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

Original Research & Contributions 4 Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating 18 A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial 24 Exploring the Reality of Using Patient THE PERMANENTE JOURNAL Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives 31 Physicians Experiencing Intense Emotions While Seeing Their Patients: What Happens? 38 Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level 45 Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model Special Reports 51 Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control 57 Evidence-Based Workflows for Thyroid and Parathyroid Surgery 74 The Truth about Truth-Telling in American Medicine: A Brief History Review Articles 78 Hyperparathyroidism of Renal Disease 84 Recurrence of Epithelioid Hemangioendo- thelioma during Pregnancy: Case Report and Systematic Review Narrative Medicine 102 The Use of Narrative as a Treatment Approach for Obesity: A Storied Educational Program Description 107 You Are Not Alone: Ten Strategies for

Surviving a Malpractice Lawsuit Follow @PermanenteJ Printed on acid-free paper.

See inside for additional content ISSN 1552-5767 as well as articles found only online www.thepermanentejournal.org

BOOKS PUBLISHED BY Summer 2016/ Volume 20 No. 3 PERMANENTE AUTHORS: The PermanenteJournal ORIGINAL RESEARCH able feedback, 4) lack of timeliness in the & CONTRIBUTIONS delivery of feedback, 5) unclear benefit of Sponsored by the National Permanente patient experience survey data as a tool for Your Guy’s Guide to Gynecology: 4 Weight Loss and the Prevention of providing resident feedback, and 6) lack of A Reference for Men and Women Medical Groups Bruce Bekkar, MD; Uda Wahn, MD Weight Regain: Evaluation of a Treat- individualized feedback. ment Model of Exercise Self-Regulation ISBN-10: 0965506746 Mission: The Permanente Journal advances Generalizing to Controlled Eating. 31 Physicians Experiencing Intense ISBN-13: 978-0965506748 knowledge in scientific research, clinical James J Annesi, PhD, FAAHB, FTOS, Emotions While Seeing Their Patients: FAPA; Ping H Johnson, PhD; East Sandwich, MA: North Star Publications medicine, and innovative health care delivery. What Happens? Joana Vilela da Silva, (Ant Hill Press); 2000. Gisèle A Tennant, PhD; Kandice J Porter, MD; Irene Carvalho, PhD Hardcover: 325 pages PhD; Kristin L McEwen $24.95 Circulation: 25,000 print readers per A self-report survey was completed by 127 For decades behavioral weight-loss treat- quarter, 6900 eTOC readers, and in 2015, physicians, with 52 (43%) reporting experi- ments have been unsuccessful beyond encing intense emotions frequently. Coping 1.4 million page views on TPJ articles the short term. In this study, women with strategies to deal with the emotion at the in PubMed from a broad international obesity were randomized into either a moment included behavioral and cognitive readership. comparison treatment that incorporated approaches. Choking-up/crying, touch- a print manual plus telephone follow-ups ing, smiling, and providing support were (n = 55) or into an experimental treatment significantly associated with an immediate Picking up the Pieces: of The Coach Approach exercise-support positive impact on the physician-patient What Everyone Needs to protocol followed after 2 months by group relationship. Withdrawing from the situa- Know When a Child Dies nutrition sessions focused on generalizing tion, imposing, and defending oneself were Adrienne L Burnell, RN, MS, PhD; self-regulatory skills from an exercise associated with a negative impact. George M Burnell, MD support to a controlled eating context ISBN-10: 1516859405 (n = 55). Improvements in all psychological 38 Difference in Effectiveness of ISBN-13: 978-1516859405 Medication Adherence Intervention ON THE COVER: measures, physical activity, and fruit and by Health Literacy Level. Ashli A createspace.com; 2015 Roman Stonemason vegetable intake were significantly greater Owen-Smith, PhD, SM; David H Smith, Paperback: 206 pages by Tom Janisse, MD, MBA in the experimental group. Change in $26.45 self-regulation best predicted weight loss, PhD, RPh; Cynthia S Rand, PhD; Jeffrey A Roman stonemason whereas change in self-efficacy best pre- O Tom, MD, MS; Reesa Laws; Amy works to repair the vulner- dicted maintenance of lost weight. Waterbury, MPH; Andrew Williams, able corner of a 1000-year- PhD; William M Vollmer, PhD 18 A Pharmacist-Staffed, Virtual Gout old structure. He stands Promoting Adherence to Improve Effective- If you are a Permanente author and would like your book cited here, Management Clinic for Achieving sturdy in his fashionably ness of Cardiovascular Disease Therapies send an e-mail to [email protected]. Target Serum Uric Acid Levels: buckled black boots, blue (PATIENT) was a randomized clinical trial A Randomized Clinical Trial. jeans with plaster-clouded designed to test the impact, compared Robert Goldfien, MD; Alice Pressman, knees, and traditional with usual care, of two technology-based PhD, MS; Alice Jacobson, MS; Michele Ng, blue work coat with lapels. interventions that leveraged interactive PharmD; Andrew Avins, MD, MPH Kneepads wait to support voice recognition to promote medication his delicate work close to the ground, hammering The authors conducted a parallel-group, adherence. The differences in intervention additional bits of marble, variously sized, to fit all filling randomized, 26-week, controlled trial of a effects for high vs low health literacy in this defects. He restores a historic work of masonry 30 pharmacist-staffed, telephone-based pro- exploratory analysis are consistent with generations after its construction and reconstruction, gram for managing hyperuricemia vs usual the hypothesis that individuals with lower done just like this in just this way, in a process first care. Among 37 participants randomized health literacy may derive greater benefit learned during the transition from wood to stone. to the intervention group, 13 (35%) had a from this type of intervention compared serum uric acid level (sUA) ≤ 6.0 mg/dL at with individuals with higher health literacy. Some hours into mixing mud, his dextrous hands with 26 weeks vs 5 of 40 participants (13%) in precision and artistry carefully prep the faces for a final the control group (p = 0.03). A structured 45 Lifestyle and Self-Management by Those fresh surface coat, smooth to the touch. When he is pharmacist-staffed program was more ef- Who Live It: Patients Engaging Patients done, the pads, hammer, slab, and bits all fit into his fective than usual care for achieving target in a Chronic Disease Model. Michelle T metal pail, then into his bicycle basket for a ride home sUA levels. These results suggest that Jesse, PhD; Elizabeth Rubinstein; Anne through Roman traffic. He looks back to view with a structured program could significantly Eshelman, PhD, ABPP; Corinne Wee; pleasure and a sure sense of contribution his master improve gout management. Mrunalini Tankasala; Jia Li, PhD; Marwan work of art. Abouljoud, MD, CPE, MMM, FACS 24 Exploring the Reality of Using Patient Of 1862 patient satisfaction surveys, 823 Dr Janisse is the Editor-in-Chief of The Permanente Experience Data to Provide Resident were returned (44.2%). Patients and their Journal and Publisher of The Permanente Press. Feedback: A Qualitative Study of supports appreciated that the program Attending Physician Perspectives. volunteer was a transplant recipient and Steffanie Campbell, MD; Heather noted gratitude for the lifestyle information. Honoré Goltz, PhD, LMSW, MEd; Sarah Five areas were associated with the suc- Njue, MPH; Bich Ngoc Dang, MD cess of Transplant Living Community: 1) 112 CME EVALUATION FORM From 7/2013 to 8/2013, in-depth, face- a “champion”; 2) a receptive health care to-face, semistructured interviews were environment; 3) a high level of visibility conducted with 9 attending physicians to physicians and staff; 4) a lifestyle plan who precept residents in internal medicine (“Play Your ACES” [Attitude, Compliance, at 2 continuity clinics (75% of eligible at- Support, and Exercise]), and 5) a strong The Permanente Journal tendings). Content analysis identified 6 volunteer structure. It is feasible to inte- 500 NE Multnomah St, Suite 100 potential barriers in using patient experi- grate a sustainable patient-led lifestyle and ence survey data: 1) perceived inability self-management educational group into Portland, Oregon 97232 of residents to learn or to incorporate a busy tertiary care clinic for patients with www.thepermanentejournal.org feedback, 2) punitive nature of feedback, complex chronic illnesses. ISSN 1552-5767 3) lack of training in the delivery of action-

Follow @PermanenteJ For information and/or rates for placing an The Permanente Journal/Perm J 2016 Summer:20(3) announcement here, please contact [email protected]. CME credits are available online at www.tpjcme.org. The mail-in CME form can be found on page 112.

REVIEW ARTICLES Special Report 78 Hyperparathyroidism of Renal Disease. 51 Improving Care in Older Patients with Noah K Yuen, MD; Shubha Ananthakrishnan, NARRATIVE MEDICINE Diabetes: A Focus on Glycemic Control. MD; Michael J Campbell, MD Eric A Lee, MD; Nancy E Gibbs, MD; 102 The Use of Narrative as a Treatment John Martin, MD; Fred Ziel, MD; Patients with renal hyperparathyroidism Approach for Obesity: A Storied Jennifer K Polzin, PharmD; Darryl (rHPT) experience increased rates of cardio- Educational Program Description. Palmer-Toy, MD, PhD vascular problems and bone disease. Guide- Marcus Griffith, MD; Jeana Griffith, PhD; lines recommend that screening and manage- Mellanese Cobb, MPH; Vladimir Oge, MPH Diabetes affects more than 25% of ment be initiated for all patients with chronic Americans older than age 65 years. The authors wrote an interventional chil- kidney disease stage III (estimated glomerular dren’s book and workbook (The Tale of This article discusses the seminal filtration rate, < 60 mL/min/1.73 m2). Improv- research findings that strongly suggest Two Athletes: The Story of Jumper and The ing medical management with vitamin D Thumper) and developed a three-step inter- that hemoglobin A1c goals should be analogs, phosphate binders, and calcimimetic relaxed in older patients. The authors vention based on the narrative. The interven- drugs has expanded the treatment options tion’s purpose is to increase public aware- then recommend an age-specific and for patients with rHPT, but some patients still functionally appropriate hemoglobin A ness, reduce stigma, and help members of 1c require a parathyroidectomy to mitigate the underserved communities become more reference range for patients receiving sequelae of this challenging disease. medications to improve glycemic control. comfortable discussing obesity. Interactive Other interventions are suggested that 84 Recurrence of Epithelioid Hemangio- storytelling is the first step. The second step should make diabetes care safer in endothelioma during Pregnancy: Case is reading. Practicing positive behaviors older patients receiving hypoglycemic Report and Systematic Review. Michael and decision making through games and medications. McCulloch, LAc, MPH, PhD; Michael exercises from the companion workbook is Russin, MD; Arian Nachat, MD the final step. Special Report 57 Evidence-Based Workflows for Thyroid The authors present a case of a 28-year-old 107 You Are Not Alone: Ten Strategies and Parathyroid Surgery. woman whose epithelioid hemangioendo- for Surviving a Malpractice Lawsuit. Charles Meltzer, MD; Amer Budayr, MD; thelioma (EHE) recurred during pregnancy, Audrey Sheridan, MD Annette Chavez, MD; Richard Dlott, suggesting hormonal involvement. They I wasn’t even scheduled to work that morning. MD; William Greif, MD; Deepak Guru- conducted a systematic review to provide I had just gone into the office for a meeting. shanthaiah, MD; Andrew Klonecke, MD; analysis and interpretation of the potential Most physicians, about 60%, will be sued Matthew Lando, MD; Joyce Leary, MD; significance of her disease recurring, with at some point in their careers. Physicians Sundeep Nayak, MD; Ryan Niederkohr, fatal outcome, during pregnancy. Very little typically do feel intense strain when faced MD; Judith Park, MD; Alison Savitz, research has explored the use of individual with a lawsuit. We are more likely to suffer MBA, MD; Henry Schwartz, MD hormonal markers. Strongly positive expres- depression and burnout. Ten techniques sion of 17-beta estradiol receptors have are offered for coping that really work: resist A need exists to reduce care variations by been reported. Expression of placenta growth standardizing the practice of thyroid and isolation, use your strengths, retrain your factor (PlGF) is noteworthy in our case, in that brain, take care of yourself, give yourself a parathyroid surgery. During the course of our patient’s disease quickly and dramatically a year, a task force developed algorithms break, set priorities, approach law as a foreign flared in the 25th week of pregnancy, near the culture, regain perspective, use distraction, representing decision points and workflows peak in maternal PlGF production. based on American Thyroid Association and focus on what you can control. guidelines and on three internal studies 109 The Handshake Layer Cake: Meeting of surgical practices in the Northern and COMMENTARY and Regreeting Difficulties for a Southern California Regions of Kaiser 90 Quality Over Quantity: Integrating Non-French Surgeon in France. Permanente conducted in collaboration Mental Health Assessment Tools into Colin G Murphy, MCh, FRCSI with Health Information Technology Primary Care Practice. Transformation & Analytics (HITTA). As always, the first work-greeting of the Darrell L Hudson, PhD, MPH day, be it a handshake or les bises, is Special Report Depression is one of the most common, complicated by context: age, seniority, work 74 The Truth about Truth-Telling in costly, and debilitating psychiatric disorders status, employer/employee status, family, American Medicine: A Brief History. in the US. Yet, mental health services are familiarity, the other people present at that Bryan Sisk, MD; Richard Frankel, PhD; underutilized throughout the US. Recent interaction, whether it is break/coffee time. Eric Kodish, MD; J Harry Isaacson, MD policy changes have encouraged depression All of this has to be balanced against the Transparency has become an ethical screening in primary care settings. However, unthinkable, not greeting someone at all, or cornerstone of American medicine. For there is not much guidance about how de- thinking (like an idiot) that the wave or nod most of American history, the intentional pression screeners are administered. There from a distance that you gave earlier in the withholding of information was the are people suffering from depression who day constituted a greeting. accepted norm in medical practice. The are not getting the treatment they need. It is important to consider whether enough care 111 Disconnection. authors trace the ethics and associated Ahmed Obeidat, MD, PhD practices of truth-telling during the past two is being taken when administering depres- centuries and outline the many pressures sion screeners in primary care settings. It was a very familiar object that I asked her that influenced physician behavior during to identify. She started to look, feel, think, 93 Plant-Based Diets: A Physician’s Guide. and she said, “It has buttons, numbers, and that time period. They conclude that the Julieanna Hever, MS, RD, CPT history of disclosure is not yet finished, glass, but I can’t put them together. I am as physicians still struggle to find the best This article provides physicians and other unsure!” The last task I asked her to perform way to share difficult information without health care practitioners with an overview of was to write a sentence, which thrilled me causing undue harm to their patients. the myriad benefits of a plant-based diet as when she wrote in beautiful script, “Doctor, well as details on how best to achieve a well- I want to know what is wrong with me.” balanced, nutrient-dense meal plan. It also This was alexia (word blindness) without defines notable nutrient sources, describes agraphia. She was a creative writer in her how to get started, and offers suggestions third decade. on how health care practitioners can encour- Contents continued on next page. age their patients to achieve goals, adhere to the plan, and experience success.

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Refining Reporting Mechanisms in Oregon’s Image Diagnosis: Pott Puffy Tumor. Future Challenges of Robotics and Artificial Patient-Centered Primary Care Home Diane Apostolakos, MD, MS; Ian Tang, MD Intelligence in Nursing: What Can We Learn Program to Improve Performance. A 20-year-old man was admitted to our hospital from Monsters in Popular Culture? Sherril Gelmon, DrPH; Billie Sandberg, PhD; with complaints of frontal headache, sinusitis, Henrik Erikson, RNT, PhD; Martin Salzmann- Nicole Merrithew, MPH; Rebekah Bally, MPH and fever for one week. Sir Percivall Pott (1714- Erikson, RN, MHN, PhD To achieve the Triple Aim, the Oregon Health 1788), a surgeon at St. Bartholomew’s Hospital The authors propose that monsters in popular Authority implemented the Patient-Centered in London, first described it as Pott Puffy tumor, culture might be studied with the hope of learning Primary Care Home (PCPCH) Program in referring to one of the four historic manifestations about situations and relationships that generate 2009. To assist in evaluating 500 primary care of inflammation noted by Aulus Cornelius Celsus empathic capacities in their monstrous exis- practices’ achievement along its 6 core attributes (c 25 BC-c 50 AD): rubor (redness), tumor tences. The aim of the article is to introduce the the research team developed an innovative (swelling), calor (warmth), and dolor (pain). theoretical framework and assumptions behind scoring method. Initial results demonstrate that this idea. Both robots and monsters are posthu- the scores enable stakeholders to compare Image Diagnosis: Tubo-ovarian Abscess man creations. The knowledge we present here results across similar practices and across with Hydrosalpinx. Kiersten L Carter, MD; gives ideas about how nursing science can ad- the model’s core attributes, and to identify Gus M Garmel, MD, FACEP, FAAEM dress the postmodern, technologic, and global opportunities for improvement and technical Risk factors of tubo-ovarian Abscess include world to come. assistance. This strategy could be replicated younger age, multiple sexual partners, nonuse in other states. The article offers insights on of barrier contraception, and a history of pelvic implementation strategies, efficacy of the PCPCH inflammatory disease. Compared with ultraso- model, and lessons learned. nography, computed tomography has increased sensitivity to detect thick-walled, rim-enhancing Metastatic Renal Cell Carcinoma Presenting adnexal masses. The aim of therapeutic man- as Painful Chewing Successfully Treated with agement is to be as noninvasive as possible. Combined Nivolumab and Sunitinib. However, if this approach fails to yield clinical Fade Mahmoud, MD, FACP; Al-Ola Abdallah, EDITORIAL & PUBLISHING OFFICE improvement within 3 days, reassessment of the The Permanente Journal, 500 NE Multnomah St, MD; Konstantinos Arnaoutakis, MD; Issam antibiotic regimen, with consideration for laparos- Suite 100, Portland, Oregon, 97232, USA; Makhoul, MD copy, laparotomy, adnexectomy, hysterectomy, or phone: 503-813-3286; fax: 503-813-2348; Metastatic renal cell carcinoma to the head and image-guided abscess drainage is necessary. E-mail: [email protected]. neck is the third-most common cause of distant Image Diagnosis: Gastric Migration of INSTRUCTIONS FOR SUBMISSION metastasis to the head and neck, after breast Instructions for Authors and Manuscript and Artwork cancer and lung cancer. A 71-year-old man with Hookworms in a Patient with Anemia. Chalapathi Rao Achanta, MD Submission Instructions are available along with a single complaint of a one-year history of pain a link to our manuscript submission center at while chewing food, but without painless hematu- A 65-year-old man presented to our hospital with www.thepermanentejournal.org/authors.html. ria, weight loss, anorexia, fatigue, or anemia. An 4 months of fatigue and weakness. He denied almost complete response of the metastatic dis- any bleeding manifestations and had pallor LETTERS TO THE EDITOR ease occurred with the combination of nivolumab on examination. The patients’ esophagus was Send your comments to: [email protected]. and sunitinib. normal, but there were motile hookworms in the PERMISSIONS AND REPRINTS gastric antrum and heavy loads of hookworms in Reprint Permission Form available at: Treatment of Tracheoinnominate Fistula the duodenum. with Ligation of the Innominate Artery: www.thepermanentejournal.org/about-us/ 5818-reprint-permissions.html. A Case Report. Image Diagnosis: Encephalopathy Resulting Rhiana S Menen, MD; Jimmy J Pak, MD; from Dural Arteriovenous Fistula. ADVERTISING/ANNOUNCEMENTS Matthew A Dowell, PA; Ashish R Patel, MD; Ana Filipa Santos, MD; Célia Machado, MD; For rates and information about advertising in Simon K Ashiku, MD; Jeffrey B Velotta, MD Sara Varanda, MD; João Pinho, MD; The Permanente Journal, e-mail Amy Eakin at [email protected]. A 76-year-old man who underwent emergent Manuel Ribeiro, MD; Jaime Rocha, MD; Ricardo Maré, MD tracheostomy placement presented on ADDRESS CHANGES postoperative day 10 with massive hemorrhage A 69-year-old woman presented to the Neurol- E-mail address changes to [email protected]. concerning for tracheoinnominate fistula and ogy Department with 2 months of progressive Please include both old and new addresses. was treated with median sternotomy and ligation psychomotor slowing, inability to concentrate, of the innominate artery. The key to good and periods of disorientation. Her past medical The Permanente Journal (ISSN 1552-5767) is outcomes is quick diagnosis and urgent surgical history was unremarkable, and she was taking no published quarterly by The Permanente Press. The intervention. medication. There was no history of trauma. The Permanente Journal is available online (ISSN 1552- 5775) at www.thepermanentejournal.org. Periodicals initiating events that led to the development of postage paid at Portland and at additional mailing Monoarticular Poncet Disease after these symptoms are not clear, but the literature Pulmonary Tuberculosis: A Rare Case Report offices. POSTMASTER, send all address changes to reports association with trauma, infection, recent The Permanente Journal, and Review of Literature. Paritosh Garg, MD; 500 NE Multnomah Street, surgery, and dural sinus thrombosis. Suite 100, Portland, Oregon, 97232. Nikhil Gupta, MD, MBBS; Mohit Arora, MS The authors describe an atypical presentation of The Editorial Staff have disclosed that they have no active pulmonary tuberculosis with monoarticular personal, professional, or financial involvement in Poncet disease of the right knee in a 24-year- any of the manuscripts they might judge. Should a conflict arise in the future, the Editorial Staff have old woman. The diagnosis of Poncet disease is agreed to recuse themselves regarding any specific mainly clinical with exclusion of other causes. It manuscripts. The Editorial Staff also will not use the generally presents as an acute or subacute form; information gained through working with manuscripts however, chronic forms have been described in for private gain. the literature.

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EDITOR-IN-CHIEF: Tom Janisse, MD, MBA EDITORIAL BOARD ASSOCIATE EDITOR-IN-CHIEF: Lee Jacobs, MD Maher A Abbas, MD, FACS, FASCRS Ellen Cosgrove, MD Tieraona Low Dog, MD Chief, Digestive Disease Institute, Vice Dean, Academic Affairs and Director, Integrative Medicine SENIOR EDITORS Cleveland Clinic, Abu Dhabi, UAE; Education, University of Nevada, Las Concepts, Pecos, New Mexico; Vincent Felitti, MD Preventive Medicine, Book Reviews Professor of Surgery, Cleveland Vegas School of Medicine, Las Vegas, President, My Own Health; Director, Clinic Lerner College of Medicine Nevada Scientific and Regulatory Affairs, Gus M Garmel, MD, FACEP, FAAEM Clinical Medicine of Case Western Reserve University, Quentin Eichbaum, MD, PhD, MPH, Healthy Lifestyle Brands; Tempe, Arthur Klatsky, MD Original Articles Cleveland, Ohio MFA, MMCH, FCAP Arizona Eric Macy, MD Research Richard Abrohams, MD Assistant Dean for Program Develop- Lewis Mehl-Madrona, MD, PhD, MPhil Scott Rasgon, MD Corridor Consult Internal Medicine and Geriatrics, ment; Associate Director of Transfu- Director of Geriatric Education, Maine The Southeast Permanente Medical sion Medicine; Associate Professor Dartmouth Family Medicine Residency; Group, Atlanta, Georgia of Pathology; Associate Professor of Director of Education and Training, ASSOCIATE EDITORS Fábio Ferreira Amorim, MD, PhD Medical Education and Administra- Coyote Institute, Augusta, Maine Mikel Aickin, PhD Professor of Medicine, Escola tion; Director, Fellowship Program Michel M Murr, MD, FACS Biostatistics Superior de Ciências da Saúde in in Transfusion Medicine; Member, Professor of Surgery, Director of James J Annesi, PhD, FAAHB, FTOS, FAPA the Department of Research and Vanderbilt Institute for Global Bariatric Surgery, University of South Health Behavior Research Scientific Communication, Brasilia, Health; Vanderbilt University School Florida Health Science Center, Ricky Chen, MD Brazil of Medicine, Nashville, Tennessee Tampa, Florida Medicine in Society Stanley W Ashley, MD Linda Fahey, RN, NP, MSN Sylvestre Quevedo, MD Gary W Chien, MD Chief Medical Officer, Brigham and Regional Manager, Quality and Department of Medicine and Global Surgery Women’s Hospital; Frank Sawyer Patient Safety, Patient Care Services, Health Sciences, University of Professor of Surgery, Harvard Medical Kaiser Permanente, Southern California, San Francisco Carrie Davino-Ramaya, MD California, Pasadena National Practice Guidelines School; Attending Surgeon, Gastroin- Ilan Rubinfeld, MD, MBA, FACS, FCCP testinal Cancer Center, Dana Farber Richard Frankel, PhD Director, Surgical Intensive Care; Charles Elder, MD Cancer Institute; Chief, General Professor of Medicine and Psychiatry, Integrative Medicine Associate Program Director, Surgery, Harvard Vanguard Medical University of Indiana School of General Surgery Residency; Henry Philip I Haigh, MD, MSc, FRCSC, FACS Associates, Boston, Massachusetts Medicine, Indianapolis Ford Hospital, Detroit, Michigan; Surgery Thomas Bodenheimer, MD Carol Havens, MD Assistant Professor of Surgery, Wayne Lisa Herrinton, PhD Professor, Dept of Family and Family Practice and Addiction State University School of Medicine, Health Systems Research Community Medicine, University Medicine, Director of Clinical Detroit, Michigan Robert Hogan, MD of California, San Francisco Education, The Permanente Medical Marilyn Schlitz, PhD Family Medicine, Health Information Technology Brian Budenholzer, MD Group, Oakland, California Ambassador for Creative Projects Ashok Krishnaswami, MD, MAS Associate Clinical Professor in the James T Hardee, MD and Global Affairs, and Senior Cardiology Department of Family Medicine at Internal Medicine, Colorado Scientist, Institute of Noetic Sciences, David Riley, MD the Brody School of Medicine at Permanente Medical Group; Petaluma, California Case Reports East Carolina University, Greenville, Associate Clinical Professor of Audrey Shafer, MD North Carolina Ruth Shaber, MD Medicine, University of Colorado Associate Professor, Dept of Women’s Health Alexander M Carson, RN, PhD School of Medicine, Westminster Anesthesia, Co-Director, Biomedical Associate Dean of Research and Ethics & Medical Humanities John Stull, MD, MPH Arthur Hayward, MD Enterprise at the Institute of Health, Scholarly Concentration, Stanford Spirit of Medicine Dialogues Internal Medicine and Geriatrics, Medical Sciences and Society at CMI Clinical Lead for Elder Care; University School of Medicine, Palo Gretchen Summer, PhD, RN Glyndwr University in Wrexham, Assistant Clinical Professor, Division Alto, California Nursing Research and Practice Wales, United Kingdom of General Medicine, Dept of Mark Snyder, MD KM Tan, MD Rita Charon, MD, PhD Internal Medicine, Oregon Health Specialist Leader, Electronic Continuing Medical Education Professor of Medicine, Founder and Sciences University, Portland Medical Record Implementation Calvin Weisberger, MD Executive Director of the Program Catherine Hickie, MBBS and Physician Adoption; 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3  ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

James J Annesi, PhD, FAAHB, FTOS, FAPA; Ping H Johnson, PhD; Gisèle A Tennant, PhD; Kandice J Porter, PhD; Kristin L McEwen Perm J 2016 Summer;20(3):15-146 E-pub: 02/01/2016 http://dx.doi.org/10.7812/TPP/15-146

ABSTRACT approximately 6 months will mostly (if Context: For decades, behavioral weight-loss treatments have been unsuccessful beyond not all) be regained within 1 to 3 years.4,5 the short term. Development and testing of innovative, theoretically based methods that Even a more modest weight loss of at least depart from current failed practices is a priority for behavioral medicine. 3% of original body weight sustained for 2 Objective: To evaluate a new, theory-based protocol in which exercise support methods years, sometimes considered to be a marker are employed to facilitate improvements in psychosocial predictors of controlled eating of both weight-loss maintenance and some and sustained weight loss. health-risk reductions,6 has been difficult Methods: Women with obesity were randomized into either a comparison treatment to attain.7 Repeating the pattern of weight that incorporated a print manual plus telephone follow-ups (n = 55) or an experimental loss and regain may have adverse effects on treatment of The Coach Approach exercise-support protocol followed after 2 months by both health risks and subsequent attempts group nutrition sessions focused on generalizing self-regulatory skills from an exercise at weight loss.8,9 support to a controlled eating context (n = 55). Repeated-measures analysis of variance contrasted group changes in weight, physical activity, fruit and vegetable intake, mood, and Previous Behavioral Treatments exercise- and eating-related self-regulation and self-efficacy over 24 months. Regression Interventions based on educating indi- analyses determined salient interrelations of change scores over both the weight-loss phase viduals on the need to lose weight by eat- (baseline-month 6) and weight-loss maintenance phase (month 6-month 24). ing more healthfully and by being more Results: Improvements in all psychological measures, physical activity, and fruit and physically active are the most common but vegetable intake were significantly greater in the experimental group where a mean weight have been ineffective.4 Their absence of loss of 5.7 kg (6.1% of initial body weight) occurred at month 6, and was largely main- foundation in established behavior-change tained at a loss of 5.1 kg (5.4%) through the full 24 months of the study. After establishing theories and research is a proposed reason temporal intervals for changes in self-regulation, self-efficacy, and mood that best predicted for this lack of success.10 Cognitive-behav- improvements in physical activity and eating, a consolidated multiple mediation model ioral methods consistent with Bandura’s suggested that change in self-regulation best predicted weight loss, whereas change in social cognitive11 and self-efficacy12 theo- self-efficacy best predicted maintenance of lost weight. ries (eg, goal setting, cognitive restructur- Conclusions: Because for most participants loss of weight remained greater than that ing) have occasionally had more favorable required for health benefits, and costs for treatment administration were comparatively low, effects13,14 and are presently considered to be the experimental protocol was considered successful. After sufficient replication, physician state-of-the-art by many researchers. Several referral and applications within health promotion and wellness settings should be considered. reviews, however, suggest that even those types of interventions simply defer weight re- INTRODUCTION cancers.2 Although improving one’s dietary gain.4,5,15 Summaries of research also suggest Approximately 69% of US adults are at behaviors (eg, increasing intake of fruits that longer treatments (eg, 6 to 12 months, a weight high enough to be considered un- and vegetables; reducing the consumption or longer) have had somewhat better effects healthy (body mass index [BMI], calculated of fats and sweets) and increasing physical than shorter treatments; but initial weight as weight in kilograms divided by height in activity will reliably reduce weight by at loss, energy-intake requirements, financial meters squared, ≥ 25 kg/m2).1 Approximate- least the 5% required to obtain clinically incentives, and focusing on fat vs kilocalories ly 36% of US women are obese (BMI ≥ 30 important health benefits,3 maintenance (kcal) do not affect the rate of weight regain kg/m2).1 As degree of overweight increases, of those behaviors has been very difficult after approximately 6 months.5 Research has so do health risks such as diabetes mellitus, for almost all individuals.4,5 It can reliably rarely sought to determine the psychosocial hypertension, heart disease, and certain be predicted that weight lost over the first factors that predict weight-loss outcomes.16

James J Annesi, PhD, FAAHB, FTOS, FAPA, is the Director of Wellness Advancement, YMCA of Metropolitan Atlanta, and Professor in the Department of Health Promotion and Physical Education at Kennesaw State University in GA. E-mail: [email protected]. Ping H Johnson, PhD, is a Professor in the Department of Health Promotion and Physical Education at Kennesaw State University in GA. E-mail: [email protected]. Gisèle A Tennant, PhD, is the President of Tennant Solutions in Calgary, Alberta, Canada. E-mail: [email protected]. Kandice J Porter, PhD, is an Associate Professor in the Department of Health Promotion and Physical Education at Kennesaw State University in GA. E-mail: [email protected]. Kristin L McEwen, is the Empower Healthy Living Lead at the YMCA of Metropolitan Atlanta in GA. E-mail: [email protected].

4 The Permanente Journal/Perm J 2016 Summer;20(3):15-146 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

A group of behavioral researchers from further consideration of their findings and through standardized cognitive-behavioral Oxford University recently incorporated the entire body of research on intervention methods (eg, The Coach Approach proto- the extant theory and research to develop outcomes, they pessimistically, yet possi- col32), it was proposed that the relation- a highly structured Cognitive Behavioural bly realistically, concluded their report by ship of exercise with maintained weight Therapy protocol (Oxford CBT) in which questioning whether continuing behavioral loss is more because of its association with maintenance of lost weight was targeted research in the area of weight management improvements in psychological predictors from the start.17 Their intervention model is even warranted any longer.21 of controlled eating than associated energy is instructive because it embodies much expenditures.33 For example, if self-regulatory of the current thinking on both obtain- Suggested Treatment Improvements skills (eg, thought-stopping) could first be in- ing and sustaining weight loss through Other researchers disagreed with the above ternalized within an intervention component evidence-based behavioral methods such conclusions, but it was acknowledged that designed to facilitate regular exercise, possibly as self-monitoring the time, location, kcal, many of the presently held assumptions treatment elements could be constructed to and type of foods and drinks consumed;18 and methods around behavioral weight-loss promote generalization of such behavioral regular self-weighing;19 and actively coun- treatments are ineffective and “fresh ideas skills to controlled eating.33 This, however, tering lifestyle barriers.20 Components of are needed for attacking the problem.”5p14 runs in opposition to treatments such as the the Oxford CBT, which were administered Following from this suggestion, the Na- Oxford CBT17 and some basic research34 by mostly clinical psychologists during in- tional Institutes of Health commissioned that suggests that self-regulation used for dividual 50-minute consultations, included a multidisciplinary working group on “In- one behavior (here exercise) might deplete an “the role of body image in weight loss,” novative Research to Improve Maintenance individual’s limited capacity of self-regulation “addressing barriers to weight loss,” “en- of Weight Loss” in 2014.22 Its final report for success with a second behavior (here re- couraging acceptance,” “common primary summarized that 1) although adherence duced kcal eating). It was also proposed that goals,” and “developing long-term weight issues need to be addressed first, exercise self-efficacy, or one’s feelings of ability and maintenance skills.”17 Tracking of foods, ini- has promising implications for maintaining mastery, could be increased by demonstrat- tially limiting to a 1500 kcal intake per day, weight loss that go well beyond its obvious ing to one’s self a better control of exercise and weighing and graphing weight changes expenditure of energy; and 2) learning behav- behaviors through the use of newly learned were key elements of the modular protocol. ioral skills before starting on weight loss might self-regulatory skills to counter barriers.33 The 24 sessions over 44 weeks designated be beneficial for weight-loss maintenance.22 Improved self-efficacy to control exercise the initial 24 to 30 weeks as a weight-loss In an unrelated review of treatment results, might, in turn, also generalize to controlled phase, with the remainder devoted to Mann and her colleagues4 also recommended eating, the other critical weight-loss behav- weight maintenance. More in common further research on exercise as possibly being ior of interest.33,35 Improvements in mood, with the available treatments, though, was the “potent factor” (for long-term weight a well-established by-product of initiating that exercise was not emphasized. The treat- loss), in lieu of any additional work on diet- even manageable amounts of exercise,33,36 ment developers suggested that its minor ing or composition of the diet. might serve to counter the common problem impact on kcal totals render physical activity Although a program of regular exercise (especially for women) of emotional eating,37 as being of minor concern for weight loss, has been shown to be the strongest predictor and “… lead to a healthier psychological and could possibly interfere with dietary of success with maintaining weight loss for climate in which individuals have more compliance. Thus, initiating physical activ- some time,23-25 it remains difficult to main- cognitive and emotional resources, as well as ity could be deferred by up to 6 months.17 tain with an expected dropout rate of 50% motivation and energy, to sustain a long-term Although the Oxford CBT was expensive to 65% within 3 to 6 months of its initia- commitment to a weight-loss program.”35p320 at an estimated professional cost of between tion.26,27 On the basis of accelerometer data Adherence to just 2 to 3 sessions per week US$3000 and US$4500 per participant, from both the 2003-2004 and 2005-2006 of behaviorally supported exercise has been it proved to be no more effective than National Health and Nutritional Examina- associated with significant improvements standard behavioral treatment.21 With its tion Surveys, less than 4% of US women in self-regulation, self-efficacy, and mood,38 sample of 49 women with obesity (ie, BMI complete the equivalent of at least 5 mod- which were found to be the most critical of 30-40 kg/m2) who were tested, approxi- erate-intensity walks per week,28,29 which is psychological predictors of improvements in mately 68% of lost weight was regained at considered to be the minimum threshold eating and weight over 6 months, even when the 2-year point, and 91% was regained for health benefits.30 Pilot research indicates previously suggested factors such as self- 3 years past treatment initiation. Possibly that even when dropout from exercise is suc- concept and body image35 were considered.39 because even this strongly evidence-based cessfully countered, typical frequencies for Additional studies are, however, required to and well-administered approach was judged formerly sedentary participants with obesity determine psychological predictors of longer- by its developers to be ineffective at sustain- are only 2 to 3 sessions per week, with an term weight-loss maintenance that might ing weight loss, they stated that it might estimated energy expenditure of less than inform both theory and the architecture of be “ethically questionable to claim that 150 kcal per session (which amounts to only improved behavioral treatments. Although psychological [behavioral] treatments for approximately 0.5 kg of weight loss every 9 exercise is frequently incorporated into obesity ‘work’ in the absence of [favorable] to 10 weeks31). Although there have been weight-loss interventions, we have found no data on their longer-term outcome.”21p712 In advances in improving adherence to exercise longer-term research where its primary focus

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was on improving psychological predictors of phases in the experimental group when Abbreviations Keys controlled healthy eating. contrasted with the comparison group. Thus, as an extension to earlier research 3. Improvements in the targeted psychologi- FV = Fruit and vegetable intake on short-term psychological, behavioral, cal variables of mood, self-regulation, and Mood = Overall negative mood and weight-loss effects,33,40-42 the present self-efficacy—related to both exercise and PA = Physical activity study was conducted. It incorporated 1) an eating—will be greater during both the SE-eating = Self-efficacy for controlling experimental treatment that initiated sup- weight-loss and weight-loss maintenance eating ported exercise 2 months before any changes phases in the experimental group when SE-exercise = Self-efficacy for exercise in nutrition in attempts to improve targeted contrasted with the comparison group. SR-eating = Self-regulation for psychological and behavioral correlates of controlled eating improved eating and weight loss, and 2) a Research Questions SR-exercise = Self-regulation for exercise comparison treatment of participants’ use 1. Was change in physical activity and of a manual that simultaneously encouraged fruit and vegetable intake from baseline- healthy eating, physical activity, and reason- month 3, baseline-month 6, or month pregnancy; 2) present use of medications able expectations, which was supplemented 3-month 6 the better predictor of weight for weight loss or a psychological/psychi- by telephone follow-ups. Both treatments change during the weight-loss phase? atric condition; 3) current participation were based on accepted behavioral theory, What temporal interval of change in in a medical, commercial, or self-help yet there were substantial differences. On physical activity and fruit and vegetable weight-loss program; and 4) participa- the basis of a research consensus indicating intake best predicted weight change dur- tion in a program of regular physical that the initial approximately 6 months af- ing the weight-loss maintenance phase? activity/exercise that averaged at least 20 ter treatment start is a time of weight loss, 2. Was change in each psychological vari- minutes per week during the year before whereas beyond 6 months weight regain able from baseline-month 3, baseline- the start of the study. Treatments were (often complete regain) can be reliably month 6, or month 3-month 6 the administered at small, community-based predicted,4,5 the present study investigated better predictor of physical activity and wellness/fitness centers in the Eastern US. 1) treatment-associated weight change, 2) fruit and vegetable intake change during Because the chance of cross-contamina- behavioral predictors of weight change (ie, the weight-loss phase? What temporal tion of participants through intergroup changes in healthy eating and physical ac- interval of change in each psychologi- interactions within the same facility tivity), and 3) hypothesized psychological cal variable best-predicted behavioral would have been high, randomization to predictors of the behavioral changes (ie, changes during the weight-loss mainte- either the comparison (COM) treatment self-regulation, self-efficacy, mood) during nance phase? (n = 55) or the experimental (EXP) treat- those 2 time frames. Data were measured 3. Did changes in mood and/or aggregated ment (n = 55) was by site (3 sites each). at baseline and months 3, 6, 12, and 24. (exercise- and eating-related) measures Institutional review board approval and This allowed contrasts of dynamic changes of self-regulation and self-efficacy written informed consent from each par- in targeted variables by group, and analyses significantly mediate relationships be- ticipant were received. The research was of which of the possible temporal intervals tween treatment type (comparison and conducted in accordance with require- best predicted weight change and weight experimental) and changes in weight ments of the Helsinki Declaration. change-related behavioral improvements. during the weight-loss and weight-loss Independent t- and χ2 tests indicated no Such findings could be instrumental for maintenance phases? significant group difference in age (mean-

determining when, and to what degree, cor- Because participant characteristics, overall ± standard deviation (SD) = 48.2 ± responding treatment processes should be initial weight, cognitive-behavioral treat- 7.8 years), BMI (35.3 ± 3.2 kg/m2), or emphasized. To enhance clarity, this report ment orientation, and focus on weight-loss racial/ethnic make-up (overall 83% white, is expressed in 3 parts corresponding to the maintenance were designed to be similar to 11% African American, and 6% of other aforementioned 3 areas. Hypotheses and those of the previously published Oxford racial/ethnic groups). On the basis of self- research questions are as follows. CBT study,21 the present weight-change reported family income, most participants data were also contrasted with the Oxford were middle class (overall 11% below Hypotheses CBT findings. $24,999, 21% = $25,000-$49,999, 41% = 1. Reduction in weight from baseline-month $50,000-$99,999, and 27% = $100,000 or 6 (weight-loss phase) will be greater, and METHODS greater). Attrition from initial study accep- regain in weight from month 6-month Participants tance to actual treatment participation was 24 (weight-loss maintenance phase) will Participant recruitment was through minimal at 7% and also did not significantly be less, in the experimental group when local print and electronic media. Inclu- differ by group. This attrition was associated contrasted with the comparison group. sion criteria were 1) women of at least 21 with either a reported illness, a newly arisen 2. Improvements in the targeted behaviors years of age, 2) BMI ≥ 30 and < 40 kg/ orthopedic issue, transportation issues, or of physical activity and fruit and vegeta- m2, and 3) a self-reported goal of weight an inability of study staff to make further ble intake will be greater during both the loss. Exclusion criteria based on self- contact after 3 attempts. There was no cost weight-loss and weight-loss maintenance report were 1) present or soon-planned or financial compensation for participation.

6 The Permanente Journal/Perm J 2016 Summer;20(3):15-146 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

Measures use of a recently calibrated scale (800KL; manage their environments, and 3) possess- The self-report measures used in this Healthometer, Buffalo Grove, IL). ing capabilities to be self-reflective of their study were 1) physical activity (PA) internal abilities. Both the EXP and COM through weekly energy expenditure, Procedure curricula incorporated cognitive-behavioral 2) healthy eating through daily fruit and Participants initially received a group methods designed to empower participants vegetable intake (FV), 3) self-regulation orientation to their assigned EXP or COM with self-regulatory skills and abilities to for exercise (SR-exercise), 4) self-regulation protocol. Wellness counselors administering deal with barriers to managing their weight for controlled eating (SR-eating), 5) self- treatments were trained in only one of the effectively, while increasing their feelings of efficacy for exercise (SE-exercise), 6) overall protocols and masked to the treatment dif- mastery and competence (ie, self-efficacy). negative mood (Mood), and 7) self-efficacy ferences and the study’s research goals. Both Both treatment protocols informed partici- for controlling eating (SE-eating). Descrip- the EXP and COM treatments were based pants of the recommended volume of weekly tions of each of these measures, along with on the social cognitive11 and self-efficacy12 exercise to gain health benefits,30 but also data on their reliability and validity, are theories of behavior where individuals are suggested that any amount was also likely to presented below (Table 1). Body weight viewed as 1) directing their own actions be beneficial. However, the administration was measured in kilograms through the through self-organization, 2) being able to formats and the proposed role of physical

Table 1. Description of study measures Measurement Measure instrument Instrument description Reliability and validity Physical activity Godin-Shephard Requires entry of number of weekly sessions of strenuous (~ 9 METs; eg, Test-retest reliability (2 weeks) was (PA) Leisure-Time running), moderate (~ 5 METs; eg, fast walking), and light (~ 3 METs; eg, easy 0.74.45 Construct validity was indicated Physical Activity walking) physical exertion for “more than 15 minutes.” Incorporates METs, or through strong correlations with both Questionnaire43 the energy costs associated with specific physical activity intensities (1 MET accelerometer and peak volume of 44 46,47 approximates the use of 3.5 ml of O2/kg/minute). oxygen uptake measurements. Healthy eating Self-report survey Foods and beverages consumed “in a typical day over the past week” are Test-retest reliability (3 weeks) was measured by fruit of FV48 based on examples and serving sizes of fruits (eg, apple, banana, peach [1 0.77-0.83 for women.33 Validated and vegetable small or 118 mL or 4 ounces canned]; raisins, dates [0.59 mL or 2 ounces]; against comprehensive food frequency intake (FV) 100% fruit juice [118 mL or 4 ounces]) and vegetables (eg, broccoli, carrots, questionnaires,54 in which pilot research tomatoes, green beans [118 mL or 4 ounces]; raw spinach [236 mL or 8 indicated strong correlations (r-values = ounces]) that correspond to both the US Department of Agriculture’s current 0.70-0.85) with the full-length Block Food MyPlate and former Food Guide Pyramid.49 Increases in FV were strongly Frequency Questionnaire.54,55 associated with both weight loss and weight-loss maintenance,50 and an increase in FV was a stronger predictor of weight loss than reduction in fat intake.51 Previous research indicates that FV alone is a strong predictor of overall energy consumption and healthfulness of the diet.52,53 Self-regulation for Adaptation of The 10 items for SR-exercise (eg, “I say positive things to myself about being Cronbach α-values for internal exercise (SR- a previously physically active”) and SR-eating (eg, “I make formal agreements with myself consistency were 0.75,56 0.83, and 0.80 exercise) and validated scale56,57 regarding my eating”) assess the degree that barriers to those behaviors are for the present versions and sample, self-regulation for addressed through the use of self-regulatory skills. Responses range from 1 respectively. Test-retest reliability (2 controlled eating (never) to 5 (often), and are summed. A higher score indicates a greater use of weeks) was 0.77.56 (SR-eating) self-regulation. Self-efficacy Exercise Self- After beginning with the stem, “I am confident I can participate in regular Cronbach α-values for internal for exercise Efficacy Scale58 exercise when ...,” each of the scale’s 5 items end with a possible barrier to consistency were 0.76-0.82. Test-retest (SE-exercise) overcome (eg, “I am tired,” “I have more enjoyable things to do”). Responses reliability (2 weeks) was 0.90.59 Cronbach range from 1 (not at all confident) to 7 (very confident), and are summed.A α-value for internal consistency for the higher score indicates greater self-efficacy. present sample was 0.80. Overall negative Profile of Mood The 30 items (5 items per factor) assess feelings during the past week on Cronbach α-values for internal mood (Mood) States Short depression (eg, “sad”), tension/anxiety (eg, “tense”), vigor (eg, “energetic”), consistency were 0.84-0.95 across Form scale fatigue (eg, “weary”), anger (eg, “angry”), and confusion (eg, “forgetful”). factors,60 and 0.79-0.89 for the present of Total Mood Responses range from 0 (not at all) to 4 (extremely) and are summed after sample. Test-retest reliability (3 weeks) Disturbance60 reversing the scores of the vigor factor. A lower score indicates better mood. averaged 0.69.60 Self-efficacy for Weight Efficacy The 20 items (4 per factor) assess feelings of ability to control eating when Cronbach α-values for internal controlling eating Lifestyle Scale61 the following situations are present: negative emotions (eg, “I can resist eating consistency were 0.70-0.90 across its (SE-eating) when I am anxious [nervous]”), food availability (eg, “I can resist eating even factors,61 and 0.74-0.81 for the present when I am at a party”), physical discomfort (eg, “I can resist eating when I am sample. uncomfortable”), positive activities (eg, “I can resist eating when I am watching TV”), and social pressure (eg, “I can resist eating even when I have to say ‘no’ to others”). Responses range from 0 (not confident) to 9 (very confident), and are summed. A higher score indicates greater self-efficacy. MET = metabolic equivalent; TV = television.

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activity/exercise in facilitating changes in eat- meetings with a trained wellness counselor After 8 weeks of concentration exclu- ing behaviors differed substantially between possessing at least 1 national certification sively on maintaining regular exercise, the the EXP and COM treatments. (eg, American College of Sports Medicine). components for eating behavior change The EXP treatment incorporated The These were conducted in a private office were sequentially added. First, guidance Coach Approach exercise-support pro- over 6.5 months. Each participant’s exercise and practice on methods for kcal tracking tocol32 paired with a nutrition behavior- plan, both initially and in revisions during was individually provided in two 30-minute change component developed for this subsequent meetings, was based on the par- meetings over 2 weeks. Energy-intake goals research. It was based on 1) results from ticipant’s preferred type of physical activity were based on each participant’s weight (eg, previous behavioral weight-management and tolerance. Most of the meeting time was, 1500 kcal/day for a weight range of 79-99 treatments,14,17,33,62-64 2) exploratory studies however, spent on the development of spe- kg), and various methods for recording food of psychosocial predictors of weight-loss cific self-regulatory skills such as long- and and corresponding kcal intake were made behaviors,33,39,57 3) findings suggesting that short-term goal setting paired with progress available (eg, through an approved Web behavioral mechanisms required to foster monitoring, dissociation from discomfort, site, an approved application for hand-held weight loss differ from those required to cognitive restructuring, stimulus control, devices, or a provided paper form and use of maintain lost weight,16,65 and 4) the sug- behavioral contracting, controlling behav- an approved “calorie counter” book). Next, gested benefits of targeting specific and ioral prompts and triggers, and relapse pre- 10 nutrition sessions of 60 minutes each measurable behaviors for change (eg, in- vention. Exercise-induced changes in mood focused on weight reduction were admin- creasing FV rather than addressing numer- (eg, anxiety, energy level) were assessed both istered by trained wellness counselors (sup- ous and detailed elements of the diet).66 in response to a single bout of physical ac- ported by a manual) at 2-week intervals in Beginning at baseline, The Coach Approach tivity and for 1 to 2 months, and displayed groups of 8-15 participants. Their primary protocol32 supported adherence to newly through responses to items embedded in the aim was to generalize, adapt, and extend initiated exercise through six 45-minute supporting computer application. self-regulatory skills developed during The

Figure 1. Timeline of the Experimental Treatment, Comparison Treatment, and Oxford Cognitive Behavioural Therapy. B = baseline; kcal = kilocalories; LEARN = lifestyle, exercise, attitudes, relationships, nutrition.

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Coach Approach exercise-support proto- col,32 to self-regulating eating behaviors (eg, dissociating from exercise-induced discomfort was generalized to dissociating from feelings of hunger; recovering from and rescheduling a missed exercise session was generalized to recovering from a day of excess kcal intake and immediately recommitting to the appropriate limit for the next day). There was a combination of brief lectures, individual tasks, and group activities within each session. The next component, now 28 weeks after baseline, was 4 group sessions in which self-regulatory skills were addressed in the context of maintaining lost weight. The Figure 2. Representation of mediation models. final 10 sessions of the EXP treatment cov- ered skills of self-regulation in both weight- loss and weight-loss maintenance contexts foods and drinks consumed, the amount a low degree of multicollinearity. During the (Figure 1). Treatment content related to the consumed and their associated kcal, their weight-loss maintenance phase, tolerances diet was primarily concentrated on increas- corresponding food group categorization, (0.22-0.86) and variance inflation factors ing FV intake, although there was a limited and optional comments. (1.16-4.58) indicated a low-moderate degree focus on minimizing the consumption of Fidelity checks were completed on ap- of multicollinearity.71 Inspection of residual fat and sugar. Because meeting time was proximately 15% of treatment components scatterplots indicated homogeneity of vari- primarily centered on the development of by study staff. Minor protocol violations ances and linearity in the data. Both skew- self-regulatory skills and the ability to in- were primarily related to adherence to re- ness and kurtosis values were < 2 standard crease self-efficacy for controlling overeating, quired time frames within sessions and were errors. Consistent with previous suggestions participants were referred to the ChooseMy- easily rectified through study staff-instructor for research within the present context, Plate.gov Web site67 for access to detailed, interactions. Surveys and weight measure- change scores were unadjusted for baseline evidence-based information on nutrition. ments were completed in a private area. values.72 Statistical significance was set atα = The COM treatment replicated methods 0.05 (2-tailed) unless otherwise noted. Sta- used previously in studies,21,42 and consisted Data Analyses tistical analyses were conducted using SPSS, of participants reviewing 1 of the 12 “les- To avoid inappropriately inflated effect version 22 (IBM, Armonk, NY). sons” of a 265-page print manual entitled sizes such as those reported in the many For all study measures, general linear The LEARN (lifestyle, exercise, attitudes, studies where data from only weight-loss model mixed-model repeated measures anal- relationships, nutrition) Program for Weight program “completers” were included, the yses of variance (ANOVAs) were computed Management (10th edition)68 every 2 weeks. conservative intention-to-treat approach to determine whether there were significant Sections related to behavior change included was used, as suggested.13 Thus, data were score changes across the 5 measurement “Dealing with Pressures to Eat,” “Preventing retained from all participants who engaged times (baseline; months 3, 6, 12, and 24), Lapse, Relapse, and Collapse,” “Interpret- in treatment processes. The expectation- and whether those changes differed between ing Your Progress,” and “Making Physical maximization algorithm69 was used to the EXP and COM groups. These were Activity Count.” Sections related to diet impute data for the 14% of missing scores. followed up by planned t tests to assess and included “Fast Foods,” “Rating Your Diet,” The required criteria of missing at random contrast within-group changes during the “Vegetables in Your Diet,” and “Breads, (no systematic bias) was indicated because weight-loss phase (using 1-tailed tests) and Cereals, Rice, and Pasta in Your Diet.” participants who were missing data at any the weight-loss maintenance phase. Their Each lesson was followed by a 15-minute assessment time did not significantly differ associated effect sizes were computed as phone conversation initiated by a wellness from the sample as a whole on demographic Cohen’s d ([meanpost - meanpre]/SDpre). Effect counselor to clarify chapter contents, review characteristics or any other study measure. sizes for ANOVA models were calculated 2 each participant’s plans for carrying out On the basis of the planned multiple regres- using partial η-squared (η p = SSeffect/[SSeffect 2 behavioral changes, and answer the partici- sion equations incorporating 3 predictor + SSerror]). For d and η p, 0.20, 0.50, 0.80; pant’s questions. The process of participants variables, and to detect the moderate effect and 0.01, 0.06, 0.14 denote small, moder- reading chapters and obtaining telephone of f2 = 0.15 that was indicated in pilot re- ate, and large effects, respectively. follow-ups started at baseline and lasted 24 search33 at the statistical power of 0.90 (α = weeks (Figure 1). The LEARN manual68 sug- 0.05), a minimum of 98 total participants Part 1: Weight Change gested that women limit their energy intake was required.70 In tests during the weight- After completing planned ANOVAs and to 1200 kcal per day. A paper monitoring loss phase, tolerances (0.60-0.82) and vari- follow-up tests on weight, and on the basis form was provided for participants to record ance inflation factors (1.23-1.67) indicated of research suggesting that ≥ 5% weight loss

The Permanente Journal/Perm J 2016 Summer;20(3):15-146 9 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

is the threshold for health benefits,3 the for the prediction of change in weight over identical to Part 2 were then completed. percentage of participants attaining this the weight-loss phase, were then contrasted. Data from the temporal intervals found criterion was reported for month 6 (end Given the data collected, all possible tempo- to have the strongest relationships served of the weight-loss phase) and month 24 ral intervals of changes in PA and FV during as the predictors of PA and FV changes in (end of the study), by group. Because ≥ the course of the 24-month investigation multiple regression equations. 3% loss has been the suggested criterion were similarly contrasted for predicting Because 1) the EXP treatment focus for maintained weight loss,6 attainment of change in weight during the weight-loss was on the carry-over of exercise-related this change was also reported at month 24. maintenance phase. As was previously self-regulation and self-efficacy to eating- Weight-change data previously published suggested,73 wherever possible, behavioral related self-regulation and self-efficacy, 2) on the Oxford CBT21 were also adapted for changes occurring during the weight-loss their strong interrelations had previously additional contrasting. phase were statistically controlled for. been supported,33 and 3) previous theory suggested their interactions,35,65 after nor- Part 2: Behavioral Predictors Part 3: Psychological Predictors malizing (centering and standardizing) of Weight Changes of Behavioral Changes scores and confirming expected interre- After completing planned ANOVAs and After completing planned ANOVAs lations, the exercise- and eating-related follow-up tests on PA and FV, data were and follow-up tests on the five psycho- self-regulation and self-efficacy measures aggregated across groups. The strengths logical variables, data were aggregated were merged for further analyses. Multiple of bivariate relationships between changes across groups. Analyses of relationships mediation models incorporating 20,000 in PA and FV from baseline-month 3, of changes in the psychological variables bootstrapped resamples74 were specified baseline-month 6, and month 3-month 6, using temporal intervals and methods where the predictor variable was treatment

Table 2a. Descriptive statistics of study measures and analyses of their changes over 24 months, by groupa Time × group Baseline Month 3 Month 6 Month 12 Month 24 Effect for timeb interaction 2 2 (mean ± SD) (mean ± SD) (mean ± SD) (mean ± SD) (mean ± SD) (F(4, 432) [η p]) (F(4, 432) [η p]) Weight (kg) Experimental 94.95 ± 11.44 92.03 ± 11.84 89.21 ± 11.57 89.40 ± 11.86 89.84 ± 13.58 26.25c [0.196] 6.84c [0.060] Comparison 95.36 ± 10.56 94.46 ± 10.63 93.27 ± 10.44 93.51 ± 11.07 94.11 ± 11.23 Oxford CBTd 92.34 ± 8.81 NA 83.29 ± 10.39 84.33 ± 11.11 89.45 ± 11.48 Physical activity (METs/week) Experimental 8.31 ± 7.30 28.65 ± 13.56 32.77 ± 15.47 32.44 ± 15.16 23.59 ± 15.15 89.01c [0.452] 9.50c [0.081] Comparison 9.65 ± 8.14 23.51 ± 15.44 22.02 ± 12.82 23.20 ± 12.60 22.40 ± 12.26 Fruit and vegetable intake (servings/day) Experimental 3.95 ± 1.97 5.81 ± 2.39 6.42 ± 2.14 6.23 ± 2.24 5.56 ± 1.90 38.92c [0.265] 4.55e [0.040] Comparison 3.30 ± 1.81 4.25 ± 2.04 4.46 ± 2.23 4.73 ± 1.99 4.62 ± 1.98 Self-regulation for exercise Experimental 22.53 ± 6.32 32.51 ± 4.36 33.04 ± 4.28 32.27 ± 4.59 29.87 ± 5.96 64.03c [0.372] 14.63c [0.119] Comparison 23.07 ± 6.32 26.96 ± 6.12 26.58 ± 6.91 26.58 ± 6.75 26.56 ± 6.69 Self-efficacy for exercise Experimental 25.87 ± 9.47 33.38 ± 10.08 34.98 ± 10.52 33.25 ± 11.73 29.36 ± 11.82 14.64c [0.119] 4.27e [0.038] Comparison 22.36 ± 9.73 25.47 ± 10.89 25.29 ± 12.25 25.98 ± 11.22 25.49 ± 10.84 Total mood disturbance Experimental 25.69 ± 15.45 9.17 ± 15.00 4.55 ± 11.54 7.96 ± 11.88 9.38 ± 13.87 53.56c [0.332] 8.62c [0.074] Comparison 21.71 ± 11.50 12.25 ± 8.12 13.89 ± 11.50 12.78 ± 11.88 13.47 ± 11.51 Self-regulation for controlled eating Experimental 23.75 ± 5.60 31.25 ± 4.57 32.51 ± 4.00 31.96 ± 4.19 29.82 ± 5.68 64.16c [0.373] 5.64c [0.050] Comparison 22.05 ± 5.78 26.91 ± 5.54 26.78 ± 5.59 26.44 ± 5.23 26.29 ± 5.20 Self-efficacy for controlled eating Experimental 87.82 ± 31.21 114.96 ± 26.95 126.48 ± 26.51 127.26 ± 26.90 124.69 ± 28.34 47.29c [0.305] 4.39e [0.039] Comparison 88.24 ± 33.80 104.65 ± 27.17 108.00 ± 30.76 110.35 ± 30.45 108.18 ± 29.90 a Experimental group, n = 55; comparison group, n = 55. b Analysis of variance effects for time, and time × group interactions, contrast changes from baseline to month 24. c p < 0.001. d These data were adapted from previous research21 for contrasting purposes. e p < 0.01. CBT = Cognitive Behavioural Therapy; MET = metabolic equivalent; SD = standard deviation.

10 The Permanente Journal/Perm J 2016 Summer;20(3):15-146 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

type (0 = COM; 1 = EXP), the outcome a multiple mediation model, significance If a significant mediator was found in variable was weight change during the of a mediator is identified when its corre- the above analysis over the weight-loss weight-loss or weight-loss maintenance sponding 95% confidence interval for an phase, follow-up simple mediation models phase, and the possible mediators were indirect effect does not include 0. A graphi- (eg, models with only a single mediator) changes in mood and the merged self- cal representation of mediation models is were then specified to determine whether regulation and self-efficacy measures. In given in Figure 2. change in that psychological variable and weight demonstrated a reciprocal relation- ship. A reciprocal relationship is identified Table 2b. Planned follow-up t-test results over the weight-loss phase (baseline-month 6) and weight-loss maintenance phase (months 6-12), by groupa if, after reversing the position of the origi- nal outcome and mediator variable within Group t(54) p vaue d a complementary mediation model, both Weight (kg) change equations demonstrate significant media- Weight-loss phase EXP -11.18 < 0.001 0.50 tion.42 Because the presence of a reciprocal COM -5.13 < 0.001 0.20 relationship may not be assessed directly Weight-loss maintenance phase EXP 0.61 0.274 0.05 through multiple mediation, or with co- COM 1.87 0.033 0.08 variates, these analyses were possible dur- Entire study period EXP -4.59 < 0.001 0.45 ing only the weight-loss phase. (baseline-month 24) COM -1.86 0.068 0.12 Physical activity change (METs/week) RESULTS Weight-loss phase EXP 11.83 < 0.001 3.18 There was no significant difference at COM 8.89 < 0.001 1.52 baseline between the EXP and COM Weight-loss maintenance phase EXP -4.42 < 0.001 0.59 groups on any study measure. Table 2a COM 0.30 0.764 0.03 provides descriptive statistics of data at Fruit and vegetable intake change (servings/day) baseline and at months 3, 6, 12, and 24. Weight-loss phase EXP 7.67 < 0.001 1.24 For all variables, there was a significant COM 3.90 < 0.001 0.64 overall effect and a significant time × group interaction during the 24-month study Weight-loss maintenance phase EXP -3.07 0.003 0.40 (Table 2a). Results of follow-up, within- COM 1.04 0.302 0.07 group t-tests, are given in Table 2b. Self-regulation for exercise change Weight-loss phase EXP 10.79 < 0.001 1.66 Part 1: Weight Change COM 4.56 < 0.001 0.56 During the weight-loss phase, although Weight-loss maintenance phase EXP -4.54 < 0.001 0.53 within-group reductions in weight in the COM -0.03 0.974 0.003 EXP group (-5.73 kg) and COM group Self-efficacy for exercise change (-2.09 kg) were both significant, the EXP Weight-loss phase EXP 8.56 < 0.001 0.96 group had a significantly greater between- COM 0.79 0.039 0.30 group reduction in weight, t(108) = 5.56, p Weight-loss maintenance phase EXP -4.10 < 0.001 0.53 < 0.001, d = 1.07. During the weight-loss COM 0.19 0.848 0.02 maintenance phase, within-group weight Total mood disturbance change regain in the EXP group (0.63 kg) was Weight-loss phase EXP -9.21 < 0.001 1.37 not significant, whereas it was significant COM -5.58 < 0.001 0.68 in the COM group (0.84 kg). During Weight-loss maintenance phase EXP 2.86 0.006 0.42 the full 24-month duration of the study, COM -0.44 0.663 0.04 reduction of weight was significant in the Self-regulation for controlled eating change EXP group (-5.11 kg), but not significant Weight-loss phase EXP 10.33 < 0.001 1.56 in the COM group (-1.25 kg). Between- group reduction in weight was significantly COM 6.54 < 0.001 0.81 greater over 24 months in the EXP group, Weight-loss maintenance phase EXP -4.25 0.001 0.67 t(108) = 2.95, p = 0.004, d = 0.58. COM -1.25 0.218 -0.08 At month 6, ≥ 5% weight loss was Self-efficacy for controlled eating change found in 65.5% of EXP and 18.2% Weight-loss phase EXP 8.15 < 0.001 1.24 of COM participants. At month 24, COM 4.37 < 0.001 0.58 ≥ 5% weight loss was found in 52.7% of Weight-loss maintenance phase EXP -0.46 0.646 0.07 EXP and 16.4% of COM participants. At COM 0.13 0.899 0.01 month 24, ≥ 3% weight loss was found a Experimental group (EXP), n = 55; Comparison group (COM), n = 55. in 63.6% of EXP and 38.2% of COM MET = metabolic equivalent.

The Permanente Journal/Perm J 2016 Summer;20(3):15-146 11 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

participants. Figure 3 provides a graphic rep- the EXP group, t(108) = 5.64, p < 0.001, Self-Regulation for Controlled Eating resentation of percentages of weight change d = 1.09. There was a significant between- During the weight-loss phase, within- for 24 months, including data adapted from group difference in SR-exercise reduction group increases in SR-eating in the EXP research on the Oxford CBT.21 during the weight-loss maintenance phase, group and the COM group were both t(108) = -3.51, p = 0.001, d = 0.67, with significant, and significantly greater in the Part 2: Behavioral Predictors the EXP group demonstrating a significant EXP group, t(108) = 3.64, p < 0.001, d = of Weight Changes within-group reduction and the COM 1.08. There was a significant between-group Physical Activity group showing no significant change. difference in SR-eating reduction during During the weight-loss phase, although Self-Efficacy for Exercise the weight-loss maintenance phase, t(108) within-group increases in PA in the EXP During the weight-loss phase, within- = -2.57, p = 0.012, d = 0.52, with the EXP group and the COM group were both group increases in SE-exercise in the EXP group having a significant within-group significant, the EXP group had a signifi- group and the COM group were both sig- reduction and the COM group showing cantly greater between-group increase, nificant, and significantly greater in the EXP no significant change. t(108) = 4.86, p < 0.001, d = 0.94. There group, t(108) = 2.94, p = 0.007, d = 0.52. Self-Efficacy for Controlled Eating was a significant between-group differ- There was a significant between-group dif- During the weight-loss phase, within- ence in PA change during the weight-loss ference in SE-exercise change during the group increases in SE-eating in the EXP maintenance phase, t(108) = -3.93, p weight-loss maintenance phase, t(108) = group and the COM group were signifi- < 0.001, d = 0.77, with the EXP group -3.39, p = 0.001, d = 0.65, with the EXP cant, and significantly greater in the EXP demonstrating a significant within-group group showing a significant within-group group, t(108) = 2.88, p = 0.005, d = 0.55. reduction and the COM group showing reduction and the COM group having no There was no significant between-group no significant change. significant change. difference in SE-eating change during the Eating Mood weight-loss maintenance phase, t(108) = During the weight-loss phase, within- During the weight-loss phase, with- -0.48, p = 0.635, d = 0.10, with neither group increases in FV in the EXP group in-group reductions in Mood score in the EXP or COM group demonstrating a and the COM group were both significant, both the EXP group and the COM significant within-group change. and significantly greater in the EXP group, group were significant, and significantly Prediction of Physical Activity Change t(108) = 2.97, p = 0.002, d = 0.57. There greater in the EXP group, t(108) = -4.98, The temporal interval that was the was a significant between-group differ- p = 0.002, d = 0.98. There was a signifi- strongest predictor of change in PA ence in FV change during the weight-loss cant between-group difference in Mood during the weight-loss phase was from maintenance phase, t(108) = -3.20, p change during the weight-loss mainte- baseline-month 6 for SR-exercise, = 0.002, d = 0.64, with the EXP group nance phase, t(108) = 2.70, p = 0.008, SE-exercise, and Mood. β(standard error)- having a significant within-group reduc- d = 0.54, with the EXP group demon- values were 0.58(0.15), 0.50(0.10), and tion and the COM group exhibiting no strating a significant within-group score -0.46(0.08), respectively; all p values < significant change. increase and the COM group exhibiting 0.001. The temporal interval that was the Prediction of Weight Change no significant change. strongest predictor of change in PA during The temporal interval that was the stron- gest predictor of weight change during the weight-loss phase was baseline-month 6 for both PA and FV. β(standard error)-values were -0.38(0.05) and -0.30(0.33), respec- tively; p values < 0.001. The temporal interval that was the strongest predictor of weight change during the weight-loss maintenance phase was month 6-month 24 for both PA and FV. β(standard error)- values were -0.45(0.11) and -0.28(0.87), respectively; p values < 0.001 and 0.018, respectively.

Part 3: Psychological Predictors of Behavioral Changes Self-Regulation for Exercise During the weight-loss phase, within- group increases in SR-exercise in the EXP group and the COM group were both Figure 3. Percentage of body weight change over 24 months, by group. significant, and significantly greater in CBT = Cognitive-Behavioural Therapy.

