. similar to that of a much smaller Swedish study in which 8 (8%) I have written this essay for physicians, to take what I have of 100 adults seeking hospital care for paroxysmal AF reported learned from these generous patients—about the prevalence, cold drinks as an AF precipitant on a questionnaire about AF prevention, and underrecognition of cold-drink AF—and share triggers.17 Neither study reported characteristics of this subpopu- it with physicians. My goal is to help them better understand lation of patients. Authors of other studies, however, suggest that and care for their patients with cold-drink AF. But I hope this patients with vagally mediated AF are typically younger and less essay finds its way also into the hands of patients with cold drink likely to have structurally abnormal atria or cardiac comorbidities heart, as our case report did. than those with sympathetic or random AF.13,14 If some of my correspondents are reading, thank you for your Regarding the demographics of patients with cold-drink AF emails. I appreciate the inspiration that your correspondence from my email writers, one cannot infer much from such a small has provided. You have reminded me that research publications number of cases, but this is all I have to go on for now. Fifteen can have far-reaching beneficial effects, including direct patient of the 16 correspondents, to date, were male. They were generally education. You also have reminded me the role patients can young; among the 9 who mentioned their age, the median was 38 have in physician education. We will be better able to care for years (range = 27-57 years), although few reported at what age you—and others like you—when we learn to listen to what you v the condition began. One 54-year-old man said his first episode have to teach us. of cold-drink AF occurred when he was 16 years old. Cold drink heart has been reported in adolescents.18 Most of my email writers

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • https://doi.org/10.7812/TPP/19.238 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.5 109 CASE REPORTS Pertussis Infection in a Naturopathic Primary Care Setting: Reflection on a Case

Luciano Garofalo, ND1,2; Joshua Corn, ND, MS1; Meghan Sperandeo, ND1 Perm J 2020;24:20.065 E-pub: 09/16/2020 https://doi.org/10.7812/TPP/20.065

ABSTRACT medical students.7-9 Research suggests an association between Introduction: Pertussis is a vaccine-preventable disease vaccine-hesitant parents and naturopathic care.10 Survey data that has made a global resurgence in the 21st century. Vaccine from Australia and Canada have demonstrated that parents who hesitancy remains a persistent barrier to achieving protective trust complementary and integrative health care professionals vaccination rates. Vaccine-hesitant individuals may be more likely as a source of information on vaccines are more likely to have to seek counsel with a naturopathic doctor. Seven more state undervaccinated children.10-12 Another study investigating use legislatures have voted to license and/or regulate naturopathic of complementary and integrative health care professionals in doctors in the last decade, illustrating the growing popularity of Washington state found that compared with the general popula- naturopathic medicine in the present health care landscape. Still, tion, undervaccinated children are more likely to use NDs, and the growth of naturopathic medicine, and its potential relation- children who visited NDs had higher rates of vaccine-prevent- ship to vaccine hesitancy, is worrisome. Naturopathic doctors can able illness.13 Licensure and scope of practice for naturopathic be advocates for immunization to vaccine-hesitant individuals, doctors (NDs) varies by region, so the limited available data but ambivalence toward vaccines within the profession remains may not be representative. Additionally, there is a growing call a public health concern. within the field for all naturopathic professional associations and Case Presentation: We report cases of pertussis in a family schools to endorse the Centers for Disease Control and Preven- treated in a naturopathic primary care clinic, where naturopathic tion (CDC) immunization schedule.14,15 Disease prevention is doctors served as vaccine advocates to a vaccine-hesitant family. one of the central principles of naturopathic medicine and is Discussion: Continued collaboration with public health consistent with the practice of vaccination. programs and conventional clinicians is necessary to improve The following case illustrates the role that NDs can serve as medical science training and vaccine advocacy in the field of vaccine advocates to vaccine-hesitant families. The case comes naturopathic medicine. from an academic health center where naturopathic medical student interns manage patients under the supervision of an INTRODUCTION attending physician. The clinics offer primary care services Pertussis is a vaccine-preventable disease that has made a to predominately uninsured patients or Medicaid recipients, global resurgence in the 21st century. There are several factors including the full regular (nontravel) CDC schedule of immu- acting simultaneously that lead to this resurgence.1 One factor nizations for children and adults as part of the federal Vaccines may be the Bordetella pertussis bacterium’s ability to change its for Children Program. antigenic isoform and avoid vaccine-conferred immunity, much in the way that bacteria develop antibiotic resistance.2 The acel- CASE PRESENTATION lular pertussis vaccine is specific to a limited number of pertussis Presenting Concerns antigens, and immunity conferred by this vaccine wanes quicker 3 A mother and 2 of her female children, aged 8 and 10 years, than is needed for pertussis control across the population. presented to the naturopathic primary care clinic complaining Until more effective pertussis vaccines are developed, high im- of a cough of 2 weeks’ duration. Two of their siblings (aged 3 munization rates are critical to protect vulnerable individuals. and 5 years) had laboratory-confirmed pertussis diagnosed by an Undervaccination is associated with increased odds of pertussis urgent care clinic 6 weeks earlier, after exposure to a confirmed infection in children aged 3 to 36 months in a dose-dependent case of pertussis at their church daycare. Both of these siblings relationship; the odds of pertussis infection increase with each 4 had been treated with antibiotics by the urgent care clinic. The dose of the vaccine that is skipped. oldest child was vaccinated according to the CDC schedule until Vaccine hesitancy, defined by the World Health Organization 15 months of age, at which time the parents decided to avoid as the “delay in acceptance or refusal of vaccines despite avail- ability of vaccination services,” remains a persistent barrier to achieving protective vaccination rates. Vaccine hesitancy tends to develop in population clusters, leaving these areas more vulner- 5 Author Affiliations able to disease outbreaks. Vaccine hesitancy has also been shown 1 6 National University of Natural Medicine, Portland, OR to persist despite outbreaks of vaccine-preventable disease. 2 University of Washington, Seattle, WA Attitudes toward vaccination in the field of naturopathic med- icine have historically been mixed, with evidence of professional Corresponding Author enculturation driving vaccine hesitancy among naturopathic Luciano Garofalo ([email protected])

Keywords: immunization, naturopathic, primary care, vaccine hesitancy, vaccines

The Permanente Journal • https://doi.org/10.7812/TPP/20.065 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 110 CASE REPORTS Pertussis Infection in a Naturopathic Primary Care Setting: Reflection on a Case

all future immunizations, citing religious reasons. The other even be counterproductive.10,22 In the effort of shared decision children were completely unvaccinated. making, clinicians should practice motivational interviewing The 2 older children’s cough was worse at night and was de- with vaccine-hesitant parents to reveal their unique beliefs and scribed as paroxysmal and spasmodic, causing episodes of apnea concerns about vaccination.23 Any subsequent education that is followed by inspiratory whooping and vomiting. The mother needed should be specific to each vaccine in question, delivered produced a list of natural remedies that she had been using to without judgment, and rooted in scientific evidence. treat her children without recommendation or supervision from Naturopathic doctors are trained to value the unique situa- a clinician. The list consisted of homeopathic remedies, vita- tion of each patient and hold patient education (docere) as a core min C, vitamin D, and more than 20 different botanicals (eg, principle, in addition to prevention. For these reasons, NDs may eucalyptus, oregano, lavender, thyme, licorice, frankincense) be uniquely positioned as immunization advocates for vaccine- prepared as teas, syrups, steam inhalations, or salves. hesitant individuals. Because NDs are labeled as complementary The children were pleasant and afebrile. Oxygen saturation, and alternative health care professionals and have a philosophi- heart rate, and respiratory rate were all within normal limits. cal affinity for nonpharmacologic therapies, they may be viewed They exhibited a mild cough but were otherwise breathing com- as more trustworthy by individuals who distrust biomedical fortably in the office. They both had anterior cervical lymphade- institutions. Also, NDs tend to spend more time with patients nopathy. Their lungs were clear on auscultation. The remaining than other doctors, and time is necessary to field concerns and physical examination findings were unremarkable. questions about immunization.24 In this case, the family pre - Therapeutic Intervention and Treatment ferred naturopathic primary care because of a value system that Based on the strong epidemiologic link and characteristic prioritized natural remedies over pharmaceuticals, as is often symptoms,16 we empirically diagnosed pertussis and notified the case for patients who use complementary and integrative the state Department of Public Health. A 5-day course of health care professionals. Furthermore, some families avoid azithromycin was prescribed for both children and the mother, conventional medicine because of conflict with clinicians over following the CDC and standard-of-care recommendations to treatment preferences and belief systems around health care. administer antibiotics to patients within 3 weeks of exposure Although the American Academy of Pediatrics advises against or within 3 weeks of symptom onset.17-19 Although antibiotics barring care to children whose parents refuse immunizations, many pediatric clinics still adopt this policy, and it is a subject may not affect the course of illness, administration of antibiot- 25 ics is recommended to reduce spread to individuals at risk of of ongoing debate. Naturopathic doctors often fill the role of development of severe pertussis infection.17,18 We instructed a safety net for such patients who would otherwise not return them to discontinue using all the natural therapies described for follow-up, and they provide culturally relevant and patient- earlier, with the exceptions of honey orally and steam inhalation centered care. Persistent counseling from vaccine-educated NDs for symptomatic relief of cough, and oral probiotics to prevent might be a key component to eventual vaccine uptake in even antibiotic-associated gastrointestinal tract issues. the most skeptical patients. We discussed vaccine avoidance with the mother. As motiva- In addition to nonpharmacologic therapies, naturopathic tion to encourage vaccination, we provided her with information medical students are currently taught standard-of-care medicine, including the CDC immunization schedule and education of about the benefits of the CDC catch-up schedule for pertussis 26 immunization, as well as the risks associated with multiple vaccine-hesitant individuals. This innovation in naturopathic antibiotic courses in childhood.20 We strongly recommended education is both in response to and in preparation for the that the children be brought up-to-date with vaccinations but expanded role of NDs in some states. However, the growth of offered reassurance that the children would continue to receive vaccine hesitancy in the US, and its potential relationship with care regardless of the parents’ decision. naturopathic medicine, is worrisome. In addition to professional Follow-up and Outcomes enculturation, nonscientific immunologic beliefs may engender vaccine hesitancy and are reflected in the real-world practice of Close follow-up was maintained with the family via tele- some licensed NDs.27,28 Such beliefs are likely multifactorial phone. All patients recovered fully without complications. A and could stem from idealistic interpretations of naturopathic case timeline appears in Table 1. The pediatric patients’ guard- philosophy. One example is the oversimplified position that ian consented to the writing and publication of this case report. synthetic drugs impede the body’s natural healing process.29 DISCUSSION Conversely, other NDs and naturopathic organizations profess support for the practice of immunization and the CDC sched- Vaccine hesitancy is complex, and each vaccine may be as- ule.14,30 We argue that a cohesive endorsement of vaccine science sociated with specific parental concerns. For example, parents across all naturopathic professional and educational organiza- who delay or refuse the pertussis vaccine for their child are tions is necessary to edify a new generation of NDs who support more likely to cite reasons such as pertussis not being a seri- the practice of immunization. ous or common disease, whereas the measles-mumps-rubella Seven state legislatures have passed bills in the last decade to (MMR) vaccine is more associated with the fear of it causing 21 license and/or regulate NDs, with the most recent being New autism. The limited studies on interventions to address vac - Mexico in 2019, where NDs are now eligible to provide pri- cine hesitancy have revealed that there is no one-size-fits-all mary care.31 This growth would not have been possible without approach. Provaccine messaging alone is ineffective and may

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.065 111 CASE REPORTS Pertussis Infection in a Naturopathic Primary Care Setting: Reflection on a Case

10. Busse JW, Walji R, Wilson K. Parents’ experiences discussing pediatric endorsements from stakeholders in conventional medicine and vaccination with healthcare providers: A survey of Canadian naturopathic patients. public health. In the treatment of patients who are more likely PLoS One. 2011;6(8). to be vaccine hesitant, it is neither safe nor sustainable for NDs 11. Wilson K, Busse JW, Gilchrist A, Vohra S, Boon H, Mills E. Characteristics of Pediatric and Adolescent Patients Attending a Naturopathic College Clinic in to remain ambivalent about the value of immunization as a Canada. Pediatrics. 2005;115:e338-e343. routine public health practice. Stronger relationships between 12. Frawley JE, Foley H, McIntyre E. The associations between medical, allied and NDs, conventional clinicians, and public health programs are complementary medicine practitioner visits and childhood vaccine uptake. Vaccine. 2018;36(6):866-872. doi:10.1016/j.vaccine.2017.12.036 needed to increase vaccine adherence in patients who use na- 13. Downey L, Tyree PT, Huebner CE, Lafferty WE. Pediatric vaccination and vaccine- turopathic medicine. preventable disease acquisition: associations with care by complementary and alternative medicine providers. Matern Child Health J. Nov 2010;14(6):922-930. CONCLUSION 14. NAPCP approves position paper on immunizations. Commun Dis Epidemiol Immunization Q [Internet]. Seattle, WA: Department of Public Health, Seattle Pertussis control requires higher immunization rates in the and King County; 2016(quarter 4):6-7 [cited 2019 Nov 14]. Available from: www. absence of a more effective vaccine. Naturopathic doctors can kingcounty.gov/depts/health/communicablediseases/~/media/depts/health/ communicable-diseases/documents/cases/communicable-disease-newsletter- be advocates for immunization to vaccine-hesitant individu- 2016-Quarter-4.ashx. als. Support for immunization among NDs is growing, but 15. Logan AC, Goldenberg JZ, Guiltinan J, Seely D, Katz DL. North American ambivalence toward immunization remains a public health naturopathic medicine in the 21st century: Time for a seventh guiding principle - Scientia Critica. Explore (NY). 2018 Sep;14(5):367-372. concern. Continued collaboration with public health programs 16. Moore A, Harnden A, Grant CC, Patel S, Irwin RS; CHEST Expert Cough Panel. and conventional clinicians is necessary to improve medical sci- Clinically Diagnosing Pertussis-associated Cough in Adults and Children: CHEST ence training and vaccine advocacy in the field of naturopathic Guideline and Expert Panel Report. Chest. 2019;155(1):147-154. doi:10.1016/j. v chest.2018.09.027 medicine. 17. Tiwari T, Murphy TV, Moran J. National Immunization Program, CDC. Recommended antimicrobial agents for the treatment and postexposure Disclosure Statement prophylaxis of pertussis: 2005 CDC Guidelines. MMWR Recomm Rep. The author(s) have no conflicts of interest to disclose. 2005;54(RR-14):1-16. 18. Sprauer MA, Cochi SL, Zell ER, et al. Prevention of secondary transmission of pertussis in households with early use of erythromycin. Am J Dis Child. Acknowledgments 1992;146(2):177-181. doi:10.1001/archpedi.1992.02160140043018. Kathleen Louden, ELS, of Louden Health Communications performed a 19. Altunaiji S, Kukuruzovic R, Curtis N, Massie J. Antibiotics for whooping cough primary copyedit. (pertussis). Cochrane Database Syst Rev. 2007;(3):CD004404. Published 2007 Jul 18. doi:10.1002/14651858.CD004404.pub3 Authors’ Contributions 20. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Luciano Garofalo was the student intern assigned to the case, Genome Med. 2016;8(1). doi:10.1186/s13073-016-0294-z conceptualized the thesis, drafted the initial manuscript, and revised the 21. Bardenheier B, Yusuf H, Schwartz B, Gust D, Barker L, Rodewald L. Are parental manuscript. Joshua Corn, ND, MS, was the resident assigned to the case vaccine safety concerns associated with receipt of measles-mumps-rubella, and reviewed and revised the manuscript. Meghan Sperandeo, ND, was the diphtheria and tetanus toxoids with acellular pertussis, or hepatitis B vaccines by attending physician on the case and reviewed and revised the manuscript. All children? Arch Pediatr Adolesc Med. 2004;158(6):569-575. authors have given final approval to the manuscript. 22. Salmon DA, Dudley MZ, Glanz JM, Omer SB. Vaccine hesitancy: Causes, consequences, and a call to action. Am J Prev Med. 2015;49(6 Suppl 4):S391-8. doi:10.1016/j.amepre.2015.06.009 References 23. Lemaitre T, Carrier N, Farrands A, Gosselin V, Petit G, Gagneur A. Impact of a 1. Lapidot R, Gill CJ. The pertussis resurgence: Putting together the pieces of the vaccination promotion intervention using motivational interview techniques on puzzle. Trop Dis Travel Med Vaccines. 2016;2(1). doi:10.1186/s40794-016-0043-8. long-term vaccine coverage: the PromoVac strategy. Hum Vaccin Immunother. 2. Sealey KL, Harris SR, Fry NK, Hurst LD, Gorringe AR, Parkhill J, Preston A. 2019;15(3):732-739. Genomic analysis of isolates from the United Kingdom 2012 pertussis outbreak 24. Boon HS, Cherkin DC, Erro J, et al. Practice patterns of naturopathic physicians: reveals that vaccine antigen genes are unusually fast evolving. J Infect Dis. results from a random survey of licensed practitioners in two US States. BMC 2015;212(2):294-301. Complement Altern Med. 2004;4:14. Published 2004 Oct 20. doi:10.1186/1472- 3. Klein NP, Bartlett J, Rowhani-Rahbar A, Fireman B, Baxter R. Waning protection 6882-4-14. after fifth dose of acellular pertussis vaccine in children. N Engl J Med. 25. Alexander K, Lacy TA, Myers AL, Lantos JD. Should pediatric practices have 2012;367(11):1012-9. policies to not care for children with vaccine-hesitant parents? Pediatrics E-pub 4. Glanz JM, Narwaney KJ, Newcomer SR, et al. Association between ahead of print September 2, 2016. doi:10.1542/peds.2016-1597 undervaccination with diphtheria, tetanus toxoids, and acellular pertussis (DTaP) 26. AANMC core competencies of the graduating naturopathic student [Internet]. vaccine and risk of pertussis infection in children 3 to 36 months of age. JAMA Washington, DC: Association of Accredited Naturopathic Medical Colleges; Pediatr. 2013;167(11):1060-1064. doi:10.1001/jamapediatrics.2013.2353 2019 [cited 2020 May 25]. Available from: https://aanmc.org/wp-content/ 5. Omer SB, Enger KS, Moulton LH, Halsey NA, Stokley S, Salmon DA. Geographic uploads/2019/10/Competencies_Amended_10.25.19.pdf. clustering of nonmedical exemptions to school immunization requirements 27. Bean SJ, Catania JA. Immunology beliefs as a factor in vaccine opposition and associations with geographic clustering of pertussis. Am J Epidemiol among complementary and alternative medical providers. SAGE Open Med. 2008;168(12):1389-1396. 2018;6:205031211880762. doi:10.1177/2050312118807625 6. Opel D, Dehart MP, Warren J, Rowhani-Rahbar A. Impact of a Pertussis Epidemic 28. Caulfield T, Rachul C. Supported by science? What Canadian naturopaths on Infant Vaccination in Washington State. Pediatrics. 2014;134(3):456-464. advertise to the public. Allergy Asthma Clin Immunol. 2011;7(1):14. doi:10.1542/peds.2013-3637 29. Bradley RS. Philosophy of naturopathic medicine. In: Pizzorno JE Jr, Murray MT, 7. Busse JW, Wilson K, Campbell JB. Attitudes towards vaccination among eds. Textbook of natural medicine. 4th ed. St Louis, MO: Churchill Livingstone; chiropractic and naturopathic students. Vaccine. 2008;26(49):6237–6243. 2013. 8. Wilson K, Mills E, Boon H, Tomlinson G, Ritvo P. A survey of attitudes towards 30. NDs for Vaccines [Internet]. 2019 [cited 2020 May 24]. https://ndsforvaccines.com/. paediatric vaccinations amongst Canadian naturopathic students. Vaccine. 31. Regulated states and regulatory authorities [Internet]. Washington, DC: American 2004;22(3-4):329-334. Association of Naturopathic Physicians; 2019 Jul. Updated 2020 Jul 29 [cited 2019 9. McMurtry A, Wilson K, Clarkin C, et al. The development of vaccination Nov 24]. https://naturopathic.org/page/RegulatedStates#. perspectives among chiropractic, naturopathic and medical students: a case study of professional enculturation. Adv Heal Sci Educ. 2015;20(5):1291-1302. doi:10.1007/s10459-015-9602-4

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Table 1. Case timeline Relevant medical history: All children in family unvaccinated except for 10-year-old child, who stopped receiving vaccinations at age 15 mo Date Summaries from history and initial visit Intervention August 25 All 4 siblings exposed to confirmed pertussis at church daycare September 5 3-year-old and 5-year-old have laboratory-confirmed pertussis Antibiotic treatment September 26 10-year-old begins to have catarrhal symptoms September 27 8-year-old begins to have catarrhal symptoms October 2 Paroxysmal cough develops in both 8-year-old and 10-year-old Mother administered homeopathic remedies, vitamins C and D, and > 20 different botanicals without a physician’s advice October 8 Initial visit: Children and mother come to naturopathic primary care Five-day course of azithromycin prescribed clinic and receive clinical diagnosis of pertussis. Natural therapies: honey and probiotics orally, steam inhalation October 14 All patients recovered fully without complications

The4 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.065 113 CASE REPORTS Hemolytic Anemia in a Glucose-6-Phosphate Dehydrogenase- Deficient Patient Receiving Hydroxychloroquine for COVID-19: A Case Report

Jorge Aguilar, MD, PhD1; Yelena Averbukh, MD Perm J 2020;24:20.158 E-pub: 08/05/2020 https://doi.org/10.7812/TPP/20.158

ABSTRACT where community-acquired pneumonia was diagnosed. He Introduction: The growing coronavirus disease 2019 (CO- was discharged to home with a prescribed 7-day course of levo- VID-19) pandemic initially led to widespread use of hydroxy- floxacin that was reportedly completed. On general worsening chloroquine sulfate as an off-label experimental treatment of of his cough and dyspnea, he arrived at our hospital and was this disease. subsequently admitted. Case Presentation: Acute hemolytic anemia developed in On admission, the patient tested positive for COVID-19, an African American man with COVID-19-related pneumonia with chest radiographic findings consistent with COVID-19 and glucose-6-phosphate dehydrogenase (G6PD) deficiency pneumonia. He initially demonstrated a supplemental oxygen who completed the standard 5-day experimental course of hy- requirement of 2 L/minute via nasal cannula, but this need droxychloroquine. Although the trigger leading to our patient’s resolved within 24 hours of hospitalization. hemolytic sequelae will never be known with certainty, his clinical course suggests that hydroxychloroquine use and/or COVID-19 Therapeutic Intervention and Treatment infection may trigger hemolysis in susceptible patients with G6PD deficiency. On day 1, the standard experimental 5-day course of hy- Discussion: This case confirms recent findings that the po- droxychloroquine (400 mg twice daily on day 1, and 400 mg tential risks of hydroxychloroquine therapy for COVID-19 may once daily on days 2-4) for treatment of COVID-19-induced outweigh the benefits. pneumonia was initiated. Testing for G6PD deficiency was done on admission; however, the result was found to be abnormal INTRODUCTION only on the sixth day of hospitalization. Notably, the patient was also found to have a creatine kinase level elevated to 4399 Hydroxychloroquine is an oral medication used for the U/L and creatinine level of 10.1 mg/dL (1.2 mg/dL before ad- treatment of malaria and several rheumatologic diseases, and it mission), which were concerning for acute kidney injury. The recently was used widely as an experimental drug to treat pneu- patient was initially managed with intravenous fluids but soon monia due to coronavirus disease 2019 (COVID-19). Hydroxy- required hemodialysis. chloroquine information resources and drug package inserts recommend caution when prescribing this medication to patients Follow-up and Outcomes with glucose-6-phosphate dehydrogenase (G6PD) deficiency, presumably because of a risk of hemolytic anemia. This risk by On the sixth day of hospitalization, one day after completion association is loosely connected to rare reports of hemolysis and of hydroxychloroquine therapy, the patient became hypoxic and death in G6PD-deficient patients who received primaquine, an required supplemental oxygen via nasal cannula, correlating antimalarial medication similar to hydroxychloroquine, for the with a decrease in hemoglobin level to 8.4 g/dL (14.5 g/dL on treatment of malaria.1 In more than 6 decades of primaquine admission). Additional studies in the subsequent 3 days revealed use by approximately 200 million people, 14 deaths have been a reticulocytosis of more than 3%, increasing lactic dehydroge- reported.2 However, to our knowledge, there is no evidence in nase level to 2575 U/L, increasing total bilirubin level to 1.5 mg/ the literature of an association between hydroxychloroquine dL (0.3 mg/dL on admission) with relatively unchanged direct and hemolytic anemia.3 In this case report, we describe a case bilirubin levels (maximum = 0.4 mg/dL throughout hospitaliza- in which a patient with previously unknown G6PD deficiency tion), low haptoglobin concentration to less than 10 mg/dL, and experienced acute hemolytic anemia in the setting of hydroxy- positive schistocytes on a peripheral blood film, suggestive of chloroquine therapy for COVID-19-related pneumonia. an acute intravascular hemolytic anemia. All other laboratory tests, including complete blood cell count, urine analysis, and CASE PRESENTATION Presenting Concerns A 51-year-old African American man with type 2 diabetes, Author Affiliations hypertension, and morbid obesity presented to our hospital with 1 Montefiore Medical Center, Bronx, New York approximately 2 to 3 weeks of subjective fevers, myalgias, dry cough, and worsening shortness of breath. One week earlier, Corresponding Author Jorge Aguilar, MD, PhD ([email protected]) he presented to an outside hospital’s Emergency Department, Keywords: COVID-19, glucose-6-phosphate dehydrogenase, G6PD, hemolytic anemia, hydroxychloroquine

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coagulation profiles had either normal results or nonspecific Second, unknown hydroxychloroquine-dependent interactions findings consistent with COVID-19 infection. alone may have served as the trigger. Although, to our knowl- The patient consequently required red blood cell transfusions edge, no reports of hydroxychloroquine-induced hemolysis on days 9, 10, and 11 of hospitalization. Afterward the patient’s exist in the published literature, the loading dose of 800 mg of hemoglobin levels stabilized to between 8 and 9 g/dL. During hydroxychloroquine in our COVID-19 pneumonia protocol is this hemolytic process, the patient’s hemodialysis catheter ir- twice the normal dose in standard rheumatologic therapy and in reversibly clogged twice, requiring 2 separate urgent catheter published studies examining the potential association between replacements. The patient became able to breathe comfortably hydroxychloroquine and hemolysis. Levofloxacin-induced he- on room air on day 16 and was discharged home with outpatient molytic anemia also remains on the differential diagnosis but hemodialysis scheduled. A case timeline appears in Table 1. is considered extremely rare. Autoimmune hemolytic anemia is typically associated with conditions that our patient lacked; thus, DISCUSSION no direct testing for it was performed. Last, there is the pos- Glucose-6-phosphate dehydrogenase deficiency is a recessive sibility that COVID-19 infection alone may trigger hemolytic X-linked blood disorder characterized by a defective mutation anemia in susceptible patients with G6PD deficiency. To our in G6PD, an enzyme that plays a critical role in protecting knowledge, this is the first reported case of hemolytic anemia in erythrocytes from oxidative damage.4 In the setting of infection a patient with COVID-19 infection or in a patient who received (eg, pneumonia) or exposure to certain foods or medications, hydroxychloroquine therapy. oxidative stress leads to excessive accumulation of free radicals, Since we submitted this article for publication, the US causing G6PD-deficient erythrocytes to burst and ultimately Food and Drug Administration revoked its emergency use leading to hemolytic anemia.5 The 2 most clinically significant authorization to use hydroxychloroquine to treat COVID-19 genetic variants of G6PD deficiency are the Mediterranean and in certain hospitalized patients, because recent results from a African types, which are both highly prevalent in geographi- large, randomized clinical trial in hospitalized patients found cal areas where malaria is endemic. It is widely accepted that this medicine did not decrease the likelihood of death or of this distinct geographic distribution of G6PD deficiency is the hastening recovery.9 product of positive selection, because these mutations may confer protection against malaria.6 CONCLUSION Antiparasitic medications have been commonly used to treat As the COVID-19 pandemic continues to grow in the United or prevent malaria for more than a century. Among them, the States, we may learn of more cases of hemolytic anemia in quinolone hydroxychloroquine has been in use as an antimalarial patients with G6PD-deficiency who received treatment with agent for more than 65 years, with a warning to prescribers that hydroxychloroquine. If so, these additional cases would fur- hydroxychloroquine may lead to hemolytic anemia in patients ther support the FDA’s decision to revoke the Emergency Use with G6PD deficiency. This warning was based on solid evidence Authorization (EUA) for hydroxychloroquine sulfate for the v that a similar quinolone to hydroxychloroquine, primaquine, treatment of COVID-19 disease. rarely causes hemolytic anemia in G6PD-deficient patients.2 However, until the time of this writing, there have been no Disclosure Statement The author(s) have no conflicts of interest to disclose. published clinical case reports or scientific evidence establish- ing an association between hydroxychloroquine and hemolysis. Acknowledgments One recent study specifically investigating this possible associa- Kathleen Louden, ELS, of Louden Health Communications performed a tion did not reveal episodes of suspected hydroxychloroquine- primary copyedit. induced hemolysis in 11 G6PD-deficient patients who received a combined 700 months of hydroxychloroquine therapy for various Authors’ Contributions 7 rheumatologic disorders. Moreover, the American College of Jorge Aguilar, MD, PhD, and Yelena Averbukh, MD, participated equally Rheumatology does not recommend screening for G6PD de- in the drafting, critical review, and submission of the final manuscript. Both ficiency before initiation of therapy with hydroxychloroquine.8 authors have given final approval to the manuscript. Nearly all patients with G6PD deficiency remain asymp- tomatic in the steady state, and hemolysis develops only in the References 1. Tarlov AR, Brewer GJ, Carson PE, Alving AS. Primaquine sensitivity. Glucose-6- setting of food or drug interactions or severe infection. Indeed, phosphate dehydrogenase deficiency: An inborn error of metabolism of medical our patient was unaware of his G6PD deficiency until this and biological significance. Arch Intern Med. 1962;109:209-34. DOI: https://doi. hospitalization. org/10.1001/archinte.1962.03620140081013. 2. Ashley EA, Recht J, White NJ. Primaquine: The risks and the benefits. Malar J. Although the trigger leading to our patient’s hemolytic se- 2014;13:418. quelae will never be known with certainty, a few potential ex- 3. Youngster I, Arcavi L, Schechmaster R, et al. Medications and glucose-6- planations merit consideration. First, our patient’s hypoxia on phosphate dehydrogenase deficiency: An evidence-based review. Drug Saf. initial presentation may have served as the trigger. Although 2010;33(9):713-26. 4. Chan DK. Glucose-6-phosphate dehydrogenase deficiency: Correlation between the patient’s hypoxia was mild and resolved after 24 hours, the genotype, biochemistry and phenotype. Ann Acad Med Singapore. 2008;37(12 the duration and/or degree of hypoxia before presentation is Suppl):81-83. unknown and may have been sufficient to trigger hemolysis. 5. Beutler E. G6PD: Population genetics and clinical manifestations. Blood Rev. 1996;10(1):45-52.

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6. Min-Oo G, Gros P. Erythrocyte variants and the nature of their malaria protective effect. Cell Microbiol. 2005;7(6):753-63. 7. Mohammad S, Clowse ME, Eudy AM, Criscione-Schreiber LG. Examination of hydroxychloroquine use and hemolytic anemia in G6PDH-deficient patients. Arthritis Care Res (Hoboken). 2018;70(3):481-85. DOI: https://doi.org/10.1002/ acr.23296. 8. Singh JA, Saag KG, Bridges SL, Jr., et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016;68(1):1-25. 9. US Food and Drug Administration. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems [cited 2020 Jun 25]. Updated June 15, 2020. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/ fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside- hospital-setting-or.

Table 1. Case timeline Relevant Medical History and Interventions A 51-year-old African American man with type 2 diabetes, hypertension, and morbid obesity received a diagnosis from another hospital of community-acquired pneumonia Date Summaries from initial and follow-up visits Diagnostic testing (including dates) Interventions 3/31/2020 Patient presents with 2-3 weeks of subjective Chest X-Ray: pneumonia Supplemental oxygen provided via fevers, myalgias, dry cough, and worsening COVID-19 PCR: positive nasal cannula or non-rebreather mask. shortness of breath, demonstrating a G6PD: positive (resulted on 4/6) supplemental oxygen requirement. 4/1/2020 Patient no longer required supplemental Creatine kinase level el-evated to 4399 U/L and 5-day course of Hydroxychlo-roquine oxygen. Creatinine level of 10.1 mg/dL (1.2 mg/dL be-fore initiated; AKI was initially managed with admission) were concerning for acute kidney injury intravenous fluids but soon required (AKI). serial he-modialysis. 4/6/2020 Patient completed 5-day course of Hg 8.4 d/gL (down from 14.5 g/dL on ad-mission) Supplemental oxygen provided via Hydroxychlo-roquine; Patient became hypoxic, nasal can-nula or non-rebreather mask requiring sup-plemental oxygen. 4/7/2020 Persistence of lethargy, dyspnea, and hypoxia, Hemolysis workup find-ings (CBC, reticulocyto- Supplemental oxygen provided via requiring supplemental oxygen. sis, LDH, bilirubin, hap-toglobin, and peripheral nasal can-nula or non-rebreather blood smear) suggestive of an acute intravascular mask. hemolytic anemia 4/9/2020 Persistence of lethargy, dyspnea, and hypoxia, Hg 5.9 Red Blood Cell (RBC) Transfusion requiring supplemental oxygen. 4/10/2020 Persistence of lethargy, dyspnea, and hypoxia, Hg 6.7 RBC Transfusion requiring supplemental oxygen. 4/11/2020 Persistence of lethargy, dyspnea, and hypoxia, Hg 6.6 RBC Transfusion requiring supplemental oxygen. 4/16/2020 Significant clinical improvement; Reso-lution Hg 8.6 of hypoxia. 4/21/2020 Patient was discharged to home.

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ABSTRACT Introduction: Bilateral and simultane- ous quadriceps tendon rupture is rarely observed. This case series evaluates 3 patients with bilateral ruptures of the quadriceps tendon. The purpose of this case series is to display the effectiveness of the suture anchor surgical repair tech- nique in these patients. Case Presentations: Three obese male patients experienced some type of traumatic injury to the knee exten- sor mechanism, resulting in bilateral quadriceps tendon ruptures. Each of Figure 1. Case 1. Magnetic resonance image showing bilateral quadriceps tendon rupture (A. left knee and the patients was evaluated and given B. right knee). operative and nonoperative treatment options, and they all elected to undergo compromise the patient’s blood supply This case report evaluates 3 patients surgical tendon repair. Two double- and/or collagen production over time, with bilateral ruptures of the knee ex- loaded anchors were placed into the which can lead to weakened tendons.2 tensor mechanism. Each patient did not superior pole of the patella, allowing This weakening of the tendons makes have a history of a systemic disease that the tendons to be reduced back to their them more vulnerable to rupture. Aside is commonly associated with quadriceps original positioning. Postoperatively, all from these risk factors, quadriceps tendon rupture but did have obesity. Although the patients were given the same guidelines ruptures are also seen when an eccentric tendon injury these patients experienced for physical therapy, and their progress load is placed on the knee during flexion, was linked to their specific trauma (sudden was monitored periodically. Each patient such as when one is attempting to land eccentric knee flexion), their obesity put returned to his normal level of physical from a jump or when falling. them at a higher risk of complete rupture activity. Range of motion at the knee Obesity has been linked to tendinopa- of the quadriceps tendon. In these difficult and weight bearing were reestablished thy because of tendon overload and chron- cases of bilateral quadriceps tendon rup- in all 3 patients. ic inflammation.3,4 Tendon overload, as it tures, it is important to perform a timely Discussion: These quadriceps tendon relates to the tendon continuum theory, repair of the extensor mechanism that al- ruptures occurred in patients with a suggests that as a tendon is continuously lows for immediate weight bearing, early predisposition to injury as a result of ex- exposed to an increased yield and load, ambulation, and knee range of motion. cessive weight bearing. When addressing it progressively degenerates until the In this case series, we review the clinical bilateral quadriceps tendon ruptures in damage is no longer reversible.3 Chronic outcomes of 3 obese patients with bilat- this patient population, we found that a inflammation is also linked to obesity. As eral quadriceps tendon tears treated with suture anchor-based construct allows for obesity advances, there is hypertrophy of a suture anchor-based repair construct. a secure repair, early initiation of physical adipocytes, which leads to an increase in therapy, and a noted improvement in macrophage secretion and production of CASE PRESENTATIONS pain scores on the Visual Analog Scale. a proinflammatory environment.4 These Case 1 2 factors contribute to structural tendon A 64-year-old man with a body mass INTRODUCTION damage as well as irritation and joint pain. index (BMI) of 41.8 kg/m2 (calculated The extensor mechanism of the knee is The rupture of a single quadriceps ten- from the patient’s weight just before an essential component of locomotion. The don represents a substantial percentage of surgery) presented with bilateral knee primary components of knee extension extensor mechanism injuries, especially in include the quadriceps muscles, quadri- patients older than the age of 50 years.5 ceps tendon, patella, and patellar tendon However, bilateral and simultaneous quad- Author Affiliations 1 as well as the retinaculum. Quadriceps riceps tendon rupture is rarely observed. 1Morehouse School of Medicine, Atlanta, GA ruptures are commonly associated with According to Neubauer and et al6, “Only 2Department of Orthopedic Surgery, Glenlake Medical Center, Atlanta, GA corticosteroid use or systemic disease, such 66 cases have been reported in the English Corresponding Author as hyperparathyroidism, renal failure, or literature between the first description in Jason Tucker ([email protected]) connective tissue disease. These diseases 1949 and 2002.” Keywords: obesity, quadriceps tendon, suture anchor

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pain, effusion, and inability to perform Table 1. Postoperative protocol after quadriceps tendon repair using suture anchors a straight leg raise after sustaining a fall Time Protocol down the stairs 1 week earlier. He de- 0-6 wk WBAT, with brace locked in extension at all times except therapy. scribed an eccentric load that was placed • Weeks 0-2: Knee flexion 0-30° on either knee during the fall. At the time • Weeks 2-4: Knee flexion 0-60° of examination, he was unable to ambu- • Weeks 4-6: Knee flexion 0-90°; begin straight leg raises while supine late and had palpable gaps superior to the 6-12 wk Unlock brace for ambulation. Wean from brace as tolerated. May discontinue crutches proximal pole of the patella. His Visual when gait normalizes. Normalize ROM. Begin exercises such as minisquats, short-crank Analog Scale (VAS) score was 10 (on a cycling, and weight shifting. 10-point scale). Routine radiographs were 3-6 mo If gait is normal, begin WBAT without assistance. If ROM is normal, begin leg performed, which showed an effusion and presses, running/jogging, agility exercises, and use of vertical climber fitness machine osteoarthritic changes. A magnetic reso- (VersaClimber, Heart Rate Inc, Santa Ana, CA). nance image was obtained of each knee, ROM = range of motion; WBAT = weight bearing as tolerated. which revealed full-thickness quadriceps tendon ruptures from the superior pole of the patella along with some degenerative intra-articular pathology (Figure 1). The patient was counseled on his con- dition and given operative and nonop- erative options of treatment. He elected to undergo bilateral quadriceps tendon repair. The surgical procedure, a suture anchor-based repair, was performed within 2 weeks of injury, as described in the Surgical Technique section after the case reports. Postoperatively, the patient was placed in hinged knee braces and locked in ex- Figure 2. Case 2. Magnetic resonance image showing bilateral quadriceps tendon rupture (A. left knee and tension for ambulation. Physical therapy B. right knee). started on postoperative day 2 to aid in recovery and strengthen his tendons. The patient was allowed to gradually increase an antalgic gait, bilateral knee effusions bilaterally, and he was back to an active his knee flexion in 30-degree increments were present, and he was unable to per- lifestyle. More than 1 year since surgery, every 2 weeks (Table 1). form a straight leg raise. His medical his- he has had no knee complaints. Six weeks postoperatively, the brace tory included hypertension and a BMI of 2 Case 3 was unlocked for ambulation. At that 36.94 kg/m (calculated from the patient’s time, the patient could ambulate without weight just before surgery). A 61-year-old man in a wheelchair an assistive device, was able to achieve full Magnetic resonance images were ob- came to our practice for evaluation of knee extension with 5 of 5 quadriceps tained of both knees. Results confirmed bilateral knee pain sustained in an in- tendon strength, and had a VAS pain bilateral quadriceps tendon ruptures jury 3 weeks earlier. Routine radiographs score of 2 of 10 (consistent with his base- (Figure 2), which had not previously been showed bilateral mild osteoarthritis and line knee arthritis). By 3 months, he was found. When he came to our practice, knee effusions. Results of magnetic reso- allowed to discontinue wearing the brace. there was documentation only of reported nance imaging confirmed bilateral quad- Now more than 2 years after surgery, the pain and swelling of the knee. After being riceps tendon ruptures (Figure 3). The patient maintains an active lifestyle. counseled on his diagnosis and treatment patient’s medical history was remarkable options, the patient chose to undergo bi- for vitamin D deficiency, prostate cancer, Case 2 lateral quadriceps tendon repair. and a BMI of 35.9 kg/m2 (calculated from A 43-year-old man presented with the The surgery was performed as de - the patient’s weight just before surgery). chief complaint of bilateral knee pain af- scribed in the Surgical Technique section. He was counseled on treatment options ter a fall while playing on a trampoline. The patient followed the postoperative and ultimately chose to undergo quadri- During the fall, this patient sustained protocol described in Table 1. ceps tendon repair. bilateral ankle fractures, which had previ- At 8 weeks postoperatively, the patient The surgery was performed as de - ously undergone open reduction internal had a VAS pain score of 0 of 10 and was scribed in the Surgical Technique section fixation at another health care facility. able to perform bilateral straight leg and was uneventful. The patient followed We examined the patient approximately raises without an extensor lag. Six months the postoperative protocol shown in 3 weeks after his injury. He walked with postoperatively, his flexion reached 120˚ Table 1.

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full extension, and the 4 pairs of sutures are sequentially tied, thus reducing the quadriceps tendon to the superior pole of the patella. The retinaculum is repaired using no. 2 or 5 nonabsorbable sutures with buried knots. The knee range of motion is checked and recorded. The knee goes through a last cycle of irriga- tion, and the wound is closed in layers. The opposite knee is prepared again, and the procedure is repeated on that knee. DISCUSSION Figure 3. Case 3. Magnetic resonance image showing bilateral quadriceps tendon rupture (A. left knee and Knee extensor mechanism ruptures B. right knee). can occur either at the patellar tendon or quadriceps tendon. The literature sug- By 6 months postoperatively, his ten- A double drape is placed, and 1 knee is gests that disruption of the knee extensor don strength reached a plateau of a 5 of covered with an additional sterile drape mechanism in individuals over the age of 5 on physical examination. His VAS pain while the opposite knee undergoes sur- 40 years typically involves the quadriceps 7 score at final follow-up was 1 of 10. Now gery. An Esmarch bandage is used to tendon. In a review of 726 patients who 1 year after surgery, the patient is back to exsanguinate the lower extremity, and experienced extensor mechanism inju- full work duty. A timeline of all 3 cases the tourniquet is inflated to 250 mmHg. ries from 1986 to 2012, a total of 210 appears in Table 2. A 6-cm to 8-cm midline incision is made (28.9%) sustained quadriceps tendon sharply over the superior patella and ruptures. Their mean age was 61.0 years old 2 SURGICAL TECHNIQUE quadriceps tendon. A Bovie cautery is (standard deviation = 13.1 years). The same surgical technique was used used to dissect down to the defect, fol- on all 3 patients. In the preoperative lowed by evacuation of the hematoma. holding area, the patient receives bilat- Blunt dissection frees up any adhesions. eral single-shot femoral blocks placed The superior pole of the patella and distal for regional anesthesia. The patient is aspect of the quadriceps tendon are pre- brought to the operating room and placed pared using a curette and rongeur. Occa- supine on a well-padded operating table. sionally, a burr is used to aid in creating a General anesthesia is induced. Nonsterile bleeding surface along the superior border tourniquets are placed on both thighs. of the patella. The knee is cycled to be sure that the Two 2.8-mm, double-loaded, all- tourniquet is not constraining excursion suture anchors (Q-FIX◊, Smith and of the quadriceps tendon. Both lower Nephew Inc, Cordova, TN) are placed extremities are scrubbed and prepared in in the superior pole of the patella (Fig- a standard fashion using chlorhexidine ure 4). A modified Krackow suture con- gluconate skin preparation (ChloraPrep, figuration is placed into the quadriceps Becton, Dickinson and Company, Frank- tendon with a single limb of each pair of Figure 4. Double-loaded suture anchors in superior lin Lakes, NJ). sutures (Figure 5). The knee is placed in pole of patella.

Table 2. Timeline of cases Ruptured Final outcome Patient Earliest recorded BMI tendons 1 41.73 kg/m2 on 9/26/2005 2/05/2016 Patient able to achieve full knee extension with 5/5 quadriceps tendon strength and had a VAS score of 2/10 (consistent with his baseline knee arthritis) 2 35.63 kg/m2 on 2/22/2015 12/11/2017 Patient reported a VAS pain scale of 0/10. He was able to perform the straight leg raise test 3 35.37 kg/m2 on 10/06/2011 4/01/2017 Patient reported a VAS pain scale of 1/10 and was back to working his full-time job BMI = body mass index; VAS = Visual Analog Scale. Figure 5. Krackow suture configuration.

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A bilateral rupture of the quadriceps Age BMI tendon is rare. There have been fewer than 100 reported cases of simultaneous bilateral quadriceps tendon ruptures in Study population the US since 1949.8 Because of the rare occurrence of this injury, the initial diag- 9 nosis can be difficult for some physicians. Patient 1 A missed diagnosis is not uncommon and can lead to delays in patient care. A thorough history and physical examina- Age and BMI and Age Patient 2 tion, understanding of the mechanism of injury, knowledge of potential pre- disposing conditions, and imaging are Patient 3 critical tools to help make an accurate and timely diagnosis.10-12 Some diagnostic indicators of bilateral quadriceps tendon 0 10 20 30 40 50 60 70 rupture include an inability to perform 2 the straight leg raise test, palpation of a Figure 6. Comparison of age (years) and body mass index (BMI, kg/m ) of a study of 210 patients with quadriceps tendon rupture by Garner et al2 versus patients in this case report. gap superior to the patella, and a limping or antalgic gait. The literature on tendinopathies sug- 18 gests multiple factors that increase the degrade tendon extracellular matrix. The suture anchor-based construct had risk of injury to the tendon. These factors, This tendon damage is often irreversible statistically significantly less gap forma-

whether they be intrinsic or extrinsic, and predisposes tendons in obese indi- tion at all forces tested in their study. are split into a mechanical theory and viduals to rupture. Clinically, we have noted less incidence 6 a vascular theory, signifying that they Neubauer et al noted a link between of extensor lag in patients with quadri- either effect the load or the perfusion of obesity and quadriceps tendon ruptures. ceps tendon tears treated with a suture the tendon, putting it at risk of injury. In their study, 28 patients sustained bilat- anchor-based repair as opposed to the Some of these factors include repetitive eral quadriceps tendon ruptures, and the transosseous approach. Although we loading, excessive force, systemic diseases most frequently documented risk factor have not formally compared both surgical (ie, diabetes mellitus, systemic lupus ery- was obesity, with 6 (21.4%) of the patients techniques, we performed a transosseous thematosus, renal failure, gout, thyroid being classified as obese. This finding is technique for 5 years, and we observed disorders), and infection.13 in agreement with what we have noted more patients having an extensor lag 6 Obesity has been linked to tendinopa- in our practice. In a review by Garner et weeks postoperatively with the transosse- 2 thies.14 Tendon overload combined with al, 210 patients with a quadriceps tendon ous technique (unpublished data). Other repetitive use can damage tendons. Ten- rupture had an average BMI of 30.0 kg/ noted benefits of a suture anchor-based 2 2 don damage is described through a con- m (standard deviation = 6.05 kg/m ). approach include higher load to fail - tinuum in which the damage progresses Findings of our case series are in line ure, reduced operative time, improved from reactive tendinopathy to tendon dis- with the results of that study supporting cosmesis, earlier initiation of range of repair and ultimately to degenerative ten- the association between obesity and risk motion and weight bearing, and less risk dinopathy. Once a tendon reaches the last of quadriceps tendon ruptures (Figure 6). of penetration to the patellar articular 16,22-24 stage of this continuum, cell death ensues, Quadriceps tendon repairs have his- cartilage. which puts the tendon at increased risk of torically been performed through a There are some contraindications as rupture.15 Individuals with obesity tend transosseous approach. This is tradition- well as theoretical risks and complica- to have an increase in adipocytes, which ally done by drilling 3 transosseous holes tions with the use of our surgical ap - leads to a pro-inflammatory tendon en- through the patella, suturing the torn proach. Some of the contraindications vironment. As adipocytes experience this tendon in a modified Krackow fashion, are as follows: Previous patellar fracture, inflammation, there is an increase in cell passing the sutures through each hole, previous knee replacement, and current hypoxia, adipocyte cell death, and leptin and tying the sutures over the inferior infection. One surgical complication may 19 production. These factors encourage pole of the patella. New techniques have occur while the surgeon is penetrating the recruitment of macrophages, which been described to repair the quadriceps the cartilage; at that time, there is a theo- secrete molecules such as interleukin 6 tendon, including a suture anchor-based retical threat of penetrating the patellar 20,21 and tumor necrosis factor-α, thus pro- repair, the technique we chose to use. tendon, causing further injury. Another moting a proinflammatory state.16,17 The In a biomechanics cadaver study by theoretical complication, fracturing of 20 release of these cytokines triggers matrix Sherman et al, the suture anchor-based the patella, is possible in a patient with metalloproteases, which work to further repair of the quadriceps tendon was com- inadequate bone stock or osteoporosis. pared with the transosseous technique. In our patients there were no issues with

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Available from: www.physio-pedia.com/index. 14. Castro A, Skare TL, Nassif PAN, Sakuma AK, bone stock, and the tendon was easily php?title=Tendon_Pathophysiology&oldid=164409 Barros WH. Tendinopathy and obesity. Arq Bras reduced to the patella. 4. Surmi BK, Hasty AH. Macrophage infiltration Cir Dig 2016;29(Suppl 1):107-10. DOI: https:// into adipose tissue: Initiation, propagation and doi.org/10.1590/0102-6720201600S10026 CONCLUSION remodeling. Future Lipidol 2008;3(5):545-56. PMID:27683789 DOI: https://doi.org/10.2217/17460875.3.5.545 15. Cook JL, Rio E, Purdam CR, Docking SI. Revisiting Bilateral quadriceps tendon ruptures are PMID:18978945 the continuum model of tendon pathology: What is disabling injuries that are detrimental to 5. Abduljabbar FH, Aljurayyan A, Ghalimah B, its merit in clinical practice and research? Br J Sports Lincoln L. Bilateral simultaneous quadriceps Med 2016 Oct;50(19):1187-91. DOI: https://doi. the knee extensor mechanism. 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Knee Surg Philadelphia, PA: Saunders Elsevier; 2015 we have found that a suture anchor-based Sports Traumatol Arthrosc 2007 Jan 15;15(1):43- 18. Del Buono A, Oliva F, Osti L, Maffulli N. construct allows for a secure repair, early 53. DOI: https://doi.org/10.1007/s00167-006-0133-7 Metalloproteases and tendinopathy. Muscles initiation of physical therapy, and a noted PMID:16951978 Ligaments Tendons J 2013 May 21;3(1):51-7. v 7. Rehabilitation guidelines for patellar tendon and DOI: https://doi.org/10.32098/mltj.01.2013.08 improvement in the VAS pain scores. quadriceps tendon repair [Internet]. Madison, WI: PMID:23885345 University of Wisconsin Health Sports Medicine; 19. Plesser S, Keilani M, Vekszler G, et al. Clinical Disclosure Statement updated 2018 Feb [cited 2018 Jun 18]. Available outcomes after treatment of quadriceps tendon The author(s) have no conflicts of interest to from: www.uwhealth.org/files/uwhealth/docs/pdf6/ ruptures show equal results independent of suture disclose. SM_pat_tendon_quad.pdf anchor or transosseus repair technique used - A 8. Neubauer T. Re: Simultaneous and spontaneous pilot study. PLoS One 2018 Mar 19;13(3):e0194376. bilateral quadriceps tendons rupture. Am J Phys DOI: https://doi.org/10.1371/journal.pone.0194376 Acknowledgments Med Rehabil 2014 Jan;93(1):97-8. DOI: https:// PMID:29554109 Kathleen Louden, ELS, of Louden Health doi.org/10.1097/PHM.0b013e318296e2d7 20. Sherman SL, Copeland ME, Milles JL, Flood DA, Communications performed a primary substantive PMID:23739272 Pfeiffer FM. Biomechanical evaluation of suture edit. 9. Kelly BM, Rao N, Louis SS, Kostes BT, Smith RM. anchor versus transosseous tunnel quadriceps Bilateral, simultaneous, spontaneous rupture of tendon repair techniques. Arthroscopy 2016 quadriceps tendons without trauma in an obese Jun;32(6):1117-24. DOI: https://doi.org/10.1016/j. How to Cite this Article patient: A case report. Arch Phys Med Rehabil arthro.2015.11.038 PMID:26895785 Tucker JE, Jones CR. Bilateral quadriceps tendon 2001 Mar;82(3):415-8. DOI: https://doi.org/10.1053/ 21. Bushnell BD, Byram IR, Weinhold PS, Creighton RA. repair with suture anchors: Case series. Perm apmr.2001.19784 PMID:11245767 The use of suture anchors in repair of the ruptured J 2020;24:19.098. DOI: https:doi.org/10.7812/ 10. Ellanti P, Davarinos N, Morris S, Rice J. Bilateral patellar tendon: A biomechanical study. Am J Sports synchronous rupture of the quadriceps tendon. Ir J Med 2006 Sep;34(9):1492-9. DOI: https://doi. TPP/19.098 Med Sci 2012 Sep;181(3):423-5. DOI: https://doi. org/10.1177/0363546506287489 PMID:16685096 org/10.1007/s11845-010-0596-x PMID:20882362 22. Amini MH. Quadriceps tendon repair using knotless 11. Assiotis A, Pengas I, Vemulapalli K. Bilateral anchors and suture tape. Arthrosc Tech 2017 Sep References quadriceps tendon rupture in a seasoned marathon 11;6(5):e1541-5. DOI: https://doi.org/10.1016/j. 1. Tuong B, White J, Louis L, Cairns R, Andrews G, runner with patellar spurs. Grand Rounds eats.2017.06.013 PMID:29354471 Forster BB. Get a kick out of this: The spectrum of 2011;11(1):77-80. DOI: https://doi.org/10.1102/1470- 23. Richards DP, Barber FA. Repair of quadriceps tendon knee extensor mechanism injuries. Br J Sports Med 5206.2011.0020 ruptures using suture anchors. Arthroscopy 2002 2011 Feb;45(2):140-6. DOI: https://doi.org/10.1136/ 12. Keogh P, Shanker S, Burke T, and O’Connell May-Jun;18(5):556-9. DOI: https://doi.org/10.1053/ bjsm.2010.076695 PMID:20966035 R. Bilateral simultaneous rupture of the jars.2002.30729 PMID:11987071 2. Garner MR, Gausden E, Berkes MB, Nguyen JT, quadriceps tendons. Clin Orthop Relat Res 1988 24. Maniscalco P, Bertone C, Rivera F, Bocchi L. A new Lorich DG. Extensor mechanism injuries of the knee: Sep;(234):139-41. DOI: https://doi.org/10.1097/ method of repair for quadriceps tendon ruptures. A Demographic characteristics and comorbidities from PHM.0b013e318296e2d7 PMID:3044659 case report. 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ABSTRACT A B Introduction: Cocaine is known to cause necrosis of the soft tissues secondary to its vasoconstrictive effects, which has negative functional and cosmetic outcomes of the midface and adjacent structures. To our knowledge, cleft lip caused by cocaine use has not been described in the literature. Case Presentation: A 52-year-old man presented with a deformity of the lip and nasal sill, septal perforation, and hard Figure 1. A. Frontal view of cleft lip-appearing defect with erosion of gingiva and palate fistula secondary to long-term cocaine use. The patient ptotic nasal tip seen during preoperative assessment. B. Lateral view of cleft underwent lip reconstruction using a modified Millard technique lip-appearing defect with ptotic nasal tip seen during preoperative assessment. and had a lasting favorable cosmetic outcome more than 5 years after surgery. A B Discussion: We report a case of cocaine abuse causing cleft lip, and successful reconstruction with a modified Millard technique. INTRODUCTION Cocaine is known to cause necrosis of the soft tissues secondary to its vasoconstrictive effects, which has negative functional and cosmetic outcomes of the midface and adjacent structures.1 This Figure 2. A. Frontal view of hypertrophic scarring and induration seen 3 weeks necrosis can lead to nasal collapse and central midface destruction, after surgery. B. Basal view of hypertrophic scarring 3 weeks after surgery. commonly involving the nasal septum, lateral nasal wall, and/or hard palate.2-5 To our knowledge, there are no reports of acquired cleft lip from cocaine abuse. We report a case of intranasal cocaine wound healing, and the patient’s unavailability for follow-up. use causing a cleft lip deformity, and successful reconstruction After 3 years, the patient eventually was able to agree to stop with a modified Millard technique. This case was presented as using cocaine for at least 2 months. He also agreed to monthly a poster at the 2019 Triological Society Combined Sections urine testing. After a 2.5-month period of cocaine abstinence Meeting; January 24, 2019, to January 26, 2019; Coronado, CA. (the longest the patient had gone in decades), he was taken to the operating room for lip reconstruction using a modified Millard CASE PRESENTATION technique. The 9th and 10th teeth had been previously extracted Presenting Concerns at this point. The medial and lateral mucosal flaps were raised. The A 52-year-old man presented with a deformity of the lip and orbicularis muscles were separated from the skin. The incision was nose, septal perforation, and hard palate fistula secondary to carried around the left ala into the nasal floor to release the alar long-term cocaine use of 30 years. The patient had been fitted base. The inferior columella formed a thin band of tissue, which with a palatal obturator in the past with excellent phonation and was left intact. The mucosa was secured to the L-flap to close off no nasal regurgitation. He wore a surgical facemask in public on the nasolabial fistula, and the muscle was reapproximated. The a daily basis to conceal his deformity. On examination, the pa- mucosal M-flap was partially deepithelialized and approximated tient had a large cleft lip-appearing deformity that exposed the to the lateral ala for nasal sill volume. A triangular flap was inset to alveolus and nasal floor and erosion of gingiva with exposure of prevent straight-line contracture. During the procedure, notable the 9th and 10th tooth roots. Because of loss of the orbicularis fibrosis of the soft tissues with reduced vascularity was noted. muscle continuity, the patient had a classic-appearing cleft lip Eleven days postoperatively, the patient was found to have a nasal deformity. The columella was shifted to the non-cleft side, V-shaped dehiscence that measured 8 mm at the nasal sill. This and the nasal ala on the cleft side was displaced laterally and dehiscence was evaluated 10 days later and was healed in with inferiorly. There was erosion of the left nasal sill and loss of the granulation tissue (Figure 2); however, there was breakdown of anterior septum as well as a ptotic nasal tip (Figure 1). The mid- hard palate demonstrated a 1-cm fistula.