12 The Permanente Journal/Perm J 2016 Summer;20(3):15-146 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

the weight-loss maintenance phase was base- during the weight-loss maintenance phase measures for the planned mediation analy- line-month 24 for SR-exercise, SE-exercise, was month 12-month 24 for SR-eating, ses. The same Mood scale was used in both and Mood. β(standard error)-values were and baseline-month 24 for both SE-eating exercise and eating contexts so no such 0.65(0.24), 0.57(0.14), and -0.52(0.17), and Mood. β(standard error)-values were merger was needed. respectively; all p values < 0.001. 0.19(0.04), 0.47(0.01), and -0.31(0.02), In a consolidated model, the SR- After incorporating the above temporal respectively; all p values < 0.050. merged, SE-merged, and Mood measures intervals into the following two models, After incorporating the above temporal (changes from baseline-month 6) were the multiple regression equation predicting intervals, the multiple regression equation entered as possible mediators of the rela- PA change during the weight-loss phase predicting FV change during the weight- tionship between treatment type (COM was significant. Changes in SR-exercise, loss phase was significant. Changes in or EXP) and weight change during the SE-exercise, and Mood were each signifi- SR-eating, SE-eating, and Mood were weight-loss phase. The overall model was cant independent predictors (after control- each significant independent predictors significant, R2 = 0.35, F(4, 105) = 14.23, ling for one another). The prediction of (after controlling for one another) (Table p < 0.001. Only change in SR-merged was PA change during the weight-loss main- 3). The prediction of FV change over the a significant mediator within the equa- tenance phase was significant. Changes weight-loss maintenance phase was sig- tion (Table 4, Analysis I). In the planned in SR-exercise and SE-exercise, but not nificant. Neither changes in SR-eating, simple mediation follow-ups, change in Mood, were significant independent pre- SE-eating, nor Mood were significant SR-merged significantly mediated the dictors (Table 3). independent predictors (Table 3). relationship between treatment type and Prediction of Eating Change Consolidated Model for Weight-Loss Effects weight change; and weight change signifi- The temporal interval that was the As expected, correlations of baseline, cantly mediated the relationship between strongest predictor of change in FV dur- baseline-month 6, and month 6-month treatment type and change in SR-merged. ing the weight-loss phase was the same for 24 scores between the exercise- and eating- This indicated a reciprocal relationship baseline-month 3 and baseline-month 6 related self-regulation measures (r-values = between increases in self-regulation and for SR-eating, and was baseline-month 6 0.61-0.66), and exercise- and eating-related lost weight during the weight-loss phase for both SE-eating and Mood. β(standard self-efficacy measuresr ( -values = 0.40-0.48) (Table 4, Analysis I-a). error)-values were 0.41(0.03), 0.45(0.01), were significant (all p values < 0.001). This The SR-merged, SE-merged, and Mood and -0.37(0.08), respectively; all p values further supported merging the exercise- measures (changes from month 6 to month < 0.001. The temporal interval that was and eating-related self-regulation (ie, SR- 24) were entered as possible mediators of the strongest predictor of change in FV merged) and self-efficacy (ie, SE-merged) the relationship between treatment type and weight change during the weight-loss maintenance phase. The overall model was Table 3. Results of multiple regression analyses for the prediction of changes in significant,R 2 = 0.20, F(7, 102) = 3.61, p physical activity and fruit and vegetable intake = 0.002. Only change in SE-merged was Standard a significant mediator within the equation Predictor β error R2 F df p value (Table 4, Analysis II). Δ Physical activity, baseline-month 6 Post Hoc Tests Model 0.42 25.96 3, 109 < 0.001 In post hoc analyses of only the EXP Δ Self-regulation for exercise 0.36 0.19 < 0.001 group, a significant quadratic (inverted- Δ Self-efficacy for exercise 0.21 0.11 0.028 U) effect was found during the 24 months Δ Overall negative mood -0.25 0.08 0.003 of the study in each of the psychological Δ Physical activity, month 6-month 24 variables, which suggested a reduction in Model 0.59 9.19 6, 109 0.006 gains acquired during the initial 6 to12 2 Δ Self-regulation for exercise 0.42 0.28 < 0.001 months. Effect sizes η( p) associated with Δ Self-efficacy for exercise 0.27 0.16 0.044 those significant ANOVA models (all p Δ Overall negative mood -0.23 0.13 0.093 values < 0.001) were stronger than for Δ Fruit and vegetable intake baseline-month 6 the corresponding linear relationship for Model 0.52 13.08 3, 109 < 0.001 SR-exercise (0.611), SE-exercise (0.417), Δ Self-regulation for controlled eating 0.20 0.04 0.048 Mood (0.504), and SR-eating (0.600); but Δ Self-efficacy for controlled eating 0.26 0.01 0.013 not SE-eating (0.374). Δ Overall negative mood -0.19 0.01 0.049 Δ Fruit and vegetable intake month 6-month 24 DISCUSSION Model 0.46 4.57 6, 109 < 0.001 Overall, findings associated with the EXP treatment were promising. The absence Δ Self-regulation for controlled eating 0.12 0.04 0.202 of significant regain of that group’s weight Δ Self-efficacy for controlled eating 0.33 0.01 0.080 loss of more than 6% was atypical, and Δ Overall negative mood -0.15 0.02 0.352 represented a notable success (Figure 3).4,5 Δ = change in.

The Permanente Journal/Perm J 2016 Summer;20(3):15-146 13 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

The experimental format not only eluci- obesity where a climb toward baseline such “slippage” through periodic telephone dated psychological correlates of behav- weight (or higher) almost always occurred and/or e-mail follow-ups after in-person ioral prerequisites to weight reduction, after about 6 months of loss.4,5 When con- treatment components conclude. These it highlighted temporal implications for trasted with the Oxford CBT (Figure 1), follow-up contacts will aim to bolster the their application within both weight-loss the EXP treatment had a far less acute slope use of previously addressed self-regulatory and weight-loss maintenance phases. of weight regain and a much larger propor- skills and feelings of control over behaviors Innovative treatment components and tion of participants who maintained ≥ 5% associated with weight management. Part administrative formats were successfully weight loss at month 24 (52.7% vs 38.8%) 3 of this study determined that changes incorporated within a practical setting (Figure 3).21 This suggestedsubstantial im- in self-regulation, self-efficacy, and mood that suggests potential for widespread provements in health risks within the EXP during the full 6 months of the weight-loss application. The cost associated with group. In Part 2, effect sizes for increases phase best-predicted increased PA and FV. implementation of the EXP treatment in both PA and FV during the weight-loss Findings also suggested that changes in approximated US$400 per participant. phase were about twice as large in the EXP self-regulation applied to eating changes This was about 10% to 15% of the cost es- group. Those large behavioral improve- might be particularly important within timated for both the Oxford CBT and an ments demonstrated a partial reversal dur- the first several months of treatment. average of the 3 commercial weight-loss ing the second year. In Part 3, within the Changes in those 3 psychological factors programs currently having the strongest weight-loss phase, effect sizes of improve- over the entire weight-maintenance phase market share.75 ments on the psychosocial predictors of PA (months 6-24) best predicted a favorable and FV within the EXP group were also direction for PA and FV. However, find- Specific Findings double those in the COM group (all large ings suggested that self-regulation for Part 1 clearly demonstrated the superi- effects withd -values of 0.96-1.66). Howev- controlled eating is especially important ority of the EXP treatment over the COM er, an inversion of some of those gains ap- during the second year. When the above treatment for weight loss at all measured peared between month 12 and month 24. results were consolidated, important find- time points. Regain of weight in the EXP Because these trajectories could adversely ings also emerged. Data suggested that group was only a nonsignificant 0.7% of impact participants’ weight-management an emphasis on self-regulation during the participants’ original weight, which has behaviors and weight in subsequent years, weight-loss phase, and an emphasis on self- not been observed in the great majority extensions of this research are presently efficacy during the weight-loss maintenance of treatment studies of individuals with evaluating noninvasive methods to lessen phase, will optimize weight-management

Table 4. Results from multiple mediation and reciprocal effects analyses (N = 110)a Pathb a Path b Path c Path c’ Indirect effect β ± standard error β ± standard error β ± standard β ± standard β ± standard Predictor Mediatorc Outcome (p value) (p value) error (p value) error (p value) error (95% CI) Analysis I: Weight-loss phase (multiple mediation) Treatment typed Δ Self-regulation Δ Weight 1.13 ± 0.24 -2.13 ± 0.70 -8.03 ± 1.44 -4.61 ± 1.55 -2.42 ± 1.05 (< 0.001) (0.002) (< 0.001) (0.004) (-4.81, -0.65) Treatment type Δ Self-efficacy Δ Weight 0.77 ± 0.24 (0.002) 0.20 ± 0.71 (0.780) -8.03 ± 1.44 -4.61 ± 1.55 0.16 ± 0.71 (< 0.001) (0.004) (-1.27, 1.71) Treatment type Δ Mood Δ Weight -0.86 ± 0.17 1.35 ± 0.79 (0.093) -8.03 ± 1.44 -4.61 ± 1.55 -1.16 ± 0.71 (< 0.001) (< 0.001) (0.004) (-2.79, 0.06) Analysis I-a: Weight-loss phase (simple mediation for reciprocal effects analysis) Treatment type Δ Self-regulation Δ Weight 1.13 ± 0.24 -2.27 ± 0.54 -8.03 ± 1.44 -5.46 ± 1.47 -2.56 ± 0.81 (< 0.001) (< 0.001) (< 0.001) (< 0.001) (-4.53, -1.23) Treatment type Δ Weight Δ Self- -8.03 ± 1.44 -0.06 ± 0.15 1.13 ± 0.24 0.63 ± 0.25 0.51 ± 0.14 regulation (< 0.001) (< 0.001) (< 0.001) (0.015) (0.26, 0.82) Analysis II: Weight-loss maintenance phase (multiple mediation) Treatment type Δ Self-regulation Δ Weight -0.17 ± 0.20 -5.91 ± 1.52 1.91 ± 2.88 1.42 ± 2.72 0.98 ± 1.21 (0.415) (< 0.001) (0.509) (0.604) (-2.20, 3.32) Treatment type Δ Self-efficacy Δ Weight -0.38 ± 0.20 2.87 ± 1.75 (0.104) 1.91 ± 2.88 1.42 ± 2.72 -1.09 ± 0.77 (0.055) (0.509) (0.604) (-3.77, -0.10) Treatment type Δ Mood Δ Weight 0.16 ± 0.14 (0.055) 3.81 ± 2.07 (0.068) 1.91 ± 2.88 1.42 ± 2.72 0.60 ± 0.60 (0.509) (0.604) (-0.14, 2.36] a Analyses are based on a bootstrapping procedure for multiple mediation incorporating 20,000 resamples.74 b Path a = predictor→mediator; Path b = mediator→outcome; Path c = predictor→outcome; Path c’ = predictor→outcome, controlling for the mediator. c Δ = change from baseline-month 6 for Analysis I and I-a; or baseline-month 24, controlling for changes from baseline-month 6 (for Analysis II). d For treatment type, 0 = comparison group, 1 = experimental group. Δ change in; 95% CI = 95% confidence interval.

14 The Permanente Journal/Perm J 2016 Summer;20(3):15-146 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

outcomes. During the weight-loss phase, salient treatment components and, thus, in replications of this research. Although changes in self-regulation and weight further enhance effects. We encourage fu- the repeated-measures design of this study appeared to reinforce one another mutu- ture related research to also study weight- was a strength, multiple administrations of ally. Overall, results supported the EXP loss and weight-loss maintenance phases the same self-report instrument increases treatment’s ability to improve mood and separately through behavioral changes and its measurement error.87 Although it is increase self-regulation and self-efficacy -re their psychological predictors, because difficult to accomplish in field settings lated to both physical activity and healthy processes within these phases appear to (that benefit the applicability of find- eating behaviors. differ from one another. Continued evalu- ings88,89), the use of more objective and ation of temporal aspects might facilitate comprehensive measures of exercise (eg, Fit with Previous Research a more precise process that further refines accelerometry) and dietary intake (eg, Although most weight-loss treatments the benefits of emphasizing specific treat- more extensive nutrition recall instru- employ an educational approach that fo- ment components at specific times, which ments) would increase accuracy of the cuses upon restricting energy intake, the might also vary by personal characteristics behavioral outcomes. Within the present use of cognitive-behavioral methods and (eg, initial weight, psychological profile). study, however, because of the length of exercise within weight-loss interventions The present determination that weight loss time required for completion of the seven is not novel. However, comprehensive might most benefit from a concentration self-report surveys, any additional time reviews suggest that even the most state- on self-regulation, whereas weight-loss burden placed on participants might have of-the-art, theory-based approaches pri- maintenance might most benefit from a challenged the quality of their responses.90 marily targeting eating changes have been concentration on self-efficacy, is a start unsuccessful beyond the very short term.4 in that direction. Although this research CONCLUSION Within this report, findings from a previ- based the architecture of the EXP treat- Although the above limitations should ously described17 and tested21 weight-loss/ ment and the selection and measurement be acknowledged, and replications are weight-loss maintenance protocol (Oxford of behavioral and psychological constructs needed, the EXP treatment has consid- CBT) was contrasted with the EXP treat- on social cognitive and self-efficacy theory erable possibilities for dissemination. Its ment because of its theoretical similarity, and the many studies following from those format allows for low-cost implementation similar research design, and seemingly paradigms, additional theories (eg, self- in community-based health-promotion strong cognitive-behavioral approach. As determination theory, theory of planned settings by staff members with general has been typical, however, exercise was behavior) might also serve as a basis in wellness credentials. It also has a strong treated as a favorable adjunct to nutritional extensions of this research. The contrast potential for physician referral. Whereas change rather than a key component of of those results with the present findings pharmacologic and surgical interventions that protocol, and its maintenance of will undoubtedly be instructive. for obesity are available, improving physi- weight loss was unsuccessful.21 Guided by cal activity and eating behaviors will effec- suggestions of the consistent relationship Study Limitations tively address obesity and their associated between exercise and maintained weight To increase confidence in findings and health risks for most affected individuals. loss,23-25 previous experimental research assess their generalizability for applica- Despite the fact that sustained improve- on (modifiable) psychosocial correlates tion, present limitations such as the use ments in eating and exercise have been dif- of weight loss,40-42,76 our own program of of a homogeneous sample of primarily ficult for behavioral medicine to effectuate, research on the generalization of exercise- white and middle-class women who were the present research introduced innovative induced psychological changes to eating motivated enough to volunteer for treat- behavior-change methods that empowered changes during the short term,33,77-85 and ment require attention. Thus, replications individuals to effectively deal with day- recommendations from the National In- with men, with other racial/ethnic and to-day barriers that consistently served stitutes of Health to address adherence to socioeconomic groups, and possibly with as impediments to maintaining clinically exercise and establish relevant behavioral participants who were strongly referred by important losses in body weight. The use skills before attempting weight loss,22 we medical practitioners (to minimize effects of manageable amounts of exercise to build substantially modified and extended previ- of volunteerism) will be beneficial. Repli- the self-regulatory skills and improvements ous approaches. We incorporated assump- cations are also required with overweight in mood that promote a newfound sense of tions that cognitive-behaviorally supported participants and participants with a more control over eating behaviors might prove exercise can facilitate changes in eating and severe degree of obesity (ie, class 3/morbid to be one of the most viable solutions to weight through associated psychological obesity). Other limitations of this research the longstanding epidemic of obesity. v changes. Although the present data can- indicate a need for better controls for social not determine precisely what treatment support and expectation effects that are Disclosure Statement component(s) or implementation methods likely to bias results when interventions The authors have no conflicts of interest to were most associated with the present posi- differ in length and amount of in-person disclose. tive results, future research designs might contact, as was the case here.86 Thus, the facilitate a more comprehensive decompo- use of an attention-matched, or a wait- Acknowledgment sition of findings to determine the most list, control group might also be useful Mary Corrado, ELS, provided editorial assistance.

The Permanente Journal/Perm J 2016 Summer;20(3):15-146 15 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

How to Cite this Article 14. Look AHEAD Research Group. Eight-year weight 30. Garber CE, Blissmer B, Deschenes MR, et al; Annesi JJ, Johnson PH, Tennant GA, Porter KJ, losses with an intensive lifestyle intervention: the American College of Sports Medicine. American McEwen KL. Weight loss and the prevention of Look AHEAD Study. Obesity (Silver Spring) 2014 College of Sports Medicine position stand. Jan;22(1):5-13. DOI: http://dx.doi.org/10.1002/ Quantity and quality of exercise for developing and weight regain: Evaluation of a treatment model of oby.20662. maintaining cardiorespiratory, musculoskeletal, and exercise self-regulation generalizing to controlled 15. Wing RR, Hill JO. Successful weight loss neuromotor fitness in apparently healthy adults: eating. Perm J 2016 Summer;20(3):15-146. DOI: maintenance. Annu Rev Nutr 2001;21:323-41. guidance for prescribing exercise. Med Sci Sport http://dx.doi.org/10.7812/TPP/15-146. DOI: http://dx.doi.org/10.1146/annurev.nutr.21.1.323. Exerc 2011 Jun;43(7):1334-59. DOI: http://dx.doi. 16. Teixeira PJ, Carraça EV, Marques MM, et al. org/10.1249/MSS.0b013e318213fefb. Successful behavior change in obesity interventions 31. Hall KD. What is the required energy deficit per unit References in adults: a systematic review of self-regulation weight loss? Int J Obes (Lond) 2008 Mar;32(3):573- 1. Flegal KM, Carroll MD, Kit BK, Ogden CL. mediators. BMC Med 2015 Apr 16;13:84. DOI: http:// 6. DOI: http://dx.doi.org/10.1038/sj.ijo.0803720. Prevalence of obesity and trends in the distribution dx.doi.org/10.1186/s12916-015-0323-6. 32. Annesi JJ, Unruh JL, Marti CN, Gorjala S, Tennant of body mass index among US adults, 1999-2010. 17. Cooper Z, Fairburn CG, Hawker DM. Cognitive- G. Effects of The Coach Approach intervention on JAMA 2012 Feb 1;307(5):491-7. DOI: http://dx.doi. behavioral treatment of obesity: a clinician’s guide. adherence to exercise in obese women: assessing org/10.1001/jama.2012.39. New York, NY: The Guilford Press; 2003. mediation of social cognitive theory factors. Res 2. Aronne LJ. Classification of obesity and assessment 18. Peterson ND, Middleton KR, Nackers LM, Q Exerc Sport 2011 Mar;82(1):99-108. DOI: http:// of obesity-related health risks. Obes Res 2002 Medina KE, Milsom VA, Perri MG. Dietary self- dx.doi.org/10.1080/02701367.2011.10599726. Dec;10 Suppl 2:105S-115S. DOI: http://dx.doi. monitoring and long-term success with weight 33. Annesi JJ. Supported exercise improves controlled org/10.1038/oby.2002.203. management. Obesity (Silver Spring) 2014 eating and weight through its effects on psychosocial 3. Flechtner-Mors M, Ditschuneit HH, Johnson TD, Sep;22(9):1962-7. DOI: http://dx.doi.org/10.1002/ factors: extending a systematic research program Suchard MA, Adler G. Metabolic and weight oby.20807. toward treatment development. Perm J 2012 loss effects of long-term dietary intervention in 19. Linde JA, Jeffery RW, French SA, Pronk NP, Winter;16(1):7-18. DOI: http://dx.doi.org/10.7812/ obese patients: four-year results. Obes Res 2000 Boyle RG. Self-weighing in weight gain prevention TPP/11-136. Aug;8(5):399-402. DOI: http://dx.doi.org/10.1038/ and weight loss trials. Ann Behav Med 2005 34. Hagger MS, Wood C, Stiff C, Chatzisarantis NL. Ego oby.2000.48. Dec;30(3):210-6. DOI: http://dx.doi.org/10.1207/ depletion and the strength model of self-control: a 4. Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels s15324796abm3003_5. meta-analysis. Psychol Bull 2010 Jul;136(4):495-525. B, Chatman J. Medicare’s search for effective 20. Wing RR, Phelan S. Long-term weight loss DOI: http://dx.doi.org/10.1037/a0019486. obesity treatments: diets are not the answer. Am maintenance. Am J Clin Nutr 2005 Jul;82(1 35. Baker CW, Brownell KD. Physical activity and Psychol 2007 Apr;62(3):220-33. DOI: http://dx.doi. Suppl):222S-225S. maintenance of weight loss: physiological and org/10.1037/0003-066X.62.3.220. 21. Cooper Z, Doll HA, Hawker DM, et al. Testing a psychological mechanisms. In: Bouchard C, editor. 5. Jeffery RW, Drewnowski A, Epstein LH, et al. new cognitive behavioural treatment for obesity: a Physical activity and obesity. 1st ed. Champaign, IL: Long-term maintenance of weight loss: current randomized controlled trial with three-year follow-up. Human Kinetics; 2000. p 311-28. status. Health Psychol 2000 Jan;19(1 Suppl):5-16. Behav Res Ther 2010 Aug;48(8):706-13. DOI: http:// 36. Landers DM, Arent SM. Physical activity and mental DOI: http://dx.doi.org/10.1037/0278-6133.19. dx.doi.org/10.1016/j.brat.2010.03.008. health. In: Singer RN, Hausenblas HA, Janelle CM, Suppl1.5. 22. MacLean PS, Wing RR, Davidson T, et al. NIH editors. Handbook of sport psychology. 2nd ed. New 6. National Heart, Lung, and Blood Institute; The working group report: innovative research to improve York, NY: John Wiley & Sons, Inc; 2001. p 740-65. National Institute of Diabetes and Digestive maintenance of weight loss. Obesity (Silver Spring) 37. Mostafavi-Darani F, Daniali SS, Azadbakht L. and Kidney Diseases. Clinical guidelines on the 2015 Jan;23(1):7-15. DOI: http://dx.doi.org/10.1002/ Relationship of body satisfaction, with nutrition and identification, evaluation, and treatment of overweight oby.20967. weight control behaviors in women. Int J Prev Med and obesity in adults: the evidence report. NIH 23. Fogelholm M, Kukkonen-Harjula K. Does physical 2013 Apr;4(4):467-74. publication no. 98-4083 [Internet]. Washington, DC: activity prevent weight gain—a systematic review. 38. Annesi JJ, Tennant GA. Generalization of theory- National Institutes of Health; 1998 Sep [cited 2015 Obes Rev 2000 Oct;1(2):95-111. DOI: http://dx.doi. based predictions for improved nutrition and weight Oct 22]. Available from: www.nhlbi.nih.gov/guidelines/ org/10.1046/j.1467-789x.2000.00016.x. loss to adults with morbid obesity: implications of obesity/ob_gdlns.pdf. 24. Clinical guidelines on the identification, evaluation, initiating exercise. Int J Clin Health Psychol 2014 7. Stevens J, Truesdale KP, McClain JE, Cai J. The and treatment of overweight and obesity in adults: Jan;14(1):1-8. DOI: http://dx.doi.org/10.1016/S1697- definition of weight maintenance. Int J Obes (Lond) the evidence report. National Institutes of Health. 2600(14)70031-6. 2006 Mar;30(3):391-9. DOI: http://dx.doi.org/10.1038/ Obes Res 1998 Sep;6 Suppl 2:51S-209S. DOI: http:// 39. Annesi JJ, Johnson PH. Theory-based psychosocial sj.ijo.0803175. dx.doi.org/10.1002/j.1550-8528.1998.tb00690.x. factors that discriminate between weight-loss 8. Amigo I, Fernández C. Effects of diets and Erratum in: Obes Res 1998 Nov;6(6):464. DOI: http:// success and failure over 6 months in women with their role in weight control. Psychol Health dx.doi.org/10.1002/j.1550-8528.1998.tb00381.x. morbid obesity receiving behavioral treatments. Eat Med 2007 May;12(3):321-7. DOI: http://dx.doi. 25. Svetkey LP, Stevens VJ, Brantley PJ, et al; Weight Weight Disord 2015 Jun;20(2):223-32. DOI: http:// org/10.1080/13548500600621545. Loss Maintenance Collaborative Research Group. dx.doi.org/10.1007/s40519-014-0159-7. 9. Kroke A, Liese AD, Schulz M, et al. Recent weight Comparison of strategies for sustaining weight loss: 40. Andrade AM, Coutinho SR, Silva MN, et al. The changes and weight cycling as predictors of the weight loss maintenance randomized controlled effect of physical activity on weight loss is mediated subsequent two year weight change in a middle- trial. JAMA 2008 Mar;299(10):1139-48. DOI: http:// by eating self-regulation. Patient Educ Couns 2010 aged cohort. Int J Obes Relat Metab Disord 2002 dx.doi.org/10.1001/jama.299.10.1139. Jun;79(3):320-6. DOI: http://dx.doi.org/10.1016/j. Mar;26(3):403-9. DOI: http://dx.doi.org/10.1038/ 26. Annesi JJ. Effects of a cognitive behavioral treatment pec.2010.01.006. sj.ijo.0801920. package on exercise attendance and drop out in 41. Mata J, Silva MN, Vieira PN, et al. Motivational 10. Baranowski T, Lin LS, Wetter DW, Resnicow K, fitness centers. Eur J Sport Sci 2003;3(2):1-16. DOI: “spill-over” during weight control: increased self- Hearn MD. Theory as mediating variables: why aren’t http://dx.doi.org/10.1080/17461390300073206. determination and exercise intrinsic motivation community interventions working as desired? Ann 27. Buckworth J, Dishman RK. Exercise psychology. predict eating self-regulation. Health Psychol 2009 Epidemiol 1997 Oct;7(7 Suppl): Champaign, IL: Human Kinetics; 2002. Nov;28(6):709-16. DOI: http://dx.doi.org/10.1037/ S89-S95. DOI: http://dx.doi.org/10.1016/S1047- a0016764. 2797(97)80011-7. 28. Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert T, McDowell M. Physical activity in the United States 42. Palmeira AL, Markland DA, Silva MN, et al. 11. Bandura A. Social foundations of thought and action: measured by accelerometer. Med Sci Sports Exerc Reciprocal effects among changes in weight, body a social cognitive theory. 1st ed. Englewood Cliffs, 2008 Jan;40(1):181-8. DOI: http://dx.doi.org/10.1249/ image, and other psychological factors during NJ: Prentice Hall; 1986. mss.0b013e31815a51b3. behavioral obesity treatment: a mediation analysis. 12. Bandura A. Self-efficacy: the exercise of control. New 29. Tudor-Locke C, Brashear MM, Johnson WD, Int J Behav Nutr Phys Act 2009 Feb 9;6:9. DOI: http:// York, NY: W.H. Freeman & Company; 1997. Katzmarzyk PT. Accelerometer profiles of physical dx.doi.org/10.1186/1479-5868-6-9. 13. Simpson SA, Shaw C, McNamara R. What is the activity and inactivity in normal weight, overweight, 43. Godin G. The Godin-Shephard Leisure-Time Physical most effective way to maintain weight loss in adults? and obese US men and women. Int J Behav Nutr Activity Questionnaire. Health & Fitness Journal of BMJ 2011 Dec 28;343:d8042. DOI: http://dx.doi. Phys Act 2010 Aug 3;7:60. DOI: http://dx.doi. Canada 2011;4(1):18-22. org/10.1136/bmj.d8042. org/10.1186/1479-5868-7-60.

16 The Permanente Journal/Perm J 2016 Summer;20(3):15-146 ORIGINAL RESEARCH & CONTRIBUTIONS Weight Loss and the Prevention of Weight Regain: Evaluation of a Treatment Model of Exercise Self-Regulation Generalizing to Controlled Eating

44. Jetté M, Sidney K, Blümchen G. Metabolic 59. McAuley E, Mihalko SL. Measuring exercise-related 19;162(10):739-740. DOI: http://dx.doi.org/10.7326/ equivalents (METS) in exercise testing, exercise self-efficacy. In: Duda JL, editor. Advances in sport L15-5130-3. prescription, and evaluation of functional capacity. and exercise psychology measurement. Morgantown, 76. Fairburn CG, Brownell KD, editors. Eating disorders Clin Cardiol 1990 Aug;13(8):555-65. DOI: http:// WV: Fitness Information Technology, Inc; 1998. p and obesity: a comprehensive handbook. 2nd ed. dx.doi.org/10.1002/clc.4960130809. 371-90. New York, NY: The Guilford Press; 2002. 45. Godin G, Shephard RJ. A simple method to assess 60. McNair DM, Heuchert JWP. Profile of Mood States: 77. Annesi J. Effects of treatment differences on exercise behavior in the community. Can J Appl Sport POMS: technical update. North Tonawanda, NY: psychosocial predictors of exercise and improved Sci 1985 Sep;10(3):141-6. Multi-Health Systems; 2007. eating in obese, middle-age adults. J Phys Act Health 46. Jacobs DR Jr, Ainsworth BE, Hartman TJ, Leon AS. 61. Clark MM, Abrams DB, Niaura RS, Eaton CA, Rossi 2013 Sep;10(7):1024-31. A simultaneous evaluation of 10 commonly used JS. Self-efficacy in weight management. J Consult 78. Annesi JJ. Moderation of age, sex, and ethnicity physical activity questionnaires. Med Sci Sports Clin Psychol 1991 Oct;59(5):739-44. DOI: http:// on psychosocial predictors of increased exercise Exerc 1993 Jan;25(1):81-91. DOI: http://dx.doi. dx.doi.org/10.1037/0022-006X.59.5.739. and improved eating. J Psychol 2013 Sep- org/10.1249/00005768-199301000-00012. 62. Baillot A, Romain AJ, Boisvert-Vigneault K, et al. Oct;147(5):455-68. DOI: http://dx.doi.org/10.1080/00 47. Miller DJ, Freedson PS, Kline GM. Comparison Effects of lifestyle interventions that include a 223980.2012.711785. of activity levels using Caltrac accelerometer physical activity component in class II and III obese 79. Annesi JJ, Tennant GA. Mediation of social cognitive and five questionnaires. Med Sci Sports Exerc individuals: a systematic review and meta-analysis. theory variables in the relationship of exercise and 1994 Mar;26(3):376-82. DOI: http://dx.doi. PLoS One 2015 Apr 1;10(4):e0119017. DOI: http:// improved eating in sedentary adults with severe org/10.1249/00005768-199403000-00016. dx.doi.org/10.1371/journal.pone.0119017. obesity. Psychol Health Med 2013;18(6):714-24. DOI: 48. Gardner DG, Cummings LL, Dunham RB, Pierce JL. 63. Kiernan M, Brown SD, Schoffman DE, et al. http://dx.doi.org/10.1080/13548506.2013.766354. Single-item versus multiple-item measurement Promoting healthy weight with “stability skills first”: 80. Annesi JJ, Porter KJ. Reciprocal effects of changes scales: an empirical comparison. Educational and a randomized trial. J Consult Clin Psychol 2013 in mood and self-regulation for controlled eating Psychological Measurement 1998 Dec;58(6):898- Apr;81(2):336-46. DOI: http://dx.doi.org/10.1037/ associated with differing nutritional treatments in 915. DOI: http://dx.doi.org/ a0030544. severely obese women. Clinical Health Promotion 10.1177/0013164498058006003. 64. McKee H, Ntoumanis N, Smith B. Weight 2013 Oct-Nov;3(2):35-41. 49. MyPlate and historical food pyramid resources maintenance: self-regulatory factors 81. Annesi JJ, Tennant GA. Exercise program-induced [Internet]. Washington, DC: US Department of underpinning success and failure. Psychol Health mood improvement and improved eating in severely Agriculture; updated 2015 Oct 23 [cited 2015 Dec 2013;28(10):1207-23. DOI: http://dx.doi.org/10.1080/ obese adults. Int Q Community Health Educ 2012- 4]. Available from: http://fnic.nal.usda.gov/dietary- 08870446.2013.799162. 2013;33(4):391-402. DOI: http://dx.doi.org/10.2190/ guidance/myplate-and-historical-food-pyramid- 65. Teixeira PJ, Silva MN, Coutinho SR, et al. Mediators IQ.33.4.f. resources. of weight loss and weight loss maintenance in 82. Annesi JJ, Mareno N. Temporal aspects of 50. Champagne CM, Broyles ST, Moran LD, et al. Dietary middle-aged women. Obesity (Silver Spring) 2010 psychosocial predictors of increased fruit and intakes associated with successful weight loss and Apr;18(4):725-35. DOI: http://dx.doi.org/10.1038/ vegetable intake in adults with severe obesity: maintenance during the Weight Loss Maintenance oby.2009.281. mediation by physical activity. J Community Trial. J Am Diet Assoc 2011 Dec;111(12):1826-35. 66. Cooper JO, Heron TE, Heward WL. Applied behavior Health 2014 Jun;39(3):454-63. DOI: http://dx.doi. DOI: http://dx.doi.org/10.1016/j.jada.2011.09.014. analysis. 2nd ed. Upper Saddle River, NJ: Pearson org/10.1007/s10900-014-9828-8. 51. Annesi JJ, Nandan M, McEwen K. Effects of two Prentice Hall; 2007. 83. Annesi JJ, Tennant GA, Mareno N. Treatment- cognitive-behavioral physical activity and nutrition 67. ChooseMyPlate.gov [homepage on the Internet]. associated changes in body composition, health treatments on psychosocial predictors of changes in Alexandria, VA: US Department of Agriculture, Center behaviors, and mood as predictors of change in body fruit/vegetable and high-fat food intake, and weight. for Nutrition Policy and Promotion; [cited 2013 Jan satisfaction in obese women: effects of age and race/ Hellenic Journal of Psychology 2015;12:40-64. 31]. Available from: www.choosemyplate.gov/. ethnicity. Health Educ Behav 2014 Dec;41(6):633-41. 52. Epstein LH, Gordy CC, Raynor HA, Beddome M, 68. Brownell KD. The LEARN program for weight DOI: http://dx.doi.org/10.1177/1090198114531783. Kilanowski CK, Paluch R. Increasing fruit and management. 10th ed. Euless, TX: American Health 84. Annesi JJ, Johnson PH, Porter KJ. Bi-directional vegetable intake and decreasing sugar intake in Publishing Company; 2004. relationship between self-regulation and improved families at risk for childhood obesity. Obes Res 69. Schafer JL, Graham JW. Missing data: our view eating: temporal associations with exercise, 2001 Mar;9(3):171-8. DOI: http://dx.doi.org/10.1038/ of the state of the art. Psychol Methods 2002 reduced fatigue, and weight loss. J Psychol 2015 oby.2001.18. Jun;7(2):147-77. DOI: http://dx.doi.org/10.1037/1082- Sep;149(6):535-53. DOI: http://dx.doi.org/10.1080/00 53. Rolls BJ, Ello-Martin JA, Tohill BC. What can 989X.7.2.147. 223980.2014.913000. intervention studies tell us about the relationship 70. Cohen J, Cohen P, West SG, Aiken LS. Applied 85. Annesi JJ, Johnson PH, McEwen KL. Changes in between fruit and vegetable consumption and weight multiple regression/correlation analysis for the self-efficacy for exercise and improved nutrition management? Nutr Rev 2004 Jan;62(1):1-17. DOI: behavioral sciences. 3rd ed. Mahwah, NJ: Lawrence fostered by increased self-regulation among adults http://dx.doi.org/10.1111/j.1753-4887.2004.tb00001.x. Erlbaum Associates, Inc; 2003. with obesity. J Prim Prev 2015 Oct;36(5):311-21. 54. Mares-Perlman JA, Klein BE, Klein R, Ritter LL, 71. Hair JF, Anderson RE, Tatham RL, Black WC. DOI: http://dx.doi.org/10.1007/s10935-015-0398-z. Fisher MR, Freudenheim JL. A diet history Multivariate data analysis. 4th ed. New York, NY: 86. Morgan WP. Methodological considerations. In: questionnaire ranks nutrient intakes in middle-aged Macmillan Publishers; 1995. Morgan WP, editor. Physical activity and mental and older men and women similarly to multiple food 72. Glymour MM, Weuve J, Berkman LF, Kawachi I, health. Washington, DC: Taylor & Francis; 1997. records. J Nutr 1993 Mar;123(3):489-501. Robins JM. When is baseline adjustment useful in p 3-32. 55. Block G, Hartman AM, Dresser CM, Carroll MD, analyses of change? An example with education 87. Nunally JC, Bernstein IH. Psychometric theory. 3rd Gannon J, Gardner L. A data-based approach to diet and cognitive change. Am J Epidemiol 2005 Aug ed. New York, NY: McGraw-Hill, Inc; 1994. questionnaire design and testing. Am J Epidemiol 1;162(3):267-78. DOI: http://dx.doi.org/10.1093/aje/ 88. Committee on Evaluating Progress of Obesity 1986 Sep;124(3):453-69. kwi187. Prevention Effort; Food and Nutrition Board; Institute 56. Saelens BE, Gehrman CA, Sallis JF, Calfas KJ, 73. Presnell K, Stice E, Seidel A, Madeley MC. of Medicine. Evaluating obesity prevention efforts: Sarkin JA, Caparosa S. Use of self-management Depression and eating pathology: prospective a plan for measuring progress. 1st ed. Washington, strategies in a 2-year cognitive-behavioral reciprocal relations in adolescents. Clin Psychol DC: National Academies Press; 2013. intervention to promote physical activity. Behav Psychother 2009 Jul-Aug;16(4):357-65. DOI: http:// 89. Glasgow RE, Emmons KM. How can we increase Ther 2000 Spring;31(2):365-79. DOI: http://dx.doi. dx.doi.org/10.1002/cpp.630. translation of research into practice? Types org/10.1016/S0005-7894(00)80020-9. 74. Preacher KJ, Hayes AF. Asymptotic and resampling of evidence needed. Annu Rev Public Health 57. Annesi JJ, Marti CN. Path analysis of exercise strategies for assessing and comparing indirect 2007;28:413-33. DOI: http://dx.doi.org/10.1146/ treatment-induced changes in psychological effects in multiple mediator models. Behav Res annurev.publhealth.28.021406.144145. factors leading to weight loss. Psychol Health 2011 Methods 2008 Aug;40(3):879-91. DOI: http://dx.doi. 90. Galesic M, Bosnjak M. Effects of questionnaire Aug;26(8):1081-98. DOI: http://dx.doi.org/ org/10.3758/BRM.40.3.879. length on participation and indictors of response 10.1080/08870446.2010.534167. 75. Gudzune KA, Doshi RS, Mehta AK, et al. Efficacy quality in a web survey. Public Opinion Quarterly 58. Marcus BH, Selby VC, Niaura RS, Rossi JS. Self- of commercial weight-loss programs: an updated 2009;73(2):349-60. DOI: http://dx.doi.org/10.1093/ efficacy and the stages of exercise behavior change. systematic review. Ann Intern Med 2015 Apr poq/nfp031. Res Q Exerc Sport 1992 Mar;63(1):60-6. DOI: http:// 7;162(7):465-532. DOI: http://dx.doi.org/10.7326/ dx.doi.org/10.1080/02701367.1992.10607557. M14-2238. Erratum in: Ann Intern Med 2015 May

The Permanente Journal/Perm J 2016 Summer;20(3):15-146 17 credits available for this article — see page 112.

ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

Robert Goldfien, MD; Alice Pressman, PhD, MS; Alice Jacobson, MS; Michele Ng, PharmD; Andrew Avins, MD, MPH Perm J 2016 Summer;20(3):15-234 E-Pub: 07/01/2016 http://dx.doi.org/10.7812/TPP/15-234

ABSTRACT including poor patient adherence; the need Context: Relatively few patients with gout receive appropriate treatment. for better patient education; and a lack of Objective: To determine whether a pharmacist-staffed gout management program is awareness of management guidelines, espe- more effective than usual care in achieving target serum uric acid (sUA) levels in gout cially among primary care physicians. No- patients. tably, unlike other forms of inflammatory Design: A parallel-group, randomized controlled trial of a pharmacist-staffed, arthritis (eg, rheumatoid arthritis), there telephone-based program for managing hyperuricemia vs usual care. Trial duration is a straightforward and easily monitored was 26 weeks. outcome measure that correlates with opti- Main Outcome Measures: Primary outcome measure was achieving sUA levels at or mal long-term outcomes in gout. Both the below 6 mg/dL at the 26-week visit. Secondary outcome was mean change in sUA levels European League Against Rheumatism15 in the control and intervention groups. Participants were adults with recurrent gout and and the American College of Rheuma- sUA levels above 6.0 mg/dL. Participants were randomly assigned to management by a tology16 recommend that patients with clinical pharmacist following protocol or to monitoring of sUA levels but management tophaceous or recurrent gout be treated of their gout by their usual treating physician. with urate-lowering therapy (ULT) to a Results: Of 102 patients who met eligibility criteria, 77 subjects obtained a baseline target sUA level below 6.0 mg/dL. Main- sUA measurement and were entered into the trial. Among 37 participants in the inter- taining the sUA at that level eventually vention group, 13 (35%) had sUA levels at or below 6.0 mg/dL at 26 weeks, compared leads to cessation of gout flares.17 This fact with 5 (13%) of 40 participants in the control group (risk ratio = 2.8, 95% confidence is particularly notable given the burden of interval [CI] = 1.1 to 7.1, p = 0.03). The mean change in sUA levels among controls gout in the US. One study found there was +0.1 mg/dL compared with -1.5 mg/dL in the intervention group (sUA difference = were 3.9 million outpatient visits for gout -1.6, 95% CI = -0.9 to -2.4, p < 0.001). in the US in 2002.18 Unfortunately, only Conclusions: A structured pharmacist-staffed program was more effective than usual a minority of patients with gout receives care for achieving target sUA levels. These results suggest a structured program could appropriate treatment, including doses of greatly improve gout management. ULT sufficient to achieve this target.11,19 Specifically, deficiencies in ULT manage- INTRODUCTION There is also a growing literature docu- ment include a lack of appropriate moni- Gout is the most common inflamma- menting the association of chronic hyper- toring, failure to treat-to-target, and fear tory arthritis in men.1,2 It is well recognized uricemia and gout with diabetes, chronic of ULT dose escalation in some patients, that successful long-term management of kidney disease, and adverse cardiovascular particularly those with chronic kidney gout and hyperuricemia remains elusive.3-5 outcomes.8-11 Therefore, improving the disease.12,13 Thus, there is a need for new, Unlike other common forms of inflamma- long-term management of gout may lead practical, and more effective approaches to tory arthritis, gout is not an autoimmune to other important health benefits as well. the management of gout. disease and instead is understood to be Guidelines for the treatment of acute To address the problem of inadequate a manifestation of chronic elevation of gout and the optimal management of adherence to gout treatment guidelines, serum uric acid (sUA). Studies of gouty hyperuricemia have been evolving and we previously developed a management arthritis have provided important insights have been the subject of several recent re- model consisting of a telephone-based into other inflammatory conditions that views.12-14 These reviews highlight several “clinic” composed of a clinical pharmacist are of great interest to rheumatologists.6,7 barriers to optimal gout management, under the supervision of a board-certified

Robert Goldfien, MD, is the Chair of the Chiefs of Rheumatology for The Permanente Medical Group in Richmond, CA. E-mail: [email protected]. Alice Pressman, PhD, MS, is the Director of Analytics and Evaluation in the Department of Research, Development, and Dissemination for Sutter Health in Walnut Creek, CA. E-mail: [email protected]. Alice Jacobson, MS, is a Senior Statistical Analyst in the Department of Research, Development, and Dissemination for Sutter Health in Walnut Creek, CA. E-mail: [email protected]. Michele Ng, PharmD, is a Clinical Pharmacist in the Department of Outpatient Pharmacy at the Oakland Medical Center in CA. E-mail: [email protected]. Andrew Avins, MD, MPH, is a Research Scientist at the Division of Research in Oakland, CA. E-mail: [email protected].

18 The Permanente Journal/Perm J 2016 Summer;20(3):15-234 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

rheumatologist.20 In this model, the the care of their primary care physician or 100 mg/day (if the estimated glomerular pharmacist uses telephone encounters to rheumatologist. If physician consent was filtration rate was less than 30 mL/min, implement a simple protocol, initiating obtained, patients were contacted by letter the starting dose was 50 mg/day), un- and adjusting standard gout medications accompanied by a description of the study less there was a known allergy or other in patients referred by their primary care and a written informed consent document. contraindication to allopurinol. After any physicians for management of recurrent or The program pharmacist telephoned the change in ULT, subjects were instructed tophaceous gout. Patients are monitored potential subject and described the study, to return for laboratory assessment (sUA, by the clinic until they have 2 consecu- answered any questions, and then obtained alanine aminotransferase, complete blood tive target sUA results at least 3 months verbal consent. Each participant was pro- cell count, and estimated glomerular filtra- apart; they are then discharged back to the vided written educational material on gout tion rate) in 2 weeks to 3 weeks, and report care of their primary physician. We previ- at the time of program entry. Randomiza- any adverse drug reactions or gout flares. ously reported a case series from this pilot tion was accomplished by assigning an Dose titration was in increments of 100 study, analyzing the outcomes of the first identification number using a balanced, mg/day. The titration process was contin- 100 patients referred to the program. The blocked randomization list with variable ued in an iterative fashion until a target results of this pilot were encouraging, and block sizes (used to reduce the likelihood of sUA level was achieved and maintained, the current study (Gout Uric Acid ReDuc- an unbalanced or biased randomization). or until the trial ended at 26 weeks. In all tion, or GUARD trial) was conducted to After randomization, a baseline labora- cases, the primary outcome—sUA level at test whether this model would be more tory assessment was required of all potential or below 6.0 mg/dL—was determined by effective than usual care in the context of participants to begin the trial. (The labora- either a second consecutive target result or a randomized controlled trial. tory measurements were obtained after the most recent result at 26 weeks (with a randomization for practical implementa- window of 24 weeks to 30 weeks). METHODS tion reasons.) This panel included sUA and Probenecid and febuxostat were second- Design alanine aminotransferase values, estimated line agents and used if allopurinol was not The GUARD study was a randomized, glomerular filtration rate, and complete tolerated. Flare prophylaxis in most cases parallel-group, open-label clinical trial of a blood cell count. The trial protocol was ap- consisted of daily oral colchicine or any pharmacist-staffed, structured gout manage- proved by the Kaiser Foundation Research nonsteroidal anti-inflammatory drug and ment program compared with usual care. Institute’s institutional review board. was continued throughout the study in the intervention group. At the conclusion of Patient Selection Group Assignments the trial, each subject’s primary physician The study sample was recruited from the Control subjects were asked to complete was informed whether or not the patient Kaiser Permanente Northern California baseline, 12-week, and 26-week laboratory achieved the target, and the most recent (KPNC) patient population. Inclusion assessments. We defined measurement win- sUA level. If the patient had achieved the criteria included at least 2 consecutive dows of between 10 weeks and 16 weeks for target, the physician was advised to con- years of Health Plan membership, an es- the 12-week measurement of sUA in the tinue the current medication and dose of tablished diagnosis of gout (International control group, and between 24 weeks and ULT. For patients not at target, the physi- Classification of Diseases, Ninth Revision 30 weeks for the closeout measurement. cian was reminded of the target level. Code 274.XX), and clear documentation In the intervention group, the clinical of at least 2 distinct episodes of acute gouty pharmacist, under a protocol approved by Outcome Variables arthritis in the preceding 12 months. To be the KPNC East Bay Pharmacy and Thera- The primary outcome was achieving an eligible for randomization, patients between peutics Committee, was authorized to or- sUA level of 6.0 mg/dL or below at the 26- the ages of 21 and 80 years had either a der relevant laboratory tests and to initiate week closeout visit. Secondary outcomes most recent sUA level above 7.0 mg/dL or to change orders for the medications included the absolute change in sUA level or no measurement of sUA in the past year. used for ULT and for flare prophylaxis. from baseline to 26 weeks and achieving Patients were excluded if they had a current In the event of acute flares or abnormal at least a 2 mg/dL decrease in sUA level at cancer diagnosis with active treatment, were laboratory results, the pharmacist con- the closeout visit. believed to be terminally ill (as judged by sulted with the rheumatologist, who could the Principal Investigator before random- prescribe treatment or advice if outside the Statistical Analyses ization), were pregnant or lactating, or had scope of the pharmacy protocol. The ULT All analyses of continuous variables end-stage renal disease or dementia. was either initiated or adjusted if the sUA were conducted with the Student t-test. For each patient fulfilling the eligibility level was above 6.0 mg/dL. Prophylaxis Categorical variables were analyzed with criteria, an e-mail was sent to his/her pri- of gout flares was prescribed in all cases the Fisher exact test or its generalization mary care physician. This e-mail included (see next paragraph). Subjects already re- for more than 2 levels.21 Analyses were a brief description of the trial, including ceiving ULT treatment had their medica- conducted and are reported here both the expectation that those assigned to tions titrated but not changed. Subjects under the principle of intention-to-treat, receive “usual care” would be instructed not receiving ULT at the start of the trial with the last value carried forward (the to continue to manage their gout under were started on a regimen of allopurinol, primary analysis), and as a per-protocol

The Permanente Journal/Perm J 2016 Summer;20(3):15-234 19 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

analysis, including only observed values. All reported p values were 2-sided with the experimental error rate set to α = 0.05, and no adjustments were made for multiple testing. Analyses were performed with SAS Version 9.3 (SAS Institute, Cary, NC) and STATA 12 (StataCorp LP, Col- lege Station, TX). RESULTS The outcomes of the selection, consent, randomization, and trial progress are shown in Figure 1. We identified 1860 potentially eligible patients from KPNC electronic health records. The records were placed in random order, and charts were then reviewed for eligibility by a board- certified rheumatologist (RG) to validate the inclusion and exclusion criteria. We screened the charts of the first 749 patients and identified 329 who were eligible for inclusion in the study. Of the 418 who were not eligible, the most common reasons were insufficient documentation of at least 2 gout flares in the prior year (n = 226, 54%), a most recent sUA level of 7.0 mg/dL or less (n = 93, 22%), and excluded comorbidities (n = 15, 4%). Ultimately, 104 patients consented to Figure 1. Flow diagram of design of Gout Uric Acid ReDuction study. participate and were randomly assigned to receive either active intervention or sUA = serum uric acid level (mg/dL). usual care. Three patients gave consent and were randomized but, on baseline laboratory evaluation, were found to have Table 1. Baseline demographic and clinical characteristics, overall and by study group sUA levels at or below 6.0 mg/dL. Of the All participants Intervention group Control group 99 remaining subjects, 51 were randomly Characteristic (N = 77) (n = 37) (n = 40) assigned to the intervention group and 48 Demographic characteristic to the control group. Of these, 12 subjects Age (years), mean (SD) 59.4 (1.4) 60.9 (2.0) 58.0 (2.0) never completed the baseline sUA assess- Male sex, no. (%) 68 (88) 36 (97) 32 (80) ment (7 in the treatment group and 5 Race/ethnicity, no. (%) in the control group). A total of 22 par- Native American 1 (1) 1 (3) 0 (0) ticipants dropped out of the study after obtaining their baseline sUA measure- Asian 9 (12) 7 (19) 2 (5) ments (8 in the control group and 14 in African American 12 (16) 5 (14) 7 (18) the intervention group); all but 1 (whose Pacific Islander 17 (22) 7 (19) 10 (25) insurance lapsed) failed to obtain required White 23 (30) 9 (24) 14 (35) laboratory assessments despite repeated Hispanic 14 (18) 7 (19) 7 (18) attempts by the study pharmacist. Of Unknown 1 (1) 1 (3) 0 (0) the 37 participants randomized to the Clinical characteristic intervention group, 32 (86%) remained Hypertension, no. (%) 49 (64) 25 (68) 24 (62) in the trial at the 12-week time point and Chronic kidney disease, no. (%) 23 (30) 13 (35) 10 (26) 29 (78%) at the 26-week closeout call; the Diabetes mellitus, no. (%) 19 (25) 9 (24) 10 (26) corresponding lab adherence numbers for Serum uric acid (mg/dL), mean (SD) 8.3 (1.4) 8.5 (1.5) 8.2 (1.3) the control group were 36 (90%) of 40 Serum creatinine (mg/dL), mean (SD) 1.2 (0.4) 1.3 (0.5) 1.1 (0.3) participants at 12 weeks and 35 (88%) at SD = standard deviation. 26 weeks. Table 1 shows the demographic

20 The Permanente Journal/Perm J 2016 Summer;20(3):15-234 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

and baseline information for all subjects entering the study (n = 77). Table 2 reports the results of the primary outcome measure. In the intention-to-treat analysis using the method of last-value- carried-forward, 13 (35%) of 37 subjects in the intervention group (95% confidence interval [CI] = 20% to 52%). However, only 5 (13%) of 40 subjects (95% CI = 4% to 27%) in the control group achieved an sUA level of 6.0 mg/dL or below at 26 weeks (Figure 2; risk ratio [RR] = 2.8, 95% CI = 1.1 to 7.1, p = 0.03). This dif- ference was greater at the 12-week time Figure 2. Comparison of mean serum uric acid during study period. Values shown are at each study time point with 15 participants (41%, 95% CI point, with error bars indicating 95% confidence intervals (intention-to-treat analysis). = 25% to 58%) in the intervention group and 3 participants (8%, 95% CI = 2% to 20%) in the control group achieving the were similar, although somewhat more To elucidate the range of outcomes targeted study outcome of sUA levels of pronounced, for the less-conservative per- among subjects in the control and inter- 6.0 or less (RR = 5.4, 95% CI = 1.7 to protocol analysis, which did not include vention groups, we plotted the individual 17.2, p = 0.001). imputed data (Table 2). change in sUA levels at week 26 for all The control group experienced a mean Figure 2 shows the mean sUA levels at participants completing the protocol increase in the sUA level at 26 weeks of baseline, 12 weeks, and 26 weeks for both (Figure 3). 0.1 mg/dL (95% CI = -0.45 to 0.69), groups for the intention-to-treat analysis. whereas the sUA in the intervention group In the control group, there was no signifi- DISCUSSION decreased by an average of 1.5 mg/dL cant change in sUA levels at either time Our premise for this study was that an (95% CI = -1.0 to -2.0). The intergroup point, whereas the intervention group important failure in the management of difference in sUA levels was -1.6 mg/dL had significant reductions of sUA at both chronic gout has been the lack of a system- (95% CI = -0.9 to -2.4, p < .001). Results time points. atic approach for identifying inadequately

Table 2. Primary and secondary outcome measures by study group Intention-to-treat analysis Per-protocol analysis Intervention group Control group Intervention group Control group Outcome (n = 37) (n = 40) p value (n = 29)a (n = 35)a p value sUA level ≤ 6 mg/dL, no. (%) 12 weeks 15 (41) 3 (8) 0.001b 15 (47) 3 (8) 0.001c 26 weeks 13 (35) 5 (13) 0.03d 13 (45) 3 (9) 0.001e sUA level change from baseline (mg/dL), mean ± SE 12 weeks -1.6 ± 0.2 0.2 ± 0.2 < 0.001 -1.9 ± 0.2 0.3 ± 0.3 < 0.001 26 weeks -1.5 ± 0.3 0.1 ± 0.3 < 0.001 -1.8 ± 0.3 0.1 ± 0.3 < 0.001 Decrease in sUA level by ≥ 2 mg/dL, no. (%) 12 weeks 16 (43) 4 (10) 0.001 16 (50) 4 (11) 0.001 26 weeks 14 (38) 5 (13) 0.02 14 (48) 3 (9) < 0.001 ALT level change from baseline (mg/dL), mean ± SE 12 weeks 8.4 ± 3.1 -2.4 ± 1.5 0.002 8.6 ± 3.2 -2.8 ± 1.7 0.003 26 weeks (mg/dL) mean ± SE 8.1 ± 3.9 -1.3 ± 1.8 0.03 6.7 ± 4.8 -0.7 ± 1.9 0.13 Creatinine level change from baseline (mg/dL), mean ± SE 12 weeks 0.01 ± 0.02 -0.02 ± 0.02 0.28 0.1 ± 0.02 -0.2 ± .02 0.27 26 weeks 0.006 ± 0.03 0.005 ± 0.03 0.99 -0.003 ± 0.03 0.2 ± .02 0.61 a Numbers refer to participants assessed at the 26-week time point. For the 12-week time point, there were 32 evaluable participants in the intervention group and 36 participants in the control group. b RR = 5.4 (95% CI = 1.7 to 17.2). c RR = 5.6 (95% CI = 1.8 to 17.7). d RR = 2.8 (95% CI = 1.1 to 7.1). e RR = 5.2 (95% CI = 1.6 to 16.6). ALT = alanine aminotransferase; CI = confidence interval; RR = risk ratio; SE = standard error; sUA = serum uric acid.

The Permanente Journal/Perm J 2016 Summer;20(3):15-234 21 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

that is achieved in a relatively low percent- age of patients with gout in the absence of a structured program. We believe that the results in the pilot study may well be a better reflection of how well our program would perform outside the constraints of the study design and length. Our study had several strengths, includ- ing a comparable randomized control group; a clear, structured intervention protocol; and objective outcome measure- ments. However, several limitations should be noted. First, there was a relatively high dropout rate from the program (22%), which was higher in the intervention group than the control group. This dif- ference did not reach statistical signifi- Figure 3. Net change in serum uric acid among individual evaluable participants in the intervention and cance, p = 0.232. Despite this difference, usual care groups. both the per-protocol and intent-to-treat analyses showed a statistically significant improvement in attaining the primary treated patients and then to treat and mon- analysis, 45% in the per-protocol analysis) outcome in our intervention group. itor them in a structured, target-driven was considerably lower than what we were Moreover, we were not able to use a con- way. In our organization, the management able to achieve in our pilot program (82%), trol group that strictly reflected usual of other chronic diseases has improved but much higher than the percentage seen care. This is because our primary outcome substantially by using such an approach.22 in the control group (8%). In our current measure required that every participant be We previously published results of a pilot trial, the lower rate of success without the tested at least two times for sUA during program designed to assess the feasibility intervention was notable but must be in- the study. Under true “usual care,” it was of using a pharmacist to manage ULT in terpreted within the context of the study. unrealistic to expect that all the patients patients with gout under the supervision In particular, unlike the pilot program, with gout would have been tested, and of a rheumatologist.20 The outcomes in this the study recruited patients not referred thus we would have been unable to assess single-cohort study were encouraging, but by their primary physicians, which may our primary outcome. Indeed, we have it was an uncontrolled study. The present have resulted in a cohort of less-motivated reviewed KPNC data for sUA among study, which included a randomized usual- patients. Although greater in the interven- patients with a gout diagnosis and found care control group, confirmed that a higher tion group, there was also a higher drop- that 29% had no sUA level measured percentage of patients randomly assigned out rate compared with that seen in our in the 5-year period before their last to a structured, goal-directed program did pilot program. It is also possible that the encounter for gout (unpublished data). lower success rate was partially caused by If anything, we believe this monitoring limitations imposed by the study protocol. requirement may have biased our results … an important failure in the Specifically, unlike the present trial, the against an intervention effect because the management of chronic gout pilot study allowed the continuation of lack of an sUA measurement during the has been the lack of a systematic the program beyond 26 weeks if the sUA study would more likely lead to a lack of approach for identifying target was not maintained for at least 3 initiation or titration of treatment. inadequately treated patients and months. Because adherence to ULT is then to treat and monitor them in known to be low compared with treatment CONCLUSION 23 a structured, target-driven way. of other chronic conditions, the success- The fact that we were able to demon- ful long-term management of gout must strate improved outcomes even with a eventually account for this by building in restrictive and time-limited intervention indeed achieve and maintain a target sUA a continued monitoring scheme that will suggests that an ongoing monitoring level at or below 6.0 mg/dL. In addition, identify nonadherent patients and allow program integrated within a primary we found a statistically significant greater further intervention. In the current study, care-centered medical system could be mean improvement in sUA level among limited to 26 weeks, we were not able to highly effective in achieving sustained patients in the intervention group. address this need. Nonetheless, initiating reduction of sUA levels in patients with The percentage of subjects in the inter- and adequately titrating pharmacologic gout. Moreover, if managed efficiently vention group who achieved the primary treatment to lower sUA level is a necessary by a pharmacist or other physician ex- outcome (35% in the intention-to-treat step toward long-term control, and one tender, this approach could result in a

22 The Permanente Journal/Perm J 2016 Summer;20(3):15-234 ORIGINAL RESEARCH & CONTRIBUTIONS A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial

cost-effective program and, over time, in can be done about it? Curr Rheumatol Rep 2011 15. Zhang W, Doherty M, Bardin T, et al; EULAR Apr;13(2):154-9. DOI: http://dx.doi.org/10.1007/ Standing Committee for International Clinical Studies a large reduction in health care utilization s11926-010-0154-6. Including Therapeutics. EULAR evidence based and cost of caring for patients with gout, 5. Pascual E, Sivera F. Why is gout so poorly recommendations for gout. Part II: management. with improved clinical outcomes. v managed? Ann Rheum Dis 2007 Oct;66(10):1269-70. Report of a task force of the EULAR Standing DOI: http://dx.doi.org/10.1136/ard.2007.078469. Committee for International Clinical Studies Including 6. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Therapeutics (ESCISIT). Ann Rheum Dis 2006 Disclosure Statement Gout-associated uric acid crystals activate Oct;65(10):1312-24. DOI: http://dx.doi.org/10.1136/ The author(s) have no conflicts of interest to the NALP3 inflammasome. Nature 2006 Mar ard.2006.055269. disclose. 9;440(7081):237-41. DOI: http://dx.doi.org/10.1038/ 16. Khanna D, Khanna PP, Fitzgerald JD, et al; American nature04516. College of Rheumatology. 2012 American College of 7. Pétrilli V, Martinon F. The inflammasome, Rheumatology guidelines for management of gout. Acknowledgments autoinflammatory diseases, and gout. Joint Bone Part 2: therapy and antiinflammatory prophylaxis of This trial was registered at www.clinicaltrials.gov Spine 2007 Dec;74(6):571-6. DOI: http://dx.doi. acute gouty arthritis. Arthritis Care Res (Hoboken) (#NCT01568879). This work was supported org/10.1016/j.jbspin.2007.04.004. 2012 Oct;64(10):1447-61. DOI: http://dx.doi. 8. Choi HK, De Vera MA, Krishnan E. Gout and the org/10.1002/acr.21773. by a Community Benefit Grant from the Kaiser 17. Schumacher HR Jr, Becker MA, Lloyd E, Foundation Research Institute, Oakland, CA. risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology (Oxford) MacDonald PA, Lademacher C. Febuxostat in Kathleen Louden, ELS, of Louden Health 2008 Oct;47(10):1567-70. DOI: http://dx.doi. the treatment of gout: 5-yr findings of the FOCUS Communications provided editorial assistance. org/10.1093/rheumatology/ken305. efficacy and safety study. Rheumatology (Oxford) 9. Krishnan E, Pandya BJ, Chung L, Hariri A, 2009 Feb;48(2):188-94. DOI: http://dx.doi. org/10.1093/rheumatology/ken457. How to Cite this Article Dabbous O. Hyperuricemia in young adults and risk 18. Krishnan E, Lienesch D, Kwoh CK. Gout in Goldfien R, Pressman A, Jacobson A, Ng M, of insulin resistance, prediabetes, and diabetes: a 15-year follow-up study. Am J Epidemiol 2012 Jul ambulatory care settings in the United States. Avins A. A pharmacist-staffed, virtual gout 15;176(2):108-16. DOI: http://dx.doi.org/10.1093/aje/ J Rheumatol 2008 Mar;35(3):498-501. management clinic for achieving target serum kws002. 19. Juraschek SP, Kovell LC, Miller ER 3rd, Gelber AC. uric acid levels: a randomized clinical trial. 10. Bose B, Badve SV, Hiremath SS, et al. Effects of Gout, urate-lowering therapy, and uric acid levels Perm J 2016 Summer;20(3):15-234. DOI: uric acid-lowering therapy on renal outcomes: a among adults in the United States. Arthritis Care Res http://dx.doi.org/10.7812/TPP/15-234. systematic review and meta-analysis. Nephrol Dial (Hoboken) 2015 Apr;67(4):588-92. DOI: http://dx.doi. Transplant 2014 Feb;29(2):406-13. DOI: http://dx.doi. org/10.1002/acr.22469. org/10.1093/ndt/gft378. 20. Goldfien RD, Ng MS, Yip G, et al. Effectiveness of a pharmacist-based gout care management References 11. Krishnan E, Pandya BJ, Chung L, Dabbous O. Hyperuricemia and the risk for subclinical programme in a large integrated health plan: 1. Lawrence RC, Felson DT, Helmick CG, et al; results from a pilot study. BMJ Open 2014 Jan National Arthritis Data Workgroup. Estimates of the coronary atherosclerosis—data from a prospective observational cohort study. Arthritis Res Ther 2011 10;4(1):e003627. DOI: http://dx.doi.org/10.1136/ prevalence of arthritis and other rheumatic conditions bmjopen-2013-003627. in the United States. Part II. Arthritis Rheum 2008 Apr 18;13(2):R66. DOI: http://dx.doi.org/10.1186/ 21. Mehta CR, Patel NR. A network algorithm for Jan;58(1):26-35. DOI: http://dx.doi.org/10.1002/ ar3322. performing Fisher’s exact test in r x c contingency art.23176. 12. Khanna PP, FitzGerald J. Evolution of management of gout: a comparison of recent guidelines. Curr Opin tables. J Am Stat Assoc 1983 Jun;78(382):427-34. 2. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and DOI: http://dx.doi.org/10.2307/2288652. hyperuricemia in the US general population: the Rheumatol 2015 Mar;27(2):139-46. DOI: http://dx.doi. 22. Jaffe MG, Lee GA, Young JD, Sidney S, Go AS. National Health and Nutrition Examination Survey org/10.1097/bor.0000000000000154. Improved blood pressure control associated with a 2007-2008. Arthritis Rheum 2011 Oct;63(10):3136- 13. Nasser-Ghodsi N, Harrold LR. Overcoming large-scale hypertension program. JAMA 2013 Aug 41. DOI: http://dx.doi.org/10.1002/art.30520. adherence issues and other barriers to optimal care in gout. Curr Opin Rheumatol 2015 21;310(7):699-705. DOI: http://dx.doi.org/10.1001/ 3. Singh JA, Hodges JS, Toscano JP, Asch SM. Quality jama.2013.108769. of care for gout in the US needs improvement. Mar;27(2):134-8. DOI: http://dx.doi.org/10.1097/ 23. Briesacher BA, Andrade SE, Fouayzi H, Chan KA. Arthritis Rheum 2007 Jun 15;57(5):822-9. DOI: http:// bor.0000000000000141. Comparison of drug adherence rates among dx.doi.org/10.1002/art.22767. 14. Wise E, Khanna PP. The impact of gout guidelines. patients with seven different medical conditions. 4. Edwards NL. Quality of care in patients with Curr Opin Rheumatol 2015 May;27(3):225-30. DOI: http://dx.doi.org/10.1097/bor.0000000000000168. Pharmacotherapy 2008 Apr;28(4):437-43. DOI: gout: why is management suboptimal and what http://dx.doi.org/10.1592/phco.28.4.437.

Favoring Disease

Gout would thus appear at least partly to depend on a loss of power … of the “uric-acid-exerting function” of the kidneys … . Any undue formation of this compound would favour the occurrence of the disease; and hence the connection between gout and uric acid, gravel and calculi ... and the influence of high living, wine, porter, want of exercise, etc, in inducing it.

— Sir Alfred Baring Garrod, FRS, 1819-1907, English physician credited with coining the term “rheumatoid arthritis”

The Permanente Journal/Perm J 2016 Summer;20(3):15-234 23 ORIGINAL RESEARCH & CONTRIBUTIONS Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives

Steffanie Campbell, MD; Heather Honoré Goltz, PhD, LMSW, MEd; Sarah Njue, MPH; Bich Ngoc Dang, MD Perm J 2016 Summer;20(3):15-154 E-Pub: 07/05/2016 http://dx.doi.org/10.7812/TPP/15-154

ABSTRACT arm had a significant increase in mean scores on a subsequent sur- Introduction: Little is known about the attitudes of faculty vey of new patients compared with residents who did not receive and residents toward the use of patient experience data as a feedback. Patient experience data paired with actionable feedback tool for providing resident feedback. The purpose of this study (ie, feedback that can change residents’ practice behavior) can be was to explore the attitudes of teaching faculty surrounding highly effective when provided by trained individuals.4 patient experience data and how those attitudes may influence Although data suggest actionable feedback has a positive impact the feedback given to trainees. on residents’ practice behaviors, many graduate medical educa- Methods: From July 2013 to August 2013, we conducted tion programs have difficulties translating this knowledge into in-depth, face-to-face, semistructured interviews with 9 attend- real-world practice.5-12 Studies evaluating feedback-based inter- ing physicians who precept residents in internal medicine at 2 ventions typically devote immense resources on the development continuity clinics (75% of eligible attendings). Interviews were and training of personnel to deliver actionable feedback that is coded using conventional content analysis. typically neither feasible nor designed for implementation in gen- Results: Content analysis identified six potential barriers in eral practice.13-20 As such, patient experience survey data are rarely using patient experience survey data to provide feedback to resi- used effectively outside the research context to deliver resident dents: 1) perceived inability of residents to learn or to incorporate feedback, owing to lack of either training or time.6,11,12,21 In ad- feedback, 2) punitive nature of feedback, 3) lack of training in dition, little is known about the attitudes of faculty and residents the delivery of actionable feedback, 4) lack of timeliness in the toward the use of patient experience data as a tool for providing delivery of feedback, 5) unclear benefit of patient experience resident feedback.22 The purpose of this study was to explore how survey data as a tool for providing resident feedback, and 6) lack attending physicians in a real-world academic setting incorporate of individualized feedback. patient experience survey data into feedback practices, explore the Conclusion: Programs may want to conduct an internal review attitudes and beliefs surrounding the use of patient experience data on how patient experience data is incorporated into the resident as a feedback tool, and identify potential areas for improvement. feedback process and how, if at all, their faculty are trained to Specifically, we were interested in exploring attendings’ attitudes provide such feedback. around giving feedback and understanding the process by which attendings provide learners with actionable feedback. INTRODUCTION Interpersonal and communication skills constitute one of METHODS the Accreditation Council for Graduate Medical Education’s Participants (ACGME’s) 6 domains of clinical competencies for graduate The study population was based on a nonrandomized con- medical education in internal medicine. The ACGME supports venience sample of attending physicians who precept residents the use of patient experience data as an outcomes-based tool for in internal medicine at two continuity clinics in Houston, TX providing resident feedback on interpersonal and communication (clinics A and B). Eligibility criteria included 1) faculty with an skills.1 The American Board of Internal Medicine is exploring ways appointment in the Department of Internal Medicine and 2) to integrate this outcomes-based approach into their physician faculty with a role as a preceptor in the internal medicine resident certification activities.2 Patient experience data can serve as an continuity clinic. This study was approved by the institutional effective tool for providing residents with feedback. In a study by review board for our institution. Cope and colleagues,3 residents in an internal medicine training program were randomized to receive a 30-minute structured feed- Data Collection back session in which they received mean scores on an experience Participants were recruited by e-mail; attending physicians survey filled out by new patients. Residents in the intervention received an e-mail from the Associate Program Director of the

Steffanie Campbell, MD, is an Assistant Professor of Medicine and an Associate Director of the Internal Medicine Residency Program at Baylor College of Medicine in Houston, TX. E-mail: [email protected]. Heather Honoré Goltz, PhD, LMSW, MEd, is an Assistant Professor at the University of Houston-Downtown and Adjunct Assistant Professor in the Section of Infectious Diseases at Baylor College of Medicine in Houston, TX. E-mail: [email protected]. Sarah Njue, MPH, is a Research Coordinator in the Section of Infectious Diseases at Baylor College of Medicine in Houston, TX. E-mail: [email protected]. Bich Ngoc Dang, MD, is an Assistant Professor of Medicine in the Section of Infectious Diseases at Baylor College of Medicine and an Investigator at the Center for Innovations in Quality, Effectiveness and Safety at the Michael E DeBakey VA Medical Center in Houston, TX. E-mail: [email protected].