Therapeutic Intervention and Treatment Author Affiliations Although the patient was anxious to have the surgery, it was 1Department of Head and Neck Surgery, Oakland Medical Center, CA cancelled several times by multiple surgeons because of the Corresponding Author patient’s continued cocaine use, the surgeons’ concern for poor David W Chou, MD ([email protected])

Keywords: cleft lip, cocaine, facial reconstruction, hard palate fistula, Millard technique

The Permanente Journal • https://doi.org/10.7812/TPP/19.197 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 122 CLINICAL MEDICINE Surgical Reconstruction of Cocaine-Induced Cleft Lip: A Case Report

A B a strict period of drug abstinence of at least 18 months prior to pursuing surgery.4 This patient developed a chronic nasolabial fistula postoperatively, which was not repaired because of its asymptomatic nature. However, given the robust and stable state of this patient’s surgical site, safe repair is thought to be feasible in the future, although care must be taken not to devascularize the tissue. In addition, the patient’s hard palate Figure 3. At 5.5 years after surgery, stable lip and nose symmetry and mild fistula was not repaired given that it was well managed with persistent deficiency of the A. vermilion were noted, and the B. nasolabial fistula his obturator. Notably, the successful implementation of local, remained stable and largely asymptomatic. regional, and free flaps for hard and soft palate reconstruction has been described in the setting of cocaine-related defects. 4,5 Millard8 described the rotation-advancement repair of the unilateral cleft lip in 1955, and most surgeons today employ some variation of this technique for these repairs.9 This patient had a lasting favorable aesthetic outcome of his lip repair more

Figure 4. At 5.5 years after surgery, Relevant past medical history the nasal tip is The patient presented with a history of long-term cocaine use, improved from before long-term septal perforation and nasal damage, and of his upper lip surgery but remained separating circa 2006. ptotic. On physical examination, patient had left lip the upper lip in the gingivobuccal sulcus, forming a small naso- deformity exposing 2008 labial fistula. One month postoperatively, the surgical incisions alveolus and nasal floor, were healing well. Although the nasal sill remained deficient, the erosion of gingiva, and nasolabial fistula was mostly closed with some fibrinous exudate. nasal deformity

Follow-up and Outcomes July Patient underwent surgical 2011 repair of cleft lip The patient was seen again 8 months postoperatively and demonstrated fairly good symmetry of the upper lip. The na- 11-d post-op: V-shaped solabial fistula was still present. The previously exposed tooth dehiscence at nasal sill roots were now covered with mucosa. During the patient’s 1-year follow-up visit, he was noted to have a ptotic, though 21-d post-op: Nasal sill stable, nasal tip with a thin columellar skin band. At this time, dehiscence healing, repair of the nasolabial fistula was deferred given that the patient formation of small had minor symptoms and to avoid the risk of devascularizing nasolabial fistula the surgical bed. 1-mo post-op: Incisions At 5.5 years from the time of surgery, the patient had an healing well, nasal sill excellent cosmetic outcome, although the nasolabial fistula remained deficient, remained (Figure 3). The nasal tip remained ptotic (Figure 4) nasolabial fistula closing with a soft tissue band of columella, although this was overall improved compared to his preoperative state. A timeline of the On follow-up, the patient case appears in Figure 5. had stable lip and nose symmetry, mild persistent DISCUSSION deficiency of the vermilion 2016 border, and stable Cocaine can cause destruction of the midface structures with nasolabial fistula. The long-term intranasal use because of its vasoconstrictive effects. nasal tip remained ptotic Nasal collapse, septal perforation, and palatal erosion have been

well documented in the literature.1-7 In this case, cocaine use led not only to a palate fistula but also to a cleft lip deformity over time. To our knowledge, there are no reports of acquired Excellent cosmetic outcome but with cleft lip from cocaine abuse. persistent nasolabial fistula and ptotic nasal tip This case was challenging because of the patient’s struggles with cocaine abuse, and a longer period of abstinence would Figure 5. Timeline of the case. have been more ideal for wound healing. Some groups advocate Post-op = postoperative

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.197 123 CLINICAL MEDICINE Surgical Reconstruction of Cocaine-Induced Cleft Lip: A Case Report

References than 5 years after surgery. This case demonstrates a novel pre- 1. Deutsch HL, Millard DR. A new cocaine abuse complex. Arch Otolaryngol sentation of cocaine-induced cleft lip and viability of the modified Head Neck Surg 1989 Feb;115(2):235-7. DOI: https://doi.org/10.1001/ Millard technique in its repair. archotol.1989.01860260109024 PMID: 2914096 2. Goodger NM, Wang J, Pogrel MA. Palatal and nasal necrosis resulting from cocaine CONCLUSION misuse. Br Dent J 2005 Mar;198:333. DOI: https://doi.org/10.1038/sj.bdj.4812171 PMID:15789087 Although surgical reconstruction of acquired cocaine-induced 3. Millard DR, Mejia FA. Reconstruction of the nose damaged by cocaine. Plast Reconstr Surg 2001 Feb;107(2):419. DOI: https://doi.org/10.1097/00006534- midface defects have been described in the literature, we are the 200102000-00018 PMID:11214057 first, to our knowledge, to report a case of cocaine-induced cleft 4. Colletti G, Autelitano L, Chiapasco M, et al. Comprehensive surgical management lip and demonstrate viable reconstruction with a modified Mil- of cocaine-induced midline destructive lesions. J Oral Maxillofac Surg 2014 v Jul;72(7):1395.e1-10. DOI: https://doi.org/10.1016/j.joms.2014.03.013 PMID: lard technique. 24947965 5. Colletti G, Allevi F, Valassina D, Bertossi D, Biglioli F. Repair of cocaine-related Disclosure Statement oronasal fistula with forearm radial free flap. J Craniofac Surg 2013 Sep;24(5):1734- The author(s) have no conflicts of interest to disclose. 38. DOI: https://doi.org/10.1097/SCS.0b013e3182a2355a PMID:24036767 6. Tend E, Steinbacher DM. Repair of the cocaine-induced cleft palate using the Acknowledgments modified double-opposing z-plasty. Cleft Palate Craniofac J 2013 Jul;50(4):494-7. DOI: https://doi.org/10.1597/11-178 PMID: 22264171 Laura King, ELS, performed a primary copy edit. 7. Brusati R, Carota F, Mortini P, Chiapasco M, Biglioli F. A peculiar case of midface reconstruction with four free flaps in a cocaine-addicted patient. J Plast Reconstr How to Cite this Article Aesthet Surg 2009 Feb;62(2):e33-40. DOI: https://doi.org/10.1016/j.bjps.2007.10.037 Chou DW, Shih C. Surgical reconstruction of cocaine-induced cleft lip: A case PMID:18165165 report. Perm J 2020;24:19.197. DOI: https://doi.org/10.7812/19.197 8. Millard R. A radical rotation in single harelip. Am J Surg 1958 Feb;95(2):318-22. DOI: https://doi.org/10.1016/0002-9610(58)90525-7 PMID:13487963 9. Weinfeld AB, Hollier LH, Spira M, Stal S. International trends in the treatment of cleft lip and palate. Clin Plast Surg 2005 Jan;32(1):19-23. DOI: https://doi.org/10.1016/j. cps.2004.08.002 PMID:15636761

The Permanente Journal • https://doi.org/10.7812/TPP/19.197 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 124 IMAGE DIAGNOSIS Roth’s Spots, a clinical diagnostic clue for Infective Endocarditis Navneet Arora MD1; Deba Prasad Dhibar MD2; Byanjana Bashyal MBBS3; Aniruddha Agarwal MS4 Perm J 2020;24:20.038 E-pub: 08/05/2020 https://doi.org/10.7812/TPP/20.038

A 24-year male was admitted to the emergency ward with a initiates the coagulation cascade leading to platelet fibrin throm- history of high-grade fever (103⁰ F) with fatigue and palpitations bus formation. They represent a non-suppurative or immunologi- for 3 months. He had a significant history of congenital heart cal phenomenon in infective endocarditis and usually occur in disease in the form of a ventricular septal defect. He had no his- less than 5% of the cases. Roth’s spots are not pathognomonic for tory of alcohol consumption or intravenous drug abuse. Cardiac infective endocarditis but are suggestive of the diagnosis. Roth’s auscultation revealed a harsh holosystolic murmur of grade 3 spots are the morphological manifestation of retinal capillary intensity over the entire precordium. The fundus examination rupture and may be found in leukemias, severe anemia, anoxia, revealed multiple pale-centered retinal hemorrhages sugges- carbon monoxide poisoning, disseminated intravascular coagula- 3v tive of Roth’s spots (Figure 1A and 1B). On transesophageal tion, hypertension or diabetic retinopathy, and pre-eclampsia. echocardiography, mobile vegetation (8x4 mm) was seen on the aortic valve. Multiple sets of blood cultures were however sterile. NOTE: Because of size, both images are on next page In the presence of a predisposing cardiac risk factor, high-grade fever, the immunological phenomenon of Roth’s spots, and aortic Author Contribution Dr. Navneet Arora: Manuscript writing and patient management valve vegetation a diagnosis of infective endocarditis was made. Dr. Deba Prasad Dibhar: Manuscript supervision and patient management The patient was treated with intravenous antibiotics (ceftriaxone, Dr. Byanjana Bashyal: Fundus Photography vancomycin, and gentamycin) for infective endocarditis for 6 Dr. Aniruddha Aggarwal: Photo legends weeks and improved subsequently. The patient was discharged after the full course of antibiotics and is on outpatient follow up. References Roth’s spots were described by Mortiz Roth in patients with 1. Roth M. Uber netzhautuffecstionen bei wundfiebrin. [Retinal manifestations of wound subacute bacterial endocarditis.1 They are round, oval, or flame- fever.] Deutsch A Chir 1872;1:471-84. 2 2. Von Barsewisch B. Perinatal retinal haemorrhages. New York: Springer-Verlag, 1979; shaped hemorrhages with a white spot in their center. The white pp 51-2. center represents a fibrin thrombus at the site of vessel rupture. 3. Dhibar DP, Sahu KK, Jinagal J, et al. Roth’s spot in megaloblastic anaemia Rupture of retinal capillaries causes extrusion of whole blood that Postgraduate Medical Journal 2018;94:66. leads to platelet adhesion to the damaged endothelium which

Author Affiliations 1 Senior Resident, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 2 Assistant Professor, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 3 MS Resident, Department of Ophthalmology, Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh 4 Assistant Professor, Department of Ophthalmology, Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh

Corresponding Author Dr. Deba Prasad Dhibar ([email protected])

Keywords: Roth’s Spots, Infective Endocarditis

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A

Figure 1A: The fundus photograph of the right eye of the patient shows the presence of a large (1/4th disc diameter) sized yellowish subretinal lesion suggestive of altered hemorrhage/exudate and two small white-centered retinal hemorrhages along the superotemporal arcade. There is a mild blurring of disc margins and superotemporal peripapillary retinal hemorrhage.

B

Figure 1B: The fundus autofluorescence image shows areas of blocked signal due to the overlying retinal hemorrhages.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.038 126 IMAGE DIAGNOSIS Image Diagnosis: Eccentric Target Sign of Focal Toxoplasma Encephalitis

Samman Verma, MBBS1; Vidhi Singla, MD1; Aditya Singh, MBBS1; Arghadip Bose, MBBS1; Ashok Kumar Pannu, MD1 Perm J 2020;24:19.181 E-pub: 04/22/2020 https://doi.org/10.7812/TPP/19.181 CASE PRESENTATION A 60-year-old woman was admitted to the hospital because of low-grade fever and altered mental status of 1-month duration. The altered sensorium was gradual in onset, in the form of confusion, decreased verbal output, and progressively worsening level of consciousness. She recently had been repeating the words said to her and was not responding to the family members. At pre- sentation, she was drowsy and disoriented. The score on the Glasgow Coma Scale (GCS) was 8 of 15 (eye opening response = 2 points, verbal response = 1 point, motor Figure 1A. Noncontrast-enhanced computed tomography scan of the brain shows large areas of hypoden- response = 5 points [E2V1M5]). Findings sity in bilateral basal ganglia with adjacent areas of cerebral edema (arrow). Magnetic resonance images of the neurologic examination did not re- of the brain after administration of gadolinium-based contrast agent. Figure 1B. T1-weighted image shows veal neck rigidity, Kernig’s sign, or cranial rim-enhancing lesion with an eccentric nodule in bilateral basal ganglia (arrow), suggestive of the “eccentric nerve palsy. The patient was moving all 4 target sign.” Figure 1C. T2-weighted image shows alternating hyperintense and hypointense areas (arrow) limbs equally and against gravity (ie, motor with marked perilesional edema power of the limbs was at least 3 of 5 on the Medical Research Council scale). Deep tendon reflexes were normal and symmetri- lymphocytes); protein, 156 mg/dL; and glu- or focal encephalitis in patients with HIV cal, and the bilateral plantar response was cose, 49 mg/dL (CSF/blood glucose ratio or AIDS. The most common form of CNS flexor. However, a detailed examination = 0.36). Cultures of blood and CSF were toxoplasmosis is cerebral abscess or focal of the motor system, sensory system, and sterile. Testing of the CSF by the nucleic- toxoplasmosis encephalitis, and these pa- gait could not be performed because of acid amplification test for Mycobacterium tients usually present with fever, headache, her altered mental status. Papilledema and tuberculosis and for cryptococcal antigen focal neurologic deficits, seizures, and al- features of retinitis were absent on fundus were negative. tered mental status. The onset is typically examination. Because the radiologic finding of “ec- subacute, and the symptoms gradually With a clinical possibility of a central centric target” led to a suspicion of toxo- evolve and progress over several weeks. nervous system (CNS) infection, noncon- plasmosis, testing for immunoglobulin G Other rare forms of cerebral toxoplasmosis trast-enhanced computed tomography of (IgG) and IgM antibodies to Toxoplasma are diffuse encephalitis without abscess the brain was performed, and these scans gondii was performed in both blood and formation and chorioretinitis.1-4 showed large areas of hypodensity in bi- CSF. Blood samples yielded a positive result The diagnosis of cerebral toxoplasmo- lateral basal ganglia with adjacent areas of for IgG with titers of 1:80. A serologic test sis is generally suspected on the basis of cerebral edema (Figure 1A). Subsequently, for HIV was reactive, and her CD4 count brain imaging findings of RELs. They are magnetic resonance imaging (MRI) of the was found to be 64/µL. usually multiple and occur in the basal brain after administration of a gadolinium- The patient was treated with cotrimoxa- ganglia, thalamus, or gray-white matter based contrast agent revealed T1-weighted zole (trimethoprim plus sulfamethoxazole). junction of the frontal and parietal lobes. rim-enhancing lesion (REL) with an ec- She received mechanical ventilation be- centric nodule in bilateral basal ganglia, cause of her low GCS score (8/15). She im- suggestive of the “eccentric target sign” proved gradually and was extubated. After (Figure 1B). T2-weighted images showed a 3-week hospital stay, she was discharged Author Affiliations alternating hyperintense and hypointense in a conscious state with a GCS score of 1 Department of Internal Medicine, Post Graduate Institute of Medical areas (Figure 1C) with marked perile- 12/15 (E3V3M6). Education and Research, Chandigarh, India. sional edema. A guided lumbar puncture DISCUSSION Corresponding Author was performed for cerebrospinal fluid Ashok Kumar Pannu, MD ([email protected]) (CSF) analysis, which showed the follow- T. gondii is the most frequent opportu- ing values: white blood cells, 30/µL (70% nistic infection causing focal brain lesions Keywords: Cerebral toxoplasmosis, eccentric target sign, focal toxoplasma encephalitis, HIV

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5. Akgoz A, Mukundan S, Lee TC. Imaging of rickettsial, The other differentials of RELs in patients newly diagnosed HIV were aged 60 years spirochetal, and parasitic infections. Neuroimaging with HIV are primary CNS lymphoma or above and were more likely to have a Clin N Am. 2012;22(4):633-657. and, less commonly, tuberculoma and late-stage diagnosis than their younger 6. Ramsay R, Gerenia GK. CNS complications of AIDS: 5-7 10 CT and MRI findings. Am J Radiol. 1988; 151:449- fungal or bacterial abscess. Nuclear counterparts. In the older age group, a 454. imaging such as thallous chloride TI 201 history of risk factors for HIV, including 7. Kumar GG, Mahadevan A, Guruprasad AS, et al. (Thallium-201) single-photon emission a sexual history, is not always forthcom- Eccentric target sign in cerebral toxoplasmosis: 11 neuropathological correlate to the imaging feature. computed tomography of the brain and ing. Our case highlights that recogni- J Magn Reson Imaging 2010;31(6):1469-72. DOI: 18F-2-fluoro-2-deoxy-D-glucose posi- tion of an AIDS-defining illness through https://doi.org/10.1002/jmri.22192 tron emission tomography may be used characteristic clinical or radiologic features 8. Vidal JE. HIV-related cerebral toxoplasmosis revisited: Current concepts and controversies of to differentiate toxoplasmosis from CNS (eg, eccentric target sign of cerebral toxo- an old disease. J Int Assoc Provid AIDS Care. lymphoma, because the former lesions are plasmosis) is crucial regardless of the age 2019;18:2325958219867315. 5 v not hypermetabolic. The definitive diag- of the patient. 9. Colombo FA, Vidal JE, Penalva de Oliveira AC, Hernandez AV, Bonasser-Filho F, Nogueira RS, et al. nosis requires a stereotactic brain biopsy. Disclosure Statement Diagnosis of cerebral toxoplasmosis in AIDS patients Because of the associated high morbidity in Brazil: Importance of molecular and immunological The author has no conflicts of interest to disclose. with the procedure, it is usually reserved methods using peripheral blood samples. J Clin Microbiol. 2005;43(10):5044-5047. for 2 conditions: 1) failure of empiric Acknowledgments 10. Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. therapy for toxoplasmosis in patients with Kathleen Louden, ELS, of Louden Health positive serologic findings forT. gondii and Diagnoses of HIV infection in the United States and Communications performed a primary copyedit. dependent areas, 2017 [Internet]. In: HIV surveillance 2) seronegative patients. report 2017. Vol 29. Atlanta, GA: Centers for Disease An IgG serologic test is positive in Author Contributions Control and Prevention; 2018 Nov [cited 2019 Mar 31]. Available from: https://www.cdc.gov/hiv/pdf/ more than 90% of patients with CNS Samman Verma, MBBS, participated in library/reports/surveillance/cdc-hiv-surveillance- toxoplasmosis, but only in less than 60% the patient management, collected patient report-2017-vol-29.pdf. in HIV-infected patients without this data, and drafted and revised the manuscript. 11. Ben-Chetrit E, Shavit L, Tvito A, Korem M, Bnaya Vidhi Singla, MD, participated in the patient A. The devil is in the details. N Engl J Med. condition. The likelihood of a REL due 2019;380(6):581-586. to toxoplasmosis is less than 10% with management, collected patient data, and helped draft the manuscript. Aditya Singh, MBBS, and negative IgG serologic findings. The di- Arghadip Bose, MBBS, participated in the patient agnosis of probable cerebral toxoplasmosis management and collected patient data. Ashok needs the presence of IgG antibodies and Kumar Pannu, MD, participated in the patient compatible imaging features in the typi- management, collected patient data, and drafted cal clinical syndrome.8 The IgG antibody and revised the manuscript. All authors have given found in toxoplasmosis is the high-avidity final approval to the manuscript. type, suggesting that the immune response How to Cite this Article is secondary to the reactivation of a latent 9 Verma S, Singla V, Singh A, Bose A, Pannu AK. infection. Therefore, IgG elevation is typi- Image diagnosis: Eccentric Target Sign of Focal cal in CNS toxoplasmosis, whereas IgM Toxoplasma Encephalitis. Perm J 2020;24:19.181. antibodies are usually absent, as in our DOI: https://doi.org/10.7812/TPP/19.181 case.1-3 The limitation of this case study is that a definite diagnosis with histopatho- References logic analysis or polymerase chain reaction 1. Bowen LN, Smith B, Reich D, Quezado M, Nath testing was not established. These tests A. HIV-associated opportunistic CNS infections: Pathophysiology, diagnosis and treatment. Nat Rev were omitted given the adequate clinical Neurol 2016;12(11):662-674. response to antitoxoplasmosis therapy. 2. Panel on Opportunistic Infections in HIV-Infected The eccentric target sign is described as Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV- an REL with an eccentric nodule along the infected adults and adolescents: Recommendations wall on a brain MRI (T1 weighted with from the Centers for Disease Control and Prevention, gadolinium enhancement). It represents a the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases necrotizing abscess, and the small eccentric Society of America. Bethesda, MD: National Institutes nodule possibly results from concentrically of Health; updated 2018 May 29 [cited 2019 Nov 16]. Available from: http://aidsinfo.nih.gov/contentfiles/ thickened blood vessels traversing the ab- lvguidelines/adult_oi.pdf. scess. This radiologic finding is considered 3. Jameson JL, Kasper DL, Longo DL, Fauci AS, to be suggestive of cerebral toxoplasmosis Hauser SL, Loscalzo J, eds. Harrison’s principles of with 95% specificity but is seen in only up internal medicine. 19th ed. New York, NY: McGraw- 5-7 Hill Education; 2018:1612-14. to one-fourth of the cases. 4. Porter SB, Sande MA. Toxoplasmosis of the central The Centers for Disease Control and nervous system in the acquired immunodeficiency Prevention, in its 2017 HIV Surveillance syndrome. N Engl J Med. 1992;327(23):1643-8. Report, stated that 6.2% of patients with

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.181 128 CLINICAL MEDICINE Image Diagnosis: Takotsubo Cardiomyopathy Mimicking an Acute ST Elevation Myocardial Infarction in the Setting of Anti-Depressant Therapy Withdrawal

Suha Na Javeed1; Seema Pursnani, MD, MPH2 Perm J 2020;24:19.095 E-pub: 04/03/2020 https://doi.org/10.7812/TPP/19.095

CASE PRESENTATION A 77-year-old woman with a history of bipolar disorder, hyper- tension, hyperlipidemia, and previous tobacco use presented to the Emergency Department (ED) with acute shortness of breath and diaphoresis. The patient was initially anxious and tearful upon presentation to the ED. While she denied acute emotional or social stressors, she did note abruptly stopping her venlafaxine (brand name Effexor) approximately 3 weeks before. Results of an initial electrocardiogram (ECG) showed an ectopic atrial rhythm Figure 2. Apical 4-chamber view echocardiogram from same patient demonstrating classic with marked diffuse ST-segment elevation most prominent in the apical takotsubo cardiomyopathy apical wall-motion abnormality at (A) end-diastole and anterolateral leads (Figure 1). Results of bedside echocardiogra- (B) end-systole. phy demonstrated a large territory of hypokinesis involving all apical segments with hypercontractile basal segments (Figure 2). angiography for a suspected acute coronary syndrome.1-3 The Emergent invasive coronary angiography was performed, which precise pathophysiology of TCM remains unclear, but current demonstrated no obstructive coronary artery disease. Initial tro- evidence suggests stimulation of the sympathetic nervous sys- ponin I level was 1.26 ng/mL (normal < 0.04 ng/mL). Results of a tem, resulting in increased levels of circulating and myocardial subsequent ECG obtained at 4-week follow-up illustrated resolu- catecholamines. This in turn causes direct myocardial toxicity tion of previously seen ST elevations, now with anterolateral T-wave and microvascular dysfunction or spasm, thereby leading to inversions (Figure 3). Results of repeat echocardiography at 4-week myocardial ischemia.4 Clinically, TCM requires the exclusion follow-up demonstrated normalization of left ventricular systolic of obstructive epicardial coronary artery disease, typically by function and no segmental wall-motion abnormalities. invasive coronary angiography. However, it may be difficult to distinguish TCM from a traditional myocardial infarction DISCUSSION caused by thrombotic arterial occlusion with recanalization or Takotsubo cardiomyopathy (TCM), also known as stress- transient epicardial coronary artery disease spasm. Indeed, these induced cardiomyopathy or broken-heart syndrome, is an pathophysiologic phenomena may be part of the same clini- increasingly recognized cardiac diagnosis, characterized by cal spectrum. In cases where TCM is not labeled as a clinical transient left ventricular systolic dysfunction in the setting of an diagnosis, it is likely that it is also masked into the broad cat- emotional or physical stressor and diagnosed more commonly egory of MINOCA (myocardial infarction with no obstructive in postmenopausal women. TCM is thought to occur in ap- coronary artery disease). proximately 1% to 2% of patients undergoing invasive coronary ECG findings in an acute ST elevation myocardial infarc- tion (STEMI) may overlap with ECG findings in TCM, as was seen in this case. Typical ECG changes include ST-segment depressions; ST-segment elevations, more likely in the precor- dial leads and without reciprocal changes; T-wave inversions; and QT-interval prolongation. A ratio of ST elevation in leads

V4-V6 to those in leads V1-V3 greater than or equal to 1 showed a specificity of 80%, a sensitivity of 77%, and an accuracy of 76% for diagnosis of TCM, as compared with a STEMI. 5 The

Author Affiliations 1 CUNY School of Medicine, New York, NY 2 Kaiser Permanente; Santa Clara, CA Figure 1. Initial 12-lead electrocardiogram demonstrating an ectopic atrial rhythm and near diffuse marked ST elevations. Corresponding Author Suha Na Javeed ([email protected])

Keywords: cardiomyopathy, electrocardiogram, emergency medicine, takotsubo cardiomyopathy (TCM), ST elevation myocardial infarction (STEMI)

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patient was on a serotonin-norepinephrine reuptake inhibitor (SNRI), a medication that increases the levels of serotonin and norepinephrine in the brain, and she had abruptly discontin- ued the medication. The correlation between TCM and SNRI therapeutic use or overdose has been suggested previously in a case series of 6 patients.10 Certainly, SNRI withdrawal and/or the uncontrolled mood disorder itself are plausible explanations for this patient’s cardiac event. Patients with depression tend to exhibit unusually high levels of norepinephrine in response to an emotional stressor.11 We recommend that comprehensive chart review and history-taking relevant to mood disorders, as Figure 3. Repeat 12-lead electrocardiogram from same patient obtained well as psychotropic medication use and/or discontinuation, approximately 4 weeks later demonstrating resolution of previously seen ST should be a routine part in the evaluation of a patient with v elevations, and anterolateral T-wave inversions suspected TCM.

Disclosure Statement combined ratio of ST elevation in the aforementioned leads and The author(s) have no conflicts of interest to disclose. the absence of reciprocal changes had a sensitivity of 100% How to Cite this Article and an overall accuracy of 91% in the diagnosis of TCM, as 5 Na Javeed S, Pursnani S. Image diagnosis: Takotsubo cardiomyopathy compared with STEMI. In addition, the time course of ECG mimicking an acute ST elevation myocardial infarction in the setting of changes in TCM compared to that seen in an acute STEMI anti-depressant therapy withdrawal. Perm J 2020;24:10.095. DOI: https:doi. varies, with deeper T-wave inversions at 3 days or later often org/10.7812/TPP/19.095 noted in TCM.6 Echocardiography may aid in the diagnosis of a classic TCM References pattern of apical ballooning with hypercontractile basal left 1. Ghadri JR, Wittstein IS, Prasad A, et al. International expert consensus document ventricular contraction, but can be difficult to distinguish from on takotsubo syndrome (part I): Clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 2018 Jun 7;39(22):2032-46. DOI: https://doi. a left anterior descending territory infarction. Midventricular org/10.1093/eurheartj/ehy076 PMID:29850871 and basal hypokinesis or focal wall-motion abnormality types 2. Akashi YJ, Nef HM, Lyon AR. Epidemiology and pathophysiology of Takotsubo have also been described, making a definitive diagnosis of TCM syndrome. Nat Rev Cardiol 2015 Jul;12(7):387-97. DOI: https://doi.org/10.1038/ nrcardio.2015.39. PMID:25855605 by echocardiogram, in isolation, limited. 3. Redfors B, Vedad R, Angerås O, et al. Mortality in takotsubo syndrome is similar to Most cases of TCM have a favorable prognosis, with reso- mortality in myocardial infarction - A report from the SWEDEHEART registry. Int J lution of left ventricular dysfunction in 1 to 4 weeks with Cardiol 2015 Apr 15;185:282-9. DOI: https://doi.org/10.1016/j.ijcard.2015.03.162. PMID:25818540 concomitant medical therapy for systolic heart failure with 4. Pelliccia F, Kaski JC, Crea F, Camici PG. Pathophysiology of takotsubo syndrome. beta blockers and angiotensin-converting enzyme inhibitors/ Circulation 2017 Jun 13;135(24):2426-41. Available from: DOI: https://doi. angiotensin receptor-blocking agents. This medical regimen is org/10.1161/CIRCULATIONAHA.116.027121 PMID:28606950 associated with a reduced recurrence rate of TCM, although 5. Ogura R, Hiasa Y, Takahashi T, et al. Specific findings of the standard 12-lead 7,8 ECG in patients with ‘Takotsubo’ cardiomyopathy: Comparison with the findings of evidence is limited. Treatment of comorbid illnesses and acute anterior myocardial infarction. Circ J 2003 Aug;67(8):687-90. DOI: https://doi. addressing emotional stressors are hypothesized to be key to org/10.1253/circj.67.687 PMID:12890911 6. Kurisu S, Inoue I, Kawagoe T, et al. Time course of electrocardiographic changes in recovery. Data from the International Takotsubo Registry iden- patients with tako-tsubo syndrome: Comparison with acute myocardial infarction with tify the presence of an acute neurologic or psychiatric illness, a minimal enzymatic release. Circ J 2004 Jan;68(1):77-81. DOI: https://doi.org/10.1253/ physical versus an emotional trigger, high troponin levels, and circj.68.77 PMID:14695470 low left ventricular ejection fraction as predictors for severe 7. Watanabe M, Izumo M, Akashi YJ. Novel understanding of Takotsubo syndrome. 9 Int Heart J 2018 Mar 30;59(2):250-5. DOI: https://doi.org/10.1536/ihj.17-586 complications, including stroke and death. PMID:29503405 Classically, the diagnosis of TCM can be made with diag- 8. Brunetti ND, Santoro F, De Gennaro Luisa, et al. Combined therapy with beta- blockers and ACE-inhibitors/angiotensin receptor blockers and recurrence of nostic cardiac imaging, in the setting of a clear precipitating Takotsubo (stress) cardiomyopathy: A meta-regression study. Int J Cardiol 2017 emotional, physical, or social stressor. While this case could Mar 1;230:281-3. DOI: 10.1016/j.ijcard.2016.12.124 have been precipitated by decompensation of the patient’s mood 9. Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med 2015 Sep 3;373(10):929-38. DOI: https://doi. disorder, it additionally raises the question of a potential cor- org/10.1056/NEJMoa1406761 PMID:26332547 relation between biochemical withdrawal from antidepressant 10. Neil CJ, Chong CR, Nguyen TH, Horowitz JD. Occurrence of Tako-Tsubo therapy and TCM. As catecholamine excess is the dominant cardiomyopathy in association with ingestion of serotonin/noradrenaline reuptake inhibitors. Heart Lung Circ 2012 Apr;21(4):203-5. DOI: https://doi.org/10.1016/j. mechanism underlying TCM, drug-induced catecholamine hlc.2011.12.004. PMID:22285074 excess with antidepressant and anti-psychotic medications 11. Ziegelstein RC. Depression and tako-tsubo cardiomyopathy. Am J Cardiol 2010 Jan could provide a similar mechanistic basis. In this case, the 15;105(2):281-2. DOI: https://doi.org/10.1016/j.amjcard.2009.09.002 PMID:20102933

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.095 130 IMAGE DIAGNOSIS Neodymium Magnetic Bead Ingestion in a Toddler Kenneth J. Hui1; Vignesh A. Arasu2,3, MD; David R. Vinson2,4,5, MD; Dale M. Cotton2,6, MD Perm J 2020;24:19.165 E-pub: 04/16/2020 https://doi.org/10.7812/TPP/19.165

CASE PRESENTATION A An 18-month-old girl presented to the Emergency Depart- ment with 36 hours of nonbloody, nonbilious emesis. She last had a bowel movement 2 days earlier, and it was normal. She had been intermittently placing her hands on her abdomen as if in pain. She had no fevers. The parents said that until this time she had been generally well without sick contacts or prior similar episodes. The physical examination findings demonstrated an alert and nontoxic appearing child with a distended abdomen and diffuse mild tenderness to abdominal palpation. The remaining physical examination findings were unremarkable. The results of her blood- work and urine analysis testing were unrevealing. An abdominal radiograph (Figure 1, A) revealed 4 4.3mm adjacent radiopaque foreign bodies (FBs) in the midabdomen with associated early or partial small-bowel obstruction. Retrospectively, her parents reported no awareness of an FB ingestion. The patient underwent an uncomplicated laparotomy with lysis of adhesions and bowel repair at 3 sites of presumed perforation, as well as removal of the 4 contiguous FBs (Figure 1, B). The child had an uncomplicated recovery. The removed FBs were determined to be neodymium magnetic beads. DISCUSSION Consumer access to high-powered neodymium magnets led to a newly described risk of bowel perforation and obstruction if ingested.1-7 This risk was not previously observed in typically accessible and lower-powered magnets. The observed injury rate Figure 1. A. Abdominal radiograph reveals 4 small adjacent radiopaque foreign from high-powered magnets rose dramatically in 2009 with the bodies in the midabdomen. marketing of a large collection of small neodymium magnetic beads commonly known as Buckyballs.8,9 This rising injury rate, including death, led to a temporary ban on the products, which was overturned in 201810-12; they are currently on the market. may have an unknown ingestion and be unable to describe or In cases of magnetic FB ingestion, patients with single or localize his/her pain.4,17 asymptomatic ingestion of multiple magnetic beads may un- Clinicians who care for young pediatric patients in all settings dergo observation with or without laxatives, or the FBs may be should keep a high index of suspicion for occult FB ingestion retrieved surgically or endoscopically.13,14 Symptomatic magnet as a potential explanation for signs or symptoms involving the ingestion (ie, with abdominal pain or vomiting) is managed abdomen, such as vomiting or abdominal pain. If the practitio- with magnet removal because of the risk of perforation. 5,13,14 ner suspects an FB ingestion or initiates a diagnostic evaluation High-powered magnets such as the ones in this case carry a higher rate of complications than do other ingested FBs. A magnet separated from another magnet or another magnetic Author Affiliations metallic object can join across tissue barriers, leading to bowel 1 California Northstate University College of Medicine, Elk Grove, California perforation.1-5,13,14 The “spot-welding” perforation of a slow tissue 2 The Permanente Medical Group, Oakland, California 3 necrosis induced by the steady pull of magnetic forces allows Department of Radiology, Kaiser Permanente Vallejo Medical Center, Vallejo, California 4 Kaiser Permanente Division of Research, Oakland, California adhesions to form concomitantly and frequently walls off the 5 4,7,8 Department of Emergency Medicine, Kaiser Permanente Sacramento Medical Center, Sacramento, perforation and prevents general peritonitis. Presumably, California this is the explanation for the often occult and insidious clinical 6 Department of Emergency Medicine, Kaiser Permanente South Sacramento Medical Center, Sacramento, 2,5,6,14-16 presentations of these patients. The difficulty of diagno- California sis is further confounded by the age range most common for FB ingestions, 6 months to 3 years. A patient in this age range Corresponding Author Dale Cotton ([email protected])

Keywords: foreign body ingestion, magnet ingestion, pediatric, vomiting

The Permanente Journal • https://doi.org/10.7812/TPP/19.165 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 131 IMAGE DIAGNOSIS Neodymium Magnetic Bead Ingestion in a Toddler

BA B References 1. Nicoara M, Liu S, Ferzli G. Laws of attraction: Management of magnetic foreign body ingestion. BMJ Case Rep 2018 Jul 6;2018:bcr-2018-225939. DOI: https://doi. org/10.1136/bcr-2018-225939. 2. Miyamoto R, Okuda M, Kaneko K, Numoto S, Okumura A. Multiple magnets ingestion followed by intestinal fistula with mild symptoms. Glob Pediatr Health 2019 Jun 11;6:2333794X19855805. DOI: https://doi.org/10.1177/2333794X19855805. 3. Tsai J, Shaul DB, Sydorak RM, Lau ST, Akmal Y, Rodriguez K. Ingestion of magnetic toys: Report of serious complications requiring surgical intervention and a proposed management algorithm. Perm J 2013 Winter;17(1):11-4. DOI: https://doi.org/10.7812/ TPP/12-097. 4. Verma S, Shinde S, Gupta C. Multiple magnet ingestion: An uncommon cause of peritonitis. J Indian Assoc Pediatr Surg 2013 Oct;18(4):160-1. DOI: https://doi. org/10.4103/0971-9261.121126. 5. Dutta S, Barzin A. Multiple magnet ingestion as a source of severe gastrointestinal complications requiring surgical intervention. Arch Pediatr Adolesc Med 2008 Feb;162(2):123-5. DOI: https://doi.org/10.1001/archpediatrics.2007.35. 6. Si X, Du B, Huang L. Multiple magnetic foreign bodies causing severe digestive tract injuries in a child. Case Reports in Gastroenterology 2016 Nov 25;10(3):720-727. DOI: https://doi.org/10.1159/000450538. 7. Centers for Disease Control and Prevention. Gastrointestinal injuries from magnet ingestion in children, United States, 2003-2006. MMWR Morb Mortal Wkly Rep 2006;55:1296-300. 8. Brown JC, Otjen JP, Drugas GT. Too attractive: The growing problem of magnet ingestions in children. Pediatr Emerg Care 2013 Nov;29(11):1170-4. DOI: https://doi. org/10.1097/PEC.0b013e3182a9e7aa. 9. Reeves PT, Nylund CM, Krishnamurthy J, Noel RA, Abbas MI. Trends of magnet ingestion in children, an ironic attraction. J Pediatr Gastroenterol Nutr 2018 May;66(5):e116-e121. DOI: https://doi.org/10.1097/MPG.0000000000001830. 10. Safety standard for magnet sets; removal of final rule vacated by court. 16 CFR part 12402. Fed Regist 2017 Mar 7;82(43). 11. CPSC issues decision on Zen magnets [Internet]. Bethesda, MD: US Consumer Product Safety Commission; 2017 Nov 3 [cited 2019 Aug 14]. Available from: www. cpsc.gov/content/cpsc-issues-decision-on-zen-magnets. 12. Zen Magnets, LLC v. United States of America Consumer Product Safety Figure 1. B. Surgically removed contiguous magnetic foreign bodies clinging to Commission. 2018. Civil action no. 17-cv-02645-RBJ. 2018 Jun 11. a surgical clamp. 13. Sola R Jr, Rosenfeld EH, Yu YR, St Peter SD, Shah SR. Magnet foreign body ingestion: rare occurrence but big consequences. J Pediatr Surg 2018 Sep;53(9):1815-1819. DOI: https://doi.org/10.1016/j.jpedsurg.2017.08.013. 14. Cho J, Sung K, Lee D. Magnetic foreign body ingestion in pediatric patients: Report of three cases. BMC Surg 2017 Jun 24;17(1):73. DOI: https://doi.org/10.1186/s12893- because of an emergent condition such as bowel obstruction, 017-0269-z. consideration should be given to plain films that may readily 15. Bauman B, McEachron K, Goldman D, et al. Emergency management of the ingested identify a radiopaque FB as the explanatory cause and obviate magnet: An algorithmic approach. Pediatr Emerg Care 2019 Aug;35(8):e141-e144. 18v the need for greater ionizing-radiation studies. DOI: https://doi.org/10.1097/PEC.0000000000001168. 16. Cho J, Sung K, Lee D. Magnetic foreign body ingestion in pediatric patients: Report of three cases. BMC Surgery 2017 Jun 24;17(1):73. DOI: https://doi.org/10.1186/ Disclosure Statement s12893-017-0269-z. The author(s) have no conflicts of interest to disclose. 17. Wyllie, R. Foreign bodies in the gastrointestinal tract. Curr Opin Pediatr 2006 Oct;18(5):563-4. DOI: https:// 10.1097/01.mop.0000245359.13949.1c. Acknowledgments 18. Pugmire BS, Lim R, Avery LL. Review of ingested and aspirated foreign bodies in children and their clinical significance for radiologists. Radiographics 2015 Aug 21; Kathleen Louden, ELS, of Louden Health Communications performed a 35(5):1528-38. DOI: https://doi.org/10.1148/rg.2015140287. primary copy edit.