24 The Permanente Journal/Perm J 2016 Summer;20(3):15-154 ORIGINAL RESEARCH & CONTRIBUTIONS Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives

Internal Medicine Residency Program (SC) inviting them to take interview was conducted at clinic A per the request of the clinic part in the study. The e-mail informed potential participants of the director, given the time constraints of the attending staff. Staff study and its purpose. Twelve attending physicians met eligibility members were willing to complete a group interview during their criteria and were recruited; 9 attending physicians participated. lunch hour, but were unable to dedicate an hour individually for Between July and August 2013, SC conducted in-depth, face-to- interviews. Participants provided verbal but not written informed face, semistructured interviews with attending physicians. She consent to protect their identities. No compensation was provided conducted 4 individual interviews at clinic B and a focus group for participation. The individual interviews lasted 30 minutes to interview involving 5 participants at clinic A. A focus group 60 minutes and the focus group lasted 60 minutes. Interviews were audiotaped using an encrypted recorder and transcribed verbatim by professional transcriptionists. The interviews were conducted using an open-ended interview guide developed by the multi- Major Topics and Key Interview Questions disciplinary team. The interview guide consisted of open-ended in Study of Resident Feedback questions to identify the process of feedback, the attitudes and Impressions of patient experience survey beliefs surrounding feedback, and the training given to attend- a • Tell me about the satisfaction surveys your patients fill out ing physicians to use patient experience survey data in providing on the residents. resident feedback (see Sidebar: Major Topics and Key Interview • Tell me about how you use patient survey data in comparison to Questions in Study of Resident Feedback). Interviews took place the other information you use to provide feedback to a resident. in conference rooms at the participants’ respective clinic sites. Training in the use of patient experience survey data • Do you feel comfortable using patient satisfaction survey Research Team and Reflexivity data to provide feedback to the residents? The research team’s professional backgrounds and research in- • How were you chosen to provide feedback to the residents? terests informed development of the interview guide, interpreta- • What was the time commitment required to learn how to use tion of codes, and understanding of emergent themes within the patient satisfaction data in order to provide feedback? context of medical education and patient care. Our multidisci- • Think about your peers who provide feedback. Why do you plinary team consisted of two physicians, a social work researcher, think they were chosen? and a research coordinator. SC, Associate Program Director of Process of feedback the Internal Medicine Residency Program, ensures quality edu- • Context framing statement: Think about the first time you cation and training for residents. BND is an Assistant Professor used patient satisfaction survey data to provide a resident of Medicine in the Section of Infectious Diseases. Her research with feedback. examines the use of patient experience metrics as a modifiable • What happens during a typical feedback session? focus for improving retention in care and adherence to medicines. • What parameters do you use to determine whether a feed- HHG, Assistant Professor in Social Work, is experienced in quali- back session was effective? tative research methods; she is interested in patients’ access to and • Have you seen or been told by a colleague how they give quality of care. SN is a master’s-trained public health professional feedback? with a background in health promotion and behavioral science. • Have you received feedback on the process? We are all [name of academic center] but our residents have continuity Data Analysis clinics at two different sites. Do you think there is anything We did not use an a priori code list. Four researchers (SC, specific to the culture of your location that impacts your HHG, SN, and BND) independently reviewed the transcripts feedback process? and coded the data, looking for examples of facilitators and bar- Attitudes/beliefs surrounding feedback riers to actionable feedback. The full research team then came • Overall, how would you describe the interaction between together to compare codes and iteratively revise and refine codes you and the resident when you use the patient survey data in until 100% consensus was reached. This occurred during several a resident feedback session? weekly team meetings. In the later stages of analysis, the team • Think about the best feedback session you had where you used examined recurrent themes across interviews and clinic sites. patient satisfaction survey data. Could you describe this to me? • Think about the worst feedback session you had where you RESULTS used patient satisfaction survey data. Could you describe this Characteristics of Participants to me? The participation rate among eligible attending physicians was Potential areas for improvement 75% (9/12). Nonparticipating physicians reported demanding • Is there anything the residency program can do to make the clinical duties and the lack of time as reasons for opting out. feedback sessions based on patient satisfaction survey data Baseline characteristics are outlined in Table 1. Given the small more effective? sample size, limited demographic characteristics are reported to • In an ideal situation, what would the process look like? preserve confidentiality. Five were female and 4 reported their a The term “satisfaction survey” was used instead of patient experience in the interview race/ethnicity as Asian. Five participants precept residents at guide because it was a term faculty were more familiar with. clinic A and 4 at clinic B.

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Table 1. Participant characteristics (N = 9) Barriers to Actionable Feedback Characteristic no. (%)a Specific patterns of feedback varied by clinic site; however, some core themes did emerge from the data. The research team Sex identified six themes corresponding to potential barriers in using Men 4 (44) patient experience survey data to provide actionable feedback to Women 5 (55) residents: 1) perceived inability of residents to learn or incorpo- Age, mean (± SD) 47 (± 10.2) rate feedback, 2) punitive nature of feedback, 3) lack of training Race in the use of patient-experience data to give feedback, 4) lack of Asian 4 (44) timeliness in providing feedback, 5) unclear benefit of patient Black or African American 3 (33) experience data as a tool to inform and frame actionable feedback, White 2 (22) and 6) lack of individualized feedback. Faculty facilitator experience, mean years 9.7 Perceived Inability of Residents to Learn or Incorporate Feedback Location On occasion, attending physicians seemed resigned to the belief Clinic A 5 (55) that it is difficult to change residents’ practice behavior. They cited Clinic B 4 (44) difficulties in teaching adult learners and difficulties in teaching a Data are no. (%) except where indicated. “soft skills” (eg, personal attributes). Three attending physicians SD = standard deviation. specifically reported difficulty in teaching “professionalism.” “It’s hard to change behavior for adults … . Just because they’re train- ees, we should not forget the fact that they are adults and they’re sup- Description of Clinic, Patient Panel Assignment, posed to be professionals, you know, so there’s only so much I can do …” and Patient Experience Survey “But you can’t change personalities and habits of people [who are] Each clinic has a unique structure for assignment of a primary old. You can do your best, but professionalism is a very difficult thing care physician. Clinic A assigns patients to a staff physician as to teach, and it’s professionalism in not just how you look or how their primary care physician. Residents are assigned to a specific you show up, but it’s also the amount of effort you put forth in what attending who then designates the resident as an associate physi- your actual duties are, you know, and how much you can relate and cian for 75 to 90 of their patients. Attempts are made to schedule communicate to the patient. So it’s hard to teach soft skills. You can follow-up appointments during the time the resident is present do your best with a resident that you might have for three years, but to create continuity of care between residents and their patients. some personalities don’t change.” At clinic B, patients are assigned a resident physician as their —Attending physicians at clinics A and B primary care physician. All follow-up appointments are made on Punitive Nature of Feedback the half-day the resident physicians are available to assure con- Punitive feedback refers to any negative approach to providing tinuity of care. Resident physicians then discuss care plans with feedback. Three of four participants at clinic B reported that they the staff physician available during that half-day. A 9-item survey approached underperforming residents in a nonpunitive way to adapted from resident evaluation tools, including those originat- address patient concerns or improve their clinical competence. ing from Saint Mary’s Hospital and Maine Medical Center, is used These attending physicians engaged the resident in coming up to measure patients’ experience with residents during a specific 23 with task-specific and actionable solutions. encounter (see Sidebar: Patient Experience Survey Questions). “I talked to the resident about what she thought had happened, These items reflect interpersonal and communication skills valued … and then we kind of brainstormed kind of what we thought had as important on the basis of the program’s educational objectives gone wrong between that. And she asked me was there anything I and the extant literature. Responses are kept anonymous and filed thought uh could be done better in the- the situation, um and then under the resident’s name. we kind of wrote back to the patient what had happened, which I think was just a miscommunication thing.” Patient Experience Survey Questions “So I learned that we have to be sensitive but at the same time 1. Overall, I was satisfied with this visit we have to get to the point because if you’re too sensitive you’re being 2. During this visit, my doctor treated me with respect too nice. And if they don’t get the message then you’re not getting to 3. My doctor answered my medical questions the feedback.” 4. My doctor used terms I understood —Attending physicians at clinic B 5. My doctor involved me in making decisions about my care In contrast, attendings at clinic A reported using punitive 6. I felt my doctor listened to my concerns feedback in response to the residents’ actions, such as removing 7. I felt my doctor spent enough time with me patients from the residents’ panel. 8. I would recommend this doctor to a friend “So that is why they [the patients] don’t want to write bad things, 9. I was seen by the doctor in a timely fashion but they will come and talk to us in person; especially because many For each questions, patients were asked to choose: Strongly of them, if you’ve been seeing them for several years, they do under- disagree, Disagree, Neither disagree nor agree, Agree, Strongly stand that these people are in training, which is okay to some extent. Agree, or Unsure. And some say, ‘No, I don’t want to see a resident; I want to see the attending.’ Then we just change the patient back to us [attendings].”

26 The Permanente Journal/Perm J 2016 Summer;20(3):15-154 ORIGINAL RESEARCH & CONTRIBUTIONS Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives

“But some of my patients I have actually removed from his panel positive. Short of that, I don’t see that they are very helpful evalua- and either brought them back to me or put them with another person tions to me or the resident, in their current state.” that I know is better at listening and communication.” “Yeah, because I’m not getting that much useful information ex- “But it’s important for the resident that he at least gets a feel that cept uh “wonderful doctor,” “the best,”… but no really constructive we are watching them and patients do have their opinions.” feedback … . We [are] doing it [patient experience surveys] just to —Attending physicians at clinic A meet this [Accreditation Council for Graduate Medical Education] Lack of Training in the Use of Patient Experience Data requirement but yet they’re not learning … . There’s no feedback and to Give Feedback they’re not learning what they should do to improve themselves. There’s Participants were asked if they received specific training in us- no purpose of doing the evaluation … . So it’s a little more difficult ing patient experience survey data to provide actionable feedback. and there’s no details on those and so it’s a little harder to give feedback Two of the five participants at clinic A reported taking a three- … . I don’t see any comments … at all so it’s hard to give the feedback.” hour institutional workshop two years prior. Per their report, the “I don’t think the residents care too much. They get evaluated so workshop explained how to provide feedback to residents, but many ways and so many times a year.” not specifically how to incorporate patient experience data into —Attending physicians at clinics A and B feedback practices. Most attendings did not like the survey format. They preferred “There’s a course at [my institution] about how to evaluate residents open-ended questions where patients could provide specific ex- and other groups … . The one that we specifically had taken was how amples and task-specific feedback. to complete evaluations.” Lack of Resident-Centered Feedback —Attending physician at clinic A Resident-centered feedback is feedback that engages the However, three of the four participants at clinic B reported no resident in discussion and allows for shared goal setting.4 One formal training in these areas. participant in clinic B reported delivering feedback by having a “No, I mean, no formal training to start off with, except I mean- face-to-face conversation. In contrast, the other three participants I mean, we had, you know, teaching as residents and a lot of teaching in clinic B reported providing feedback electronically; they cited built into our primary care residency.” lack of time and the high number of assigned residents as barriers —Attending physician at clinic B to resident-centered feedback. Lack of Timeliness in Providing Feedback “Unfortunately we don’t sit down … We don’t sit down with any Lack of timeliness refers to delays in providing feedback to the one of them except the ones who actually um have difficulty. Then residents. Branch and Paranjas24 suggest residents should receive we meet, we talk to that person personally, but other than that we feedback at least every two to three months. In our analysis, two just do it electronically so we don’t actually have that feedback-like attending physicians at clinic B reported completing evaluations oral feedback session.” twice a year; they reported time constraints as a barrier to timely —Attending physician at clinic B feedback. “I mean, ideally, yes, it would be lovely to have them come, sit, “It’s time consuming because I have 28 residents.” go through everything, see how you’re doing, whatever, but there’s so “We just do it electronically so we don’t actually have that feed- many of them.” back like oral feedback session because they come at different times.” —Attending physician at clinic B —Attending physicians at clinic B These attendings acknowledge that use of an electronic medium “I’d rather not deal with it than deal with that because then you’re alone can create a barrier to resident-centered feedback because it sending more work for me … . Every year, every year now, I have does not provide an opportunity for the resident to reflect, com- one that is wasting my time.” ment, or engage in the solution-making process. —Attending physician at clinic A Unclear Benefit of Patient Experience Data as a Tool DISCUSSION to Inform and Frame Actionable Feedback This study provides insight into how attending physicians use Benefit refers to the degree with which the attending physi- patient-reported experience measures to provide feedback for cians consider patient experience survey data as a beneficial residents in an internal medicine training program. We identified tool for providing actionable feedback. Only one of five par- six core themes influencing the use of patient experience data in ticipants at clinic B reported that the surveys were a suitable providing resident feedback: 1) perceived inability of residents to tool for providing feedback to the residents. However, of the learn or to incorporate feedback, 2) punitive nature of feedback, nine participants overall, eight questioned the value of patient 3) lack of training in the delivery of actionable feedback, 4) lack experience survey data in providing resident feedback. These of timeliness in the delivery of feedback, 5) unclear benefit of attendings reported that the surveys were not beneficial; they patient experience survey data as a tool for providing resident felt that the information obtained from the surveys was in- feedback, and 6) lack of individualized feedback. In 2001, the sufficient to address patient issues or give effective feedback Institute of Medicine codified patient-centeredness as one of six to the residents. health care quality aims.25 Patient experience is a critical facet of “I don’t see that they are a big help to the resident, nor to me, unless patient-centeredness. Moreover, studies have linked better patient the patient very specifically writes something, you know, out of the experiences to favorable health behaviors and outcomes.26-39 In ordinary that the resident did, whether it be egregious or something alignment with this aim, the Institute of Medicine advocates

The Permanente Journal/Perm J 2016 Summer;20(3):15-154 27 ORIGINAL RESEARCH & CONTRIBUTIONS Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives

Steps to Using Patient Experience Data to feedback.46,47 One potential method for incorporating patient Provide Residents with Actionable Feedback experience data into actionable feedback for the resident is the 1. Generate a feedback sheet for each resident, comparing use of a framework grounded in feedback-intervention theory. the individual scores with the scores for the entire group of Feedback should be individualized, and recommendations residents; see example in Table 2 (individualized). should be solutions oriented (ie, task-specific and actionable). 2. Provide an in-depth feedback session with the resident; use The highest, most effective form of feedback de-emphasizes the feedback sheet to tailor feedback on the basis of areas hierarchy and embraces a supportive dialogue between the at- where the resident scored low compared to his/her peers. tending and resident. Beyond identifying competency gaps, it 3. Have the resident comment on his/her scores (resident- requires the attending to understand the resident as a learner centered). (ie, understand the resident’s motivations and goal orientation). The attending can then leverage this knowledge to engage and 4. Collaboratively discuss different solutions for improving motivate the resident to reflect on his/her performance, and to areas with low scores (nonpunitive). set goals and develop an action plan to achieve those goals. To 5. Have the resident set specific goals and solutions to improve close the feedback loop, the attending should follow-up to de- low-scoring areas. termine if the resident has made progress in achieving goals.48,49 6. Follow-up to determine if the resident has made progress in The Sidebar: Steps to Using Patient Experience Data to Provide achieving his/her goals. Residents with Actionable Feedback details the steps to using patient experience data to provide residents with actionable feedback. These steps use an individualized, resident-centered, the use of patient experience data as a patient-centered tool for and nonpunitive approach to providing feedback. A feedback promoting quality care. Concrete patient experience data can sheet (Table 2) provides the resident’s average score on each item define key points of intervention for improving the care experi- of a patient experience survey, and compares those scores with ence. These data argue for greater training on the use of patient a group of peers. Items where residents score below a certain experience survey data to effect practice change and ultimately to improve health behaviors and outcomes. Physicians in training are an ideal population to intervene because they are at an early Feedback should be individualized, and stage in their career and may be more malleable.8,40-43 Thus, ac- recommendations should be solutions oriented … The tionable feedback may have a greater effect on practice behaviors. highest, most effective form of feedback de-emphasizes Implementation science dictates that a tool or system must hierarchy and embraces a supportive dialogue between be accepted by the stakeholders for it to be successful.44 Low ac- the attending and resident. … it requires the attending ceptability of patient experience data was noted in our study and to understand the resident as a learner … previously at other institutions.45 Thus, methods for increasing attending buy-in on the merits of patient experience measures as tools to inform actionable feedback need to be explored. In- cut-off point (eg, the lowest quartile) can identify critical areas creased buy-in could be achieved by involving attending physi- where residents can improve. A plan to improve the identified cians in the implementation process. For example, participants areas, in the context of specific goals, should be formulated. in our study suggested including open-ended questions and For example, if “listening” is identified as an area of weakness, comment areas to elicit more detailed patient experience data. specific goals may be 1) using more eye contact during the visit, Previous studies suggest that medical education programs can and 2) making reflective statements to summarize what the pa- benefit from more intense support and from training on how to tient has said.50 By using this or other identified tools, one can interpret patient experience survey data and to deliver actionable create a robust and effective feedback process.

Table 2. Sample feedback table providing performance data on the patient experience survey in comparison to peers1 Individual Total (n = X) Component experience Scalea Mean SD Mean SD 25thb 50thb 75thb Shared decision making 1. Offer choices in your medical care 1-5 2. Discuss the pros and cons of each choice with you 1-5 3. Get you to state which option or choice you prefer 1-5 4. Take your preferences into account when making 1-5 treatment decisions a 1 = none of the time; 2 = a little of the time; 3 = some of the time; 4 = most of the time; 5 = all of the time. b percentile. 1 Cope DW, Linn LS, Leake BD, Barrett PA. Modification of residents’ behavior by preceptor feedback of patient satisfaction. J Gen Intern Med 1986 Nov-Dec;1(6):394-8. DOI: http://dx.doi.org/10.1007/BF02596425. SD = standard deviation. High SD indicates greater variability in patient responses (ie, responses vary a lot across patients)

28 The Permanente Journal/Perm J 2016 Summer;20(3):15-154 ORIGINAL RESEARCH & CONTRIBUTIONS Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives

An important strength of our study is that we are one of the 2. Earning Maintenance of Certification points [Internet]. Philadelphia, A:P American Board of Internal Medicine; 2004-2016 [cited 2016 Mar 4]. Available from: www.abim. first to explore how patient experience data is incorporated into org/maintenance-of-certification/earning-points.aspx. the resident feedback process. We identified six core themes that 3. Cope DW, Linn LS, Leake BD, Barrett PA. Modification of residents’ behavior residency programs can use in assessing and modifying their own by preceptor feedback of patient satisfaction. J Gen Intern Med 1986 Nov- Dec;1(6):394-8. DOI: http://dx.doi.org/10.1007/BF02596425. resident feedback process. On the basis of our findings, we believe 4. Hysong SJ, Best RG, Pugh JA. Audit and feedback and clinical practice guideline that patient experience data can be successfully used to augment adherence: making feedback actionable. Implement Sci 2006 Apr 28;1:9. DOI: http:// existing evaluation processes. dx.doi.org/10.1186/1748-5908-1-9. 5. Al-Mously N, Nabil NM, Al-Babtain SA, Fouad Abbas MA. Undergraduate medical students’ perceptions on the quality of feedback received during clinical rotations. Limitations Med Teach 2014 Apr;36 Suppl 1:S17-23. DOI: http://dx.doi.org/10.3109/014215 The findings in our study should be interpreted with the fol- 9X.2014.886009. 6. Bing-You RG, Trowbridge RL. Why medical educators may be failing at feedback. lowing limitations in mind. Although our sample size is small, our JAMA 2009 Sep 23;302(12):1330-1. DOI: http://dx.doi.org/10.1001/jama.2009.1393. participation rate of 75% is acceptable for exploratory analyses. 7. DaRosa DA, Skeff K, Friedland JA, et al. Barriers to effective teaching. Acad Med In a qualitative study using 60 interviews, core themes were pres- 2011 Apr;86(4):453-9. DOI: http://dx.doi.org/10.1097/ACM.0b013e31820defbe. ent as early as 6 interviews and data saturation was reached at 12 8. Ende J. Feedback in clinical medical education. JAMA 1983 Aug 12;250(6):777-81. 51 DOI: http://dx.doi.org/10.1001/jama.1983.03340060055026. interviews. Although we collected data at 2 very different insti- 9. Kogan JR, Conforti LN, Bernabeo EC, Durning SJ, Hauer KE, Holmboe ES. tutions, these institutions are affiliated with the same academic Faculty staff perceptions of feedback to residents after direct observation of clinical center. Our findings may not be generalizable. We were forced to skills. Med Educ 2012 Feb;46(2):201-15. DOI: http://dx.doi.org/10.1111/j.1365- 2923.2011.04137.x. use mixed methods by combining data from individual interviews 10. Perron NJ, Sommer J, Hudelson P, et al. Clinical supervisors’ perceived needs for and focus groups. In a focus group there is the concern that 1 teaching communication skills in clinical practice. Med Teach 2009 Jul;31(7):316-22. or 2 individuals can dominate the conversation. However, there DOI: http://dx.doi.org/10.1080/01421590802650134. 11. Stewart EA, Marzio DH, Guggenheim DE, Gotto J, Veloski JJ, Kane GC. Resident is also the opportunity for individuals to motivate each other to scores on a patient satisfaction survey: evidence for maintenance of communication express their thoughts. It has been noted that integration of these skills throughout residency. J Grad Med Educ 2011 Dec;3(4):487-9. DOI: http://dx.doi. 2 study methods may provide data enrichment.52 org/10.4300/JGME-D-11-00047.1. 12. Tamblyn R, Benaroya S, Snell L, McLeod P, Schnarch B, Abrahamowicz M. The feasibility and value of using patient satisfaction ratings to evaluate internal medicine CONCLUSION residents. J Gen Intern Med 1994 Mar;9(3):146-52. DOI: http://dx.doi.org/10.1007/ Graduate Medical Education programs may want to conduct BF02600030. 13. Hewson MG, Little ML. Giving feedback in medical education: verification of their own internal assessment of the resident feedback process. recommended techniques. J Gen Intern Med 1998 Feb;13(2):111-6. DOI: http:// Such assessments should review how patient experience data is dx.doi.org/10.1046/j.1525-1497.1998.00027.x. incorporated into the resident feedback process and how, if at 14. Junod Perron N, Nendaz M, Louis-Simonet M, et al. Effectiveness of a training program in supervisors’ ability to provide feedback on residents’ communication skills. all, their faculty are trained to provide such feedback. We believe Adv Health Sci Educ Theory Pract 2013 Dec;18(5):901-15. DOI: http://dx.doi.org/ there is value in adhering to the ACGME guidelines in both spirit 10.1007/s10459-012-9429-1. and content so that residents emerge from training with greater 15. McLean M, Cilliers F, Van Wyk JM. Faculty development: yesterday, today and tomorrow. Med Teach 2008;30(6):555-84. DOI: http://dx.doi. competency in interpreting and using patient experience data to org/10.1080/01421590802109834. improve their interpersonal and communication behaviors. v 16. Puri A, Graves D, Lowenstein A, Hsu L. New faculty’s perception of faculty development initiatives at small teaching institutions. International Scholarly Research Notices [Internet] 2012 [cited 2015 Oct 29];2012:[about 13 p]. Available from: Disclosure Statement www.hindawi.com/journals/isrn/2012/726270/. DOI: http://dx.doi.org/ This work was supported in part by the facilities and resources of the Center 10.5402/2012/726270. for Innovations in Quality, Effectiveness and Safety at the Michael E DeBakey 17. Richmond M, Canavan C, Holtman MC, Katsufrakis PJ. Feasibility of implementing VA Medical Center (#CIN 13-413), and the facilities and resources of Harris a standardized multisource feedback program in the graduate medical education Health System. The views expressed in this article are those of the authors and environment. J Grad Med Educ 2011 Dec;3(4):511-6. DOI: http://dx.doi.org/10.4300/ do not necessarily represent the views of the Department of Veterans Affairs. JGME-D-10-00088.1. The author(s) have no other conflicts of interest to disclose. 18. Searle NS, Thibault GE, Greenberg SB. Faculty development for medical educators: current barriers and future directions. Acad Med 2011 Apr;86(4):405-6. DOI: http:// dx.doi.org/10.1097/ACM.0b013e31820dc1b3. Acknowledgments 19. Steinert Y, Mann K, Centeno A, et al. A systematic review of faculty development We thank Aanand D Naik, MD, and Sylvia J Hysong, PhD, for their critical initiatives designed to improve teaching effectiveness in medical education: review of an earlier draft of this manuscript. BEME Guide No. 8. Med Teach 2006 Sep;28(6):497-526. DOI: http://dx.doi. org/10.1080/01421590600902976. Mary Corrado, ELS, provided editorial assistance. 20. Steinert Y, McLeod PJ, Boillat M, Meterissian S, Elizov M, Macdonald ME. Faculty development: a ‘field of dreams’? Med Educ 2009 Jan;43(1):42-9. DOI: http://dx.doi. How to Cite this Article org/10.1111/j.1365-2923.2008.03246.x. Campbell S, Goltz HH, Njue S, Dang BN. Exploring the reality of using patient 21. Hutul OA, Carpenter RO, Tarpley JL, Lomis KD. Missed opportunities: a descriptive experience data to provide resident feedback: A qualitative study of attending assessment of teaching and attitudes regarding communication skills in a surgical physician perspectives. Perm J 2016 Summer;20(3):15-154. DOI: http://dx.doi. residency. Curr Surg 2006 Nov-Dec;63(6):401-9. DOI: http://dx.doi.org/10.1016/j. cursur.2006.06.016. org/10.7812/TPP/15-154. 22. Wood J, Collins J, Burnside ES, et al. Patient, faculty, and self-assessment of radiology resident performance: a 360-degree method of measuring professionalism and interpersonal/communication skills. Acad Radiol 2004 Aug;11(8):931-9. DOI: References http://dx.doi.org/10.1016/j.acra.2004.04.016. 1. Nasca TJ, Philibert I, Brigham T, Flynn TC. The next GME accreditation system— 23. Residency evaluation tools [Internet]. Alexandria, VA: Alliance for Academic Internal rationale and benefits. N Engl J Med 2012 Mar 15;366(11):1051-6. DOI: http://dx.doi. Medicine; c2015 [cited 2015 Sep 24]. Available from: http://connect.im.org/p/cm/ld/ org/10.1056/NEJMsr1200117. fid=701.

The Permanente Journal/Perm J 2016 Summer;20(3):15-154 29 ORIGINAL RESEARCH & CONTRIBUTIONS Exploring the Reality of Using Patient Experience Data to Provide Resident Feedback: A Qualitative Study of Attending Physician Perspectives

24. Branch WT Jr, Paranjape A. Feedback and reflection: teaching methods for 38. Sequist TD, Schneider EC, Anastario M, et al. Quality monitoring of physicians: clinical settings. Acad Med 2002 Dec;77(12 Pt 1):1185-8. DOI: http://dx.doi. linking patients’ experiences of care to clinical quality and outcomes. J Gen Intern org/10.1097/00001888-200212000-00005. Med 2008 Nov;23(11):1784-90. DOI: http://dx.doi.org/10.1007/s11606-008-0760-4. 25. Corrigan JM, Donaldson MS, Kohn LT, Maguire SK, Pike KC. Crossing the quality 39. Zolnierek KB, Dimatteo MR. Physician communication and patient adherence to chasm: a new health system for the 21st century. Washington, DC: National treatment: a meta-analysis. Med Care 2009 Aug;47(8):826-34. DOI: http://dx.doi.org/ Academies Press; 2001. 10.1097/MLR.0b013e31819a5acc. 26. Barbosa CD, Balp MM, Kulich K, Germain N, Rofail D. A literature review to explore 40. Chatman JA. Improving interactional organizational research: a model of person- the link between treatment satisfaction and adherence, compliance, and persistence. organization fit. Acad Manage Rev 1989 Jul;14(3):333-49. DOI: http://dx.doi. Patient Prefer Adherence 2012;6:39-48. DOI: http://dx.doi.org/10.2147/PPA.S24752. org/10.2307/258171. 27. Bartlett EE, Grayson M, Barker R, Levine DM, Golden A, Libber S. The effects of 41. Dornan T. Workplace learning. Perspect Med Educ 2012 Mar;1(1):15-23. DOI: physician communications skills on patient satisfaction; recall, and adherence. http://dx.doi.org/10.1007/s40037-012-0005-4. J Chronic Dis 1984;37(9-10):755-64. DOI: http://dx.doi.org/10.1016/0021- 42. Knowles MS. The adult learner: a neglected species. 3rd ed. Houston, TX: Gulf 9681(84)90044-4. Publishing Co; 1989. 28. Carroll JG, Monroe J. Teaching medical interviewing: a critique of educational 43. Norman GR. The adult learner: a mythical species. Acad Med 1999 Aug;74(8):886-9. research and practice. J Med Educ 1979 Jun;54(6):498-500. DOI: http://dx.doi. DOI: http://dx.doi.org/10.1097/00001888-199908000-00011. org/10.1097/00001888-197906000-00009. 44. Peters DH, Adam T, Alonge O, Agyepong IA, Tran N. Implementation research: what 29. Dang BN, Westbrook RA, Black WC, Rodriguez-Barradas MC, Giordano TP. it is and how to do it. BMJ 2013 Nov 20;347:f6753. DOI: http://dx.doi.org/10.1136/bmj. Examining the link between patient satisfaction and adherence to HIV care: f6753. a structural equation model. Plos One 2013;8(1):e54729. DOI: http://dx.doi. 45. Burford B, Illing J, Kergon C, Morrow G, Livingston M. User perceptions of multi- org/10.1371/journal.pone.0054729. source feedback tools for junior doctors. Med Educ 2010 Feb;44(2):165-76. DOI: 30. Dang BN, Westbrook RA, Hartman CM, Giordano TP. Retaining HIV patients in http://dx.doi.org/10.1111/j.1365-2923.2009.03565.x. care: the role of initial patient care experiences. AIDS Behav 2016 Feb 24. Epub 46. Greenberg LW, Goldberg RM, Jewett LS. Teaching in the clinical setting: factors ahead of print. influencing residents’ perceptions, confidence and behaviour. Med Educ 1984 31. Doyle C, Lennox L, Bell D. A systematic review of evidence on the links between Sep;18(5):360-5. DOI: http://dx.doi.org/10.1111/j.1365-2923.1984.tb01283.x. patient experience and clinical safety and effectiveness. BMJ Open 2013 Jan 47. Wilkerson L, Armstrong E, Lesky L. Faculty development for ambulatory teaching. 3;3(1):e001570. DOI: http://dx.doi.org/10.1136/bmjopen-2012-001570. J Gen Intern Med 1990 Jan-Feb;5(1 Suppl):S44-53. DOI: http://dx.doi.org/10.1007/ 32. Greenfield S, Kaplan SH, Ware JE Jr, Yano EM, Frank HJ. Patients’ participation BF02600437. in medical care: effects on blood sugar control and quality of life in diabetes. J Gen 48. Hysong SJ, Teal CR, Khan MJ, Haidet P. Improving quality of care through Intern Med 1988 Sep-Oct;3(5):448-57. DOI: http://dx.doi.org/10.1007/BF02595921. improved audit and feedback. Implement Sci 2012 May 18;7:45. DOI: http://dx.doi. 33. Hojat M, Louis DZ, Markham FW, Wender R, Rabinowitz C, Gonnella JS. Physicians’ org/10.1186/1748-5908-7-45. empathy and clinical outcomes for diabetic patients. Acad Med 2011 Mar;86(3):359- 49. Luhanga U. Qualitative study of attendings’ and residents’ perspectives on 64. DOI: http://dx.doi.org/10.1097/ACM.0b013e3182086fe1. feedback in pediatrics clinical settings [Internet: Doctoral dissertation]. Kingston, 34. Jha AK, Orav EJ, Zheng J, Epstein AM. Patients’ perception of hospital care in Ontario, Canada: Queen’s University; 2015 [cited 2015 Sep 24]. Available the United States. N Engl J Med 2008 Oct 30;359(18):1921-31. DOI: http://dx.doi. from: https://qspace.library.queensu.ca/bitstream/1974/13867/1/Luhanga_ org/10.1056/NEJMsa0804116. Ulemu_201512_PhD.pdf. 35. Ratanawongsa N, Karter AJ, Parker MM, et al. Communication and medication refill 50. Carlisle A, Jacobson KL, Di Francesco L, Parker RM. Practical strategies to adherence: the Diabetes Study of Northern California. JAMA Intern Med 2013 Feb improve communication with patients. P T 2011 Sep;36(9):576-89. 11;173(3):210-8. DOI: http://dx.doi.org/10.1001/jamainternmed.2013.1216. 51. Guest G, Bunce A, Johnson L. How many interviews are enough? An experiment 36. Roberts KJ. Physician-patient relationships, patient satisfaction, and antiretroviral with data saturation and variability. Field Methods 2006 Feb;18(1):59-82. DOI: medication adherence among HIV-infected adults attending a public health http://dx.doi.org/10.1177/1525822X05279903. clinic. AIDS Patient Care STDS 2002 Jan;16(1):43-50. DOI: http://dx.doi. 52. Lambert SD, Loiselle CG. Combining individual interviews and focus groups to org/10.1089/108729102753429398. enhance data richness. J Adv Nurs 2008 Apr;62(2):228-37. DOI: http://dx.doi. 37. Schneider J, Kaplan SH, Greenfield S, Li W, Wilson IB. Better physician-patient org/10.1111/j.1365-2648.2007.04559.x. relationships are associated with higher reported adherence to antiretroviral therapy in patients with HIV infection. J Gen Intern Med 2004 Nov;19(11):1096-103. DOI: http://dx.doi.org/10.1111/j.1525-1497.2004.30418.x.

Compassion

The greatest single quality which the intern should develop is that of compassion for the sick, the afflicted and the suffering. … No single attribute of medical practice is more demanding, more difficult to acquire and more exacting to maintain than the bond which exists between the patient and the doctor.

— The Internship. Roscoe L Pullen. Springfield, IL: Charles C Thomas; 1952

30 The Permanente Journal/Perm J 2016 Summer;20(3):15-154 ORIGINAL RESEARCH & CONTRIBUTIONS Physicians Experiencing Intense Emotions While Seeing Their Patients: What Happens?

Joana Vilela da Silva, MD; Irene Carvalho, PhD Perm J 2016 Summer;20(3):15-229 E-pub: 07/29/2016 http://dx.doi.org/10.7812/TPP/15-229

ABSTRACT physicians’ intense emotions constitute particular challenges Objectives: Physicians often deal with emotions arising that are more difficult to ignore and possibly to manage at the from both patients and themselves; however, management of moment. The way physicians react and manage these emotions intense emotions when they arise in the presence of patients is can affect both the physician and the patient1,4 and shape the overlooked in research. The aim of this study is to inspect physi- clinical relationship in fundamental ways. What happens when cians’ intense emotions in this context, how these emotions are physicians experience strong emotions in the presence of their displayed, coping strategies used, adjustment behaviors, and patients? Although numerous studies have focused on patients’ the impact of the emotional reactions on the physician-patient emotions and on how physicians deal with them,5,6 physicians’ relationship. own emotions arising when they are seeing their patients have Methods: A total of 127 physicians completed a self-report received less attention. survey, built from a literature review. Participants were recruited Research on physicians’ emotions highlights the importance in 3 different ways: through a snowball sampling procedure, via of physicians’ awareness of their emotional states during the institutional e-mails, and in person during service meetings. medical encounter. Unrecognized emotions may impede the Results: Fifty-two physicians (43.0%) reported experiencing use of patient-centered skills and may be associated with harm- intense emotions frequently. Although most physicians (88.6%) ful behaviors, such as inappropriately interrupting the patient, tried to control their reactions, several reported not controlling changing the subject, avoiding patients’ psychological issues, themselves. Coping strategies to deal with the emotion at the avoiding bonding with patients to prevent suffering, avoiding moment included behavioral and cognitive approaches. Only conducting certain medical procedures again, or avoiding pa- the type of reaction (but not the emotion’s valence, duration, tients altogether.7-10 One study showed that physicians them- relative control, or coping strategies used) seemed to affect the selves perceive their emotional states as influencing medical physician-patient relationship. Choking-up/crying, touching, acts such as prescribing, talking to patients, and referring.11 In smiling, and providing support were significantly associated addition, lack of recognition of one’s emotions and low-level with an immediate positive impact. Withdrawing from the situ- choices, more than clinical knowledge or medical skills, have ation, imposing, and defending oneself were associated with a been proposed to be associated with medical error.7,8 Along with negative impact. Some reactions also had an extended impact the effects of emotional unawareness on patient care, research into future interactions. has also examined the impact of physicians’ emotions on their Conclusion: Experiencing intense emotions in the presence own well-being. Unexplored feelings may be associated with dis- of patients was frequent among physicians, and the type of reac- tress, poor judgment, loss of privileges, social isolation, increased tion affected the clinical relationship. Because many physicians workload, risk of litigation, burnout, reduced work satisfaction, reported experiencing long-lasting emotions, these may have and an increase in alcohol and other substance use.12-16 important clinical implications for patients visiting physicians This research is informative of important systematic and lasting while these emotions last. Further studies are needed to clarify effects of emotions experienced by physicians after the encounter these results. with patients. However, it does not address how physicians man- age their intense emotions when these arise in the presence of their INTRODUCTION patients. How these emotions are displayed to the patient and Emotions play a significant role in human interactions, yield- their impact on the relationship are overlooked. Most previous ing communicative intentions, modeling behavior, promoting studies that focus on physicians’ emotions deal with the extreme attachment, influencing information processing, and even deter- contexts of dying patients, medical errors, safety-related events, mining choices.1,2 Physicians’ emotions in professional settings, and treatment complications.17-20 Emotions in these contexts traditionally considered to be unprofessional and a taboo, have include hurt feelings, anger, frustration, remorse, sadness, guilt, increasingly been addressed in medical education as a result of the and unhappiness,21 and disturbing emotions can last for years.19 recognition that physicians often deal with emotions arising from Coping strategies used in these contexts include obtaining emo- both the patient and themselves.3,4 Even if feelings of moderate tional support from others, trying to have a positive perspective intensity are manageable or unnoticeable in medical encounters, over the situation, getting back to work to clear the mind,22 talking

Joana Vilela da Silva, MD, is an Intern Physician of Otorhinolaryngology Head and Neck Surgery in Vila Nova de Gaia/Espinho Hospital Center, Portugal. E-mail: [email protected]. Irene Carvalho, PhD, is a Professor of Clinical Neurosciences and Mental Health at Oporto University in Portugal. E-mail: [email protected].

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to other physicians or family members, doing physical exercise,20 life] when you experienced an intense emotion, either positive or doing nothing, and talking to the patient.21 negative. The events might have been brought about by you, [by a However, these situations are limited to a few extreme scenarios patient], by someone else, or by [other] causes.” Next, physicians associated with negative emotions (one study did identify positive were asked to recall and briefly describe a situation of their daily daily emotions, including gratitude, happiness, compassion, pride, clinical practice in which they experienced an intense emotion and relief, but these emerged among medical trainees and were while they were seeing their patients; to name the emotion expe- associated with connecting with patients and with colleagues, re- rienced; to indicate how long ago they experienced the emotion, ceiving recognition for one’s work, learning, being part of modern how long the emotion lasted, where it took place, and the atti- medicine, and receiving emotional support).23 Intense emotions tude they had at that moment (options ranging from complete during interactions with patients in less extreme scenarios may control of the emotion to uncontrolled emotional reaction); to present a bigger challenge for physicians. They may impair an describe the actual reaction (if they had one); to indicate what ongoing clinical interaction, lessen empathy, or jeopardize the they did after realizing they reacted openly (eg, returned to their physician-patient relationship. Physicians must make decisions previous posture, apologized); to describe the strategies used to while experiencing powerful feelings, and they need to manage control the emotion; and to describe how the emotional reaction these emotions in front of their patients. The aim of this study is affected their relationship with the patient at that moment and to explore intense emotions physicians experience in their daily in future encounters. Two final questions were added for a better practice while with patients, how these emotions are displayed understanding of the occurrence of strong emotional experiences to the patients, the strategies used to manage these emotions at that moment, and the impact the emotional reactions have on Table 1. Sample characteristics of physician survey the physician-patient relationship. respondents METHODS Respondent characteristics (N = 124) Valuea Procedures Age (years), mean (SD; range) 37.8 (12.8; 25-66) In this cross-sectional, retrospective study, participants were re- Professional experience (years), mean (SD; range) 12.0 (12.3; < 1-40) cruited through 1) a snowball sampling procedure, 2) institutional Sex (n = 122) e-mails (from the School of Medicine of Oporto University, the Women 75 (61.5) Portuguese League against Cancer, and the Oporto Health Campus Men 47 (38.5) Ministry), and 3) in-person contact during service meetings at the Professional level (n = 121) major central hospital in Oporto and in several primary care centers Attending 56 (46.3) in that geographic area. Data were collected between June 2012 Resident 65 (53.7) and February 2013. Physicians were informed about the aim of the Currently practicing 124 (100) study, as well as the confidential, anonymous, and voluntary nature Geographic work location (n = 123) of their participation. Agreement to participate served as informed Urban 115 (93.5) consent. The hospital ethics committee approved the study. Nonurban 8 (6.5) Instrument Northern country 118 (95.9) South (Madeira Island) 5 (4.1) A questionnaire on physicians’ emotional experiences was devel- oped for this study after a literature review. The Geneva Appraisal Medical specialty (n = 119) Questionnaire24 assesses individual appraisal processes in the case General practice 46 (38.7) of an emotional episode and was close to the goals of this study. Internal medicine 13 (10.9) Several items from its version 3 were translated and used in their Ophthalmology 11 (9.2) original form or in a modified version. Three additional items Psychiatry 6 (5.0) were included in the questionnaire to address specific issues in Infectious diseases 5 (4.2) this study (eg, strategies used to control the emotional expression). Nephrology 5 (4.2) The questionnaire was then applied to a sample of physicians Legal medicine 4 (3.4) and medical students who were not participating in the study Endocrinology 4 (3.4) to check for meaning, accuracy, and completeness. Ambiguous/ Cardiology 3 (2.5) incomplete items were modified, and the survey was again tested Pediatrics 3 (2.5) with a different sample of physicians and medical students. This Neurology 2 (1.7) procedure was repeated until the final version of the survey was Gynecology 2 (1.7) approved. The final 21-item version combines open-ended and Pathology 2 (1.7) multiple-choice questions (presenting either 4, 5, or 6 options, General surgery 1 (0.8) plus an additional option that can be either “I don’t know” or Pulmonology 1 (0.8) “other—specify”). N/A (1st-year interns) 11 (9.2) The questionnaire starts with the following instruction: “In a Data are no. (%) of physician survey respondents unless otherwise indicated. this questionnaire, we ask you to recall moments [in your clinical SD = standard deviation.

32 The Permanente Journal/Perm J 2016 Summer;20(3):15-229 ORIGINAL RESEARCH & CONTRIBUTIONS Physicians Experiencing Intense Emotions While Seeing Their Patients: What Happens?

in clinical practice throughout physicians’ careers: to indicate (as emotions while interacting with patients and 1 woman who de- many as applicable) intense emotions experienced when seeing scribed a situation outside of the study’s goals). The final sample patients in situations other than the one already described (the (depicted in Table 1) comprised 124 actively practicing physicians list included 24 emotional reactions; eg, deep sadness, depression, working mostly in the north of the country (95.9%) and in urban enthusiasm, intense fear, total relief, intense joy, and deep shock); areas (93.5%). Because of missing values and nonapplicability and to indicate how frequently intense emotions were experienced of some items to subgroups of respondents, the total number of in the presence of patients. Participants additionally answered participants included in each analysis varied between 53 and 124. questions on demographic and professional characteristics (eg, sex, birth date, level of medical training, medical specialty, years Analyses of medical experience, and current professional status, whether A content analysis was applied to the description of the episode, practicing or not). with both authors independently coding the situations. Observa- tions were compared, with Cohen’s K = 1 in 12 categories, plus Participants K = 0.91, K = 0.92, and K = 0.96 in the 3 remaining categories, A total of 127 participants completed the questionnaire. Three respectively. The shorter-answer, open-ended questions were were excluded (2 men who reported never experiencing intense also independently coded, with final categories reached through

Table 2. Fifteen types of situations eliciting intense emotions in daily practice from 122 physician survey respondentsa Categories of situations n (%) Indicators Health deterioration/death 35 (28.7) I watched a patient die before the medical team’s powerlessness and anguish. The patient was conscious and we could tell by his facial expression that he could understand what was going on. He tried to tell us something but it was not perceptible. Physical or psychosocial suffering 14 (11.5) I followed-up with a patient in the intensive care unit. She was young and suffered from severe systemic lupus. She had a tracheostomy and was ventilated but conscious. In one of the medical visits she asked me for a paper and wrote, “Help me.” She was in very bad shape and eventually died. End-of-life patients 13 (10.7) She was a terminal patient receiving comfort measures in the intensive care unit. For four years I could never get her to accept her illness and start treatment. I felt frustrated watching her die and could not do anything. Then, she grabbed my hand and looked at me in a way I will never forget, and smiled. I felt that her look meant, “It was my fault, you did everything you could. I am in peace.” Aggressive patients 11 (9.0) During a consultation a patient pointed a gun at himself. In the ER the family of a patient invaded my office and threatened me because I was taking too long to see her .… I felt very vulnerable around them all. They were threatening to destroy everything, using inappropriate language, hitting the wall, and dropping material that was over the desk. Communicating bad news 11 (9.0) Having to tell a young patient that her husband and children died. Solving the patient’s problem 8 (6.6) The first time I alone diagnosed and successfully treated a patient in the ER. A patient who was amazed about the surgery that restored his sight. Patients’ rudeness 7 (5.7) While I was with a patient, his wife spent the entire time reading the newspaper. I felt disrespected. Unexpected disabling condition 7 (5.7) A young patient entered the emergency room in cardiac arrest. She was alone at that moment without any family members who could provide any information. After two cycles of advanced life support, she recovered. When we could collect a clinical history, we found out that she had terminal brain cancer. Accusations of malpractice 7 (5.7) During a consultation, a patient confronted me with the desire to have a routine examination check for everything, and about my obligation to do it. He said, “I have paid taxes for many years and now I have the right to have the exams I want. Nowadays, doctors study medicine for money. In the old days, we had good doctors that did the exams we wanted.” A family member of a patient I had seen the day before came to tell me that the patient died on her way home. He criticized me for not sending her to the emergency room instead. Disagreeing about the proposed 4 (3.3) The team told a patient’s family that he would die and that the situation was inevitable. I believed that a treatment bigger effort on our part could still save him. Patient telling disturbing information 1 (0.8) I felt repulsed after a patient mentioned that during an impulsive episode she killed her pets. Making harmful decisions 1 (0.8) A patient asked me for a compulsory detention of her mother, who took care of a bedridden brother. This brother would be abandoned for lack of social and family support. Stress at work 1 (0.8) Stress in the operating room. Demanding patients 1 (0.8) Following-up a patient with a personality disorder. She questioned every medical intervention, saying nothing was working. She had multiple complaints and was very demanding. Dealing with her husband’s pressure (“You have to make her better”). Patients’ gratitude 1 (0.8) A patient’s widow offered me a reminder of her husband, who had died three months earlier. I never met him, only supervised some aspects for his well-being during his palliative phase. a In this particular question only 122 physicians answered; 2 participants reported the emotion but not the situation that elicited it. ER = emergency room.

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consensus. Chi-squared tests and independent-sample t-tests were p = 0.022), and only smiled when experiencing positive emotions conducted in PASW, version 20 (IBM, Armonk, NY). (χ2(1) = 39.375, p < 0.001). All other reactions occurred only during negative and mixed emotional experiences. RESULTS Several participants who reported not completely control- Physicians indicated experiencing many and varied strong emo- ling their emotional reactions adjusted their behaviors after tions in the presence of their patients throughout their careers they reacted (n = 58). Of these, 16 (27.6%) said they tried to (median = 6.00; interquartile range = 4; range, 1-16 emotions return to their previous posture, 3 (5.2%) apologized for their per physician). The emotional spectrum includes both positive reaction, 1 (1.7%) allowed room for the patient to apologize. and negative feelings, and though most emotions in the list we Thirty-eight (65.5%) felt that their reactions were expected and provided were negative, several positive emotions appeared at the that no further action was necessary. No significant differences top of the list as frequently experienced (enthusiasm was the most were observed between physicians who attempted to adjust their signaled emotion in the list). Forty-eight participants (39.7% of behavior afterwards and physicians who did not, regarding the the 121 who answered this question) reported experiencing strong different types of reactions. emotions only a few times per year while interacting with patients. To cope with their intense emotions at the moment, physicians But 18 (14.9%) mentioned monthly occurrences, and 34 (28.1%) resorted to several types of strategies (Table 5). These strategies reported weekly and daily experiences of intense emotions in the were reported especially by physicians who considered they con- presence of patients. Frequency was independent from physi- trolled or attempted to control their emotions (73 [96.1%] of cians’ gender and geographic work location. However, physicians the 76 participants who reported using these strategies, χ2[1] = reporting frequent strong emotions had fewer years of medical 10.900, p = 0.001). The difference from physicians who did not practice (mean ± standard deviation [SD], 8.40 ± 11.03) than control their emotions (n = 3 [3.95%)] was statistically significant those reporting more sporadic experiences of strong emotional (χ2[1] = 10.900, p = 0.001). Though most physicians resorting to reactions (mean ± SD, 15.43 ± 12.73), t(109) = 3.12, p = 0.002. coping strategies reported intense negative feelings (63 [84.00%], Regarding the specific emotional event described in the ques- comparing with 12 reporting positive and mixed feelings), using tionnaire, most physicians reported situations that occurred long coping strategies was not significantly associated with negative ago: years ago in 48 cases (38.7%) and months or weeks ago in emotions, and the same types of strategies were generally used 59 cases (47.6%) of all 124 physicians. Only 17 (13.7%) re- to deal with negative and with mixed emotions. Using coping called an event that occurred days or hours ago. These situations strategies was reported in association with positive emotions in included several extreme events (the most frequently mentioned 3 cases: breathing, refocusing attention, and a combination of was, “Dealing with patients’ health deterioration or death”), but these 2 to deal, respectively, with intense relief (1 case) and with also less extreme scenarios (eg, “A patient did not want to greet happiness (2 cases). me with a handshake”). Additionally, some situations were posi- Of the 89 physicians who considered that a relationship with tive experiences (“A patient was amazed about the surgery that the patient existed, most (47 [52.8%]) considered that their restored his sight”; Table 2). emotional reactions had no impact in the relationships with their Physicians’ emotions associated with these situations are de- picted in Table 3 according to their positive, negative, or mixed (comprising compassion and surprise) valence. Mostly, physicians Table 3. Physician respondents’ intense emotions experienced reported negative emotions (139 instances, or 85.8% of all 162 in the presence of patients reported emotions). For 47 participants (39.8% of the 118 who Emotions experienced No. (%)a answered this question), these emotions lasted longer than a few Negative minutes or hours: more than 1 day for 34 physicians (28.8%) Sadness 41 (25.3) and more than 1 week for 13 participants (11.0%), and 2 par- Fear/anxiety (nervousness, fright, panic, apprehension) 34 (21.0) ticipants offered that the emotion is still retrieved upon recalling Frustration (powerlessness, incapacity) 32 (19.8) the situation. Most physicians (109 of the 123 who answered this question Anger (revolt, indignation) 24 (14.8) [88.6%]) at least tried to control their emotions, and 33 (26.8%) Disappointment 3 (1.9) reported they completely controlled themselves. Only 14 par- Repulsion (contempt) 2 (1.2) ticipants (11.4%) reported they did not control their emotional Guilt 2 (1.2) reaction. Only participants experiencing negative emotions Shame 1 (0.6) reported controlling them completely in the presence of their Positive patients (χ2(1) = 9.379, p = 0.001). The difference from physi- Happiness (joy, self-fulfillment) 7 (4.3) cians experiencing positive and mixed emotions was statistically Relief 2 (1.2) significant (χ2(1) = 9.379, p = 0.001), though some of the latter Mixed also attempted to control themselves. Compassion (empathy, tenderness, solidarity) 12 (7.4) Table 4 depicts physicians’ actual reactions. Physicians were Surprise/confusion 2 (1.2) more likely to touch the patient when experiencing positive emo- a N = 162 reported emotions. Some survey respondents reported more than one tions than when experiencing negative emotions (χ2(1) = 6.563, emotion.

34 The Permanente Journal/Perm J 2016 Summer;20(3):15-229 ORIGINAL RESEARCH & CONTRIBUTIONS Physicians Experiencing Intense Emotions While Seeing Their Patients: What Happens?

patients; 33 (37.1%) considered a positive impact; and only a few (χ2(1) = 7.814, p = 0.009) or in future interactions (χ2(1) = 5.181, (9 [10.1%]) reported negative consequences at the moment. Ad- p = 0.038). On the other hand, withdrawing from the situation, ditionally, 23 participants (43.4% of the 53 who answered this imposing oneself and defending oneself were significantly associ- question) reported that the impact of the episode in their relation- ated with an immediate negative impact in the physician-patient ship with the patient extended beyond the immediate moment relation (χ2(1) = 16.774, p < 0.001). These reactions tended to into future interactions. For 17 (73.9%) of these 23 participants, result in negative consequences for physicians who considered the result was positive, whereas for 6 participants (26.1%), it was that their reactions required no subsequent adjustment and in negative. Positive consequences included sense of relief, ability to positive consequences for physicians who tried to subsequently clarify the situation, awareness of one’s fallibility, increased under- adjust their behavior and repair the situation. These tendencies standing of the patient’s reality, attitudes, increased admiration were statistically nonsignificant, though. Withdrawing from the and interest for the patient, increased attention to the patient’s situation, imposing oneself, and engaging in medical procedures needs, increased empathy, increased relationship strength, close- were further associated with a negative impact in future physician- ness, mutual consideration and trust, and increased adequacy of patient interactions (χ2(1) = 8.727, p = 0.009). Defending oneself the patient’s behavior. Negative consequences included increased was associated with a positive impact in future interactions for the defensiveness, avoidance of the patient, loss of empathy and of 1 physician who attempted to go back to his previous posture. trust in the patient, and relationship termination. Additionally, the physician who withdrew from the situation but The (immediate or extended) impact of the emotional reac- allowed room for the patient to eventually apologize reported a tion on the physician-patient relationship was not significantly positive impact in future interactions with that patient. However, associated with valence, duration, relative control of the emo- these tendencies referred to small numbers of physicians and were tion, or coping strategies used. However, specific reactions had a statistically nonsignificant. significant impact in physician-patient relationships. Touching, The type of emotion and its relative control were not signifi- smiling, providing support, and choking up/crying did not yield a cantly associated with physicians’ gender or number of years of negative impact in physician-patient relationships at the moment medical experience. However, a greater percentage of physicians

Table 4. Physician respondents’ reactions while experiencing strong emotions in the presence of patients Categories of reactions Indicators No. (%)a Touching the patient Touching/holding the patient’s hand; hugging; shaking hands 13 (18.6) Performing medical procedures Writing a prescription; starting life support 10 (14.3) Withdrawing from the situation Leaving the room; avoiding the patient (eg, telling him to switch physicians, passing the telephone 9 (12.9) to another physician); refusing to see the patient Providing support Maintaining silence, respect, presence; comforting, attempting to understand or to communicate 8 (11.4) empathically; offering material help (money, goods) Choking up/crying Showing grief; feeling moved; unable to speak; crying 8 (11.4) Imposing oneself Speaking with authority; raising tone of voice; shouting; gesticulating; shaking one’s head; getting up; 7 (10.0) walking back and forth Smiling 5 (7.1) Defending oneself Explicitly legitimizing one’s perspective 4 (5.7) Explaining Providing clarification, including one physician who looked at the patient’s eyes and assumed 4 (5.7) responsibility for what happened Expelling the patient Standing up and ending the consultation, expelling the patient 2 (2.9) a N = 70 respondents reported reactions.

Table 5. Reported coping strategies to deal with emotional reactions in the presence of patients Categories of coping strategies Indicators No. (%)a Breathing Breathing; taking a deep breath; holding one’s breath 34 (44.7) Keeping the emotion away/focusing on Ignoring; keeping emotional distance from the situation; continuing the encounter as if nothing was 21 (27.6) something else happening; focusing on the (next) task, on the patient, on one’s posture; thinking as a professional; thinking of a solution; mentally counting Talking/listening to the patient Speaking calmly, gradually, with openness; maintaining silence; empathy; understanding; letting the 7 (9.2) patient express himself; keeping eye contact Breaking eye contact Gaining time; organizing thoughts 6 (7.9) Reframing Thinking of/providing an optimistic, hopeful perspective; rationalizing; accepting 5 (6.6) Withholding the emotion Blocking the feelings; not crying 3 (3.9) a N = 76 strategies.

The Permanente Journal/Perm J 2016 Summer;20(3):15-229 35 ORIGINAL RESEARCH & CONTRIBUTIONS Physicians Experiencing Intense Emotions While Seeing Their Patients: What Happens?

working in rural areas (37.5%) reported compassion, compared felt that negative emotions were … physicians with physicians working in urban areas (8.1%, χ2[1] = 7.110, less appropriate during clinical p = 0.033), and physicians from the South (ie, Madeira Island) additionally used interactions. reported controlling their reactions more than physicians from other strategies in the To deal with these emotions, the North part of Portugal (χ2[1] = 14.061, p = 0.001). However, moment, like breathing physicians used both cognitive the interpretation of these results needs caution because very few deeply, focusing on and behavioral coping strategies. physicians in the study were from southern Portugal or from their posture, thinking After-the-fact coping strategies nonurban centers. Physicians’ specific reactions were not signifi- about the next action, reported in previous research cantly associated with number of years of medical experience or being empathic, appeared in our study as ways of geographic work location. But explaining the situation and expel- listening to the patient managing emotions at the mo- ling the patient were exclusive to male physicians in this sample more, and mentally ment (eg, changing perspectives, (χ2[1] = 9.488, p = 0.005). Physicians of both genders used the keeping emotional distance, or counting. various coping strategies described, but women tended to resort talking to the patient).10,21,22 In to breathing more than men (χ2[1] = 5.250, p = 0.022). Breaking our study, physicians addition- eye contact was significantly associated with fewer years of medical ally used other strategies in the moment, like breathing deeply, experience (t[22] = 2.115, p = 0.046). Finally, the duration of the focusing on their posture, thinking about the next action, being emotion, the type of behavioral adjustment attempted after the empathic, listening to the patient more, and mentally counting. emotional reaction, and the (immediate or extended) impact of Whether or not controlled, in most cases physicians’ emotional the emotional reaction on the physician-patient relationship were reactions did not affect relationships with patients, at least from statistically unrelated with gender, geographic work location, and physicians’ perspectives. The impact was also independent from years of medical experience. emotional valence (though no positive emotion had a negative impact on the relationship) and duration, and from the coping DISCUSSION strategies used. Some specific reactions, however, did have an Results indicate that experiencing negative and positive intense impact. Choking up/crying, touching, smiling, and providing emotions in the presence of patients is frequent among physicians. support were significantly associated with an immediate positive The fact that experiencing intense emotions was more frequent impact and with no impact. This impact also extended into future among those with fewer years of clinical practice suggests that interactions. Not surprisingly, withdrawing from the situation, repeated exposure to these situations or increased clinical experi- imposing, and defending oneself were associated with a negative ence may contribute to attenuating the emotional response, as immediate impact. The former two reactions plus engaging in previous studies indicate.25 medical procedures had a further extended negative impact in Previous research on physicians’ emotions has specifically future interactions. But the tendency for readjusting the behavior focused on extreme scenarios associated with negative strong after the reaction to be less associated with a negative impact than emotional reactions.18,19 Such scenarios and associated intense when no readjustment existed, though not statistically significant, negative feelings were frequent also in this study. However, other suggests that the clinical relationship may be shaped by interac- contexts emerged as well, including less extreme scenarios (eg, tions beyond the display of strong negative reactions, and that the dealing with patients’ rudeness) and situations triggering intense reaction does not, per se, necessarily lead to a negative impact on positive emotions (the most frequent being resolving the patient’s the relationship, as long as interveners have the ability to repair it. problem). The fact that most situations described here elicited This study took a first step in the inspection of what happens negative feelings may suggest that negative emotions are more when physicians experience strong emotions while seeing patients, strongly felt by physicians, or that these may be recalled more and further research is needed for a better understanding of the re- easily than positive experiences.26 An interesting finding is that, sults. Specifically, better discrimination of the effects of particular as in previous studies,19 many physicians reported experiencing reactions on medical relationships is necessary. Also, the sampling longlasting emotions. This may have important clinical implica- strategy in this study limited our goal of forming a representative tions for patients visiting physicians while these emotions last, sample of physicians in the country, which restricts the generaliz- namely regarding decision processes.11 ability of the results. It is possible that physicians who agreed to Most physicians in this study tried to control the emotion, participate were particularly interested in the theme, introducing which may partly explain the lack of perceived impact of their biases (eg, increasing the prevalence of intense emotions in clini- reaction on their relationship with patients. This attempted con- cal practice). Because we used a self-report, retrospective instru- trol suggests that physicians may consider displaying emotional ment, recall or report biases may also exist. Finally, the sample reactions to be inappropriate in the presence of patients, although size may prevent the analysis and the observation of effects that possibly less so if the emotion is positive. Smiling was associated could be visible with larger numbers of participants per group. only with positive emotions, and physicians touched the patient Future research needs to consider additional aspects that could significantly more if they were experiencing positive feelings. On affect physician-patient relationships (eg, duration and kind of the other hand, only participants experiencing negative emotions relationship with the physician) on a larger sample. It is also reported controlling them completely, probably because they important to assess patients’ perceptions of physicians’ emotions and of their impact on the clinical relationship, in addition to

36 The Permanente Journal/Perm J 2016 Summer;20(3):15-229 ORIGINAL RESEARCH & CONTRIBUTIONS Physicians Experiencing Intense Emotions While Seeing Their Patients: What Happens?

assessing patients’ own reactions to the situations. The inclusion 7. Ely JW, Levinson W, Elder NC, Mainous AG 3rd, Vinson DC. Perceived causes of of other clinical implications is also crucial, such as the effect of family physicians’ errors. J Fam Pract 1995 Apr;40(4):337-44. physicians’ emotional state in appropriate medical management, 8. Borrell-Carrió F, Epstein RM. Preventing errors in clinical practice: a call for as suggested in previous studies.11 self-awareness. Ann Fam Med 2004 Jul-Aug;2(4):310-6. DOI: http://dx.doi.org/ 10.1370/afm.80. 9. Smith RC, Dwamena FC, Fortin AH 6th. Teaching personal awareness. J Gen Intern CONCLUSION Med 2005 Feb;20(2):201-7. DOI: http://dx.doi.org/10.1111/j.1525-1497.2005.40212.x. Although the display of emotions in medical encounters may be 10. Hendin H, Lipschitz A, Maltsberger JT, Haas AP, Wynecoop S. Therapists’ reactions considered unprofessional, the experience of intense emotions by to patients’ suicides. Am J Psychiatry 2000 Dec;157(12):2022-7. DOI: http://dx.doi. org/10.1176/appi.ajp.157.12.2022. physicians in the presence of patients seems frequent. Physicians 11. Kushnir T, Kushnir J, Sarel A, Cohen AH. Exploring physician perceptions of the control the display of intense negative emotions more than that of impact of emotions on behaviour during interactions with patients. Fam Pract 2011 positive reactions. However, relative control of the emotion, cop- Feb;28(1):75-81. DOI: http://dx.doi.org/10.1093/fampra/cmq070. 12. Ramirez AJ, Graham J, Richards MA, et al. Burnout and psychiatric disorder among ing strategies used, the valence (positive, negative, or mixed), and cancer clinicians. Br J Cancer 1995 Jun;71(6):1263-9. DOI: http://dx.doi.org/10.1038/ the duration of the emotion do not affect the clinical relationship. bjc.1995.244. Specific emotional reactions do. Choking up/crying, touching, 13. Pfifferling JH. The disruptive physician. A quality of professional life factor. Physician Exec 1999 Mar-Apr;25(2):56-61. smiling, and providing support did not affect relationships in 14. Cooper CL, Rout U, Faragher B. Mental health, job satisfaction, and job stress negative ways, but leaving the patient, imposing, and defending among general practitioners. BMJ 1989 Feb 11;298(6670):366-70. DOI: http://dx.doi. oneself did. The fact that the impact of these reactions could be org/10.1057/9781137310651.0026. 15. Blanchard P, Truchot D, Albiges-Sauvin L, et al. Prevalence and causes of burnout different according to physicians’ subsequent adjusted behavior amongst oncology residents: a comprehensive nationwide cross-sectional study. Eur suggests that this impact may be modulated by the interlocutors’ J Cancer 2010 Oct;46(15):2708-15. DOI: http://dx.doi.org/10.1016/j.ejca.2010.05.014. following actions, namely attempts at repairing the situation. 16. Ekman E, Halpern J. Professional distress and meaning in health care: Why v professional empathy can help. Social Work Health Care 2015;54(7):633-50. DOI: Future studies are needed to clarify these results. http://dx.doi.org/10.1080/00981389.2015.1046575. 17. Patel AM, Ingalls NK, Mansour MA, Sherman S, Davis AT, Chung MH. Collateral Disclosure Statement damage: the effect of patient complications on the surgeon’s psyche. Surgery 2010 The author(s) have no conflicts of interest to disclose. Oct;148(4):824-8. DOI: http://dx.doi.org/10.1016/j.surg.2010.07.024. 18. O’Beirne M, Sterling P, Palacios-Derflingher L, Hohman S, Zwicker K. Emotional impact of patient safety incidents on family physicians and their office staff. J Acknowledgment Am Board Fam Med 2012 Mar-Apr;25(2):177-83. DOI: http://dx.doi.org/10.3122/ Mary Corrado, ELS, provided editorial assistance. jabfm.2012.02.110166. 19. Jackson VA, Sullivan AM, Gadmer NM, et al. “It was haunting...”: physicians’ How to Cite this Article descriptions of emotionally powerful patient deaths. Acad Med 2005 Jul;80(7):648-56. DOI: http://dx.doi.org/10.1097/00001888-200507000-00007. da Silva JV, Carvalho I. Physicians experiencing intense emotions while 20. Scott SD, Hirschinger LE, Cox KR, McCoig M, Brandt J, Hall LW. The natural seeing their patients: What happens? Perm J 2016 Summer;20(3):15-229. history of recovery for the healthcare provider “second victim” after adverse patient DOI: http://dx.doi.org/10.7812/TPP/15-229. events. Qual Saf Health Care 2009 Oct;18(5):325-30. DOI: http://dx.doi.org/10.1136/ qshc.2009.032870. 21. Masia RT, Basson WJ, Ogunbanjo GA. Emotional reactions of medical doctors References and students following the loss of their patients at the Dr George Mukhari Hospital 1. Croskerry P, Abbass A, Wu AW. Emotional influences in patient safety. J Patient Saf emergency unit, South Africa. S Afr Fam Pract 2010;52(4):356-63. DOI: http://dx.doi. 2010 Dec;6(4):199-205. DOI: http://dx.doi.org/10.1097/pts.0b013e3181f6c01a. org/10.1080/20786204.2010.10874006. 2. Hareli S, Hess U. The social signal value of emotions. Cogn Emot 2012;26(3):385-9. 22. Redinbaugh EM, Sullivan AM, Block SD, et al. Doctors’ emotional reactions to DOI: http://dx.doi.org/10.1080/02699931.2012.665029. recent death of a patient: cross sectional study of hospital doctors. BMJ 2003 Jul 3. Dessy E. Effective communication in difficult situations: preventing stress and burnout 26;327(7408):185. DOI: http://dx.doi.org/10.1136/bmj.327.7408.185. in the NICU. Early Hum Dev 2009 Oct;85(10 Suppl):S39-41. DOI: http://dx.doi. 23. Kasman DL, Fryer-Edwards K, Braddock CH 3rd. Educating for professionalism: org/10.1016/j.earlhumdev.2009.08.012. trainees’ emotional experiences on IM and pediatrics inpatient wards. Acad Med 2003 4. Meier DE, Back AL, Morrison RS. The inner life of physicians and care of the Jul;78(7):730-41. DOI: http://dx.doi.org/10.1097/00001888-200307000-00017. seriously ill. JAMA 2001 Dec 19;286(23):3007-14. DOI: http://dx.doi.org/10.1001/ 24. Scherer KR, Schorr A, Johnstone T. Appraisal processes in emotion: theory, methods, jama.286.23.3007. research. New York, NY: Oxford University Press, USA; 2001 Apr 9. 5. Stewart M, Brown JB, Donner A, et al. The impact of patient-centered care on 25. Paul S, Simon D, Kniesche R, Kathmann N, Endrass T. Timing effects of outcomes. J Fam Pract 2000 Sep;49(9):796-804. antecedent- and response-focused emotion regulation strategies. Biol Psychol 2013 6. Maguire P. Improving communication with cancer patients. Eur J Cancer 1999 Sep;94(1):136-42. DOI: http://dx.doi.org/10.1016/j.biopsycho.2013.05.019. Dec;35(14):2058-65. DOI: http://dx.doi.org/10.1016/s0959-8049(99)00301-9. 26. Baumeister RF, Bratslavsky E, Finkenauer C, Vohs KD. Bad is stronger than good. Review of General Psychology 2001;5(4):323-70. DOI: http://dx.doi. org/10.1037//1089-2680.5.4.323.

What Counts

It is the human touch after all that counts for most in our relation with our patients.