How to Cite this Article Hui KJ, Arasu VA, Vinson DR, Cotton DM. Image Diagnosis: Neodymium Magnetic Bead Ingestion in a Toddler. Perm J 2020;24:19.165. DOI: https://doi. org/10.7812/TPP/19.165

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.165 132 COMMENTARY Addressing Vaccine Hesitancy

Ryan Bradley, ND, MPH;1,2 Charles Elder, MD, MPH3 Perm J 2020;24:20.216 E-pub: 09/16/2020 https://doi.org/10.7812/TPP/20.216

INTRODUCTION distrust and fueling antimedical establishment ideologies. A focus As vaccines against the severe acute respiratory syndrome- on a vaccination-only strategy may also preclude effective delivery coronavirus 2 (SARS-CoV-2) become available, vaccine hesitancy of other evidence-based preventive services, such as US Preventive may become a critical public health issue. The Permanente Journal Services Task Force recommendations for behavioral counseling to published a case report by Garofalo et al1 reporting on naturo- reduce sexually transmitted infections, including hepatitis B and pathic counseling of a family toward appropriate vaccinations for human papillomavirus.6 Informed consent and patient autonomy their children through vaccine education. Their case illustration (not to mention beneficence and nonmaleficence) are cornerstones is important for several reasons, but perhaps most importantly in medical ethics; ultimately vaccination decisions should be no it counters a prevalent belief that naturopathic physicians and exception to their mandated inclusion and accuracy, although the other complementary and integrative health (CIH) practitioners best approach to balance societal benefit and individual choice are “anti-vaccination”.2 All accredited naturopathic colleges and remains unknown and controversial.7,8 universities educate medical students on prevention of vaccine- As pointed out by Garofalo et al,1 findings of several observa- preventable diseases and the current vaccination schedule recom- tional studies suggest that undervaccinated children are more likely mended by the Centers for Disease Control and Prevention. to receive care by naturopathic doctors (NDs).9,10 One possible ex- planation for this finding may be that some NDs do not adhere to VACCINE HESITANCY or promote recommended vaccine schedules. On the other hand, Five key predictors of vaccine hesitancy have been identified in it may also be the case, as illustrated by Garofalo and colleagues,1 recent meta-analyses, including: risk conceptualization; mistrust that NDs are respecting patient preferences for care, facilitating toward pharmaceutical companies and health care providers; al- the provision of continued care independently of individual choices ternative health beliefs about immunity, vaccine scheduling, and and providing sources of other recommended preventive services risks of vaccinations; varying views on parental responsibility; as strategies to develop trust and establish long-term relationships and parental knowledge.3 All these factors could, at least in part, with those families. In that way, vaccination decisions can be revis- potentially be modified by a trusting doctor-patient relationship, ited if the knowledge or risk of those families changes. Of course, including patient-centered counseling that allows for assessment the actual clinical recommendations delivered in such encounters of patient knowledge and health beliefs. This counseling should be cannot be determined observationally without access to detailed supported by adequate time spent in respectful and culturally sensi- health records data. Likewise, limited, claims-based observational tive health education activities. In fact, similar interventions have studies cannot alone inform which pattern of care is more dominant been recommended in expert reviews focused on increasing vaccine among NDs. Pending further research, uninformed assumptions uptake, including a specific recommendation for communication may lead to erroneous conclusions and suboptimal patient care. to “focus on listening and not unidirectional provision of infor- In managing vaccine hesitancy, we recommend applying basic mation”.4 Importantly, CIH practitioners commonly emphasize tenets of patient-centered care, which are specifically included in principles of patient-centered care, including patient preferences the philosophy of naturopathic medicine: find and address the in care and patient-centered communication strategies, includ- cause (of vaccine hesitancy), treat the whole person (respecting ing motivational interviewing, in their interactions with patients. his/her current knowledge and beliefs), and serve as a teacher (by Patient preferences in care were also considered in the pertussis providing accurate information). case report by Garofalo et al,1 a concept considered controversial in the context of vaccination,5 in which the option of choice is highly CONCLUSION discouraged by numerous authorities. Conventional medical doc- Rather than criticize NDs and other CIH practitioners as be- tors, of course, rightly emphasize patient preferences and shared ing antivaccination, the provision of a referral of a vaccine-hesitant decision making in their clinical encounters as well. Suspending patient to such clinicians for vaccine education may provide an these considerations in the setting of the vaccination discussion, however, can have negative consequences. Clinical situations in which the choices are the most controversial are precisely those Author Affiliations situations in which provider-patient trust becomes critical in the 1 Helfgott Research Institute, National University of Natural Medicine, Portland, OR doctor-patient encounter. Developing a trusting relationship has 2 Wertheim School of Public Health and Human Longevity Science, University of California, the potential to affect choices in care over time. For example, a deci- San Diego, La Jolla, CA 3 sion not to vaccinate today may become a decision to vaccinate in Kaiser Permanente Northwest and Kaiser Permanente Center for Health Research, Portland, OR the future if patients feel their beliefs and preferences are respected. Corresponding Author Likewise, discharging or otherwise refusing care for patients who Ryan Bradley, ND, MPH ([email protected]) refuse to vaccinate has the potential to backfire, by perpetuating Keywords: antivaccination, immunization, naturopathic medicine, vaccine-preventable disease, vaccine refusal, vaccine hesitancy

The Permanente Journal • https://doi.org/10.7812/TPP/20.216 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 133 COMMENTARY Addressing Vaccine Hesitancy

3. Diaz Crescitelli, M.E., et al., A meta-synthesis study of the key elements involved in important gesture of respect and support to the patient. Coordi- childhood vaccine hesitancy. Public Health, 2020. 180: p. 38-45. nated interprovider communication has the potential to influence 4. MacDonald, N.E., R. Butler, and E. Dube, Addressing barriers to vaccine acceptance: patients’ vaccine-related choices toward prevention—a goal we all an overview. Hum Vaccin Immunother, 2018. 14(1): p. 218-224. share. This issue may become particularly important as vaccines v 5. Fisher, K.A., et al., Keeping the patient in the center: Common challenges in the for SARS-CoV-2 become available. practice of shared decision making. Patient Educ Couns, 2018. 101(12): p. 2195- 2201. Disclosure Statement 6. Sexually transmitted infections: Behavioral counseling [Internet]. Rockville, MD: US The author(s) have no conflicts of interest to disclose. Preventive Services Task Force; 2014 Sept 22 [cited 2020 Jul 8]. Available from: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/sexually- transmitted-infections-behavioral-counseling. Acknowledgments 7. Hendrix, K.S., et al., Ethics and Childhood Vaccination Policy in the United States. Kathleen Louden, ELS, of Louden Health Communications performed a Am J Public Health, 2016. 106(2): p. 273-8. primary copyedit. 8. Williamson, L. and H. Glaab, Addressing vaccine hesitancy requires an ethically consistent health strategy. BMC Med Ethics, 2018. 19(1): p. 84. 9. Frawley, J.E., H. Foley, and E. McIntyre, The associations between medical, allied References and complementary medicine practitioner visits and childhood vaccine uptake. 1. Garofalo L, Corn J, Sperandeo M. Pertussis Infection in a Naturopathic Primary Care Vaccine, 2018. 36(6): p. 866-872. Setting: Reflection on a Case. Perm J 2020;24:20.065. DOI: https://doi.org/ 10.7812/ 10. Downey, L., et al., Pediatric vaccination and vaccine-preventable disease acquisition: TPP/20.065 associations with care by complementary and alternative medicine providers. Matern 2. Kajetanowicz A, Kajetanowicz A. Why parents refuse immunization? Wiad Lek Child Health J, 2010. 14(6): p. 922-30. 2016;69(3 Pt 1):346-51.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.216 134 COMMENTARY CARE for COVID-19: A Checklist for Documentation of Coronavirus Disease 2019 Case Reports and Case Series

Paul G Werthmann, MD1,2; David Riley, MD3,4; Gunver Sophia Kienle, MD1,2 Perm J 2020;24:20.127 E-pub: 08/12/2020 https://doi.org/10.7812/TPP/20.127

ABSTRACT clinicians and researchers who want to present new information Coronavirus disease 2019 (COVID-19) is a new, rapidly spreading with importance for the medical community. pandemic that can lead to a life-threatening disease. Accurate and transparent COVID-19 case reports provide systematic clini- Guideline Development cal observations supporting researchers designing clinical trials For elaboration of this guideline, data from clinical and scien- and clinicians delivering health care. The checklist described here tific literature (eg,1,3-10,17,18 ) and from current research projects (eg, is designed to systematically and accurately capture data from NCT04331509, NCT04333407, NCT04291053, NCT04344171, case reports and case series for documentation on COVID-19. It NCT04323332, DRKS0002114519) were screened and included is aligned with the CARE guidelines, available from the EQUATOR in the elaboration of the checklist. Items were especially included (Enhancing the QUAlity and Transparency Of health Research) if they represent a special characteristic of the patient regarding Network. risk, diagnostic certainty, and severity of the disease. This checklist is compatible with the Lean European Open Survey on SARS- INTRODUCTION CoV-2 (LEOSS; https://leoss.net), the publicly funded European Coronavirus disease 2019 (COVID-19) is a viral infection with COVID-19 registry. As the disease has different grades of severity severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), and complications (Figure 1), additional items ask to give details first detected in December 2019 in Wuhan, China.1 COVID-19 about the patient’s course in the intensive care unit. spread as a pandemic throughout the world, with more than 9 mil- The item collection was done by 1 author (PGW) and checked lion confirmed cases and more than 470,000 deaths worldwide as by 2 others (GSK, DR). After completion, the checklist was sent of June 23, 2020.2 The widespread and sometimes fatal outcome out to several researchers and physicians in charge of patients with of this pandemic necessitates the acquisition of reliable knowledge COVID-19. Feedback from these experts was included in the re- about this disease. Much of the early evidence has come from case vision of the checklist. The checklist was then sent out in English reports and case series.3-10 Prospective clinical research trials and and in translations (German, Portuguese, and Spanish) to physi- reviews on COVID-19 have begun; however, the clinical observa- cians in charge of patients with COVID-19. Their feedback was tions of patients captured in accurate and transparent COVID-19 included in another revision of the current checklist. The checklist case reports provide systematic clinical observations supporting is currently available in English, German, Portuguese, Russian, and researchers designing clinical trials and clinicians delivering health Spanish (see supplemental material to this article available at www. care. This information will gather important observations across thepermanentejournal.org/files/2020/20.127supp.pdf). different fields of medicine treating different patients with differ- ent treatment approaches as well as the frequency and types of How to Use This Checklist adverse events and complications. In 2013 and 2017 the CARE This checklist can be used to achieve a more complete docu- Group published the health research reporting guideline for case mentation and description of patients with COVID-19, includ- reports,11,12 which has been adopted and adapted by many medi- ing therapeutic treatment with off-label conventional medicine cal fields.13,14 or complementary and alternative therapies. In case reports and case series mentioning new therapeutic interventions, additional DOCUMENTATION CHECKLIST CARE FOR COVID-19 information may be necessary such as TIDieR (template for We present here a documentation checklist for the elaboration intervention description and replication),20 a guideline designed of COVID-19 case reports (Table 1). This checklist is designed to systematically and accurately capture data from case reports and case series for documentation on COVID-19 and is aligned with 15 Author Affiliations the CARE guidelines; this and other health research reporting 1 16 Faculty of Medicine, University of Freiburg, Institute for Infection Prevention and Hospital Epidemiology, guidelines are available from the EQUATOR (Enhancing the Center for Complementary Medicine, Freiburg, Germany QUAlity and Transparency Of health Research) Network. This 2 Institute for Applied Epistemology and Medical Methodology, University of Witten/Herdecke, Freiburg, checklist aims to support the collection of important clinical in- Germany formation as generally given in the items 5, 6, 8, 9, and 10 of the 3 Scientific Writing in Health and Medicine, Portland, OR CARE Guideline Checklist.11 The checklist has been elaborated 4 National University of Natural Medicine, Portland, OR by 3 members of the CARE Group and represents a tool for Corresponding Author Paul G Werthmann, MD ([email protected])

Keywords: case report, case series, coronavirus disease 2019, COVID-19, publication guideline, SARS-CoV-2

The Permanente Journal • https://doi.org/10.7812/TPP/20.127 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 135 COMMENTARY CARE for COVID-19: A Checklist for Documentation of Coronavirus Disease 2019 Case Reports and Case Series

5. Tapé C, Byrd KM, Aung S, Lonks JR, Flanigan TP, Rybak NR. COVID-19 in a to clarify therapeutic interventions that is available from the Patient Presenting with Syncope and a Normal Chest X-ray. R I Med J (2013). 16 EQUATOR Network. 2020;103(3):50-51. For the preparation of a COVID-19 case report or case se- 6. Zhang B, Liu S, Tan T, et al. Treatment with convalescent plasma for critically ill 11 patients with SARS-CoV-2 infection. Chest. Published online March 31, 2020. ries, follow the structure of the CARE guideline checklist. For doi:10.1016/j.chest.2020.03.039 the details about the patient information, use this CARE for 7. Blanco-Colino R, Vilallonga R, Martín R, Petrola C, Armengol M. Suspected acute COVID-19 checklist to include all important items. Judge for abdomen as an extrapulmonary manifestation of Covid-19 infection. Cir Esp. Published online April 3, 2020. doi:10.1016/j.ciresp.2020.03.006 yourself whether all the items of this list are applicable to your 8. Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of report and use those that are applicable. Covid-19 in the young. New England Journal of Medicine. Published online April 28, 2020:e60. doi:10.1056/NEJMc2009787 Improvement of This Checklist and Future Outlook 9. Eliezer M, Hautefort C, Hamel A-L, et al. Sudden and complete olfactory loss function as a possible symptom of COVID-19. JAMA Otolaryngology–Head & Neck Surgery. Although more than 2000 articles about COVID-19 are al- Published online April 8, 2020. doi:10.1001/jamaoto.2020.0832 ready displayed in MEDLINE, the knowledge about this disease 10. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. Journal of the American Academy of Dermatology. 2020;82(5):e177. doi:10.1016/j. is still growing rapidly. Future progress in diagnosis and treatment jaad.2020.03.036 of this disease will lead to a more precise description about the 11. Gagnier JJ, Riley D, Altman DG, Moher D, Sox H, Kienle GS. The CARE guidelines: main symptoms, rarer symptoms, classification of disease stages, Consensus-based clinical case reporting guideline development. Dtsch Arztebl complications, pathophysiology, immune processes, interventions, International. 2013;110(37):603-608. 12. Riley DS, Barber MS, Kienle GS, et al. CARE 2013 Explanation and elaborations: long-term outcomes, and ethical issues related to it. We tried to Reporting guidelines for case reports. Journal of Clinical Epidemiology. implement the current knowledge from the literature and signs 2017;89(Supplement C):218-235. doi:10.1016/j.jclinepi.2017.04.026 and symptoms from clinicians into this checklist while leaving it 13. Agha RA, Fowler AJ, Saeta A, Barai I, Rajmohan S, Orgill DP. The SCARE Statement: Consensus-based surgical case report guidelines. International Journal of lean and clear for easy use. The checklist might therefore expand Surgery. 2016;34:180-186. doi:10.1016/j.ijsu.2016.08.014 or change over time to account for the change in our knowledge 14. Lavergne V, Ouellet G, Bouchard J, et al. Guidelines for reporting case studies on of COVID-19 and potential therapeutic interventions. extracorporeal treatments in poisonings: methodology. SeminDial. 2014;27(1525- 139X (Electronic)):407-414. We hope this checklist will help to build up a well-funded 15. CARE Case Report Guidelines. What are the CARE Case Report Guidelines? [cited evidence base in this disease, and it might become an example 2020 Apr 20]. Available from: www.care-statement.org. v for new emerging diseases in the future. 16. EQUATOR Network. Enhancing the QUAlity and Transparency Of health Research [cited 2020 Apr 20]. Available from: www.equator-network.org/. Disclosure Statement 17. Akima S, McLintock C, Hunt BJ. RE: ISTH interim guidance to recognition and management of coagulopathy in COVID‐19. Journal of Thrombosis and Haemostasis. The author(s) have no conflicts of interest to disclose. Published online April 17, 2020. doi:10.1111/jth.14853 18. McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms Acknowledgments of pulmonary intravascular coagulopathy in COVID-19 pneumonia. The Lancet We thank the researchers and physicians in charge of patients with Rheumatology. Published online May 2020. doi:10.1016/S2665-9913(20)30121-1 COVID-19 for reviewing the item collection checklist. For help in translating 19. Vehreschild JJ, Schons M, Stecher M, et al. LEOSS: Lean European Open Survey on SARS-CoV-2: Study protocol [cited 2020 Jun 26]. Published online 2020 Mar the CARE for COVID-19 Checklist, we thank Iracema de Almeida Benevides, 16. Available from: https://leoss.net/wp-content/uploads/2020/03/LEOSS-Protocol- MD, public health consultant, Belo Horizonte, Brazil; Dr Denis Koshechkin, MD, Submission-1-20200316.pdf Medical Centrum “Terapeuticum,” St Petersburg, Russia; and Dr Yván Villegas, 20. Hoffmann T, Glasziou P, Boutron I, et al. Better reporting of interventions: template MD, Centro Médico Antroposófico, Lima, Peru. for intervention description and replication (TIDieR) checklist and guide. BMJ Kathleen Louden, ELS, of Louden Health Communications performed a 2014;348:g1687. DOI: https://doi.org/10.1136/bmj.g1687. primary copy edit.

Authors’ Contributions Paul Georg Werthmann, MD, created the item collection checklist and wrote the first draft of the article. David Riley, MD, and Gunver Sophia Kienle, MD, checked the item collection checklist and revised and contributed to the article. All authors read and approved the final version of the article.

References 1. World Health Organization. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) [cited 2020 Jun 25]. Available from: www who int/docs/ default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report pdf. Published online 2020 Feb. 2. COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) [cited 2020 Jun 23]. Available from: www.arcgis. com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. Cited in: Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020 May;20(5):533-34. doi:10.1016/S1473- 3099(20)30120-1 3. Lei J, Li J, Li X, Qi X. CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020;295(1):18. doi:10.1148/radiol.2020200236 4. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809-815. doi:10.1016/S0140- 6736(20)30360-3

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.127 136 COMMENTARY CARE for COVID-19: A Checklist for Documentation of Coronavirus Disease 2019 Case Reports and Case Series

asymtomatic need for oxygen need for catecholamines improvement by one supplementation degree of severity OR life-threatening cardiac according to this scheme paO2 at room air < 70 arrhythmia Phase Phase symptoms of upper Phase respiratory tract mmHg mechanical ventilation AND infection SO2 at room air < 90 % (invasive or non- defervescence nausea, emesis, GOT or GPT > 5x ULN invasive)

diarrhea, fever new cardiac arrhythmia Phase Critical liver failure with quick < 50 % new pericardial effusion Recovery qSOFA >= 2 > 1 cm Complicated new heart failure with renal failure in need of dialysis Uncomplicated pulmonary edema congestive hepatopathy or peripheral edema

Figure:Figure 1. Stages Stages ofof COVID-19 COVID19 disease disease according according to LEOSS. to Reprinted LEOSS with(with permission permission of Vehreschild of the et authors al.19 [Vehreschild et al. 2020]) COVID-19 = coronavirus disease 2019; LEOSS = Lean European Open Survey on SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2); GOT = glutamic-oxaloacetate transaminase (now called aspar- tate aminotransferase); GPT = glutamic-pyruvic transaminase (now called alanine aminotransferase); paO2 = arterial partial pressure of oxygen; qSOFA = quick Sepsis Related Organ Failure Assessment; SO2 = oxygen saturation; ULN = upper limit of normal.

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Table 1 CARE for COVID19 – Werthmann, Riley, Kienle 2020 Checklist for Case Documentation of COVID19 Patients Documentation if available / if applicable: Key Data Additional Data • Age • Occupation • Gender • Ethnicity • Weight and height (BMI) • Mobility (restricted? • Concomitant diseases (with severity) bedridden?) especially pre-existing conditions that increase the risk of a severe • Living environment (e.g., course of COVID19: senior citizens’ residence, Arterial hypertension o facility for the disabled) o Cardiovascular disease o Chronic lung disease o Chronic liver disease o Chronic kidney disease o Diabetes mellitus o Cancer o Immunocompromising diseases or treatments (immunodeficiencies, immunosuppressants,

Patient Data Patient cytostatics, cortisone, ...) • Smoking (specify pack years or frequency) • Regular medication, especially o ACE inhibitors o Calcium antagonists o Statins o Steroids o Non-steroidal anti-inflammatory drugs (NSAIDs) o Calcineurin/mTor inhibitors o Anti-TNF-alpha inhibitors o other immunosuppressants o Chemotherapy o Anticoagulants • Known contact with an infected person? • Travel history Infection • Presumed date of infection • Exposure and exposure • Onset of symptoms risks

• Location of specimen collection (e.g., throat swab) • Type of test: • Test date • L- or S-strain • Test result • Highest viral load • lowest PCR cycles • Antibody titer • Other Tests: Influenza COVID19Testing A/B Name all known symptoms indicate their severity (e.g. mild, moderate, severe) and describe their course. • Fever (grade, duration, course) • Nausea/vomiting • Delirious, confused, disorientated • Nasal congestion • Fatigue / Exhaustion (how much limited by this?) • Diarrhea • • Cough Abdominal pain • Hoarse voice • Chest pain • Sore throat • Skin symptoms course • Sputum • Shortness of breath • Headache ClinicalCOVID19 symptoms • Aching limbs • Chills Describecomplaints in detail during the • Loss of smell / taste

1

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CARE for COVID19 – Werthmann, Riley, Kienle 2020

Indication of the stage of disease at first presentation (see figure below)

• Respiratory rate • RR

• O2 saturation • Pulse and

• paO2 • paCO2 Vitalsigns duringcourse the findingsin detail Describe pathological pathological Describe

• Thoracic x-ray, CT,

/ ultrasound • Echocardiography • Evidence of vascular Imaging

diagnostics events, thrombosis or (if applicable) (if embolism • CRP • IL-6 • GOT/AST • PCT • GPT/ALT • Ferritin • GGT • IL-2

• Bilirubin • LDH • • D-dimers

detail Creatine Lab

in • Leukocytes • plasma fibrinogen • Lymphocytes • Troponin • Platelets • Lipase • Prothrombin time (PT) • Blood type Describe pathological findings findings pathological Describe • Partial thromboplastin time (PTT) Application Yes/No, specify preparation if yes • Application with • Antivirals duration (days, precise

• Antibiotics reference to disease • Anticoagulants findings), dosage (see • Steroids above), application • Immunoglobulins form • Beta blockers and/or anti-arrhythmics • Tocilizumab • Plasmapheresis For treatment in intensive care units • Catecholamines (with duration in days) • Invasive / non-invasive ventilation (with duration in days)

Therapeuticmeasures for COVID19 • ECMO and comparable procedures • Cardiac assist device

2

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CARE for COVID19 – Werthmann, Riley, Kienle 2020 • Detailed description of the medications / applications / measures / recommendations (e.g.,

diet, exercise, lifestyle changes) medical • Dosage, frequency and application form • Start time and end time •

therapies Changes during the course

Experimental and and Experimental complementary • Duration § of symptomatic course • Imaging during the § course of hospital stay § of stay in intensive care unit § of ventilation • Clinical signs, vital signs, laboratory up parameters during the course • Duration of the individual phases of the follow - disease (see figure below) • Outcome

Clinicalcourse, outcome, § Healthy, still symptomatic, deceased • Follow-up § Lung function after the disease? § Any other persistent symptoms? • Intensive care diagnosis (e.g., acute lung failure (ARDS), kidney failure, multiple organ failure, shock) • First values after intubation of § SO2, RR, pulse, PaO2, PaCO2,

§ PEEP, Pmax, frequency, FiO2 • Worst values of § GOT/AST, GPT/ALT, GGT, bilirubine, creatine, lipase, leukocytes, lymphocytes, platelets, troponin, CRP, IL-6, PCT, ferritin,

Intensivedatacare IL-2, LDH, D-dimers § SO2, RR, pulse, PaO2, PaCO2, § PEEP, Pmax, frequency, FiO2 § SOFA score • Proven super-infection (bacterial, fungal)

3

The6 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.127 140 COMMENTARY A Day in the Life during COVID-19: Long-term Care Providers in Durham, North Carolina

Nathan A Boucher, DrPH, PA, MS, MPA, CPHQ1-4; Courtney H Van Houtven, PhD, MSPH3,4 Perm J 2020;24:20.165 E-pub: 08/05/2020 https://doi.org/10.7812/TPP/20.165

INTRODUCTION the limiting factor is protective gear. There aren’t nearly enough As parts of America slowly start reopening during the recovery masks to follow the approved protocol, and I’ve started to bring phases of the coronavirus disease 2019 (COVID-19) pandemic, masks I’ve made at home5 rather than contaminate my patients our national focus is too often on the people who are flooding the by wearing the same manufactured mask all day. My homemade streets, shops, and beaches. Meanwhile, we are not giving enough mask isn’t nearly as effective as ones designed for healthcare use,6 attention to the people we cannot see, who are most at risk to be and I know nursing home workers have died after making the seriously affected by COVID-19. More than 8 million Americans switch.5 But knowing the death rates due to COVID-19 in LTC use long-term care (LTC) such as home health agencies, nursing residents,7 I’ve decided to take the risk for my residents. After I homes, and hospices.1 What is more is that those Americans are am dressed in protective gear, I make the rounds to examine each being cared for by a large number of health care workers, who patient for symptoms to ensure there aren’t any new cases of CO- are risking their own health as well as their families’ health as es- VID-19. I do this every day, without fail, even though it feels like sential workers. a fool’s errand given how often coronavirus is asymptomatic. Still, People in LTC are the epitome of high risk of COVID-19; they some of my residents seem to enjoy me checking on them. For are overwhelmingly above the age of 65 years, chronically ill, and/or some of them, without communal meals or family visits allowed immunocompromised.1 Furthermore, they use LTC because they currently, it is some of the only human contact they get all day. need hands-on assistance from another person, meaning they are 12 pm: We try to make the facility as social and homelike as pos- in close contact with 1 if not multiple care providers. sible, but we are limited by the need for social distancing. At lunch, The following day-in-the-life amalgam is based on the recently everyone eats alone in their rooms. It’s heartbreaking to see how reported experiences of 6 health care providers working in LTC the residents react to having much less community time.8 It isn’t who responded to an online question and answer session; we cou- like quarantining at home with your family. Most of the residents pled this with evidence from news sources and reports in March aren’t whipping out Zoom for virtual cocktail hour, and they’re so and April 2020. All responding care providers are currently deal- vulnerable to COVID-19, there truly is no wiggle room allowed ing with COVID-19 in LTC settings in Durham, NC. Notably for unnecessary contact. My patients are not only bored but also absent from this day-in-the-life scenario are the family and friend cripplingly lonely, and I’m forced to watch their mental health caregivers who have not been able to visit the facilities because of plummet because I don’t have the time or physical ability to make policies restricting visitors. This narrative is a breakdown of life sure their emotional needs are met. Social distancing is not only inside some of the most emotionally and physically perilous places mentally dangerous but also physically dangerous. First, the resi- to be in America right now. dents are likely not moving around as much given the restrictions, so they could be losing strength gradually. More immediately, we LIFE INSIDE LONG-TERM CARE have several residents who struggle to eat without choking, yet we 6 am: I wake up in the morning and try not to disturb my kids try to be [1.8 m] 6 ft away from them as they painstakingly eat.8 and partner as they sleep. I’m up earlier than anyone else in the 3 pm: We’ve started to transition into telecommunications for house. Even if my family members were awake, I would try my our medical appointments. It’s definitely safer for both the health hardest to keep away. They’ve been socially distancing, but given care providers and the patients to limit actual contact, but we don’t how common asymptomatic coronavirus cases are2 and how vulner- have the kind of telehealth access we need.9 Our Wi-Fi is unreli- able my patients are, I can’t take chances. It’s hard to make some able, and telehealth can’t take a patient’s temperature. We risk ev- space in my house, but it’s even harder at the nursing home, where eryone’s health to get a good patient assessment. Also, regulations the close quarters of living circumstances and shared rooms can make social distancing almost impossible.3 This close living situa- tion is one of the many reasons the residents are so vulnerable to Author Affiliations infection, and their vulnerability is one of the many reasons I no 1 Duke University Sanford School of Public Policy, Durham, NC longer hug my children. 2 Geriatric Medicine, Duke University School of Medicine, Durham, NC 7 am: Once I get to the nursing home, the first thing I do is put 3 Population Health Sciences, Duke University School of Medicine, Durham, NC on my personal protective equipment, which has been in the news 4 Durham Veterans Affairs (VA) Center of Innovation to Accelerate Discovery and Practice Transformation a lot lately, referred to as PPE. Much like every health care center (ADAPT), Durham VA Health System, Durham, NC in America, my workplace is in dire need of PPE, and the way I’m Corresponding Author forced to use and reuse my PPE puts myself, my family, and my Nathan A Boucher, DrPH, PA, MS, MPA, CPHQ ([email protected]) patients at risk.4 Our facility has an infection control specialist, but Keywords: clinicians, coronavirus, long-term care, nursing homes

The Permanente Journal • https://doi.org/10.7812/TPP/20.165 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 141 COMMENTARY A Day in the Life during COVID-19: Long-term Care Providers in Durham, North Carolina

Authors’ Contributions stipulate that new patients aren’t allowed to use telehealth services, Nathan A Boucher, DrPH, PA, MS, MPA, CPHQ, and Courtney H Van meaning that the patients who are the most likely to be harboring Houtven, PhD, MSPH, handled data collection and writing of the manuscript. COVID-19 are the patients we are mandated to physically exam- Both authors have given final approval to the manuscript. ine.9 Hospitals are looking to move patients to our facility, but we worry about taking care of the high-need residents we currently References have. Communication between our facility and the hospital and 1. Friedland RB, reviewer. Selected long-term care statistics. San Francisco, CA: Family Caregiver Alliance; 2015 [cited 2020 May 25]. Available from: https://www.caregiver. the state were strained early on but have moderately improved. org/selected-long-term-care-statistics. 5 pm: We have individualized goals-of-care conversations with 2. Asymptomatic spread makes COVID-19 tough to contain. Baltimore, MD: Johns each resident and his/her health care power of attorney to deter- Hopkins University Hub; 2020 May 12 [cited 2020 May 25]. Available from: https:// hub.jhu.edu/2020/05/12/gigi-gronvall-asymptomatic-spread-covid-19-immunity- mine the resident’s wishes in the event of terminal illness due to passports/. COVID-19. We want to make sure that the residents receive the 3. Kamp J, Wilde Mathews A. Coronavirus deaths in U.S. nursing, long-term care desired care and that we do not transfer people to the hospital facilities top 10,000 [cited 2020 May 25]. Wall Street Journal Updated 2020 Apr 22. Available from: https://www.wsj.com./articles/coronavirus-deaths-in-u-s-nursing-long- who would rather receive supportive care as they die at our facil- term-care-facilities-top-10-000-11587586237. ity. Luckily, our health care providers also see patients at the local 4. Flynn M. PPE shortages to play central role in future nursing home lawsuits academic medical center, so there are resources to keep up to date [cited 2020 May 25]. Skilled Nursing News 2020 Apr 14. Available from: https:// skillednursingnews.com/2020/04/ppe-shortages-to-play-central-role-in-future-nursing- on changing COVID-19 requirements, and LTC advocacy can home-lawsuits/. occur with medical center leaders. I am not sure it is the same at 5. Mahr J. Short staffing. PPE shortages. Few inspections. Why calls are growing for all facilities; some may not be well equipped to handle a patient Illinois nursing home regulators to step up efforts on COVID-19 [cited 2020 May 25]. Chicago Tribune 2020 May 13. Available from: https://www.chicagotribune.com/ who has COVID-19. coronavirus/ct-coronavirus-illinois-nursing-homes-regulators-pritzker-20200513- 7 pm: When I finally get home, I don’t embrace my kids. I des- 3bdofjnaivhadg2yt7kcf2psm4-story.html. perately want to, but it’s not safe. They’re too young to understand 6. Wilson AM, Abney SE, King MF, et al. COVID-19 and non-traditional mask use: How do various materials compare in reducing the infection risk for mask why I won’t play with them anymore, or why they can’t go outside wearers? [published online ahead of print, 2020 Jun 2]. J Hosp Infect. 2020;S0195- and see their friends. I try to feel thankful for the chance to even 6701(20)30276-0. doi:10.1016/j.jhin.2020.05.036. see my family; none of my residents have been allowed visitors for 7. Margolies J. As death toll in nursing homes climbs, calls to redesign them grow [cited 10 2020 May 25]. New York Times 2020 May 12. Updated 2020 May 21. Available from: months. For so many of them, the best things in their lives have https://www.nytimes.com/2020/05/12/business/nursing-homes-coronavirus.html. been taken away, and I know so many of them don’t understand 8. Cerulli P. Coronavirus: The role of social distancing in senior care facilities [cited fully why their loved ones haven’t been to see them in so long. I 2020 May 25]. iAdvance Senior Care 2020 Mar 18. Available from: https://www. don’t hug my children, and the nursing home residents cannot hug iadvanceseniorcare.com/coronavirus-the-role-of-social-distancing-in-senior-care- 10 facilities/. theirs. I cannot even tell them how long it will be until they will 9. Yamshon L. As coronavirus concerns grow, skilled nursing facilities find relief in next get the chance. telehealth — but gaps remain [cited 2020 May 25]. Skilled Nursing News 2020 Mar 10. Available from: https://skillednursingnews.com/2020/03/as-coronavirus-concerns- 9 pm: As I wind down, I watch the nightly news and brace my- grow-skilled-nursing-facilities-find-relief-in-telehealth-but-gaps-remain/. self for the latest piece of horrifying information. I mourn for all 10. Director, Quality, Safety & Oversight Group, Centers for Medicare and Medicaid the health care workers across America whose lives have been cut Services. Guidance for infection control and prevention of coronavirus disease 2019 (COVID-19) in nursing homes (revised) [cited 2020 May 25]. Ref: QSO-20-14-NH. short by COVID-19, and I can’t help but ponder if I will be next. Baltimore, MD: Centers for Medicare and Medicaid Services; 2020 Mar 13. Available I wonder if hospital workers are more hopeful, compared with from: https://www.cms.gov/files/document/3-13-2020-nursing-home-guidance- those of us who work in LTC. I wonder why all the news cameras covid-19.pdf. seem to be focused on big-city hospitals, when nearly half of all 11. Yourish K, Lai KK, Ivory D, Smith M. One-third of all U.S. coronavirus deaths are 11,12 nursing home residents or workers [cited 2020 May 25]. New York Times Updated COVID-19-related deaths have happened in nursing homes. 2020 May 11. Available from: https://www.nytimes.com/interactive/2020/05/09/us/ I wonder if my nursing home will be the next to lose a quarter of coronavirus-cases-nursing-homes-us.html. its residents.13 My mind doesn’t stop racing with questions like 12. 43% of U.S. Coronavirus Deaths Are Linked to Nursing Homes. June 27, 2020. Available from: https://www.nytimes.com/interactive/2020/us/coronavirus-nursing- these until I finally fall asleep, hoping to get enough rest to face v homes.html another day. 13. Girvin, G. Nursing Homes & Assisted Living Facilities Account for 45% of COVID-19 Deaths. May 7, 2020. Available from: https://freopp.org/the-covid-19-nursing-home- Disclosure Statement crisis-by-the-numbers-3a47433c3f70 The author(s) have no conflicts of interest to disclose. 14. Cohen JS, Coryne H. A quarter of the residents at this nursing home died from COVID-19. Families want answers. [cited 2020 May 25]. Chicago, IL: ProPublica Illinois; 2020 May 14. Available from: https://www.propublica.org/article/a-quarter-of- Acknowledgments the-residents-at-this-nursing-home-died-from-covid-19-families-want-answers. We thank the following clinical leaders for sharing their experiences (unlisted clinicians wished to remain anonymous): Gwen Buhr, MD, MHS; Liza Genao, MD; Milta Little, DO, CMD; Dev Sangvai, MD; Holly Wenger, GNP; and Heidi White, MD. Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.165 142 COMMENTARY More Than Words: Reflections to Build Resilience during the COVID-19 Pandemic

David R Lee, MD, MBA;1 Karina Chavez, MD1 Perm J 2020;24:20.149 E-pub: 09/16/2020 https://doi.org/10.7812/TPP/20.149

ABSTRACT our patient’s only or primary social connection, and the use of Physicians often forget to reflect or take time to process chal- newer technologies to stay connected, such as video conferencing, lenging patient encounters, which can ultimately contribute to did not work for him.2 Loneliness has also been associated with burnout. This is even more relevant given the increased stressors adverse health outcomes, including functional decline and mor- on patients, families, and health care providers during the corona- tality,1 yet not enough public health policies were in place before virus disease 2019 (COVID-19) pandemic. Two resident physicians the COVID-19 pandemic to support social interactions. As we wrote this commentary to process a difficult experience in the implement mitigation strategies to flatten the spread of the virus, hospital. It touches on the ramifications of health care institutions’ we need to implement policies to provide older adults with Internet COVID-19 policies in relation to key geriatric syndromes includ- capabilities and phone options to alleviate the effects of loneliness. ing loneliness, mental health in older adults, and processing of Second, although this patient’s suicidal ideation may be circum- our own emotions and feelings through narrative medicine. As stantial because he was alone, I wondered if there was an undiag- part of the future health care workforce, we are motivated and nosed mental health disorder. This highlighted another key learning optimistic about our future contributions, all the while practicing point: depression can present differently in older adults and, as a compassion and empathy. result, can often go undetected.3 Depression in geriatric patients is associated with negative health outcomes, including cardiac INTRODUCTION disease and death.4,5 Being more aware of potentially undiagnosed Part of the role as chief resident in internal medicine at our mental health disorders and how they may manifest in our older institution is to lead an inpatient hospital team several times a adult population is important, especially given the added stressors month. One memorable day at our hospital occurred in March brought on by the COVID-19 pandemic. 2020, early in the coronavirus disease 2019 (COVID-19) pan- Last, this experience weighed heavily on my mind as I attempted demic, when the local government had ordered people to shelter to empathize with and understand his feelings. Some of my col- in place. I (DRL) received an unusual call from a nurse who stated, leagues have had similar experiences regarding the no-visitor “Doctor, the patient wants to kill himself. Can you please come?” policy, with one resident being called “unethical” and “irrational” by I immediately ran to the patient’s bedside a bit flustered and saw patients and family members. I found that writing helped process an older man stating, “This is all just too much. Help me die.” As these emotions. As resident physicians, we often forget to reflect on I observed him, he was sitting at the side of his bed, crying and the high-stress experiences that come with training in the medical appearing afraid. This was my first time meeting him, and he was field, which can contribute to high resident and fellow burnout.6 hospitalized for a nonrespiratory illness. When I asked why he felt One of my colleagues spoke during grand rounds regarding the this way, he simply stated, “I want to see my wife.” importance of narrative medicine and how it can help physicians Our hospital had adopted a no-visitor policy regardless of CO- process emotions.7 Expressing my thoughts and feelings by writ- VID-19 status to help decrease the spread of the viral infection. ing about this experience helped me gain closure. Ultimately, this His wife had been told to stay home and that updates regarding experience showed me that narrative medicine can go beyond re- her husband’s medical care would be communicated through phone flection and help shape how we interact and understand patients.8 calls. At the time, this felt like a reasonable solution because we wanted to protect not only the patient but also his wife from pos- CONCLUSION sible exposure. Although this patient tested negative for the severe As I inquired more about the patient’s feelings, he explained to acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), he and me that this was the first night he had been away from his wife in his wife had to endure the ramifications of COVID-related policies. more than 20 years. Being apart for even 1 night was unbearable. Sadly, this experience was not unique to this patient. The results He missed her. He wanted to see her. His pleas still sit with me of these hospital policies affect patients, family members, and today. After further discussion with the patient and his wife, it was health care providers. LESSONS LEARNED On reflection, this interaction highlighted several key learn- Author Affiliations ing points for me moving forward as a future geriatrician. First, I 1 Department of Medicine, Kaiser Permanente Oakland Medical Center, Oakland, CA learned that the COVID-19 pandemic can exacerbate loneliness in older adults, which has already been identified as a major issue Corresponding Author in our geriatric population.1 I have no doubt this policy severed David R Lee ([email protected])

Keywords: coronavirus, loneliness, mental health, narrative medicine, physician burnout

The Permanente Journal • https://doi.org/10.7812/TPP/20.149 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 143 COMMENTARY More Than Words: Reflections to Build Resilience during the COVID-19 Pandemic

Authors’ Contributions agreed the harms of separating this couple were greater than the David Lee, MD, MBA, developed and conceptualized this commentary and risks associated with COVID-19. contributed to the writing and editing of the manuscript. Karina Chavez, MD, When the patient was eventually reunited with his wife, he provided critical feedback and contributed to the writing and editing of the thanked the hospital staff and me. However, he did not regret any manuscript. Both authors have given final approval to the manuscript. of his actions. He meant every word, and I had empathy for him. Looking back, if I were in his situation, I could see myself advocat- References ing for my needs in a similar way. 1. Perissinotto CM, Stijacic Cenzer I, Covinsky KE. Loneliness in older persons: A predictor of functional decline and death. Arch Intern Med 2012 Jul;172(14):1078-83. Social distancing and infection control are important to contain DOI: https://doi.org./10.1001/archinternmed.2012.1993. this virus. Yet, just as strategies to prevent individuals from dying 2. Anderson M, Perrin A. Tech adoption climbs among older adults. Washington, DC: alone are being implemented,9 similar strategies need to be con- Pew Research Center; 2017 May 17 [cited 2020 Aug 17]. https://www.pewresearch. org/internet/2017/05/17/tech-adoption-climbs-among-older-adults/. sidered for those hospitalized individuals experiencing loneliness. 3. Park M, Unützer J. Geriatric depression in primary care. Psychiatr Clin North Am As a future geriatrician, I worry about the emotional and mental 2011;34(2):469-x. DOI:10.1016/j.psc.2011.02.009 harms this virus will have on our patient population and health 4. Liguori I, Russo G, Curcio F, et al. Depression and chronic heart failure in the elderly: care providers, and I am motivated and honored to be part of the An intriguing relationship. J Geriatr Cardiol 2018;15(6):451-59. DOI: 10.11909/j. v issn.1671-5411.2018.06.014 relief effort. 5. Ganzini L, Smith DM, Fenn DS, Lee MA. Depression and mortality in medically ill older adults. J Am Geriatr Soc 1997;45(3):307-12. DOI:10.1111/j.1532-5415.1997. Disclosure Statement tb00945.x The author(s) have no conflicts of interest to disclose. 6. Dyrbye LN, West CP, Satele D, et al. Burnout among U.S. medical students, residents, and early career physicians relative to the general U.S. population. Acad Med. 2014;89(3):443-451. DOI:10.1097/ACM.0000000000000134 Acknowledgments 7. Rabow MW, McPhee SJ. Doctoring to heal: Fostering well-being among physicians We would like to thank Leslea Brickner, MD; Trisha Sengupta, MD; and through personal reflection. West J Med 2001;174(1):66-69. DOI: 10.1136/ H Nicole Tran, MD, PhD, for their input and thoughts regarding the patient ewjm.174.1.66. PMID: 11154679. situation and the manuscript, and for providing on-the-job emotional support to 8. Charon R. Narrative medicine: A model for empathy, reflection, profession, and trust. the authors. JAMA 2001;286(15):1897-1902. DOI:10.1001/jama.286.15.1897. Kathleen Louden, ELS, of Louden Health Communications performed a 9. Curley MA, Broden EG, Meyer EC. Alone, the hardest part. Intens Care Med 2020;8:1. DOI: https://doi.org/10.1007/s00134-020-06145-9. PMID: 32514596. primary copyedit.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.149 144 COMMENTARY Is the Psychiatric History Losing Its Relevance?

Richard J Moldawsky, MD1 Perm J 2020;24:19.186 E-pub: 08/05/2020 https://doi.org/10.7812/TPP/19.186

ABSTRACT OBSERVATIONS ON HISTORY-TAKING One of the axioms of medical practice is that obtaining a good It must be acknowledged at the outset that, among mental health history is key to making a correct diagnosis and developing a practitioners, there is an unresolved tension as to the primacy of treatment plan. This is particularly true in psychiatry, in which the medical model in history-taking. The importance of making laboratory or imaging investigations are not typically of great a diagnosis from the Diagnostic and Statistical Manual of Mental value. Any factor that compromises a history may compromise Disorders, Fifth Edition (DSM-V) widely varies depending on care. This area of practice has not been formally studied, although the clinical situation and the evaluator, and therefore taking a it is widely believed to be true. In mental health settings, there are diagnosis-oriented history is irrelevant to some.4 That said, in most many factors that affect obtaining the history. Among these are the settings (if for no other reason than regulatory or billing purposes), skills of the clinician in eliciting relevant information in a limited a DSM-V diagnosis must be made. time, the clinician’s philosophy regarding the importance of such Much of this discussion is based on the widespread belief that history, and lack of formal training in history-taking. Nonphysician obtaining a full history is essential to a correct diagnosis and for clinicians may be more likely than psychiatrists to confront these treatment planning. As with many aspects of clinical practice that barriers. Practice settings may, in their effort to maximize access, are held to be true, there is no good evidence that validates this patient turnover, and cost control, convey a here-and-now ap- belief. Even the recent American Psychiatric Association Guide- proach to patient care, implicitly downplaying the importance of lines on the Psychiatric Evaluation of Adults,5 based on broad a complete history. There may be some cultural factors at play as input from “expert” psychiatrists and others, cites virtual unanim- well, reflecting American society’s gradually decreased interest in ity on the critical importance of the history while noting the lack the study of history. Despite these understandable barriers, the of study of this link. need for a complete history is still the highest priority in an initial The approach to history-taking traditionally starts with the pa- evaluation. Some suggestions are offered to support clinicians’ tient’s chief concern followed by the history of the present illness and organizations’ struggles to keep a comprehensive history at (HPI). The HPI is intended to reflect some sequence of events the forefront of care. and symptoms, which start at whatever point the patient began to experience changes from whatever his/her baseline was. The as- INTRODUCTION sumption is that the patient was in a relatively stable state before One axiom of medical practice is that a good history is key to that onset; on the basis of the patient’s prior history of psychiatric making a diagnosis and developing a treatment plan with the pa- problems and functional level, his/her ability to manage stressors, tient. Despite a clinician’s best efforts, errors will still occur.1, 2 There and current symptoms would vary accordingly, but the HPI dates seems to be relatively little in the published literature or clinical from that point. At times, the HPI may reflect a continuation of guidelines that addresses errors in psychiatric care. Much of what some illness that had never remitted. has been published concerns itself with medications.3 The importance of this (as it relates to diagnosis) is that focusing Psychiatric diagnoses are largely dependent on the patient his- too much on the immediate issue, without assessing the premorbid tory. Although few studies look specifically at history-taking in status, can lead to a less severe diagnosis than is truly called for. psychiatric care, it stands to reason that barriers to obtaining a For example, a patient who reports a few weeks of anxiety and in- proper history will lead to less accurate diagnoses. This Commen- somnia in the context of job stress, leading to perhaps a diagnosis tary identifies some of these barriers—some specific to psychiatric of adjustment disorder or occupational problem, may have a his- history-taking, some more broadly applicable to other specialties— tory of similar episodes that are not work-related but suggest, for and considers some other possible factors not directly related to example, an anxiety, mood, or personality disorder. The premorbid medical care. This is not a catalog of the myriad errors that can be status is relevant to a more accurate diagnosis. Treatment of a less made in taking a history. severe (but incorrect) diagnosis would not likely be very successful, I offer what follows largely on the basis of my own observations and the patient will have unintentionally been denied better care. as a psychiatrist in several interdisciplinary settings over 40 years, including 15 years’ experience as a peer reviewer for the Kaiser Per- manente (KP) Orange County-Anaheim Medical Service Area’s Author Affiliations Department of Psychiatry in CA, and 3 years as an expert reviewer 1 Departments of Psychiatry and Addiction Medicine, Southern California Permanente Medical Group, in psychiatry for the Medical Board of California. Although most Laguna Hills, CA of my work has been with KP, I believe that these observations are Corresponding Author not unique to that model of care. Richard J Moldawsky, MD ([email protected])

Keywords: history, history-taking errors, mental health, mental health evaluation, mental health practitioner, psychiatric history, psychiatric history-taking, psychiatry

The Permanente Journal • https://doi.org/10.7812/TPP/19.186 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 145 COMMENTARY Is the Psychiatric History Losing Its Relevance?

CAUSES OF ERRORS history will necessarily have treatment plans based on precious Errors or omissions in history-taking have many causes, of little information. course, and no one is immune from making them. Clinicians of all In recent years, the focus on customer service and satisfaction disciplines vary in their fund of knowledge and skills regarding di- has led to providing the treatment that a patient wants and will agnostic acumen and interviewing ability. Although such variation accept. Although such patient preferences cannot and should not is likely the most salient factor affecting the quality of the history, be ignored, the odds that that preferred treatment will be effective there are some other factors worth identifying that also play a role. may be quite low if the history is limited. The approach that says, Some form of the medical model generally predominates in most “What can I do for you today?” often presupposes a here-and- mental health settings. However, not all practitioners consider the now framework, which limits how the problem is addressed. The organization of the history that way (ie, HPI and other traditional “quick fix” may be satisfying to the patient, even if not necessarily categories as the personal or developmental history, the family in his/her best interests over the longer term. An organization that history, the social history, and the medical history) as immediately overemphasizes that approach may be doing a disservice to its pa- relevant or helpful to the person being evaluated. If a practitioner’s tients, especially as it tries to simultaneously address broader issues toolkit includes primarily psychotherapies and psychoeducation, of access and cost control. Many mental illnesses are chronic and the role of genetic or medical factors may not seem pertinent. Some recurring, for which a quick-fix model is of limited effectiveness. practitioners are untrained and/or uncomfortable asking about POSSIBLE ROLE OF SOCIETAL FACTORS such factors, so it is predictable that genetic or medical factors are at higher risk of being overlooked. Having discussed some of the clinician and environmental fac- All practitioners are prone to error. Among the better known and tors affecting history-taking, I here briefly review some evidence studied errors are 1) confirmation bias,6 by which we look for data that our American society’s interest in history as a field of study that support what we initially think is the problem, and dismiss or has dwindled, and I speculate that this could have an indirect not pursue data that would cause us to change our first formulation; effect on both clinicians’ and patients’ views of the relevance and 2) premature closure,7 by which we too rapidly decide on a of history to the initial health care evaluation. If our society is, diagnosis and begin to plan treatment for that diagnosis, as if there as a whole, more “here-and-now” oriented and less interested might not be concurrent diagnoses and/or alternative diagnoses to in history in its broader context, such a trend might permeate entertain. To these errors I would add confusing correlation with clinical practice. causation, for example, assuming that the existence of prior trauma Recent data indicate that fewer college students are majoring 8 or substance abuse is the cause of the current clinical situation. in history. This appears to be independent of students’ sex or Each of these kinds of errors closes off the history-taking, and it ethnicity and is correlated with the increased interest in science, is done at the peril of the patient. technology, engineering, and mathematics in school curricula. A practitioner’s professional discipline or theoretical orientation There is also some evidence that history courses offered in colleges also can lead to errors. Psychiatrists who are primarily psycho- are shifting more toward special-interest foci, such as sex-based pharmacologists are at risk of looking narrowly for medication- or ethnic perspectives, and away from the traditional courses 9 responsive symptoms. Those who work in substance abuse are at that address the major historical events or periods. Perhaps the risk of overemphasizing the role of substance use or seeing any newer offerings, although they may well provide some balance situation in terms of addictive behaviors. Those who do primarily and alternate perspectives, do so at the expense of teaching what cognitive behavioral therapy are at risk of ignoring psychodynamic most would call the basics of a given historical era. Might clini- or family factors. In my experience, nonphysician practitioners are cians sometimes be distracted from the basics of a clinical his- more prone than physicians to miss or normalize milder but poten- tory by their own special interests? Might younger clinicians be tially important signs of a major mental disorder, such as suspicion less focused on a patient’s longitudinal history as well? Linking without formal delusions, or heightened self-consciousness without these clinical and societal factors would admittedly be difficult overt paranoia. All mental health practitioners are at risk of not to investigate systematically, but I propose that it may play a role. recognizing medical factors that may be causative or important I posit that the recent interest in the narrower range of some contributors to a set of symptoms. None of the errors described college courses is paralleled by some of the narrowly focused here is unique to any professional discipline or theoretical orienta- histories that I have come across more frequently in my work. tion, and we must all be humble. Examples include the “trauma-focused” history or the “addiction- Errors in history-taking cannot be fully understood without focused” history. Although such histories are often critical, they regard to the practice setting. The pressures of working in a high- should be interpreted in a broader history; otherwise, the errors volume, high-demand environment naturally add stress to an of premature closure and confirmation bias are more likely. The evaluation. This stress, although most commonly experienced in value of a generalist approach to history-taking is that such errors the outpatient setting, also often applies to Emergency Depart- are less likely to reflect a clinician’s bias or expertise, and it allows ment and medical inpatient settings. The need to rapidly assess and the treatment plan to be more comprehensive and accurate. To develop a plan of action in a short time is often achieved at the complete the parallel, one who studies history through, say, the expense of a fuller history. Patients who come to an appointment lens of ethnicity or sex, may find it harder to see a bigger picture. late or are intoxicated or otherwise unable to provide a coherent

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.186 146 COMMENTARY Is the Psychiatric History Losing Its Relevance?

RECOMMENDATIONS How to Cite this Article Moldawsky RJ. Is the psychiatric history losing its relevance. Perm J After the earlier categorization of history-taking errors into 2020;24:19.186. DOI: https://doi.org/10.7812/TPP/19.186 those centered on the clinician, the practice setting, and larger cultural factors, it is appropriate to offer some ideas for decreas- References ing such errors. 1. Crumlish N, Kelly BD. How psychiatrists think. Adv Psychiatr Treat 2009;15(1):72-9. Although not firmly based on scientific study, the expert con- DOI: https://doi.org/10.1192/apt.bp.107.005298 2. Bordage G. Why did I miss the diagnosis? Some cognitive explanations and sensus on the importance of a thorough history should be the educational implications. Acad Med 1999 Oct;74(10 Suppl):S138-43. DOI: https://doi. “default” position. There are times when deviation from a thor- org/10.1097/00001888-199910000-00065 PMID:10536619 ough history is unavoidable, but the clinician must endeavor to 3. Bakhsh HT, Perona SJ, Shields WA, Salek S, Sanders AB, Patanwala AE. Medication errors in psychiatric patients boarded in the emergency department. Int J Risk Saf obtain that history. It means that clinicians need to improve their Med 2014;26(4):191-8. DOI: https://doi.org/10.3233/JRS-140634 PMID:25420761 skills at asking questions and eliciting information in the time 4. Frances A. The new crisis of confidence in psychiatric diagnosis. Ann Intern Med allotted. There are many snares that move the clinician away from 2013;159(3):221-2. DOI: https:doi.org/10.7326/0003-4819-159-3-201308060-00655 PMID:23685989 this task, and therein lies the challenge. Clinicians must be aware 5. Silverman JJ, Galanter M, Jackson-Triche M, et al; APA Work Group on Psychiatric that many diagnoses will fit a patient’s initial complaint and keep Evaluation. The American Psychiatric Association practice guidelines for the as many of those in mind as possible while obtaining the history psychiatric evaluation of adults [Internet]. 3rd ed. Arlington, VA: American Psychiatric Publishing; 2016 [cited 2020 Feb 4]. Available from: https://psychiatryonline.org/doi/ that rules in or out those diagnoses. Such an approach should pdf/10.1176/appi.books.9780890426760 decrease the incidence of the errors discussed earlier. There is no 6. Mendel R, Traut-Mattausch E, Jonas E, et al. Confirmation bias: Why psychiatrists pathognomonic finding for any psychiatric condition. Despite stick to wrong preliminary diagnoses. Psychol Med 2011 Dec;41(12):2651-9. DOI: https://doi.org/10.1017/S0033291711000808 PMID:21733217 the shortcomings of DSM-V both as a diagnostic aid and as a 7. Voytovich AE, Rippey RM, Suffredini A. Premature conclusions in diagnostic helper in treatment planning, there is for now no better system, reasoning. J Med Educ 1985 Apr;60(4):302-7. PMID:3981589 and it is the “coin of the realm.” It can be tempting to dismiss 8. Schmidt BM. The history BA since the great recession. Perspectives on History 2018;56(9). diagnosis altogether, but that has greater risks. 9. Ferguson N. The decline and fall of history [Internet video]. Washington, DC: Health system leaders and clinical managers need to be clear American Council of Trustees and Alumni; 2016 Oct 28 [cited 4 Feb 2020]. Available with clinicians as to what the reasonable expectations are for such from: https://www.goacta.org/higher_ed_now/the_decline_and_fall_of_history initial evaluations, including how to address these individual and system challenges. The use of a template can point a clinician to what the categories are, but without instruction, supervision, and support, the template degenerates into a stereotyped set of preprogrammed phrases without providing clinically meaningful data. Most patient questionnaires and validated rating scales help in highlighting areas for further historical and current exploration but are not, in themselves, diagnostic. Accepting what a patient reports, in an interview or questionnaire, on face value must be resisted; handled sensitively, it will not disrupt the formation of a therapeutic alliance but will reflect the clinician’s desire to more

fully understand the patient. CONCLUSION This Commentary has discussed the link between a good his- tory and good treatment. That this link has not been rigorously studied speaks to the difficult methodologic issues in such a study but perhaps even more to the power of the belief in that link. The noble impulse to be rapidly helpful is only noble if well placed and well timed. Clinicians (and the organizations in which they serve) need to see that the more complete the his- tory, the better the chance to direct that impulse for good. Good treatment demands the best possible history, and despite the unrelenting competing pressures, mental health clinicians must v still aim high.

Disclosure Statement The author(s) have no conflicts of interest to disclose.