— Robert Tuttle Morris, 1857-1945, American surgeon and author

The Permanente Journal/Perm J 2016 Summer;20(3):15-229 37 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

Ashli A Owen-Smith, PhD, SM; David H Smith, PhD, RPh; Cynthia S Rand, PhD; Jeffrey O Tom, MD, MS; Reesa Laws; Amy Waterbury, MPH; Andrew Williams, PhD; William M Vollmer, PhD Perm J 2016 Summer;20(3):15-200 E-Pub: 06/29/2016 http://dx.doi.org/10.7812/TPP/15-200

ABSTRACT group received automated telephone re- Context: There is little research investigating whether health information technolo- minder calls followed by mailed letters. gies, such as interactive voice recognition, are effective ways to deliver information to The intervention improved initial fill rates individuals with lower health literacy. during the next 25 days by 16 percentage Objective: Determine the extent to which the impact of an interactive voice points. These and other studies suggest that recognition-based intervention to improve medication adherence appeared to vary by HIT-based reminder interventions offer a participants’ health literacy level. promising, “light-touch” option for pro- Design: Promoting Adherence to Improve Effectiveness of Cardiovascular Disease moting adherence in large populations.11-14 Therapies (PATIENT) was a randomized clinical trial designed to test the impact, compared Although HIT-based interventions with usual care, of 2 technology-based interventions that leveraged interactive voice may be more easily disseminated, reach recognition to promote medication adherence. A 14% subset of participants was sent a a greater number of people, and be lower survey that included questions on health literacy. This exploratory analysis was limited cost, they may exacerbate certain health to the 833 individuals who responded to the survey and provided data on health literacy. disparities, because more educated and Main Outcome Measures: Adherence to statins and/or angiotensin-converting enzyme technologically advanced individuals inhibitors and/or angiotensin II receptor blockers. will benefit disproportionately from Results: Although intervention effects did not differ significantly by level of health such advances.15,16 Patients with low literacy, the data were suggestive of differential intervention effects by health literacy level. health literacy—individuals who face Conclusions: The differences in intervention effects for high vs low health literacy in challenges with respect to their capacity this exploratory analysis are consistent with the hypothesis that individuals with lower to obtain, process, and understand basic health literacy may derive greater benefit from this type of intervention compared with health information and services needed individuals with higher health literacy. Additional studies are needed to further explore to make appropriate health decisions17— this finding. are likely to be particularly vulnerable in this regard.18 Individuals with low health INTRODUCTION specialized counseling skills, which can literacy, for example, are much less likely Treatment nonadherence with cardio- limit the likelihood for dissemination. to use computers, mobile applications, vascular disease (CVD) therapy has been Furthermore, most interventions evaluated and other consumer and patient medical well documented1 and is a major con- thus far have enrolled highly select and devices.19,20 Consequently, it has been tributor to increased cardiovascular risk small patient populations, thus limiting argued that interactive voice recogni- and morbidity.2 At the population level, generalizability. More recently, research tion (IVR) is one type of HIT that may low adherence is often the broken link has focused on using health information be particularly well suited for delivering between effective new therapies and im- technologies (HIT) to develop low-cost interventions to low-literacy individuals proved health outcomes.3 Nonadherence interventions that can be delivered to because it 1) delivers information via has also been identified as a key target for large populations to promote adherence speech instead of text and 2) uses the reducing unnecessary health care costs.4,5 for patients with chronic illness.7-9 For telephone so that computer access and The most effective adherence interven- example, one recent study described an computer literacy are not required.19,21,22 tions include both educational and behav- intervention among 5216 adults who were An Institute of Medicine report23 in ioral strategies6; however, these strategies newly prescribed a statin but had failed to 2004 called for studies that establish ef- are costly and require both staff time and fill the prescription.10 The intervention fective approaches to reduce the negative

Ashli A Owen-Smith, PhD, SM, is an Assistant Professor of Health Management and Policy at the Georgia State University School of Public Health in Atlanta. E-mail: [email protected]. David H Smith, PhD, RPh, is a Senior Investigator at The Kaiser Permanente Center for Health Research in Portland, OR. E-mail: [email protected]. Cynthia S Rand, PhD, is a Professor of Medicine in the Department of Medicine at the Johns Hopkins School of Medicine in Baltimore, MD. E-mail: [email protected]. Jeffrey O Tom, MD, MS, is an Assistant Clinical Professor in the Department of Pediatrics at the University of Hawaii John A Burns School of Medicine in Honolulu. E-mail: [email protected]. Reesa Laws is the Research and Data Analytics Center Manager and Technical Research Program Manager at The Kaiser Permanente Center for Health Research in Portland, OR. E-mail: [email protected]. Amy Waterbury, MPH, is a Research Program Manager at The Kaiser Permanente Center for Health Research in Portland, OR. E-mail: [email protected]. Andrew Williams, PhD, is a Faculty Scientist in the Center for Outcomes Research and Evaluation at the Maine Medical Center Research Institute in Scarborough. E-mail: [email protected]. William M Vollmer, PhD, is a Senior Investigator at The Kaiser Permanente Center for Health Research in Portland, OR. E-mail: [email protected].

38 The Permanente Journal/Perm J 2016 Summer;20(3):15-200 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

effects of limited health literacy. However, The PATIENT Study Health Literacy Questions there is still little research to date investi- We have previously described the 1. How often do you need to have gating whether IVR systems are, in fact, PATIENT study in detail.24 Using each Re- someone help you when you read effective ways to deliver health information gion’s electronic medical records (EMRs), instructions, pamphlets, or other to lower health literacy individuals with we identified participants aged 40 years written materials from your doctor chronic disease. and older with diabetes mellitus and/or or pharmacy? The purpose of the present exploratory CVD, with suboptimal (< 90%) adher- 2. How confident are you filling out analysis was to explore whether an IVR- ence to a statin or ACEI/ARB during the medical forms by yourself? based intervention to improve medication previous 12 months, and who were due or 3. How would you rate your ability adherence among individuals with CVD overdue for a refill. Individuals with medi- to read? or diabetes mellitus would yield differences cal conditions that might contraindicate in outcomes according to participants’ the use of these medications (eg, allergic health literacy level. to the medication, liver failure, cirrhosis, at the time of randomization, we modified rhabdomyolysis, end-stage renal disease, the Proportion of Days Covered to include METHODS chronic kidney disease) and those on KP’s the whole follow-up period as the denomi- Study Design “do not contact” list were excluded. In each nator timeframe rather than time from first The Promoting Adherence to Improve Region, we randomly assigned a sample dispensing.26 We also accounted for medica- Effectiveness of Cardiovascular Disease of eligible members to the 3 study arms tion on hand at randomization and ignored Therapies (PATIENT) study was a ran- (usual care and 2 intervention arms) in a any medication remaining at the end of domized pragmatic clinical trial in which 1:1:1 ratio at the study outset and repeated follow-up. We computed the modified 21,752 adults were randomly assigned to this process for newly eligible members Proportion of Days Covered separately for receive either usual care or 1 of 2 HIT- for each of the following 5 months. Study statins and ACEI/ARBs. To simplify enroll- based interventions designed to increase enrollment began in December 2011 and ment logistics, we defined study eligibility adherence to statins, angiotensin-convert- continued through May 2012. Interven- at baseline using the simpler Medication ing enzyme inhibitors (ACEIs), and angio- tion and outcome assessment continued Possession Ratio, which we computed by tensin II receptor blockers (ARBs). Before through November 2012. dividing total days’ dispensed supply by randomization at baseline, a subgroup of In the first intervention arm, IVR, par- 365 and capping at 1. potentially eligible individuals (n = 2965) ticipants received automated phone calls We used the EMR to capture age, race, were recruited to participate in an inter- when they were due or overdue for a refill sex, physical and mental health comorbidi- viewer-administered survey via telephone of their ACE/ARB and/or statin. Patients ties, smoking status, body mass index, num- in English, which was conducted centrally were offered a transfer to KP’s automated ber of medications dispensed, health care by a team of experienced interviewers. The pharmacy refill line. In the second inter- utilization, hospital and Emergency Depart- baseline survey was administered from vention arm, enhanced IVR, participants ment visits, and blood pressure and lipid lev- September through December 2011 and received the same calls as in the IVR arm els. We defined baseline systolic and diastolic had a completion rate of 57% (n = 1678). but also received a personalized reminder blood pressure levels as the mean of the 6 Among those who completed the survey, letter if they were 60 to 90 days overdue most recent measurements taken during the 833 respondents ultimately were randomly and a live outreach call if they were 90 days 12 months before randomization. Follow-up assigned to participate in the intervention. or more overdue, as well as EMR-based blood pressure was defined as the mean of the Data for the present study were based on feedback to their primary care clinicians. 6 most recent measurements taken before the this subgroup of individuals. Participants in the enhanced IVR arm end of the study period, which ranged from received additional written and graphic 6 to 12 months of follow-up depending on Research Setting materials, including a personalized health when randomization occurred. We defined Participants were members of 1 of 3 Re- report with their most recent blood pres- blood pressure control as blood pressure gions of Kaiser Permanente (KP), a health sure and cholesterol levels, a pill organizer, below 140/90 mmHg and lipid control as maintenance organization providing and bimonthly mailings to answer com- a low-density-lipoprotein cholesterol level comprehensive, prepaid health care to its mon questions. The IVR call scripts, let- below 100 mg/dL. members. The three Regions, Northwest ters, and other mailings were written at a Survey Data (KPNW), Hawaii (KPHI), and Georgia sixth-grade reading level. Participants were asked three single- (KPGA), collectively serve a population item health literacy questions (see Side- of about 944,000 individuals. The insti- Study Measurements bar: Health Literacy Questions). The first tutional review boards at all 3 study sites Electronic Medical Record Data question, used previously by Williams and approved the study. An external data and We used a modified version of the Pro- colleagues,27 aimed to assess participants’ safety monitoring board and local clinician portion of Days Covered for our primary use of a surrogate reader: “How often do advisory boards at each site approved the measure of medication adherence.25 Because you need to have someone help you when study protocol and monitored the study we were measuring long-term medications you read instructions, pamphlets, or other for safety and data quality. that the patients were known to be taking written materials from your doctor or

The Permanente Journal/Perm J 2016 Summer;20(3):15-200 39 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

Table 1. Characteristics of study population, total and by health literacy level Health literacy level Total Low High Characteristic (N = 833) (n = 148) (n = 685) Significancea Age, years (mean ± SD ) 65.2 ± 11.6 69.5 ± 13.2 64.3 ± 11.0 t = -5.01, p = < 0.001 Sex, % Women 51.0 51.3 50.9 χ2 = 0.008, p = 0.93 Men 49.0 48.7 49.1 Race/ethnicity, % Asian 12.9 19.1 11.6 χ2 = 10.70, p = 0.03 Black/African American 17.0 12.9 17.9 Native Hawaiian/Pacific Islander 6.1 5.4 6.2 White 57.7 53.1 58.7 Other 6.3 9.5 5.6 Hispanic 2.7b 1.0c 3.06d χ2 = 1.31, p = 0.25 Highest level of education, % High school or less 34.3 60.8 28.5 χ2 = 34.82, p = < 0.001 Some college/college degree 53.9 33.8 58.2 Some graduate school/graduate degree 11.9 5.4 13.3 Household income, % < $25,000 20.6 36.9 17.3 χ2 = 39.21, p = < 0.001 $25,000-$49,000 35.5 43.4 33.8 $50,000-$74,999 20.5 10.7 22.5 ≥ $75,000 23.4 9.0 26.4 Marital status, % Single 13.3 10.8 13.9 χ2 = 5.48, p = 0.07 Married/partnered 62.8 58.1 63.9 Separated/divorced/widowed 23.8 31.1 22.2 Health history Uncontrolled blood pressure,% 14.7 19.3 13.7 χ2 = 3.03, p = 0.08 Uncontrolled LDL cholesterol, % 30.2 27.3 30.8 χ2 = 0.59, p = 0.44 Baseline statin adherence among users, mean ± SD 0.59 ± 0.27 0.60 ± 0.25 0.59 ± 0.27 t = -0.11, p = 0.91 Baseline ACEI/ARB adherence among users, mean ± SD 0.65 ± 0.30 0.62 ± 0.32 0.66 ± 0.29 t = 1.11, p = 0.27 No. of medications dispensed, % 1-5 39.1 41.9 38.5 χ2 = 0.17, p = 0.68 6-12 39.1 32.4 40.6 ≥ 13 21.7 25.7 20.9 ED visit in last 6 months, % 10.6 13.5 9.9 χ2 = 1.66, p = 0.20 Hospitalization in last 6 months, % 4.2 3.4 4.4 χ2 = 0.30, p = 0.58 Health care utilization in last 6 months, mean 6.5 ± 6.8 7.8 ± 8.3 6.2 ± 6.3 t = −2.64, p = 0.01 HUI2, mean ± SD 0.84 ± 0.17 0.79 ± 0.20 0.85 ± 0.17 t = 3.06, p = 0.00 HUI3, mean ± SD 0.77 ± 0.28 0.60 ± 0.35 0.80 ± 0.25 t = 7.43, p = < 0.001 Satisfied with care, % 93.0 92.6 93.1 χ2 = 0.06, p = 0.81 Depression diagnosis, % 3.4 6.1 2.8 χ2 = 4.10, p = 0.04 BMI,e % 18.5-24.9 11.8 14.9 11.1 χ2 = 3.30, p = 0.07 25.0-29.9 29.7 39.2 27.8 30.0-39.9 47.2 35.1 49.7 ≥ 40 11.3 10.8 11.4 Smoker, % 10.1 11.2 9.9 χ2 = 0.23, p = 0.23 a Two-sided p values based on F test for continuous variables, Pearson χ2 test for unordered categorical data, and Mantel-Haenszel χ2 test for ordered categorical data; b N = 589. c n = 1. d n = 15. e kg/m2. ACEI/ARB = angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker; BMI = body mass index; ED = Emergency Department; HUI = Health Utilities Index mark; LDL = low-density lipoprotein; SD = standard deviation.

40 The Permanente Journal/Perm J 2016 Summer;20(3):15-200 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

pharmacy?” Participants responded using a Participants were asked whether they Because the study was not designed to five-item Likert scale ranging from “never” were satisfied with the care they received examine whether the intervention effects to “always.” We considered participants from their clinicians and whether they differed by health literacy level, these post who indicated that they “always” or “often” could indicate that they were “very satis- hoc analyses are inevitably exploratory in needed help as having low health literacy fied,” “satisfied,” “uncertain,” “unsatisfied,” nature, and we made no adjustment for for this question. The second question, or “very unsatisfied.” Individuals were multiple comparisons or to conduct ret- used by Chew and colleagues,28,29 aimed categorized as satisfied with their health rospective power calculations. Statistical to assess participants’ confidence with care if they endorsed that they were either software (SAS v9.2, SAS Institute, Cary, medical forms: “How confident are you “very satisfied” or “satisfied” in response NC) was used for statistical analyses. filling out medical forms by yourself?” to this question. Participants responded using a five-item Finally, participants were asked about RESULTS Likert scale ranging from “not at all” to their highest level of schooling completed, The study population was approximately “extremely.” We considered participants total household income, and marital status. 65 years of age on average, equally men who indicated that they were “not at all” and women, predominantly white (ap- or “a little bit” confident as having low Statistical Analysis proximately 58%), had some college or a health literacy for this question. The third Among those who participated in the college degree (approximately 54%), were question, also used by Williams and col- baseline survey (N = 1678), complete middle income, and were currently married leagues,27 aimed to assess participants’ health literacy and intervention outcome or with a partner (approximately 63%). Ap- self-rated reading ability: “How would data were available for only 833 of these proximately 18% of participants had low you rate your ability to read?” Participants individuals. The other 845 individuals who health literacy (n = 148). Participants who responded using a six-item Likert scale completed the survey were not randomly had low health literacy were more likely to ranging from “very poor” to “excellent.” assigned to participate in the intervention. be older, have a lower level of education, We considered participants who indicated Therefore, our analyses are restricted to this report a lower total household income, use that their reading ability was “very poor” or subset of 833 participants. For bivariate health care services more frequently, report “poor” as having low health literacy for this analyses, we used t-tests for comparisons poorer health status, and have a depression question. For the purposes of this study, of means of continuous variables, Pearson diagnosis compared with participants who we assigned individuals to the low health χ2 tests for comparing unordered categori- had higher health literacy (Table 1). literacy group if their responses met those cal data, and Mantel-Haenszel χ2 tests Although both the IVR and enhanced criteria on any of the three questions. for comparing ordered categorical data. IVR interventions increased adherence to Participants were asked about their cur- Separate analyses were conducted for users statins and ACEIs/ARBs compared with rent health status and health-related quality of statins and users of ACEI/ARBs. We as- usual care in the full trial analysis, in this of life using the Health Utilities Index. Both sessed whether intervention effects differed much smaller sample we did not observe the Mark 2 and Mark 3 Health Utilities by health literacy level in general linear statistically significant differences between Index instruments were used to provide a models with main effects for treatment either IVR or enhanced IVR and usual care comprehensive health status classification arm, health literacy, and their interaction. in subgroups defined by health literacy based on the domains of health and levels of Main effect estimates were adjusted for status (Table 2). Of more immediate rel- functional ability/disability in each domain. site and sex. We assessed follow-up from evance to the focus of this exploratory anal- These domains included vision, hearing, randomization until the end of the study ysis, however, the data were suggestive of speech, ambulation, dexterity, cognition, or loss of Health Plan coverage, whichever differential intervention effects for low and pain, self-care, and emotion.30 came first. high health literacy. Among participants

Table 2. Analysis of adherence by health literacy level Follow-up Enhanced Interactive Enhanced interactive voice Interactive voice adherence by interactive voice voice Usual recognition vs usual care recognition vs usual care health literacy level recognition recognition care Δa Significanceb Δa Significanceb Adherence to statins (interaction p = 0.202) Low 0.61 ± 0.034c 0.56 ± 0.36 0.52 ± 0.32 0.105 (-0.035, 0.246) 0.143 0.09 (-0.061, 0.241) 0.244 High 0.58 ± 0.34 0.58 ± 0.29 0.59 ± 0.32 -0.026 (-0.094, 0.042) 0.460 -0.032 (-0.101, 0.036) 0.359 Adherence to ACEI/ARBs (interaction p = 0.116) Low 0.70 ± 0.32 0.62 ± 0.37 0.52 ± 0.33 0.146 (-0.023, 0.316) 0.091 0.075 (-0.091, 0.241) 0.375 High 0.58 ± 0.37 0.62 ± 0.31 0.62 ± 0.31 -0.053 (-0.133, 0.027) 0.196 -0.011 (-0.089, 0.067) 0.780 a Net intervention effect, expressed as mean (and 95% confidence interval). b Two-tailed significance level based on linear regression analysis adjusting for site and sex as fixed main effects. Health literacy subgroup analyses also include the corresponding treatment by subgroup interaction. c Raw, unadjusted adherence, expressed as mean ± standard deviation. ACEI/ARB = angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker.

The Permanente Journal/Perm J 2016 Summer;20(3):15-200 41 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

with low health literacy, for example, the who decided to participate in the survey … lower health literacy IVR and enhanced IVR interventions were may differ from those who declined to associated with statin adherence that was populations may be more participate. For example, previous stud- 9% to 10.5% higher than for usual care. responsive to this type ies suggest that certain subgroups may By contrast, among participants with high of interactive voice recognition- be less likely to participate in telephone health literacy, statin adherence in the IVR based intervention compared surveys, including men, those with less and enhanced IVR groups was 2.6% to with higher health literacy education, and individuals in poorer 3.2% lower than for usual care. populations, a finding that health.56-58 Third, because the survey was We observed a similar pattern for ACEI/ may lead to even more efficient administered only in English, individuals ARB adherence. Participants with low patient outreach. for whom English was a second language health literacy in either IVR group (IVR and/or who were uncomfortable or unable or enhanced IVR) had ACEI/ARB adher- to complete the survey in English were not ence that was 7.5 percentage points to 14.6 Individuals with low health literacy in included; therefore, our findings cannot be percentage points higher than for usual the present study were more likely to have generalized to these populations. Fourth, care, whereas among participants with high poorer health-related quality of life and a although we used 3 well-validated, reliable, health literacy the IVR and enhanced IVR depression diagnosis compared with those single-item measures for identifying poor interventions were associated with ACEI/ with high health literacy. Prior studies have health literacy,59 our summed health literacy ARB adherence that was 1.1 percentage consistently reported that lower health score based on these 3 items has not been points to 5.3 percentage points lower literacy populations frequently experience compared against one of the gold standard than for usual care. However, although poorer health status as indicated by 1) instruments, such as the Rapid Estimate consistent with an interaction effect, none specific biochemical and biometric health of Adult Literacy in Medicine60 or the Test of the tests of health literacy by treatment outcomes such as higher blood pressure37,40 of Functional Health Literacy in Adults.61 interactions was statistically significant. and poor control of Type 2 diabetes,32,41,42 However, Hardie and colleagues51 simi- 2) disease prevalence and incidence such as larly provided a summed health literacy DISCUSSION higher rates of depression,43-46 and 3) global score based on participants’ responses to Although not statistically significant, the health status.31,33,38,47-49 In contrast to pre- 3 single-item questions and reported that differences in observed intervention effects vious studies, individuals with low health these questions correctly identified indi- for high vs low health literacy in the study literacy in this study were not more likely viduals with inadequate health literacy sample are certainly consistent with the hy- to have Emergency Department visits or 90% to 95% of the time. Therefore, we pothesis that individuals with lower health hospitalizations in the previous six months feel confident that we have accurately literacy may derive greater benefit from compared with individuals with higher categorized the individuals who have low this type of intervention compared with health literacy.50-53 They were, however, health literacy in our population. Another individuals with higher health literacy. In more likely to use other health services benefit of using these 3 items includes a a review of promising HIT interventions such as regular office visits compared with shorter time burden for patients, as they for diabetes, Boren21 identified telephone individuals with higher health literacy. take only a few minutes to complete (in interventions for education, counseling, Interestingly, individuals with low contrast to the Test of Functional Health and reminding as an appropriate method health literacy did not differ from indi- Literacy in Adults, which can take up to for individuals with limited health literacy. viduals with high health literacy with 30 minutes). In addition, these questions Our results provide some preliminary sup- respect to baseline statin or ACEI/ARB pose less risk of embarrassment to patients port for this notion. adherence. Although one study found a in contrast to the Rapid Estimate of Adult Approximately 18% of the study positive association between poor health Literacy in Medicine, which asks patients population in the present study had low literacy and low adherence to cardiovas- to read aloud medical terms such as herpes, health literacy; this estimate is generally cular medications,54 a recent systematic testicle, and hemorrhoids. consistent with prior studies. Depending review examining this phenomenon con- on the study population and health lit- cluded that the current evidence does not CONCLUSIONS eracy measure employed, the prevalence show a consistent relationship between Attractive features of health interven- of low health literacy ranges from 11% to health literacy and medication adherence tions include both effectiveness and cost 44%.31-35 Also consistent with the prior in adults with CVD or diabetes.55 savings. With use of HIT and automation literature, we found that individuals with The present study has several limita- of the delivery of such health education lower health literacy are more likely to be tions. First, the small intervention effect messaging, there are possible cost savings of lower socioeconomic status compared seen in the parent trial, combined with associated with reduced personnel time.62 with higher health literacy individuals. the much smaller sample size for this Furthermore, our findings suggest that For example, other studies have similarly analysis, greatly limits our power to detect lower health literacy populations may reported that years of school complet- significant interactions. Second, although be more responsive to this type of IVR- ed31-34,36-39 and income32-34,38,39 are signifi- the survey completion rate was satisfac- based intervention compared with higher cantly associated with health literacy level. tory (approximately 57%), individuals health literacy populations, a finding that

42 The Permanente Journal/Perm J 2016 Summer;20(3):15-200 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

may lead to even more efficient patient adherence. Am J Manag Care 2011 Dec;17(12 Spec and persistence using automated databases. No.):SP79-87. Pharmacoepidemiol Drug Saf 2006 Aug;15(8):565- outreach. By allowing the health system 10. Derose SF, Green K, Marrett E, et al. Automated 74; discussion 575-7. DOI: http://dx.doi.org/10.1002/ to better tailor intervention activities to outreach to increase primary adherence to pds.1230. specific patient characteristics, limited cholesterol-lowering medications. JAMA Intern Med 26. Vollmer WM, Xu M, Feldstein A, Smith D, 2013 Jan 14;173(1):38-43. DOI: http://dx.doi.org/ Waterbury A, Rand C. Comparison of pharmacy- financial resources can be allocated where 10.1001/2013.jamainternmed.717. based measures of medication adherence. BMC there is the potential for the greatest im- 11. Christakis DA, Garrison MM, Lozano P, Meischke H, Health Serv Res 2012 Jun 12;12:155. DOI: pact. Future studies are needed to explore Zhou C, Zimmerman FJ. Improving parental http://dx.doi.org/10.1186/1472-6963-12-155. adherence with asthma treatment guidelines: a 27. Williams MV, Parker RM, Baker DW, et al. the most effective and efficient methods randomized controlled trial of an interactive website. Inadequate functional health literacy among for identifying and reaching individuals Acad Pediatr 2012 Jul-Aug;12(4):302-11. DOI: http:// patients at two public hospitals. JAMA 1995 Dec with lower health literacy. v dx.doi.org/10.1016/j.acap.2012.03.006. 6;274(21):1677-82. DOI: http://dx.doi.org/10.1001/ 12. McMahon GT, Fonda SJ, Gomes HE, Alexis G, jama.1995.03530210031026. Conlin PR. A randomized comparison of online- and 28. Chew LD, Griffin JM, Partin MR, et al. Validation of Disclosure Statement telephone-based care management with internet screening questions for limited health literacy in a The author(s) have no conflicts of interest to training alone in adult patients with poorly controlled large VA outpatient population. J Gen Intern Med disclose. type 2 diabetes. Diabetes Technol Ther 2012 2008 May;23(5):561-6. DOI: http:/dx.doi.org/10.1007/ Nov;14(11):1060-7. DOI: http://dx.doi.org/10.1089/ s11606-008-0520-5. dia.2012.0137. 29. Chew LD, Bradley KA, Boyko EJ. Brief questions Acknowledgment 13. Piette JD, Weinberger M, Kraemer FB, McPhee SJ. to identify patients with inadequate health literacy. Kathleen Louden, ELS, of Louden Health Impact of automated calls with nurse follow-up on Fam Med 2004 Sep;36(8):588-94. Communications provided editorial assistance. diabetes treatment outcomes in a Department of 30. Horsman J, Furlong W, Feeny D, Torrance G. The Veterans Affairs health care system: a randomized Health Utilities Index (HUI): concepts, measurement controlled trial. Diabetes Care 2001 Feb;24(2):202-8. properties and applications. Health Qual Life How to Cite this Article DOI: http://dx.doi.org/10.2337/diacare.24.2.202. Outcomes 2003 Oct 16;1:54. DOI: http://dx.doi. Owen-Smith AA, Smith DH, Rand CS, et al. 14. Vervloet M, Linn AJ, van Weert JC, de Bakker DH, org/10.1186/1477-7525-1-54. Difference in effectiveness of medication adherence Bouvy ML, van Dijk L. The effectiveness of 31. Gazmararian JA, Baker DW, Williams MV, et al. intervention by health literacy level. Perm J 2016 interventions using electronic reminders to improve Health literacy among Medicare enrollees in a Summer;20(3):15-200. DOI: http://dx.doi.org/ adherence to chronic medication: a systematic review managed care organization. JAMA 1999 Feb of the literature. J Am Med Inform Assoc 2012 Sep- 10;281(6):545-51. DOI: http://dx.doi.org/10.1001/ 10.7812/TPP/15-200. Oct;19(5):696-704. DOI: http://dx.doi.org/10.1136/ jama.281.6.545. amiajnl-2011-000748. 32. Kim S, Love F, Quistberg DA, Shea JA. Association 15. Bodie GD, Dutta MJ. Understanding health literacy of health literacy with self-management behavior References for strategic health marketing: eHealth literacy, in patients with diabetes. Diabetes Care 2004 1. Naderi SH, Bestwick JP, Wald DS. Adherence health disparities, and the digital divide. Health Dec;27(12):2980-2. DOI: http://dx.doi.org/10.2337/ to drugs that prevent cardiovascular disease: Mark Q 2008;25(1-2):175-203. DOI: http://dx.doi. diacare.27.12.2980. meta-analysis on 376,162 patients. Am J Med org/10.1080/07359680802126301. 33. Sudore RL, Mehta KM, Simonsick EM, et al. Limited Sep;125(9):882-7.e1. DOI: http://dx.doi.org/10.1016/ 16. Norman CD, Skinner HA. eHealth literacy: essential literacy in older people and disparities in health j.amjmed.2011.12.013. skills for consumer health in a networked world. and healthcare access. J Am Geriatr Soc 2006 2. Ho PM, Bryson CL, Rumsfeld JS. Medication J Med Internet Res 2006;8(2):e9. DOI: http://dx.doi. May;54(5):770-6. DOI: http://dx.doi.org/10.1111/ adherence: its importance in cardiovascular org/10.2196/jmir.8.2.e9. j.1532-5415.2006.00691.x. outcomes. Circulation 2009 Jun 16;119(23): 17. Healthy People 2010: Understanding and improving 34. von Wagner C, Knight K, Steptoe A, Wardle J. 3028-35. DOI: http://dx.doi.org/10.1161/ health. 2nd ed. Washington, DC: US Department of Functional health literacy and health-promoting CIRCULATIONAHA.108.768986. Health and Human Services; 2000. behavior in a national sample of British adults. J 3. Thinking outside the pillbox: a system-wide approach 18. Bickmore TW, Pfeifer LM, Byron D, et al. Usability of Epidemiol Community Health 2007 Dec;61(12):1086- to improving patient medication adherence for conversational agents by patients with inadequate 90. DOI: http://dx.doi.org/10.1136/jech.2006.053967. chronic disease. Cambridge, MA: New England health literacy: evidence from two clinical trials. J 35. Adeseun GA, Bonney CC, Rosas SE. Health Healthcare Institute; 2009 Aug 12. p 12-4. Health Commun 2010;15 Suppl 2:197-210. DOI: literacy associated with blood pressure but not other 4. Sokol MC, McGuigan KA, Verbrugge RR, http://dx.doi.org/10.1080/10810730.2010.499991. cardiovascular disease risk factors among dialysis Epstein RS. Impact of medication adherence 19. Bickmore TW, Paasche-Orlow MK. The role of patients. Am J Hypertens 2012 Mar;25(3):348-53. on hospitalization risk and healthcare cost. Med information technology in health literacy research. DOI: http://dx.doi.org/10.1038/ajh.2011.252. Care 2005 Jun;43(6):521-30. DOI: http://dx.doi. J Health Commun 2012;17 Suppl 3:23-9. 36. Mancuso JM. Impact of health literacy and patient org/10.1097/01.mlr.0000163641.86870.af. 20. Kutner M, Greenberg E, Jin Y, Paulsen C. The health trust on glycemic control in an urban USA population. 5. Steiner JF. Rethinking adherence. Ann Intern literacy of America’s adults: results from the 2003 Nurs Health Sci 2010 Mar;12(1):94-104. DOI: http:// Med 2012 Oct 16;157(8):580-5. DOI: http://dx.doi. National Assessment of Adult Literacy. Washington, dx.doi.org/10.1111/j.1442-2018.2009.00506.x. org/10.7326/0003-4819-157-8-201210160-00013. DC: US Department of Education; 2006 Sep. 37. Pandit AU, Tang JW, Bailey SC, et al. Education, 6. Haynes RB, Ackloo E, Sahota N, McDonald HP, 21. Boren SA. A review of health literacy and diabetes: literacy, and health: mediating effects on Yao X. Interventions for enhancing medication opportunities for technology. J Diabetes Sci Technol hypertension knowledge and control. Patient Educ adherence. Cochrane Database Syst Rev 2008 2009 Jan;3(1):202-9. Couns 2009 Jun;75(3):381-5. DOI: http://dx.doi. Apr 16;(2):CD000011. DOI: http://dx.doi.org/ 22. Piette JD. Interactive voice response systems in org/10.1016/j.pec.2009.04.006. 10.1002/14651858.CD000011.pub3. the diagnosis and management of chronic disease. 38. Wolf MS, Gazmararian JA, Baker DW. Health literacy 7. Misono AS, Cutrona SL, Choudhry NK, et al. Am J Manag Care 2000 Jul;6(7):817-27. and functional health status among older adults. Healthcare information technology interventions to 23. Health literacy: a prescription to end confusion Arch Intern Med 2005 Sep 26;165(17):1946-52. DOI: improve cardiovascular and diabetes medication [Internet]. Washington, DC: Institute of Medicine; http://dx.doi.org/10.1001/archinte.165.17.1946. adherence. Am J Manag Care 2010 Dec;16(12 Suppl 2004 Apr [cited 2014 Jul 30]. Available from: www. 39. Kim SH. Health literacy and functional health HIT):SP82-92. iom.edu/~/media/Files/Report%20Files/2004/ status in Korean older adults. J Clin Nurs 2009 8. Howren MB, Van Liew JR, Christensen AJ. Advances Health-Literacy-A-Prescription-to-End-Confusion/ Aug;18(16):2337-43. DOI: http://dx.doi.org/10.1111/ in patient adherence to medical treatment regimens: healthliteracyfinal.pdf. j.1365-2702.2008.02739.x. the emerging role of technology in adherence 24. Vollmer WM, Owen-Smith A, Tom JO, et al. Improving 40. Powers BJ, Olsen MK, Oddone EZ, Thorpe CT, monitoring and management. Social and Personality adherence to cardiovascular disease medications Bosworth HB. Literacy and blood pressure—do Psychology Compass 2013 July;7(7): with information technology. Am J Manag Care 2014 healthcare systems influence this relationship? A 427-43. DOI: http://dx.doi.org/10.1111/spc3.12033. Nov;20(11 Spec no. 17):SP502-10. cross-sectional study. BMC Health Serv Res 2008 9. Vollmer WM, Feldstein A, Smith DH, et al. Use of 25. Andrade SE, Kahler KH, Frech F, Chan KA. Oct 23;8:219. DOI: http://dx.doi.org/10.1186/1472- health information technology to improve medication Methods for evaluation of medication adherence 6963-8-219.

The Permanente Journal/Perm J 2016 Summer;20(3):15-200 43 ORIGINAL RESEARCH & CONTRIBUTIONS Difference in Effectiveness of Medication Adherence Intervention by Health Literacy Level

41. Williams MV, Baker DW, Parker RM, Nurss JR. 48. Baker DW, Parker RM, Williams MV, Clark WS, or diabetes medication and health literacy in older Relationship of functional health literacy to patients’ Nurss J. The relationship of patient reading ability to adults. Ann Pharmacother 2012 Jun;46(6):863-72. knowledge of their chronic disease. A study of self-reported health and use of health services. Am DOI: http://dx.doi.org/10.1345/aph.1q718. patients with hypertension and diabetes. Arch Intern J Public Health 1997 Jun;87(6):1027-30. DOI: http:// 56. Hoeymans N, Feskens EJ, Van Den Bos GA, Med 1998 Jan 26;158(2):166-72. DOI: http://dx.doi. dx.doi.org/10.2105/ajph.87.6.1027. Kromhout D. Non-response bias in a study of org/10.1001/archinte.158.2.166. 49. Weiss BD, Blanchard JS, McGee DL, et al. Illiteracy cardiovascular diseases, functional status and self- 42. Schillinger D, Grumbach K, Piette J, et al. Association among Medicaid recipients and its relationship to rated health among elderly men. Age Ageing 1998 of health literacy with diabetes outcomes. JAMA health care costs. J Health Care Poor Underserved Jan;27(1):35-40. DOI: http://dx.doi.org/10.1093/ 2002 Jul 24-31;288(4):475-82. DOI: http://dx.doi. 1994;5(2):99-111. DOI: http://dx.doi.org/10.1353/ ageing/27.1.35. org/10.1001/jama.288.4.475. hpu.2010.0272. 57. Korkeila K, Suominen S, Ahvenainen J. Non- 43. Gazmararian J, Baker D, Parker R, Blazer DG. 50. Marrie RA, Salter A, Tyry T, Fox RJ, Cutter GR. response and related factors in a nation-wide health A multivariate analysis of factors associated with Health literacy association with health behaviors survey. Eur J Epidemiol 2001;17(11):991-9. depression: evaluating the role of health literacy as and health care utilization in multiple sclerosis: a 58. Van Loon AJ, Tijhuis M, Picavet HS, Surtees PG, a potential contributor. Arch Intern Med 2000 Nov cross-sectional study. Interact J Med Res 2014 Feb Ormel J. Survey non-response in the Netherlands: 27;160(21):3307-14. DOI: http://dx.doi.org/10.1001/ 10;3(1):e3. DOI: http://dx.doi.org/10.2196/ijmr.2993. effects on prevalence estimates and associations. archinte.160.21.3307. 51. Hardie NA, Kyanko K, Busch S, Losasso AT, Ann Epidemiol 2003 Feb;13(2):105-10. DOI: http:// 44. Gordon MM, Hampson R, Capell HA, Madhok R. Levin RA. Health literacy and health care spending dx.doi.org/10.1016/s1047-2797(02)00257-0. Illiteracy in rheumatoid arthritis patients as and utilization in a consumer-driven health plan. 59. Powers BJ, Trinh JV, Bosworth HB. Can this patient determined by the Rapid Estimate of Adult Literacy J Health Commun 2011;16 Suppl 3:308-21. DOI: read and understand written health information? in Medicine (REALM) score. Rheumatology (Oxford) http://dx.doi.org/10.1080/10810730.2011.604703. JAMA 2010 Jul 7;304(1):76-84. DOI: http://dx.doi. 2002 Jul;41(7):750-4. DOI: http://dx.doi.org/10.1093/ 52. Mitchell SE, Sadikova E, Jack BW, Paasche- org/10.1001/jama.2010.896. rheumatology/41.7.750. Orlow MK. Health literacy and 30-day postdischarge 60. Davis TC, Long SW, Jackson RH, et al. Rapid estimate 45. TenHave TR, Van Horn B, Kumanyika S, Askov E, hospital utilization. J Health Commun 2012;17 Suppl of adult literacy in medicine: a shortened screening Matthews Y, Adams-Campbell LL. Literacy 3:325-38. DOI: http://dx.doi.org/10.1080/10810730. instrument. Fam Med 1993 Jun;25(6):391-5. assessment in a cardiovascular nutrition education 2012.715233. 61. Parker RM, Baker DW, Williams MV, Nurss JR. The setting. Patient Educ Couns 1997 Jun;31(2):139-50. 53. Omachi TA, Sarkar U, Yelin EH, Blanc PD, Katz PP. test of functional health literacy in adults: a new DOI: http://dx.doi.org/10.1016/s0738-3991(97)01003-3. Lower health literacy is associated with poorer instrument for measuring patients’ literacy skills. J 46. Zaslow MJ, Hair EC, Dion MR, Ahluwalia SK, health status and outcomes in chronic obstructive Gen Intern Med 1995 Oct;10(10):537-41. DOI: http:// Sargent J. Maternal depressive symptoms and pulmonary disease. J Gen Intern Med 2013 dx.doi.org/10.1007/bf02640361. low literacy as potential barriers to employment in Jan;28(1):74-81. DOI: http://dx.doi.org/10.1007/ 62. Noell J, Glasgow RE. Interactive technology a sample of families receiving welfare: are there s11606-012-2177-3. applications for behavioral counseling: issues and two-generational implications? Women Health 54. Kripalani S, Gatti ME, Jacobson TA. Association of opportunities for health care settings. Am J Prev 2001;32(3):211-51. DOI: http://dx.doi.org/10.1300/ age, health literacy, and medication management Med 1999 Nov;17(4):269-74. DOI: http://dx.doi. j013v32n03_03. strategies with cardiovascular medication adherence. org/10.1016/S0749-3797(99)00093-8. 47. Berkman ND, Sheridan SL, Donahue KE, et al. Patient Educ Couns 2010 Nov;81(2):177-81. DOI: Health literacy interventions and outcomes: an http://dx.doi.org/10.1016/j.pec.2010.04.030. updated systematic review. Evid Rep Technol Assess 55. Loke YK, Hinz I, Wang X, Salter C. Systematic review (Full Rep) 2011 Mar;(199):1-941. of consistency between adherence to cardiovascular

People Are Not Like This

Nowadays people are not like this [ie, temperate in eating and drinking]; they use wine as beverage and they adopt reckless behavior … . Their passions exhaust their vital forces; their cravings dissipate their true [essence]; they do not know how to find contentment within themselves; they are not skilled in the control of their spirits. They devote all their attention to the amusement of their minds, thus cutting themselves off from the joys of long [life]. Their rising and retiring is without regularity. For these reasons they reach only one half of the hundred years and then they degenerate.

— The Yellow Emperor’s Classic of Internal Medicine, Huangdi, c 2704 BC - 2598 BC, known as the Yellow Emperor, a legendary Chinese sovereign and culture hero

44 The Permanente Journal/Perm J 2016 Summer;20(3):15-200 ORIGINAL RESEARCH & CONTRIBUTIONS Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model

Michelle T Jesse, PhD; Elizabeth Rubinstein; Anne Eshelman, PhD, ABPP; Corinne Wee; Mrunalini Tankasala; Jia Li, PhD; Marwan Abouljoud, MD, CPE, MMM, FACS Perm J 2016 Summer;20(3):15-207 E-pub: 07/13/2016 http://dx.doi.org/10.7812/TPP/15-207

ABSTRACT and mental health.21 Additionally, the Background: Patients pursuing organ transplantation have complex medical needs, positive effects of educational interven- undergo comprehensive evaluation for possible listing, and require extensive education. tions are sustained longer with support However, transplant patients and their supports frequently report the need for more involvement.21 Both transplant patients lifestyle and self-management strategies for living with organ transplantation. and their supports report the need for Objectives: First, to explore feasibility of a successful, patient-run transplant lifestyle more comprehensive education and, in educational group (Transplant Living Community), designed to complement medical particular, lifestyle and long-term self- care and integrated into the clinical setting; and second, to report the major themes management, because this is frequently of patients’ and supports’ qualitative and quantitative feedback regarding the group. not addressed or not adequately addressed Methods: Informal programmatic review and patient satisfaction surveys. by hospital staff.5,22-25 However, there are Results: A total of 1862 patient satisfaction surveys were disseminated and 823 were gaps in available evidence on the educa- returned (response rate, 44.2%). Patients and their supports reported positive feedback tion of support systems in the context of regarding the group, including appreciation that the volunteer was a transplant recipient organ transplantation. and gratitude for the lifestyle information. Five areas were associated with the success The provision of patient-centered care of Transplant Living Community: 1) a “champion” dedicated to the program and its suc- with efficient use of resources has become cessful integration into a multidisciplinary team; 2) a health care environment receptive the quality standard in today’s health to integration of a patient-led group with ongoing community development; 3) a high care environment.26,27 Integration of the level of visibility to physicians and staff, patients, and supports; 4) a clearly presented posttransplant patient into the plan of and manageable lifestyle plan (“Play Your ACES”a [Attitude, Compliance, Exercise, and care provides an alternative way to meet a Support]), and 5) a strong volunteer structure with thoughtful training with the ultimate quality standard that has been successful objective of volunteers taking ownership of the program. with other patient populations.28 However, Conclusion: It is feasible to integrate a sustainable patient-led lifestyle and self- strategies to address lifestyle and self-man- management educational group into a busy tertiary care clinic for patients with complex agement in organ transplant patients have chronic illnesses. been limited to information gathering (eg, patient focus groups), nurse-led education INTRODUCTION Disease management programs are consid- groups, or other multidisciplinary team- Patients with end-stage organ disease ered an important component of care for protocol refinements.3,29-31 Although these referred for possible organ transplanta- patients living with a transplanted organ5,6 are important first steps, their findings sup- tion are a highly complex, multimorbidity and have been associated with positive port the need for integration of transplant population. Given the medical and psy- outcomes such as improved patient satis- patients in the refinement of resources and chosocial complexities, including poten- faction and adherence.7,8 education on successful lifestyle and self- tial patient impairments (eg, cognitive or Patients with end-stage organ disease management strategies. physical disability) and provision of care have increased risks for cognitive impair- The purpose of this study was 2-fold: through multidisciplinary teams, these ments secondary to their illnesses.9-17 Edu- 1) to explore the feasibility of a successful, patients require a great deal of education cational programs must take into account patient-run transplant lifestyle educational on the transplant process and ongoing sup- the patient’s ability to process and recall group designed to complement medical port.1 Nurses, social workers, physicians, educational information provided.18-20 care and integrated into the clinical setting, and surgeons are the most frequent provid- Involvement of family members in the and 2) to report patients’ and supports’ ers of education to end-stage organ disease care of patients with chronic diseases qualitative and quantitative feedback re- patients who are pursuing transplant.2-4 significantly increases patient physical garding the group.

Michelle T Jesse, PhD, is a Bioscientist for the Transplant Institute and Senior Staff Psychologist in the Behavioral Health Department at the Henry Ford Health System in Detroit, MI. E-mail: [email protected]. Elizabeth Rubinstein is a Patient Advocate for the Transplant Institute at the Henry Ford Health System in Detroit, MI. E-mail: [email protected]. Anne Eshelman, PhD, ABPP, is a Senior Staff Psychologist for the Transplant Institute at the Henry Ford Health System in Detroit, MI. E-mail: [email protected]. Corinne Wee is a Research Assistant for the Transplant Institute at the Henry Ford Health System in Detroit, MI. E-mail: [email protected]. Mrunalini Tankasala is a Research Assistant for the Transplant Institute at the Henry Ford Health System in Detroit, MI. E-mail: [email protected]. Jia Li, PhD, is an Assistant Scientist in Public Health Sciences at the Henry Ford Health System in Detroit, MI. E-mail: [email protected]. Marwan Abouljoud, MD, CPE, MMM, FACS, is the Director of the Transplant Institute and Hepatobiliary Surgery for the Henry Ford Health System in Detroit, MI. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-207 45 ORIGINAL RESEARCH & CONTRIBUTIONS Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model

Transplant Living Community: focuses on the lifestyle elements of adher- of the education on self-management Program Success and Feasibility ing to a complicated treatment regimen skills and posttransplant lifestyle changes. The Henry Ford Health System Trans- amid real-life circumstances, which could Within the TLC education, both patients plant Living Community (TLC) was es- create obstacles or challenges to taking op- and supports are addressed as a team unit tablished in 2008 via a collective patient timal care of oneself—for example, explor- where specific conceptualized home sup- initiative. TLC is a patient-to-patient or- ing and strategizing on environmental or port team assignments are identified to gan transplant education program aimed social barriers that may hinder the patient’s include all family members, other sup- at increasing patient and family awareness ability to adhere. Exercise includes redefin- ports, and extended support structures. of necessary lifestyle changes throughout ing exercise to make it attainable with small For patients who undergo transplanta- the transplant process. The framework for incremental increases in activity (eg, walk- tion, a TLC ambassador visits the patient the program incorporates foundational ing 25 steps today, 35 steps tomorrow) and before discharge and provides him or her principles of successful hospice, geriatric, using charting tools to track progress. This with a TLC Toolkit complementing prior pediatric, and cancer patient advocacy. The allows for small successes to be recognized pretransplant TLC education. The TLC program is subject to institutional over- and reinforces physical activity. Lastly, sup- Toolkit contains personal health recording sight and exists as an “ambassador” (vol- unteer) program to support patients, living The primary goal of TLC is expressed to patients as “Play Your ACES!”a donors, supports, and families throughout (Attitude, Compliance, Exercise, and Support) … are not unitary constructs the transplant process. Transplant recipi- but represent an adaptive lifestyle approach while living with chronic illness. ents are welcome to volunteer (beginning the service no sooner than 10 months after the transplant) and undergo an extensive port is a multimember team for long-term tools with a tabbed notebook for Medi- training curriculum that covers empathic support. TLC defines the duties of each cations, Lab Tests, To Do Lists, Medical listening skills, appropriate medical referral person with a conceptualized approach. Records, and General Information. Other to physicians, Health Insurance Portabil- Some of the support roles include CEO materials consist of support team contact ity and Accountability Act regulations, or primary care manager, assistant CEO, and assigned duty outline, medical team TLC platform materials, and continued drivers, medication manager, comedian, contact card sleeve, calendar, medication mentoring. Training occurs during 2 full exercise buddy, spiritual caretaker, and charting tools, medication box, pill cut- days (16 hours) followed by several weeks other tangible support (eg, mowing the ter, medication travel bag, thermometer, of supervised in-clinic training with estab- lawn, making meals, babysitting). All pedometer, emergency medication key lished ambassadors. All ambassador volun- education and materials are presented in fob, surgical masks, TLC button for social teers are transplant recipients, representing the patient voice (avoiding medical jargon) experiment, hand sanitizer, “Play Your heart, lung, kidney, pancreas, liver, mul- from a patient perspective and address ACES”a support materials, food safety tivisceral, and bone marrow transplants. only lifestyle components. All medical guide, transplant lifestyle information, However, ambassadors and patients are aspects of transplant are referred directly organ donation (Gift of Life) and registry not matched based upon organ received. to medical staff and remain in the medical information, donor contact guidelines, and Ambassador volunteers provide interactive, domain. TLC provides organizational tools tote bag. The TLC ambassador volunteer onsite support within clinic and inpatient and education to help patients navigate reviews educational resources within the floors daily Monday through Friday. Since their medical care on a daily basis. TLC toolkit in addition to answering or refer- 2008, there have been more than 40 active addresses caregivers as team members and ring any questions of concern. ambassadors. provides a stylized support team approach The primary goal of TLC is expressed involving the entire family in a positive, METHODS to patients as “Play Your ACES!”a (Atti- cooperative manner throughout the con- Informal Program Evaluation tude, Compliance, Exercise, and Support), tinuum of care. TLC has undergone continuous in- which highlight important areas of self- What is truly unique about TLC, be- formal programmatic evaluation since its management skills necessary for successful sides being entirely patient run, is its suc- inception in 2008. First, as part of the transplant, with an easy-to-understand, cessful integration into routine clinical kits provided to patients, there is a feed- patient-centered approach. The elements care. Within the waiting room of the main back form for suggestions to improve any of “Play Your ACES!”a are not unitary con- clinic there is an information table, staffed resources or processes. Second, as part of structs but represent an adaptive lifestyle by an ambassador volunteer during normal a Patient Family Advisory Council, which approach while living with chronic illness. clinic hours, dedicated to providing TLC involves physicians, staff representation Attitude refers to more than positivity; it educational and related materials. Medical from each hospital unit, and TLC ambas- means having a “fighting attitude,” which personnel can also “refer” patients to TLC. sadors, all participating members provide is a more active coping strategy to manage When patients and supports return for feedback and recommendations. For the the instability of living with chronic illness the routine educational meeting (“family purposes of this article, the contributing and embracing the new normal of living meeting”), required for listing for trans- authors identified and reviewed the ele- with an organ transplant. Compliance plantation, TLC provides a component ments of TLC that were thought to have

46 The Permanente Journal/Perm J 2016 Summer;20(3):15-207 ORIGINAL RESEARCH & CONTRIBUTIONS Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model

a high level of impact on the feasibility and were invited to return surveys either di- qualitative feedback on what they liked the sustainability of the group. The results of rectly to staff or in a locked box located best and least about the TLC portion of the programmatic evaluation are in the within the clinic. Data collected in the the informational session. The assessment discussion section. survey included basic demographic char- is available online at: www.thepermanente- acteristics (sex, race/ethnicity), organ need- journal.org/files/15-207Appx1.pdf. Patient and Support Feedback Evaluation ing transplant, and whether the respondent All data were collected with full insti- was the patient, primary caregiver, or other Analyses tutional research and administrative ap- support person. Respondents were then Participant’s responses were compared proval. A patient and support satisfaction asked to rate the TLC educational program between groups by χ2 test for categori- survey was developed for the purposes of on length, helpfulness, understandability, cal variables and Kruskal-Wallis H test this study to assess patient and support whether it met expectations for educa- for continuous variables. For qualitative satisfaction with TLC-related education. tion, and confidence that the information responses, 3 of the authors (ER, CW, and The surveys were disseminated (via passive provided would help them navigate the MT) individually classified the responses consent; the cover letter that explained transplant process. They were assessed on the basis of content and assigned nu- completion of survey indicated consent) for recall of basic information presented merical labels to the comments (dummy before the TLC component of the rou- in the TLC portion of the presentation coding) corresponding to thematic con- tine educational meeting for listing for (eg, “What does ACES stand for?” and tent. Following dummy coding, all numer- transplant and were entirely anonymous asked to write in a response). Lastly, they ics were sent to another author (MJ), who to maximize response rates. Respondents were given the opportunity to provide reviewed the data and selected scoring on the basis of a majority of responses. For ex- Table 1. Characteristics of 823 respondents in study of Transplant Living Communitya ample, if 2 coders reported a statement was a “2” but a third coder reported the state- Patients Primary caregivers Other supports Characteristic (n = 217) (n = 255) (n = 351) ment was a “3,” the statement was coded Sex as a “2.” Frequencies of all codes were then Men 130 (59.9) 56 (22.0) 140 (39.9) analyzed for frequency of content. Women 72 (33.2) 188 (73.7) 201 (57.3) RESULTS Hispanic/Latino Patient Evaluation and Feedback Yes 9 (4.1) 10 (3.9) 11 (3.1) Surveys were collected from January No 176 (81.1) 209 (82.0) 305 (86.9) through November 2013. Of the 1862 Prefer not to respond 5 (2.3) 5 (2.0) 2 (0.6) surveys disseminated, 823 surveys were Middle Eastern returned (response rate, 44.2%). The mean Yes 5 (2.3) 4 (1.6) 2 (0.6) (standard deviation) age of patients was No 172 (79.3) 209 (82.0) 310 (88.3) 54.1 (11.5) years, of primary supports was Prefer not to respond 4 (1.8) 5 (2.0) 3 (0.9) 51.97 (14.24) years, and of other supports Race was 46.48 (16.22) years. Additional demo- American Indian or Alaskan Native 2 (0.9) — 5 (1.4) graphic and respondent characteristics are Black or African American 70 (32.3) 57 (22.4) 64 (18.2) presented in Table 1. Other Pacific Islander 1 (0.5) 1 (0.4) 1 (0.3) Table 2 provides the frequency of cor- Asian 2 (0.9) 4 (1.6) 1 (0.3) rect responses on defining compliance and White 127 (58.5) 174 (68.2) 256 (72.9) ACES. There was no significant difference Other 5 (2.3) 2 (0.8) 6 (1.7) between respondent groups in defining Prefer not to respond 1 (0.5) 2 (0.8) 8 (2.3) ACES but there was a significant differ- Multi-ethnic 5 (2.3) 8 (3.1) 4 (1.1) ence in defining compliance, with patients Organ having the highest frequency of incorrect responses. Liver 112 (51.6) 171 (67.1) 285 (81.2) A Kruskal-Wallis H test was run to Heart — 1 (0.4) — compare patients, primary supports, and Kidney 94 (43.3) 66 (25.9) 52 (14.8) other supports on satisfaction with the Pancreas 2 (0.9) 1 (0.4) — TLC presentation. There was a statisti- Lung 1 (0.5) 1 (0.4) — cally significant difference on how con- Liver/kidney 3 (1.4) 3 (1.2) 4 (1.1) fident respondents reported feeling after Kidney/pancreas 2 (0.9) 2 (0.8) 1 (0.3) meeting with the TLC ambassador (p = Other 2 (0.9) 1 (0.4) — 0.002), with secondary supports report- a Data are presented as number (% of category) unless otherwise noted. Within categories, columns do not consistently ing the highest confidence followed by add up to the total because of missing data. primary support and lastly patients. There — = no affirmative responses.

The Permanente Journal/Perm J 2016 Summer;20(3):15-207 47 ORIGINAL RESEARCH & CONTRIBUTIONS Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model

were no significant differences between about the TLC portion of the educational (24.2%) responded. Themes identified (in respondent groups on expectations being session. Several respondents received order of frequency of occurrence) are also met (p = 0.699), information being easy more than 1 code if the content of their reported in Table 4. to follow and understand (p = 0.241), response addressed more than 1 thematic whether the information presented will area. Aspects of the program that gener- DISCUSSION help navigate the transplant process (p = ated the most frequent positive responses TLC is a unique, sustainable, patient-led 0.174), or length of the session (p = 0.364); are included in Table 4 (percentages are lifestyle and self-management educational see Table 3. out of those who provided qualitative program providing a valuable resource for For qualitative data, as scored above, feedback). When asked what they liked organ transplantation patients and their 633 of the respondents (76.9%) wrote the least about the TLC portion of the ed- caregivers. Prior research has shown that in a reply for what they liked the most ucational session, 199 of the respondents transplant patients report a lack of care- giver education and acknowledge the need for distributed educational opportunities Table 2. Responses to survey about Attitude, Compliance, Exercise, and Support during the course of transplant.5 The In- a in study of Transplant Living Community stitute of Medicine’s 2000 report32 called Patients Primary caregivers Other supports for engaging and empowering patients Survey responses (n = 217) (n = 255) (n = 351) p value in health care. Since this seminal report, What does compliance mean? patients are becoming more proactive con- Responded correctly 171 (78.8) 219 (85.9) 308 (87.8) 0.008 sumers, actively participating in their care. Responded incorrectly 39 (18.0) 32 (12.5) 32 (9.1) However, as others have outlined, practical Did not respond 7 (3.2) 4 (1.6) 11 (3.1) guidance on how to engage patients has Attitudeb been limited.33-35 For patient engagement Answered correctly 173 (79.7) 188 (73.7) 266 (75.8) 0.462 to be successful, patient education must Answered incorrectly 3 (1.4) 9 (3.5) 11 (3.1) address lifestyle skills. This education will Did not respond 41 (18.9) 58 (22.7) 74 (21.1) need to come from the patient’s perspec- Complianceb tive, complement medical care, and in- Answered correctly 171 (78.8) 191 (74.9) 271 (77.2) 0.820 volve patients, caregivers, and extended Answered incorrectly 4 (1.8) 6 (2.4) 10 (2.8) social support members. An example of Did not respond 42 (19.4) 58 (22.7) 70 (19.9) this approach, in which lifestyle methods Exerciseb are applicable across many chronic disease populations, is the TLC. Patients and sup- Answered correctly 172 (79.3) 189 (74.1) 272 (77.5) 0.500 ports reported high levels of satisfaction Answered incorrectly 1 (0.5) 5 (0.2) 4 (1.1) with the lifestyle and self-management Did not respond 44 (20.3) 61 (23.9) 75 (21.4) skills presented by the TLC. Respondents b Support also frequently indicated appreciation Answered correctly 169 (77.9) 183 (71.8) 256 (72.9) 0.163 for having an actual transplant recipient Answered incorrectly 3 (1.4) 4 (1.6) 13 (3.7) providing the information as they felt this Did not respond 45 (20.7) 68 (26.7) 82 (24.2) made the information more accessible and a Data are presented as number (% of category). Percentages may not total 100 because of rounding. gave them hope for the future. When asked b Responses to the questions: What does ACES stand for? about possible improvements, most of the responses indicated nothing, or provided Table 3. Respondent satisfaction with Transplant Living Communitya suggestions that were logistical or unre- Patients Primary support Other supports lated to TLC (eg, protocol requirements Respondent satisfaction metrics (n = 217) (n = 255) (n = 351) for transplant). Adequate or not enough time in the TLC 201 (92.6) 235 (92.2) 332 (94.6) An interesting finding was that patients information session were significantly less likely to correctly The information presented was helpful or very 204 (94.0) 240 (94.1) 323 (92.0) identify the components of compliance helpful in managing the transplant process than were primary or other supports. As The information presented was understandable 211 (97.2) 243 (95.3) 335 (95.4%) outlined in the introduction, end-stage or very understandable and easy to follow organ disease has a well-documented asso- The TLC program met or exceeded expectations 203 (93.5) 237 (92.9) 322 (91.7) ciation with the development of cognitive Respondents were mostly or completely 191 (88.0) 211 (82.7) 284 (80.9) impairments.9-17 This underlines the im- confident they could navigate the transplant portance of providing relatable lifestyle and process with the information provided by the self-management education not only to the TLC ambassador patient but also to primary and secondary a Data represent affirmative responses. Data are presented as number (% of category). supports throughout the care continuum. TLC = Transplant Living Community.

48 The Permanente Journal/Perm J 2016 Summer;20(3):15-207 ORIGINAL RESEARCH & CONTRIBUTIONS Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model

Also interesting was that secondary sup- Transplant recipients have recognized the different following repeated exposure (as ports reported the greatest confidence in value of patient-to-patient interaction.23 that is the TLC model) or the overall ex- being able to manage the transplant pro- Secondly, a health care environment must perience with the program. Second, there cess following the TLC education class. be receptive to integration of a patient-led is the potential for response bias. Patients For supports other than the patient’s pri- group with ongoing community devel- and their supports were asked to complete mary support, the TLC lifestyle and self- opment. Internally, a representative of the survey after an approximately three- management education is often their first TLC attends the selection committee to hour educational session, which owing to exposure to the seriousness and extensive advocate for patients. TLC ambassadors patient fatigue or other factors may have nature of care for organ transplants. “Other have been instrumental within the Pa- reduced our response size. Lastly, given supports” often come in knowing only that tient Family Advisory Council, driving that TLC is a well-established community their relative or friend needs a transplant the patient and family needs agenda with of ambassadors integrated into the clinic and may have had minimal tangible sup- staff in a structured fashion. Medical staff with patients routinely exposed to the port requirements placed on them. The trust has been developed and maintained TLC group, whether TLC has a significant potential of secondary supports to be con- through continual dialogue, the provision impact on patient outcomes at this time sidered as integral support team members of a consistent curriculum, field mentor- could not be determined. To ascertain to assist the primary support role has not ing of ambassadors, standardization of whether this is the case, randomized con- been explored and could be considered for lifestyle resources and related tools, and trolled trials would need to be performed. further research to determine the accuracy routine practice of referring medical ques- Future research should attempt to parse of this interpretation. tions back to medical staff. Anecdotally, the effects of similar interventions on There are a number of factors unique TLC involvement has fostered positive patient-related outcomes. However, one to the TLC and considered integral to its outcomes that reinforce ongoing trust of the true strengths of this group is its sustainability that would be useful in inte- from medical staff. At our center, there visibility and accessibility, suggesting a grating a similar program. First, a “cham- are several examples of patients who were multisite study with similar patient so- pion” or at least one person should be determined not to be transplant candidates ciodemographic characteristics would be dedicated to the program and its successful but, through interactions with TLC and its an optimal strategy. integration into a multidisciplinary team. tenants, were able to meet eligibility for listing for organ transplantation. Third, CONCLUSION the program must be accessible and vis- It is entirely feasible and sustainable to Table 4. Frequency of qualitative ible to patients, supports, and staff. TLC integrate a patient-led lifestyle and self- (themes) responses to “liked most” or has a centralized presence on the clinic management educational group into a “liked least” about Transplant Living floor via an educational table full of re- busy tertiary care clinic for patients with Communitya sources manned by a TLC ambassador complex chronic illnesses. This requires in addition to TLC dedicated e-mail a receptive and supportive health care Theme for “liked most” and voicemail access. Fourth, a clearly environment, a coordinated and cohesive The volunteer/that the volunteer 359 (56.7) was a transplant recipient presented and manageable lifestyle plan patient volunteer structure, and continued (“Play Your ACES”a) is needed. Related improvement. Furthermore, overwhelm- Information provided 195 (30.8) information and resources are presented ingly positive feedback from patients and Overall positive experience with 69 (10.9) the program in a clear and useful format accessible to their supports regarding such a group most patients. Resources (eg, informa- suggest that these groups could provide Quality of the presentation 66 (10.4) tional packet, brochures) are routinely substantial benefits in the care of complex Have a reference for lifestyle- 21 (3.3) v related questions evaluated and updated or improved to illnesses. maximize utility and accuracy. Lastly, a Theme for “liked least” a strong volunteer structure with thoughtful “Play Your ACES” is service marked. For those interested Disliked nothing 136 (68.7) in more information, please contact Elizabeth Rubinstein training/orientation contains the ultimate at [email protected]. Aspects other than the TLC 23 (11.5) presentation (eg, interruptions) objective of volunteers taking ownership of the program. Transplant recipients are Disclosure Statements Inadequate time with TLC 12 (6.0) invited to become ambassador volunteers The author(s) have no conflicts of interest to Desired more information 10 (5.0) only after a minimum of ten months after disclose. Disliked the group format (would 9 (3.9) the transplant to ensure adequate physi- have preferred individual) cal and psychological recovery, wellness, Acknowledgments Disliked requirements or 8 (4.0) and stability. We thank the volunteers of Transplant Living compliance factors related to Community, the patients and supports who transplant This study has several limitations. First, completed the survey, the entire Transplant Institute Disliked the individual presenting 5 (2.5) the assessment of the satisfaction of pa- staff for their ongoing and exemplary care of a Data are presented as number (% of those who tients and supports was at a single time patients, and the Gift of Life Foundation and the provided qualitative feedback for that theme). point and therefore the level of satisfac- Benson Ford Endowment. TLC = Transplant Living Community. tion and information retained may be Mary Corrado, ELS, provided editorial assistance.

The Permanente Journal/Perm J 2016 Summer;20(3):15-207 49 ORIGINAL RESEARCH & CONTRIBUTIONS Lifestyle and Self-Management by Those Who Live It: Patients Engaging Patients in a Chronic Disease Model

Role of the Funding Source 10. Vogels SC, Emmelot-Vonk MH, Verhaar HJ, with the education and information received by Funding for the Transplant Living Community is Koek HL. The association of chronic kidney disease patients immediately after kidney transplant: a mixed- from a grant from the Gift of Life Foundation and with brain lesions on MRI or CT: a systematic review. models study. Prog Transplant 2013 Mar;23(1):12-22. Maturitas 2012 Apr;71(4):331-6. DOI: http://dx.doi. DOI: http://dx.doi.org/10.7182/pit2013249. the Benson Ford Endowment for Transplantation. org/10.1016/j.maturitas.2012.01.008. 23. Moloney S, Cicutto L, Hutcheon M, Singer L. There was no funding for the collection or analysis 11. Moodalbail DG, Reiser KA, Detre JA, et al. Deciding about lung transplantation: informational of these data or the development of this article. Systematic review of structural and functional needs of patients and support persons. Prog neuroimaging findings in children and adults with Transplant 2007 Sep;17(3):183-92. DOI: http://dx.doi. How to Cite this Article CKD. Clin J am Soc Nephrol 2013 Aug;8(8):1429-48. org/10.7182/prtr.17.3.k4x28156403g6735. DOI: http://dx.doi.org/10.2215/cjn.11601112. Jesse MT, Rubinstein E, Eshelman A, et al. Lifestyle 24. Myers J, Pellino TA. Developing new ways to 12. Hoffman BM, Blumenthal JA, Carney RC, et al. address learning needs of adult abdominal organ and self-management by those who live it: Patients Changes in neurocognitive functioning following transplant recipients. Prog Transplant 2009 engaging patients in a chronic disease model. lung transplantation. Am J Transplant 2012 Jun;19(2):160-6. DOI: http://dx.doi.org/10.7182/ Perm J 2016 Summer;20(3):15-207. DOI: Sep;12(9):2519-25. DOI: http://dx.doi.org/10.1111/ prtr.19.2.2084g543676202j6. http://dx.doi.org/10.7812/TPP/15-207. j.1600-6143.2012.04072.x. 25. Schmid-Mohler G, Schäfer-Keller P, Frei A, Fehr T, 13. Mapelli D, Bardi L, Mojoli M, et al. Spirig R. A mixed-method study to explore patients’ Neuropsychological profile in a large group of heart perspective of self-management tasks in the early References transplant candidates. PloS One 2011;6(12):e28313. phase after kidney transplant. Prog Transplant 2014 1. Dunbar SB, Jacobson LH, Deaton C. Heart failure: DOI: http://dx.doi.org/10.1371/journal.pone.0028313. Mar;24(1):8-18. DOI: http://dx.doi.org/10.7182/ strategies to enhance patient self-management. 14. Parekh PI, Blumenthal JA, Babyak MA, et al; pit2014728. AACN Clin Issues 1998 May;9(2):244-56. DOI: http:// INSPIRE Investigators. Gas exchange and exercise 26. Davis K, Schoen C, Schoenbaum SC. A 2020 vision dx.doi.org/10.1097/00044067-199805000-00007. capacity affect neurocognitive performance in for American health care. Arch Intern Med 2000 2. Gordon EJ, Caicedo JC, Ladner DP, Reddy E, patients with lung disease. Psychosom Med Dec 11-25;160(22):3357-62. DOI: http://dx.doi. Abecassis MM. Transplant center provision of 2005 May-Jun;67(3):425-32. DOI: http://dx.doi. org/10.1001/archinte.160.22.3357. education and culturally and linguistically competent org/10.1097/01.psy.0000160479.99765.18. 27. Davis K, Schoenbaum SC, Audet AM. A 2020 vision care: a national study. Am J Transplant 2010 15. Pegum N, Connor JP, Feeney GF, Young RM. of patient-centered primary care. J Gen Intern Dec;10(12):2701-7. DOI: http://dx.doi.org/10.1111/ Neuropsychological functioning in patients with Med 2005 Oct;20(10):953-7. DOI: http://dx.doi. j.1600-6143.2010.03304.x. alcohol-related liver disease before and after org/10.1111/j.1525-1497.2005.0178.x. 3. Berron K. Transplant patients’ perceptions about liver transplantation. Transplantation 2011 Dec 28. Funnell MM. Peer-based behavioural strategies effective preoperative teaching. J Heart Transplant 27;92(12):1371-7. DOI: http://dx.doi.org/10.1097/ to improve chronic disease self-management and 1986 Mar-Apr;5(2):162-5. tp.0b013e3182375881. clinical outcomes: evidence, logistics, evaluation 4. Frank-Bader M, Beltran K, Dojlidko D. Improving 16. Putzke JD, Williams MA, Rayburn BK, Kirklin JK, considerations and needs for future research. Fam transplant discharge education using a structured Boll TJ. The relationship between cardiac Prac 2010 Jun;27 Suppl 1:i17-22. DOI: http://dx.doi. teaching approach. Prog Transplant 2011 function and neuropsychological status among org/10.1093/fampra/cmp027. Dec;21(4):332-9. DOI: http://dx.doi.org/10.7182/ heart transplant candidates. J Card Fail 1998 29. Ashcroft P. Adapting patient education for potential prtr.21.4.pp1042023304p710. Dec;4(4):295-303. DOI: http://dx.doi.org/10.1016/ liver transplant recipients in a climate of chronic s1071-9164(98)90235-4. 5. Davis LA, Ryszkiewicz E, Schenk E, et al. Lung donor organ shortfall. Prog Transplant 2009 transplant or bust: patients’ recommendations for 17. Sauvé MJ, Lewis WR, Blankenbiller M, Mar;19(1):59-63. DOI: http://dx.doi.org/10.7182/ ideal lung transplant education. Prog Transplant 2014 Rickabaugh B, Pressler SJ. Cognitive impairments prtr.19.1.k18316t43n071j31. Jun;24(2):132-41. DOI: http://dx.doi.org/10.7182/ in chronic heart failure: a case controlled study. 30. Armstrong N, Herbert G, Aveling EL, Dixon-Woods M, pit2014432. J Card Fail 2009 Feb;15(1):1-10. DOI: http://dx.doi. Martin G. Optimizing patient involvement in quality org/10.1016/j.cardfail.2008.08.007. 6. Redman BK. Patient adherence or patient self- improvement. Health Expect 2013 Sep;16(3):e36-47. management in transplantation: an ethical analysis. 18. Wilson EA, Wolf MS. Working memory and DOI: http://dx.doi.org/10.1111/hex.12039. Prog Transplant 2009 Mar;19(1):90-4. DOI: http:// the design of health materials: a cognitive 31. Baldoni L, De Simone P, Paganelli R, et al. The “You dx.doi.org/10.7182/prtr.19.1.86211l267l074873. factors perspective. Patient Educ Couns 2009 Are Not Alone” care program for liver transplantation. Mar;74(3):318-22. DOI: http://dx.doi.org/10.1016/j. 7. Weingarten SR, Henning JM, Badamgarav E, et Transplant Proc 2008 Jul-Aug;40(6):1983-5. DOI: pec.2008.11.005. al. Interventions used in disease management http://dx.doi.org/10.1016/j.transproceed.2008.05.066. programmes for patients with chronic illness—which 19. Wilson EA, Wolf MS, Curtis LM, et al. Literacy, 32. Institute of Medicine: Committee on Quality Health ones work? Meta-analysis of published reports. cognitive ability, and the retention of health-related Care in America. Crossing the quality chasm: a new BMJ 2002 Oct 26;325(7370):925. DOI: http://dx.doi. information about colorectal cancer screening. J health system for the 21st century. Washington, DC: org/10.1136/bmj.325.7370.925. Health Commun 2010;15 Suppl 2:116-25. DOI: http:// National Academies Press; 2001 Mar 1. dx.doi.org/10.1080/10810730.2010.499984. 8. Ofman JJ, Badamgarav E, Henning JM, et al. 33. Clancy CM. Paitient engagement in health care. Does disease management improve clinical and 20. Wolf MS, Curtis LM, Wilson EA, et al. Literacy, Health Serv Res 2011 Apr;46(2):389-93. DOI: http:// economic outcomes in patients with chronic cognitive function, and health: results of the LitCog dx.doi.org/10.1111/j.1475-6773.2011.01254.x. diseases? A systematic review. Am J Med 2004 Aug study. J Gen Intern Med 2012 Oct;27(10):1300-7. 34. Coulter A. Patient engagement—what works? J 1;117(3):182-92. DOI: http://dx.doi.org/10.1016/j. DOI: http://dx.doi.org/10.1007/s11606-012-2079-4. Ambul Care Manage 2012 Apr-Jun;35(2):80-9. DOI: amjmed.2004.03.018. 21. Hartmann M, Bäzner E, Wild B, Eisler I, Herzog W. http://dx.doi.org/10.1097/jac.0b013e318249e0fd. 9. Bugnicourt JM, Godefroy O, Chillon JM, Effects of interventions involving the family 35. Gruman J, Rovner MH, French ME, et al. From Choukroun G, Massy ZA. Cognitive disorders and in the treatment of adult patients with chronic patient education to patient engagement: implications dementia in CKD: the neglected kidney-brain axis. physical diseases: a meta-analysis. Psychother for the field of patient education. Patient Educ J Am Soc Nephrol 2013 Feb;24(3):353-63. DOI: Psychosom 2010;79(3):136-48. DOI: http://dx.doi. Couns 2010 Mar;78(3):250-6. DOI: http://dx.doi. http://dx.doi.org/10.1681/asn.2012050536. org/10.1159/000286958. org/10.1016/j.pec.2010.02.002. 22. Haspeslagh A, De Bondt K, Kuypers D, Naesens M, Breunig C, Dobbels F. Completeness and satisfaction

To Interact

It is our duty to remember at all times and anew that medicine is not only a science, but also the art of letting our own individuality interact with the individuality of the patient.