Acknowledgments Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

The Permanente Journal • https://doi.org/10.7812/TPP/19.186 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.3 147 COMMENTARY Furin Protease: From SARS CoV-2 to Anthrax, Diabetes, and Hypertension

Kara Fitzgerald, ND1 Perm J 2020;24:20.187 E-pub: 09/16/2020 https://doi.org/10.7812/TPP/20.187

ABSTRACT from Bacillus anthracis, and furin cleavage allows the anthrax toxin Furin is a protease that is ubiquitous in mammalian metabo- to flood the body before innate immunity kicks in effectively,7 lism. One of the innovations that make sudden acute respiratory greatly increasing lethality. Similarly, the SARS-CoV-2 viral load syndrome-coronavirus 2 (SARS-CoV-2) more infectious than its can overwhelm the system before innate immunity can bring it ancestor viruses is the addition of a furin cleavage site. Conditions under control.8 It is well known that underlying comorbidities associated with elevated furin levels, including diabetes, obe- have a pronounced effect on the lethality of coronavirus disease sity, and hypertension, overlap greatly with vulnerability to the 2019 (COVID-19). Here, we explore the possibility that baseline severe form of coronavirus disease 2019 (COVID-19). We suggest inflammation contributes to a delayed response from the innate that diet and lifestyle modifications that reduce the associated immune system, and that furin itself might hold a key role in both comorbidities may prevent the development of severe COVID-19 the virus-initiated delayed immune response and the influence of by, in part, lowering circulating furin levels. Likewise, natural and comorbidities. pharmaceutical inhibitors of furin may be candidate prophylactic interventions or, if used early in the COVID-19, may prevent the ROLE OF FURIN IN DISEASE development of critical symptoms. Furin is a key protease in humans. It is ubiquitous in nature, including other mammals, where it is found in the Golgi apparatus INTRODUCTION and on the cell surface of most tissue cell types. Furin exists in both The sudden acute respiratory syndrome-coronavirus 2 (SARS- membrane-bound and secreted forms. Furin cleaves and activates a CoV-2) has a spike protein that binds to a cell’s angiotensin-con- diverse group of more than 100 proproteins and peptides in normal verting enzyme 2 (ACE2) receptor, locking it on the cell membrane. human physiology. Higher plasma furin levels have been identi- To enter the cell, however, the virus must leave the spike protein fied in individuals on the cardiometabolic continuum years before behind. Coutard et al1 recently proposed that the SARS-CoV-2 the onset of diabetes. Furin, independent of all other risk factors, spike glycoprotein (S) contains a furin cleavage complex (FCC). is associated with an increased risk of diabetes, hyperinsulinemia, The FCC adds to SARS-CoV-2 infectivity and pathogenicity in hypertension, hyperlipidemia, obesity, and all-cause mortality.9,10 multiple ways. Fernandez and colleagues9 explain: “Regarding potential mecha- nisms, as furin is responsible for the maturation of the insulin pro- VIRAL HIJACKING OF FURIN PROTEASE receptor, one could speculate that more furin in circulation reflects a Furin is a protease essential to the mammalian host’s biochemis- compensatory mechanism to increase the synthesis of active insulin recep- try, but in this instance, it is hijacked by SARS-CoV-2 to facilitate tors. Another possible mechanism of action of furin in [diabetes mellitus] the separation preliminary to entering the cell. The FCC greatly development may be via pancreatic β-cells; furin has been demonstrated enhances the virus’s infectivity, and it is a strong candidate as the to control the proliferation and differentiation of pancreaticβ -cell lines gain-of-function2 mutation that enabled SARS-CoV-2 to jump and to be involved in the maturation of insulin secretory granules.” from animals to humans and rapidly spread to pandemic levels. Why has the US been overwhelmed with COVID-19 cases? In addition to using furin to gain entry into the host cell, SARS- More than 1 in 3 Americans have cardiometabolic disease,11 and CoV-2 also uses endogenous furin to cleave the S protein in the individuals on the cardiometabolic continuum are hardest hit by the trans-Golgi network right after virion assembly. This latter mecha- virus. A reason for this finding may be the presence of elevated furin nism separates furin from other virally hijacked proteases (eg, TM- levels identified in this population, even well before the onset of RPCC2), potently increasing the pathogenicity of SARS-CoV-2.2 disease, making them particularly vulnerable to the SARS-CoV-2 Infection with a variant of SARS-CoV-2 that omits the FCC site cellular entry and replication. resulted in a blunted illness in hamsters.3 Braun and Sauter4 note Beyond entry and replication, furin also activates a number of that the ability of viruses to exploit furin may have major effects peptides in normal human physiology that may influence CO- on their pathogenicity. In fact, as observed in the hamster study VID-19 pathogenesis. For example, furin modulates the renin by Lau et al,3 the same virus without the FCC might be avirulent, whereas the addition of the FCC can allow the virus to spread systemically and cause higher rates of mortality. Furin is present 5 Author Affiliations in most tissues and is highly expressed in the lungs. 1 Institute for Functional Medicine, Federal Way, WA We already know that furin plays a role in the potent virulence of dengue fever and other aggressive infections, including HIV Corresponding Author and various avian influenzas.6 Anthrax toxin is liberated by furin Kara Fitzgerald, ND ([email protected])

Keywords: furin, furin cleavage complex, furin protease, SARS-CoV-2

The Permanente Journal • https://doi.org/10.7812/TPP/20.187 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 148 COMMENTARY Furin Protease: From SARS CoV-2 to Anthrax, Diabetes, and Hypertension

angiotensin aldosterone system (RAAS)12 by activating the pro- through diet, lifestyle modifications, and pharmacologic manage- renin receptor, which mediates formation of vasoconstrictor angio- ment is a logical strategy for reducing COVID-19 pathogenicity. tensin. Recall angiotensin promotes release of aldosterone, sparing Natural and pharmacologic furin inhibitors may prove highly useful v sodium at the expense of potassium. Hypokalemia (and RAAS to inhibit viral entry and propagation. interference through ACE2) are present in COVID-19,13 although whether furin plays a key role here remains to be elucidated. Disclosure Statement The author(s) have no conflicts of interest to disclose. Coagulopathy and associated hypoxia involving von Willebrand factor and clotting factor VIII appear to play a central role in Acknowledgments COVID-19 pathology. Furin is necessary for activation of clot- 14 Kathleen Louden, ELS, of Louden Health Communications performed a ting factor VIII. Notably, furin expression is potently induced primary copyedit. by hypoxia,4 as all 3 FUR promoters harbor binding sites for the hypoxia inducible factor-1 (HIF-1). Severe hypoxia is, of course, How to Cite This Article a hallmark finding in the most severe COVID-19 cases. Fitzgerald K. Furin protease: From SARS CoV-2 to anthrax, diabetes, and The following questions remain to be answered: hypertension. Perm J 2020;24:20.187. DOI: https://doi.org/10.7812/TPP/20.187. 1. Do individuals with the comorbidities associated with CO- VID-19 have higher baseline furin levels that increase SARS- References CoV-2 infectivity and pathogenicity? 1. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site 2. Given the ubiquitous nature of furin proteases in normal absent in CoV of the same clade. Antiviral Res 2020 Feb;176:104742. DOI: https:// human physiology, could this coincide with known SARS- doi.org/10.1016/j.antiviral.2020.104742. CoV-2 pathogenic mechanisms? 2. Li H, Wu C, Yang Y, et al. Furin, a potential therapeutic target for COVID-19 [Chinese]. ChinaXiv 2020 Feb 23;202002.00062 [cited 2020 Aug 24]. Available from: 3. Could these coincidences increase when the baseline furin www.chinaxiv.org/abs/202002.00062. level is increased? 3. Lau S-Y, Wang P, Mok BW-Y, et al. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction. Emerg Microbes Infect 2020 May 4;175:1-15. DOI: https://doi.org/ TREATMENT OPTIONS 10.1080/22221751.2020.1756700. 4. Braun E, Sauter D. Furin-mediated protein processing in infectious diseases and Nonspecific furin inhibition may be associated with substantial cancer. Clin Transl Immunol 2019 Aug 5;8(8):e1073. DOI: https://doi.org/10.1002/ side effects given the myriad roles furin plays in human physiology. cti2.1073. 5 5. Belen-Apak FB, Sarialioglu F. The old but new: Can unfractioned heparin and low Heparin, however, is a furin inhibitor with a known and generally molecular weight heparins inhibit proteolytic activation and cellular internalization accepted risk-benefit ratio. Given the risk of coagulopathy seen in of SARS-CoV2 by inhibition of host cell proteases? Med Hypotheses 2020 some patients with COVID-19, it isn’t surprising that heparin use Sep;142:109743. DOI: https://doi.org/10.1016/j.mehy.2020.109743. 15 6. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, has been associated with lower mortality in hospitalized patients. and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020 Apr 16;181(2):281- Furin expression is potently induced by hypoxia, as all 3 FUR gene 92.e6. DOI: https://doi.org/10.1016/j.cell.2020.02.058. promoters harbor binding sites for hypoxia-inducible factor-1 7. Stubbs MT II. Anthrax X-rayed: New opportunities for biodefence. Trends Pharmacol Sci 2002 Dec;23(12):539-41. DOI: https://doi.org/10.1016/S0165-6147(02)02127-2. (HIF-1). Berberine is an HIF-1 inhibitor, and may therefore be 16 8. Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential a treatment consideration for COVID-19 patients. Resolving vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy cardiometabolic diseases through diet, lifestyle modifications, and Immunol 2020 Mar;38(1):1-9. DOI: https://doi.org/10.12932/AP-200220-0772. 9. Fernandez C, Rysä J, Almgren P, et al. Plasma levels of the proprotein convertase pharmaceutical interventions should reduce furin levels and base- furin and incidence of diabetes and mortality. J Intern Med 2018 Oct;284(4):377-87. line inflammation, which could reduce viral entry and replication, DOI: https://doi.org/10.1111/joim.12783. allowing the innate immune system to better respond and leading 10. Ji H-L, Zhao R, Matalon S, Matthay M. Elevated plasmin(ogen) as a common risk factor for COVID-19 susceptibility. J Physiol Rev 2020 Jul;100(3):1065-75. DOI: to a more benign course of illness. Natural compounds with in https://doi.org/10.1152/physrev.00013.2020. vitro evidence of potential effectiveness and a good safety profile 11. Prediabetes—Your chance to prevent type 2 diabetes. Atlanta, GA: Centers for include 4 flavonoids that appear to inhibit furin catalytic activity: Disease Control and Prevention. Reviewed 2020 Jun 11 [cited 2020 Sep 2]. Available (1) luteolin (> 95% inhibition in vitro),17 (2) baicalein, (3) chrysin, from: https://www.cdc.gov/diabetes/basics/prediabetes.html. 18 12. Cilhoroz BT, Schifano ED, Panza GA, et al. FURIN variant associations with and (4) oroxylin. postexercise hypotension are intensity and race dependent. Physiol Rep 2019 Feb;7(3):1-13. DOI: https://doi.org/10.14814/phy2.13952. LABORATORY TESTING 13. Chen D, Li X, Song Q, et al. Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China. JAMA Netw Open If furin proves to play an important role in COVID-19 patho- 2020;3(6):e2011122. doi: https://doi.org/10.1001/jamanetworkopen.2020.11122. genesis, serum furin measurement could be useful. However, furin 14. Mazurkiewicz-Pisarek A, Płucienniczak G, Ciach T, Płucienniczak A. The factor testing is currently limited to the research setting only. VIII protein and its function. Acta Biochim Pol 2016;63(1):11-16. DOI: https://doi. org/10.18388/abp.2015_1056. 15. Ayerbe L, Risco C, Ayis S. The association between treatment with heparin and CONCLUSION survival in patients with Covid-19. J Thromb Thrombolysis 2020 Aug;50(2):298-301. Comorbidities associated with COVID-19 include those that DOI: https://doi.org/10.1007/s11239-020-02162-z. 16. Lin S, Tsai S-C, Lee C-C, Wang B-W, Liou J-Y, Shyu K-G. Berberine inhibits HIF-1α comprise cardiometabolic disease, including obesity, diabetes, and expression via enhanced proteolysis. Mol Pharmacol 2004 Sep;66(3):612-19. hypertension. These conditions are associated with increased cir- 17. Peng M, Watanabe S, Chan K, et al. Luteolin restricts dengue virus replication culating furin levels. Because SARS-CoV-2 uses elevated furin to through inhibition of the proprotein convertase furin. Antiviral Res 2017 Jul;143:176- 85. DOI: https://doi.org/10.1016/j.antiviral.2017.03.026. both gain cellular entry (through the FCC gain-of-function muta- 18. Majumdar S, Mohanta BC, Chowdhury DR, Banik R, Dinda B, Basak A. Proprotein tion) and to propagate with a high level of efficiency, it overwhelms convertase inhibitory activities of flavonoids isolated from oroxylum indicum. Curr the body’s ability to orchestrate an effective immune response. Med Chem 2020;17(19):2049-58. DOI: https://doi.org/10.2174/092986710791233643. Addressing comorbidities (and associated elevated furin levels)

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Arthur L Klatsky, MD1; H Nicole Tran, MD, PhD2 Perm J 2020;24:19.162 E-pub: 04/03/2020 https://doi.org/10.7812/TPP/19.162

How quaint the ways of Paradox! other evidence of cardiac activity—hence (mostly Asian Indians but also Pakistanis, At common sense she gaily mocks! the pulsus paradoxus. Modern physiologic Sri Lankans, Nepalese, and Bangladeshi), Though counting in the usual way, explanations usually invoke fixation of the and 1242 other Asians (mostly Koreans Years twenty-one I’ve been alive. pericardium to adjacent structures plus or Vietnamese). Only 10% of the SA in- Yet, reckoning by my natal day, increased venous return during inspiration. dividuals were born in the US. I am a little boy of five! — Frederick, in The Pirates of Penzance, PARADOXES ABOUND SOUTH ASIAN DISPARITIES 1 WS Gilbert and A. Sullivan, 1879 Epidemiologists have an appreciation of The 3 most striking disparities we found the paradox concept. Widely cited examples involved SAs (Table 1). The SA individuals ABSTRACT include the following: 1) The French paradox, had 1) higher CAD risk than whites or any For several decades we have studied which refers to the low incidence of athero- other ASAM group,7,8 2) lower cancer risk health outcomes in identified Asian Ameri- sclerotic coronary artery disease (CAD) in than whites or any other ASAM group,9 can (ASAM) ethnic groups, comparing southern France despite a high-fat diet3,4; and 3) similar venous thromboembolism ASAM subgroups to whites and to each 2) the Hispanic paradox or Latino paradox, (VTE) risk to whites, whereas Chinese, other. The most striking disparities we which refers to the finding that Latinos Filipino, Japanese, and other Asian groups found involved South Asians (SAs). The tend to have health outcomes comparable each had lower VTE risk.10 As these find- SA individuals had higher coronary artery to or better than those of their US non- ings unfolded, it seemed that the health disease (CAD) risk and lower cancer risk Hispanic white counterparts, even though risks in SAs differed in some important but than whites or any other ASAM group. The Hispanics have lower mean income and unclear ways from the other ASAM groups SA individuals also did not share the lower education5; and 3) the obesity paradox, in our cohorts. Temporarily stretching the venous thromboembolism risk of all other which refers to the relatively favorable prog- precise definition of paradox cited at the ASAM groups. The relatively low prevalence nosis of obese patients with cardiovascular beginning of this article, we thought of our of CAD risk traits in SAs with high CAD disease.6 Determining the explanations for observations as SA paradoxes. incidence defines a paradox. Exploration of such phenomena is intellectually satisfying The high risk of CAD among SAs is these data might help the search for thera- and often scientifically useful. None of these confirmed by previous reports,10 and the peutic and preventive medical benefits. phenomena has an established explanation. relationship could plausibly be consid- Among suggestions in the literature are the ered established.11 The association is not BACKGROUND: A USEFUL PARADOX Mediterranean diet, including wine, as a ba- limited to ASAMs and has been reported We all enjoy solving a riddle, although sis for the French paradox, selective migration in SA populations in the UK, Singapore, we probably wish for a more challenging of healthy persons as a factor in the Latino India, and other locations.5,10,11 Proposed conundrum than a leap year February 29th paradox, and diagnosis earlier in the disease hypothetical mechanisms include high birthday. Usually defined as a seemingly course as a basis for the obesity paradox. prevalence of the metabolic syndrome, self-contradictory or absurd statement or heightened genetic susceptibility to con- proposition, the appropriateness of the term KAISER PERMANENTE ASIAN ventional risk factors, nonconventional paradox is often unclear. For example, medi- ETHNICITY STUDIES dyslipidemia traits, and lifestyle traits, such cal students learn about pulsus paradoxus For several decades we have studied as ingestion of ghee (clarified butter). The or paradoxical pulse, usually defined as an health measurements and outcomes in evidence for none of these seems convinc- abnormally large decrease (≥ 10 mmHg) in identified Asian American (ASAM) eth- ing to us. In our cohort, SAs had a slightly systolic blood pressure during inspiration. nic groups. The underlying hypothesis of lower prevalence of conventional CAD risk A fairly reliable sign in pericardial effusion this work was that the evident sociocultur- factors at baseline.7,9 Furthermore, after age with cardiac tamponade, the term pulsus al diversity of these groups would lead to paradoxus sometimes seems a misnomer. important disparities in incident medical The phenomenon is actually not paradoxical conditions. We compared all ASAM and because it is an exaggeration of the normal individual ASAM ethnicities to whites, Author Affiliations 1 Division of Cardiology, Kaiser Permanente Medical Center, Oakland CA inspiratory blood pressure response rather the largest group, and made inter-ASAM 2 comparisons within the ASAM stratum. Department of Adult and Family Medicine and Graduate Medical than an opposite or contradictory one. To Education, Kaiser Permanente Medical Center, Oakland CA understand the use of the term, one must Our largest cohort with defined ASAM look to early descriptions by Kussmaul subgroups included 273,843 persons of Corresponding Author and others.2 In severe cardiac tamponade, whom 20,685 (7.6%) were ASAM. The Arthur L Klatsky, MD ( [email protected]) an absent pulse was noted during inspira- ASAMs included 9519 Chinese, 5898 tion simultaneous with heart sounds or Filipinos, 2999 Japanese, 1117 SAs Keywords: Asian Americans, cancer, coronary disease, epidemiology, ethnicity, paradox, race, risk factors, South Asian, venous thromboembolism

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adjustment, covariate control had little ef- There are other reports of low VTE risk with respect to culture, religion, and his- fect on our CAD risk estimates. in Asians,14,15 although we believe that our tory. Using linguistic roots as an indicator The high CAD risk of SAs in the face of recent publication may be the first to show over the ages, China is the major cultural relatively low prevalence of CAD risk traits the disparity between SA and other Asian influence on East Asia (Korea, Japan, Viet is the inverse of the French paradox. The groups. Published hypothetical explana- Nam, and others). Linguistic and cultural French have a low CAD rate despite rela- tions for lower VTE risk among Asians roots of the SA countries are complex, tively high prevalence of CAD risk traits. have focused on genetic factors.16,17 with evidence of evolution from several Thus, both phenomena have internal incon- Indo-Aryan languages, including Dravid- sistency and, in Mr Gilbert’s memorable GEOGRAPHY AND GENEALOGY ian, Bengali, Tamil, Punjabi, Dardic, and words, “gaily mock common sense.”1 Both We use the term geography as a rough in- others. Southeast Asia has linguistic roots phenomena seem to fit the paradox defini- dicator of environment or nurture, whereas in China, India, and Western culture, es- tion. Management of the known risk factors the term genealogy is an indicator of genes pecially in colonized countries such as the substantially reduces CAD risk in Western or nature. Few medical conditions are not Philippines. Ample basis exists for SA vs populations. It is unknown whether this is influenced by both, and this is clearly the East Asian diversity in environmental risk true for SAs, but in the absence of explana- case for the conditions considered in this factors for disease. There is less basis for tion, intensive management of traditional Commentary. Much is known about en- disparity between the East and Southeast risk traits is our only logical recourse, vironmental risk traits for CAD, various Asian countries. This simplistic discus- The low cancer risk among SAs is a cancers, and VTE, and data about genetic sion does not consider North Asian and surprising finding and has been sparsely factors are rapidly being uncovered. Western Asian areas, but we studied no reported. The phenomenon is not attrib- Asia’s land area of 17,212,000 square subgroups from those areas. utable to a lower risk of only a few cancer miles composes approximately 30% of the The vast Indian subcontinent is substan- types.13 Comparison of risk of SAs with Earth’s total, and its 4.5 billion people rep- tially separated from East and Southeast whites for the 10 most common cancer resent approximately 60% of the world’s Asia by the world’s highest mountains. types showed that SA men had lower risk population.18,19 Asia is bounded by the Thus, its inhabitants have had less genetic for 9 of these types and SA women were Arctic Ocean to the north, the Pacific and cultural interaction with East and at lower risk for 8 types.13 Because SAs are Ocean to the east, the Indian Ocean to the Southeast Asians than the latter have had not known to have a high prevalence of south, the Red Sea (as well as the inland with each other.20 To complicate mat- cancer risk traits, their low cancer incidence seas of the Atlantic Ocean: The Mediter- ters, there is considerable phenotypic and is not paradoxical. Finding explanations and ranean and the Black) to the southwest, culturally heterogeneity within the SA naturally present genetic factors that may and Europe to the west. Asian climate population itself. Genetic studies based on decrease the risk of cancers could lead to zones range from the Arctic to the tropi- fossilized bone involved 25 diverse groups targeted therapy and prevention. cal and desert. Ethnic diversity abounds and strongly suggested that 2 genetically

Table 1. South Asian health disparities Coronary artery diseasea Cancerb Venous thromboembolismc Ethnicity OR (95% CI) p value OR (95% CI) p value OR (95% CI) p value Adjusted risk of conditions vs whites White 1.0 [Reference] — 1.0 [Reference] — 1.0 [Reference] — All Asian 1.0 (0.9-1.0) 0.2 1.0 (0.9-1.1) 0.5 0.5 (0.5-0.6) < 0.001 Chinese 0.8 (0.7-0.9) < 0.001 1.1 (1.1-1.2) 0.002 0.5 (0.4-0.6) < 0.001 Japanese 0.9 (0.7-1.1) 0.2 1.1 (1.0-1.3) 0.2 0.5 (0.3-0.6) < 0.001 Filipino 1.2 (1.0-1.3) 0.02 0.9 (0.8-1.0) 0.02 0.6 (0.5-0.7) < 0.001 South Asian 2.4 (1.9-3.2) < 0.001 0.5 (0.3-0.7) < 0.001 0.9 (0.5-1.4) 0.6 Other Asiand 0.8 (0.5-1.1) 0.4 0.8 (0.6-1.1) 0.2 0.4 (0.0-0.8) 0.005 Adjusted risk of conditions vs South Asians South Asian 1.0 [Reference] — 1.0 [Reference] — 1.0 [Reference] — Chinese 0.3 (0.2-0.3) < 0.001 3.3 (2.0-5.0) < 0.001 0.6 (0.3-0.9) 0.02 Japanese 0.3 (0.2-0.4) < 0.001 2.5 (2.0-5.0) < 0.001 0.4 (0.2-0.9) 0.01 Filipino 0.3 (0.3-0.4) < 0.001 2.0 (1.1-3.3) 0.01 0.5 (0.2-0.9) 0.10 Other Asiand 0.4 (0.2-0.3) < 0.001 2.5 (1.3-5.0) 0.005 0.4 (0.2-1.0) 0.04 a Cox proportional hazards regression models in 7658 persons with coronary artery disease hospitalization vs 118,430 without coronary artery disease hospitalization, controlling for age, sex, smoking, alcohol, body mass index, educational level, marital status, and cardiorespiratory composite.7 b Logistic regressions controlling for baseline age, sex, educational level, body mass index, and smoking in 273,843 persons with 28,303 deaths attributed to cancer.5 c Logistic regressions controlling for baseline age, sex, educational level, body mass index, and smoking in 61,459 persons, with 4674 diagnosed with venous thromboembolism.9 d Mostly Korean and Vietnamese. CI = confidence interval; OR = odds ratio.

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5. Iribarren C, Darbinian JA, Fireman BH, Burchard EG. divergent ancient populations were an- age (years of life vs number of birthdays) Birthplace and mortality among insured Latinos: The cestral to contemporary SA.20 Neither is readily resolved the age paradox of our paradox revisited. Am J Epidemiol 2003;158:585-95 genetically close to East Asians. One, called birthday boy, Frederick. Defining paradox 6. Elagizi A, Kachur S, Lavie CJ, et al. An Overview and Update on Obesity and the Obesity Paradox in Ancestral North Indians, is “genetically is more difficult, but after agreeing that Cardiovascular Diseases. Prog Cardiovasc Dis 2018 close to middle Easterners, Central Asians, internally contradictory data are the es- Jul - Aug;61(2):142-50. DOI: https://doi.org/10.1016/j. and Europeans.”20 The other, called Ances- sence of a paradox, we saw that the high pcad.2018.07.003. [Review] PMID:29981771 7. Klatsky AL, Tekawa I, Armstrong MA, Sidney S. The tral South Indians, is genetically “as distinct CAD risk of SA could be labeled as such. risk of hospitalization for ischemic heart disease from Ancestral North Indians and East The other SA disparities fail to satisfy the among Asian Americans in Northern California. Am J Asians as they are from each other.”19 These paradox definition. Public Health 1994 Oct;84(10):1672-5. DOI: https://doi. org/10.2105/AJPH.84.10.1672 PMID:7943495 facts are compatible with the existence of a A paradox, with its contradictory evi- 8. Hajra A, Li Y, Siu S, et al. Risk of coronary artery genetic factor in the disparateness between dence, may evoke a feeling of something disease in South Asian Americans. J Am Coll Cardiol SAs and East Asians for risk of CAD, mysterious, possibly larger and more basic 2013 Aug;62(7):644-5. DOI: https://doi.org/10.1016/j. jacc.2013.05.048 PMID:23770164 cancer, and VTE. In fact, we suspect that than a mere research query. The use of the 9. Tran HN, Udaltsova N, Li Y, Klatsky AL. Low cancer genetic factors are the dominant explana- term may draw extra focus by researchers risk of South Asians: A brief report. Perm J 2018;22:17- tion for the differences between SAs and and clinicians, which is not necessarily a 095. DOI: https://doi.org/10.7812/TPP/17-095 PMID:29616905 East Asians. They also may help to explain bad thing as long as other unanswered 10. Tran HN, Klatsky AL. Lower risk of venous the SA vs white differences for CAD and queries receive proper attention. In fact, thromboembolism in multiple Asian ethnic groups. cancer. popularization of the SA paradox concept Prev Med Rep 2019 Jan 15;13:268-9. DOI: https://doi. org/10.1016/j.pmedr.2019.01.006 PMID:30723661 The racial groups called Asian in our might promptly enhance changes to salu- 11. O’Connor A. Why do South Asians have such high studies were chosen because of adequate tary health behaviors. rates of heart disease? The New York Times 2019 Feb ASAM numbers and identification by 12; Sect D:4 CONCLUSION 12. Volgman AS, Palaniappan LS, Aggarwal NT, et al.; national origin. The same is true for most American Heart Association Council on Epidemiology other studies of ASAMs. These epide- Disparities in SA health outcomes and Prevention; Cardiovascular Disease and Stroke miologic reports clearly do not include all include a puzzling high CAD risk, here in Women and Special Populations Committee of the Council on Clinical Cardiology; Council on geographic Asians. More importantly, in called the SA paradox. We hope that future Cardiovascular and Stroke Nursing; Council on view of the cultural and genetic dispari- investigations will lead to elucidation of Quality of Care and Outcomes Research; and Stroke Council. Atherosclerotic Cardiovascular Disease in ties we have cited, why should one expect new remediable environmental CAD risk South Asians in the United States: Epidemiology, similarities among all Asians? traits and to a better understanding of the Risk Factors, and Treatments: A Scientific Statement Many of the individuals we studied role of genetic variants in the risk of mul- From the American Heart Association. Circulation v 2018 Jul 3;138(1):e1-34. DOI: https://doi.org/10.1161/ (118,430 of 273,843 [43.2%]) had an tiple diseases. CIR.0000000000000580 PMID:29794080 opportunity to self-classify race by the 13. Tran HN, Li Y, Udaltsova N, Armstrong MA, query, “What is your race?” There were 6 Disclosure Statement Friedman GD, Klatsky AL. Risk of cancer in Asian The author(s) have no conflicts of interest to Americans: A Kaiser Permanente cohort study. check sheet options (white, black, Asian, disclose. Cancer Causes Control 2016 Oct;27(10):1197-207. Hispanic, mixed, or other), with 4 Asian DOI: https://doi.org/10.1007/s10552-016-0798-2 subcategory options (Chinese, Japanese, PMID:27562672 Acknowledgments 14. Heit JA, Spencer FA, White RH. The epidemiology of Filipino, or other Asian). We ultimately Laura King, ELS, performed a primary copy edit. venous thromboembolism. J Thromb Thrombolysis classified 714 of these individuals as 2016 Jan;41(1):3-14. DOI: https://doi.org/10.1007/ SA. Slightly more than half (374 of 714 How to Cite this Article s11239-015-1311-6 PMID:26780736 15. Lee LH, Gallus A, Jindal R, Wang C, Wu CC. [52%]) had checked the major category Klatsky AL, Tran HN. The South Asian paradox. Incidence of Venous Thromboembolism in Asian other rather than Asian, suggesting that a Perm J 2020;24:19.162. DOI: https://doi. Populations: A Systematic Review. Thromb Haemost large proportion of SAs did not consider org/10.7812/TPP/19.162 2017 Dec;117(12):2243-60. DOI: https://doi. org/10.1160/TH17-02-0134 PMID:29212112 themselves Asian. Anecdotal evidence 16. Klatsky AL, Armstrong MA, Poggi J. Risk of pulmonary leads us to believe that most of these per- References embolism and/or deep venous thrombosis in Asian- sons equated Asian with East Asian and/ 1. Gilbert WS, Sullivan A. The pirates of penzance. Americans. Am J Cardiol 2000 Jun 1;85(11):1334-7. London, UK: Novello and Company; 1879 DOI: https://doi.org/10.1016/S0002-9149(00)00766-9 or Southeast Asian. This ambiguity about 2. Bilchick KC, Wise RA. Paradoxical physical findings PMID:10831950 race reminds us that some argue that race described by Kussmaul: Pulsus paradoxus and 17. Klatsky AL, Baer D. What protects Asians from venous is primarily not genetic but rather a social Kussmaul’s sign. Lancet 2002 Jun 1;359(9321):1940- thromboembolism? Am J Med 2004 Apr 1;116(7):493- 2. DOI: https://doi.org/10.1016/S0140-6736(02)08763- 5. DOI: https://doi.org/10.1016/j.amjmed.2004.01.005 construct. Although we only partially 9 PMID:12057571 PMID:15047041 agree, it seems clear that the term needs 3. St Leger AS, Cochrane AL, Moore F. Factors 18. National Geographic Family Reference Atlas of the definition in scientific studies. associated with cardiac mortality in developed World. Washington, DC: National Geographic Society; countries with particular reference to the consumption 2006. p 264 of wine. Lancet 1979 May 12;1(8124):1017-20. DOI: 19. Ethnic groups Prehistoric centres and ancient THE POWER OF WORDS https://doi.org/10.1016/S0140-6736(79)92765-X migrations [Internet]. Chicago, IL: Encyclopedia Clear scientific discourse requires accu- PMID:86728 Britannica; 2020 [cited 2020 Jan 27]. Available from: 4. Klatsky AL. Alcohol and cardiovascular diseases: www.britannica.com/place/Asia/Ethnic-groups rate concise definitions. It is not always easy Where do we stand today? J Intern Med 2015 20. Reich D, Thangaraj K, Patterson N, Singh L. to reach agreement, but, when achieved, Sep;278(3):238-50. DOI: https://doi.org/10.1111/ Reconstructing Indian population history. Nature definitions make it easier to point to errors. joim.12390 PMID:26158548 2009 Sep 24;461(7263):489-94. DOI: https://doi. org/10.1038/nature08365 PMID:19779445 Reconciliation of conflicting definitions of

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Created by Kelly Collins BSN, RN, CWOCN1 and Erika Yazdanbakhsh MSN, CNL, RN, CWON2 Perm J 2020;24:19.118 E-pub: 08/05/2020 https://doi.org/10.7812/TPP/19.118

In the Hospital setting, having a Certified Wound Ostomy The guide template is being used in our hospital wound educa- Continence Nurse (CWOCN) to direct wound care treatment is tion sessions. The registered nurses in attendance are given the guide incredibly helpful to the physician, surgeon and nurses. However, template, shown a series of complex wounds and asked to choose there are times when there is no CWOCN available. It became a dressing. A Skin and Wound Assessment Team (SWAT), made evident that staff needed a better resource or tool to refer to when up of nurses interested in and specially trained in wound care, use there was no CWOCN coverage. The Hospital CWOCN sought the Kaiser Santa Rosa Hospital version of the guide template on to find a wound care guide to be used by staff when there was no the medical surgical units to offer dressing suggestions. Feedback CWOCN coverage, however, all the resources she found seemed has been very positive from physicians and nurses who have suc- one directional and were unable to account for multiple wound cessfully used this version of the guide template when there was characteristics. Wound care treatment recommendations need to no CWOCN available. be decided based upon a multitude of factors, not just a linear set of questions that lead to one answer which may be an improper CONSENT treatment recommendation and can cause important factors to go Kelly Collins and Erika Yazdanbakhsh give consent to publish unrecognized or untreated. Collins Complex Wound Guide Template online in the Nursing This is what inspired the creation of the Collins Complex Wound Research and Practice section of The Permanente Journal. Guide Template (available at www.thepermanentejournal.org/ Collins Complex Wound Guide Template is not research and v files/2020/19.118supp.pdf ). The guide template was developed does not include PHI. by a board certified wound, ostomy and continence nurse of many years’ experience, in consultation with other CWOCN nurses and hospitalists who see patients with complex wounds. The goals set for this Complex Wound Guide Template were to develop a guide template that could: - Address complex wounds as these seem to be the most intimi- dating types of wounds staff encounter. -Lead the clinician to a safe treatment recommendation every time. -Be simple enough that anyone, (a layperson) could technically use the guide template and select a safe treatment recommenda- tion.) SUMMARY OF GUIDE TEMPLATE

Collins Guide Templet has a row of five complex wound pictures, each with a brief description of the therapy goal. The clinician chooses the wound most closely resembling the wound needing a dressing. In the next row, the clinician chooses between depth or no depth based upon the appearance of the wound. The clinician then selects the amount of drainage and is led to a box that has safe treatment options for the wound. This multidirectional approach is essential to aid the clinician to a safe treatment option and this is why the guide is successful. It is imperative, however, that the treatment options inserted into the guide template are entered under the professional guidance of a CWOCN in conjunction with the MD using facility approved Author Affiliations product formulary items and with consideration of patient care 1 Inpatient Wound and Ostomy Nurse Specialist for Kaiser Foundation Hospital in Santa Rosa, California setting. Collins Complex Wound Guide Template has been shared 2 Ostomy Nurse Specialist for Kaiser Permanente in Portland, Oregon with the Kaiser Northern California WOCN Peer Group and has been utilized by other CWOCNs at Kaiser Permanente facilities Corresponding Authors who have adjusted the dressing options listed in the Kaiser Santa Kelly Collins BSN, RN, CWOCN ([email protected]) Erika Yazdanbakhsh MSN, CNL, RN, CWON ([email protected]) Rosa Hospital version to fit their facility’s needs. Keywords: wound, nursing, complex wounds, pressure injury, treatment options

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HEALTH CARE COMMUNICATION Narrations In Psychiatry Training Hena Jawaid, MBBS, FCPS (Psychiatry)1,2 Perm J 2020;24:19.218 E-pub: 04/16/2020 https://doi.org/10.7812/TPP/19.218

“… and then he yelled over me and I was confused about what to All it requires is active listening, keeping aside checklists and say. I wanted to stop him, but I was overwhelmed by the memories criteria. and flashbacks of my childhood when my father used to shout at my With time, a person gradually gets a grip on personality types, mother in a same way …” coping mechanisms, varying life circumstances, and diverse I was looking at her lips, fingers, and body language, which backgrounds. The opportunity to see a person beyond the arena were following the tone of her speech and the context while she of didactic explanations enriches a trainee. was telling me her thoughts and how she responded to one of The urgency of diagnosis incites a trainee into a spiral of quick her stressors. I was conceptualizing her story in my mind, trying prescription, treatment, alternatives, and thus, poor management. to piece together the whole picture into an algorithm of Inter- The havoc creates anxiety and worry in patients and their families national Classification of Diseases, 11th Edition or Diagnostic (and physicians too) that is mind-wrecking and damaging for the and Statistical Manual of Mental Disorders, Fifth Edition—an physician-patient alliance as well. algorithm of guidelines, concepts, criteria, definitions, and sche- The whole phenomenon of deciphering the issue takes time mas. I was trying to squeeze the protruded ends of her story,, and patience. It requires one good psychiatrist to view things ranging from the date of her birth until this moment, into a box holistically from the window of the presenting complaints (using of fixed theories. a biopsychosocial and spiritual model) to reach the innermost It was my first year in psychiatry training. closet of a persona. Tracing from her childhood to link it with parenting, relation- Narrations should be given significance in the process of psy- ships, attachment, strengths and weaknesses, failures and achieve- chiatric training in the form of story-telling, art, music, poems, ments, ego, personality makeup, temperament and preferences. essays, and novel writing. It enriches the trainee to be acquainted The whole panorama of her life was imprinting on my mental with different perspectives of life. It widens the horizons of mental sketch board with the colors of her tone, gestures, and emotions. acuity to think in broad lines and in diverse ways. It offers patience It becomes hard to avoid an irresistible urge to follow the bio- and deepens the information process to understand events and v medical model of disease in the process to become a psychiatrist. reactions at different levels. It is partly because trainees have a background of studying 5 years of basic medicine. Disclosure Statement The author(s) have no conflicts of interest to disclose. Experience and time are the best teachers in how to link patients’ narrations holistically to create out a mental map of a How to Cite this Article person. Not to mention, the knowledge of basic theories is inevi- Jawaid H. Narrations in psychiatry training. Perm J 2020;24:19.218. DOI: table. However, overemphasis on defined concepts to the point https://doi.org/10.7812/TPP/19.218 to adjust living pictures in the logbooks is inapt. Training requires the capacity to delay gratification. Delaying gratification is a significant milestone to achieving anything in life. For an amateur trainee, it becomes quite difficult not to jump to conclusions, to avoid a reductionist approach and to hold back from diminishing abstract thoughts into concrete facts.

Author Affiliations 1 Aga Khan University, Karachi, Pakistan 2 Minaret College, Officer, Victoria, Australia

Corresponding Author Hena Jawaid, MBBS, FCPS (Psychiatry) ([email protected])

Keywords: behavioral health, mind-body, narrative medicine, physician-patient communication

The Permanente Journal • https://doi.org/10.7812/TPP/19.218 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 156 NARRATIVE MEDICINE The Rekindled Flame

Julio C. Ramirez, MD Perm J 2020;24:20.005 E-pub: 07/24/2020 https://doi.org/10.7812/TPP/20.005

I describe an impactful patient experience from my early medical or her abilities in that most trying time. The experience was bitter- career that has had a lasting impression on me not only as a clinician sweet; on the one hand, there was a certain triumph in being part but also as a human and, importantly, as a father. The experience is of a multi-faceted team – nurses, respiratory therapists, residents, that of a patient who had undergone heart surgery and subsequently sub-specialists – that was delivering unwavering, unified care in died; I identified with the patient on a personal level. The challenge the face of trepidation. On the other hand, the difficult reality was was not in providing medical care, but in providing medical care that even high-quality care turned out to be futile. that did not result in his survival. Encountering death is a difficult I can’t remember the exact length of time that lapsed between reminder of why we practice medicine – to help others. Yet even the start and the end of the Code. An infinity, perhaps? During healers, at times, need words of encouragement. some interval in time, his wife, who was present, was approached We start the morning with CPR. “He’s coding,” a nurse said. We and was told the most unbearable words: “There is nothing more had all anticipated that it was just a matter of time before hearing we can do.” The sounds of agony could not have pierced the room those words. We rushed to his room and began resuscitation during with greater intensity. I felt my own existence being ripped apart. his Code Blue. The patient had survived several heart surgeries since Next came the sound of silence. childhood, and he was determined to survive one more. After his Modern medicine is meant to be a beacon of light, yet its bright surgery, he was placed on a heart bypass machine, and tubes were fire was dimmed that day by death’s grip. No longer will he be left in his chest to drain any blood that remained post-operatively. able to say that he had another heart surgery. No longer will he The output should have decreased with every passing day; his be able to spend time with friends and family. No longer will he output only continued to increase, requiring blood transfusion be able to play with his children. No longer. The thought of facing after transfusion. Despite receiving near constant blood products, his children, with smiles across their faces, expecting to hear the his heart had begun showing signs of failing, and he required an good news that daddy was safe and had had a good day, conjured increasing number of medicines to keep it from doing so. up images of my own little ones. No such good news would be As we began performing CPR, I couldn’t help but think of the given, and thus I believed that they would undoubtedly be my person that he is – a son, a husband, a father. He has kids, both judge, jury, and executioner. I would have been weighed, measured, of whom are about the same age as my own. I thought quietly to and be found wanting. myself, “I would like nothing more than for you to be able to go We provided the family with privacy, and shared our condo- back home to your kids like I will be able to do today.” I was selfish. lences as we made our way out of the room. I felt a false sense of I wanted him to be able to see his kids again in order to lessen my security out in the hall – outside of the war room. It was there that own survival guilt. I could imagine all of his family’s birthdays, the his mother found me. I expected her to cast rightful rage on me. get-togethers, the movie nights – time spent together as a family. I I expected her words to cut through me like blades. As she closed could also imagine the worst-case scenario – all of the times that the distance between us, I expected to catch ablaze from her aura “good night” will not be said, all of the warm embraces that will that resembled that of the sun, as I expected her to emanate fury. not be given during the holidays, and all of the photographs that Instead, she gently embraced my shoulder before saying, “Thank will not include him; all of the moments that he will not be a part you for everything you did. You are part of a wonderful profession.” of. I could imagine it all in that instant. Time stood still for a moment as the fresh memories of what had The harder I pressed on his chest, the more I felt the tears well- just happened all came flooding back, and I found myself being ing up in my eyes. I had to distance myself from my emotions so transported back to the battlefield. I again contemplated if my that I could bring myself closer to him. My compressions became compressions were adequate before tears started melting down mechanical – up and then down. I made a silent promise that my face. I blamed myself for the defeat. The response that I con- was as much to him as it was to myself: “I have to focus on the sidered giving was that I didn’t deserve to be there and that I was compressions. I have to focus on keeping you alive.” That was the an impostor playing the role of a real doctor. I wanted to say that best I could do for him, and he deserved nothing less. I broke my it was all my fault. I wanted to say I was sorry he wasn’t there to own promise almost immediately, as my emotions fought to take celebrate another victory. Such words began to take form on my a foothold of my focus. lips. Instead, all I could say was, “Thank you.” My inner flame as a v The defibrillator’s automated message, “Good compressions,” was medical doctor was rekindled. a poignant reminder that I had to keep back the tears in order to continue pressing on his chest. In that moment, it became apparent that he had touched many lives during his hospital stay, as several other members of the healthcare team began to shed silent tears. Author Affiliations Perhaps they, too, were remembering his positive outlook on life, 1 Department of Pediatrics, Saint Louis University School of Medicine, Cardinal-Glennon Children’s Hospital, or the smiles and laughs shared with him and his family. St. Louis, Missouri Every member of the medical team worked tirelessly and effec- Corresponding Author tively to deliver high-quality, compassionate care to the best of his Julio C. Ramirez, MD ([email protected])

The Permanente Journal • https://doi.org/10.7812/TPP/20.005 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 157 NARRATIVE MEDICINE From Cultural Competency to Cultural Immersion: Lessons from A Community Advocate in Guatemala

Yolande M. Pengetnze, MD1 and Zoila Gonzalez, RN, NP2 Perm J 2020;24:20.017 E-pub: 07/24/2020 https://doi.org/10.7812/TPP/20.017

ABSTRACT This cultural and political context contributed to high rates of The article introduces the novel concept of “Cultural Immersion”, underage pregnancies in deprived communities, towing along poor going beyond cultural competency to immerse oneself into the outcomes for both the child and the mother, still a child herself. In local culture for sustainable community impact. 2008, the government’s response to the problem was to promulgate another law criminalizing underage pregnancies fathered by any male 16 years or older. Birth attendants were to report underage It’s 7:30 pm on this spring evening in Sarstún. University of pregnancies to the local prosecutor who would initiate a criminal Texas Southwestern Medical Students and their preceptors have investigation to bring the responsible male to justice. Convictions just completed a long day of clinical, surgical, and dental care at could lead to 5-12 years in prison. Clinica Regional de Sarstún (“The Clinic”) in Sarstún, Guatemala. Mayan communities in Sarstún are opposed to the latter law, The Clinic is supported by a United-States-based non-profit orga- which they perceive as a threat to their matrimonial and child- nization, Refuge International. Sitting on inflatable mattresses and bearing customs. Consequently, many underage pregnant girls wooden benches, we listen to Zoila Gonzalez, The Clinic’s Nurse are not brought in for prenatal care for fear of being reported to Practitioner and Midwife, talk about the challenge of underage authorities, and many end up with unassisted home births in re- pregnancies in Sarstún. mote villages. Moreover, children born to underage mothers are Sarstún is a small fishing community on the shores of the Sarstún often not recorded in vital statistics registries to avoid contact with River, a waterway that separates Guatemala and Belize. The region authorities, leading to a crucial lack of important documents such encompasses multiple Mayan villages embedded in the mountains as birth certificates when children are ready for school. In this and remote from the coast. Ladinos and Mayans are the two pre- context, the true prevalence and burden of underage pregnancies dominant ethnic groups in Guatemala. Ladinos have a Spaniard in Sarstún remains vastly unknown. background and speak primarily Spanish. Mayans are the indig- As Zoila immersed herself into the community and gained enous population and speak primarily one of twenty-one Mayan understanding of the cultural, legal, and political context, she languages. Q’eqchi’ (pronounced “Kek Chee”) is the predominant conceived the idea of a community-driven approach to address Mayan language in Sarstún. the issue of underage pregnancies among Mayan girls in Sarstún. Zoila is a Ladina from the neighboring multi-cultural town of She developed a trusting relationship with the community. She Livingston. She is a Licensed Professional Midwife. Ten years ago, led and facilitated community conversations about the clinical and when she joined The Clinic, Zoila elected to also register as a Tradi- legal risks of underage pregnancies, the benefits and availability tional Midwife, the other professional group performing midwifery of affordable and reversible birth control methods, the benefits of in Guatemala. As a Traditional Midwife, Zoila was most likely to delayed pregnancies, and the importance of young girls’ education. gain the trust of the Mayan people she serves, although the move Together with the community, they co-designed a community- was controversial among other Licensed Professional Midwives. wide birth control program for married girls under 17 years old, to As she began to work in Sarstún, Zoila noticed a high preva- delay the onset of pregnancy until after their 17th birthday. With lence of underage pregnancies among Mayan girls age 13 to 15 Zoila’s guidance, the community took charge and set program years. Zoila immersed herself in the local Mayan culture to better parameters. For instance, they indicated preference for medium- understand the problem. She traveled on foot to remote Mayan term depo-progesterone injections as the birth control method of villages to meet community members, participate in community choice. Eligible girls either would come to The Clinic once every activities, and build relationships. She learned that in Sarstún’s three months for depo-progesterone shots or would receive their Mayan culture, girls 12 years and older are deemed ready for shots during community outreach events organized conjointly marriage. Young girls are typically married off to a boy/man 16 by The Clinic and the government-owned Center of Health in years or older, and the couple is off to start a family. Moreover, a Guatemalan law promulgated in the 1990’s provides financial as- sistance from the government to families with multiple children. Author Affiliations Impoverished families, therefore, are pervasively incentivized to 1 University of Texas Southwestern Medical School, Dallas, Texas marry off young girls to collect government financial subsidies for 2 Refuge International, Longview, Texas children born of these unions. 3 Oak Crest Private School, Carrollton, Texas

Corresponding Author Yolande Pengetnze, MD ([email protected])

Keywords: global health, At-Risk Communities, pregnancy, cultural, competency

The Permanente Journal • https://doi.org/10.7812/TPP/20.017 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 158 NARRATIVE MEDICINE From Cultural Competency to Cultural Immersion: Lessons from A Community Advocate in Guatemala

Livingston. This approach addressed the problem of underage ecosystem, thus potentially creating the breeding ground for un- pregnancies in a culturally sensitive manner that preserved local desired behaviors detrimental to community health and wellbeing. Mayan matrimonial customs. As the evening conversation winds down, the team is deeply Community participation was timid at first, with only a few reflective, as we realize the lift required to make a lasting impact parents showing interest. Four years into the program, however, in a community. The key to success is a mixture of ingredients, more and more parents, especially mothers, proactively reach out including compassion, respect, humility, courage, inventiveness, to Zoila at the first indication of an upcoming betrothal to discuss dedication, sacrifice, collaboration, persistence, planning, education birth control. Zoila screens and enrolls at-risk girls in the program and, most certainly, “Cultural Immersion.” Zoila showed courage and keeps a registry of eligible and enrolled patients for commu- and inventiveness by striking the right balance between providing nity outreach planning, inventory management, and medication care and obeying the law. She only achieved success because she adherence monitoring. As part of a comprehensive approach to immersed herself into Sarstún’s Mayan culture and was compas- community care, Zoila also has established a community-wide sionate enough to “walk a mile” with these young Mayan girls in v prenatal care program with onsite visits at The Clinic and com- their pregnancy journey. munity outreach into the villages, to give all pregnant women access to quality prenatal care. To maintain the hard-earned community trust, the program has elected not to proactively report underage Disclosure Statement The author(s) have no conflicts of interest to disclose. pregnancies cared for at The Clinic to authorities, except per fam- ily request. Community members have also designed workaround Acknowledgments solutions such as reporting inaccurate ages for underage mothers Patti Pagels1, PA, Alana Carrasco1, Jamala Christopher1, Natalie Bonner1, when establishing a birth certificate for a newborn, to avoid brush- Luke Dosselman1, Isabel Garcia1, Christopher Gluckman1, Joel Rodriguez1, ing with authorities. Virginia Wang1, William Young1, Lucio Zapata1, Sarah Y Djomo3, Kimberly As Zoila speaks passionately of the community birth control Johnson2. program in the beautiful Sarstún sunset, she proudly points to a 17-year-old pregnant woman who was seen for prenatal care in The Clinic that morning. The patient’s story is an example of program success. She got married at age 13 to a 16-year-old male right about the time the program began. Zoila and community stakeholders convinced the patient’s family and husband to enroll her in the community birth control program. They agreed, and the patient assiduously received depo-progesterone injections ev- ery three months for four years. A few months ago, as she turned 17, the patient discontinued birth control. She is currently seven months pregnant. She comes down the mountain every month for prenatal care with Zoila at The Clinic, and she is due to deliver her first child in two months. Zoila has catalyzed a meaningful community transformation. She has identified an important problem and immersed herself into the community to uncover its roots. She has engaged the community to codesign and implement a culturally sensitive birth control program, which has led to community-level health behavior change and empowerment to reduce underage pregnancies among young Mayan girls in Sarstún. She has secured strong community Figure 1. Zoila Gonzalez, Nurse, Sarstún Clinic, Izabal Department, Guatemala engagement and ownership, and developed a collaboration with the local government-owned health system, to ensure program sustainability. She has extended prenatal care services offerings to all pregnant women in a comprehensive approach to community health, and she continues to work on expanding the reach and breadth of the program in Sarstún. Remarkable progress has been made, but much remains to be accomplished. In Sarstún, underage Mayan girls are still being married and subjected to precocious sex and underage pregnancies. The prevalence and scope of underage pregnancies remain elusive in Sarstún and in other communities, partly exacerbated by the un- predictable political context in Guatemala. Laws are implemented by administrations with varied political interests and scarcely ever evaluated for their full impact on communities within their cultural

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/20.017 159 NARRATIVE MEDICINE Narrating the Cycle of Life

Tatiana Valverde da Conceição, MD, PhD1; Gabriel Graça de Oliveira, MD, PhD2 Perm J 2020;24:19.139 E-pub: 05/13/2020 https://doi.org/10.7812/TPP/19.139

ABSTRACT the multiple and reciprocally influencing factors (environmental, Narrative medicine (NM) is an approach that values the patient’s genetic, and social), as well as the specifics of the doctor-patient narrative about his/her disease as central to the clinical encounter relationship in each phase (pregnancy, childhood, adolescence, and helps doctors to be more attentive to their patients’ perspec- adulthood, senescense and death). The knowledge of these various tives in the diagnostic and therapeutic process. A curricular change stages and their potential crises is a useful tool in understanding enabled a greater insertion of the humanities in the curriculum of the emotional experiences of the human being and also the pos- the Faculty of Medicine of the University of Brasília in Brasília, Brazil. sible suffering of the patient. We asked ourselves as teachers how In this context, NM was incorporated into one of the disciplines of to make the study of the life cycle interesting for students who the third semester. During the semester, students are encouraged are aged 18 to 19 years and who have not yet experienced many to write, in small groups, a narrative combining fictional and real of those phases. We know that we are not alone in this belief that aspects of the history of life (and disease) of one patient. In the teaching human development is a great challenge,2 especially if we present article, the authors describe the educational experience of want students to understand major developmental theories and not the insertion of NM in the medical curriculum and share personal just memorize developmental milestones. We believe that studying impressions about the multiple possibilities of this approach. human development is to study how we all become who we are, to understand not only the generalizations of theories but also that every human being has his/her own unique trajectory of life. In The first “A Narrative Future for Health Care” conference, short, it takes a good deal of creativity and innovation to create co-sponsored by the Centre for the Humanities and Health at stimulating ways to teach human development.3 King’s College London in London, UK; the Program in Narra- Considering that challenge, in this discipline, we chose to use tive Medicine, Columbia University, New York, New York; and narrative medicine as a didactic resource, in addition to chapters the Wellcome Trust in London, UK, took place at the King Col- from books on human development, articles that discuss risk and lege Guy’s Hospital Campus in London, UK, from June 19 to protection factors, and films that illustrate several developmen- 21, 2013. That conference had important influence on the 2016 tal stages from gestation to death. Narrative medicine is, in Dr medical curricular reform at the University of Brasília Medical Charon’s4 words, “a medicine practiced with narrative competence School, Brasília, Brazil. Given the need to adapt the curriculum … the competence that human beings use to absorb, interpret, and to the new priorities in the training of physicians listed in Brazil’s respond to stories.” Thus, in addition to the theoretical discussions 2014 National Curricular Guidelines for the Undergraduate Course on the various stages of the life cycle, we ask students to write, in in Medicine1 and to optimize the acquisition of attitudinal skills, it a small group of 5 students, a narrative about some patient whose was necessary to develop new educational approaches. These ap- clinical encounter influenced or marked them. proaches needed to be oriented to interdisciplinarity, empathy, and We stimulate them to combine truthful data from clinical his- care of one’s own physical and mental health, as well as attitudes tory with fictional elements, and to imagine how their patient/ necessary for a good doctor-patient relationship. character is or may be at the most diverse stages since childhood. Among the different learning axes of the new curriculum, a new We observe that the theoretical study of developmental theories axis called “Knowledge of Self and of the Other” was created. This helps them to imagine possibilities of life trajectories and to write longitudinal axis is in the curricular matrix from the first to the a coherent narrative. Among the various themes that emerge in eighth semesters of the medical curriculum, being divided into 8 the narratives are, for example, the difficult situation experienced disciplines. Among its objectives are the growth of the affective by war refugees, the indigenous population, feminism, and even dimension of the medical student and the development of inter- suicide among medical students. In the process of elaborating personal skills and attitudes that favor the therapeutic relation- the narrative, the students do much research on the themes that ship. The University’s Laboratory of Psychiatry and Humanities arise, including medical subjects that they have not yet studied, was responsible for the organization of the disciplines. However, suggesting a possibility of vertical integration with other subjects in view of the interdisciplinary nature of the content, researchers of the coursework. In the end, the group makes a presentation of from other disciplines, such as psychology, education, and sociology, also have participated in discussions with students in small groups inspired by active learning methods. Author Affiliations In the third semester of the axis, the content includes human 1 Department of Psychiatry, Faculty of Medicine, Queen’s University, Kingston, ON, Canada development throughout the life cycle, with a focus on its emo- 2 Department of Psychiatry, University of Brasília, Brasília, DF, Brazil tional domain and the complex connections there are between Corresponding Author Tatiana Valverde da Conceição, MD, PhD ([email protected])

Keywords: education, human development, mental health, narrative medicine, teaching

The Permanente Journal • https://doi.org/10.7812/TPP/19.139 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 160 NARRATIVE MEDICINE Narrating the Cycle of Life

Acknowledgments its narrative to the whole class and the teachers, and frequently Kathleen Louden, ELS, of Louden Health Communications performed a professors and students of other disciplines also attend these pre- primary copyedit. sentations. In some cases the group makes a short enactment of the narrative. During class discussions of developmental themes in Authors’ Contributions small groups, we realize that the students make immediate connec- Tatiana Valverde da Conceição, MD,PhD and Gabriel Graça de Oliveira, MD, tions between their personal experiences and the topics discussed. PhD participated in the manuscript intellectual concept and its preparation and Often they talk to family members to explore and understand review. The Corresponding Author has given final approval of the manuscript. aspects of their own past. According to the students’ reports, this approach to narrative References 1. Diretrizes Curriculares Nacionais para o curso de graduação em Medicina em medicine has contributed to the understanding of developmental 2014- Resolução CNE/CES no 3, de 20 de junho de 2014. (National Curricular themes that are sometimes not yet lived or are distant for them, Guidelines for the Undergraduate Course in Medicine). Available from: http://portal. and to the way they think about the doctor-patient relationship, mec.gov.br/index.php?option=com_docman&view=download&alias=15874-rces003- 14&category_slug=junho-2014-pdf&Itemid=30192 broadening their listening. There have been poster presentations 2. Fox G, Katz D, Eddins-Folesbee F, Folesbee R. Teaching development in written about the theme with an increasing interest in research on undergraduate and graduate medical education. Child Adolesc Psychiatric Clin N Am. the subject among teachers and students. 2007; 16: 67-94. 3. Prager L. Appreciating “normal” development: How did we get here? J Am Acad Child For the teachers of the discipline, this has been an enriching Adolesc Psychiatry. 2013; 11: 1121-23. and rewarding experience as we observe the development of our 4. Charon R. Narrative medicine: A model for empathy, reflection, profession and trust. students as people and doctors in formation. We believe that nar- JAMA. 2001; 286(15): 1897-1902. rative medicine is a powerful tool for teaching human development 5. Batt-Rawden S, Chisolm M, Anton B, Flickinger T. Teaching empathy to medical students: An updated, systematic review. Acad Med. 2013; 88:1171-77. and that it holds the potential to aid in building empathic ability, self-reflection, and formation of identity.5 All these are fundamental v skills for physicians in training.

Disclosure Statement The author(s) have no conflicts of interest to disclose. A review by the institutional review board was deemed not necessary because of the nature of this article, which does not contain any research project-related material.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.139 161 NARRATIVE MEDICINE The Insomnia Plague in Fictional Macondo

Alejandro Velásquez-Torres, MD, MSc1; Andrés Díaz-Forero2; Claudia Talero-Gutiérrez, MD1 Perm J 2020;24:19.192 E-pub: 06/24/2020 https://doi.org/10.7812/TPP/19.192

ABSTRACT Visitación accepts the circumstance and explains to the Buendías Disease and medicine are found throughout Gabriel García that the loss of sleep is not the gravest part of the disease, “but its Márquez’s work. This article examines the insomnia plague de- inexorable evolution toward a more critical manifestation: A loss scribed in the novel One Hundred Years of Solitude and performs of memory.”5p43-44 In addition, Visitación describes the manner a differential diagnosis exercise with conditions that affect both in which once the person “became used to his state of vigil, the sleep and memory. The main finding is that the insomnia plague recollection of his childhood began to be erased from his memory, narrated by García Márquez, with its clinical manifestations, the then the name and the notion of things, and finally, the identity sequence of symptoms, and its resolution, cannot be associated of people and even the awareness of his one being, until he sank with any specific diagnosis. However, similarities to and differences into a kind of idiocy that had no past.”5p44 from several clinical conditions are discussed, as well as the relation Rapidly, the other inhabitants of the house experience insom- between the neurophysiologic phenomena of sleep and memory. nia, and this symptom is welcomed with euphoria, as Aureliano Buendía says, “That way we can get more out of life.”5p43 Sub- INTRODUCTION sequently, the symptom that reportedly produced the most ter- Disease and medicine are present in several works of Gabriel ror—forgetfulness—appears. The sweets that Úrsula makes and García Márquez. Some cases documented bear considerable simi- sells in town spread the disease throughout Macondo: “Children larities to actual medical practice, whereas in others, they are trans- and adults sucked with delight on the delicious green roosters of formed by the use of magical realism. In García Márquez’s short insomnia, the exquisite pink fish of insomnia, and the tender yel- story No One Writes to the Colonel,1 a physician uses the Lieben low ponies of insomnia.”5p45 reaction to diagnose diabetes in the protagonist. In the novel Love The inhabitants of Macondo initially welcome insomnia posi- in the Time of Cholera,2 another physician detects the smell of bitter tively and use the time to perform necessary tasks; however, when almonds and describes the changes in a corpse due to cyanide poi- they complete their tasks, they begin to feel melancholic because soning. Moreover, there is an extremely detailed description of an they no longer have dreams on account of the insomnia. Thereaf- autopsy performed on Santiago Nasar in the novella Chronicle of a ter, they start repeating the same jokes and stories between them. Death Foretold.3,4 One Hundred Years of Solitude is a novel about the To combat the insomnia, Úrsula prepares an aconite (Aconitum Buendía family and their lives in the fantastical town of Macondo, sp) concoction and gives it to her relatives. The remedy does not located in Colombia on the Caribbean coast, where an insomnia induce drowsiness but produces dreams while they are awake. In plague occurs.5 The heads of the family are José Arcadio Buendía this state, they see the images of their own dreams and those that and his wife, Úrsula Iguarán. others dream. The objective of this article is to make a differential diagnosis of The inhabitants of Macondo quickly recognize the contagious the insomnia plague reported in One Hundred Years of Solitude,5 with characteristics of the plague and establish a quarantine to prevent real clinical pictures, in an attempt to determine parallels between any visitors coming to town from contracting the disease. Outsiders the Macondian world and the real world. The insomnia plague are forbidden from drinking or eating anything and are required that is described in the third chapter of the novel will be analyzed. to carry bells to report that they are healthy. When oblivion begins to affect their daily lives, Aureliano invents CLINICAL FEATURES OF INSOMNIA PLAGUE a way to remember the names of objects—by writing their names The insomnia plague appears in the plot ofOne Hundred Years of on them. Subsequently, the information on the labels requires fur- Solitude5 with the arrival of the natives Visitación and Cataure from ther description to include the details of the object that is being La Guajira, Colombia, who come to Macondo fleeing from an evil named: “This is the cow. She must be milked every morning so that that attacked their tribe. Thereafter, Rebeca, an orphan girl from she will produce milk, and the milk must be boiled in order to be La Guajira, is delivered by an emissary with a letter that entrusts her to the Buendías. She is mute, apparently lacks understanding of Spanish, and rejects any food. At night, she sneaks eating dirt Author Affiliations and lime from the walls. To address the girl’s behavior, Úrsula uses 1 Neuroscience Research Group Neuros, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, homemade therapies (orange juice with rhubarb) and punishments. Bogota, Colombia. One night, Visitación finds the girl awake, sucking her fingers 2 Undergraduate Neuroscience Research Group Semineuros, Escuela de Medicina y Ciencias de la Salud, “with her eyes lighted up in the darkness like those of a cat.” See- Universidad del Rosario, Bogota, Colombia. ing this, Visitación acknowledges that the insomnia plague has Corresponding Author reached Macondo. Although her brother, Cataure, runs away, Alejandro Velásquez-Torres, MD, MSc ([email protected])