— Albert Schweitzer, 1875-1965, French-German theologian, organist, philosopher, and physician

50 The Permanente Journal/Perm J 2016 Summer;20(3):15-207 credits available for this article — see page 112.

ORIGINAL RESEARCH & CONTRIBUTIONS

Special Report Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control

Eric A Lee, MD; Nancy E Gibbs, MD; John Martin, MD; Fred Ziel, MD; Jennifer K Polzin, PharmD; Darryl Palmer-Toy, MD, PhD Perm J 2016 Summer;20(3):15-080 E-pub: 06/29/2016 http://dx.doi.org/10.7812/TPP/15-080

ABSTRACT Older patients are at high risk of drug toxicity. Because they Diabetes affects more than 25% of Americans older than age are more likely than younger patients to have multiple medical 65 years. The medical care of older patients must differ from the problems, older patients take more medications, which often care of their younger counterparts. Older patients are at high leads to incorrect and unnecessary administration of prescribed

risk of drug toxicity. A hemoglobin A1c (HbA1c) level less than medications. Additionally, the metabolism of drugs is reduced 7.0% has historically been the goal of all patients with diabetes, in older patients because of decreased lean body mass with in- regardless of age. Recent research has demonstrated that using creased body fat and a higher likelihood of having renal, hepatic, medications to achieve such tight glycemic control is not neces- and/or cardiac insufficiency. Finally, drug-drug and drug-disease sary and is often not safe. interactions make older patients at high risk of iatrogenic com- This article discusses the seminal research findings that plications of drug toxicity.

strongly suggest that HbA1c goals should be relaxed in older “Overuse” of medications has been categorized as when the patients. The authors then recommend an age-specific and func- benefits of the additional medication are negligible (eg, anti-

tionally appropriate HbA1c reference range for patients receiving biotics for a sore throat), when the risks outweigh the benefits medications to improve glycemic control. Other interventions (eg, muscle relaxant for neck pain), or use of a medication that are suggested that should make diabetes care safer in older a competent patient would have otherwise declined after shared patients receiving hypoglycemic medications. decision making (eg, morphine for mild knee pain).1,2 Use of hypoglycemic medications for the treatment of diabetes in older INTRODUCTION patients using standard guidelines often fit all three categories Care of Older Adult Patients of “overuse.” The clinical benefits of additional hypoglycemic The medical care of older patients must differ from the care medications are often minimal, the harms are common and of their younger counterparts. Complications from “standard” lasting, and the patient often lacks understanding of the time medical care are much more common in the geriatric popula- needed to accrue benefits from hypoglycemic medications. Hy- tion because of reduced reserve physiologic capacity, leading to poglycemia occurs frequently in older patients with diabetes, functional decline. For example, among the sickest patients— more often contributing to functional decline and lasting dis- hospitalized older patients—lasting disability is more common ability compared with their younger counterparts. The goals of compared with hospitalized younger patients because of at least glycemic control and the treatment using hypoglycemic diabetic three mechanisms: medications in patients with diabetes must differ depending on 1. Incomplete recovery from a classic medical diagnosis (eg, oxy- age and functional status. gen dependence after pneumonia or chronic dyspnea after a myocardial infarction) Diabetes Care in Older Adult Patients 2. Exacerbation of a preexisting geriatric syndrome (eg, height- Since 2003, there has been general acceptance by geriatric- ened fear of falls caused by hospital-related deconditioning focused physicians that glycemic control should be tempered with leg weakness or worsening dizziness caused by additional by a sense of life expectancy, goals of care, cognitive status, and polypharmacy from new medications) physical functional status.3 The one-size-fits-all model is not -ap 3. Iatrogenic complications during a hospitalization (eg, nosocomial propriate in frail older patients receiving hypoglycemic medica- Clostridium difficile colitis leading to nursing home placement tions, for whom the risks of these medications often outweigh or hospital-acquired incident delirium leading to dementia). their benefits. Rather, shared decision making is necessary.

Eric A Lee, MD, is the Assistant Chief of Internal Medicine at the West Los Angeles Medical Center and Co-Chair of the Southern California Permanente Medical Group High Risk Drugs in the Elderly Committee in Pasadena. E-mail: [email protected]. Nancy E Gibbs, MD, is the former Regional Coordinating Chair for Geriatrics and Continuing Care for Kaiser Permanente Southern California and Co-Chair of the Southern California Permanente Medical Group High Risk Drugs in the Elderly Committee in Pasadena. E-mail: [email protected]. John Martin, MD, is an Internist at the Los Angeles Medical Center and Co-Director of the Southern California Permanente Medical Group Diabetes Complete Care Program in Pasadena. E-mail: [email protected]. Fred Ziel, MD, is the Physician-in-Charge of Endocrinology at the Woodland Hills Medical Center in CA and the Regional Coordinating Chair for Endocrinology for Kaiser Permanente Southern California. E-mail: [email protected]. Jennifer K Polzin, PharmD, is the former Clinical Operations Senior Pharmacy Consultant for Medication Management and Safety for the Southern California Permanente Medical Group in Pasadena. Darryl Palmer-Toy, MD, PhD, is the Medical Director of the Regional Reference Laboratories and the Regional Assistant Medical Director of Laboratory Services for the Southern California Permanente Medical Group in Pasadena. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-080 51 ORIGINAL RESEARCH & CONTRIBUTIONS Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control

Historically, glycemic goals target a hemoglobin A1c (HbA1c) assigned to receive either standard control of blood glucose or in- level below 7.0% without differentiation by age. The 2013 tensive control (intervention). After an average follow-up of 6.5 American Association of Clinical Endocrinologists (AACE) ex- years, the DCCT (conducted from 1983 to 1993) demonstrated

ecutive summary for diabetes management states that the HbA1c that patients with tight glycemic control had a delay in onset goal is 6.5% or lower for healthy patients without concurrent (primary prevention) or progression (secondary prevention) of illness and who are at low hypoglycemic risk.4 The AACE states nephropathy, neuropathy, and retinopathy.9 The intervention

that the goal should be individualized to an HbA1c measurement group had a mean HbA1c of 7.4%; the conventional treatment above 6.5% for patients with concurrent illness and who are group had a mean HbA1c of 9.1%. The 11-year, postinterven- at risk of hypoglycemia.4 Although this AACE position states tion follow-up published in 2005 showed a 42% reduction in 10 that the goals should be individualized on the basis of age and any cardiovascular disease event. (In 2004, the mean HbA1c comorbidity, guidance on comorbidity criteria is absent. We in the intervention group was 7.9% compared with 7.8% in believe that the lack of clarity in the AACE’s statement perpetu- the control group.10) Notably, the widespread applicability of ates the “lower-is-better” myth and encourages the overuse of the DCCT investigators’ conclusions to most patients with dia- potentially dangerous hypoglycemic medications. betes was properly questioned.11 Less than 10% of all patients The American Diabetes Association’s (ADA’s) 9-page executive with diabetes have Type 1 diabetes, and the pathophysiology summary of its 67-page position statement, “Standards of Medi- of Type 1 diabetes (formerly called juvenile diabetes) is markedly

cal Care in Diabetes 2014,” states that an HbA1c under 7.0% is different from that in most patients with Type 2 (formerly called “a reasonable goal” for many nonpregnant patients.5 Also, the adult-onset) diabetes, particularly those older than 65 years. ADA recommends that “older adults who are functional, cogni- The UK Prospective Diabetes Study (UKPDS), whose results tively intact, and have significant life expectancy should receive were published in 1998, attempted to mitigate these concerns diabetes care with goals similar to those developed for younger and validate the importance of tight glycemic control in patients adults” and that “glycemic goals for some older adults might with Type 2 diabetes.12 In this study, 3867 patients with newly reasonably be relaxed, using individual criteria, but hyperglyce- diagnosed Type 2 diabetes (mean age = 54 years) were randomly mia leading to symptoms or acute hyperglycemic complications given intensive therapy or conventional treatment. Patients should be avoided … .”5 Like the 2013 AACE executive sum- older than age 65 years were excluded from enrollment in the mary, the 2014 ADA executive summary possibly lacks proper UKPDS.12 After 10 years of follow-up, the intensive therapy

guidance for clinicians on when HbA1c goals should be relaxed. group (mean HbA1c = 7.0%) had delays in microvascular com- However, in the text of the ADA’s 2014 position statement, plications, with less retinopathy and nephropathy compared

HbA1c goals of below 7.5%, below 8.0%, and below 8.5% are with those who received conventional treatment (mean HbA1c recommended for older patients who have, respectively, good = 7.9%).12 Macrovascular complications were not shown to be health, complex/intermediate health, and very complex/poor prevented or delayed during the initial publication in 1998. health.6 This recommendation is more aligned with the position After the end of the randomization of the 2 groups, shortly of the American Geriatrics Society (AGS), in which the target after the 1998 publication, the glycemic control equalized in both

goal is set for an HbA1c between 7.5% and 8.0% in most older study groups. The 10-year postsurveillance results of the UKPDS, patients, and higher HbA1c targets between 8.0% and 9.0% published in 2008, suggested there was a “legacy effect,” or long- are recommended with multiple comorbidities, poor health, delayed benefit, in preventing myocardial infarctions and death and limited life expectancy.7 These recommendations from in the intensive therapy group compared with the conventional the AGS have been adopted and publicized by the “Choosing group.13 Earlier intensive glycemic control during the first 10 Wisely” campaign sponsored by the American Board of Inter- years after the diagnosis of diabetes could reduce macrovascu- nal Medicine (ABIM) Foundation.8 On the basis of results of lar events 10 to 19 years later, the study found. The UKPDS

pivotal historical trials, we strongly agree with the glycemic goal influenced the adoption of HbA1c goals below 7.0% in adult of having HbA1c below 7.0% in most patients under 65 years patients with Type 2 diabetes. of age. In this article, we discuss the scientific foundation for treating hyperglycemia to the historic goal of less than 7.0% in Fallacy of Applying these Studies to Older Adult Patients patients older than age 65 years (still generally considered the In 2014, Selvin et al14 published data from the National threshold for proper glycemic control in patients with diabetes Health and Nutrition Examination Survey (NHANES, con- of all ages), and why we believe that these goals should be relaxed ducted by the Centers for Disease Control and Prevention). to the standards set by the AGS. The authors labeled patients with diabetes of all ages who re-

ceived hypoglycemic medications and had an HbA1c of 7.0% Historical Context for Lower Glycemic Targets or greater as being suboptimally controlled.14 We think that an

The Diabetes Control and Complications Trial (DCCT) was HbA1c below 7.0% should not necessarily be the goal in older the first trial to establish that microvascular and macrovascular patients with diabetes receiving hypoglycemic medications, and complications of hyperglycemia could be delayed with tighter conclusions from influential articles such as NHANES mislead glycemic control. In this seminal work published in 1993, a total both clinicians and older patients with diabetes, potentially lead- of 1441 patients with Type 1 diabetes (mean age = 27 years), ing to harm. In NHANES, 40% of the patients with diabetes with and without microvascular complications, were randomly were older than age 65 years. We know that up to 57% of older

52 The Permanente Journal/Perm J 2016 Summer;20(3):15-080 ORIGINAL RESEARCH & CONTRIBUTIONS Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control

patients with diabetes have substantial comorbidities and geriat- significantly increased rate of hospitalization in the intervention ric syndromes, which often leads these patients to change their group. The only microvascular benefit with intense treatment was goals of medical care.15 Given the known reduced life expectancy a statistically significant reduction in albuminuria.18 In 2014, the in older patients, particularly in frail older patients, we believe follow-up study in ADVANCE demonstrated no reduction in

that the age-neutral historic target of an HbA1c below 7.0% is macrovascular disease after the 6-year, postsurveillance follow- fallacious. This target is based on results of studies (UKPDS up. The legacy effect in preventing macrovascular disease seen and DCCT) that did not allow for enrollment of patients aged in the UKPDS was not seen in ADVANCE.19 65 years or older, and hence these glycemic goals should not In 2009, the Veterans Affairs Diabetes Trial assessed 1791 translate to older patients. military veterans with suboptimally controlled Type 2 diabetes

The microscopic complications related to higher HbA1c con- (mean age = 60 years; mean duration of diabetes mellitus = 11.5 centrations may not be clinically relevant in older patients with years; 40% with vascular disease).20 The goal in the interven- new-onset diabetes. In a theoretical construct model comparing tion group receiving intensive glucose control was to reduce

an HbA1c of 8.0% vs 7.0% in patients with the onset of diabetes the HbA1c by 1.5%. After 6 years, there were significantly at age 65 years, the additional lifetime risk of blindness caused more serious events in the intervention group (mean HbA1c = by retinopathy was reduced by 0.2% (number needed to treat 6.9%), including hypoglycemia, vs the controls (mean HbA1c = 500) and the additional lifetime risk of end-stage renal dis- = 8.4%), which received standard glucose control. There were ease was reduced by 0.2% (number needed to treat = 500).16 no statistically significant changes in composite microvascular Therefore, the clinical significance of preventing microvascular outcomes, although a statistically significant reduction did oc- disease is questionable. Later, the UKPDS showed that tight cur in the progression of proteinuria. No statistical differences glycemic control might reduce the development of macrovas- existed in the number of eye surgical procedures, but there was cular disease by 10 to 19 years, but in a patient with limited a trend for reduced retinopathy. There also were no significant life expectancy or onset of diabetes after the age of 65 years, reductions in macrovascular events (stroke, cardiac events and the relevance of aggressive lowering of glucose levels becomes procedures) or amputations in the intervention group compared less clear. Furthermore, if microalbuminuria portends future with the control group.20 macrovascular complications, the control of hypertension and hyperlipidemia with the appropriate use of cardioprotective medications (aspirin, angiotensin-converting enzyme inhibitors, … the age-neutral historic target of an HbA1c below and statins) plays an equal if not a more important role in the 7.0% is fallacious [and] based on results of studies prevention of cardiovascular complications. … that did not allow for enrollment of patients For older adult patients with long-standing diabetes and aged 65 years or older, and hence these glycemic multiple medical problems, at least 3 randomized trials have goals should not translate to older patients.

demonstrated that an HbA1c of about 7.5% is appropriate and safe and that an HbA1c below 6.5% might be dangerous. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Complications of Hypoglycemia trial published in 2008 assessed 10,251 patients (mean age = In 2011, the second most likely medication leading an older 62 years; average duration of diabetes = 10 years) with multiple patient to be hospitalized through the Emergency Department

comorbidities who received intensive treatment (mean HbA1c because of an adverse drug event was insulin, and the fourth most 17 = 6.4%) or conventional therapy (mean HbA1c = 7.5%). The likely medication was an oral hypoglycemic agent, according to study was halted prematurely after 3.5 years because it showed authors from the Centers for Disease Control and Prevention.21 that there was one additional death in the intervention group This group estimated that the numbers of hospitalizations in older for every 95 patients over 3.5 years. In addition, 10% of the patients occurring annually in the US because of insulin and oral intervention group had hypoglycemic events that required hypoglycemic agents were 13,854 and 10,656 respectively. More medical assistance vs 3% for the control group, and 28% of the than 94% of these hospitalizations were caused by complications intervention group had more than 10-kg weight gain compared of hypoglycemia, clearly demonstrating the potential dangers with 14% in the control group.17 of these endocrine agents. This same group later published that Also in 2008, the Action in Diabetes and Vascular Disease: patients older than age 80 years who were receiving insulin were Preterax and Diamicron Modified Release Controlled Evaluation twice as likely to go to the Emergency Department and 5 times as (ADVANCE) trial took place in 11,140 older patients (mean likely to be hospitalized because of insulin-related hypoglycemia age = 66 years; average duration of diabetes = 8 years) with se- and errors compared with 45- to 64-year-old patients, suggesting vere cardiovascular disease or cardiovascular disease risk factors or the need for looser glycemic targets based on age.22 preexisting microvascular complications.18 The ADVANCE trial Kaiser Permanente Northern California (KPNC) data showed found no macrovascular benefit or increased rate of death in the that hypoglycemia was the second most common nonfatal diabetic

intense treatment group (mean HbA1c = 6.5%) vs conventional complication (after cardiovascular complications) in patients age therapy (mean HbA1c = 7.3%) after 5 years. Severe hypoglyce- 70 to 79 years with a duration of diabetes for more than 10 years mia was significantly more common in the intervention group and the third most common cause of nonfatal complications in (2.7% vs 1.5% in the control group), which contributed to the patients with diabetes for less than 10 years (after cardiovascular

The Permanente Journal/Perm J 2016 Summer;20(3):15-080 53 ORIGINAL RESEARCH & CONTRIBUTIONS Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control

complications and eye disease).23 Additionally, among patients age (as well as geriatric syndromes) more negatively affects an older 70 to 79 years, the incidence of hypoglycemia was 6 times more patient’s quality of life than do other diabetic complications (eg, likely than acute hyperglycemic events in those who had diabetes neuropathy, blindness, and end-stage renal disease).26 for less than 10 years, and 19 times more likely in patients with diabetes for greater than 10 years.23 Hypoglycemia Continues in Older Patients As noted earlier, whether macrovascular disease can be prevent- As already discussed, the literature shows that an unexpected ed with tight glycemic control among older patients with a long- higher death rate was found in the intervention group of the standing history of diabetes is questionable. Hypoglycemia might ACCORD study and that hypoglycemic agents often lead to also increase the risk of dementia later in life.24 In a KPNC diabetic emergent hospitalizations in older patients, with hospitalizations registry from 1980 to 2007, of 16,667 patients with a mean age frequently leading to lasting disability. Other research showed of 65 years, 1465 patients had at least 1 visit to the Emergency that older patients with multiple comorbid conditions and long-

Department or hospital for a hypoglycemic event. The absolute standing diabetes with an HbA1c between 6.4% and 6.9% did risk in these patients of dementia developing per year of follow- not have improved macrovascular outcomes or clinically signifi- up was 2.3%.25 Other KPNC data showed that hypoglycemia cant improved microvascular outcomes compared with those

with an HbA1c of 7.3% to 8.1%. Given this body of evidence, the physician mantra of “do no harm” would suggest that only Table 1. Kaiser Permanente Southern California’s electronic a small percentage of patients older than 65 years would have an HbA1c below 7.0% and be receiving hypoglycemic medications. medical record flag for elevated hemoglobin 1cA in patients with diabetes, used through December 2015a Yet, in published KPNC data, of 9786 patients between age 70 and 79 years with a duration of diabetes mellitus for longer than High flag 23 10 years, 41% had an HbA1c below 7.0%. Although only 7% Age (HbA1c, %) Comments All agesb ≥ 7.0 Actual blood glucose measurements may differ of these patients were not receiving any hypoglycemic medica- from the estimated average glucose because tion, 61% of these patients were on a regimen of a sulfonylurea of differences in test timing, stability of glycemic and 39% were receiving insulin.23 control, and RBC lifespan In a Veterans Affairs study in 2009 of 205,857 patients at a As of October 12, 2012, a separate test was created in Kaiser Permanente Southern high risk of hypoglycemia because of age older than 74 years, California for screening patients who did not have a diagnosis of diabetes. The a creatinine level above 2.0 mg/dL, or presence of cognitive reference range for that test is 4.8% to 5.6%. b impairment while receiving a sulfonylurea and/or insulin, 50% Patients of all ages were flagged as having elevated blood glucose levels if HbA1c measurement was ≥ 7.0%. of patients had a level of HbA1c under 7.0%, 27% had HbA1c HbA = hemoglobin A ; RBC = red blood cell. 27 1c 1c below 6.5%, and 11% had HbA1c less than 6.0%. These find- ings suggest overtreatment with hypoglycemic medications. Table 2. Kaiser Permanente Southern California’s updated DISCUSSION hemoglobin A reference range for different age bandsa 1c Many hypoglycemic episodes are avoidable. Many patients Age, High flag may not know to take less hypoglycemic medication when their years (HbA , %) Comments 1c oral intake is reduced (because of, for example, poor access to ≤ 17 ≥ 7.5 Actual blood glucose measurements may differ food caused by an acute medical event such as an upper respira- from the estimated average glucose because of differences in test timing, stability of glycemic tory tract infection with consequent anorexia). All clinicians, control, and RBC lifespan while educating older adult patients with diabetes, should in- struct them to reduce their hypoglycemic agents during times 18-64 ≥ 7.0 A less stringent HbA1c goal of < 8.0% may be appropriate for an individual patient with of poor nutritional intake and to carry candy and a glucagon a history of severe hypoglycemia, limited injection with them in the event of a hypoglycemic episode. The life expectancy, advanced microvascular or first-line treatment of most diseases should be education and 65-75 ≥ 7.5 macrovascular complications, or extensive other nonpharmaceutical interventions. In Kaiser Permanente comorbid conditions Southern California (KPSC), patients with diabetes mellitus ≥ 76 ≥ 8.0 A less stringent HbA goal of < 9.0% may be 1c have better glycemic control if they have taken health educa- appropriate for an individual elderly patient with tion classes at KPSC (personal communication; Ray Nanda, a history of severe hypoglycemia, advanced a microvascular or macrovascular complications, MD; 2016 Feb 22). or extensive comorbid conditions There may be financial ramifications to overtreatment with a Convened by the manuscript’s authors, multiple relevant Kaiser Permanente Southern hypoglycemic agents. Medicare has been reducing reimburse-

California committees assisted in updating the HbA1c (diabetic monitoring) reference ments for care because of events thought to be avoidable (“never range. The consensus reference range is shown here. In use since January 2016, this events” during a hospitalization or readmission). In 2012, it was updated reference range has been flagged as abnormal at an HbA1c level of ≥ 7.5% in patients with diabetes between 65 and 75 years of age and has been flagged estimated that in the US there was $213 billion of avoidable

as abnormal at an HbA1c ≥ 8.0 in patients with diabetes ≥ 76 years of age. The health care costs, of which $20 billion in costs were caused by

corresponding comments will allow clinicians to choose a more tailored HbA1c goal on medication errors and $1.3 billion was caused by mismatched the basis of the patient’s function and comorbidities. polypharmacy in elderly individuals.28 Given the alarming rate HbA1c = hemoglobin A1c; RBC = red blood cell.

54 The Permanente Journal/Perm J 2016 Summer;20(3):15-080 ORIGINAL RESEARCH & CONTRIBUTIONS Improving Care in Older Patients with Diabetes: A Focus on Glycemic Control

of possible overtreatment with hypoglycemic agents in older Acknowledgments patients, the US Department of Health and Human Services The authors would like to thanks the following Kaiser Permanente (KP) is developing a National Action Plan for Adverse Drug Event Southern California (KPSC) physicians: Jeffrey Brettler, MD (Assistant Area Medical Director, KP West Los Angeles [LA]); Richard Chen, MD (Physican Prevention that focuses on 3 classes of medications: opiates, Lead, Health Connect Clinical Content Lead and Decision Support, KPSC); 29 warfarin, and hypoglycemic agents. Howard Fullman, MD (Area Medical Director, KP West LA); Timothy Ho, MD We believe that the excessive burdens such as hypoglycemic (Regional Assistant Medical Director, Quality and Clinical Analysis, KPSC); episodes and other adverse medication reactions can be reduced Kisung Steve Hong, MD (Regional Coordinating Chair of General Internal through the following multi-interventional approach: Medicine, KPSC); Michael Kanter, MD (Regional Medical Director of Quality 1. Establish a new reference range for HbA levels in older & Clinical Analysis, KPSC); Gregorio Saccone, MD (Regional Physician 1c Director, Health Connect Communications, KPSC); Steve Steinberg, MD patients with diabetes that synthesize the recommendations (Regional Coordinating Chair for Family Medicine, KPSC) for their lively from the ADA, Choosing Wisely (sponsored by the ABIM discussion and integral involvement in re-evaluating the glycemic goals of Foundation), and the AGS. older adults with diabetes. Without their support, the KPSC updated age-

2. Educate and encourage clinicians to reduce hypoglycemic banded HbA1c reference range would not have been released. medications in older patients at risk of functional loss or with Kathleen Louden, ELS, of Louden Health Communications provided editorial assistance. multiple medical problems when their HbA1c level is below 7.0%. Accounting for risks of polypharmacy and the goals of How to Cite this Article care, for a healthy older patient with diabetes and an HbA1c Lee EA, Gibbs NE, Martin J, Ziel F, Polzin JK, Palmer-Toy D. Improving care level below 7.0%, prescribing metformin as the only agent in older patients with diabetes: a focus on glycemic control. Perm J 2016 may be appropriate. There is importance in using antidiabetes Summer;20(3):15-080. DOI: http://dx.doi.org/10.7812/TPP/15-080. medications to reduce glucose burden because hyperglycemia can also cause substantial morbidity. Our (KPSC) updated References reference range can guide physicians to prescribe on the basis 1. Caverly TJ, Combs BP, Moriates C, Shah N, Grady D. Too much medicine of function and morbidity (Tables 1 and 2). happens too often: the teachable moment and a call for manuscripts from clinical 3. Prescribe metformin as the first-line agent when a physician trainees. JAMA Internal Med 2014 Jan;174(1):8-9. DOI: http://dx.doi.org/10.1001/ jamainternmed.2013.9967. initiates therapy with a hypoglycemic medication because of 2. Chassin MR, Galvin RW. The urgent need to improve health care quality. Institute its low risk for hypoglycemia and its safety profile. of Medicine National Roundtable on Health Care Quality. JAMA 1998 Sep 4. Use the electronic medical record to identify patients receiving 16;280(11):1000-5. DOI: http://dx.doi.org/10.1001/jama.280.11.1000. 3. Brown AF, Mangione CM, Saliba D, Sarkisian CA; California Healthcare Foundation/ hypoglycemic agents who have an HbA1c level below 7.0% American Geriatrics Society Panel on Improving Care for Elders with Diabetes. and who are older than 80 years old or who have dementia Guidelines for improving the care of the older person with diabetes mellitus. or chronic kidney disease stage 4 or greater. J Am Geriatr Soc 2003 May;51(5 Suppl Guidelines):S265-80. DOI: http://dx.doi. org/10.1046/j.1532-5415.51.5s.1.x. 5. Educate patients and caretakers, as well as provide written 4. Garber AJ, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical instruction after the office visit, to decrease the dosing of Endocrinologists’ comprehensive diabetes management algorithm 2013 consensus hypoglycemic medications when the patient’s oral intake is statement—executive summary. Endocr Pract 2013 May-Jun;19(3):536-57. DOI: http://dx.doi.org/10.4158/ep13176.cs. reduced because of illness or poor access to food. 5. American Diabetes Association. Executive summary: standards of medical care 6. Prescribe glucagon for older patients with diabetes receiving in diabetes—2014. Diabetes Care 2014 Jan;37 Suppl 1:S5-13. DOI: http://dx.doi. hypoglycemic medications, which can be used emergently org/10.2337/dc14-s005. 6. American Diabetes Association. Standards of medical care in diabetes—2014. during symptoms of hypoglycemia. Diabetes Care 2014 Jan;37 Suppl 1:S14-80. DOI: http://dx.doi.org/10.2337/ 7. Encourage older patients with diabetes who are receiving dc14-s014. hypoglycemic medications to always carry glucose tablets 7. American Geriatrics Society Expert Panel on the Care of Older Adults with Diabetes Mellitus, Moreno G, Mangione CM, Kimbro L, Vaisberg E. Guidelines abstracted from or glucose-rich foods with them and to monitor their blood the American Geriatrics Society Guidelines for Improving the Care of Older Adults glucose level before driving. with Diabetes Mellitus: 2013 update. J Am Geriatr Soc 2013 Nov;61(11):2020-6. DOI: 8. Use the electronic medical record to identify older patients receiv- http://dx.doi.org/10.1111/jgs.12514. 8. American Academy of Family Physicians. Choosing wisely [Internet]. Philadelphia, ing hypoglycemic medications who have 2 consecutive HbA1c PA: ABIM Foundation; 2012 Apr [cited 2016 Feb 5]. Available from: www. measurements below 6.5% in a period longer than 1 month. choosingwisely.org. By implementing the proposed interventions to reduce hy- 9. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control poglycemia, we can keep older patients with diabetes safer and and Complications Trial Research Group. N Engl J Med 1993 Sep 30;329(14):977- more functional, without having any clinically significant health 86. DOI: http://dx.doi.org/10.1097/00006982-199414030-00022. consequences from less intensive glycemic control. v 10. Nathan DM, Cleary PA, Backlund JY, et al; Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study a Chair of Health Education and Promotion, Kaiser Permanente Southern California, Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005 Dec 22;353(25):2643-53. DOI: http://dx.doi. Pasadena, CA. org/10.1056/nejmoa052187. 11. King P, Peacock I, Donnelly R. The UK prospective diabetes study (UKPDS): Disclosure Statement clinical and therapeutic implications for type 2 diabetes. Br J Clin Phamacol 1999 The author(s) have no conflicts of interest to disclose. Nov;48(5):643-8. DOI: http://dx.doi.org/10.1046/j.1365-2125.1999.00092.x. 12. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998 Sep

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12;352(9131):837-53. DOI: http://dx.doi.org/10.1016/S0140-6736(98)07019-6. 22. Geller AI, Shehab N, Lovegrove MC, et al. National estimates of insulin- Erratum in: Lancet 1999 Aug 14;354(9178):602. DOI: 10.1016/S0140- related hypoglycemia and errors leading to emergency department visits and 6736(05)77965-4. hospitalizations. JAMA Intern Med 2014 May;174(5):678-86. DOI: http://dx.doi. 13. Homan RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of org/10.1001/jamainternmed.2014.136. intensive glucose control in type 2 diabetes. N Engl J Med 2008 Oct 9;359(15):1577- 23. Huang ES, Laiteerapong N, Liu JY, John PM, Moffett HH, Karter AJ. Rates of 89. DOI: http://dx.doi.org/10.1056/NEJMoa0806470. complications and mortality in older patients with diabetes mellitus: the diabetes 14. Selvin E, Parrinello CM, Sacks DB, Coresh J. Trends in prevalence and control of and aging study. JAMA Intern Med 2014 Feb 1;174(2):251-8. DOI: http://dx.doi. diabetes in the United States, 1988-1994 and 1999-2010. Ann Intern Med 2014 Apr org/10.1001/jamainternmed.2013.12956. 15;160(8):517-25. DOI: http://dx.doi.org/10.7326/m13-2411. 24. Yaffe K, Falvey CM, Hamilton N, et al; Health ABC Study. Association between 15. AGS Choosing Wisely Workgroup. American Geriatrics Society identifies five things hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. that healthcare providers and patients should question. J Am Geriatr Soc 2013 JAMA Intern Med 2013 Jul 22;173(14):1300-6. DOI: http://dx.doi.org/10.1001/ Apr;61(4):622-31. DOI: http://dx.doi.org/10.1111/jgs.12226. jamainternmed.2013.6176. 16. Vijan S, Hofer TP, Hayward RA. Estimated benefits of glycemic control in 25. Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV. Hypoglycemic microvascular complications in type 2 diabetes. Ann Intern Med 1997 Nov episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 1;127(9):788-95. DOI: http://dx.doi.org/10.7326/0003-4819-127-9-199711010-00003. 2009 Apr 15;301(15):1565-72. DOI: http://dx.doi.org/10.1001/jama.2009.460. 17. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, 26. Laiteerapong N, Karter AJ, Liu JY, et al. Correlates of quality of life in older adults with Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. diabetes: the diabetes & aging study. Diabetes Care 2011 Aug;34(8):1749-53. DOI: N Engl J Med 2008 Jun 12;358(24):2545-59. DOI: http://dx.doi.org/10.1056/ http://dx.doi.org/10.2337/dc10-2424. NEJMoa0802743. 27. Tseng CL, Soroka O, Maney M, Aron DC, Pogach LM. Assessing potential glycemic 18. ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, et al. Intensive overtreatment in persons at hypoglycemic risk. JAMA Intern Med 2014 Feb blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl 1;174(2):259-68. DOI: http://dx.doi.org/10.1001/jamainternmed.2013.12963. J Med 2008 Jun 12;358(24):2560-72. DOI: http://dx.doi.org/10.1056/nejmoa0802987. 28. Aitken M. Avoidable costs in US healthcare: the $200 billion opportunity from using 19. Zoungas S, Chalmers J, Neal B, et al; ADVANCE-ON Collaborative Group. Follow- medicines more responsibly [Internet]. Danbury, CT: IMS Health Incorporated; c2016 up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med [cited 2016 Mar 9]. Available from: www.imshealth.com/en/thought-leadership/ 2014 Oct 9;371(15):1392-406. DOI: http://dx.doi.org/10.1056/nejmoa1407963. webinar-library/avoidable-costs-in-us-healthcare-200-billion-opportunity. 20. Duckworth W, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and 29. National action plan for adverse drug event protection [Internet]. Washington, DC: vascular complications in veterans with type 2 diabetes. N Engl J Med 2009 Jan US Department of Health and Human Services, Office of Disease Prevention and 8;360(2):129-39. DOI: http://dx.doi.org/10.1056/NEJMoa0808431. Health Promotion; 2014 [cited 2016 Feb 5]. Available from: www.health.gov/hai/pdfs/ 21. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for ADE-Action-Plan-508c.pdf. adverse drug events in older Americans. N Engl J Med 2011 Nov 24;365(21):2002- 12. DOI: http://dx.doi.org/10.1056/nejmsa1103053.

Attending to Old People

Not only physicians, but everybody else attending old people, being accustomed to their constant complaints, and knowing their ill-tempered and difficult manners, realize how noble and important, how serious and difficult, how useful and even indispensable is that part of practical Medicine, called Gerocomica, which deals with the conservation of old people and the healing of their diseases.

—François Ranchin, MD, 1564-1641, French physician and professor and chancellor of the Université de Médecin, Montpelier, France

56 The Permanente Journal/Perm J 2016 Summer;20(3):15-080 credits available for this article — see page 112.

ORIGINAL RESEARCH & CONTRIBUTIONS

Special Report Evidence-Based Workflows for Thyroid and Parathyroid Surgery

Charles Meltzer, MD; Amer Budayr, MD; Annette Chavez, MD; Richard Dlott, MD; William Greif, MD; Deepak Gurushanthaiah, MD; Andrew Klonecke, MD; Matthew Lando, MD; Joyce Leary, MD; Sundeep Nayak, MD; Ryan Niederkohr, MD; Judith Park, MD; Alison Savitz, MBA, MD; Henry Schwartz, MD Perm J 2016 Summer:20(3):16-035 E-pub: 07/29/2016 http://dx.doi.org/10.7812/TPP/16-035

ABSTRACT 30-day complications, mortality, readmission, and Emergency A need exists to reduce care variations by standardizing the Department visits; proportion of outpatient procedures; inci- practice of thyroid and parathyroid surgery. During the course of sion-to-closure (“cut-to-close”) time; and length of stay were a year, a task force developed algorithms representing decision assessed. For hemithyroidectomies, high-volume surgeons had points and workflows based on American Thyroid Association fewer readmitted patients, more outpatient procedures, shorter guidelines and three internal studies of surgical practices in the lengths of stay, and shorter cut-to-close times. For total thyroid- Northern and Southern California Regions of Kaiser Permanente ectomies, high-volume surgeons had lower rates of all surgery- conducted in collaboration with Health Information Technology related complications and of the individual complications of Transformation & Analytics (HITTA). hypocalcemia and surgical site infections, more outpatient procedures, and shorter lengths of stay and cut-to-close times. INTRODUCTION We concluded that high-volume surgeons improve patient safety In keeping with a movement toward specialty redesign based and have the potential to contribute to organizational efficiency on standardization and subspecialization, workflows were that may be underutilized in some settings. developed between March 2015 and March 2016 to guide The third study used decision-tree analysis to identify patient- evidence-based best practices and reduce disparities in care. level characteristics associated with 30-day complications after The evidence base for thyroid and parathyroid workup and thyroid and parathyroid surgery.4 Among patients undergoing surgical procedures includes American Thyroid Association thyroidectomies, the most important predictor of risk was thy- (ATA) guidelines1 and three studies2-3 of surgical practices in roid cancer. For patients with thyroid cancer, additional risk Kaiser Permanente (KP) Northern California and KP Southern predictors included coronary artery disease and central neck California conducted in collaboration with Health Information dissection. For patients without thyroid cancer, additional risk Technology Transformation & Analytics (HITTA). predictors included coronary artery disease, dyspnea, complete The first study used a robust set of variables and propensity thyroidectomy, and lobe size. Among patients undergoing score methods to match 2362 patients undergoing hemithy- parathyroidectomies, the most important risk predictor was roidectomy, total thyroidectomy, or parathyroidectomy as coronary artery disease, followed by cerebrovascular disease and outpatients (discharge within 8 hours of completion) to 2362 chronic kidney disease.3 patients undergoing the same procedures as inpatients.2 Out- Summaries of the evidence-based workflows are presented here. comes assessed were 30-day rates of complications, Emergency Department visits, all-cause hospital readmissions, and mortal- THYROID NODULE: WORKUP ity. No statistically significant differences between inpatients and Figure 1 diagrams the workup of the patient with thyroid outpatients were found for complication rates or postdischarge nodules. Thyroid nodules are evaluated to rule out cancer and utilization, and we concluded that outpatient surgery should rarely to address local symptoms. Palpable thyroid nodules are be used for all patients for whom it is appropriate.2 uncommon. Nonpalpable nodules are identified frequently on The second study used similarly robust variables and pro- imaging studies. Thyroid nodule evaluation requires a dedicated pensity score methods to match 3135 patients who underwent ultrasound examination of the thyroid and adjacent lymph hemithyroidectomy and total thyroidectomy, or parathyroid- nodes. Whereas most nodules are benign, clinically significant ectomy performed by a high-volume surgeon (> 40 cases per thyroid cancer is seen in a small minority of patients, and surgi- year) to 3135 patients with the same procedure performed by cal treatment may be necessary. Nearly all thyroid cancers are a low-volume surgeon (≤ 20 cases per year).3 Rates of all-cause differentiated (papillary, follicular, or mixed).

Charles Meltzer, MD, is the Regional Chair of Chiefs of Head and Neck Surgery for The Permanente Medical Group in Oakland, CA. E-mail: [email protected]. Amer Budayr, MD, is an Endocrinologist at the Oakland Medical Center in CA. E-mail: [email protected]. Annette Chavez, MD, is a General Surgeon at the Santa Clara Medical Center in CA. E-mail: [email protected]. Richard Dlott, MD, is an Endocrinologist at the Walnut Creek Medical Center in CA. E-mail: [email protected]. William Greif, MD, is a General Surgeon at the Walnut Creek Medical Center in CA. E-mail: [email protected]. Deepak Gurushanthaiah, MD, is an Otolaryngologist at the Oakland Medical Center in CA. E-mail: [email protected]. Andrew Klonecke, MD, is a Nuclear Medicine Specialist at the Sacramento Medical Center in CA. E-mail: [email protected]. Matthew Lando, MD, is an Otolaryngologist at the Union City Medical Center in CA. E-mail: [email protected]. Joyce Leary, MD, is an Endocrinologist at the Sacramento Medical Center in CA. E-mail: [email protected]. Sundeep Nayak, MD, is a Diagnostic Radiologist and Nuclear Medicine Physician at the San Leandro Medical Center in CA. E-mail: [email protected]. Ryan Niederkohr, MD, is the Chief of Nuclear Medicine at the Santa Clara Medical Center in CA. E-mail: [email protected]. Judith Park, MD, is a General Surgeon at the Richmond Medical Center in CA. E-mail: [email protected]. Alison Savitz, MBA, MD, is a General Surgeon at the Walnut Creek Medical Center in CA. E-mail: [email protected]. Henry Schwartz, MD, is an Endocrinologist at the Santa Rosa Medical Center in CA. E-mail: [email protected]

The Permanente Journal/Perm J 2016 Summer:20(3):16-035 57 ORIGINAL RESEARCH & CONTRIBUTIONS Evidence-Based Workflows for Thyroid and Parathyroid Surgery

Figure 1. Thyroid nodule: Workup (full-size, color version available at: www.thepermanentejournal.org/files/Summer2016/16035-1.pdf). a Consider observation alone depending on patient characteristics, comorbidities, and imaging features. b Bethesda System for Reporting Thyroid Cytopathology categories: I = nondiagnostic or unsatisfactory; II = benign; III = atypia of unknown significance; IV = follicular neoplasm or suspicious; V = suspicious for malignancy; VI = malignant. AUS = atypia of unknown significance; CT = computed tomography; FNA = fine-needle aspiration; I = iodine; MRI = magnetic resonance imaging;

Tg = thyroglobulin; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasound; X 2 = twice.

58 The Permanente Journal/Perm J 2016 Summer:20(3):16-035 ORIGINAL RESEARCH & CONTRIBUTIONS Evidence-Based Workflows for Thyroid and Parathyroid Surgery

The Permanente Journal/Perm J 2016 Summer:20(3):16-035 59 ORIGINAL RESEARCH & CONTRIBUTIONS Evidence-Based Workflows for Thyroid and Parathyroid Surgery

Serum thyroid-stimulating hormone (TSH, thyrotropin) FNA or ultrasound monitoring at 6 to 12 months is recom- levels should be measured as part of the initial evaluation of mended for low-risk nodules. If the repeated FNA is negative, a thyroid nodule. If serum TSH level is suppressed, further no further sonography is recommended. For high-risk nodules, workup for hyperthyroidism is warranted by confirming sup- repeated sonography and/or FNA in 6 to 12 months is recom-

pressed TSH level and checking the serum thyroxine (T4) level. mended. If the repeated FNA is also benign, repeated sonogra- If the TSH level remains suppressed, the patient should undergo phy is recommended in 2 or 3 years. a radioiodine thyroid uptake and scan. The workup and manage- The endocrinologist should discuss the indication for and ment of hyperthyroidism is beyond the scope of this summary. extent of thyroid surgery with the patient. All patients with a Observation is recommended for nodules that are predomi- diagnosis of thyroid cancer or a suspected thyroid cancer should nantly cystic or spongiform, for nodules smaller than 1.5 cm and be referred for surgery. It is advisable to refer patients to a high- in the absence of sonographic high-risk features, and for nodules volume surgeon with expertise in thyroid and parathyroid surgery. smaller than 1 cm and suspicious but with no high-risk factors. Diagnostic fine-needle aspiration (FNA) is recommended for THYROID NODULE: cytologic evaluation of nodules greater than 1 cm with a high- PERIOPERATIVE MANAGEMENT suspicion sonographic pattern. FNA is recommended for most Figure 2 displays the evidence-based recommendations for nodules 1.5 cm or larger. In addition to size criteria, high-risk perioperative management of thyroid nodules. Our KP study factors, including family history or other clinical features, may demonstrated increased efficiency and decreased complications influence the decision to perform an FNA of a smaller thyroid when management included a consultation with a high- nodule. volume thyroid surgeon (defined as having completed more Ultrasound-guided FNA is the procedure of choice in the than 40 cases per calendar year as the primary surgeon).3 evaluation of thyroid nodules. In the case of an incidentally Further analysis will inform our goal of directing care to noted thyroid nodule in a patient with clinically significant mor- higher-volume surgeons who perform at least 20 cases of bidities or a limitation in functional status, pursuing a diagnostic thyroid and parathyroid surgeries per year. Surgical risks and workup of the nodule may not be relevant. The most common potential postoperative complications should be carefully practice is to acquire two to three cytologic aspirates from each reviewed with the patient using a standardized procedure- nodule. If multiple nodules are found, the clinician should evalu- specific consent form. Patients with clinically significant ate each on the basis of size criteria and sonographic findings. substernal extension should be referred to a center with Medical therapy with levothyroxine is not indicated for the thoracic surgery backup. management of benign thyroid nodules. Preoperative documentation of the patient’s voice is rec- For indeterminate cytologic findings, such as the Bethesda ommended. Documentation can be accomplished by using System for Reporting Thyroid Cytopathology5 categories “atypia a patient-reported outcome tool, such as the Voice Handicap of undetermined significance or follicular lesion of undeter- Index, or by examination. Direct laryngeal evaluation should mined significance” or “follicular neoplasm or suspicious for be performed in patients with previous neck or thoracic sur- a follicular neoplasm,” molecular testing may be considered. gery, abnormal voice, or known thyroid cancer. Intraoperative Results of molecular testing may suggest the need for either monitoring of the recurrent laryngeal nerve is optional, but observation or total thyroidectomy. In the absence of molecular identification and preservation of the nerves is recommended. testing, diagnostic lobectomy remains the recommended initial Steps also should be taken to preserve the external branch of surgical procedure because malignancy may be present in up to the superior laryngeal nerve. 15% of these cases. The parathyroid glands should be preserved. Perioperative If abnormal results of cytologic evaluation are found and antibiotics are not routinely recommended unless the case is surgery is advised, it is important to have a detailed evaluation longer than anticipated or includes possible entrance into the of cervical lymph nodes to assist in surgical planning. If it has upper aerodigestive tract or a sternotomy. Drains also are not not been done already, the clinician should refer the patient for recommended unless there is a large residual space, lateral neck diagnostic imaging for a nodal compartment neck sonogram to dissection, or sternotomy. be available at the time of surgical consultation. Sonographi- Diagnostic lobectomy is typically appropriate for indeter- cally abnormal lymph nodes warrant added diagnostic workup minate lesions, atypia of undetermined significance lesions, by the endocrinologist or interventional radiologist, who will or suspicious for malignancy lesions smaller than 4 cm. Well- perform nodal FNA for cytologic analysis or thyroglobulin differentiated thyroid cancer that presents in a low-risk patient washout or both. as a nodule between 1 cm and 4 cm without extracapsular Primary hyperparathyroidism is uncommon but represents spread may be treated with thyroid lobectomy alone. Patients an important potential comorbidity for patients undergoing with nodules exceeding 4 cm or with contralateral nodules thyroid surgery. We recommend there be evidence of a serum should be considered for total thyroidectomy. However, the calcium level at least one year in advance of surgery to screen treatment team may recommend, or the patient may consider, for hypercalcemia. total thyroidectomy to avoid reoperation and/or to enable ra- A single benign FNA cytologic result does not guarantee dioactive iodine (RAI) ablation therapy. Thyroidectomy with- nodule benignity. The false-negative rate is 1% to 3%. Repeated out prophylactic central neck dissection may be appropriate for

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small T1 or T2 noninvasive, clinically node-negative papillary by the surgeon or by the patient, the clinician should conduct a thyroid carcinomas (cN0) and for most follicular cancers. laryngeal evaluation with early referral to speech therapy if dys- Patients with T3, T4, or any TN(+) or M(+) disease should function is present or suspected. undergo a near-total or total thyroidectomy, with therapeutic The endocrinologist is responsible for requesting postopera- central compartment (Level VI) neck dissection in the presence tive thyroid hormone replacement therapy and obtaining TSH of clinically involved nodes. Prophylactic central neck dissection and thyroglobulin measurements six to eight weeks after surgery. (ipsilateral or bilateral) should be considered in patients with advanced primary well-differentiated tumors with clinically in- THYROID CANCER: volved lateral neck lymph nodes or clinically uninvolved central POSTOPERATIVE INITIAL THERAPY neck lymph nodes (cN0) if the information will be used to plan The goal is to standardize initial postoperative treatment on further steps in therapy. Therapeutic lymph node dissection of the basis of postoperative ATA risk group determination and the the lateral neck compartment should be performed for patients patient’s early response to treatment (Figure 3). Using these in- with biopsy-proven metastatic lateral cervical lymphadenopathy. dividualized dynamic risk assessment tools, TSH treatment goals Postsurgical management of patients who undergo complete and early decisions about RAI therapy can be made. thyroidectomy includes levothyroxine supplementation with a The clinician should obtain TSH, thyroglobulin, and thyro- recommended standard dose of 1.5 µg/kg and adjustment to globulin antibody (TgAb) levels six to eight weeks after surgery. 1.0 µg/kg to 1.4 µg/kg for older patients or those with comor- Appropriate treatment planning is guided by correct cancer stag- bidities, such as cardiac disease. ing. Staging should be updated as additional clinical information Hypocalcemia management may be achieved with empirical becomes available. therapy or by obtaining intraoperative parathyroid hormone Using both the MACIS (metastasis, age at presentation, com- (PTH) levels, which can be drawn at the time the incision is pleteness of excision, invasion, size) scoring system (Figure 4) and closed. If the intraoperative PTH level exceeds 20 pg/mL, no sup- the ATA guidelines will help clarify the patient’s risk. Although plementation is recommended. For an intraoperative PTH level MACIS may be a better predictor of future survival/mortality, of 10 pg/mL to 20 pg/mL, we recommend prescribing calcium ATA risk stratification may be more predictive of local recur- supplementation at discharge; if the level is less than 10 pg/mL, the rence. When using the MACIS calculator (available on the clinician should recommend calcium supplements and prescribe Internet at www.thyroid.org/thyroid-cancer-staging-calculator calcitriol. If the intraoperative PTH level is less than 6 pg/mL or on KP HealthConnect in Northern California), one should or the patient is at high risk of postsurgical hypocalcemia and is assume no distant metastases to calculate the score unless dis- receiving empirical therapy or is symptomatic, one should con- tant metastases are known. The endocrinologist should note the sider checking a serum calcium level by the third postsurgical day. stage, MACIS score, ATA risk group, initial and current TSH Six to eight weeks postoperatively, the patient should undergo goal, appropriate tumor marker, use of RAI, and posttreatment a voice assessment via a telephone appointment visit and/or us- whole-body scan results as well as planned or last postoperative ing the Voice Handicap Index. If abnormal voice quality is noted thyroid ultrasonography.

MODIFIED 2009 ATA RISK STRATIFICATION (2015) LOW RISK INTERMEDIATE RISK HIGH RISK • No local or distant metastases • Microscopic invasion of tumor into • Macroscopic invasion of tumor • Clinically N0 or N1 micrometastases the perithyroidal soft tissues into the perithyroidal soft tissues (< 5 involved nodes with lesions < 2 mm) • Clinical N1 or > 5 pathologic N1 (gross extrathyroidal extension) • All macroscopic tumor resected with all involved lymph nodes • Incomplete tumor resection • No local invasion (no extrathyroidal < 3 cm in largest dimension • Distant metastases extension) • Radioactive iodine avid metastatic • Pathologic N1 with any metastatic • No vascular invasion foci in the neck on the first posttreat- LN ≥ 3 cm in largest dimension • If Iodine-131 given, no uptake except ment whole body radioactive iodine • Postoperative serum thyroglobulin in the thyroid bed scan suggestive of distant metastases • No aggressive history • Aggressive histology (eg, Tall cell, • Follicular thyroid cancer with • Intrathyroidal encapsulated follicular hobnail variant, columnar cell carci- extensive vascular invasion variant papillary thyroid cancer noma) (> 4 foci of vascular invasion) • Intrathyroidal well-differentiated fol- • Papillary thyroid cancer with > 4 foci licular with only capsular invasion of vascular invasion • Intrathyroidal well-differentiated • Intrathyroidal, papillary thyroid follicular with ≤ 4 foci of vascular cancer, primary tumor 1 cm - 4 cm, invasion V600E BRAF mutated (if known) • Intrathyroidal papillary microcarcino- • Multifocal papillary microcarcinoma ma, unifocal or multifocal, including with extrathyroidal extension and V600 BRAF mutated (if known) V600E BRAF mutated (if known)

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Figure 2. Thyroid nodule: Perioperative management (full-size, color version available at: www.thepermanentejournal.org/files/Summer2016/16035-2.pdf). AUS = atypia of unknown significance; FN = follicular neoplasm; ioPTH = intraoperative parathyroid hormone (pg/mL); RLN = recurrent laryngeal nerve;

T4 = thyroxine; TAV = telephone appointment “visit”; Tg = thyroglobulin; TID = three times a day; TSH = thyroid-stimulating hormone; X 2 = twice.

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Figure 3. Thyroid cancer: Postoperative initial therapy (full-size, color version available at: www.thepermanentejournal.org/files/Summer2016/16035-3.pdf). a Calculate MACIS (metastasis, age at presentation, completeness of excision, invasion, size) score as if there are no distant metastases, unless known. If Tg level is out of proportion to presumed burden of disease and MACIS score is borderline for therapy, proceed with radioactive iodine therapy. b See Sidebar: Modified 2009 ATA Risk Stratification (2015). ATA = American Thyroid Association; I = iodine; MACIS = metastasis, age at presentation, completeness of excision, invasion, size; RAI = radioactive iodine; rhTSH = recombinant human TSH; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone, mIU/L; THW = thyroid hormone withdrawal; USC = University of Southern California Endocrine Laboratories.

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A postoperative thyroglobulin level below 10 ng/mL suggests local disease, including lateral neck nodes, 150 mCi for pulmo- a low likelihood of clinically significant persistent disease. How- nary metastases, and 200 mCi for skeletal or other metastases. ever, a thyroglobulin level exceeding 10 ng/mL does not always Dosimetry can help avoid overtreatment in the case of co- indicate clinically significant residual disease, and confirmation morbid renal failure or widespread pulmonary metastases. If by a posttherapy scan is recommended. Initial thyroglobulin dosimetry in renal failure is not possible, the patient’s dialysis testing should be done using an assay sensitive for thyroglobulin schedule can guide empirical reduction of iodine(I)-131. If di- antibodies, given that the presence of antibodies can reduce the alysis occurs the day after treatment, the clinician should give validity of thyroglobulin measurements. 40% of the dose calculated as if the patient had normal renal On the basis of ATA risk group and response to therapy, function. If dialysis will occur 2 days later, 22% of the calculated patients with low-risk disease should be assessed for possible dose should be given. thyroid remnant ablation therapy with RAI. RAI remnant The likelihood of sufficient iodine clearance after a contrast ablation is an early option for patients who do not appear to computed tomography (CT) study at 4 months is approximately be heading for an excellent response to therapy. For most cases 95%. Patients may be treated after thyroid hormone withdrawal of remnant ablation, stimulation with recombinant human or after recombinant human TSH stimulation depending on TSH is recommended. Unifocal micropapillary disease is usu- risk stratification. ally treated only when the postoperative thyroglobulin level is higher than expected. THYROID CANCER: SURVEILLANCE Some patients with intermediate-risk disease and almost all Surveillance for differentiated thyroid cancer can be divided patients with high-risk disease benefit from RAI treatment. Thy- into biochemical and anatomic components (Figure 5). Bio- roglobulin and TgAb levels six to eight weeks after surgery aid chemical surveillance uses thyroglobulin and TgAb testing. Ana- in deciding which intermediate-risk patients might benefit from tomic surveillance is primarily done with neck ultrasonography. RAI. For the treatment of high-risk patients with known or sus- At 6 to 12 months postoperatively, thyroglobulin and TgAb pected metastatic disease, thyroid hormone withdrawal therapy testing should be performed with an assay highly sensitive for is recommended, often with pretherapy diagnostic scanning. TgAb. If TgAb levels are detectable, this same highly sensitive High-risk patients should be treated with recombinant hu- assay should be used for long-term surveillance of antibody levels. man TSH stimulation only if thyroid hormone withdrawal is If the TgAb level is undetectable, thyroglobulin levels can be medically contraindicated. Typical RAI doses are 125 mCi for used reliably for biochemical surveillance in most patients. Use of a thyroglobulin assay with detectability to below 0.2 ng/mL allows confidence in determination of a biochemically complete response to therapy and is preferred over less sensitive assays. Thyroglobulin and TgAb levels should be obtained every 3 to 12 months, depending on the patient’s ATA risk category. If the thyroglobulin or TgAb level increases 50% or more above the baseline for a given patient and is well above the limit of detec- tion, ultrasound evaluation should be obtained. Alongside regular biochemical surveillance, imaging with ultrasound is recommended 6 to 12 months after the initial therapy and periodically thereafter even if thyroglobulin/TgAb levels remain stable. Central lymph nodes less than 0.8 cm in the anterior-posterior dimension and lateral lymph nodes less than 1 cm in the anterior-posterior dimension should be monitored with serial imaging if thyroglobulin/TgAb markers are stable. If lymph nodes exceed these dimensions, they should undergo FNA biopsy with thyroglobulin washout. Patients with biopsy- proven or thyroglobulin washout-proven metastatic disease Figure 4. Screenshot of thyroid cancer staging: MACIS (metastasis, age should be referred for additional surgery. at presentation, completeness of excision, invasion, size) score calculator In the event that thyroglobulin/TgAb levels are rising but (full-size, color version available at: www.thepermanentejournal.org/files/Sum- enlarged lymph nodes are negative on FNA biopsy and thy- 1 mer2016/16035-4.pdf). roglobulin washout, additional imaging with CT or magnetic a Final prognostic score was defined as MACIS = 3.1 (if age ≤ 39 years) or 0.08 × age (if resonance imaging (MRI) should be performed. Any findings age ≥ 40 years), + 0.3 × tumor size (in centimeters), + 1 (if incompletely resected), + 1 (if locally invasive), + 3 (if distant metastases are present). on additional imaging should be considered for biopsy or b Twenty-year cause-specific survival rates are as follows for each MACIS score: MACIS surgery. However, if all imaging has normal findings in the < 6 = 99%; MACIS 6-6.99 = 89%; MACIS 7-7.99 = 56%; MACIS ≥ 8 = 24%. setting of rising thyroglobulin/TgAb levels, an I-123 whole- 1 Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a body scan is indicated. Disease identified on an I-123 scan

cohort of 1779 patients surgically treated at one institution during 1940 through 1989. can be treated with I-131 up to 150 mCi. In patients with Surgery 1993 Dec;114(6):1050-7; discussion 1057-8. thyroglobulin levels exceeding 10 ng/mL and no findings on

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Figure 5. Thyroid cancer: Surveillance (full-size, color version available at: www.thepermanentejournal.org/files/Summer2016/16035-5.pdf). CT = computed tomography; EBRT = external beam radiation therapy; 18FDG = fludeoxyglucose F 18; FNA = fine-needle aspiration; I = iodine; IR = interventional radiology; mets = metastases; MRI = magnetic resonance imaging; NED = no evidence of disease; path = pathology; PET = positron emission tomography; RAI = radioactive iodine;

T4 = thyroxine; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone, mIU/L; US = ultrasound; USC = University of Southern California Endocrine Laboratories; uTG = ultrasensitive thyroglobulin; X 2 = twice.

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ultrasound, CT or MRI, and I-123 scan, the clinician should 19% to 27% will remain in this category, and 8% to 27% will consider positron emission tomography-CT and case discus- experience a recurrence. sion with his/her local tumor board. Patients with “structurally incomplete responses” to therapy External beam radiation therapy is recommended for RAI- have persistent or newly identified locoregional or distantly meta- refractory disease or for treatment of symptomatic metastatic static disease, either biopsy-proven or likely disease as determined lesions. Tyrosine kinase inhibitors and clinical trials should be by imaging. In 5 to 10 years, 29% to 51% of these patients will considered for patients with progressive, RAI-refractory disease. move into the “excellent response” category. Mortality rates for Patients who are candidates for tyrosine kinase inhibitors should this group are highest, with death occurring in 11% of those with be thoroughly counseled on the potential risks and benefits of locoregional disease and 57% of those with distant metastases. this therapy as well as alternative therapeutic approaches, in- Finally, patients with “indeterminate responses” to therapy are cluding supportive care. those with nonspecific lesions and thyroglobulin/TgAb levels To facilitate understanding of probable long-term outcomes between 0.3 and 1 ng/mL. Most of these patients do well; at 5 and thereby guide surveillance frequency, one should ensure to 10 years, 80% to 87% will move into the “excellent response” that responses to therapy follow ATA recommendations and be group while 13% to 20% will move into the “biochemically” documented as “excellent response,” “biochemically incomplete or “structurally incomplete response” group. response,” “structurally incomplete response,” or “indeterminate All patients require TSH monitoring at least annually. Patients response” (Table 1). who are determined to be biochemically and structurally free of Patients with an “excellent response” to therapy have no disease and those with indeterminate responses should have TSH clinical, biochemical, or structural evidence of disease. For this levels maintained at 0.4 mIU/L to 2.0 mIU/L. Patients with designation, thyroglobulin levels must be below 0.2 ng/mL in biochemically or structurally incomplete responses to therapy the setting of negative TgAb levels, or the TgAb level must have should have TSH levels maintained at below 0.1 mIU/L if rea- dropped 50% or more from baseline. The recurrence rate in this sonable in the context of coexisting conditions and patient age. group is believed to be 1% or 2%. Patients with “biochemically incomplete responses” to therapy PRIMARY HYPERPARATHYROIDISM: have persistent thyroglobulin/TgAb levels in the absence of PREOPERATIVE PREPARATION localizable disease. Studies have shown no increase in disease- Overproduction of PTH resulting in abnormal calcium specific mortality for this group. At 5 to 10 years, 56% to 68% homeostasis covers a wide spectrum of presentations, including of these patients will move into the “excellent response” category, the following: • hypercalcemia with elevated PTH level • hypercalcemia with normal but inappropriate PTH level Table 1. Relationship of response to therapy at 6 to 18 months • eucalcemia with elevated PTH level in the absence of second- to initial risk stratification and outcomes at 5 to 15 years ary causes. Response to therapy at Symptoms may or may not be present and include but are not 6 to 18 months, % a a a limited to osteoporotic fractures, renal stones, constipation or Measure NED IDR BIR SIR abdominal pain, peripheral neuropathy, headaches, or psychiat- b Initial risk stratification ric symptoms. One should suspect primary hyperparathyroidism Low 86-91 12-29 11-19 2-6 (PHPT) in patients with hypercalcemia, inappropriately low Intermediate 57-63 8-23 21-22 19-28 bone density for age, or family history (hyperparathyroidism- High 14-16 0-4 16-18 67-75 jaw tumor syndrome, multiple endocrine neoplasia, and familial Outcomes at 5 to 15 years isolated hyperparathyroidism). No evidence of disease (NED)c 97-99 1-3 Secondary hyperparathyroidism often results from prolonged re- Indeterminant response (IDR)d 80-87 13-20 nal disease, especially after kidney transplantation when prolonged Biologically incomplete response (BIR)e 56-86 19-27 8-17 pretransplant parathyroid stimulation could result in autonomous Structurally incomplete response (SIR)f 29-51 PTH production and hypercalcemia. Patients treated with lithium, a Blank boxes indicate that the proportion of patients in the category is not reported in especially for prolonged periods, may present with secondary hyper- the literature. parathyroidism; lithium alters calcium sensing, causing four-gland b Modified 2009 American Thyroid Association Risk Stratification System (2015), hyperplasia. Some patients could harbor an unrelated underlying assessed 6 to 8 weeks postoperatively. c No clinical, biochemical, or structural evidence of disease (thyroglobulin antibody adenoma, and PHPT is detected in associated monitoring. [TgAb] negative: unstimulated thyroglobulin < 0.2 ng/mL; TgAb positive: > 50% drop in The ideal workup includes a simultaneous fasting serum calcium TgAb from preoperative level and no structural or functional disease). test and PTH measurement (Figure 6). When in doubt, one should d Nonspecific lesions and indeterminate thyroglobulin and TgAb values. e Persistent thyroglobulin or TgAb with no localizable disease; detectable nonstimulated repeat the PTH estimation. The most common causes of hypercal- thyroglobulin or positive TgAb without structural disease; typically, nonstimulated cemia other than PHPT are thiazide diuretics (through decreased re- thyroglobulin level > 1 ng/mL and < 50% drop in TgAb. sorption of calcium in the kidney) and malignancy (through a variety f Structural or functional (radioactive iodine, fludeoxyglucose F 18-positron emission tomography) evidence of persistent or newly identified locoregional or distant of mechanisms). Rarely, excess calcium ingestion or granulomatous metastases. Of patients with structurally incomplete response, 29% to 51% move to processes (including but not limited to tuberculosis and sarcoid- NED after follow-up surgery. The 15-year mortality for structurally incomplete response osis) can cause high serum calcium levels with suppressed PTH. is 11% for locoregional disease and 57% for structural distant metastases.

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Figure 6. Primary hyperparathyroidism: Preoperative management (full-size, color version available at: www.thepermanentejournal.org/files/Summer2016/16035-6.pdf). CT = computed tomography; GFR = glomerular filtration rate; HPT = hyperparathyroidism; MIBISPECT = technetium Tc 99 sestamibi single-photon emission-computed tomography scintigraphy; PTH = parathyroid hormone; SPECT CT = single-photon emission computed tomography; TAV = telephone appointment “visit”; US = ultrasound.

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Figure 7. Hyperparathyroidism: Intraoperative and postoperative management (full-size, color version available at: www.thepermanentejournal.org/files/Summer2016/16035-7.pdf). HPT = hyperparathyroidism; ioPTH = intraoperative parathyroid hormone (pg/mL); US = ultrasound; X 2 = twice.

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Diagnostic serum testing should include measurement of se- change the scope of the surgery. If the sonogram is nonlocalizing, rum creatinine to rule out renal disease, 25-hydroxyvitamin D, most experts proceed to parathyroid scintigraphy using techne- phosphorus, ionized calcium, albumin, and alkaline phospha- tium Tc 99m pertechnetate sestamibi washout imaging with or tase. The latter may be elevated in predominant bone disease, without SPECT (or SPECT CT) to improve localization together identifying high turnover and a resulting risk of hungry bone with sonography. Multiphasic CT may also be considered if the syndrome. combination of sonography and scintigraphy is nonlocalizing In determining whether surgical removal of parathyroid tissue is or discordant. A presurgical discussion about the likelihood of warranted, the clinician can use several criteria depending on the hyperplasia or multiple adenomas is recommended because of its presence or absence of symptoms. A 24-hour urine collection for potential to alter the surgical approach. calcium and creatinine will allow the calculation of renal calcium clearance. High urinary calcium loss may warrant surgical inter- HYPERPARATHYROIDISM: INTRAOPERATIVE vention; this is often present in PHPT. Low urinary calcium loss AND POSTOPERATIVE MANAGEMENT suggests familial hypocalciuric hypercalcemia, a benign condition Parathyroid Localization Studies for which surgery is not indicated. In advance of most surgical procedures, the surgeon knows Once the diagnosis of PHPT has been established, surgery is what will be resected and from which location (Figure 7). Para- the treatment of choice in the absence of a contraindication, such thyroid surgical therapy differs because the glands are small and as limited life expectancy, or evidence of end-organ damage (eg, of variable number and location. Although localization studies renal compromise, osteoporosis), especially in the presence of have improved greatly in the past three decades, we are sometimes evidence of disease progression. unable to reliably determine the number and location of all dis- If the patient is asymptomatic, we adhere to the guidelines for eased glands preoperatively. surgery from the Management of Asymptomatic PHPT Fourth With the advent of an inexpensive and relatively rapid intraopera- International Workshop in 2013.6 We would consider surgery if tive PTH assay, localization studies have become increasingly im- any of the following is present (see Figure 6): portant because minimally invasive procedures may be performed • hypercalcemia: serum calcium level exceeding 1 mg/dL above in approximately 85% of cases. As localization studies continue to the upper limit of normal be refined and new modalities are developed, our algorithm will • skeletal compromise evolve: we currently recommend a combination of sonography and - low bone mineral density determined by dual-energy x-ray sestamibi washout scintigraphy as first-line localization studies. absorptiometry: T-score at or below -2.5 at the lumbar spine, Parathyroid surgeons should become facile with in-office -so total hip, femoral neck, or distal one-third radius (standard nography. They have an excellent grasp of the anatomy and both bone density measurement sites); use Z-scores for premeno- typical and atypical locations of the parathyroid glands; therefore, pausal women and men younger than age 50 years using basic sonography skills, parathyroid surgeons may quickly - vertebral fracture demonstrated using radiography, CT, or become proficient at parathyroid sonography. Sestamibi washout vertebral fracture analysis scintigraphy is helpful should the sonogram be nonlocalizing, - history of fragility fracture (considered a skeletal complica- especially in mediastinal disease, in which there is no utility of tion of PHPT) sonography. Sestamibi washout scintigraphy is limited in the • renal compromise presence of multiglandular parathyroid disease or synchronous - glomerular filtration rate below 60 mL/min/1.73 m2 hyperfunctioning thyroid nodules. Multiphasic enhanced neck - 24-hour urine calcium level above 400 mg/day and increased CT may be of benefit when the sonography and scintigraphy are stone risk by biochemical stone analysis nonlocalizing, discordant, or both but has a distinct disadvantage - nephrolithiasis or nephrocalcinosis by x-ray, ultrasound, or CT of a very high radiation dose; it is thus not currently recom- • age under 50 years. mended as an initial localizing study. Additional studies—MRI, Meeting only a single criterion indicates the need for surgery. FNA with sonographic guidance, and venous sampling—may Other general criteria that the workshop itemized as an indica- be used, especially in revision cases for which we recommend tion for surgery include having concordant results with at least two modalities before • Medical surveillance is neither desired nor possible reexploration whenever possible. • The disease has progressed • The patient prefers surgery in the absence of meeting the afore- Intraoperative and Postoperative Management mentioned criteria (as long as there are no contraindications). A skilled parathyroid surgeon navigates the subtleties and The task force members thought that the defining criteria for a complexities of hyperparathyroidism. Before taking the patient neurocognitive component (including but not limited to fatigue to the operating theater, the surgeon will have thoroughly re- and depression) were not definitive. viewed the case and its corresponding localization studies to be Once the decision to proceed with surgical consultation is certain of the diagnosis of PHPT. If a localization study is not made, a preliminary thyroid sonogram is acquired to identify validated in the operating room and four normal glands are thyroid nodules and potentially localize a parathyroid adenoma. found, a surgeon who is certain of the diagnosis may confidently Ruling out medullary thyroid cancer (associated with MEN2A) expand the exploration, find the abnormal gland, and conclude in a nodule and workup of thyroid nodules before surgery may surgery successfully.

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A baseline intraoperative PTH measurement is critical for a Disclosure Statement focused exploration and also helps determine when to stop in a The author(s) have no conflicts of interest to disclose. bilateral exploration; more than 4 glands are present in approxi- mately 6% of cases. Owing to variable PTH kinetics, no perfect Acknowledgment criterion exists for terminating an operation. The more stringent The authors would like to thank Violeta Rabrenovich for material support of this work. Jennifer Green provided editorial assistance. the criteria, the higher the number of unnecessary explorations Kathleen Louden, ELS, of Louden Health Communications provided editorial that will occur. We now recognize that a drop in intraoperative assistance. PTH level exceeding 50% from the preexcision value does not result in an adequate cure rate, and we recommend continued How to Cite this Article exploration if the final PTH exceeds 65 pg/mL. In addition, Meltzer C, Budayr A, Chavez A, et al. Evidence-based workflows for current thinking suggests that patients with values exceeding thyroid and parathyroid surgery. Perm J 2016 Summer;20(3):16-035. 40 pg/mL may have hyperplasia. It is almost always better to DOI: http://dx.doi.org/10.7812/TPP/16-035. perform a bilateral exploration than to return at a later date to face a scarred operative field, where finding the diseased gland References 1. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association is more challenging and could result in greater complications. management guidelines for adult patients with thyroid nodules and differentiated The nature of renal hyperparathyroidism mandates bilateral thyroid cancer: the American Thyroid Association guidelines task force on thyroid exploration. A hyperplastic process involving all the glands is nodules and differentiated thyroid cancer. Thyroid 2016 Jan;26(1):1-133. DOI: http://dx.doi.org/10.1089/thy.2015.0020. generally present even when a localization study identifies only 2. Meltzer C, Klau M, Gurushanthaiah D, et al. Safety of outpatient thyroid and one or two abnormal glands, and hyperplastic glands can vary parathyroid surgery: a propensity score-matched study. Otolaryngol Head Neck greatly in size. Postsurgical hypercalcemia should be expected in Surg 2016 May;154(5):789-96. DOI: http://dx.doi.org/10.1177/0194599816636842. 3. Meltzer C, Klau M, Gurushanthaiah D, et al. Surgeon volume in thyroid and most cases of renal hyperparathyroidism. Monitor patients who parathyroid surgery: surgical efficiency, outcomes, and utilization. Laryngoscope have clinically significant bone disease with special vigilance. 2016 Jun 23 [Epub ahead of print]. DOI: http://dx.doi.org/10.1002/lary.26119. 4. Meltzer C, Klau M, Gurushanthaiah D, et al. Risk of complications after thyroidectomy and parathyroidectomy: a case series with planned chart review. Otolaryngol Head CONCLUSION Neck Surg 2016 May 3 [Epub ahead of print]. DOI: http://dx.doi.org/10.1177/ These workflows synthesize the best evidence currently avail- 0194599816644727. able about caring for patients with thyroid nodules and PHPT 5. Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda system for reporting thyroid cytopathology. Am J Clin Pathol 2009 Nov;132(5):658-65. and represent an attempt to standardize the care of patients with DOI: http://dx.doi.org/10.1309/AJCPPHLWMI3JV4LA. thyroid and parathyroid diseases. The evidence-based decision 6. Udelsman R, Akerstrom G, Biagini C, et al. The surgical management of points and workflows presented here support an initiative of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab 2014 Oct;99(10):3596-606. DOI: http://dx.doi. specialty care redesign to provide consistency in delivery of care org/10.1210/jc.2014-2000. and outcomes for our patient population. v

The Third View

The practical surgical question as to whether the cretinous symptoms following thyroidectomy are due to—1) Chronic asphyxia, as believed by Kocher; 2) Injury of the sympathetic and other nerve trunks; 3) Arrest of function of the thyroid gland; is almost settled in favor of the third view, and with it also the pathology of Myxoedema.

— Sir Victor Alexander Haden Horsley, FRS, 1857-1916, English neurosurgeon and neuroscientist

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Special Report The Truth about Truth-Telling in American Medicine: A Brief History

Bryan Sisk, MD; Richard Frankel, PhD; Eric Kodish, MD; J Harry Isaacson, MD Perm J 2016 Summer;20(3):15-219 E-pub 06/22/2016 http://dx.doi.org/10.7812/TPP/15-219

ABSTRACT physician should be the minister of hope and comfort to the sick Transparency has become an ethical cornerstone of American that by such cordials to the drooping spirit he may smooth the bed medicine. Today, patients have the right to know their health in- of death, revive expiring life, and counteract the depressing influ- formation, and physicians are obliged to provide it. It is expected ence of those maladies which rob the philosopher of fortitude, and that patients will be informed of their medical condition regardless the Christian consolation.”2 In his writings, Percival also discussed of the severity or prognosis. This ethos of transparency is ingrained whether a “falsehood may lose the essence of lying, and become in modern trainees from the first day of medical school onward. even praiseworthy, when the adherence to truth is incompatible However, for most of American history, the intentional withhold- with the practice of some other virtue of still higher obligation.”2 ing of information was the accepted norm in medical practice. It At the same time, there were less benevolent incentives for physi- was not until 1979 that a majority of physicians reported disclos- cians to occasionally refrain from honesty. American medicine in the ing cancer diagnoses to their patients. To appreciate the current mid-19th century was poorly organized and had limited authority state of the physician-patient relationship, it is important to un- in society. Physicians were the product of a fractured apprenticeship derstand how physician-patient communication has developed model with no oversight to ensure quality of training, which led to an over time and the forces that led to these changes. In this article, increase in the number of physicians, many of them poorly trained, we trace the ethics and associated practices of truth-telling during while professional competition also loomed from other medical sects, the past two centuries, and outline the many pressures that influ- including Thomsonians, eclectics, and homeopaths.3 In short, the enced physician behavior during that time period. We conclude mid-19th century medical market was saturated with physicians. that the history of disclosure is not yet finished, as physicians still For physicians to succeed, ensuring an ample number of patients struggle to find the best way to share difficult information without was paramount, and honesty occasionally took a backseat. In his causing undue harm to their patients. 1888 manual for success as a physician, DW Cathell intricately laid out methods by which physicians could create respectable images of A HISTORY OF DISCLOSURE IN MEDICINE themselves while also protecting their claim to patient populations.4 Pre-20th Century Communication Neuhauser5 observed, “His book was so popular that it was in its Disclosing bad news to patients has challenged physicians since 10th edition in 1892, last revised in 1922 and republished finally in the early days of American medicine. In the 19th century, physicians 1932.” In addition to meticulously describing the type of clothing to often made medical decisions on behalf of their patients, in what wear and the medical paraphernalia to display in the office, Cathell they perceived to be the patient’s best interest. This paternalistic also encouraged physicians to withhold information to prevent approach led most physicians to disclose only information that they patients from becoming medically self-sufficient. For example, he believed would not harm the patient, as embodied in the 1847 Code encouraged physicians to inscribe Latinate terms on medication of Ethics of the newly founded American Medical Association: vials to conceal their ingredients. He also believed that physicians A physician should not be forward to make gloomy prognos- should “avoid giving self-sufficient people therapeutic points that tications, because they savour of empiricism. … But he should they can thereafter resort to. … It is not your duty to cheat either not fail, on proper occasions, to give to the friends of the patient yourself or the other physicians out of legitimate practice by sup- timely notice of danger, when it really occurs; and even to the plying this person and that with a word-of-mouth pharmacopoeia patient himself, if absolutely necessary. … For, the physician for general use.”4 For both benevolent and self-serving reasons, should be the minister of hope and comfort to the sick.1 honesty was lower on the physician’s list of priorities. On one level, paternalism in this period was rooted in benevolent concern for the patient’s well-being. As further stated in the Code: THE DAWN OF THE 20TH CENTURY “The life of a sick person can be shortened, not only by the acts As the 20th century dawned, the physician’s standing in society but also by the words or the manner of a physician. It is, there- began to rise, in part because medical science was growing more so- fore, a sacred duty to guard himself carefully in this respect, and phisticated and physicians were becoming indispensable. “Every man, to avoid all things which have a tendency to discourage the patient it became clear, could not be his own physician.”3 This enhancement and to depress his spirits.”1 This ethical standard followed directly of status furthered a social divide between physicians and laymen, as from Thomas Percival’s 1803 treatise on medical ethics: “For the evidenced by an 1898 excerpt from the Philadelphia Medical Journal:

Bryan Sisk, MD, is a Pediatrics Resident at the St Louis Children’s Hospital in MO. E-mail: [email protected]. Richard Frankel, PhD, is a Professor of Medicine and Geriatrics at the Indiana University School of Medicine Education Institute in Indianapolis. E-mail: [email protected]. Eric Kodish, MD, is the Director of the Center for Ethics, Humanities and Spiritual Care at the Cleveland Clinic in OH. E-mail: [email protected]. J Harry Isaacson, MD, is the Director of Clinical Education at the Cleveland Clinic Lerner College of Medicine and an Internist in the Department of General Internal Medicine at the Cleveland Clinic in OH. E-mail: [email protected]

74 The Permanente Journal/Perm J 2016 Summer;20(3):15-219 ORIGINAL RESEARCH & CONTRIBUTIONS The Truth about Truth-Telling in American Medicine: A Brief History

Into many homes the doctor brings the only refinement the status quo. The Civil Rights Movement pushed for passage of and culture that its inmates ever come in contact with. They the Civil Rights Bill18 and the Voting Rights Act.19 The feminist recognize it, just as do even dumb animals, and it must have movement demanded more autonomous control of women’s re- an elevating effect, if only a temporary one. His quiet air of productive health and a shift in society’s view of women.20,21 The composure, and that reserved force which education and cul- 1960s also marked the beginning of a psychedelic culture of drug ture set up in a man, appeal to poor fallen wretches as some- experimentation, the sexual revolution, and the countercultural thing worthy of admiration, even if they have not the strength “hippie” movement.22 It was not uncommon for people to wear remaining to care to strive toward it.6 buttons stating “Question Authority.” As society was redefining The growing class divide and the perceived dangers of bad news itself, “a new wave of individualism was breaking over the Western perpetuated the paternalistic approach of benevolent deception. world—most marked and most advanced in the United States.”23 An article in 1898, more than 50 years after the initial American Long-held social norms were being turned upside down in all Medical Association Code of Ethics, repeated this same prin- segments of society, including the physician-patient relationship. ciple of nondisclosure nearly verbatim: “In regard to cancer, the Owing in part to several well-publicized controversies, there was consensus of opinion is that patients be kept in ignorance of the a new call for protection from the medical establishment. In 1963, it nature and probable outcome of the disease as long as possible, was revealed that researchers in New York had injected humans with in this way obviating the severe mental depression which invari- live cancer cells without consent.24 In 1964, a surgeon transplanted ably accompanies such knowledge.”7 The cause for concern was chimpanzee kidneys into patients with renal failure without medical unchanged: “It is not merely the danger of ‘fatal shock’ that should approval from the hospital.25 By 1966, Henry Beecher published a restrain a physician in many cases from disclosing the truth to his special report highlighting and summarizing the widespread pres- patient, but the almost certainty that such a disclosure will be the ence of “troubling practices” in clinical research.26 greatest obstacle to a cure.”8 In 1909, William Osler declared, “It Perhaps most notably, the ethical concerns of the Tuskegee Syphi- is a hard matter … to tell a patient that he is past all hope. As Sir lis Study came to light in July 1972. This study, initiated in 1932, Thomas Browne says: ‘It is the hardest stone you can throw at a was a “long-term evaluation of the effect of untreated syphilis in man to tell him that he is at the end of his tether.’”9 The reason- the male Negro.”27 Physicians informed participants that they were ing was simple. “With many hospital patients once we gain their being treated for “bad blood” but not specifically syphilis. When confidence and inspire them with hope, the battle is won.”9 the study began, treatments for syphilis were harsh and minimally effective. However, penicillin was established as an effective treat- MID-20TH CENTURY AND BEYOND ment and became readily available by the late 1940s.28 Yet 20 years Although there were some opponents of benevolent deception, later, only 33% of participants had received curative therapy, and physician surveys during the first half of the 20th century con- many had died of complications from syphilis.27 This story quickly sistently demonstrated a belief in nondisclosure. As recently as became front-page news in the New York Times29 on July 25, 1972 1961, 90% of physicians preferred not to disclose cancer diagnoses with the headline “Syphilis Victims in US Study Went Untreated to patients.10 This was despite the results of a 1950 study show- for 40 Years.” Other headlines in the following weeks included “A ing that a vast majority of patients wanted to know the truth.11 Shocking Medical Experiment,” “Humans as Guinea Pigs,” and “A On the basis of his observations in a veterans’ hospital in 1966, Violation of Human Dignity.” The fallout from this exposé further Glaser12 proposed several factors that influenced the physicians’ exacerbated the adversarial relationship between medicine and so- approaches to disclosure: ciety, especially in the African American community. Few doctors get to know each terminal patient well enough Twenty years earlier in 1951, an African American woman to judge his desire for disclosure or his capacity to withstand named Henrietta Lacks was diagnosed with cervical cancer in the shock of disclosure … . Some doctors simply feel unable Baltimore, MD. When the physicians diagnosed her with cancer, to handle themselves well enough during disclosure. … Others they took a specimen from her cervix without her knowledge or do not tell because they did not want the patient to “lean” on consent. She died soon after, but her cells lived on as the HeLa them for emotional support, or because they simply wish to cell line, using the first 2 letters of her first and last name. These preserve peace on the ward by preventing a scene.12 cells had an enormous impact on public health and the advance- During the 1960s, tremors of change began rumbling through ment of science, but the family was not informed until the 1970s, American society. After the assassination of President John Ken- 20 years after Ms Lacks’ death.30 Though this was not as widely nedy, President Lyndon Johnson “sponsored the largest reform publicized as the Tuskegee scandal, it provides yet another example agenda since Roosevelt’s New Deal.”13 From 1963 through 1966, of troubling research practices at that time. Johnson undertook a major reform agenda that touched on many As controversies grew, new protections for patients and research aspects of society. With the expansion of Social Security to include subjects were established. In 1962, the Senate passed the Kefauver- Medicare and Medicaid, as well as the passage of the Food Stamp Harris Drug Amendments,31 requiring for the first time that drug Act,14 Housing and Urban Development Act,15 Child Protection manufacturers “prove to FDA the effectiveness of their products Act,16 and the Child Nutrition Act,17 the government assumed ad- before marketing them.”32 That same year, President Kennedy pro- ditional responsibility for the safety and well-being of its citizens. claimed a “Consumer Bill of Rights,” which included “the right to The 1960s also marked the start of a great transformation in safety, the right to be informed, the right to choose, and the right American social norms as underrepresented groups challenged to be heard.”32 In 1964, the World Medical Association published

The Permanente Journal/Perm J 2016 Summer;20(3):15-219 75 ORIGINAL RESEARCH & CONTRIBUTIONS The Truth about Truth-Telling in American Medicine: A Brief History

the Declaration of Helsinki, an international code of research ethics Standards of care now include an explicit focus on disclosure affirming that the physician’s first duty is to the research subject.33 and communication skills. In 2013, the Institute of Medicine Simultaneously, informed consent law was growing in strength, published a monograph on delivering high-quality cancer care mandating honest communication between physicians and pa- that focused an entire chapter on evidence for best practices in tients under threat of legal liability. Also, Dame Cicely Saunders communicating with cancer patients.42 The National Cancer In- introduced the concept of hospice and palliative care to the US in stitute produced an entire monograph on patient-centered com- the 1960s, further encouraging discussions between physician and munication in cancer care, devoting four of its six chapters to key patient about death. By 1973, the American Hospital Association communication skills including delivery of difficult news.43 Most created “A Patient’s Bill of Rights,” stating that “The patient has recently in 2014, the Institute of Medicine issued a new report that the right to and is encouraged to obtain from physicians and their focused on end-of-life care in America, much of which centered direct caregivers relevant, current, and understandable information on ways to improve the physician-patient dialogue about bad concerning diagnosis, treatment, and prognosis.”34 news.44 Medical students and residents are now routinely trained Responding to these pressures, physicians began calling for in how to effectively communicate in challenging situations, and more transparency with patients. Nahum noted in 1963, “The patients expect transparency in their interactions with physicians. responsible physician should have no hesitation in frankly but However, communication in medicine is still far from perfect. tactfully and at the correct time answering questions asked by the For example, a recent report from the Alzheimer’s Association patient,” with the goal of being “truthful with the patient while in 2015 showed that less than half of patients with Alzheimer’s at the same time avoiding a major emotional upset.” However, disease or their family members had knowledge of their loved Nahum moderated this approach with a list of stipulations. “In one’s or their own diagnosis.45 One physician noted in a media patients judged to be unstable emotionally, the exact information interview following the report, “It’s difficult to disclose a diagnosis should be withheld.” Additionally, “if he does not [ask for specific of a fatal brain disease in just a few minutes.”46 In parallel with information], then the doctor’s legal and moral obligations have these changes, the American Medical Association Code of Ethics been discharged for such a person … is aware of his trouble but has evolved substantially since 1847, with its current form stating does not wish to have it put into words.”35 An article from 1974 “The patient has the right to receive information from physicians pushed disclosure further, concluding that several factors could and to discuss the benefits, risks, and costs of appropriate treat- “justify me in modifying my primary approach and making the ment alternatives.”47 patient or his relatives, directly or indirectly, aware of the diagnosis Reinforcing these changes, the medical record has also evolved and perhaps even of the prognosis, grave as it may be.”36 In 1969, from a tool solely for physicians to a new means of communicat- Kubler-Ross37 declared, “The question should not be ‘Should ing with patients. In 1973, Shenkin and Warner48 proposed that we tell…?’ but rather ‘How do I share this with my patient?’” “legislation be passed to require that a complete and unexpurgated The medical profession was transitioning from paternalism to a copy of all medical records … be issued routinely and automati- partnership-based medical ethics where patients participated in cally to patients as soon as the services provided are recorded.” the decision-making process. In 1979, a landmark study using the This article furthered the belief that patients are owners of their same research questionnaire from 1961 showed that more than medical information. In 1991, McLaren49 proposed that medical 90% of a new cohort of physicians preferred disclosing cancer records should not only be available, but also be understandable diagnoses, a complete reversal from 18 years prior.38 to patients. The Health Insurance Portability and Accountability The progressive movement of the 1960s and 1970s pushed Act50 was passed in 1996, creating new protections for patient physicians toward more open and transparent communication confidentiality by restricting disclosure of medical information with patients. This transition was reinforced by social pressure, le- without the patient’s consent. This act reinforced the patient’s gal mandates, and large numbers of young, progressive physicians authority over his or her health information, while also mandating entering the field. In the midst of these changes, Family Practice that physicians respect their patients’ confidentiality. (now Family Medicine) developed as a new field, with an emphasis Communication in medicine has undergone dramatic changes on the individual patient and his or her social environment. This during the past 170 years. Where once physicians withheld informa- trend toward transparency has continued over the ensuing de- tion for the benefit of the patient, it is now clearly recognized that cades, reinforced in part by developments in the field of bioethics. patients have a right to know the truth. The medical profession has The 1979 “Belmont Report” established the fundamental ethical responded to both internal and external pressures and developed a principles of research on human subjects, including respect for standard of care based on honesty and patient-centered communica- persons, beneficence, and justice.39 These principles have served as tion. However, many uncertainties remain. How much disclosure the foundation for current research practices. is enough? How much is too much? Can we cause harm by telling Advancements in research on physician-patient communication too much or in the wrong way? Is there ever a role for benevolent have also supported the trend toward disclosure. In 1987, Mena- deception? Should physicians be the gatekeepers of medical infor- hem40 showed that communication in a partnership model was mation? How will the recent emphasis on shared medical records more effective than either a laissez-faire or physician-dominated affect this relationship? Currently, several organizations are actively model. In 1995, Girgis and Sanson-Fisher41 published consensus promoting sharing of medical data and notes with patients.51 Some guidelines for giving bad news, which have provided a basis for current-day patients might have their test results available electroni- discussion and improvement of communication in medicine. cally before ever speaking with their physicians.

76 The Permanente Journal/Perm J 2016 Summer;20(3):15-219 ORIGINAL RESEARCH & CONTRIBUTIONS The Truth about Truth-Telling in American Medicine: A Brief History

Though we can certainly say that “patients ought to know,” it is 22. Freedman DX. On the use and abuse of LSD. Arch Gen Psychiatry 1968 Mar;18(3):330-47. DOI: http://dx.doi.org/10.1001/archpsyc.1968.01740030074008. difficult to know exactlywhat they ought to know, and how to best 23. Cassell EJ. The nature of suffering and the goals of medicine. 2nd ed. New York, NY: share this information. These are critical questions that are worthy of Oxford University Press; 2004. study. The truth about truth-telling is that it is an unfinished history 24. Katz J. Experimentation with human beings: the authority of the investigator, subject, professions, and state in the human experimentation process. New York, NY: Russell that continues to evolve. Physicians and patients will undoubtedly Sage Foundation; 1972. need to partner to develop the next chapter in this story. v 25. Reemtsma K, McCracken BH, Schlegel JU, Pearl M. Heterotransplantation of the kidney: two clinical experiences. Science 1964 Feb 14;143(3607):700-2. DOI: http:// Disclosure Statement dx.doi.org/10.1126/science.143.3607.700. 26. Beecher HK. Ethics and clinical research. N Engl J Med 1966 Jun 16;274(24):1354-60. The author(s) have no conflicts of interest to disclose. DOI: http://dx.doi.org/10.1056/nejm196606162742405. 27. Rockwell DH, Yobs AR, Moore MB Jr. The Tuskegee study of untreated syphilis; the Acknowledgments 30th year of observation. Arch Intern Med 1964 Dec;114:792-8. DOI: http://dx.doi.org/ Thank you to Lauren Yaeger, MA, MLIS, medical librarian at St Louis 10.1001/archinte.1964.03860120104011. Children’s Hospital, for assisting our research in Internet databases and the 28. Kampmeier RH. The Tuskegee study of untreated sphilis. South Med J 1972 Oct;65(10):1247-51. DOI: http://dx.doi.org/10.1097/00007611-197210000-00016. historical archives. 29. Heller J. Syphilis victims in US study went untreated for 40 years. The New York Times Mary Corrado, ELS, provided editorial assistance. 1972 Jul 26;pp 1, 8. 30. Skloot R. The immortal life of Henrietta Lacks. New York, NY: Broadway Paperbacks; 2011. How to Cite this Article 31. The Drug Amendments of 1962. Public Law 87-781, 87th Congress, 76 Stat 780, Sisk B, Frankel R, Kodish E, Isaacson JH. The truth about truth-telling in enacted 1962 Oct 10. American medicine: a brief history. Perm J 2016 Summer;20(3):15-219. 32. Significant dates in US food and drug law history [Internet]. Silver Spring, MD: US Food DOI: http://dx.doi.org/10.7812/TPP/15-219. and Drug Administration; 2014 Dec 19 [cited 2015 Sep 21]. Available from: www.fda. gov/AboutFDA/WhatWeDo/History/Milestones/ucm128305.htm. 33. Rickham PP. Human experimentation. Code of ethics of the World Medical Association. References Declaration of Helsinki. Br Med J 1964 Jul 18;5(5402):177. 1. Code of ethics of the American Medical Association [Internet]. Chicago, IL: American 34. A patient’s bill of rights [Internet]. Chicago, IL: American Hospital Association; 1973 Medical Association; 1847 [cited 2015 Sep 21]. Available from: https://collections.nlm. [revised 1992; cited 2015 Sep 21]. Available from: www.carroll.edu/msmillie/bioethics/ nih.gov/bookviewer?PID=nlm:nlmuid-63310420R-bk. patbillofrights.htm. 2. Percival T. Medical ethics or, a code of institutes and precepts, adapted to the 35. Nahum LH. To tell the truth. Conn Med 1963 Aug;27:443-5. professional conduct of physicians and surgeons: to which is added an appendix. 3rd 36. Snyman HW. Should the doctor tell? South Afr Cancer Bull 1974 Oct-Dec;18(4):130-4. ed. Oxford, United Kingdom: Oxford University Press; 1849. p 48-9, 135. 37. Kubler-Ross E. On death and dying. New York, NY: Macmillan; 1969. 3. Starr P. The social transformation of American medicine: the rise of a sovereign 38. Novack DH, Plumer R, Smith RL, Ochitill H, Morrow GR, Bennett JM. Changes in profession and the making of a vast industry. 1st ed. New York, NY: Basic Books; 1982. physicians’ attitudes toward telling the cancer patient. JAMA 1979 Mar 2;241(9):897- 4. Cathell DW. Book on the physician himself and things that concern his reputation and 900. DOI: http://dx.doi.org/10.1001/jama.241.9.897. success. 9th ed [Internet]. Philadelphia, PA: F. A. Davis; 1889 [cited 2015 Sep 21]. 39. The National Commission for the Protection of Human Subjects of Biomedical and p 176. Available from: www.archive.org/details/cu31924000283626. Behavioral Research. The Belmont report: ethical principles and guidelines for the 5. Neuhauser D. Public opinion is our supreme court: D W Cathell MD, the physician protection of human subjects of research [Internet]. Washington, DC: US Department himself. Qual Saf Health Care 2005 Oct;14(5):389-90. http://dx.doi.org/10.1136/ of Health and Human Services; 1979 Apr 18 [cited 2014 Dec 15]. Available from: qshc.2005.015750. www.hhs.gov/ohrp/humansubjects/guidance/belmont.html. 6. Conway WB. The relation between physician and patient. The Philadelphia Medical 40. Menahem S. Teaching students of medicine to listen: the missed diagnosis from a Journal 1898 Jul-Dec;2:918-9. hidden agenda. J R Soc Med 1987 Jun;80(6):343-6. 7. Mapes CC. Shall patients be informed that they have cancer or syphilis? New York 41. Girgis A, Sanson-Fisher RW. Breaking bad news: consensus guidelines for medical Medical Journal 1898 Oct;5:560-2. practitioners. J Clin Oncol 1995 Sep;13(9):2449-56. 8. Sutro T. Do professional ethics require a physician to disclose to his patient an 42. Levit LA, Balogh EP, Nass SJ, Ganz PA, editors. Delivering high-quality cancer care: unfavorable prognosis. The Medical Times 1915 Apr;43:115-7. charting a new course for a system in crisis. Washington, DC: Institute of Medicine of 9. Osler W. An address on the treatment of disease: being the address in medicine the National Academies; 2013 Sep 10. before the Ontario Medical Association, Toronto, June 3rd, 1909. Br Med J 1909 Jul 43. Epstein RM, Street RJ Jr. Patient-centered communication in cancer care: promoting 24;2(2534):185-9. healing and reducing suffering. NIH publication no. 07-6225. Bethesda, MD: National 10. Oken D. What to tell cancer patients. A study of medical attitudes. JAMA 1961 Apr Cancer Institute; 2007. 1;175:1120-8. DOI: http://dx.doi.org/10.1001/jama.1961.03040130004002. 44. Committee on Approaching Death: Addressing Key End-of-Life Issues. Dying in 11. Kelly WD, Friesen SR. Do cancer patients want to be told? Surgery 1950 Jun;27(6):822-6. America: improving quality and honoring individual preferences near the end of life. Washington, DC: The National Academies Press; 2014 Sep 17. 12. Glaser BG. Disclosure of terminal illness. J Health Hum Behav 1966 Summer;7(2): 83-91. DOI: http://dx.doi.org/10.2307/2948723. 45. 2015 Alzheimer’s disease facts and figures. Alzheimer’s & dementia 2015 [Internet]. Portland, OR: Alzheimer’s Association; 2015 [cited 2015 Apr 1]. Available from: 13. 56e. Lyndon Johnson’s “Great Society” [Internet]. Philadelphia, PA: Independence Hall www.alz.org/facts/downloads/facts_figures_2015.pdf. Association; c2014 [cited 2015 Sep 21]. Available from: www.ushistory.org/us/56e.asp. 46. Hamilton J. Many doctors who diagnose Alzheimer’s fail to tell the patient [Internet]. 14. The Food Stamp Act of 1964. Public Law 88-525, 88th Congress, 78 Stat 703, HR Washington, DC: National Public Radio; 2015 Mar 24 [updated 2015 Apr 1; cited 2015 10222, enacted 1964 Aug 31. Apr 1]. Available from: www.npr.org/sections/health-shots/2015/03/24/394927484/many- 15. The Housing and Urban Development Act of 1965. Public Law 89-117, 89th Congress, doctors-who-diagnose-alzheimers-fail-to-tell-the-patient. 79 Stat 451, HR 7984, enacted 1965 Aug 10. 47. AMA’s code of medical ethics [Internet]. Chicago, IL: American Medical Association; 16. The Child Protection Act of 2012. Public Law 112-206, 112th Congress, 126 Stat 1490, 1957 Jun [revised 2001 Jun; cited 2015 Sep 21]. Available from: www.ama-assn.org/ HR 6063, enacted 2012 Dec 7. ama/pub/physician-resources/medical-ethics/code-medical-ethics.page?. 17. The Child Nutrition Act of 1966. Public Law 89-642, 89th Congress, 80 Stat 885, 48. Shenkin BN, Warner DC. Sounding board. Giving the patient his medical record: a enacted 1966 Oct 11. proposal to improve the system. N Engl J Med 1973 Sep 27;289(13):688-92. DOI: 18. The Civil Rights Act of 1964. Public Law 88-352, 88th Congress, 78 Stat 241, HR 7152, http://dx.doi.org/10.1056/nejm197309272891311. enacted 1964 Jul 2. 49. McLaren P. The right to know. BMJ 1991 Oct 19;303(6808):937-8. DOI: http://dx.doi. 19. The Voting Rights Act of 1965. Public Law 89-110, 89th Congress, 79 Stat 437, enacted org/10.1136/bmj.303.6808.937. 1965 Aug 6. 50. The Health Insurance Portability and Accountability Act of 1996. Public Law 104-191, 20. Millenson ML. Spock, feminists, and the fight for participatory medicine: a history. J 104th Congress, 110 Stat 1936, HR 3103, enacted 1996 Aug 21. Particip Med 2011 Jun 21;3:e27. 51. Foundations unite to support access to clinical notes for 50 million patients nationwide 21. Eagly AH, Eaton A, Rose SM, Riger S, McHugh MC. Feminism and psychology: [Internet]. OpenNotes.org; 2015 Dec 15 [cited 2016 Mar 22]. Available from: www.opennotes. analysis of a half-century of research on women and gender. Am Psychol 2012 org/foundations-unite-to-support-access-to-clinical-notes-for-50-million-patients-nationwide. Apr;67(3):211-30. DOI: http://dx.doi.org/10.1037/a0027260.

The Permanente Journal/Perm J 2016 Summer;20(3):15-219 77 REVIEW ARTICLE Hyperparathyroidism of Renal Disease

Noah K Yuen, MD; Shubha Ananthakrishnan, MD; Michael J Campbell, MD Perm J 2016 Summer;20(3):15-127 E-pub: 07/22/2016 http://dx.doi.org/10.7812/TPP/15-127

ABSTRACT NORMAL CALCIUM AND PHOSPHORUS HOMEOSTASIS Renal hyperparathyroidism (rHPT) is a common complication Calcium and phosphorus homeostasis is maintained through of chronic kidney disease characterized by elevated parathyroid a complex relationship between the bones, intestine, kidneys, hormone levels secondary to derangements in the homeostasis of and parathyroid glands. PTH is probably the most important calcium, phosphate, and vitamin D. Patients with rHPT experience regulator of calcium metabolism and functions primarily via 3 increased rates of cardiovascular problems and bone disease. The mechanisms: Kidney Disease: Improving Global Outcomes guidelines recom- 1. PTH is thought to stimulate PTH receptors mainly on osteo- mend that screening and management of rHPT be initiated for all blasts, which then, through multiple cell-to-cell mechanisms, patients with chronic kidney disease stage 3 (estimated glomerular stimulate osteoclast formation and bone resorption, leading filtration rate, < 60 mL/min/1.73 m2). Since the 1990s, improving to increased serum calcium and phosphorus levels.13 medical management with vitamin D analogs, phosphate binders, 2. PTH activates 1-α-hydroxylase in the kidney, which catalyzes and calcimimetic drugs has expanded the treatment options for the conversion of nonactive 25-hydroxy (25-OH) vitamin D patients with rHPT, but some patients still require a parathyroid- to activated 1,25 dihydroxy (1,25-OH) vitamin D. This leads ectomy to mitigate the sequelae of this challenging disease. to increased absorption of calcium and phosphorus in the gut. 3. PTH increases reabsorption of calcium and decreases reab- BACKGROUND sorption of phosphorus in the kidney. In the US, chronic kidney disease (CKD) affects 14% of the Recently, there has been much interest in the role of fibro- population,1,2 including approximately 660,000 patients with blast growth factor 23 (FGF-23), a protein secreted by bone in end-stage renal disease (ESRD) who are dialysis-dependent.2 response to hyperphosphatemia, which functions primarily in Renal hyperparathyroidism (rHPT) is a common complication maintaining phosphorus homeostasis. FGF-23 stimulates phos- of CKD characterized by derangements in the homeostasis of phorus excretion in the kidney mainly through reduced action of calcium, phosphorus, and vitamin D.3 rHPT is associated with sodium-phosphate co-transporter in the proximal tubule. It also increased cardiovascular morbidity and mortality4-8 and has a decreases 1-α-hydroxylase activity, leading to reduced 1,25-OH significant economic burden on the US health care system.9 vitamin D levels.14,15 In CKD, FGF-23 levels progressively rise rHPT is classically broken into 2 types on the basis of the and are initially thought to be beneficial, given the phosphatu- patient’s serum calcium level. Secondary hyperparathyroidism ric effects. However, increasing FGF levels are also associated (2° HPT) is the elevation of parathyroid hormone (PTH) in with increased cardiovascular mortality in patients with CKD.16 response to hypocalcemia induced by phosphate retention and reduced calcitriol synthesis as a consequence of reduced renal func- PATHOGENESIS tion.10 In 2° HPT, all the parathyroid glands become enlarged ow- The pathogenesis of rHPT is complex and incompletely ing to parathyroid hyperplasia. Because 2° HPT is a compensatory understood (Figure 1). An increase in PTH levels typically de- mechanism of the parathyroid glands, it commonly resolves with velops when the glomerular filtration rate (GFR) drops below normalization of calcium and phosphorus homeostasis (eg, renal 60 mL/min/1.73 m2. Abnormalities in serum levels of phospho- transplantation). Tertiary hyperparathyroidism (3° HPT) is seen rus and calcium tend to occur much later in the course of CKD when a patient with longstanding 2° HPT develops autonomous (typically when the GFR drops below 40 mL/min/1.73 m2).17 PTH secretion, often associated with hypercalcemia. This is ob- Initially, the elevated PTH levels serve to increase renal phos- served in up to 30% of patients with ESRD, who then undergo phorus excretion. However, as the GFR declines further, se- renal transplant.11 3° HPT is classically thought to have come from rum phosphorus levels start to rise and induce hypocalcemia

parathyroid hyperplasia, but some studies have suggested that by binding bioavailable calcium as CaHPO4, which indirectly up to 20% of patients may have single or double adenomas.11,12 leads to a further rise in PTH production. CKD also leads to Since the 1990s, improving medical management with vi- decreased activity of 1-α-hydroxylase, thereby decreasing 1,25- tamin D analogs, phosphate binders, and calcimimetic drugs OH vitamin D. A lack of 1,25-OH vitamin D inhibits gastro- has expanded the treatment options for patients with rHPT, intestinal absorption of calcium and also directly stimulates the but parathyroidectomy remains necessary for many patients. parathyroid glands.14

Noah K Yuen, MD, is a Surgical Resident at the University of California, Davis in Sacramento. E-mail: [email protected]. Shubha Ananthakrishnan, MD, is an Assistant Professor of Internal Medicine at the University of California, Davis in Sacramento. E-mail: [email protected]. Michael J Campbell, MD, is an Assistant Professor in the Department of Surgery at the University of California, Davis in Sacramento. E-mail: [email protected].

78 The Permanente Journal/Perm J 2016 Summer;20(3):15-127 REVIEW ARTICLE Hyperparathyroidism of Renal Disease

CLINICAL MANIFESTATIONS The two most important sequelae of rHPT are 1) renal os- teodystrophy and 2) cardiovascular disease. Recognizing that the bone and cardiovascular complications seen in CKD are manifestations of a broader interrelated syndrome, the National Kidney Foundation initiated the term “CKD-mineral and bone disorder” to describe the complex pathophysiology of the cal- cium, phosphorus, and PTH derangements seen in CKD. The paradigm of “think beyond the bones” is emphasized to bring early attention to the complications of rHPT in an attempt to improve morbidity and mortality.20 Renal osteodystrophy refers to a group of bone disorders caused by dysregulation of mineral metabolism in CKD, including osteomalacia, adynamic bone disease, and osteitis fibrosa cystica. Osteomalacia is a state of low bone turnover leading to poor mineralization. Adynamic bone disease is also a low-turnover pathology with normal mineralization that prob- ably results from a low PTH state. The incidence of adynamic bone disease increasing is likely secondary to PTH oversup- pression from vitamin D agents, calcimimetics, and phosphate 14,21 Figure 1. Schematic of the pathogenesis of renal hyperparathyroidism. binders. Osteitis fibrosis cystica is a high-turnover bone CKD = chronic kidney disease; FGF-23 = fibroblast growth factor 23. disease that stems from elevated PTH concentrations stimu- lating osteoclast activity, bone breakdown, and resorption. This can lead to subsequent bone pain and fractures.22 With In CKD, chronic stimulation of the parathyroid glands trig- longstanding bone resorption, patients may develop localized gers diffuse polyclonal hyperplasia. As the chronic stimulation regions of bone loss that are then replaced by fibrous tissue, of CKD continues, the parathyroids begin to develop mono- resulting in a brown tumor. These “tumors” appear as well- clonal nodules within a background of parathyroid hyperplasia. defined, lytic lesions on radiograph and may be mistaken for These nodules demonstrate increased resistance to vitamin D metastasis (Figure 2). and calcimimetic medications and may be the etiology of the The derangements in calcium and phosphate that result from loss of negative feedback seen in 3° HPT.18,19 rHPT may accelerate vascular calcification, including coronary artery calcification. Calcification of the cardiovascular tissue can affect the myocardium, atrial-ventricular conduction, and valvular function.23 Furthermore, coronary calcification may put patients at an increased risk of cardiovascular events and death.24 It is difficult to distinguish the unique detrimental ef- fects of rHPT from those of hyperphosphatemia, which is also associated with cardiovascular disease in patients with CKD. Some studies have suggested that FGF-23 may induce arte- rial smooth muscle myocytes to change into osteoblast-like cells that lead to vascular calcification.17 Moderate to severe hyperparathyroidism (PTH concentrations ≥ 600 pg/mL) may increase risk of cardiovascular death,7 though the causality of this association is debatable. There is an association between CKD and medial calcification in the arterioles of the skin and soft tissue leading to vascular compromise and ulceration. This constellation of complications was formerly called calciphylaxis but is now termed calcific uremic arteriolopathy, and it is associated with an eight-fold increase in mortality rate.25 Tumoral calcinosis is an uncommon complication of longstanding rHPT and is classically associated with high serum levels of calcium and phosphorus. In tumoral Figure 2. Radiograph of the hands of a 55-year-old patient with renal osteodys- calcinosis, the patient can develop soft-tissue calcium deposits trophy and brown tumors of the fourth metacarpal and third phalanx of the left that can appear to be soft-tissue malignant tumors on imaging hand (arrows). Image is courtesy of John Hunter, MD. studies (Figure 3).26

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The National Kidney Foundation previously recommended that patients with CKD restrict dietary phosphorus to 800 to 1000 mg/day. However, it should be noted that there is a paucity of good quality data regarding dietary phosphorus restriction and outcomes in CKD.

Phosphate Binders Because of the difficulty in maintaining a low phosphorus diet, phosphate binders are usually an essential part of medical therapy for patients with CKD. Phosphate binders have been shown to decrease serum phosphorous and PTH levels.28 Isa- kova et al29 reported that treatment with phosphorus binders was independently associated with decreased mortality when compared with no treatment. Several phosphate binders are available, including aluminum hydroxide, calcium salts, sevelamer hydrochloride, sevelamer Figure 3. Radiograph of the right hip of a 63-year-old man with tumoral calcinosis. carbonate, and lanthanum carbonate. In general, aluminum hydroxide should be limited to a short period because of the risk of aluminum toxicity. Newer agents such as lanthanum have unknown long-term effects of bone deposition. Iron-based bind- DIAGNOSIS AND MANAGEMENT ers such as sucroferric oxyhydroxide are also available to lower The Kidney Disease: Improving Global Outcomes work serum phosphorous. The Kidney Disease Outcomes Quality group recommends screening and management of rHPT be Initiative recommends for patients with CKD stages 3 and 4, initiated for all patients with CKD stage 3 (estimated GFR < that phosphate binders be used if phosphorus levels cannot be 60 mL/min). The frequency of monitoring for serum calcium, controlled within the target range despite dietary phosphorus phosphorus, and PTH are listed in Table 1.27 restriction. In patients who remain hyperphosphatemic despite The initial management of rHPT follows a stepwise ap- initiation of a single phosphate binder, combination therapy proach with the goal of optimizing serum phosphorus and can be used.23 It is interesting to note that lanthanum, being a calcium levels through a combination of a low phosphorus heavy metal, commonly shows up as radiopaque in noncontrast diet, phosphate binders, vitamin D derivatives, and calcimi- radiologic studies of the gastrointestinal tract.30 metic medications. Vitamin D Analogs Low Phosphorus Diet As described above, 1,25-OH vitamin D deficiency is a ma- A low phosphorus diet is recommended for patients with jor mechanism of rHPT, and vitamin D replacement has been CKD and 2° HPT with hyperphosphatemia.27 Dietary restric- shown to effectively suppress PTH secretion.31-34 Several forms tion of phosphorus in patients without elevated levels of phos- of vitamin D are available, including ergocalciferol (which re- phorus, but with elevated PTH levels only, is controversial. quires activation in the kidney to 1,25-OH vitamin D), as well Unfortunately, this is very difficult given the high prevalence of as activated forms such as calcitriol, paricalcitol, and doxercal- phosphorus in Western diets. Dietary phosphorus comes from 2 ciferol. Although observational studies have suggested improved sources: 1) protein-rich food groups such as meat and milk; and survival in patients treated with vitamin D analogs, a 2007 meta- 2) phosphorus additives, which are used to process meats and analysis showed no difference in mortality, bone pain, vascular cheeses. Phosphorus used as an additive is often only implied in disease, or rate of parathyroidectomy when comparing patients the ingredients list, and not individually reported on the food on vitamin D analogs versus those not taking vitamin D.14,35 label. Therefore, the true amount of phosphorus contained in a The Kidney Disease: Improving Global Outcomes work group product may be underestimated.14 Patient education regarding recommends that in patients with CKD stages 3 to 5 (not on this distinction may help them avoid phosphorous-rich foods. dialysis), attempts to control hyperphosphatemia, hypocalcemia,

Table 1. Summary of National Kidney Foundation guidelines on evaluation of calcium and phosphorus metabolism and parathyroid hormone CKD stage GFR range (mL/min/1.73 m2) Measure PTH Measure calcium and phosphorus Target PTH (pg/mL) Progressive stage 3 30-59 Baseline 6-12 months < the upper limit of normal for assay Stage 4 15-29 6-12 months 3-6 months < the upper limit of normal for assay Stage 5 < 15 or dialysis 3-6 months 1-3 months 2-9 x the normal limit of the assay CKD = chronic kidney disease; GFR = glomerular filtration rate; PTH = parathyroid hormone.

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and vitamin D deficiency be made first. If PTH remains elevated Foundation recommends that the criteria in the Sidebar: Indica- or is progressively rising, treatment with calcitriol or vitamin tions for Consideration for Parathyroidectomy be used to merit D analogs is suggested. Close attention must be paid to serum referral to an experienced surgeon for evaluation.42 levels of calcium and phosphorus, which if greater than 10.2 The three most common surgical procedures used in the treat- mg/dL and 4.6 mg/dL, respectively, may warrant modification in ment of rHPT are total parathyroidectomy (TPX) alone, TPX therapy. In patients with CKD stage 5 on dialysis, active vitamin with auto-transplantation, and subtotal parathyroidectomy.21 D sterols (such as calcitriol, paricalcitol, or doxercalciferol) are Each of these procedures may be accompanied by a bilateral used to control hyperparathyroidism. cervical thymectomy to minimize the risk of recurrence.43 TPX involves identification and removal of all parathyroid Calcimimetics glands. This operation may be associated with the lowest rate Cinacalcet HCL is a calcimimetic agent that exhibits allosteric of recurrent hyperparathyroidism.44 The clear disadvantage of modulation of the calcium receptor on the parathyroid gland, in- TPX is permanent hypoparathyroidism, and patients undergo- creasing sensitivity to extracellular calcium and thereby suppress- ing TPX require lifelong calcium and vitamin D replacement. In ing PTH secretion.36 The effectiveness of cinacalcet in lowering TPX with autotransplantation, all 4 glands are removed, followed PTH concentrations in ESRD patients has been demonstrated by autologous reimplantation of 20 mg to 70 mg of the most in multiple studies. Combined analysis of these studies showed normal-appearing gland into the sternocleidomastoid muscle, that cinacalcet decreases rates of parathyroidectomy, fractures, pectoralis major muscle, or forearm brachioradialis muscle. and cardiovascular hospitalization. Patients receiving cinacalcet This implant typically takes 3 to 4 weeks to revascularize and treatment rather than placebo also have improvements in self- resume function. The advantage of removal and reimplanta- reported physical function and less bodily pain.37 tion of parathyroid tissue into an ectopic site is ease of access In 2012, the Evaluation of Cinacalcet Hydrochloride Therapy in the event of recurrence and reoperation. This avoids the to Lower Cardiovascular Events Trial randomized patients with morbidity associated with re-exploration of the neck. Subtotal ESRD and moderate to severe rHPT to cinacalcet or placebo parathyroidectomy entails removal of 3½ parathyroid glands, and found that cinacalcet did not significantly reduce overall or leaving the remaining partial gland intact in its original ana- cardiovascular mortality.38 A recent Cochrane review corrobo- tomic location. Subtotal parathyroidectomy has the advantage rated these findings but did find that patients taking cinacalcet of minimizing the period of postoperative hypoparathyroidism had a significant increase in the rate of nausea, vomiting, and and therefore likely shortens a patient’s hospital course, but it hypocalcemia, suggesting that the potential risks associated with requires reoperation in the neck in the event of a recurrence. cinacalcet use in ESRD patients may outweigh the benefits.39 This may be associated with an increased risk of injury to the These clinical uncertainties further bring into question the costs recurrent laryngeal nerve. All 3 operations are accepted surgical of cinacalcet treatment. Currently the US spends $260 million treatment options for rHPT, and each is associated with specific annually on cinacalcet, accounting for the largest single drug cost advantages and disadvantages.45 in dialysis patients.40 Despite maximal medical interventions, Successful parathyroidectomy can dramatically improve surgical parathyroidectomy is still required for many patients.41 symptoms, including bone pain, arthralgia, muscle weakness, and psychological disturbances.45,46 Biopsy-proven changes in Indications for Surgical Treatment trabecular bone mineral content and accelerated bone forma- As stated in the Clinical Practice Guidelines for Bone Metabolism tion have been demonstrated within 1 week after surgery.47 and Disease in Chronic Kidney Disease, published in 2003 by the Parathyroidectomy is associated with a 30-day postoperative Kidney Disease Outcomes Quality Initiative, the indications for mortality of 3.1% throughout the US.48 Other risks of surgery parathyroidectomy are not well defined. High-quality studies are include recurrent laryngeal nerve injury (< 2%) and hematoma currently lacking to evaluate which patients might benefit from requiring re-exploration (< 1 %). parathyroidectomy. In lieu of such data, the National Kidney Several studies have suggested a survival benefit from para- thyroidectomy in the treatment of rHPT, including significant reductions in the incidence of major cardiovascular events and Indications for Consideration for Parathyroidectomy all-cause mortality.49,50 Long-term relative risks of death are re- Medical management of rHPT > 6 months with duced by 10% to 15%, and long-term survival is improved com- 50 Hypercalcemia or hyperphosphatemia pared with those not undergoing surgery. Parathyroidectomy PTH > 800 pg/mL is effective in improving hemoglobin levels for ESRD-associated 51 Calciphylaxis with documented elevated PTH levels anemia, and it has beneficial effects on the immune system 52 Osteoporosis (T-score > 2.5 SD below mean), pathologic and overall nutrition. Parathyroidectomy has also been shown bone fracture to be more cost-effective than cinacalcet in nearly all dialysis Symptoms/signs patient subgroups, with the exception of those with high opera- Pruritus tive mortality risk, patients remaining on dialysis for less than 7 Bone pain months, and/or individuals expecting kidney transplant quickly. Severe vascular calcifications Myopathy PTH = parathyroid hormone; rHPT = renal hyperparathyroidism, SD = standard deviation.

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CONCLUSION 10. Martin KJ, Gonzalez EA. Metabolic bone disease in chronic kidney disease. J Am Soc Nephrol 2007 Mar;18(3):875-85. DOI: http://dx.doi.org/10.1681/ rHPT is a common complication of CKD that stems from hy- ASN.2006070771. pocalcemia, reduced bioactivity of vitamin D, and elevated levels 11. Kerby J, Rue LW, Blair H, Hudson S, Sellers MT, Diethelm AG. Operative of FGF-23. rHPT leads to a host of bone and cardiovascular treatment of tertiary hyperparathyroidism: a single-center experience. Ann Surg 1998 Jun;227(6):878-86. problems that ultimately can cause fractures, decreased quality 12. Kilgo M, Pirsch J, Warner T, Starling JR. Tertiary hyperparathyroidism after renal of life, and an increased risk of death. A range of nonsurgical transplantation: surgical strategy. Surgery 1998 Oct;124(4):677-83; discussion options are available, including initiating a low phosphorus diet, 683-4. 13. Li X, Qin L, Bergenstock M, Beyelock LM, Novack DV, Partridge NC. Parathyroid phosphate binders, vitamin D analogs, and calcimimetic agents, hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the but unfortunately the data on the efficacy of these treatments fusion of pre/osteoclasts. J Biol Chem 2007 Nov 9;282(45):3098-106. at improving overall and cardiovascular mortality are mixed. 14. Slaiba W, El-Haddad B. Secondary hyperparathyroidism: pathophysiology and treatment. J Am Board Fam Med 2009 Sep-Oct;22(5):574-81. Some patients require parathyroidectomy, which may improve 15. Weinman EJ, Lederer ED. NHERF-1 and the regulation of renal phosphate symptoms and reduce cardiovascular and overall mortality, but reabsoption: a tale of three hormones. Am J Physiol Renal Physiol 2012 it carries the expected risks of surgery. v Aug;303(3):F321-7. DOI: http://dx.doi.org/10.1152/ajprenal.00093.2012. 16. Quarles LD. Role of FGF23 in vitamin D and phosphate metabolism: implications in chronic kidney disease. Exp Cell Res 2012 May 15;318(9):1040-8. DOI: http:// Author Contributions dx.doi.org/10.1016/j.yexcr.2012.02.027. Noah K Yuen, MD, provided study conception and design and participated 17. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, in analysis and interpretation of data and writing the manuscript. Shubha PTH, calcium, and phosphorus in patients with chronic kidney disease: results of Ananthakrishnan, MD, participated in writing the manuscript and in critical the study to evaluate early kidney disease. Kidney Int Jan 2007;71(1):31-8. revision of the manuscript. Michael J Campbell, MD, provided study conception 18. Madorin C, Owen RP, Fraser WD, et al. The surgical management of renal hyperparathyroidism. Eur Arch Otorhinolaryngol 2012 Jun;269(6):1565-76. DOI: and design and participated in analysis and interpretation of data, writing the http://dx.doi.org/10.1007/s00405-011-1833-2. manuscript, and the decision to submit for publication. 19. Tominaga Y, Tanaka Y, Sato K, Nagasaka T, Takagi H. Histopathology, pathophysiology, and indications for surgical treatment of renal Disclosure Statement hyperparathyroidism. Semin Surg Oncol 1997 Mar-Apr;13(2):78-86. The author(s) have no conflicts of interest to disclose. 20. Moe S, Drueke T, Cunningham J, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006 Jun;69(11):1945-53. Acknowledgment 21. Andress DL. Adynamic bone in patients with chronic kidney disease. Kidney Int Mary Corrado, ELS, provided editorial assistance. 2008 Jun;73(12):1345-54. DOI: http://dx.doi.org/10.1038/ki.2008.60. 22. Pitt S, Sipple R, Chen H. Secondary and tertiary hyperparathyroidism, state of the art surgical management. Surg Clin North Am 2009 Oct;89(5):1227-39. DOI: How to Cite this Article http://dx.doi.org/10.1016/j.suc.2009.06.011. Yuen NK, Ananthakrishnan S, Campbell MJ. Hyperparathyroidism of renal 23. Goodman WG. The consequences of uncontrolled secondary disease. Perm J 2016 Summer;20(3):15-127. DOI: http://dx.doi.org/10.7812/ hyperparathyroidism and its treatment in chronic kidney disease. Semin Dial TPP/15-127. 2004 May-Jun;17(3):209-16. 24. Wilkieson TJ, Rahman MO, Gangji AS, et al. Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients References on hemodialysis. Can J Kidney Health Dis 2015 Aug 12;2:29. DOI: http://dx.doi. 1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney org/ 10.1186/s40697-015-0065-6. disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 25. Mazhar A, Johnson R, Gillen D, et al. Risk factors and mortality associated with suppl 1):S1-S266. calciphylaxis in end-stage renal disease. Kidney Int 2001 Jul;60(1):324-32. 2. US Renal Data System. USRDS 2015 annual data report: atlas of chronic kidney 26. Cohen RA, Parikh SM. Images in clinical medicine. Calcinosis associated with disease and end-stage renal disease in the United States. Bethesda, MD: renal failure N Engl J Med 2007 Dec 20;357(25):2615. National Institutes of Health, National Institute of Diabetes and Digestive and 27. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. Kidney Diseases; 2015. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and 3. Levin A, Bakris GL, Molitch M et al. Prevalence of abnormal serum vitamin D, treatment of chronic kidney disease—mineral and bone disorder (CKD-MBD). PTH, calcium, and phosphorus in patients with chronic kidney disease: results of Kidney Int Suppl 2009 Aug;76(113):S1-130. DOI: http://dx.doi.org/10.1038/ the study to evaluate early kidney disease. Kidney Int 2007 Jan;71(1):31-8. ki.2009.188. 4. De Boer IH, Gorodetskaya I, Young B, Hsu CY, Chertow GM. The severity of 28. Slatopolsky EA, Burke SK, Dillon MA. RenaGel, a nonabsorbed calcium- and secondary hyperparathyroidism in chronic renal insufficiency is GFR-dependent, aluminum-free phosphate binder, lowers serum phosphorus and parathyroid race-dependent, and associated with cardiovascular disease. J Am Soc Nephrol hormone. The RenaGel Study Group. Kidney Int 1999 Jan;55(1):299-307. 2002;13(11):2762-9. 29. Isakova T, Gutierrez OM, Chang Y, et al. Phosphorus binders and survival on 5. Fellner SK, Lang RM, Neumann A, Bushinsky DA, Borow KM. Parathyroid hemodialysis. J Am Soc Nephrol 2009 Feb;20(2)388-96. hormone and myocardial performance in dialysis patients. Am J Kidney Dis 1991 30. Cerny S, Kunzendorf U. Images in clinical medicine. Radiographic appearance Sep;18(3):320-5. of lanthanum. N Engl J Med 2006 Sep 14;355(11):1160. 6. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral 31. Costa AF, dos Reis LM, Ribeiro MC, Moysés RM, Jorgetti V. Effects of metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc calcitriol on parathyroid function and on bone remodeling in secondary Nephrol 2004 Aug;15(8):2208-18. hyperparathyroidism. Nephrol Dial Transplant 2003 Apr;18(4):743-49. 7. Kalantar-Zadeh K, Kuwae N, Regidor DL et al. Survival predictability of time- 32. Gallieni M, Brancaccio D, Padovese P, et al. Low-dose intravenous calcitriol varying indicators of bone disease in maintenance hemodialysis patients. Kidney treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Int 2006 Aug;70(4):771-80. Group for the Study of Intravenous Calcitriol. Kidney Int 1992 Nov;42(5):1191-8 8. Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association 33. Martin KJ, Gonzalez EA, Gellens M, Hamm LL, Abboud H, Lindberg J. 19-Nor- of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with 1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001 the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Oct;12(10):2131-8. Nephrol 1998 Aug;9(8):1427-32. 9. Lee A, Belozeroff V, Song X, Diakun D, Goodman W. Costs of treatment and 34. Andress DL, Norris KC, Coburn JW, Slatopolsky EA, Sherrard DJ. Intravenous clinical events for secondary hyperparathyroidism. Am J Pharm Benefits calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. N 2013;5(2):e24-e35. Engl J Med 1989 Aug;321(5):274-9.

82 The Permanente Journal/Perm J 2016 Summer;20(3):15-127 REVIEW ARTICLE Hyperparathyroidism of Renal Disease

35. Palmer SC, McGregor DO, Macaskill P, Craig JC, Elder GJ, Strippoli GE. Meta- reoperative parathyroidectomy. World J Surg 2013 Sep;37(9):2155-61. DOI: http:// analysis: vitamin D compounds in chronic kidney disease. Ann Intern Med 2007 dx.doi.org/10.1007/s00268-013-2091-9. Dec 18;147(12):840-53 44. Higgins RM, Richardson AJ, Ratcliffe PJ, Woods CG, Oliver DO, Morris PJ. Total 36. Cunningham J, Danese M, Olson K, Klassen P, Chertow, GM. Effects of the parathyroidectomy alone or with autograft for renal hyperparathyroidism? Q J Med calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health- 1991 Apr;79(288):323-32. related quality of life in secondary hyperparathyroidism. Kidney Int 2005 45. Dumasius V, Angelos P. Parathyroid surgery in renal failure patients. Otolaryngol Oct;68(4):1793-800. Clin North Am 2010 Apr;43(2):433-40, x-xi. DOI: http://dx.doi.org/10.1016/j. 37. Block GA, Martin KJ, De Francisco AL, et al. Cinacalcet for secondary otc.2010.01.010. hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004 Apr 46. Tominaga Y. Surgical management of secondary hyperparathyroidism in uremia. Am 8;350(15):1516-25. J Med Sci 1999 Jun;317(6):390-7. 38. EVOLVE Trial Inestigators; Chertow GM, Block GA, Correa-Rotter R, et al. 47. Yajima A, Ogawa Y, Takahashi HF, Tominaga Y, Inou T, Otsubo O. Changes of bone Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. remodeling immediately after parathyroidectomy for secondary hyperparathyroidism. N Engl J Med 2012 Dec 27;367(26):2482-94. DOI: http://dx.doi.org/10.1056/ Am J Kidney Dis 2003 Oct;42(4):729-38. NEJMoa1205624. 48. Kestenbaum B, Andress DL, Schwartz SM, et al. Survival following parathyroidectomy 39. Ballinger AE, Palmer SC, Nistor I, Craig JC, Strippoli GF.. Calcimimetics for among United States dialysis patients. Kidney Int 2004 Nov;66(5):2010-6. secondary hyperparathyroidism in chronic kidney disease patients. Cochrane 49. Costa-Hong V, Jorgetti V, Gowdak LHW, Moyses RM, Krieger EM, De Lima JJ. Database Syst Rev 2014;12:CD006254. DOI: http://dx.doi.org/10.1002/14651858. Parathyroidectomy reduces cardiovascular events and mortality in renal CD006254.pub2. hyperparathyroidism. Surgery 2007 Nov;142(5):699-703. 40. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney 50. Sharma J, Raggi P, Kutner N, et al. Improved long-term survival of dialysis patients Diseases, Division of Kidney, Urologic, and Hematologic Diseases. 2012 USRDS after near-total parathyroidectomy. J Am Coll Surg 2012 Apr;214(4):400-7, discussion annual data report volume one: atlas of chronic kidney disease in the United States. 407-8. DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2011.12.046. Bethesda, MD: National Institutes of Health; 2012. 51. Chow TL, Chan TT, Ho YW, Lam SH. Improvement of anemia after parathyroidectomy 41. Li S, Chen Y, Peng Y, Foley RN, St PeterWL. Trends in parathyroidectomy rates in in Chinese patients with renal failure undergoing long-term dialysis. Arch Surg 2007 US hemodialysis patients from 1992 to 2007. Am J Kidney Dis 2007 Apr;57(4):602- Jul;142(7):644-8. 11. DOI: http://dx.doi.org/10.1053/j.ajkd.2010.10.041. 52. Yasunaga C, Nakamoto M, Matsuo K, Nishihara G, Yoshida T, Goya T. Effects of a 42. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and parathyroidectomy on the immune system and nutritional condition in chronic dialysis disease in chronic kidney disease. Am J Kidney Dis 2003 Oct;42(4 Suppl 3):S1-201. patients with secondary hyperparathyroidism. Am J Surg 1999 Oct;78(4);332-6. 43. Schneider R, Bartsch DK, Schlosser K. Relevance of bilateral cervical thymectomy in patients with renal hyperparathyroidism: analysis of 161 patients undergoing

A Small Organ Hardly as Big as a Hemp Seed

About three years ago I found on the thyroid gland … a small organ, hardly as big as a hemp seed, which was enclosed in the same connective tissue capsule as the thyroid, but could be distinguished therefrom by a lighter color. A superficial examination revealed an organ of totally different structure from that of the thyroid, and with a very rich vascularity. … [I] suggest the use of the name Glandulae parathyreoidea; a name in which the characteristic of being bye-glands to the thyroid is expressed.

— Ivar Victor Sandström, 1852-1889, Swedish physician

The Permanente Journal/Perm J 2016 Summer;20(3):15-127 83 REVIEW ARTICLE Recurrence of Epithelioid Hemangioendothelioma during Pregnancy: Case Report and Systematic Review

Michael McCulloch, LAc, MPH, PhD; Michael Russin, MD; Arian Nachat, MD Perm J 2016 Summer;20(3):15-152 E-pub: 07/25/2016 http://dx.doi.org/10.7812/TPP/15-152

ABSTRACT (p = 0.1). There was additionally nonsig- Introduction: Epithelioid hemangioendothelioma (EHE) is a family of blood vessel nificant lower 5-year survival in meta- tumors originating in blood vessels, bone, brain, kidney, liver, and lung. EHE is more com- static (69%) compared with localized mon in women, and chemotherapy, radiation, and surgery have brought few successes. (78.3%) disease (p = 0.7). Treatment with Case presentation: We present a case of a 28-year-old woman whose EHE recurred any chemotherapy decreased 5-year sur- during pregnancy, suggesting hormonal involvement. We conducted a systematic re- vival, compared with no chemotherapy view to provide analysis and interpretation of the potential significance of her disease (43.6% vs 82.9%; p = 0.02).7 recurring, with fatal outcome, during pregnancy. Diagnostic approaches to EHE include Discussion: Very little research has explored the use of individual hormonal markers. computed tomography (CT),8 magnetic Strongly positive expression of placenta growth factor (PlGF) and 17-beta estradiol resonance imaging,9,10 CT and magnetic receptors have been reported. Expression of PlGF is noteworthy in our case, in that our resonance imaging,9 and serial bone patient’s disease quickly and dramatically flared in the 25th week of pregnancy, near the scintigraphy.11 (18)F-fluorodeoxyglucose- peak in maternal PlGF production. PlGF binds to vascular endothelial growth factor-1 positron emission tomography with (VEGF-1), and PlGF may accelerate VEGF-induced angiogenesis. Taken together, these strong (18)F-fluorodeoxyglucose uptake factors may explain our patient’s EHE recurrence and rapid flare-up during pregnancy. has been used12 but is limited by lack of Treatment of EHE with VEGF inhibition, potentially in combination with other antian- correlation between lesion size and maxi- giogenic and tumor-inhibiting therapies such as lenalidomide, thalidomide, sorafenib, mum standardized uptake value.13 and sunitinib, may also hold promise. Little is known about efficacy of ther- apy because the low incidence of EHE INTRODUCTION which can significantly worsen progno- precludes conduct of human clinical Epithelioid hemangioendothelioma sis.4 Little is known about prognostic trials. Options currently include che- (EHE) is a family of vascular tumors, factors for patients with EHE, although motherapy, radiation, hormone therapy, originating in the endothelium and recent work has identified genetic altera- thermo-ablation, and surgery, although sharing clinical characteristics with both tions involving activation of the ROS1 most do not change the usually poor angiosarcoma and benign hemangioma. receptor tyrosine kinase, which for other prognosis of a diagnosis with EHE. In EHE was first identified in 19821 and is cancers has led to effective therapies patients with primary hepatic EHE, extremely rare, with an incidence rate working through ROS1 inhibition.5 overall survival is no different following of 0.1 per 100,000, and fewer than Two case series have described the liver resection or transcatheter arterial 200 cases ever reported in the medical prognosis of patients with hepatic EHE. chemoembolization (p = 0.50).6 Al- literature.2 Because there is limited re- In a series from China (N = 33), survival though patients with hepatic EHE have search on prognosis, a layperson registry was longer in patients younger than age longer median survival compared with has been established. The International 47 years (hazard ratio, 7.0; p = 0.035), those with other hepatic vascular tumors, Hemangioendothioma, Epithelioid in those without symptoms (hazard ra- in these patients surgical resection does Hemangioendothelioma, and Related tio, 86.5; p = 0.001), and in those with not improve survival.14 Vascular Disorders Support Group has serum cancer antigen 19-9 below 37 Development and testing of newer tracked more than 260 patients.3 units/mL (hazard ratio, 5.0; p = 0.018).6 therapies based on vascular endothe- The clinical presentation of EHE is In a series from the United Kingdom lial growth factor (VEGF) inhibition quite varied; it can originate in bone, (N = 50), patients with bilateral hepatic is supported by recent studies showing brain, kidney, liver, lung, and vascu- disease had shorter 5-year survival (51%) positive expression of VEGF receptor lar and other soft tissues. Diagnosis is compared with those with unilateral dis- in biopsied lesions.15,16 Additional case sometimes delayed owing to uncertainty ease (81%), although the study size was reports of success with lenalidomide,17 about correct pathologic classification, too small to show a significant difference thalidomide,2 sorafenib (possessing both

Michael McCulloch, LAc, MPH, PhD, is the Research Lead for Integrative Medicine at the Walnut Creek Hospital in CA and a Research Chief at the Pine Street Foundation in San Anselmo, CA. E-mail: [email protected]. Michael Russin, MD, is the Oncology Chief at the Walnut Creek Hospital in CA. E-mail: [email protected]. Arian Nachat, MD, is the Director of Integrative Medicine at the Walnut Creek Hospital in CA. E-mail: [email protected].

84 The Permanente Journal/Perm J 2016 Summer;20(3):15-152 REVIEW ARTICLE Recurrence of Epithelioid Hemangioendothelioma during Pregnancy: Case Report and Systematic Review

antiangiogenic and antiproliferative ac- tivity),18 and sunitinib19 suggest other targeted molecular therapies may also hold promise. The current case report documents di- agnosis of recurrent EHE in a pregnant woman and discusses the case in the con- text of a systematic review of the current literature. This report was prepared in ac- cordance with the CARE (CAse REport) guidelines.20 Figure 1. Hematoxylin/eosin stain showing epithe- lioid cells with cytoplasmic vacuoles (magnification CASE PRESENTATION ×400). We report a case of a 28-year-old woman originally diagnosed with EHE in 2002, at age 18 years. CT-guided biopsy of 1 of her liver lesions revealed EHE based on hematoxylin/eosin and im- Figure 5. Computed tomography angiography of the chest, showing stable disease in 2008. munohistochemical stains (Figures 1-4). Repeated CT of her chest, abdomen, and pelvis 3 months later showed progression of disease. At that time she underwent 6 cycles of carboplatin and etoposide with stabilization of disease; however, signifi- cant chest pain remained, requiring high doses of opiates. She received 1 dose of Figure 2. Hematoxylin/eosin stain showing epithe- interferon, which was not tolerated. The lioid cells with cytoplasmic vacuoles (magnification patient was then followed up with serial ×600). CT scan showing stable disease through 2011 (Figures 5 and 6). In 2012, the patient presented to the Emergency Department with chest pain and in acute respiratory distress. A pos- terior-anterior/lateral chest radiograph revealed multiple pulmonary nodules bi- laterally, confirmed as “innumerable” by chest CT, along with bulky mediastinal Figure 6. Computed tomography angiography of the adenopathy and multiple liver lesions con- chest, showing stable disease in 2011. sistent with metastatic disease (Figure 7). In mid-2012, the patient presented with diffuse joint pain 6 months into Figure 3. Immunohistochemical stain positive for scan was consistent with hypertrophic vascular marker CD31 (magnification ×600). her first pregnancy, and went into labor osteoarthropathy. During this time her at 25 weeks. The baby was delivered and respiratory status continued to worsen: died 8 days later. The patient’s pain then chest CT revealed compression of the continued to escalate and she developed right upper lobe bronchus and right pleu- severe cough. Repeat CT scan of her chest, ral effusion. A right-sided chest tube was abdomen, and pelvis revealed significant inserted with drainage of a large amount progression of disease, especially in the of pleural fluid and palliative radiation to lungs and mediastinum. Biopsy of medi- the mediastinal adenopathy was started. astinal adenopathy confirmed recurrent Unfortunately the patient’s respiratory EHE, and the diffuse nature of disease status continued to decline from progres- precluded surgery. sive disease as well as pneumonia. She The patient’s diffuse joint and bone was intubated; her condition continued pain continued to worsen, resulting in to decline; she was placed on comfort Figure 4. Immunohistochemical stain positive for hospitalization for pain control. Bone measures, and she subsequently died. vascular marker CD34 (magnification ×600).