Keywords: Alzheimer disease, dementia, encephalitis lethargica, fatal familial insomnia, forgetfulness, Gabriel García Márquez, infectious encephalitis, insomnia, Korsakoff syndrome, literature, magical realism, neurocysticercosis, semantic dementia, sleep and memory, variant Creutzfeldt-Jakob disease

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mixed with coffee to make coffee and milk.”5p47 However, this sys- affected is a child, Rebeca, who has a very similar pattern to an tem “would escape irremediably when they forgot the value of the adult’s disease. written letters.”5p47 As the oblivion deepens, the inhabitants resort to reading sets of playing cards regarding the past and “began to Encephalitis Lethargica live in a world built by the uncertain alternatives on the cards.”5p47 In 1916 in Europe, a clinical picture appeared characterized Aureliano attempts to invent a memory machine that would by fever, drowsiness, eye movement alterations, and abnormal allow individuals to remember the activities of each day, function- movements, among other signs and symptoms. Constantine von ing as a “spinning dictionary.” While Aureliano is working on the Economo reportedly evaluated a substantial number of those construction of this device, Melquiades returns to Macondo. This affected by this condition and called it encephalitis lethargica.10 old friend of the family and alchemist provides Aureliano a sub- This epidemic spread worldwide until the mid-1930s.11 The clini- stance of “gentle” color from which he, and subsequently the entire cal symptoms were initially nonspecific similar to a flulike state. town, regain their memory. Months later, Macondo is visited by the The condition can occur in an acute form, which is character- minstrel Francisco el Hombre, who along with his songs, brings ized by the symptoms just described and is associated with high the stories of the events in the villages he has visited. mortality. In addition, there is a chronic form that presents with parkinsonism, sleep disturbances, involuntary movements, and DIFFERENTIAL DIAGNOSIS OF INSOMNIA PLAGUE language disorders, among other symptoms. The cause of this This chapter from the novelOne Hundred Years of Solitude,5 in disease remains unknown, and hypotheses, such as environmental which the alteration of the sleep and memories of the Buendía fam- and infectious causes, have been proposed.11,12 ily is narrated and which extends throughout Macondo, leads us to In García Márquez’s description of the insomnia plague, there conduct a differential diagnostic exercise. The form of presentation, is no fever, no mortality, and no motor symptoms, and, contrary sequence of the appearance of different symptoms, and outcome to the drowsiness that occurs in this encephalitis, in the insomnia for the solution of the epidemic demonstrate characteristics that do plague, the characteristic symptom was the complete absence not facilitate the definitive diagnosis of a clinical syndrome. Here, of sleep. Interestingly, encephalitis lethargica has an epidemic the use of fantasy and imagination in this García Márquez novel behavior like the insomnia plague. is evident and is a part of a literary style called magical realism. This style is characterized by the inclusion of magical, miraculous, Variant Creutzfeldt-Jakob disease mythical, and fantastical elements in a realistic piece of fiction.6 Variant Creutzfeldt-Jakob disease (vCJD) is a rare infection of In García Márquez’s work, partial representations of the reality the central nervous system caused by prions. It can affect various of a disease are common. Regarding these disease descriptions, in animal species including humans.13 The first cases were described some works the description is considerably similar to the actual in Germany in 1922 and are important in terms of public health clinical presentation; however, in the case of the insomnia plague, because of their zoonotic variant and high mortality.13,14 This it is possibly full of symbolism and therefore does not resemble infection is characterized by rapidly progressive dementia and any medical condition described. However, we will review some any of the following symptoms: Myoclonus, visual or cerebellar possible clinical pictures consistent with this condition (Table 1). signs, pyramidal or extrapyramidal signs, and akinetic mutism.14 Although vCJD is contagious, it occurs more frequently in Infectious Encephalitis cohabiting family groups, which suggests a genetic susceptibil- Infectious encephalitis is an acute clinical syndrome charac- ity. 15 The symptoms of vCJD are not comparable with the clinical terized by focal neurologic deficits, generalized or focal seizures, symptoms described by García Márquez because vCJD is clearly altered mental status, behavioral changes, and fever (optional pre- a rapidly progressive condition that triggers dementia and has sentation).7 The incidence of this infection is 1.5 to 7/100,000/y.8 varied neurologic symptoms, with high mortality, which was not It is usually caused by a virus but also can be caused by bacteria, the case in Macondo. fungi, and some parasites. It can be a parainfectious or postinfec- tious phenomenon. Some of the autoimmune encephalitides can Neurocysticercosis present with sleep disturbances.7 Neurocysticercosis is the infection of the nervous system by Although the insomnia plague has an infectious behavior, none larvae of the parasite Taenia solium.16 Patients affected with this of those affected had a fever, focal neurologic symptoms, seizures, or condition may exhibit various neurologic symptoms depending behavioral changes. In addition, memory disorders are not always on the location of the larval cysts. Symptoms include seizures, part of the clinical symptoms. Sleep disturbances, which are com- illusions and hallucinations, catatonia, and cognitive disorders, mon to some autoimmune encephalitis cases, are predominantly such as amnesia. Some authors term this syndrome as “dementia characterized by nighttime awakenings and drowsiness.7 In García due to cysticercosis.” This form of dementia can affect individu- Márquez’s plague the insomnia is the main symptom. als of any age; early diagnosis is important because with proper However, the insomnia plague indiscriminately affects children medical treatment, it is a curable condition.17 and adults, like some types of infectious encephalitis. Typically, In the Caribbean Colombian region, where the imaginary town in pediatric patients, encephalitis presents in more severe forms, of Macondo was located, this condition is highly prevalent.18 usually accompanied by motor disorders, such as choreoathetosis, Neurocysticercosis is acquired via contaminated pork,16 whereas and rapid compromise of consciousness.9 In Macondo, the first in Macondo, the plague is dispersed throughout the village by

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the sweets prepared in the Buendía house. In neurocysticercosis, and the insomnia plague, insomnia should be noted as a cardi- sleep disorders are unusual, whereas insomnia was a cardinal nal symptom of the Macondo epidemic, as noted by Heilman28 symptom in the plague. These differences render the diagnosis of in a commentary on the article by Rascovsky et al.27 In García cysticercosis as a possible cause of the insomnia plague unlikely. Márquez’s story, the clinical symptoms have a contagious behav- ior and indiscriminately affect all age groups, whereas semantic Fatal Familial Insomnia dementia is a sporadic condition that mainly affects individuals Fatal familial insomnia is an autosomal dominant genetic dis- older than 65 years.29 ease caused by a mutation in PRNP D178N, the prion protein The characteristics of forgetting words while maintaining the gene.19,20 It was first described in 1986 and has been reported in initial preservation of verbal expression, without grammatical more than 100 families. The clinical symptoms include insomnia, errors, are consistent with semantic dementia in its initial stages. sleep fragmentation, an impaired consciousness state, sympathetic However, the progression of deterioration in the Macondo cases hyperactivity, and progressive cognitive impairment (memory does not lead to the absence of language; on the contrary, it in- impairment). To date, there is no treatment, and all cases lead to duces the inhabitants to search for alternatives, such as reading death within an average of 18 months.20 playing cards, to help structure new memories. Semantic de- Sghirlanzoni and Carella21 compared some of the charac- mentia progresses toward death, whereas in the insomnia plague, teristics of fatal familial insomnia with the clinical symptoms the clinical picture of the population is reversed by Melquiades’ described by García Márquez. Their analysis, however, is more gentle-colored substance. focused on the literary characteristics, which are not unique to this author but have been used in other great works of literature Alzheimer disease that employ different diseases as a narrative resource. Alzheimer disease is the most prevalent cause of dementia in In the case of the Buendía family, the clinical symptoms of sleep the world. It constitutes a neurodegenerative disorder that pro- disturbance and memory impairment are severe; however, there gressively compromises memory and other cognitive abilities. It is no description of altered consciousness state or symptoms that is characterized by the aggregations of Aβ and tau proteins in suggest dysautonomia. Furthermore, the outcome is not fatal, as amyloid plaques as well as neuofibrilary tangles in the nervous evidenced by the improvement of the population after the therapy tissue that are related to deterioration of this patients.30 Two forms offered by Melquiades. of disease presentation have been described: Early-onset and late-onset. Early-onset Alzheimer disease usually is a phenotypic Semantic Dementia variant of nonfamilial neurodegenerative diseases with important In 1892, Pick and Sérieux described a condition characterized clinical variability,31 or it can have an autosomal dominant in- by the asymmetrical atrophy of the frontal and temporal lobes. In heritance.32 On the other hand, late-onset Alzheimer disease is 1975, Elizabeth Warrington22 described a group of patients with multifactorial that includes genetic, environmental, and lifestyle difficulty naming things but showed the preservation of grammar factors. The late-onset form typically begins in the middle of the and language phonology, accompanied by atrophy of the frontal seventh decade of life and is the most frequent form.33,34 and temporal lobes. In 1989, Julie Snowden and colleagues23 At the beginning of the disease, the most characteristic symp- called this semantic dementia. It is currently considered to be a tom is forgetfulness. As memory deterioration becomes more semantic variant of primary progressive aphasia.24 evident, both spoken and written language and arithmetic skills Semantic dementia is a condition whose clinical symptoms are compromised. There is deterioration of visuospatial orienta- commence with difficulty naming objects, while the affected in- tion, and as the disease progresses, apraxia appears. Motor skills dividual retains the ability to describe the use of the object, tone are altered, and behavior is impaired. In terminal forms, there is of voice, prosody, and memory. As the disease progresses, there global amnesia, mutism, akinesia, and loss of sphincter control; is greater difficulty in naming objects, accompanied by impaired in addition, there are associated dysautonomias and ultimately understanding; in addition, there are issues with reading and death.33 recognizing faces. The terminal state is characterized by a com- Early-onset forms are noted in populations where inbreeding plete loss of communication, considerable changes in behavior, is frequent. In Colombia, in the Antioquia department (region), eating disorders, and ultimately death.25 In the initial stages, there is a family group with an extremely severe form of Alzheim- episodic and autobiographical memory are preserved, and rigid- er disease. It begins in the fourth decade of life, and patients show ity of thought and apathy are typical.24 In more advanced stages, rapid deterioration35; this form of early-onset Alzheimer disease autobiographical memory is lost, and this seems to be associated is frequent in this region of Colombia. The insomnia plague had with the semanticization of this information.26 no age preference, and children were also affected. Rascovsky et al27 analyzed the insomnia plague in One Hundred For the inhabitants of Macondo, memory loss begins with Years of Solitude5 and proposed semantic dementia as a diagnostic forgetting words, followed by the loss of childhood memories and possibility. The loss of the ability to name objects and write a list the “notion of things.” However, forgetfulness does not progress of words that serve as a guide to retain information is described completely. On the contrary, sufficient functions are maintained in the article. Initial preservation of childhood memories is noted, as the ill residents find a way to re-create or build new memories whereas the most recent memories are lost. Despite important using various supports. Moreover, there is no deterioration of similarities between the characteristics of semantic dementia other functions, such as orientation or behavior. Additionally, in

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the insomnia plague, all individuals with the disease recover their factor has been identified as a precursor for relevant genes within memory and do not progress inexorably toward death. memory formation, because it promotes synthesis of the CREB protein.42 In studies in animal models in which brain-derived Korsakoff Syndrome neurotrophic factor is blocked, results have demonstrated the Korsakoff syndrome was described by Korsakoff and colleagues inability to create new memories.40 in 1889 in alcoholic individuals in whom a memory disorder de- Sleep is a process of the nervous system that is regulated by veloped, accompanied by apathy, a dreary mood, and confabula- the suprachiasmatic nucleus of the hypothalamus in a circadian tions. Declarative memory impairment is the main characteristic, manner. During the course of sleep, different phases can be iden- with a greater compromise of recent memory and preservation tified that are regulated by multiple substances, which include of older memories. Semantic memory is preserved, but patients melatonin, prostaglandins, and adenosine.43 with this condition find it difficult to learn new semantic cat- Multiple studies have been conducted regarding the benefits egories.36 Memory impairments that involve long-term and that sleep brings to memory, and it is considered to play a fun- semantic memory lead to confabulations, which are defined as damental role in the consolidation of new memories.44 Results the mechanisms by which memory gaps are filled by the patient of research in university students undergoing sleep deprivation with facts, data and events, or general information, without the have been shown to generate consequences on academic perfor- intention of deceit.37 mance, with worsened academic results.45 In addition, functional The syndrome is caused by thiamine deficiency, and although imaging studies showed that sleep deprivation causes a decrease the main cause is the nutritional deficiency associated with alco- in cortical activity in areas related to memory.44 holism, it has been described in hyperemesis gravidarum, bariatric In recent years, an exclusive lymphatic system for nervous tis- surgery, starvation, and AIDS, among others.36 sue called the glymphatic system has been described. This system The insomnia plague does not seem to be a deficiency con- has been attributed to toxin degradation during sleep. Findings dition, and memory loss begins with forgetting the oldest of of studies in animal models subjected to sleep deprivation have memories. Finally, it is important to note the compromise of the shown the accumulation of Aβ-amyloid plaques and other semantic memory. Among the inhabitants of Macondo, there is degradation products, which further results in mild cognitive disease awareness, which causes them to activate quarantine pro- impairment.46 cedures to protect those who are in the town temporarily. On the It has experimentally been proved that the storage of recent contrary, in the case of Korsakoff syndrome, recent memories are learning and attention levels, which are apparently not compro- lost, and semantic memory is preserved. However, the resource mised in García Márquez’s characters, are altered because of in- of creating new memories from reading the playing cards could somnia. Chronic insomnia has other effects besides those related be a form of confabulation. to memory, which include emotional issues and poor adaptive responses to stress.44 These aspects are not compromised in the SLEEP AND MEMORY inhabitants of Macondo, who, on the contrary, develop adaptive Beginning in the last century, sleep started to be considered mechanisms that allow them to continue with their lives. a fundamental component of memory consolidation. For a long time, it was thought that the rapid eye movement stage of sleep CONCLUSION was the key factor. More recently, slow-wave sleep has been proved In the interviews with García Márquez that appear in The Fra- to influence memory consolidation. These conclusions were based grance of Guava,47 he explains that One Hundred Years of Solitude on experimental studies. Molecular biology in the last decades is not based on any real event and is full of representations that has been useful for the understanding of the physiologic and only he and his closest friends understand.47 In this interview, he neurochemical dynamics between sleep and memory.38 refers to the forgetfulness of the Colombian individuals. However, Luria is reported to have definedmemory as the recording, re- in this work, there are references to different historical events, tention, and reproduction of the traces of experience that allow such as the War of a Thousand Days or the Banana Massacre of the accumulation of information.39 Memory is a fundamental bio- 1928. The insomnia plague, according to García Márquez, is based logical function of human survival allowing us build our identity, on other literary works that explore the emergence of different store experiences, and relate to our environment.40 plagues and communities’ reaction to them.47 Different classifications of memory have been proposed with We analyzed the differences and similarities of different dis- respect to temporary acquisition (short or long term), cerebral eases proposed as a differential diagnosis for the insomnia plague. location (dependent and independent of the hippocampus), and García Márquez’s insomnia plague is described as a unique clinical functional (declarative and nondeclarative) criteria.39 Studies in presentation that does not fully resemble any real-world disease animal models and humans who present with nervous system (Table 1). However, it is interesting to note the close resem- lesions have allowed us to identify brain regions associated with blance of García Márquez’s description of a sleep and memory memory. Some of these regions are the medial temporal lobe, disorder with the clinical disorders discussed in this article. The corpus striatum, neocortex, amygdala, and cerebellum.41 similarity of the descriptions relating to health and illness are so With the advances in neuroscience, some molecular path- profound that this is not the first medical dissertation on García v ways that are considered fundamental for learning and memory Márquez’s works. processes have been clarified. The brain-derived neurotrophic

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Disclosure Statement 25. Klimova B, Novotny M, Kuca K. Semantic dementia: A mini-review. Mini Rev Med The author(s) have no conflicts of interest to disclose. Chem 2018;18(1):3-8. PMID:28019640 26. Montembeault M, Brambati SM, Gorno-Tempini ML, Migliaccio R. Clinical, anatomical, and pathological features in the three variants of primary progressive Acknowledgments aphasia: A review. Front Neurol 2018 Aug 21;9:692. DOI: https://doi.org/10.3389/ The authors thank to The Permanente Journal reviewers and editors for their fneur.2018.00692 PMID:30186225 help in this article preparation. 27. Rascovsky K, Growdon ME, Pardo IR, Grossman S, Miller BL. ‘The quicksand of forgetfulness’: Semantic dementia in One hundred years of solitude. Brain 2009 Sep;132(Pt 9):2609-16. DOI: https://doi.org/10.1093/brain/awp100 PMID:19447824 References 28. Heilman KM. A literary dementia plague [Internet]. Waltham, MA: NEJM Journal 1. García Márquez G. El coronel no tiene quien le escriba. 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Acta Neurol Colomb 2013;29:73-86. North Am 2015 Dec;38(4):615-44. DOI: https://doi.org/10.1016/j.psc.2015.07.002 19. Lu T, Pan Y, Peng L, et al. Fatal familial insomnia with abnormal signals on routine PMID:26600100 MRI: A case report and literature review. BMC Neurol 2017 May 26;17(1):104. DOI: 44. Peigneux P, Laureys S, Delbeuck X, Maquet P. Sleeping brain, learning brain. The https://doi.org/10.1186/s12883-017-0886-2 PMID:28549449 role of sleep for memory systems. Neuroreport 2001 Dec 21;12(18):A111-24. DOI: 20. Llorens F, Zarranz JJ, Fischer A, Zerr I, Ferrer I. Fatal Familial Insomnia: Clinical https://doi.org/10.1097/00001756-200112210-00001 PMID:11742260 Aspects and Molecular Alterations. Curr Neurol Neurosci Rep 2017 Apr;17(4):30. 45. Potkin KT, Bunney WE Jr. Sleep improves memory: The effect of sleep on long DOI: https://doi.org/10.1007/s11910-017-0743-0 PMID:28324299 term memory in early adolescence. PLoS One 2012;7(8):e42191. DOI: https://doi. 21. Sghirlanzoni A, Carella F. The insomnia plague: A Gabriel García Márquez story. org/10.1371/journal.pone.0042191 PMID:22879917 Neurol Sci 2000 Aug;21(4):251-3. DOI: https://doi.org/10.1007/s100720070085 46. Benveniste H, Heerdt PM, Fontes M, Rothman DL, Volkow ND. Glymphatic PMID:11214666 System Function in Relation to Anesthesia and Sleep States. Anesth Analg 22. Warrington EK. The selective impairment of semantic memory. Q J Exp Psychol 1975 2019 Apr;128(4):747-58. DOI: https://doi.org/10.1213/ANE.0000000000004069 Nov;27(4):635-57. DOI: https://doi.org/10.1080/14640747508400525 PMID:30883420 23. Snowden JS, Goulding PJ, Neary D. Semantic dementia: A form of circumscribed 47. García Márquez G, Apuleyo Mendoza P. El olor de la guayaba: conversaciones con cerebral atrophy. Behav Neurol 1989 Jan;2(3):167-82. [Cited in: Gorno-Tempini ML, Gabriel García Márquez. Bogota, Colombia: La Oveja Negra; 1982. Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. 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Table 1. The insomnia plague and its differential diagnoses

Characteristic Insomnia Infectious Encephalitis Variant Neurocysticercosis Fatal Semantic Alzheimer’s Korsakoff plague encephalitis lethargica Creutzfeldt- familial dementia disease syndrome Jakob insomnia disease Insomnia + - - - - + - + - Memory loss + + - + + + + + + Behavioral - - + + + + + + + changes Fever - + + ------Mortality - + + + - + + + - Infectious + + ? + + - - - - pattern Treatment + + - - + - - - +

+ = present; - = absent.

The6 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.192 167 NARRATIVE MEDICINE Our Guest

Leonidas Nye Walthall, MD1 Perm J 2020;24:19.161 E-pub: 04/22/2020 https://doi.org/10.7812/TPP/19.161

ABSTRACT One of the first things we learned about him was how much he An atypical encounter with a homeless man affects a physician’s liked coffee, because that seemed to be one of the few sentences practice. his aphasia did not affect. After hours of conversation, our guest tried valiantly to provide A SURPRISE ENCOUNTER a friend’s phone number at our request. After I made a couple “I was looking for a pizza joint.” of calls to phone numbers that were apparently just 1 digit off, Initially, it seemed a normal sort of request—directions to a he managed to give me the right number. His friend confirmed restaurant serving one of America’s favorite meals. However, the many of the details of his life we had gleaned through long ef- gentleman in front of me repeated that same sentence 3 times, forts at communication: Our guest had been a scientist, but a despite my beginning to answer him each time. He did not smell stroke a few years ago had rendered communication remarkably of alcohol, but he was wearing paper scrubs and a hospital iden- difficult for him. Thereafter, he had been in and out of various tification bracelet. Feeling unsure how to help, I gave him direc- facilities and hospitals, often assumed to be inebriated in EDs. tions, and my wife and I continued to walk our dog toward home. Because he had no cell phone, family and friends had lost touch By the time we arrived, we had decided to bring him some water with him. His friend was unable to assist in his care but said he and a granola bar. A poor salve, admittedly, for this man’s needs. would check with any other contacts he could find. We found him again and attempted further conversation, but Unfortunately, the next morning, our guest had a partial seizure, we were met with similar perseverative statements. I finally sur- and we called emergency medical services. The cycle seemed to rendered nonclinical conversation and asked directed orientation continue as he was returned to the ED from which he had just questions. His eyes darted with effort, and he confirmed that he been discharged. was in the city of Charleston, SC, though when asked about the I realize how much I left undone for our guest. Could I have year, he again answered, “Charleston.” identified and supplied his needed medications? Could I have After attempting for several minutes to gain a hint of an ad- triggered the turning of the wheel of social services on a Saturday dress, contact information for a relative, or anything by which evening? How can we begin to consider the scope of caring for we could help him, he offered his discharge paperwork from a the US homeless population, with the Department of Housing local Emergency Department (ED) It was from a different ED and Urban Development’s estimate that more than 550,000 than the one his wrist bracelet identified. The discharge diagnosis people experienced homelessness on a single night in January listed was “homeless.” 2018?1 I do not pretend my experience with our guest is easily After some coaxing, he agreed to let me drive him back to replicable. However, I do think we all have opportunities to take the ED. However, while driving, I realized that he had been a small step further than feels comfortable in an effort to help a discharged from 2 different EDs that same day. The discharge fellow human being. paperwork from the second ED revealed he had been seen within the hour. I discussed with him a course change, thinking he may RENEWED CONNECTIONS be better served by a homeless shelter. We drove to several of the Before my experience with our guest, burnout had removed shelters offered by this beautiful city, but at every stop we received much of my desire to connect with patients beyond what was the same answer: There was no room. clinically necessary. At times, my list of patients began to feel like just a list of diagnoses. However, my small steps for our guest AN UNCOMFORTABLE OFFER renewed my sense of meaning at work. The next day, conversation Although it felt uncomfortable, we could not come up with with my suddenly human patients took on new color with 1 or a solution other than offering to take him home as our guest. 2 more questions that I previously considered irrelevant. Those The next 20 hours involved sharing meals, observing his text- few minutes of personal interaction became what I appreciated book right-sided neglect (he ate only the left half of his plate the most. until we turned it), and a great deal of laughter on all our parts. Regarding our guest, I have some good news. He was ad- He laughed after nearly every fifth sentence he said. His laugh mitted to the hospital for treatment of his seizure. A few days was so contagious (and of his aphasic remarks were, admittedly, so off the wall) that we found ourselves all laughing together a good portion of the evening. We also had many challenges, such Author Affiliations as finding a way to assist in a sponge bath on the neglected side 1 Medical University of South Carolina, Charleston, SC of his body while maintaining his sense of privacy and dignity. Corresponding Author Leonidas Nye Walthall, MD ([email protected])

Keywords: access to care, burnout, homelessness, medical humanities, vulnerable populations

The Permanente Journal • https://doi.org/10.7812/TPP/19.161 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 168 NARRATIVE MEDICINE Our Guest

Acknowledgments later, I received a call from his brother, who had been given my Kathleen Louden, ELS, of Louden Health Communications performed a number by the friend I had managed to contact. He had flown primary copy edit. to Charleston to ensure his brother received the care he needed. He answered the call for 1 of the 550,000. How to Cite this Article Now, whenever I go to visit our guest at his nursing facility, Walthall LN. Our guest. Perm J 2020;24:19.161. DOI: https://doi.org/10.7812/ he is easy to find. TPP/19.161 v I just follow the laughter. References Disclosure Statement 1. Henry M, Mahathey A, Morrill T, Robinson A, Shivji A, Watt R. The 2018 annual The author(s) have no conflicts of interest to disclose. homeless assessment report to Congress [Internet]. Washington, DC: US Department of Housing and Urban Development; 2018 Dec:1 [cited 2020 Jan 2]. Available from: https:// files.hudexchange.info/resources/documents/2018-AHAR-Part-1.pdf.

The2 Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved. The Permanente Journal • https://doi.org/10.7812/TPP/19.161 169 NARRATIVE MEDICINE Death by the Numbers

Wesley Chou1 Perm J 2020;24:19.231 E-pub: 04/22/2020 https://doi.org/10.7812/TPP/19.231

“Your patient is trying to die on us,” the nurse practitioner That patient’s death was a little more than a year ago. Did it chimed in through the doorway. As I sprang up to follow her al- upset me? Yes, but I was not haunted by her death in the same way ready receding figure, I wondered about this choice of phrase, one as by the deaths of other patients whom I had known better. And that made death sound like a tantrum put on by a sullen toddler. yet it gnawed at me, even though I know full well that this same It lent an air of petulance to the patients who more often than not drama has unfolded innumerable times in wards the world over; I hovered in a strange purgatory between consciousness and oblivion. can see how someone could quickly grow accustomed to death in For my fellow medical students and me, our week on the surgical this environment. But I wish that her death had been brought up intensive care unit (ICU) was a “chill” one, seen as a break from by attending the next morning on rounds. I had been unsure about the surgery rotation’s grueling schedule. Expectations were lenient. how to broach this the next day: “So about the lady who passed My main tasks were to present 1 or 2 patient cases on morning away last night…” I imagined a confused reply: “Oh yes, the lady rounds and then watch any procedures being performed that day. in 11A, what about her?” The attending physicians would often be kind enough to let me I am reminded of an earlier time, when my classmates and I out by early afternoon, telling me to enjoy this freedom while it began laboratory sessions for anatomy. I had loved those sessions, lasted. I would pack up my belongings and leave them, still in a the visual and tactile nature of appreciating anatomical structures, reverie, reminiscing about waking up at 3 am to take vital signs on even if they did not automatically present themselves in the beau- patients and hunt down paper charts. tiful fashion of our surgical atlas. That excitement of learning the As I slipped into the ever-increasing crowd perched outside body’s roadmap has persisted, such that I plan to enter a surgical my patient’s room, I thought about how it felt like death was field. But I remember amid those highs, how at the end of anatomy, happening by the numbers vs whatever macabre caricature I had we zipped the cadavers back into their bags and pushed their carts envisioned. There was no dramatic bleed-out, screams of agony, or into a corner. I felt an unease, not dissimilar from the one I expe- heroic resuscitation efforts. Over the next hour or so, I received a rienced returning to the ICU, at this seemingly unceremonious blow-by-blow commentary of climbing lactate levels, resistant to departure. In talking with classmates afterward, I learned how for the fluids the healthcare providers were pushing in, as well as blood many of them anatomy had been an upsetting experience. Perhaps pressures that remained tolerable only by virtue of the astronomical they felt guilt at having “squandered” their donor’s final gift by volume of vasopressors pouring in. not learning as much as they should have or were reminded about It was all happening so fast. The patient had required a little their own experience with a deceased loved one. At the time, those bit of help maintaining her blood pressure in the operating room conversations and my own unease motivated me to help organize yesterday but had been stable immediately afterward. This after- a memorial service for our anatomical donors. I aimed to provide noon was another story. Throughout the quiet chaos, the vague a space for my peers to express their emotions and to give a more familiarity of the patient’s name made me realize that she had been proper goodbye to our donors, even if we had not known who one of the patients followed up by the urology specialists when I they had been in life. was with that team 2 weeks previously. I had not been following I want to similarly recognize the disparate reactions that a up this patient specifically, and try as I might, I could not recall shared experience may provoke. I hope that as a future physician, a single moment with them amid the various gown changes and I will remember that medical student who attempts not to jut out dashes between rooms on morning rounds. awkwardly and pokes his head up hopefully when it looks like Besides the morsels of information available in the social his- something interesting is occurring. I want to remember that what tory in past medical record notes (that she had been an activist in is another Tuesday afternoon for me might be the student’s first her community, for example), I knew little about who the patient time experiencing something, be it thrilling or harrowing. And I was as a person. It was only when various relatives began arriving hope that after one of those moments, even if the list is overwhelm- that her existence began to feel truly reified and gave me a sense ing or the hours long, that I can take a moment to pause and ask v of the impending loss at hand. Seeing the sister weeping, a lump them: “How are you feeling?” in my throat began to rise. And even if that was reflexive, it made the surreal slightly more recognizable. Later that night, as I rode the subway to meet a friend, I found myself reflexively scrolling through the patient’s electronic medi- cal record on my smart phone app, tracking various notes from Author Affiliations spiritual care staff and nurses anticipating extubation. A doubting 1 Harvard Medical School, MA notification popped up: “You are entering the chart of a deceased patient. Are you sure you want to continue?” Corresponding Author Wesley Chou ([email protected])

Keywords: death, medical education, narrative medicine

The Permanente Journal • https://doi.org/10.7812/TPP/19.231 The Permanente Journal • For personal use only. No other uses without permission. Copyright © 2020 The Permanente Press. All rights reserved.1 170 STORIES AND POETRY Shorelines

Kacper Niburski1 Perm J 2020;24:19.183 E-pub: 07/08/2020 https://doi.org/10.7812/TPP/19.183

she just died and the room is dark and i can hear her family pleading with the stars during their night’s embrace and just be- fore i stood like a solemn sun atop of her and i compressed and i compressed and i compressed and her lips were still glossed with beat-red lipstick and they were still still no matter what i did and i remember when i was 13 and my parents told me that it did not matter what i did either and so i wore outrageous makeup to shock them into quiet attention that i was a thing that could never be still even though now the silence wraps the neck of the entire room for i have stopped crushing her chest where she just died and five days ago she hugged me with a big glorious grin and six days ago it was decided that she could finally go home and she was happy and she said it was a long admission and it wasn’t always easy and it was made shorter by people like me who had a soft careful heart and my hands rattled when i stopped collapsing into her body and her hands drifted in the air around like the drowned and i met her 8 weeks ago when the water first sloshed in her lungs and a thick yellow coated her lips and she told me that back in the day she was a swimsuit model that could bend sunlight and she laughed with the roar of an ocean and the room remains dark now where she just died and the family continues to beg the stars for please another day and my attending takes me away from the room for it is too noisy so he can tell me that i did well cracking open her lungs to the sun and we’ll all have fruity funny drinks later to celebrate my first code and the shift streams on by and before i leave the hospital for what promises to be a lively night when i will come home very warm and very drunk and very lost, i pass the open mouth of her room where only the total quiet rests. a mop weeps on the floor of v the ward near the exit. i nearly slip.

Author Affiliations 1 McGill University and Genome Quebec Innovation Centre - Medicine, Montreal Ontario

Corresponding Author Kacper Niburski ([email protected])

Keywords: art, coding, culture, humanitarian, literature, loss

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