The Permanente Journal/Perm J 2016 Summer;20(3):15-152 85 REVIEW ARTICLE Recurrence of Epithelioid Hemangioendothelioma during Pregnancy: Case Report and Systematic Review

A timeline showing progression of the In Table 1 we present results of a sys- case is provided in Figure 8. tematic search of treatment outcomes published since January 2011. Tumor DISCUSSION marker expression in EHE has been re- Despite numerous publications, EHE ported for endothelial markers (CD31, remains a little-understood disease of poor CD34, and factor VIII-related antigen),21 prognosis. In the case of localized disease, VEGF and VEGF receptor 2,15 and strong prompt surgical resection appears to con- expression of CD31 and vimentin.12 fer a survival advantage. Improvements in Errani et al22,23 reported that WWTR1- early clinical identification of suspected CAMTA1 fusion is a genetic hallmark lesions may be accelerated by further re- of EHE, regardless of site of origin; they Figure 7. Computed tomography angiography of the chest, following disease recurrence in 2012. search on the integration of tumor marker also used reverse transcription-polymerase and/or hormonal testing. chain reaction and gene sequencing to

Table 1. Epithelioid hemangioendothelioma primary tumor sites, first-line therapy, and maximum reported survival with therapy Primary Extent First-line Author, year tumor site of disease therapy Patient(s) Survival Case series Angelini et al,1 2014 Bone Unifocal (49%); Wide excision or intralesional N = 62; men, n = 39; Survival at 10 years: multifocal (13%) surgery women, n = 23; mean unifocal, 97%; multifocal, age = 39 years 74% Zheng et al,2 2012 Brain Intracranial, with Surgery 25-year-old man; 9 years localized extension to 44-year-old woman bone and muscle Agulnik et al,3 2013 Multifocal Metastatic Bevacizumab N = 7 Partial response, n = 2; stable disease, n = 4; progressive disease, n = 1 Wang et al,4 2012 Liver Localized and Liver resection, transcatheter N = 33 Up to 3 years of follow-up extrahepatic arterial chemoembolization (TACE), resection and TACE, or liver transplantation Theodosopoulos et al,5 Intracranial Metastatic Surgery N = 38; men, n = 23; 2 months-11 years 2013 women, n = 15 Case reports Gherman and Fodor,6 Bone Localized Wide surgical excision 24-year-old man No local recurrence or 2011 metastasis at 2 years Sumrall et al,7 2010 Brain Intracranial, localized Lenalidomide 31-year-old woman 6 years, stable disease extension to skull, connective tissue Osawa et al,8 2012 Carotid artery Localized Surgery 59-year-old man; 14 Rapid death years after embolization for carotid aneurysm Tolkach et al,9 2012 Kidney Metastatic Sunitinib 53-year-old man 3 years, stable disease Harada et al,10 2011 Liver Localized Transcatheter arterial 83-year-old man Metastatic recurrence chemoembolization after 3 months Grenader et al,11 2011 Liver Localized Pegylated liposomal 32-year-old man 2 years, stable disease doxorubicin with maintenance therapy at time of publication Sangro et al,12 2012 Liver Metastatic to lungs Sorafenib 22-year-old man 2 years Salech et al,13 2011 Liver Metastatic to lungs Thalidomide 40-year-old woman 9 years, stable disease Mizota et al,14 2011 Lung Localized Bevacizumab 59-year-old woman 3 months Iimuro et al,15 2012 Retroperitoneum Localized, then distant Surgical removal of both 48-year-old woman No recurrence at 13 lymph metastasis occurrences months after resection of months later metastasis Kerry et al,16 2012 Spinal region Multifocal Endovascular embolization, 25-year-old man 8 weeks radiochemotherapy De Palma et al,17 2012 Vascular Localized Surgical removal of entire 47-year-old man No recurrence at 1 year azygos vein (Continued on next page)

86 The Permanente Journal/Perm J 2016 Summer;20(3):15-152 REVIEW ARTICLE Recurrence of Epithelioid Hemangioendothelioma during Pregnancy: Case Report and Systematic Review

ascertain that in multifocal EHE, those EHE is more common in women, Very little research has explored the multiple sites are monoclonal in nature, and there are 3 prior case reports of its clinical utility of individual hormonal and therefore metastatic implants of the diagnosis during pregnancy,17 with ours markers in EHE. There was strongly posi- same tumor and not simultaneous oc- being the fourth. A case report has also tive expression of placenta growth factor currence of multiple neoplastic clones. been published of successful management (PlGF) in 1 case,33 positive expression of Additionally, both CD31 and VEGF of multifocal hepatic infantile heman- 17-beta estradiol receptors in only 1 of a are overexpressed in non-small cell lung gioendothelioma with tamoxifen-based series of 5 EHE patients,34 and no estro- cancer,24 breast cancer,25 prostate can- therapy.32 Tamoxifen (20 mg daily) was gen or progesterone receptors in another cer,26 renal cell carcinoma,27 mantle cell part of the management strategy used for case.35 Expression of PlGF is noteworthy lymphoma,28 meningioma,29 pituitary our patient over a 9-day course during her in our case, in that our patient’s disease adenomas,30 and uveal melanoma.31 acute disease recurrence. quickly and dramatically flared in the

(Continued from previous page) Primary Extent First-line Author, year tumor site of disease therapy Patient(s) Survival Case reports (continued) Wu et al,18 2014 Vascular Localized Surgery 58-year-old woman 2 years, stable at time of publication Demir et al,19 2013 Liver Parenchymal lesion Carboplatin, pharmorubucin 24-year-old woman with metastases to lung Kiratli et al,20 2013 Eyelid Localized Excisional biopsy 22-year-old woman No recurrence at 44 months Pálföldi et al,21 2013 Lung Metastatic to bone Carboplatin, docetaxel, 49-year-old woman Stable disease 1 year pharmorubucin after diagnosis Yu et al,22 2013 Lung Lung (localized to Carboplatin/etoposide, 39-year-old woman Alive 14 months after myocardium) followed by surgical excision surgery 1 Angelini A, Mavrogenis AF, Gambarotti M, Merlino B, Picci P, Ruggieri P. Surgical treatment and results of 62 patients with epithelioid hemangioendothelioma of bone. J Surg Oncol 2014 Jun;109(8):791-7. DOI: http://dx.doi.org/10.1002/jso.23587. 2 Zheng J, Liu L, Wang J, Wang S, Cao Y, Zhao J. Primary intracranial epithelioid hemangioendothelioma: a low-proliferation tumor exhibiting clinically malignant behavior. J Neurooncol 2012 Oct;110(1):119-27. DOI: http://dx.doi.org/10.1007/s11060-012-0945-x. 3 Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol 2013 Jan;24(1):257-63. DOI: http://dx.doi.org/10.1093/annonc/mds237. 4 Wang LR, Zhou JM, Zhao YM, et al. Clinical experience with primary hepatic epithelioid hemangioendothelioma: retrospective study of 33 patients. World J Surg 2012 Nov;36(11):2677-83. DOI: http://dx.doi.org/10.1007/s00268-012-1714-x. 5 Theodosopoulos T, Dellaportas D, Tsangkas A, et al. Clinicopathological features and management of hepatic vascular tumors. A 20-year experience in a Greek University Hospital. J BUON 2013 Oct-Dec;18(4):1026-31. 6 Gherman CD, Fodor D. Epithelioid hemangioendothelioma of the forearm with radius involvement. Case report. Diagn Pathol 2011 Dec 6;6:120. DOI: http://dx.doi.org/10.1186/1746-1596-6-120. 7 Sumrall A, Fredericks R, Berthold A, Shumaker G. Lenalidomide stops progression of multifocal epithelioid hemangioendothelioma including intracranial disease. J Neurooncol 2010 Apr;97(2):275-7. DOI: http://dx.doi.org/10.1007/s11060-009-0017-z. 8 Osawa S, Saito A, Shimizu H, Ogawa T, Watanabe M, Tominaga T. A case of intravascular epithelioid hemangioendothelioma occurring 14 years after coil embolization for an extracranial internal carotid artery aneurysm. J Vasc Surg 2012 Jan;55(1):230-3. DOI: http://dx.doi.org/10.1016/j.jvs.2011.06.108. 9 Tolkach Y, Petrov S, Lerut E, Van Poppel H. Epithelioid hemangioendothelioma of the kidney treated with sunitinib. Onkologie 2012;35(6):376-8. DOI: http://dx.doi.org/10.1159/000338944. 10 Harada J, Yoshida H, Ueda J, et al. Malignant hepatic epithelioid hemangioendothelioma with abdominal pain due to rapid progression. J Nippon Med Sch 2011;78(4):246-51. DOI: http:// dx.doi.org/10.1272/jnms.78.246. 11 Grenader T, Vernea F, Reinus C, Gabizon A. Malignant epithelioid hemangioendothelioma of the liver successfully treated with pegylated liposomal doxorubicin. J Clin Oncol 2011 Sep 1;29(25):e722-4. DOI: http://dx.doi.org/10.1200/jco.2011.35.5891. 12 Sangro B, Iñarrairaegui M, Fernández-Ros N. Malignant epithelioid hemangioendothelioma of the liver successfully treated with Sorafenib. Rare Tumors 2012 Apr 12;4(2):e34. DOI: http:// dx.doi.org/10.4081/rt.2012.e34. 13 Salech F, Valderrama S, Nervi B, et al. Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: a case report with a long term follow-up. Ann Hepatol 2011 Jan-Mar;10(1):99-102. 14 Mizota A, Shitara K, Fukui T. Bevacizumab chemotherapy for pulmonary epithelioid hemangioendothelioma with severe dyspnea. J Thorac Oncol 2011 Mar;6(3):651-2. DOI: http://dx.doi. org/10.1097/jto.0b013e31820b9e23. 15 Iimuro Y, Nakai N, Asano Y, et al. Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case. Surg Today 2012 Oct;42(10):1026-31. DOI: http://dx.doi.org/10.1007/ s00595-012-0173-1. 16 Kerry G, Marx O, Kraus D, et al. Multifocal epithelioid hemangioendothelioma derived from the spine region: case report and literature review. Case Rep Oncol 2012 Jan;5(1):91-8. DOI: http://dx.doi.org/10.1159/000336947. 17 De Palma A, Pagliarulo V, Ardò N, Loizzi D. Surgical treatment of a rare case of epithelioid hemangioendothelioma of the azygos vein. Interact Cardiovasc Thorac Surg 2012 Jan;14(1):91- 3. DOI: http://dx.doi.org/10.1093/icvts/ivr064. 18 Wu XN, Chen MJ, Li DQ, Hu JG, Yu FL. Pulmonary artery pseudoaneurysm caused by a rare vascular tumor: epithelioid hemangioendothelioma. Thorac Cardiovasc Surg 2014 Feb;62(1):92-4. DOI: http://dx.doi.org/10.1055/s-0031-1299588. 19 Demir L, Can A, Oztop R, et al. Malignant epithelioid hemangioendothelioma progressing after chemotherapy and Interferon treatment: a case presentation and a brief review of the literature. J Cancer Res Ther 2013 Jan-Mar;9(1):125-7. DOI: http://dx.doi.org/10.4103/0973-1482.110386. 20 Kiratli H, Tarlan B, Ruacan S. Epitheloid hemangioendothelioma of the palpebral lobe of the lacrimal gland. Orbit 2013 Apr;32(2):120-3. DOI: http://dx.doi.org/10.3109/01676830.2013.764443. 21 Pálföldi R, Radács M, Csada E, et al. Pulmonary epithelioid haemangioendothelioma studies in vitro and in vivo: new diagnostic and treatment methods. In Vivo 2013 Mar-Apr;27(2):221-5. 22 Yu L, Gu T, Xiu Z, Shi E, Zhao X. Primary pleural epithelioid hemangioendothelioma compressing the myocardium. J Card Surg 2013 May;28(3):266-8. DOI: http://dx.doi.org/10.1111/jocs.12094.

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4. Osawa S, Saito A, Shimizu H, Ogawa T, Watanabe M, Tominaga T. A case of intravascular epithelioid hemangioendothelioma occurring 14 years after coil embolization for an extracranial internal carotid artery aneurysm. J Vasc Surg 2012 Jan;55(1):230-3. DOI: http://dx.doi.org/10.1016/j. jvs.2011.06.108. 5. Davies KD, Doebele RC. Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res 2013 Aug 1;19(15):4040-5. DOI: http://dx.doi.org/10.1158/1078- 0432.ccr-12-2851. 6. Wang LR, Zhou JM, Zhao YM, et al. Clinical experience with primary hepatic epithelioid hemangioendothelioma: retrospective study of 33 patients. World J Surg 2012 Nov;36(11):2677-83. DOI: http://dx.doi.org/10.1007/s00268-012-1714-x. 7. Thomas RM, Aloia TA, Truty MJ, et al. Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma. HPB (Oxford) 2014 Jul;16(7):677-85. DOI: http://dx.doi.org/10.1111/ hpb.12202. 8. Marchiori E, Hochhegger B, Zanetti G. Optimizing the utility of computed tomography in diagnosing pulmonary epithelioid hemangioendothelioma. Isr Med Assoc J 2012 Jun;14(6):403. 9. Lin J, Ji Y. CT and MRI diagnosis of hepatic epithelioid hemangioendothelioma. Hepatobiliary Pancreat Dis Int 2010 Apr;9(2):154-8. 10. Rocha Oliveira PC, Alcantara FP, de Souza- Vianna PE, Brito AP. Cerebral epithelioid Figure 8. Timeline of the patient’s case. hemangioendothelioma with thoracic simultaneous CT = computed tomography scan. involvement: advanced MRI features. Arq Neuropsiquiatr 2012 Aug;70(8):637-8. DOI: http:// dx.doi.org/10.1590/s0004-282x2012000800015. 11. Swainson I, Chan WL, Abbati D. Serial bone 25th week of pregnancy, near the peak anti-angiogenic, hormonal, and anti- scintigraphy in a case of malignant epithelioid in maternal PlGF production. Although VEGF agents has value as an avenue of hemangioendothelioma. Clin Nucl Med 2012 Apr;37(4):396-9. DOI: http://dx.doi.org/10.1097/ in our patient’s case PlGF was not tested, future clinical investigation. v rlu.0b013e31823eaac4. we did note an abnormally low human 12. Iimuro Y, Nakai N, Asano Y, et al. Primary epithelioid chorionic gonadotropin level during Disclosure Statement hemangioendothelioma of the retroperitoneum: report of a case. Surg Today 2012 Oct;42(10):1026-31. the second trimester of pregnancy of The author(s) have no conflicts of interest to DOI: http://dx.doi.org/10.1007/s00595-012-0173-1. 23 IU/mL. disclose. 13. Dong A, Dong H, Wang Y, Gong J, Lu J, Zuo C. MRI A translocation involving PlGF has and FDG PET/CT findings of hepatic epithelioid hemangioendothelioma. Clin Nucl Med 2013 15 Acknowledgment also been discovered in a case of EHE. Feb;38(2):e66-73. DOI: http://dx.doi.org/10.1097/ Furthermore, it is known that there is Mary Corrado, ELS, provided editorial assistance. rlu.0b013e318266ceca. binding of PlGF to VEGF receptor-1, 14. Groeschl RT, Miura JT, Oshima K, Gamblin TC, How to Cite this Article Turaga KK. Does histology predict outcome for and that PlGF may influence VEGF- malignant vascular tumors of the liver? J Surg McCulloch M, Russin M, Nachat A. Recurrence induced angiogenesis,36 which may ex- Oncol 2014 Apr;109(5):483-6. DOI: http://dx.doi. of epithelioid hemangioendothelioma during plain our patient’s rapid disease flare-up. org/10.1002/jso.23517. pregnancy: Case report and systematic review. 15. Matsuzawa S, Kanazawa T, Yamaguchi T, Nishino H, Although the scarcity of cases im- Perm J 2016 Summer;20(3):15-152. Kawada K, Ichimura K. Case of high-risk epithelioid pedes rapid progress in histochemical DOI: http://dx.doi.org/10.7812/TPP/15-152 hemangioendothelioma of the neck. Head Neck 2013 Oct;35(10):E317-20. DOI: http://dx.doi.org/10.1002/ characterization of EHE, a composite hed.23160. picture has begun to emerge that may References 16. Park MS, Ravi V, Araujo DM. Inhibiting the VEGF- aid researchers in its early identifica- 1. Weiss SW, Enzinger FM. Epithelioid VEGFR pathway in angiosarcoma, epithelioid hemangioendothelioma: a vascular tumor hemangioendothelioma, and hemangiopericytoma/ tion, perhaps leading to earlier diagnosis often mistaken for a carcinoma. Cancer solitary fibrous tumor. Curr Opin Oncol 2010 and more definitive treatment. VEGF 1982 Sep 1;50(5):970-81. DOI: http://dx.doi. Jul;22(4):351-5. DOI: http://dx.doi.org/10.1097/ expression15 and hormonal receptor org/10.1002/1097-0142(19820901)50:5<970::aid- cco.0b013e32833aaad4. cncr2820500527>3.0.co;2-z. 17. Sumrall A, Fredericks R, Berthold A, Shumaker G. expression have been reported in EHE. 2. Salech F, Valderrama S, Nervi B, et al. Thalidomide Lenalidomide stops progression of multifocal Furthermore, there are multiple reports for the treatment of metastatic hepatic epithelioid epithelioid hemangioendothelioma including of successful management of this vascu- hemangioendothelioma: a case report with a intracranial disease. J Neurooncol 2010 long term follow-up. Ann Hepatol 2011 Jan- Apr;97(2):275-7. DOI: http://dx.doi.org/10.1007/ lar cancer with antiangiogenic therapy Mar;10(1):99-102. s11060-009-0017-z. 17,18 2,37-39 (lenalidomide, thalidomide, 3. Lau K, Massad M, Pollak C, et al. Clinical patterns 18. Sangro B, Iñarrairaegui M, Fernández-Ros N. and sorafenib18). We therefore suggest and outcome in epithelioid hemangioendothelioma Malignant epithelioid hemangioendothelioma of with or without pulmonary involvement: insights from the liver successfully treated with Sorafenib. Rare it is possible that combination therapy an internet registry in the study of a rare cancer. Tumors 2012 Apr 12;4(2):e34. DOI: http://dx.doi. of EHE with sequenced or concurrent Chest 2011 Nov;140(5):1312-8. DOI: http://dx.doi. org/10.4081/rt.2012.e34. org/10.1378/chest.11-0039.

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19. Tolkach Y, Petrov S, Lerut E, Van Poppel H. VEGFR-3, CD31 and tumor metastases in Chinese with PlGF expression: report of a case. Thorac Epithelioid hemangioendothelioma of the kidney with prostate cancer]. [Article in Chinese]. Shi Yan Cardiovasc Surg 2011 Mar;59(2):128-30. DOI: treated with sunitinib. Onkologie 2012;35(6):376-8. Sheng Wu Xue Bao 2005 Jun;38(3):257-64. http://dx.doi.org/10.1055/s-0030-1250086. DOI: http://dx.doi.org/10.1159/000338944. 27. Yilmazer D, Han U, Onal B. A comparison of 34. Ohori NP, Yousem SA, Sonmez-Alpan E, Colby 20. Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, the vascular density of VEGF expression with TV. Estrogen and progesterone receptors Riley D; CARE Group. The CARE guidelines: microvascular density determined with CD34 in lymphangioleiomyomatosis, epithelioid consensus-based clinical case report guideline and CD31 staining and conventional prognostic hemangioendothelioma, and sclerosing hemangioma development. J Clin Epidemiol 2014 Jan;67(1):46-51. markers in renal cell carcinoma. Int Urol Nephrol of the lung. Am J Clin Pathol 1991 Oct;96(4):529-35. DOI: http://dx.doi.org/10.1016/j.jclinepi.2013.08.003. 2007;39(3):691-8. DOI: http://dx.doi.org/10.1007/ 35. Bollinger BK, Laskin WB, Knight CB. Epithelioid 21. Zhao AL, Zhou LX, Li XH. [Hepatic epithelioid s11255-006-9123-4. hemangioendothelioma with multiple site hemangioendothelioma in needle biopsy specimens: 28. Molinský J, Klánová M, Maswabi B, et al. In vivo involvement. Literature review and observations. report of 5 cases with review of literature]. [Article growth of mantle cell lymphoma xenografts in Cancer 1994 Feb;73(3):610-5. DOI: http://dx.doi. in Chinese]. Zhonghua Bing Li Xue Za Zhi 2011 immunodeficient mice is positively regulated by org/10.1002/1097-0142(19940201)73:3<610::aid- Jan;40(1):23-6. VEGF and associated with significant up-regulation cncr2820730318>3.0.co;2-3. 22. Errani C, Sung YS, Zhang L, Healey JH, of CD31/PECAM1. Folia Biol (Praha) 2013;59(1): 36. He M, Das K, Blacksin M, Benevenia J, Antonescu CR. Monoclonality of multifocal epithelioid 26-31. Hameed M. A translocation involving the placental hemangioendothelioma of the liver by analysis 29. Lewy-Trenda I, Omulecka A, Janczukowicz J, growth factor gene is identified in an epithelioid of WWTR1-CAMTA1 breakpoints. Cancer Genet Papierz W. The morphological analysis of vasculature hemangioendothelioma. Cancer Genet Cytogenet 2012 Jan-Feb;205(1-2):12-7. DOI: http://dx.doi. and angiogenic potential in meningiomas: 2006 Jul 15;168(2):150-4. DOI: http://dx.doi. org/10.1016/j.cancergen.2011.10.008. immunoexpression of CD31 and VEGF antibodies. org/10.1016/j.cancergencyto.2006.02.010. 23. Errani C, Zhang L, Sung YS, et al. A novel WWTR1- Folia Neuropathol 2003;41(3):149-53. 37. Bölke E, Gripp S, Peiper M, et al. Multifocal CAMTA1 gene fusion is a consistent abnormality 30. Cristina C, Perez-Millan MI, Luque G, et al. VEGF epithelioid hemangioendothelioma: case report of a in epithelioid hemangioendothelioma of different and CD31 association in pituitary adenomas. Endocr clinical chamaeleon. Eur J Med Res 2006 Nov 30; anatomic sites. Genes Chromosomes Cancer 2011 Pathol 2010 Sep;21(3):154-60. DOI: http://dx.doi. 11(11):462-6. Aug;50(8):644-53. DOI: http://dx.doi.org/10.1002/ org/10.1007/s12022-010-9119-6. 38. Mascarenhas RC, Sanghvi AN, Friedlander L, gcc.20886. 31. Mouriaux F, Sanschagrin F, Diorio C, et al. Increased Geyer SJ, Beasley HS, Van Thiel DH. Thalidomide 24. Mineo TC, Ambrogi V, Baldi A, et al. Prognostic HIF-1α expression correlates with cell proliferation inhibits the growth and progression of hepatic impact of VEGF, CD31, CD34, and CD105 and vascular markers CD31 and VEGF-A in uveal epithelioid hemangioendothelioma. Oncology expression and tumour vessel invasion after radical melanoma. Invest Ophthalmol Vis Sci 2014 Mar 2004;67(5-6):471-5. DOI: http://dx.doi.org/ surgery for IB-IIA non-small cell lung cancer. J Clin 4;55(3):1277-83. DOI: http://dx.doi.org/10.1167/ 10.1159/000082932. Pathol 2004 Jun;57(6):591-7. DOI: http://dx.doi. iovs.13-13345. 39. Raphael C, Hudson E, Williams L, Lester JF, org/10.1136/jcp.2003.013508. 32. Sondhi V, Kurkure PA, Vora T, et al. Successful Savage PM. Successful treatment of metastatic 25. Arihiro K, Kaneko M, Fujii S, Inai K. Loss of CD9 with management of multi-focal hepatic infantile hepatic epithelioid hemangioendothelioma with expression of CD31 and VEGF in breast carcinoma, hemangioendothelioma using TACE/surgery followed thalidomide: a case report. J Med Case Rep 2010 as predictive factors of lymph node metastasis. by maintenance metronomic therapy. BMJ Case Rep Dec 22;4:413. DOI: http://dx.doi.org/10.1186/1752- Breast Cancer 1998 Apr 25;5(2):131-8. DOI: http:// 2012 Mar 8;2012. DOI: http://dx.doi.org/10.1136/ 1947-4-413. dx.doi.org/10.1007/bf02966685. bcr.12.2011.5456. 26. Ding GF, Li JC, Xu YF, Sun Y, Tao L. [Correlation 33. Haruki T, Arai T, Nakamura H, Nosaka K, Shomori K, between the expression of VEGF-C mRNA, Ito H. Pulmonary epithelioid hemangioendothelioma

All Attempts at a Rational Method of Cure

The main part of the science of disease is of a purely descriptive character, a scientific interpretation of facts and a clear insight into the intimate connection subsisting between different phenomena, which may precede all attempts at a rational method of cure, having been attained in a few instances only. … Therapeutic researchers must be regulated in the same manner as pathological. … The more careful tracing of the progress of morbid processes, and the insight into their modes of origin and retrogression, enable us to determine the principles of treatment with greater clearness than formerly.

— Friedrich Theodor von Frerichs, 1819-1885, German pathologist

The Permanente Journal/Perm J 2016 Summer;20(3):15-152 89 COMMENTARY Quality Over Quantity: Integrating Mental Health Assessment Tools into Primary Care Practice

Darrell L Hudson, PhD, MPH Perm J 2016 Summer;20(3):15-148 E-pub: 06/17/2016 http://dx.doi.org/10.7812/TPP/15-148

ABSTRACT educational attainment and income earned as well as increased Depression is one of the most common, costly, and debilitating days off work.6-10 Depression is also associated with suicide11-13 psychiatric disorders in the US. There are also strong associations in addition to a wide range of chronic diseases such as heart between depression and physical health outcomes, particularly disease and diabetes mellitus.14-18 Recent national policy changes chronic diseases such as diabetes mellitus. Yet, mental health related to mental health coverage, namely the Patient Protection services are underutilized throughout the US. Recent policy and Affordable Care Act of 201019 and the Mental Health Parity changes have encouraged depression screening in primary care and Addiction Equity Act,20 have promoted the integration of settings. However, there is not much guidance about how de- mental health screening and treatment into primary care set- pression screeners are administered. There are people suffering tings. Indeed, most patients are initially diagnosed and treated from depression who are not getting the treatment they need. It is for mental health problems within primary care settings.21,22 important to consider whether enough care is being taken when Many practices and health care systems, such as Kaiser Per- administering depression screeners in primary care settings. manente, use the PHQ to screen for mental health problems. Results from numerous studies indicate that this measure is I was at the doctor’s office, a family medicine practice for a effective in screening for mental health problems in primary routine check-up. care settings; even versions with fewer items do a good job of “I have to ask you these questions about mental health,” the identifying depression.23-25 nurse said sheepishly after recording my heart rate and blood Although there are numerous resources that describe different pressure. versions of the PHQ as well as information about reliability and The preface immediately put me on guard and I tensed up. validity, in addition to steps on how to score the screener, there On the one hand, I thought, does anyone suspect that some- are no clear guidelines about how clinicians should go about thing is wrong with me? Could they tell I was anxious because asking patients questions about their mental health. However, I forgot to get cash and would have to dive for quarters in my the manner in which questions are asked and by whom have a glove box to get out of their parking deck? On the other hand, profound effect on the answers that patients provide.26,27 This is I conduct mental health research, so I knew the nurse was especially true when asking about sensitive information.27 Race/ probably going to ask me questions from the Patient Health ethnicity, sex, social class, and sexual orientation are additional Questionnaire (PHQ). I was encouraged that mental health was considerations that mental health service clinicians must con- being integrated into a medical visit in a primary care setting. tend with and which make recognition and treatment of depres- During the past two weeks, have you found little interest or sion even more challenging. Further, mental health conditions pleasure in doing things? remain highly stigmatized. This seems to be an important factor Have you felt down, depressed, or hopeless? that should be addressed at the individual clinician level as well The answer to both of these questions was no. But the opening as at the system level. statement from the nurse about her obligation to ask questions Practices and health care plans should be applauded for tak- about mental health set me on edge a bit. The nurse’s demeanor ing steps to integrate mental health and primary care. Despite changed from when she was taking my blood pressure and re- the efficacy and effectiveness of the PHQ, I wondered how cording my weight. In one sentence, she made it abundantly probable someone suffering from depression would be to share clear that she was asking only because of obligation, she was such feelings during a similar clinical interaction. I wondered not comfortable asking, and she was not particularly interested if the nurse’s preface and, more importantly, her demeanor in hearing my answers to the questions. I wondered, if I was would affect the comfort of patients who do suffer from men- feeling down or losing interest in doing things I had previously tal health problems and give them pause about answering the enjoyed, would I feel comfortable telling her? Considering her questions honestly. apparent disinterest, did she even care? Would I believe that she Is it enough to simply ask questions, especially if the person would do anything about my feelings? asking the question does not seem the least bit interested or Depression is one of the most common, costly, and debili- enthused about doing so? If the goal is to screen patients who tating conditions in the US, affecting millions of Americans may be suffering from depression and other mental health each year.1-5 Disability from depression is associated with lower problems, there must be better care in the administration of

Darrell L Hudson, PhD, MPH, is an Assistant Professor at the Brown School of Social Work at Washington University in St Louis, MO. E-mail: [email protected].

90 The Permanente Journal/Perm J 2016 Summer;20(3):15-148 COMMENTARY Quality Over Quantity: Integrating Mental Health Assessment Tools into Primary Care Practice

the PHQ within primary care settings. If patients are anxious How to Cite this Article about their answers or fear judgment, they might give biased Hudson DL. Quality over quantity: integrating mental health assessment answers. And that will not help anyone. If the nurse’s preface to tools into primary care practice. Perm J 2016 Summer;20(3):15-148. DOI: http://dx.doi.org/10.7812/TPP/15-148 the questions put me on guard, I wondered how other primary care patients might feel. A search of the literature for best practices in administering References 1. Greenberg PE, Kessler RC, Birnbaum HG, et al. The economic burden of depression the PHQ or other depression screeners did not produce any spe- in the United States: how did it change between 1990 and 2000? J Clin Psychiatry cific guidelines to help clinicians to most effectively administer 2003 Dec;64(12):1465-75. DOI: http://dx.doi.org/10.4088/JCP.v64n1211. these instruments. However, clinicians could help to mitigate 2. Demyttenaere K, Bruffaerts R, Posada-Villa J, et al; WHO World Mental Health Survey Consortium. Prevalence, severity, and unmet need for treatment of mental disorders stigma by establishing rapport and asking about patients’ overall in the World Health Organization World Mental Health Surveys. JAMA 2004 Jun 2; well-being, whether they are feeling very stressed, and whether 291(21):2581-90. DOI: http://dx.doi.org/10.1001/jama.291.21.2581. there have been any substantial changes in their lives. It may 3. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey also help to have physicians incorporate these questions into Replication. Arch Gen Psychiatry 2005 Jun;62(6):617-27. DOI: http://dx.doi.org/ their general physical examination so that patients understand 10.1001/archpsyc.62.6.617. that mental health is essential to overall well-being. Further- 4. Ustün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJ. Global burden of depressive disorders in the year 2000. Br J Psychiatry 2004 May;184(5):386-92. more, there should be clinician continuity in who administers DOI: http://dx.doi.org/10.1192/bjp.184.5.386. depression screeners. In my case, a nurse with whom I do not 5. Gwynn RC, McQuistion HL, McVeigh KH, Garg RK, Frieden TR, Thorpe LE. recall interacting before my visit administered the PHQ before Prevalence, diagnosis, and treatment of depression and generalized anxiety disorder in a diverse urban community. Psychiatr Serv 2008 Jun;59(6):641-7. I saw my regular physician. I did not have a relationship with DOI: http://dx.doi.org/10.1176/appi.ps.59.6.641. her and would have found the screener questions less obtrusive 6. Kessler RC, Foster CL, Saunders WB, Stang PE. Social consequences of psychiatric if they were incorporated into time with the physician, whom I disorders, I: educational attainment. Am J Psychiatry 1995 Jul;152(7):1026-32. have been seeing for several years. The PHQ and other depres- DOI: http://dx.doi.org/10.1176/ajp.152.7.1026. 7. Kessler RC, McLaughlin KA, Green JG, et al. Childhood adversities and adult sion screeners avoid psychiatric terms that may be stigmatized psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry 2010 or confusing to patients. Similarly, clinicians should avoid these Nov;197(5):378-85. DOI: http://dx.doi.org/10.1192/bjp.bp.110.080499. terms. Additionally, once clinicians ask questions about mental 8. Breslau J, Lane M, Sampson N, Kessler RC. Mental disorders and subsequent educational attainment in a US national sample. J Psychiatr Res 2008 Jul;42(9): health, they must be prepared to discuss the challenges that pa- 708-16. DOI: http://dx.doi.org/10.1016/j.jpsychires.2008.01.016. tients are facing and be ready to provide referrals and resources 9. Lorant V, Deliège D, Eaton W, Robert A, Philippot P, Ansseau M. Socioeconomic to help patients with mental health conditions. inequalities in depression: a meta-analysis. Am J Epidemiol 2003 Jan 15;157(2): 98-112. DOI: http://dx.doi.org/10.1093/aje/kwf182. There are probably many missed opportunities to address the 10. Muntaner C, Eaton WW, Miech R, O’Campo P. Socioeconomic position and major mental health needs of Americans. It is no secret that mental mental disorders. Epidemiol Rev 2004;26:53-62. DOI: http://dx.doi.org/10.1093/ health services are underutilized in the US.28-30 Fewer than epirev/mxh001. 11. Brownhill S, Wilhelm K, Barclay L, Schmied V. ‘Big build’: hidden depression in half of the people who have a mental health problem ever men. Aust N Z J Psychiatry 2005 Oct;39(10):921-31. DOI: http://dx.doi.org/10.1111/ seek services.31 Even in highly vulnerable populations, like j.1440-1614.2005.01665.x. those who have diabetes, depression recognition (eg, diagno- 12. Oquendo MA, Ellis SP, Greenwald S, Malone KM, Weissman MM, Mann JJ. Ethnic and sex differences in suicide rates relative to major depression in the United States. sis, medication, referral to mental health specialty care) can Am J Psychiatry 2001 Oct;158(10):1652-8. DOI: http://dx.doi.org/10.1176/appi. be poor.32 It is probable that there are patients suffering from ajp.158.10.1652. mental health problems who do not seek treatment or who are 13. Joe S. Explaining changes in the patterns of black suicide in the United States from 1981 to 2002: an age, cohort, and period analysis. J Black Psychol 2006 Aug not being recognized with these problems when they interact 1;32(3):262-84. DOI: http://dx.doi.org/10.1177/0095798406290465. with clinicians for medical concerns. It is important to con- 14. Katon W, Lin EH, Von Korff M, et al. Integrating depression and chronic disease sider whether enough care is being taken when administering care among patients with diabetes and/or coronary heart disease: the design of the TEAMcare study. Contemp Clin Trials 2010 Jul;31(4):312-22. DOI: http://dx.doi.org/ depression screeners in primary care settings. Furthermore, it 10.1016/j.cct.2010.03.009. may be important to alert patients that they should expect to 15. Mezuk B, Eaton WW, Albrecht S, Golden SH. Depression and type 2 diabetes over be screened for mental health issues even if they are visiting the lifespan: a meta-analysis. Diabetes Care 2008 Dec;31(12):2383-90. DOI: http:// v dx.doi.org/10.2337/dc08-0985. for their physical examinations. 16. Carney RM, Freedland KE, Sheps DS. Depression is a risk factor for mortality in coronary heart disease. Psychosom Med 2004 Nov-Dec;66(6):799-801. DOI: http:// Disclosure Statement dx.doi.org/10.1097/01.psy.0000146795.38162.b1. This work was supported by the Barnes-Jewish Hospital Foundation in 17. Katon W, Russo J, Lin EH, et al. Diabetes and poor disease control: is comorbid addition to Grant Number 1P30DK092950 from the National Institute of depression associated with poor medication adherence or lack of treatment intensification? Psychosom Med 2009 Nov;71(9):965-72. DOI: http://dx.doi.org/ Diabetes and Digestive and Kidney Diseases, and its contents are solely the 10.1097/PSY.0b013e3181bd8f55. responsibility of the authors and do not necessarily represent the official views 18. Katon WJ, Lin EH, Von Korff M, et al. Collaborative care for patients with depression of the National Institute of Diabetes and Digestive and Kidney Diseases. The and chronic illnesses. N Engl J Med 2010 Dec 30;363(27):2611-20. DOI: http:// funding agreement ensured the authors’ independence in designing the study, dx.doi.org/10.1056/NEJMoa1003955. collecting and interpreting the data, writing, and publishing the results. 19. The Patient Protection and Affordable Care Act of 2010. Public Law 111-148, 111th The author(s) have no other conflicts of interest to disclose. Congress, 124 Stat 119, HR 3590, enacted 2010 Mar 23. 20. Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008. Public Law 110-460, 110th Congress, HR 6983, enacted 2008 Oct 3. Acknowledgment 21. Unützer J, Schoenbaum M, Druss BG, Katon WJ. Transforming mental health care at Mary Corrado, ELS, provided editorial assistance. the interface with general medicine: report for the presidents commission. Psychiatr Serv 2006 Jan;57(1):37-47. DOI: http://dx.doi.org/10.1176/appi.ps.57.1.37.

The Permanente Journal/Perm J 2016 Summer;20(3):15-148 91 COMMENTARY Quality Over Quantity: Integrating Mental Health Assessment Tools into Primary Care Practice

22. US Preventive Services Task Force. Screening for depression: recommendations 28. Substance Abuse and Mental Health Services Administration. Racial/ethnic and rationale. Ann Intern Med 2002 May 21;136(10):760-4. DOI: http://dx.doi. differences in mental health service use among adults. HHS publication no. SMA- org/10.7326/0003-4819-136-10-200205210-00012. 15-4906 [Internet]. Rockville, MD: Substance Abuse and Mental Health Services 23. Kroenke K, Strine TW, Spitzer RL, Williams JB, Berry JT, Mokdad AH. The PHQ-8 Administration; 2015 [cited 2015 Oct 28]. Available from: www.samhsa.gov/data/sites/ as a measure of current depression in the general population. J Affect Disord 2009 default/files/MHServicesUseAmongAdults/MHServicesUseAmongAdults.pdf. Apr;114(1-3):163-73. DOI: http://dx.doi.org/10.1016/j.jad.2008.06.026. 29. Wang PS, Berglund P, Kessler RC. Recent care of common mental disorders in the 24. Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity United States: prevalence and conformance with evidence-based recommendations. of a two-item depression screener. Med Care 2003 Nov;41(11):1284-92. DOI: J Gen Intern Med 2000 May;15(5):284-92. DOI: http://dx.doi.org/10.1046/j.1525-1497. http://dx.doi.org/010.1097/01.MLR.0000093487.78664.3C. 2000.9908044.x. 25. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments 30. González HM, Vega WA, Williams DR, Tarraf W, West BT, Neighbors HW. for depression. Two questions are as good as many. J Gen Intern Med 1997 Depression care in the United States: too little for too few. Arch Gen Psychiatry 2010 Jul;12(7):439-45. DOI: http://dx.doi.org/10.1046/j.1525-1497.1997.00076.x. Jan;67(1):37-46. DOI: http://dx.doi.org/10.1001/archgenpsychiatry.2009.168. 26. Ross CE, Mirowsky J. Socially-desirable response and acquiescence in a cross- 31. Office of the Surgeon General; Center for Mental Health Service; National Institute cultural survey of mental health. J Health Soc Behav 1984 Jun;25(2):189-97. DOI: of Mental Health. Mental health: culture, race, and ethnicity: executive summary. http://dx.doi.org/10.2307/2136668. A supplement to mental health: a report of the Surgeon General. Rockville, MD: 27. Groves RM, Fowler FJ Jr, Couper MP, Lepkowski JM, Singer E, Tourangeau R. Substance Abuse and Mental Health Services Administration; 2001. Survey methodolgy. 1st ed. Hoboken, NJ: John Wiley & Sons; 2004. 32. Hudson DL, Karter AJ, Fernandez A, et al. Differences in the clinical recognition of depression in diabetes patients: the Diabetes Study of Northern California (DISTANCE). Am J Manag Care 2013 May;19(5):344-52.

Mental Distress

Every day brought some fresh proof of how great was the influence of mental distress in augmenting bodily pain and sickness. Whatever circumstances were calculated to make a strong impression upon the spirits, threw them back at once from a state of convalescence, into absolute disease … . Passions and affections of the mind are wont to show their power over the body especially by the manner in which they influence the heart, even the healthy heart; rousing it to tumultuous and irregular action and engendering pain within it.

— Peter Mere Latham, 1789-1875, physician and medical educator

92 The Permanente Journal/Perm J 2016 Summer;20(3):15-148 COMMENTARY Plant-Based Diets: A Physician’s Guide

Julieanna Hever, MS, RD, CPT Perm J 2016 Summer;20(3):15-082 E-pub: 07/06/2016 http://dx.doi.org/10.7812/TPP/15-082

ABSTRACT growth factor-1, more is generated Because of the ever-increasing body of evidence in support of the health advantages endogenously.21 Fostering growth as a of plant-based nutrition, there is a need for guidance on implementing its practice. This full-grown adult can promote cancer article provides physicians and other health care practitioners an overview of the myriad proliferation. benefits of a plant-based diet as well as details on how best to achieve a well-balanced, • Heme iron: Although heme iron, found nutrient-dense meal plan. It also defines notable nutrient sources, describes how to get in animal products, is absorbed at a started, and offers suggestions on how health care practitioners can encourage their higher rate than nonheme iron, found patients to achieve goals, adhere to the plan, and experience success. in plant-based and fortified foods, absorption of nonheme iron can be SUMMARY OF HEALTH BENEFITS recommendations15 for a heart-healthy increased by pairing plant-based pro- Plant-based nutrition has exploded in diet to include no more than 5% to tein sources with foods high in vitamin popularity, and many advantages have 6% of total calories from saturated fat, C.22 Additionally, research suggests that been well documented over the past sev- which is just the amount found natu- excess iron is pro-oxidative23 and may eral decades.1 Not only is there a broad rally in a vegan diet (one consisting of increase colorectal cancer risk24 and expansion of the research database sup- no animal products). promote atherosclerosis25 and reduced porting the myriad benefits of plant-based • Dietary cholesterol: Human bodies insulin sensitivity.26 diets, but also health care practitioners produce enough cholesterol for ad- • Chemical contaminants formed from are seeing awe-inspiring results with equate functioning. Although evidence high temperature cooking of cooked their patients across multiple unique suggests that dietary cholesterol may animal products: When flesh is cooked, subspecialties. Plant-based diets have only be a minor player in elevated serum compounds called polycyclic aromatic been associated with lowering overall cholesterol levels, high intakes are linked hydrocarbons,27 heterocyclic amines,28 and ischemic heart disease mortality2; to increased susceptibility to low-density and advanced glycation end products29 supporting sustainable weight manage- lipoprotein oxidation, both of which are formed. These compounds are ment3; reducing medication needs4-6; low- are associated with the promotion of carcinogenic, pro-inflammatory, pro- ering the risk for most chronic diseases7,8; CVD.16-18 Dietary cholesterol is found oxidative, and contributive to chronic decreasing the incidence and severity of almost exclusively in animal products. disease. high-risk conditions, including obesity,9 • Antibiotics: The vast majority (70% to • Carnitine: Carnitine, found primar- hypertension,10 hyperlipidemia,11 and hy- 80%) of antibiotics used19,20 in the US ily in meat, may be converted in the perglycemia;11 and even possibly reversing are given to healthy livestock animals body by the gut bacteria to produce advanced coronary artery disease12,13 and to avoid infections inherent in the trimethylamine N-oxide (TMAO). type 2 diabetes.6 types of environments in which they High levels of trimethylamine n-oxide The reason for these outcomes is two- are kept. This is, therefore, the num- are associated with inflammation, ath- fold. First, there are inherent benefits to ber one contributor to the increasingly erosclerosis, heart attack, stroke, and eating a wide variety of health-promoting virulent antibiotic-resistant infections death.30 plants. Second, there is additional benefit of the type that sickened 2 million and • N-Glycolylneuraminic acid (Neu5Gc): from crowding out—and thereby avoid- killed 23,000 Americans in 2013.20 This compound is found in meat and ing—the injurious constituents found in • Insulin-like growth factor-1: Insulin- promotes chronic inflammation.31,32 animal products, including the following: like growth factor-1 is a hormone On the other hand, there are infinite • Saturated fats: Saturated fats are a naturally found in animals, includ- advantages to the vast array of nutrients group of fatty acids found primarily in ing humans. This hormone promotes found in plant foods. Phytochemicals animal products (but also in the plant growth. When insulin-like growth and fibers are the two categories of nu- kingdom—mostly in tropical oils, such factor-1 is consumed, not only is the trients that are possibly the most health as coconut and palm) that are well es- added exogenous dose itself taken in, promoting and disease fighting. Plants are tablished in the literature as promoting but because the amino acid profile the only source of these nutrients; they cardiovascular disease (CVD).14,15 The typical of animal protein stimulates are completely absent in animals. Plants American Heart Association lowered its the body’s production of insulin-like contain thousands of phytochemicals,

Julieanna Hever, MS, RD, CPT, is a Dietitian and Author in Los Angeles, CA. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-082 93 COMMENTARY Plant-Based Diets: A Physician’s Guide

such as carotenoids, glucosinolates, and Table 1. Food group recommended servings per day flavonoids, which perform a multitude of Food group Recommended servings per day beneficial functions, including: Vegetables, all types, including starchy Ad libitum, with a variety of colors represented • Antioxidation, neutralizing free radicals33 • Anti-inflammation34 Fruits, all types 2-4 servings (1 serving = 1 medium piece or 1/2 cup) • Cancer activity reduction via several Whole grains (eg, quinoa, brown rice, oats) 6-11 servings (1 serving = 1/2 cup cooked or 1 slice whole grain bread) mechanisms, including inhibiting tu- mor growth, detoxifying carcinogens, Legumes (beans, peas, lentils, soy foods) 2-3 servings (1 serving = 1/2 cup cooked) retarding cell growth, and preventing Leafy green vegetables (eg, kale, lettuce, At least 2-3 servings (1 serving = 1 cup raw or broccoli) 1/2 cup cooked) cancer formation35 Nuts (eg, walnuts, almonds, pistachios) 1-2 ounces • Immunity enhancement36 • Protection against certain diseases, such Seeds (eg, chia, hemp, and flax seeds) 1-3 tablespoons as osteoporosis, some cancers, CVD, Fortified plant milks (eg, soy, almond, cashew) Optional, 2-3 cups macular degeneration, and cataracts37-39 Fresh herbs and spices Optional, ad libitum • Optimization of serum cholesterol.40,41 Fibers found in whole plant foods powerfully support the gastrointestinal, “well-planned vegetarian diets are appro- Seeds, too, are special in that their es- cardiovascular, and immune systems priate for individuals during all stages of sential fat ratios are well-balanced, and through multiple mechanisms. Yet more the life cycle, including pregnancy, lacta- they contain multiple trace minerals and than 90% of adults and children in the US tion, infancy, childhood, and adolescence, phytochemicals. One or 2 tablespoons per do not get the minimum recommended and for athletes.” Because any type of meal day will boost overall nutrition. Opting for dietary fiber.42 plan should be approached with careful whole food sources of fats, as opposed to Thus, it can be advantageous for physi- thought, it is helpful to note that plant- extracted fats as found in oils, is optimal cians to recommend and support plant- based diets, including calorie-restricted, to decrease caloric density and increase based eating to achieve optimal health weight-loss diets, have been found to be nutrient and fiber consumption. Herbs outcomes and possibly minimize the need more nutritionally sound than typical and spices also contain phytochemicals for procedures, medications, and other dietary patterns.45 and help make food delicious, varied, and treatments. Aiming for lifestyle changes A well-balanced, plant-based diet is exciting, and should be used according as primary prevention has been estimated composed of vegetables, fruits, whole to preference. Food group recommended to save upwards of 70% to 80% of health grains, legumes, herbs, spices, and a small servings per day are shown in Table 1. care costs because 75% of health care amount of nuts and seeds. Half of the plate spending in the US goes to treat people should consist of vegetables and fruits in PLANT-BASED MACRONUTRITION with chronic conditions.43 Offering this accordance with the US Department of All calories (kcals) come from some option and guiding patients through the Agriculture, American Cancer Society, combination of carbohydrates (4 kcals/g), logistics and their concerns about plant- and American Heart Association, because proteins (4 kcals/g), and fats (9 kcals/g). based eating is a viable first line of therapy they are filled with fiber, potassium, mag- Alcohol also provides calories (7 kcals/g) in the clinical setting. This article will nesium, iron, folate, and vitamins C and but is not considered an essential nutri- delineate how best to achieve a well-bal- A—almost all of the nutrients that tend ent. The ideal ratio of intake of these 3 anced, nutrient-dense meal plan, define to run low in the American population, macronutrients is highly controversial notable nutrient sources, describe how according to the Scientific Report of the and debatable. There is plenty of evidence to get started, and offer suggestions on 2015 Dietary Guidelines Advisory Com- supporting health and weight management how physicians can encourage and work mittee.46 Legumes are excellent sources of benefits of low-fat/high-carbohydrate di- with their patients who are interested to lysine (an amino acid that may fall short ets, as seen in the traditional Okinawan maintain adherence and enjoy success. in a plant-based diet), fiber, calcium, iron, diet51 and in Dean Ornish, MD’s12 and zinc, and selenium. It is ideal to consume Caldwell Esselstyn, MD’s13 reversal of ad- NOTABLE NUTRIENTS one to one-and-a-half cups of legumes vanced coronary artery disease and Neal Although nutrient deficiency is a per day. Substantiating meals with whole Barnard, MD’s6 reduction of glycemia in primary concern for many people when grains aids with satiety, energy, and versa- type 2 diabetes using a plant-based diet considering plant-based eating, the Acad- tility in cuisine. Nuts are nutritional nug- with 10% of calories from fat. Similarly, emy of Nutrition and Dietetics states44 gets, brimming with essential fats, protein, the Mediterranean52 and many raw food53 that “vegetarian diets, including total fiber, vitamin E, and plant sterols, and have diets consisting of upwards of 36% or vegetarian or vegan diets, are healthful, been shown to promote cardiovascular more of calories from fat show consistently nutritionally adequate, and may provide health47 and protect against type 2 diabetes positive health advantages. Thus, it appears health benefits in the prevention and treat- and obesity,48 macular degeneration,49 and that it is likely the quality of the diet that ment of certain diseases.” The Academy’s cholelithiasis.50 One oz to 2 oz (or 30 g to is responsible for health outcomes rather position paper goes on to conclude that 60 g) of nuts per day is recommended. than the ratio of macronutrients.

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Carbohydrates metals, such as mercury, lead, and cad- production of hormones, vitamin D, The Institute of Medicine’s adequate mium, as well as industrial pollutants.55 and bile acids, the liver produces enough intake of carbohydrates54 is 130 g/d for Also, plant sources are more sustainable cholesterol on its own. Excessive intake everyone (except during pregnancy and than fish sources.56 of dietary cholesterol is associated with lactation) beginning at age 1 year. Optimal Monounsaturated fats are not essential increased risk of CVD. sources of carbohydrates, such as whole- but have been found to impart either a Phytosterols, which are similar to cho- some vegetables, fruits, whole grains, and neutral or slightly beneficial effect on lesterol, are plant-based sterols found in legumes, are high in fiber and nutrients. serum cholesterol levels, depending on all plant foods (especially wheat germ, Refined carbohydrates from sugars, flours, which nutrient they are replacing. When nuts, seeds, whole grains, legumes, and and other processed foods can lead to mal- swapped for saturated fats, trans fats, or unrefined plant oils). Phytosterols reduce nourishment and promote illness. refined carbohydrates, monounsaturated cholesterol absorption in the gut, thereby fats may lower low-density lipoprotein optimizing lipid profiles. Together with Protein and raise high-density lipoprotein cho- viscous fibers, soy proteins, and almonds, Adequate intake54 of protein is based lesterol. These fatty acids are found in phytosterols have been found to be as ef- on weight and is estimated at 1.5 g/kg/d olives, avocados, macadamia nuts, hazel- fective as statins in some studies in lower- for infants, 1.1 g/kg/d for 1 to 3 year olds, nuts, pecans, peanuts, and their respec- ing low-density lipoprotein cholesterol.5,58 0.95 g/kg/d for 4 to 13 year olds, 0.85 g/kg/d tive oils, as well as in canola, sunflower, It is crucial to note that all whole foods for 14 to 18 year olds, 0.8 g/kg/d for adults, and safflower oils. contain all three macronutrients. It is a and 1.1 g/kg/d for pregnant (using prepreg- Saturated fats, as mentioned above, pervasive misunderstanding to identify nancy weight) and lactating women. Protein are not essential in the diet and can a food as a “carb,” “protein,” or “fat.” is readily available throughout the plant promote CVD. They are found primar- Instead, these are all nutrients within a kingdom, but those foods that are particu- ily in animal products but are available complex of other myriad constituents larly rich in protein include legumes, nuts in some plant foods, mostly in tropical that are beyond the oversimplification and nut butters, seeds and seed butters, soy fats and oils, such as palm and coconut, perpetuated by the media and trendy foods, and intact whole grains. and also in other high-fat foods, includ- diet fads. ing avocados, olives, nuts, and seeds. If a Ideally, a healthful diet is loaded with Fats vegan diet contains an average of 5% to wholesome carbohydrates, moderate Fats—or fatty acids—are more com- 6% of kcals from saturated fat, which is in fat, and temperate in protein. The plicated because there are several differ- what the American Heart Organization emphasis must be on the quality of the ent chemical varieties based on level and recommends for a heart-healthy diet, any totality of foods coming from whole type of saturation. Each category of fatty added serving of animal products will plant sources as opposed to calculations acid performs different functions and significantly increase the total intake. and perfect ratios. acts uniquely in the body.14 Trans fatty acids are laboratory-made The essential fatty acids are polyun- via hydrogenation and are found in pro- PLANT-BASED MICRONUTRITION saturated and include both omega-3 and cessed, fried, and fast foods. Although All nutrients, with the exception of vi- omega-6 fatty acids. Omega-3 fats are they were originally developed to be a tamin B12 and possibly vitamin D, which found in their shorter chain form as al- healthy alternative to butter and lard, is ideally sourced from the skin’s exposure pha linolenic acid and are used as energy. trans fatty acids were found to signifi- to the sun’s ultraviolet rays, can be found They are also converted by the body to cantly increase CVD risk. In November in plants. They are also packaged together the longer-chain eicosapentaenoic acid 2013, the US Food and Drug Admin- with thousands of powerful disease-fight- (EPA) and then docosahexaenoic acid istration issued a notice that trans fatty ing nutrients that work synergistically to (DHA). Because this conversion pro- acids were no longer considered safe57 support optimal health.59 cess can be inefficient, some people may and is now trying to eliminate artifi- require a direct source of these longer- cially produced trans fatty acids (there Vitamin B12 chain EPA and DHA in the form of a are small amounts found naturally in Cobalamin, commonly referred to microalgae supplement. Alpha linolenic meat and dairy products) from the food as vitamin B12, is the only nutrient not acid can be found in flaxseeds, hemp- supply. Be aware that a nutritional label directly available from plants. This is seeds, chia seeds, leafy green vegetables can state a food product contains “0 g because vitamin B12 is synthesized by mi- (both terrestrial and marine), soybeans trans fats” even if it contains up to 0.5 g croorganisms, bacteria, fungi, and algae, and soy products, walnuts, and wheat per serving. Thus, advise your patients but not by plants or animals. Animals germ, as well as in their respective oils. to focus on the ingredient list on food consume these microorganisms along A direct plant source of EPA and DHA products and to avoid anything with the with their food, which is why this vitamin is microalgae, through which fish acquire words “partially hydrogenated.” can be found in their meat, organs, and

them. Plant sources may be superior be- Dietary cholesterol is a sterol that is byproducts (eggs and dairy). Vitamin B12 cause they do not contain the contami- found primarily in animal products. deficiency can lead to irreversible neuro- nants that fish contain, including heavy Although cholesterol is required for the logic disorders, gastrointestinal problems,

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and megaloblastic anemia. Among other appears to be a worldwide epidemic respect to bone mineral optimization dur- populations, vegans who do not supple- of deficiency. Vitamin D is not widely ing the lifespan. However, because bone

ment with a reliable source of vitamin B12 available from the food supply. Sources metabolism is multifactorial and complex, or breastfeeding infants of vegan mothers of preformed vitamin D include fish it is important to emphasize consumption who are not consuming a regular reli- liver oil, oily fish, liver, and in smaller of ample sources of calcium as well as vi-

able source of vitamin B12 are at risk for doses, meat and egg yolk—foods that also tamins K and B12, fluoride, magnesium, deficiency. contain high concentrations of saturated phosphorus, and potassium; to maintain

The body can store vitamin B12 for ap- fat, cholesterol, and other less-than-ideal serum vitamin D levels; and to ensure con- proximately three to five years, but after components. Vitamin D from sunshine sistent exercise. Throughout the lifespan, that, with no repletion or with inability to and animal sources is in the form of dietary recommendations for adequate 62 absorb, deficiency symptoms may present; cholecalciferol, or vitamin D3. A second intake of calcium fluctuate. deficiency may also be asymptomatic. Be- form called ergocalciferol, or vitamin Excellent plant sources of calcium in-

cause of this lag time and because serum D2, is found in plant sources, mostly clude leafy green vegetables—especially tests for B12 levels can be skewed by other in ultraviolet B-irradiated mushrooms. bok choy, broccoli, napa cabbage, collard variables, irreversible damage may occur However, a plant-derived version of D3 greens, dandelion greens, kale, turnip before a deficiency is caught. made by lichen was recently discovered.60 greens, and watercress—as well as forti-

In a vegan diet, vitamin B12 can be Dietary supplements may contain either fied plant milks, calcium-set tofu, dried found in fortified plant milks, cereals, D2 or D3, both of which can be effective figs, sesame seeds and tahini, tempeh, al- or nutritional yeast. However, these are at optimizing blood levels. monds and almond butter, oranges, sweet

not dependable means of achieving B12 More and more physicians are testing potatoes, and beans. requirements. Although there are claims for serum levels of vitamin D using the No matter how much calcium is con- that fermented foods, spirulina, chlorella, 25-hydroxyvitamin D test. The Institute sumed, the amount that is actually absorbed certain mushrooms, and sea vegetables, of Medicine concluded that adequate is more significant. Many variables affect

among other foods, can provide B12, the serum 25-hydroxyvitamin D levels are ≥ calcium levels via absorption or excretion, vitamin is not usually biologically active. 50 nmol/L (≥ 20 ng/mL).61 including:

These inactive forms act as 12B analogues, If patients have suboptimal levels, em- • Overall consumption determines how attaching to B12 receptors, preventing phasizing food sources (especially fortified much is absorbed. Only about 500 mg absorption of the functional version, and plant milks) as well as supplements may can be absorbed at a time, and absorption thereby promoting deficiency. The most be helpful. Dosing may be tricky because decreases as calcium intake increases reliable method of avoiding deficiency for of variable responses in individuals and • Age. Calcium absorption peaks in in- vegans or anyone else at risk is to take a differences in types of vitamin D formu- fants and children, as they are rapidly

B12 supplement. las. Of note, although both of the 2 forms growing bone, and then progressively Because the body can absorb only ap- of vitamin D—cholecalciferol (D3) and decreases with age proximately 1.5 µg to 2.0 µg at a time, it ergocalciferol (D2)—are effective at rais- • Phytates, compounds found in whole is ideal to supplement with a dose greater ing serum D levels in small doses (4000 grains, beans, seeds, nuts, and wheat

than the Recommended Dietary Allow- IU or less), cholecalciferol (D3) is supe- bran, can bind with calcium as well as ance (RDA) to ensure adequate intake. rior when using large boluses. Because with other minerals and inhibit absorp- Plant-based nutrition experts recommend the supplement industry is not regulated tion. Soaking, sprouting, leavening, and a total weekly dose of 2000 µg to 2500 µg. by the Food and Drug Administration, fermenting improve absorption This can be split into daily doses or into it is “buyer beware” in the supplement • Oxalates are constituents found in some 2 to 3 doses of 1000 µg each per week to market. Thus, aim to find well-reputed leafy green vegetables, such as spinach, help enhance absorption. Because vitamin companies. A few organizations, such as Swiss chard, collard greens, parsley,

B12 is water soluble, toxicity is rare. Consumer Lab, NSF International, and leeks, and beet greens; berries; almonds; US Pharmacopeia, act as independent cashews; peanuts; soybeans; okra; qui- Vitamin D third parties and offer seals of approval noa; cocoa; tea; and chocolate. They Vitamin D, or calciferol, is also known after testing products for potency and may also somewhat inhibit absorption as the “sunshine vitamin” because it is contaminants. They do not, however, test of calcium and other minerals, but some the only nutrient that is acquired from for safety or efficacy. may still be absorbed. Emphasizing vari- the sun. Although vitamin D is classified ety in the foods eaten on a regular basis as and treated like a fat-soluble vitamin, Calcium encourages adequate absorption it is actually a prohormone produced in Calcium, a macromineral, is the most • Serum vitamin D levels must be within the skin upon exposure to ultraviolet B abundant mineral in the human body. A optimum range in order for the body to sun radiation and then activated by the mere 1% of the body’s calcium circulates absorb calcium. liver and kidneys. in the blood and tissues; 99% is stored in • Excessive intake of sodium, protein, Although human bodies evolved to the bones and teeth. Calcium is a nutrient caffeine, and phosphorus (as from dark produce vitamin D via the sun, there of concern for the general population with sodas) may enhance calcium excretion.62

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Iron soy products, dark chocolate, blackstrap of consuming a source of iodine to avoid Ironically, iron is one of the most molasses, sesame seeds, tahini, pumpkin thyroid issues. Sources of iodine include abundant metals on Earth and yet iron seeds, sunflower seeds, raisins, prunes, iodized salt and sea vegetables. However, deficiency is one of the most common and cashews. it is important to note that iodine is not and widespread nutritional deficiencies. Iron absorption may be diminished found in sea salts, gourmet salts, or other It is the most common deficiency in the in the presence of phytates, tannic acids salty foods. One half-teaspoon of iodized world and is a public health problem in from tea, calcium in dairy, fiber, poly- salt provides the daily recommended both industrialized and nonindustrialized phenols in coffee and cocoa, and certain 150-µg dose. Also, iodine levels in sea countries.63 It is particularly prevalent spices (eg, turmeric, coriander, chilies, vegetables fluctuate dramatically, with in women of childbearing age, pregnant and tamarind). To minimize this, separate some (especially dulse and nori) contain- women, infants, children, teenage girls, iron-rich foods from these nutrients as ing safe amounts and others (such as kelp) and anyone experiencing bleeding, such much as possible. An example is to drink harboring toxic doses. Hijiki, also spelled as people with ulcers, inflamed intestines coffee or tea separately from meals or to hiziki, should be avoided owing to its ex- caused by malabsorptive disorders, or mix up meal combinations. One of the cessive arsenic levels. A preexisting iodine heavy menstruation. Iron-deficiency ane- best tips for optimizing iron absorption deficiency, a selenium deficiency, or high mia is no more common in vegetarians is to eat iron-rich foods in combination intake of goitrogens (antinutrients found than in nonvegetarians. with foods high in vitamin C and organic in cruciferous vegetables, soy products, Because plant-sourced iron is nonheme acids. This improves solubility, thereby flaxseeds, millet, peanuts, peaches, pears, iron, which is susceptible to compounds facilitating absorption. Examples of such pine nuts, spinach, sweet potatoes, and that inhibit and enhance its absorption, optimizing food combinations are a green strawberries) can interfere with iodine the recommendation for vegans and veg- smoothie with leafy greens (iron) and fruit absorption. There is no need to avoid etarians is to aim for slightly more iron (vitamin C) or salad greens (iron) with goitrogenic foods as long as iodine intake than nonvegetarians. Fortunately, this is tomatoes (vitamin C). is sufficient. If a patient does not enjoy sea easy to do with the wide array of iron-rich vegetables or is minimizing intake of salt, food choices in the plant kingdom. Leafy Iodine an iodine supplement may be warranted. greens and legumes are excellent sources Dietary sources of the trace mineral of iron and a multitude of other nutrients, iodine are unreliable and fluctuate geo- Selenium so it is advantageous to include these graphically because of varying soil quali- Selenium is a potent antioxidant that foods often. Other good choices include ties. It is crucial for vegans to be mindful protects against cellular damage and also plays a role in thyroid hormone regula- tion, reproduction, and dialpha nucleic Table 2. Sources of notable nutrients acid (DNA) synthesis. Brazil nuts are Nutrient Food sources an especially rich source of selenium in Protein legumes (beans, lentils, peas, peanuts), nuts, seeds, soy foods (tempeh, tofu) the plant kingdom. Although selenium Omega-3 fats seeds (chia, hemp, flax), leafy green vegetables, microalgae, soybeans and soy foods, content varies depending on the source, walnuts, wheat germ an average ounce (approximately 6 to 8 Fiber vegetables, fruits (berries, pears, papaya, dried fruits), avocado, legumes (beans, nuts) can provide 777% of the RDA. lentils, peas), nuts, seeds, whole grains When accessible, one Brazil nut a day is Calcium low-oxalate leafy greens (broccoli, bok choy, cabbage, collard, dandelion, kale, an ideal way of meeting selenium recom- watercress), calcium-set tofu, almonds, almond butter, fortified plant milks, sesame mendations. Other plant sources include seeds, tahini, figs, blackstrap molasses whole grains, legumes, vegetables, seeds, Iodine sea vegetables (arame, dulse, nori, wakame), iodized salt and other nuts. Iron legumes (beans, lentils, peas, peanuts), leafy greens, soybeans and soy foods, quinoa, potatoes, dried fruit, dark chocolate, tahini, seeds (pumpkin, sesame, Zinc sunflower), sea vegetables (dulse, nori) Zinc supports immune function and Zinc legumes (beans, lentils, peas, peanuts), soy foods, nuts, seeds, oats wound healing; synthesis of protein and Choline legumes (beans, lentils, peas, peanuts), bananas, broccoli, oats, oranges, quinoa, soy DNA; and growth and development foods throughout pregnancy, childhood, and Folate leafy green vegetables, almonds, asparagus, avocado, beets, enriched grains (breads, adolescence. Because of the presence of pasta, rice), oranges, quinoa, nutritional yeast phytates, bioavailability of zinc from Vitamin B12 fortified foods (nutritional yeast, plant milks), supplement (2500 mg per week) plants is lower than from animal prod- Vitamin C fruits (especially berries, citrus, cantaloupe, kiwifruit, mango, papaya, pineapple), leafy ucts. Zinc deficiency may be difficult green vegetables, potatoes, peas, bell peppers, chili peppers, tomatoes to detect in blood tests but can show Vitamin D sun, fortified plant milks, supplement if deficient up clinically as delayed wound healing, Vitamin K leafy green vegetables, sea vegetables, asparagus, avocado, broccoli, Brussels growth retardation, hair loss, diminished sprouts, cauliflower, lentils, peas, nattō (a traditional Japanese food made from immunity, suppressed appetite, taste soybeans fermented with Bacillus subtilis var nattō)

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abnormalities, or skin or eye lesions. • How many times per week do you eat Suggested Internet Nutrition Resources Consider advising patients to aim for fried foods/red meat/processed meat/ 50% or greater than the RDA of zinc refined sugars? www.nlm.nih.gov daily by including legumes, cashews and • How often do you choose whole grains https://ndb.nal.usda.gov other nuts, seeds, soy products, and whole over refined grains? http://vegetariannutrition.net grains. Preparation methods such as soak- • Do you eat at least a cup to a cup-and- http://nutritionfacts.org ing, sprouting, leavening, and fermenting a-half of legumes (beans, lentils, peas) www.pcrm.org will improve absorption. Table 2 provides per day? www.brendadavisrd.com a convenient chart highlighting excellent • Do you include leafy green vegetables www.veganhealth.org sources of notable nutrients. in your daily diet? http://plantbaseddietitian.com 2. When discussing a patient’s treatment www.theveganrd.com HELPING PATIENTS GET STARTED plan, include diet as a viable option with www.vrg.org/nutrition/ To support patients to delve into positive effects (eg, improved gastrointes- https://fnic.nal.usda.gov/lifecycle- this therapeutic nutrition plan to help tinal function, decreased risk for chronic nutrition/vegetarian-nutrition them prevent or manage chronic disease diseases, and better outcomes for existing www.vegansociety.com and improve or maintain their state of conditions). health, it is crucial to provide optimis- 3. Advocate simple suggestions to start tic, simple, and strategic guidance. See off. Instead of overwhelming a patient with Label-Reading Protocol Sidebar: Six-Step Guide for Initiating drastic renovations to their current way of and Maintaining a Nutrition Dialogue eating, begin with a few changes that can • Ignore misleading marketing ter- with Patients. be made within reason. Some examples minology on labels (eg, “excellent include the following: source of,” “free of,” “natural”) GUIDE FOR INITIATING AND • Incorporate leafy green vegetables with • Focus solely on ingredient list and MAINTAINING A NUTRITION at least two meals or snacks each day ignore rest of packaging DIALOGUE WITH PATIENTS (enjoy a salad, add broccoli to pasta, • Strive to purchase foods with: 1. During the first part of an office visit try a green smoothie for breakfast or a - Only recognizable ingredients when interviewing patients regarding well- snack). - Few total ingredients listed ness behaviors (typically covering exercise • Start reducing intake of red and pro- - Absence of artificial colors/ and smoking), include questions about cessed meat to once per week or less. flavorings/sweeteners, diet, such as the following: • Opt for whole grains over refined (eg, refined sugars, preservatives, • Do you eat at least 7 to 9 servings of brown rice instead of white rice, whole stabilizers, thickeners, or any vegetables and fruits every day?64 grain pasta instead of white pasta, 100% unrecognizable names whole grain or sprouted bread).

Six-Step Guide for Initiating and Maintaining a Nutrition Dialogue with Patients 1. During the first part 3. Advocate simple suggestions to 5. Offer patients educational support (see Sidebar: of an office visit when start off. Instead of overwhelming Suggested Educational Support). Information in interviewing patients a patient with drastic renovations the form of pamphlets, onsite nutrition counsel- regarding wellness behav- to their current way of eating, ing, in-house cooking classes, and articles on iors (typically covering begin with a few changes that can the Internet (see Sidebar: Suggested Internet exercise and smoking), be made within reason. Nutrition Resources) is ideal because there are include questions about 4. Educate patients on both the risks multiple points of reference and communication diet. associated with inadequate intake for patients. 2. When discussing a pa- of produce and regular con- 6. Maintain a plan for follow-up and continued tient’s treatment plan, in- sumption of refined sugars and encouragement. It is common for people to lose clude diet as a viable op- animal products as well as the motivation, and to become frustrated over time, tion with positive effects advantages of emphasizing whole particularly if there is not a strong support system (eg, improved gastrointes- plant foods. Enlist all health care in place (see Sidebar: Tips for Patient Motivation). tinal function, decreased practitioners on the patient’s team Engage patients by ensuring they are enrolled risk for chronic diseases, to be aware of diet modification in classes, have family or friends participat- and better outcomes for goals. One way to simplify this is ing alongside them, are connected to others in existing conditions). by charting progress and goals. similar phases of transition, and have access to continued information, as designated above.55

98 The Permanente Journal/Perm J 2016 Summer;20(3):15-082 COMMENTARY Plant-Based Diets: A Physician’s Guide

• Enjoy 2 to 4 servings of fruit per day. 4. Educate patients on both the risks Internet Nutrition Resources) is ideal • Include colorful vegetables with each associated with inadequate intake of because there are multiple points of ref- meal. produce and regular consumption of erence and communication for patients. • Try making a plant-based meal and then refined sugars and animal products as It is also important to educate pa- an entire plant-based day by prioritizing well as the advantages of emphasizing tients on the importance of reading previously loved plant-based dishes (eg, whole plant foods. Enlist all health labels (see Sidebar: Label-Reading pasta primavera, bean and rice burrito, care practitioners on the patient’s team Protocol). bean chili). to be aware of diet modification goals. 6. Maintain a plan for follow-up and • Aim to eat a rainbow every day (foods One way to simplify this is by charting continued encouragement. It is common naturally red, orange, yellow, green, and progress and goals. for people to lose motivation, and to be- blue/purple). 5. Offer patients educational support come frustrated over time, particularly if For those patients eager to make more (see Sidebar: Suggested Educational there is not a strong support system in dramatic changes, encourage switching Support). Information in the form of place (see Sidebar: Tips for Patient Mo- to eating a combination of vegetables, pamphlets, onsite nutrition counseling, tivation). Engage patients by ensuring fruits, legumes, and whole grains, ac- in-house cooking classes, and articles they are enrolled in classes, have family cording to the recommendations above. on the Internet (see Sidebar: Suggested or friends participating alongside them, are connected to others in similar phases of transition, and have access to contin- Suggested Educational Support ued information.65 • Informational sheets, such as pamphlets and handouts, of meal options, recipes, nutrient sources (as in Table 2), sample meal plans, benefits of eating CONCLUSION healthfully, additional resources, and advice based on the information in this Ultimately, it is a win-win situation— guide will support the patient in pursuing plant-based eating at home. for patients, and for health care practi- • Individual nutrition counseling as prescribed by a physician provides encour- tioners—to have plant-based eating as a agement, reinforces positive outcomes, and helps address needs and concerns. powerful tool in the toolbox. Pharmaceu- • Cooking classes, available in many communities, led by plant-based chefs or ticals are an important tool in a physician’s registered dietitians are excellent tools for successful adaptation of healthy armamentarium, particularly in treating cooking patterns in the home. Demonstrations and interactive methods where- acute illness, but lifestyle changes, eg diet, by participants are able to prepare food or at least taste samples and receive can be an important and powerful tool in recipes to take home will inspire adherence. treating chronic illness. To facilitate lower • Articles on the Internet (see Sidebar: Internet Nutrition Resources) and other health care costs and likely better health online resources (or even nutrition-specific Web sites) are opportunities to outcomes, let food be medicine and the v provide patients with ready-to-go information and perhaps a 24-hour interac- route of the future. tive resource. Disclosure Statement The author(s) have no conflicts of interest to disclose. Tips for Patient Motivation Acknowledgment • Focus on optimism. Encourage every positive choice because food is deeply Mary Corrado, ELS, provided editorial assistance. personal and making significant changes is challenging for most people. Every bite matters. How to Cite this Article Hever J. Plant-based diets: A physician’s guide. • Encourage the conversation with patients who are interested. The single person Perm J 2016 Summer;20(3):15-082. most people trust for advice and recommendations on health, diet, and well- DOI: http://dx.doi.org/10.7812/TPP/15-082. ness is their physician. It is an honor and special occasion to be able to open up the dialogue from a place of caring and support and without judgment. Of- fer advice and an ear to help propel patients onto the path of long-term health. References 1. Graffeo C. Is there evidence to support a vegetarian • Make it fun. Recalculating diet is similar to learning a new language. Initially, diet in common chronic diseases? [Internet]. New a few new ingredients are discovered, which is like learning some new words. York, NY: Clinical Correlations; 2013 Jun 20 [cited Then enjoyable recipes and meals become part of the repertoire, which is simi- 2015 Mar 17]:[about 8 p]. Available from: www. clinicalcorrelations.org/?p=6186. lar to learning some phrases in the new language. Finally, the knowledge base 2. Orlich MJ, Singh PN, Sabaté J, et al. Vegetarian expands so greatly that it becomes second nature to choose and prepare plant- dietary patterns and mortality in Adventist Health based meals, akin to speaking the language fluently. Health care practitioners Study 2. JAMA Intern Med 2013 Jul 8;173(13): 1230-8. DOI: http://dx.doi.org/10.1001/ are ideally situated to easily guide patients toward fluency and success in this jamainternmed.2013.6473. new language. 3. Rosell M, Appleby P, Spencer E, Key T. Weight gain over 5 years in 21,966 meat-eating, fish-eating, vegetarian, and vegan men and women in EPIC-

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Oxford. Int J Obes (Lond) 2006 Sep;30(9):1389-96. Control and Prevention; 2014 Jul 17 [cited 2015 Molecules 2012 Dec 27;18(1):322-53. DOI: http:// DOI: http://dx.doi.org/10.1038/sj.ijo.0803305. Apr 7]. Available from: www.cdc.gov/drugresistance/ dx.doi.org/10.3390/molecules18010322. 4. Ornish D. Statins and the soul of medicine. Am J threat-report-2013/. 35. Phytochemicals: the cancer fighters in the foods we Cardiol 2002 Jun 1;89(11):1286-90. DOI: http:// 21. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi eat [Internet]. Washington, DC: American Institute dx.doi.org/10.1016/S0002-9149(02)02327-5. S, Key TJ. The associations of diet with serum for Cancer Research; 2013 Apr 10 [cited 2015 5. Jenkins DJ, Kendall CW, Marchie A, et al. Direct insulin-like growth factor I and its main binding Apr 17]. Available from: www.aicr.org/reduce-your- comparison of a dietary portfolio of cholesterol- proteins in 292 women meat-eaters, vegetarians, cancer-risk/diet/elements_phytochemicals.html. lowering foods with a statin in hypercholesterolemic and vegans. Cancer Epidemiol Biomarkers Prev 36. Schmitz H, Chevaux, K. Defining the role of dietary participants. Am J Clin Nutr 2005 Feb;81(2):380-7. 2002 Nov;11(11):1441-8. phytochemicals in modulating human immune 6. Barnard ND, Cohen J, Jenkins DJ, et al. A low- 22. Iron: dietary supplement fact sheet [Internet]. function. In: Gershwin ME, German JB, Keen CL, fat vegan diet and a conventional diabetes diet in Bethesda, MD: National Institutes of Health, Office editors. Nutrition and immunology: principles and the treatment of type 2 diabetes: a randomized, of Dietary Supplements; 2015 Feb 19 [cited 2015 practice. Totowa, NJ: Humana Press Inc; 2000. controlled, 74-wk clinical trial. Am J Clin Nutr Apr 12]. Available from: http://ods.od.nih.gov/ p 107-19. 2009 May;89(5):1588S-1596S. DOI: http://dx.doi. factsheets/Iron-HealthProfessional/. 37. Taku K, Melby MK, Nishi N, Omori T, Kurzer org/10.3945/ajcn.2009.26736H. 23. Jomova K, Valko M. Advances in metal-induced MS. Soy isoflavones for osteoporosis: an 7. Huang T, Yang B, Zheng J, Li G, Wahlqvist ML, oxidative stress and human disease. Toxicology evidence-based approach. Maturitas 2011 Li D. Cardiovascular disease mortality and cancer 2011 May 10;283(2-3):65-87. DOI: http://dx.doi. Dec;70(4):333-8. DOI: http://dx.doi.org/10.1016/j. incidence in vegetarians: a meta-analysis and org/10.1016/j.tox.2011.03.001. maturitas.2011.09.001. systematic review. Ann Nutr Metab 2012;60(4):233- 24. Bastide NM, Pierre FH, Corpet DE. Heme iron from 38. Wei P, Liu M, Chen Y, Chen DC. Systematic review 40. DOI: http://dx.doi.org/10.1159/000337301. meat and risk of colorectal cancer: a meta-analysis of soy isoflavone supplements on osteoporosis in 8. Tuso PJ, Ismail MH, Ha BP, Bartolotto C. Nutritional and a review of the mechanisms involved. Cancer women. Asian Pac J Trop Med 2012 Mar;5(3): update for physicians: plant-based diets. Perm J Prev Res (Phila) 2011 Feb;4(2):177-84. DOI: http:// 243-8. DOI: http://dx.doi.org/10.1016/S1995- 2013 Spring;17(2):61-6. DOI: http://dx.doi.org/ dx.doi.org/10.1158/1940-6207.CAPR-10-0113. 7645(12)60033-9. 10.7812/TPP/12-085. 25. Ahluwalia N, Genoux A, Ferrieres J, et al. Iron 39. Basu HN, Del Vecchio AJ, Filder F, Orthoeter FT. 9. Tonstad S, Butler T, Yan R, Fraser GE. Type of status is associated with carotid atherosclerotic Nutritional and potential disease prevention vegetarian diet, body weight, and prevalence of type plaques in middle-aged adults. J Nutr 2010 properties of carotenoids. J Am Oil Chem Soc 2001 2 diabetes. Diabetes Care 2009 May;32(5):791-6. Apr;140(4):812-6. DOI: http://dx.doi.org/10.3945/ Jul;78(7):665-75. DOI: http://dx.doi.org/10.1007/ DOI: http://dx.doi.org/10.2337/dc08-1886. jn.109.110353. s11746-001-0324-x. 10. Appleby PN, Davey GK, Key TJ. Hypertension and 26. Hunt JR. Bioavailability of iron, zinc, and other trace 40. Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, blood pressure among meat eaters, fish eaters, minerals from vegetarian diets. Am J Clin Nutr 2003 Watanabe S. Soy isoflavones lower serum total and vegetarians and vegans in EPIC-Oxford. Public Sep;78(3 Suppl):633S-639S. LDL cholesterol in humans: a meta-analysis of 11 Health Nutr 2002 Oct;5(5):645-54. DOI: http:// 27. European Commission Scientific Committee randomized controlled trials. Am J Clin Nutr 2007 dx.doi.org/10.1079/PHN2002332. on Food. Polycyclic aromatic hydrocarbons— Apr;85(4):1148-56. 11. Ferdowsian HR, Barnard ND. Effects of plant- occurrence in foods, dietary exposure and health 41. Howard BV, Kritchevsky D. Phytochemicals and based diets on plasma lipids. Am J Cardiol effects [Internet]. Brussels, Belgium: European cardiovascular disease. A statement for healthcare 2009 Oct 1;104(7):947-56. DOI: http://dx.doi. Commission Health and Consumer Protection professionals from the American Heart Association. org/10.1016/j.amjcard.2009.05.032. Directorate-General; 2002 Dec 4 [cited 2015 Apr 7]. Circulation 1997 Jun 3;95(11):2591-3. DOI: http:// 12. Ornish D, Scherwitz LW, Billings JH, et al. Intensive Available from: http://ec.europa.eu/food/fs/sc/scf/ dx.doi.org/10.1161/01.CIR.95.11.2591. lifestyle changes for reversal of coronary heart out154_en.pdf. 42. Clemens R, Kranz S, Mobley AR, et al. Filling disease. JAMA 1998 Dec 16;280(23):2001-7. DOI: 28. Chemicals in meat cooked at high temperatures America’s fiber intake gap: summary of a roundtable http://dx.doi.org/10.1001/jama.280.23.2001. and cancer risk [Internet]. Bethesda, MD: National to probe realistic solutions with a focus on grain- 13. Esselstyn CB Jr, Gendy G, Doyle J, Golubic M, Cancer Institute at the National Institutes of Health; based foods. J Nutr 2012 Jul;142(7):1390S-401S. Roizen MF. A way to reverse CAD? J Fam Pract 2010 Oct 15 [cited 2015 Apr 7]. Available from: DOI: http://dx.doi.org/10.3945/jn.112.160176. 2014 Jul;63(7):356-364b. www.cancer.gov/cancertopics/causes-prevention/ 43. National Center for Chronic Disease Prevention and 14. Vannice G, Rasmussen H. Position of the risk/diet/cooked-meats-fact-sheet. Health Promotion. The power of prevention: chronic Academy of Nutrition and Dietetics: dietary fatty 29. Uribarri J, Woodruff S, Goodman S, et al. Advanced disease … the public health challenge of the 21st acids for healthy adults. J Acad Nutr Diet 2014 glycation end products in foods and a practical century [Internet]. Atlanta, GA: Centers for Disease Jan;114(1):136-53. DOI: http://dx.doi.org/10.1016/j. guide to their reduction in the diet. J Am Diet Control and Prevention; 2009 [cited 2015 Mar jand.2013.11.001. Erratum in: J Acad Nutr Diet 2014 Assoc 2010 Jun;110(6):911-6. DOI: http://dx.doi. 17]. Available from: www.cdc.gov/chronicdisease/ Apr;114(4):644. DOI: http://dx.doi.org/10.1016/j. org/10.1016/j.jada.2010.03.018. pdf/2009-power-of-prevention.pdf. jand.2014.02.014. 30. Koeth RA, Wang Z, Levison BS, et al. Intestinal 44. Craig WJ, Mangels AR; American Dietetic 15. Saturated Fats [Internet]. Dallas, TX: American microbiota metabolism of L-carnitine, a nutrient in Association. Position of the American Dietetic Heart Association; 2015 Jan 12 [cited 2015 Mar red meat, promotes atherosclerosis. Nat Med 2013 Association: vegetarian diets. J Am Diet Assoc 2009 17]. Available from: www.heart.org/HEARTORG/ May;19(5):576-85. DOI: http://dx.doi.org/10.1038/ Jul;109(7):1266-82. DOI: http://dx.doi.org/10.1016/j. GettingHealthy/NutritionCenter/HealthyEating/ nm.3145. jada.2009.05.027. Saturated-Fats_UCM_301110_Article.jsp. 31. Hedlund M, Padler-Karavani V, Varki NM, Varki A. 45. Farmer B, Larson BT, Fulgoni VL III, Rainville AJ, 16. Hopkins PN. Effects of dietary cholesterol on serum Evidence for a human-specific mechanism for diet Liepa GU. A vegetarian diet pattern as a nutrient- cholesterol: a meta-analysis and review. Am J Clin and antibody-mediated inflammation in carcinoma dense approach to weight management: an analysis Nutr 1992 Jun;55(6):1060-70. progression. Proc Natl Acad Sci U S A 2008 Dec of the national health and nutrition examination 17. Howell WH, McNamara DJ, Tosca MA, Smith BT, 2;105(48):18936-41. DOI: http://dx.doi.org/10.1073/ survey 1999-2004. J Am Diet Assoc 2011 Gaines JA. Plasma lipid and lipoprotein responses pnas.0803943105. Jun;111(6):819-27. DOI: http://dx.doi.org/10.1016/j. to dietary fat and cholesterol: a meta-analysis. Am J 32. Taylor RE, Gregg CJ, Padler-Karavani V, et al. jada.2011.03.012. Clin Nutr 1997 Jun;65(6):1747-64. Novel mechanism for the generation of human 46. 2015 Dietary Guidelines Advisory Committee. 18. Spence JD, Jenkins DJ, Davignon J. Dietary xeno-autoantibodies against the nonhuman Scientific report of the 2015 Dietary Guidelines cholesterol and egg yolks: not for patients at sialic acid N-glycolylneuraminic acid. J Exp Med Advisory Committee: advisory report to the risk of vascular disease. Can J Cardiol 2010 2010 Aug 2;207(8):1637-46. DOI: http://dx.doi. Secretary of Health and Human Services and the Nov;26(9):e336-9. org/10.1084/jem.20100575. Secretary of Agriculture [Internet]. Washington, DC: USDA, Department of Health and Human Services; 19. Record-high antibiotic sales for meat and poultry 33. Food Insight. Functional foods fact sheet: 2015 Feb [cited 2015 Mar 18]. Available from: production [Internet]. Philadelphia, PA: The Pew antioxidants [Internet]. Washington, DC: www.health.gov/dietaryguidelines/2015-scientific- Charitable Trusts; 2013 Feb 6 [cited 2015 Apr 7]. International Food Information Council Foundation; report/PDFs/Scientific-Report-of-the-2015-Dietary- Available from: www.pewtrusts.org/en/about/news- 2009 Oct 14 [cited 2015 Apr 17]. Available from: Guidelines-Advisory-Committee.pdf. room/news/2013/02/06/recordhigh-antibiotic-sales- www.foodinsight.org/Functional_Foods_Fact_ for-meat-and-poultry-production. Sheet_Antioxidants. 47. Sabaté J. Nut consumption, vegetarian diets, ischemic heart disease risk, and all-cause mortality: 20. Antibiotic resistance threats in the United States, 34. Bellik Y, Boukraâ L, Alzahrani HA, et al. Molecular evidence from epidemiologic studies. Am J Clin Nutr 2013 [Internet]. Atlanta, GA: Centers for Disease mechanism underlying anti-inflammatory and anti- allergic activities of phytochemicals: an update. 1999 Sep;70(3 Suppl):500S-503S.

100 The Permanente Journal/Perm J 2016 Summer;20(3):15-082 COMMENTARY Plant-Based Diets: A Physician’s Guide

48. O’Neil CE, Keast DR, Nicklas TA, Fulgoni VL 3rd. National Academies; 2005 [cited 2015 Apr 15]. Suppliers2/Veggie-vitamin-D3-maker-explores- Nut consumption is associated with decreased Available from: https://iom.nationalacademies.org/~/ novel-production-process-to-secure-future-supplies. health risk factors for cardiovascular disease and media/Files/Activity%20Files/Nutrition/DRIs/DRI_ 61. Ross AC, Manson JE, Abrams SA, et al. The 2011 metabolic syndrome in US adults: NHANES 1999- Macronutrients.pdf. report on dietary reference intakes for calcium 2004. J Am Coll Nutr 2011 Dec;30(6):502-10. DOI: 55. Fish [Internet]. Washington, DC: Physicians and vitamin D from the Institute of Medicine: what http://dx.doi.org/10.1080/07315724.2011.10719996. Committee for Responsible Medicine; 2009 Jan clinicians need to know. J Clin Endocrinol Metab 49. Seddon JM, Cote J, Rosner B. Progression [cited 2016 Mar 17]. Available from: www.pcrm.org/ 2011 Jan;96(1):53-8. DOI: http://dx.doi.org/10.1210/ of age-related macular degeneration: health/reports/fish. jc.2010-2704. association with dietary fat, transunsaturated 56. Worm B, Barbier EB, Beaumont N, et al. Impacts 62. National Institutes of Health Office of Dietary fat, nuts, and fish intake. Arch Ophthalmol of biodiversity loss on ocean ecosystem services. Supplements. Calcium: dietary supplement fact 2003 Dec;121(12):1728-37. DOI: http://dx.doi. Science 2006 Nov 3;314(5800):787-90. DOI: http:// sheet [Internet]. Washington, DC: National Institutes org/10.1001/archopht.121.12.1728. Erratum in: Arch dx.doi.org/10.1126/science.1132294. of Health; 2013 Nov 21 [cited 2015 Mar 26]. Ophthalmol 2004 Mar;122(3):426. DOI: http://dx.doi. 57. FDA cuts trans fats in processed foods [Internet]. Available from: http://ods.od.nih.gov/factsheets/ org/10.1001/archopht.122.3.426. Washington, DC: US Food and Drug Administration; Calcium-HealthProfessional/. 50. Tsai CJ, Leitzmann MF, Hu FB, Willett WC, 2015 Jun 16 [2016 Mar 17]. Available from: www. 63. Part II. Evaluating the public health significance Giovannucci EL. Frequent nut consumption and fda.gov/ForConsumers/ConsumerUpdates/ of micronutrient malnutrition. In: Allen L, decreased risk of cholecystectomy in women. Am J ucm372915.htm. de Benoist B, Dary O, Hurrell R, editors. Guidelines Clin Nutr 2004 Jul;80(1):76-81. 58. Jenkins DJ, Kendall CW, Marchie A, et al. Effects of on food fortification with micronutrients. Geneva, 51. Wilcox DC, Wilcox BJ, Todoriki H, Suzuki M. a dietary portfolio of cholesterol-lowering foods vs Switzerland: World Health Organization; 2006. The Okinawan diet: health implications of a low- lovastatin on serum lipids and C-reactive protein. p 43-56. calorie, nutrient-dense, antioxidant-rich dietary JAMA 2003 Jul 23;290(4):502-10. DOI: http://dx.doi. 64. Oyebode O, Gordon-Dseagu V, Walker A, pattern low in glycemic load. J Am Coll Nutr 2009 org/10.1001/jama.290.4.502. Mindell JS. Fruit and vegetable consumption and Aug;28(Suppl):500S-516S. DOI: http://dx.doi.org/10 59. Jacobs DR Jr, Gross MD, Tapsell LC. Food synergy: all-cause, cancer and CVD mortality: analysis .1080/07315724.2009.10718117. an operational concept for understanding nutrition. of Health Survey for England data. J Epidemiol 52. Allbaugh L. Crete: a case study of an Am J Clin Nutr 2009 May;89(5):1543S-1548S. DOI: Community Health 2014 Sep;68(9):856-62. DOI: underdeveloped area. Princeton, NJ: Princeton http://dx.doi.org/10.3945/ajcn.2009.26736B. http://dx.doi.org/10.1136/jech-2013-203500. University Press; 1953. 60. Watson E. Veggie vitamin D3 maker explores 65. Gallant MP. The influence of social support on 53. Davis B, Melina V. Becoming vegan: comprehensive novel production process to secure future supplies chronic illness self-management: a review and edition. Summertown, TN: Book Publishing [Internet]. Montpelier, France: William Reed directions for research. Health Educ Behav Company; 2014. Business Media; 2012 Mar 13 [cited 2016 Jun 6]. 2003 Apr;30(2):170-95. DOI: http://dx.doi.org/ 54. Dietary reference intakes: macronutrients [Internet]. Available from: www.nutraingredients-usa.com/ 10.1177/1090198102251030. Washinton, DC: Institute of Medicine of the

Food Rules

Eat food. Not too much. Mostly plants.

— Food Rules, Michael Pollan, b 1955, American author, journalist, activist, and professor of journalism

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Marcus Griffith, MD; Jeana Griffith, PhD; Mellanese Cobb, MPH; Vladimir Oge, MPH Perm J 2016 Summer;20(3):15-029 E-pub: 03/17/2016 http://dx.doi.org/10.7812/TPP/15-029

ABSTRACT person may be overweight because of extra Introduction: Childhood obesity is a health care crisis according to the leading muscle, bone, water, and/or fat.7 Although pediatric advocacy groups (National Medical Association, American Academy of obesity rates have reached epidemic propor- Pediatrics, and American Diabetes Association) and the White House. The problem tions, there is a lack of culturally competent has reached epidemic proportions for all children, but it has an even greater impact interventions to educate the public and to on racial minorities. The subject of childhood obesity can lead to a host of medical, prevent and combat this condition. We psychological, and social problems, including low self-esteem and discrimination. developed an innovative, culturally com- We wrote an interventional children’s book and workbook (The Tale of Two Athletes: petent approach with narrative to address The Story of Jumper and The Thumper) and developed a three-step intervention based this deficiency. on the narrative. The intervention’s purpose is to increase public awareness, reduce The statistics on obesity in both children stigma, and to help members of underserved communities become more comfortable and adults are alarming; however, facts, fig- discussing obesity. ures, and epidemiologic information do not Methods: In classrooms and other community settings, a storied education program is tell the whole story. Obesity has grown into presented to students of various ages. Interactive storytelling is the first step: live narration such an enormous public health problem with direct listening and active participation. Didactic information on obesity is shared, that even the untrained observer can recog- including a sociocultural explanation for why the issue is more problematic among racial nize that it is out of hand. The challenges minorities. The audience is then introduced to the story of Jumper and The Thumper, faced in elementary school lunchrooms are two larger-than-life characters who experience different outcomes as a result of their one clue to this growing problem. Accord- choices about diet and exercise. True examples are described during the narration about ing to the National Health and Nutrition these two young men, accompanied by cartoons and photographs for visual emphasis. Examination Survey, more than 33% of The next step is reading: audience members are provided with a book to reinforce adults and 17% of youths in the US are what was learned. Readers are allowed to more closely examine the importance of obese.8 Rates of obesity among children making healthy choices. and adolescents have tripled since 1980, Practicing positive behaviors and decision making through games and exercises with an estimated 12.5 million children and from the companion workbook is the final step. These activities help children and their adolescents aged 2 to 19 years identified as families live a healthier lifestyle. The goal is that these three steps, linked to a common obese or overweight.8 narrative, will have a meaningful impact on obesity by creating behavioral change. The problem of obesity in children and Results: Children, parents, and health care professionals have stated their enthusiastic adolescents is perhaps one of the most response to the information and message and that they have made positive changes in pressing public health concerns in the US. children’s eating and exercise habits. The program has been presented in community Studies suggest that individuals who expe- forums, churches, medical meetings, and elementary schools in at-risk communities. rience problems with excess weight during Conclusion: New strategies must be developed to lead, uplift, and empower through childhood are commonly overweight or health and wellness education and through community collaboration if we are to change obese as adults. The best method for pre- the direction of course toward this devastating condition that affects our most valuable venting this potentially lifelong problem commodity—our children. This community-based educational approach is a means to is to control it during childhood through help recognize and treat obesity in underserved communities. education and behavioral intervention.9 Obesity may have the greatest impact INTRODUCTION Pediatrics,2 American Diabetes Association,3 on racial minorities. Minority populations Obesity is a health care crisis accord- American Medical Association,4 and Na- and low-income communities appear to ing to leading medical and patient advo- tional Medical Association5) and the White have the highest risk. The 2001 report The cacy groups (Centers for Disease Control House.6 Obesity is defined by excess body Surgeon General’s Call to Action to Prevent and Prevention,1 American Academy of fat, which is not the same as overweight. A and Decrease Overweight and Obesity10 was

Marcus Griffith, MD, is a Diplomate of The American Board of Obesity Medicine, a Staff Physician for Kaiser Permanente, and Clinical Assistant Professor in the Department of Psychiatry for Morehouse School of Medicine and Emory University School of Medicine in Atlanta, GA. E-mail: [email protected]. Jeana Griffith, PhD, is an Associate Director of Psychological and Health Services for Georgia State University in Atlanta, GA. E-mail: [email protected] Cobb, MPH, is a Senior Pharmaceutical Specialist with Boehringer Ingelheim in Atlanta, GA. E-mail: [email protected]. Vladimir Oge, MPH, is the Director of Health Promotion for Georgia Institute of Technology in Atlanta. E-mail: [email protected].

102 The Permanente Journal/Perm J 2016 Summer;20(3):15-029 NARRATIVE MEDICINE The Use of Narrative as a Treatment Approach for Obesity: A Storied Educational Program Description

one of the first to call attention to obesity as a major health problem. More recently, First Lady Michelle Obama launched the Let’s Move initiative to examine root causes and offer practical solutions.11 Obesity is believed to be a preventable illness that many believe will one day have greater rates of morbidity and mortality than any other health condition. Because racial minorities experience higher rates of obesity than whites, this disease state is linked to health care disparities in the US. According to a 2001 Institute of Medicine report, racial and ethnic disparities exist regardless of socioeconomic status.12 The reported data suggest that racial and ethnic minorities tend to receive a lower quality Marcus Griffith, MD, telling the story of The Tale of Two Athletes at the Boys and Girls Club in Seaside, CA. of health care than whites, even when analyses control for access-related factors, such as insurance status and income. Key of accomplishment and excitement; but public awareness, to reduce stigma, and to epidemiologic indices on these differences instead, it was overshadowed with grief. help constituents of underserved popula- include higher morbidity and mortality That night I experienced a profound sense tions become more comfortable discussing from the leading causes of death, poorer of loss, and I made a commitment to fight obesity. The program also incorporates quality of care, and worse outcomes.12 obesity. When I opened my office the fol- nutrition, exercise, and other behav- lowing day, I began to incorporate that ioral strategies to combat weight gain. A COMMUNITY-BASED fight into my daily clinical practice. Over Community-based educational programs EDUCATIONAL APPROACH the years, I have continued to explore new that teach the benefits of healthy eating, A critical service line in the battle against education and prevention strategies de- nutrition, and exercise have proved to be obesity is the need for new methods of signed for clinical and community settings. effective tools for controlling weight and communication between health care or- I (MG) wrote the story of Jumper and promoting positive behavioral change.14 ganizations and underserved communities. The Thumper several years later, while The initiative centers around a children’s Traditional strategies for communicating working in a mental health treatment cen- book that my wife and I (MG) wrote, en- messages about obesity and other chronic ter for children and adolescents with severe titled The Tale of Two Athletes—The Story diseases have failed to improve population behavioral and emotional problems. The of Jumper and The Thumper. The story in health, as evidenced by worsening rates. vast majority of the patients were African the book is told through the eyes of a little New, culturally competent interventions American, low-income, and were obese or girl named Jasmine who attended one of must be developed so as to build relation- overweight. The children learned about my presentations at a community event ships between people from different races, diet, nutrition, and exercise as components in Seaside, CA. Jasmine is battling child- cultures, and ethnicities. The spectrum of for improving their mental and physical hood obesity and heard the story The Tale health-related problems linked to obesity health. As we worked with dieticians, of Two Athletes. This inspirational story is is well documented; it includes diabetes, encouraged a reduction in television and based on my lifelong friendship with Joe hypertension, respiratory problems, and video game time, and promoted increased Drake, a professional football player who depression. Low self-esteem, depression, physical activity, our activities reinforced died prematurely because of obesity. Re- and social discrimination associated with the guidelines on obesity recommended cently, after reading a magazine article on childhood obesity are frequently unad- by the American Academy of Pediatrics.13 the number of football players who have dressed.10 Battling the medical complica- During the last several years I (MG) died from obesity-related complications, tions of obesity and forming solutions for traveled throughout the US and received a I discovered from an ESPN story that Joe associated emotional distress has been the number of awards for my work on obesity. was the heaviest player in the history of the focus of my (MG’s) work. The work began through telling a story National Football League to die.15 On the eve of the grand opening of my about how a dear friend lost his life be- Following the presentation, Jasmine (MG’s) medical practice, in 1994, I got cause of complications from obesity. I then sought me (MG) out and asked if I could the sad news that my best friend had died used the story as a platform to develop a help her. She told me that she had also from a massive heart attack. I had always community-based educational program to struggled with her weight all through her dreamed of becoming a physician and address both the mental and the physical life and could relate to many of the points running my own office. I had imagined health problems associated with obesity. in the story. As we talked, Jasmine was curi- that this day would be filled with a sense The intervention’s purpose is to increase ous about the two characters, Jumper and

The Permanente Journal/Perm J 2016 Summer;20(3):15-029 103 NARRATIVE MEDICINE The Use of Narrative as a Treatment Approach for Obesity: A Storied Educational Program Description

The Thumper, and wanted to know more with the most severe behavioral issues were emotional experience, especially consider- about their lives. She stated that she would placed in my group, with the appropriate ing what had happened the night before never forget the story and did not want to accompanying staff. No major issues were opening my office in 1994. The moment end up like The Thumper. Jasmine made a encountered. of closure marked for me a beginning and promise that she would begin trying to live One rainy day when we were unable to an end at the same time. Although it was a healthier lifestyle. In addition to children, go outside for our nature hike, a young an end to my private practice, a new op- adults struggling with obesity are receptive man shared with me the pain he experi- portunity began in my quest to honor my to the program’s message. The interactive enced because of excess weight. I (MG) friend in the fight against obesity through narrative, based on a true story, attempts asked him to write down his feelings, the telling of The Tale of Two Athletes. to inspire change and create solutions. It is and he entitled his story “My Life as an an alternative approach for examining the Obese Child.” His name just happened NARRATIVES— causes of obesity and forming solutions, to be Joseph—the same name as my late A THREE-STEP APPROACH especially in the context of racial minorities friend. I was inspired to create a story and I (MG) developed a three-step approach and underserved communities. use it as a component of a comprehensive based on The Tale of Two Athletesto educate One of the activities that generated obesity program at the center (up until the community about obesity. Storytell- the most excitement resulted from the the book was written the story was told ing is the primary concept that moves relationship that we formed with the park from memory in the old tradition of story from active listening to live narration as rangers at Davidson-Arabia Nature Pre- telling). I told the story about Jumper and the first step. Live narration aims to make serve in DeKalb County, GA. Two park The Thumper so as to convey a powerful an impact on the audience through direct rangers and I (MG) led three groups of message about obesity, from and about listening and active participation. Didactic patients on a series of nature hikes through someone the children knew. information on obesity is shared, includ- the forest in an effort to increase exercise The story about my (MG’s) relationship ing statistics, easy-to-understand epide- and to create exposure to a new experi- with Joe Drake continues to be integral to miologic information, and a sociocultural ence. We instructed the patients on the my personal and professional life. On Feb- explanation for why the issue is more prob- importance of exercise and appreciation ruary 28, 2012, I closed my private prac- lematic among racial minorities. Jumper of nature. Staff members from the day tice after 18 years of service and accepted and The Thumper are then introduced treatment program also participated to a position with Kaiser Permanente in GA. to the audience as two larger-than-life help ensure safety. To my surprise, many of Coincidently, as I was closing my office for characters who experience different out- the children had never been outside of the the final time and was saying goodbye to comes resulting from their choices in diet city or spent time in the woods. The heal- my patients, the first copy of the published and exercise. The true examples about the ing power of nature was quite evident as book arrived. Closing my office and simul- young men are described during the nar- their negative behaviors decreased during taneously receiving the first printed copy ration, accompanied by cartoons and pho- our outings. I made sure that the children of The Tale of Two Athletes was a powerfully tographs to enhance the visual experience and highlight the realities of the problem. At the end of the story, when The Thumper dies, the true names of the characters and a photograph of the characters are revealed. The audience then realizes that the narrator is Jumper, which hopefully inspires them and impresses on them the importance of diet, nutrition, and exercise in the battle against obesity. The next step of the educational process is reading the book to reinforce what was learned in the live community educational program. The book provides more intimate details about the two young men and allows the reader to more closely examine and identify with the characters and to realize the importance of making healthy choices. The final step of the program uses the companion workbook that my wife and coauthor, Jeana Griffith, PhD, wrote to personalize the story for each reader. Marcus Griffith, MD, introducing Jumper and The Thumper to students at Hamilton Holmes Elementary Participants practice positive behaviors School in Atlanta, GA. and decision making through games and

104 The Permanente Journal/Perm J 2016 Summer;20(3):15-029 NARRATIVE MEDICINE The Use of Narrative as a Treatment Approach for Obesity: A Storied Educational Program Description

environment, including neighborhood violence, loss, abortion, sexual violence, and bullying. Personal experiences were incorporated into a narrative-driven game. The game was used in an interactive method to educate and to test knowledge on sexual health and other topics, such as rape, gender inequality, incarceration, and parent communication. Following the intervention the authors found that the participants were more knowledgeable and had improved critical thinking with regard to the subject matter.17 Similarly, the children’s workbook cre- ated from The Tale of Two Athletes uses games, images, and concepts from the story to improve knowledge and criti- cal thinking about obesity and healthy Book signing with Marcus Griffith, MD, Jeana Griffith, PhD, and two children following a community outreach lifestyle choices. Using the workbook is program at the Stonecrest Library in Lithonia, GA. the third and final step, following active listening to the story and reading the exercises that help them set goals for of how stories can incorporate games to book. Once families are inspired by the physical activity and a healthier diet. The engage audiences and reinforce learning. story to make changes in their lifestyle, hope is that these three steps, linked to a The University of Chicago and the the workbook shows them, step by step, common narrative, will make a meaning- University of Ibadan, in Nigeria, formed how to make these changes. Games and ful impact for creating behavioral change a partnership for reducing gaps in how fun activities in the workbook further related to obesity. adolescents receive knowledge on sexual educate participants about obesity and The use of narratives and storytelling health in disadvantaged communities. healthier food intake. The workbook also is now recognized as a culturally compe- The researchers developed this initiative has charts and provides resources to help tent approach for reaching racial minori- as they observed similarities between dis- families set individual goals. ties and underserved populations. This advantaged communities in developing method may be a more effective process African nations and the US.17 Gilliam DISCUSSION for sharing health information in com- et al17 combined traditional storytelling Storytelling has been used since the munities where traditional health educa- with technologies of social media and beginning of human communication as a tion has failed. Storytelling may also be a game design to reshape adolescent sexual means to preserve history, culture, ideas, means of easing the disconnect between health behaviors. They believe that stories and teaching. Ideally it is an interactive health care professionals and underserved and games can be used to communicate process between the storyteller and the au- communities.16 information about other preventable ill- dience that helps listeners to conceptualize The intention is to offer a culturally nesses where traditional health messaging and makes the message more meaningful. I competent message that allows the audi- has been unsuccessful. (MG) have been using a narrative approach ence to see, hear, understand, and feel in my obesity education programs as a what obesity is all about and that they means of conveying health information are not alone in their struggles. The story The use of narratives and to diverse populations (African-American about the two characters, Jumper and The storytelling is now recognized as and Hispanic populations). I have attempt- Thumper, offers an opportunity for the a culturally competent approach ed to construct a program that engages the participants to build a relationship with for reaching racial minorities and audience and inspires behavioral change the characters and the storyteller. An ex- underserved populations. through humor, didactic material, and a pectation is that the listeners will become true, compelling story. immersed in the story and identify with Health interventions typically focus on the message. This process, which Banks16 The researchers on the initiative de- changing individual behavior through tra- describes, emphasizes the importance of veloped a script with integrated images, ditional health policy and communications. building trust between the presenter and music, videos and personal messaging to These approaches have done little to reduce the audience, using the experiences within appeal to a select audience. Story content the differences in prevalence, mortality, and the story to create “a sense of oneness.”16 was developed through a series of work- burden of chronic diseases in underserved Furthermore, the companion workbook shops with South Side Chicago youth communities. Examples include heart to The Tale of Two Athletes is an example and touched on themes significant to that disease, diabetes, preterm births, human

The Permanente Journal/Perm J 2016 Summer;20(3):15-029 105 NARRATIVE MEDICINE The Use of Narrative as a Treatment Approach for Obesity: A Storied Educational Program Description

immunodeficiency virus, and obesity, which References Internet 2012;16(4):440-9. DOI: http://dx.doi.org/10.1 1. Adult obesity. Atlanta, GA: CDC Vitalsigns; 2010 080/15398285.2012.726049. continue to disproportionately affect Afri- August 3. 10. Office of the Surgeon General; Office of Disease can Americans, Hispanic, Native Ameri- 2. Committee on Nutrition. Policy Statement: Prevention Prevention and Health Promotion; Centers for cans, and low-income communities.16 of pediatric overweight and obesity. Pediatrics 2003 Disease Control and Prevention; National Institutes August;112(2):424-30. Reaffirmed 2010. of Health. The Surgeon General’s call to action 3. Marks JB. Obesity in America: It’s getting worse. to prevent and decrease overweight and obesity CONCLUSION Clinical Diabetes 2004 Jan;22(1):1-2. DOI: [Internet]. Rockville, MD: Office of the Surgeon Next steps are to expand programs http://dx.doi.org/10.2337/diaclin.22.1.1. General; 2001 [cited 2015 Aug 24]. Available from: www.ncbi.nlm.nih.gov/books/NBK44206/. by obtaining grants and sponsorships to 4. D-440.980 Recognizing and taking action in response to the obesity crisis [Internet]. Chicago, 11. Learn the facts [Internet]. Washington DC: Let’s promote it. We hope the three-step ap- IL: American Medical Association; 1995-2016 [cited Move: White House Task Force on Childhood proach of active listening to the narrative, 2016 Jan 5]. Available from: www.ama-assn.org/ssl3/ Obesity; [cited 2015 Sep 17]. Available from: www. ecomm/PolicyFinderForm.pl?site=www.ama-assn. letsmove.gov/learn-facts/epidemic-childhood-obesity. reading the book, and practicing what was org&uri=/resources/html/PolicyFinder/policyfiles/ 12. Betancourt JR, Maina AW. The Institute of Medicine learned by using the workbook will serve DIR/D-440.980.HTM. report “Unequal Treatment”: implications for as an additional model in the fight against 5. NMA President’s Task Force obesity task force academic health centers. Mt Sinai J Med 2004 members [Internet]. Silver Spring, MD: National Oct;71(5):314-21. obesity. Up to this point, the program has Medical Association; 2011 [cited 2016 Jan 5]. 13. Council on Sports Medicine and Fitness; Council on been funded by the article’s authors. The Available from: www.nmanet.org/index.php/national- School Health. Active healthy living: prevention of resources to get it done were inspired by programs/nma-fact-sheets/nma-task-force/obesity- childhood obesity through increased physical activity. task-force. Pediatrics 2006 May;117(5):1834-42. DOI: http:// the love of a friend and all those who have 6. Solving the problem of childhood obesity within a dx.doi.org/10.1542/peds.2006-0472. lost someone because of obesity. v generation: White House Task Force on childhood 14. Whetstone LM, Kolasa KM, Collier DN. Participation obesity report to the President [Internet]. Washington, in community-originated interventions is associated DC: White House Task Force on Childhood Obesity; with positive changes in weight status and health Disclosure Statement 2010 May [cited 2016 Jan 5]. Available from: www. behaviors in youth. Am J Health Promot 2012 Sep- The author(s) have no conflicts of interest to letsmove.gov/sites/letsmove.gov/files/TaskForce_on_ Oct;27(1):10-6. DOI: http://dx.doi.org/10.4278/ disclose. Childhood_Obesity_May2010_FullReport.pdf. ajhp.100415-QUAN-117. 7. Obesity: MedlinePlus [Internet]. Bethesda, MD: 15. Hargrove T. Heavy NFL players twice as likely to die National Institutes of Health, US National Library of before 50 [Internet]. Bristol, CT: ESPN; 2006 Jan Acknowledgment Medicine; 2014 Oct 1 [updated 2015 Apr 21; cited 31 [cited 2015 Aug 24]. Available from: http://sports. Leslie Parker, ELS, provided editorial assistance. 2015 Aug 24]. Available from: www.nlm.nih.gov/ espn.go.com/nfl/news/story?id=2313476. medlineplus/obesity.html. 16. Banks J. Storytelling to access social context and How to Cite this Article 8. Ogden CL, Carroll MD, Kit BK, Flegal KM. advance health equity research. Prev Med 2012 Prevalence of childhood and adult obesity in Nov;55(5):394-7. DOI: http://dx.doi.org/10.1016/j. Griffith M, Griffith J, Cobb M, Oge V. The use of the United States, 2011-2012. JAMA 2014 Feb ypmed.2011.10.015. narrative as a treatment approach for obesity: A 26;311(8):806-14. DOI: http://dx.doi.org/10.1001/ 17. Gilliam M, Orzalli S, Heathcock S, et al. From storied educational program description. Perm J jama.2014.732. intervention to invitation: reshaping adolescent 2016 Summer;20(3):15-029. DOI: http://dx.doi.org/ 9. Stephenson PL, Taylor MV. Obesity in children and sexual health through story telling and games. 10.7812/TPP/15-029. adolescents: a webliography. J Consum Health Afr J Reprod Health 2012 Jun;16(2):189-96.

Powerful Drugs

In medicine, as in stagecraft and propaganda, words are sometimes the most powerful drugs we can use.

— Anonymous; Sara Murrah Jordan’s obituary in The New York Times

106 The Permanente Journal/Perm J 2016 Summer;20(3):15-029 credits available for this article — see page 112.

NARRATIVE MEDICINE You Are Not Alone: Ten Strategies for Surviving a Malpractice Lawsuit

Audrey Sheridan, MD Perm J 2016 Summer;20(3):16-004 E-pub: 06/20/2016 http://dx.doi.org/10.7812/TPP/16-004

I wasn’t even scheduled to work that RESIST ISOLATION to them now. Focus, persistence, prepara- morning; I had just gone into the office Asking for help can be tough for physi- tion, not taking things personally—we for a meeting. Chatting with coworkers cians; we’re used to being the ones people know how to do these things. on my way out the door, I was told there come to for help, not the ones who need was someone asking for me at the reception help. You will be advised not to talk with RETRAIN YOUR BRAIN desk. So it was there, in front of a waiting anyone about the case, but you’ve got to We all have habitual thought patterns, room full of patients, that I received the know that you’re not alone. Conversations places our minds go when under stress. But papers notifying me of the lawsuit. “Have with certain people are protected from you can create new patterns for yourself. a nice day,” the woman called out to me discovery. Ask your attorney for advice Use your rational mind to respond to the as she left. here, but typically it is acceptable to talk sometimes overwhelming fears that come Over the next months, as the legalities to family members, counselors, and your up; this is a technique that clinicians tend played out, I struggled to keep moving. My personal physician. And you can generally to practice a lot. When the ugly thoughts confidence evaporated. I’d been taught that feel safe discussing your emotions while begin to spiral, and you start thinking physicians who build good relationships avoiding the medical details of the case. that you’re obviously a fraud, and no one are less likely to be sued, so I had obviously Some liability insurance providers cover should trust you to care for them, stop failed. I didn’t know how I could face my psychological counseling costs, so make and remind yourself of the patients you’ve patients—I felt like a fraud. I couldn’t sure to ask about this option. If you think helped, the procedures that went well, and sleep. I lost my appetite. Sometimes my you might benefit from talking to someone the successes you’ve had. These new neural experience felt surreal, especially when my who has had a similar experience, check to pathways will become more ingrained as attorney told me: “This case will not affect see if your organization or insurance pro- you continue to practice them. your life in any way.” vider offers a peer support team. Research by Martin Seligman, MD, I wondered if I would lose my job, It’s common for physicians undergo- shows that a simple gratitude exercise in- my license, my home. Even worse, I ing litigation to contemplate suicide.2 If creases happiness and resilience (read his wondered if I had lost the trust of my you’re having thoughts of suicide, pick up book Flourish3 or go to http://ggia.berke- colleagues. the phone and call someone immediately: ley.edu/practice/three-good-things). Take I met a coworker who had survived a 911, your physician, a counselor, your a few moments each evening to consider lawsuit; she had been as stressed as I was, spiritual advisor, or a friend or family what went well and write it down. At first and knowing that my reaction was not member. Don’t do anything until you’ve all you may be able to come up with is that abnormal reassured me. I began to prac- spoken with someone. Keep a list in your you have clean sheets, or that you had a tice strategies to help myself cope, and life phone of people you can call for support. really great piece of chocolate for dessert. slowly improved. If you are so depressed or anxious that But as you begin to look for the good, you As much as we hate to think about it, you can’t stop the negative thoughts, if see it more, even when life seems bleak. most physicians, about 60%, will be sued you’re not eating or not sleeping, or if I look forward to this “what went well” at some point in their career.1 Not everyone you feel overwhelmed, medication may exercise at the end of my day. will be as unnerved as I was, but physi- be helpful. Do not prescribe for yourself; cians typically do feel intense strain when talk to a physician you can trust. It could TAKE CARE OF YOURSELF faced with a lawsuit. Our trust in ourselves save your life. It’s important to make room in your and in our patients is shaken. We practice hectic schedule for some downtime. more defensively. We are more likely to USE YOUR STRENGTHS Staying busy can make you feel more in suffer depression and burnout. We may We all developed skills for managing control. It can distract you and keep you feel anxious, depressed, angry, and afraid. stress as we made our way through college, from fixating on the case. But you need all Here I offer ten techniques for coping that medical school, and residency. Remind your strength right now, so you’ve got to really work. yourself that you have these tools, and turn preserve that. Sleep is crucial, to give your

Audrey Sheridan, MD, is an Obstetrician/Gynecologist for the Colorado Permanente Medical Group in Westminster. E-mail: [email protected]

The Permanente Journal/Perm J 2016 Summer;20(3):16-004 107 NARRATIVE MEDICINE You Are Not Alone: Ten Strategies for Surviving a Malpractice Lawsuit

brain time to recover from the stress of to find out that they need an IV to have to me, “We gotta focus on what we can each day. Exercise helps release stress. surgery whereas you take it for granted, control.” And he’s right: stressing and ob- Eating well fuels your body and brain you may find the legal process confusing sessing about what someone else may do (but give yourself enough slack to turn and your attorney unaware of your uneasi- doesn’t help. We’ve all heard the Serenity to comfort food when you most need ness. So ask questions, and ask for prepa- Prayer: “God, grant me the serenity to it—I might not have survived without ration. If you’ve never given a deposition accept the things I cannot change, the mint Newman-O’s). Take some relax- before, ask to have the process explained courage to change the things I can, and ation time, whether it’s for a massage, in detail. Again, use your strengths and the wisdom to know the difference.” Make bedtime reading to your kids, a hot prepare as you would prepare for oral board this your mantra. bath, yoga, or meditation (research has exams. You can even do a practice run, I encourage you to experiment to see shown the effectiveness of Jon Kabat- answering questions in front of a video what works for you. None of these strate- Zinn, MD’s mindfulness-based stress- camera. If you think that might help you, gies will make the lawsuit, or the stress, reduction program, for example). Just be ask your attorney to arrange it. disappear. For me, they took the edge off careful about using alcohol or drugs to There will be times of relative quiet, and and made the situation bearable when I check out—they can quickly cause more then a period that is acutely stressful, like wasn’t sure that bearing it was possible. problems than they solve when used to the deposition. I realized that I needed to My case is over now, and I wish I could self-medicate. approach those episodes the way I would a tell you that there was a nice, neat end- crash C-section—push aside the emotions ing—but there wasn’t; it was messy and GIVE YOURSELF A BREAK and just do it. lasted much longer than I had hoped. Physicians tend to be perfectionists, and The case will require your time and en- The unexpected good news is that I feel being sued seems only to reinforce the ex- ergy, but be reassured that generally your more engaged now with my work than pectation to be perfect. Much of the time liability insurance will cover the financial ever. I’m more clear about the help and we are our own worst critics, and we say aspects. healing that I have to offer my patients. things to ourselves that we’d never say to I have confidence that I can survive what a colleague. Show yourself the same com- REGAIN PERSPECTIVE I thought was the worst thing that could passion you’d show your child, patient, or Almost every day in my work, and every happen to me in my career. Stress, both best friend. Read Kristin Neff, MD’s work time I do my volunteer shift with people personal and professional, is inevitable. for more information on self-compassion living on the streets, I am reminded of the These techniques help me cope.v (http://self-compassion.org/). relative ease of my life. My problems still feel big to me, but not insurmountable. Disclosure Statement SET PRIORITIES The author(s) have no conflicts of interest to It’s important to do things that make USE DISTRACTION disclose. you feel like you’re living in line with your If your thoughts are stuck in a nega- values: be a great parent to your kids, vol- tive spiral, use distraction to pull yourself Acknowledgment unteer to do work you care about, spend out of the descent: movies, audiobooks, Leslie Parker, ELS, provided editorial assistance. time with your religious community. Find printed books, intense exercise, time with How to Cite this Article some activities that engage you enough to your kids, a hobby that engages you, a call Sheridan A. You are not alone: Ten strategies distract you from your worries and that to a friend; find something that works for for surviving a malpractice lawsuit. Perm J 2016 feed your soul. you. I learned to queue up an audiobook Summer;20(3):16-004. DOI: http://dx.doi.org/ for my drive to work, so that I didn’t start 10.7812/TPP/16-004. APPROACH LAW AS A FOREIGN CULTURE my day in worry, and to listen to a guided As physicians we’re used to having time meditation if I woke up feeling anxious References pressures. Review the stat labs now! Call during the night. 1. Jena AB, Seabury S, Lakdawalla D, Chandra A. the patient before you go home! Get to Malpractice risk according to physician specialty. N Engl J Med 2011 Aug 18;365(7):629-36. DOI: the OR immediately! Things move much FOCUS ON WHAT YOU CAN CONTROL http://dx.doi.org/10.1056/NEJMsa1012370. differently in the legal world. Scheduling In the legal process, as in life generally, 2. Balch CM, Oreskovich MR, Dyrebye LN, et al. a meeting may take days, weeks, or even there are some things you can control Personal consequences of malpractice lawsuits on American surgeons. J Am Coll Surg 2011 Nov; months. Phone calls may not be returned but many more things you cannot. As 213(5):657-67. DOI: http://dx.doi.org/10.1016/j. the same day. It can be frustrating to just physicians we tend to believe that we’re in jamcollsurg.2011.08.005. wait when you’re used to taking care of charge, so it can be hard for us to accept 3. Seligman MEP. Flourish: a visionary new understanding of happiness and well-being. things quickly. that there are things we can’t control. But New York, NY: Simon & Schuster; 2011. Your attorney is there to help you navi- acceptance can bring relief. After one very gate. But just as a patient may be surprised long and frustrating day, my attorney said

108 The Permanente Journal/Perm J 2016 Summer;20(3):16-004 NARRATIVE MEDICINE The Handshake Layer Cake: Meeting and Regreeting Difficulties for a Non-French Surgeon in France

Colin G Murphy, MCh, FRCSI Perm J 2016 Summer;20(3):15-232 E-pub: 06/27/2016 http://dx.doi.org/10.7812/TPP/15-232

“I’m not shaking hands with you,” my rarely seem to eat in the hospital cafete- obviates the need to offer either hand or friend and colleague says loudly. With a ria—unsurprising given the quality of the index finger. dramatic flourish, he withdraws his hand plat du jour at the local café), say with a Maybe the index-finger shake is the and hides it behind his back, pointing his different colleague, where seven doctors informal fist-pump to the more formal chin and lower lip towards me in a classic are sitting down eating away and chatting handshake? I’m going to have to watch my Gallic pout. No one else present bats an animatedly. You don’t interrupt, but you French gangster movies again to be sure, eyelid. The chomping of lunch and chew- both start at the head of the table and but it seems one doesn’t regreet a senior ing the fat continues around the table, work your way around shaking hands or ranking surgeon with the index shake, or and I am left offering my hand to empty giving les bises (the cheek-kissing of a fe- thumb-to-nose-with-fingerwiggle. Layers space. This response is slightly better than male colleague). Sixth of seven at the table on layers. And so different from home. the “Aaaagh, salaud” (“Agh, bastard”) I is the colleague you greeted earlier that Coming from a culture where work greet- received a few days earlier when commit- morning in passing in the corridor. He is ings are mostly nonverbal, this represents ting the same social faux pas. Twice in one deep in chat, holding court. What do you a quantum change. Eye contact and a week—not good. do? Your colleague ahead of you has just nod are considered eminently sufficient These are two of the more aggressive re- shaken his hand (first greeting of the day for both greeting and regreeting. Verbal sponses to this particular social bêtise and for those two), and not wanting to make greetings are also acceptable; for colleagues pointed reminders of the highly codified a fuss or interrupt the flow of invective a clipped, “Morning” or “Doctor”; for the systems of salutations here in France. Just of your seated colleagues, you might be consultant surgeon a “Mr/Ms O’Brien,” when this Irishman abroad thinks he has tempted to offer your hand to him, again. usually with eye contact and a nod (if the natives cracked, he realizes the mag- Big mistake. Prepare to be taken to task. feeling particularly effusive one could add nitude of his ignorance for a new social You have just created a scene as now he in a temporal “Good morning/afternoon situation. Happily these rebukes are usu- stops talking, leans back in his chair af- Mr/Ms O’Brien”). Tactile greetings in ally followed, and were immediately in the fecting deep insult, and pointedly refuses Irish hospitals are almost unheard of. On two above cases, by a grin, a pppffffhhhh, to shake hands. one six-month rotation, the only physical or a backslap. The best strategy for the regreet sce- contact I had with any of my bosses was a There are kinder rebukes: “HEEEEY, nario is very much person and situation backslap from the senior ranking surgeon on croise les doigts cette fois-ci?” (“Hey, how dependent. I am becoming a big fan of on the morning he came in late for the ’bout we shake fingers this time instead?”), the index-finger shake, which can be done morbidity and mortality conference after or a big, exaggerated outstretched hand with the same familiar and safe nonverbal I stood to vacate the chair nearest the exit followed by withdrawing the hand to do cues as a full handshake: approaching his door for him. the thumb-to-nose and wiggling fingers or her personal space, making eye contact, But it’s not just the handshakes. Les maneuver—like we did when we were and lifting your hand, but only the index bises is another minefield and much more kids—and a “OOOH, on se connaît déjà finger is offered for a playful sword-cross complex than handshakes. I frequently nous!” (“Hey, we already know each other!”). style greeting. It is perfectly acceptable for cringe at the different ways I achieve so- It is strange to see grown Frenchmen doing this all to be done without speaking. cial awkwardness at work by getting even this at you at work and stranger still that For regreeting a senior colleague you the primary greeting wrong, let alone the you get used to it. don’t know well enough yet to tutoyer (to ad- regreeting. We have all done it: offer the Typically the regreet conundrum de- dress someone in French using the familiar cheek when she puts out the hand or vice velops like this: say you see a colleague form of the pronoun “you”—“tu”—rather versa. At work, after a few months here walking down the corridor, maybe with than the more formal form of “vous”), I and meeting the same folks daily, playing a patient. You shake hands in passing and copy my own boss who does an elegant l’etranger card just isn’t an option anymore. give a Bonjour/Ça va?/Ça va, the absolute- head nod and an “On s’est déjà vu” (“We’ve Reluctance to experiment with social greet- scraping-the-barrel-bare-minimum of con- already met”). This avoids committing to ings with female work colleagues means, versational interactions. Then at lunch you a second-person singular familiar/second- happily, that I can’t shed any light on the walk into the Café En Face (my colleagues person singular respectful pronoun and regreet avec bises conundrum, but here is

Colin G Murphy, MCh, FRCSI, is a Consultant Orthopedic Surgeon with Galway University Hospitals in Ireland. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-232 109 NARRATIVE MEDICINE The Handshake Layer Cake: Meeting and Regreeting Difficulties for a Non-French Surgeon in France

a quick summary of what I have observed gloved handshake that people will offer to be the Initial Daily Greet the Ladies On mature reflection, when it their bare forearm to shake instead of a at Work Rules: no handshake or bises for comes to the regreet dilemma, gloved hand. Offering a gloved hand, even the secretaries, just verbal Bonjour/Ça va?/ it is probably better to receive the to someone wearing gloves, ce n’est pas cool, Ça va; a handshake for the female docs playful rebuke for attempting to and it’s not just because they might be one doesn’t know well; bises for the ones steal a second handshake than dirty or contaminated. As Serge, one of one does know well; bises for any woman the sharp word for none at all, the theater porters, pointed out to me in sitting in the Café En Face regardless of but it is infinitely better, as with no uncertain terms in my first week with whether one knows her or not (it’s a social most operative procedures, a slow head shake and a tut-tut, “Doc, c’est context); bises for one’s scrub nurses (who to get it right the first time. pas cool du tout ça.” are friends at this stage), but only if they All of this has to be balanced against aren’t scrubbed, and there isn’t an awake the unthinkable, not greeting someone patient in the room, in which case neither to round speedily and efficiently, he previ- at all, or thinking (like an idiot) that the bises nor handshake just verbal greeting; ously only ever paused to give bises to those wave or nod from a distance that you gave no bises for the nurses on the ward or the nurses he knew very well and liked (and earlier in the day constituted a greeting. physiotherapists—except the pretty physio not infrequently the new, leggy or pretty Failure to execute the primary, most basic who is a friend of the boss and who has nurse he hadn’t met before), but on this salutation of the day is le nec plus ultra of a slightly disinhibited demeanor and a day he stopped to faires les bises with every social ignorance, regardless of distractions desire to chat about Irlande every time we single female nurse, nurses’ assistant, and or confounding factors. It is perceived as meet—she gets the bises greetings. catering staff on each ward (and it seemed a calculated snub, one that folks have no A particular ward round crystallized this a few nurses who came back for seconds). problem letting you know about by march- morass of mores for me. When I arrived Romain, the solitary male nurse, got the ing up to you (regardless of who you are for the very first ward round on New Year’s handshake. While giving un bisou, the boss with or what task you are engaged in) and Day, I found all the nurses in the ward of- wished each of the nurses the New Year trio enquiring, “What’s the matter with you?”, fice were wearing little Santa hats, cheer- of greetings—Bonne année, bonne santé, “Have I annoyed you?”, “I didn’t realize fully calling, “Bonjour, Docteur.” I held et meilleurs voeux—and moved on. He we aren’t friends anymore, you and me?”, my distance, in truth a little intimidated finished covered in lipstick and perfume, or the classic “Ey-oh, tu fais la tête?” (“Are by an office full of French nurses all mak- looking very pleased with himself. I haven’t you sulking?”). ing eye contact, all chirping in sync and been on a round that took so long since I Always the fine line in this wonderful looking expectantly at me. I remained in was a student doing general medicine in a country. On mature reflection, when it the doorway, offered neither hand nor peripheral country hospital. comes to the regreet dilemma, it is prob- cheek, but offered a group reply (in formal- As always, the first work-greeting of ably better to receive the playful rebuke platitude-banter mode) “Bonjour, vous allez the day, be it a handshake or les bises, is for attempting to steal a second handshake bien? Pas trop débordées?” (“All good? Not complicated by context: age, seniority, than the sharp word for none at all, but it too busy?”). There followed The Pause, the work status, employer/employee status, is infinitely better, as with most operative one with which I am now quite familiar, family, familiarity, the other people pres- procedures, to get it right the first time.v the one that corresponds with an ever-so- ent at that interaction, whether it is break/ perceptible thaw in the room that tells you coffee time—these are all variables in play. How to Cite this Article you’ve missed a social cue. The boss walked In the operating theater it gets further Murphy CG. The handshake layer cake: meeting in behind me, and I realized the magnitude complicated by physical barriers: being and regreeting difficulties for a non-French surgeon of the faux pas and how a seasonal trick scrubbed, wearing a facemask, and glove- in France. Perm J 2016 Summer;20(3):15-232. had been missed. Admirable in his ability related issues. Such is the disdain for the DOI: http://dx.doi.org/10.7812/TPP/15-232.

Who You Are

What you see and hear depends a good deal on where you are standing; it also depends on what sort of person you are.

— CS Lewis, 1898-1963, British novelist, poet, academic, medievalist, literary critic, lay theologian, broadcaster, lecturer, and Christian apologist

110 The Permanente Journal/Perm J 2016 Summer;20(3):15-232 NARRATIVE MEDICINE Disconnection

Ahmed Obeidat, MD, PhD Perm J 2016 Summer;20(3):15-165 E-pub: 06/17/2016 http://dx.doi.org/10.7812/TPP/15-165

It was a very familiar object that I asked her to identify. She started without agraphia; it may pass unnoticed. Sometimes, even if ob- to look, feel, think, and she said, “It has buttons, numbers, and glass, served, it can still be overlooked and blamed on its frequent fellow but I cannot put them together, I am unsure!” I then pushed a but- traveler, “homonymous hemianopia.” Alexia without agraphia is ton and asked again. With an assertive voice, she said, “It’s a radio.” very disabling, very frustrating, and much more important than I asked, “What else could it be?” With a tentative voice, she said, “A its corresponding low stroke scale assessment score. The sum total video player?” I whispered, “You are so close, it’s a television.” of our decision to treat or not weighs what we can’t always capture Then, I asked her to identify numbers. She said “four” instead of by a number. The decision to treat or not emphasizes the concept “three” and “one” instead of “five.” Despite her confidence, her an- of art in our daily practice of medicine. swers appeared random. I asked her to read the letters of my name Several months after the event, she lives with her loving parents; as spelled on my hospital ID. She spelled “TLOPZ” for “AHMED”; she is gradually coping with her loss. I talked to her again but this no pattern that I could identify. I then pointed to my black jacket time away from the Emergency Department. and asked her to identify what it was, including what color. She said, She said, “I lost some capabilities. For example, I am not driving after a thoughtful pause, “I have seen it before, but I am unsure.” anymore: it is hard to read the signs or even follow the navigation She started to cry but then felt my jacket with her hand and readily system directions. Occasionally, I ask for help when I want to dress said, “Oh, it’s your jacket, and it is blue.” The last task I asked her for an important event. Otherwise, a perfectly matching outfit to perform was to write a sentence. I was thrilled that she wrote in means little to me. I believe in the beauty of each color and the beautiful script, “Doctor, I want to know what is wrong with me.” beauty of each soul.” I then asked about her writing. She looked Yes, this was alexia (word blindness), without agraphia, associ- at me and smiled. She said, “I still enjoy writing and I love it even ated with color anomia and visual/color agnosia (the inability to more now! I write on my small notebook and then listen to my interpret visual information and color). All implied a disconnec- mother’s voice carrying my own words; she reads them out loud, tion tragedy in her young brain. She was a creative writer in her once, twice, three times and sometimes even more; I enjoy and third decade of life who had battled lupus and antiphospholipid then refine!” She went on to say, “I feel that I am learning again. syndrome for 12 years. Now her disease ravaged her left visual I believe that my perception and my ability to read are going to cortex and further interrupted the connection between her intact eventually come back, but I also know that it might be long before right occipital lobe and the dominant hemisphere, leaving her that moment arrives!” blind to her own words. Apart from alexia, anomia, and visual During that visit, I asked her to read some simple sentences; agnosia, she had no other language problems; she was able to I was so excited to observe her success. She was able to read a express her ideas in speech and in writing, and could fully com- few letters and some simple words. Although it was still difficult prehend spoken English. I quantified her deficits using the -Na for her to name the colors or group them on the basis of their tional Institutes of Health stroke scale assessment.1 Though the similarities, she made some improvement. I can see her young, examination earned her only 2 points, 1 for the field cut, and 1 talented brain marching on the path to recovery perhaps through for the naming difficulty, her disability was beyond what this scale a “detour” bypassing the “disconnection.” could convey. Nevertheless, her coming to our attention after a Finally, by observing her voyage, I gained significant insight into day of symptoms precluded the use of a clot buster medication. the intricacies of brain connections, and most importantly, the She was praying that her difficulties represented migraine with consequences of such seemingly minor deficits in a person’s life.v visual disturbances. But symptoms lasted longer than they should and her ophthalmologist asked her to go to the Emergency De- Disclosure Statement partment to be evaluated. I wondered whether an early arrival The author(s) have no conflicts of interest to disclose. might have made me consider treating with tissue plasminogen activator despite her low stroke scale assessment score. Acknowledgment I feel safe carrying the stroke scale card in my pocket daily; it The author would like to thank Alberto Espay, MD, MS, and Rhonna Shatz, MD, reflects an inventory of brain functions that makes such a com- for comments on an earlier draft of this article. plicated machine comprehensible and under control. The naming How to Cite this Article page reminds us to look for subtleties. Being able to name glove, Obeidat A. Disconnection. Perm J 2016 Summer;20(3):15-165. DOI: http:// key, chair, cactus, feather, and hammock can be very reassuring, dx.doi.org/10.7812/TPP/15-165. whereas losing that ability is worrisome. Moreover, being able to tell the story of the inattentive mother and her sneaky kids reaching Reference for the cookie jar helps us ferret out the elusive signs of language 1. NIH stroke scale [Internet]. Bethesda, MD: National Institute of Health, National and speech disorders. But, it is challenging to diagnose alexia Institute of Neurological Disorders and Stroke; 2013 Dec [cited 2016 Mar 3]. Available from: www.ninds.nih.gov/doctors/stroke_scale_training.htm

Ahmed Obeidat, MD, PhD, is a Resident in Neurology at the University of Cincinnati in Ohio. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-165 111 CASE REPORTS Metastatic Renal Cell Carcinoma Presenting as Painful Chewing Successfully Treated with Combined Nivolumab and Sunitinib

Fade Mahmoud, MD, FACP; Al-Ola Abdallah, MD; Konstantinos Arnaoutakis, MD; Issam Makhoul, MD Perm J 2016 Summer;20(3):15-149 E-pub: 06/27/2016 http://dx.doi.org/10.7812/TPP/15-149

ABSTRACT INTRODUCTION patients who are not fit for HDIL-2.6 Introduction: Metastatic renal cell Renal cell carcinoma (RCC) is more The recent advent of immunotherapy carcinoma (RCC) to the head and neck is common in men than in women, with an with checkpoint inhibitors has brought rare. It is the third-most common cause of overall annual incidence of approximately hope to patients with metastatic renal distant metastasis to the head and neck, 3.7%.1 The median age of onset is around cell carcinoma. In this case we discuss a after breast cancer and lung cancer. Sev- 64 years.1 Approximately 62,000 new cases unique presentation of metastatic renal eral drugs are available to treat metastatic and 14,000 deaths caused by RCC occur cell carcinoma. Also we report an excellent RCC including high-dose interleukin and annually.1 Up to 30% of patients with sustained tumor response to combined targeted therapy. Immunotherapy with RCC present with metastatic disease.1 sunitinib and nivolumab. nivolumab was recently approved by the Most patients are asymptomatic until US Food and Drug Administration (FDA) the disease is advanced. The classic triad CASE PRESENTATION as a second-line treatment for patients of flank pain, hematuria, and a palpable A 71-year-old man presented with pain with metastatic RCC. abdominal mass is present in only 9% of while chewing, progressively worse, during Case Presentation: We present a patients. Several risk factors are thought to the last year. He initially saw his dentist, case of metastatic RCC in a 71-year- play a role in the etiology of RCC; these and an oral exam did not reveal any ab- old man with a single complaint of a include smoking, hypertension, obesity, normalities. Pain medications were pre- 1-year history of pain while chewing renal cystic disease, use of nonsteroidal scribed for use as needed. His symptoms food. Positron emission tomography- anti-inflammatory drugs and other anal- gradually got worse, so he was referred to computed tomography showed diffuse gesics, chronic hepatitis C infection, and an otolaryngologist. metastatic disease. Nivolumab, off-label history of kidney stones.2-5 Soft tissue neck computed tomogra- use before its recent FDA approval, was High-dose interleukin (HDIL-2) is the phy (CT) with contrast revealed a 5-cm combined with sunitinib and resulted only therapy that provides a potential cure intensely enhancing mass with extensive in an excellent and ongoing response. in a minority of patients.6 Several targeted vascular supply in the left masticator space Discussion: RCC is the third-most therapies are approved as first-line for those (Figure 1). Fine needle aspiration of the common cause of distant metastasis to the head and neck. The patient de- scribed in this case did not have any symptoms commonly seen in RCC, such as painless hematuria, weight loss, anorexia, fatigue, or anemia, despite the bulk of his disease. The other important aspect of this case is the almost com- plete response of his metastatic disease to the combination of nivolumab and sunitinib that was used off label before the FDA issued the approval. Future clinical trials should look at combining immunotherapy with targeted therapy in metastatic RCC. Figure 1. Soft tissue neck computed tomography revealing a 5-cm intensely enhancing mass with extensive vascular supply in the left masticator space. A. Sagittal view. B. Transverse view.

Fade Mahmoud, MD, FACP, is an Assistant Professor of Medicine in the Department of Hematology and Oncology at the University of Arkansas for Medical Sciences in Little Rock. E-mail: [email protected]. Al-Ola Abdallah, MD, is a Fellow in the Department of Hematology and Oncology at the University of Arkansas for Medical Sciences in Little Rock. E-mail: [email protected]. Konstantinos Arnaoutakis, MD, is an Associate Professor of Medicine in the Department of Hematology and Oncology at the University of Arkansas for Medical Sciences in Little Rock. E-mail: [email protected]. Issam Makhoul, MD, is an Associate Professor of Medicine in the Department of Hematology and Oncology at the University of Arkansas for Medical Sciences in Little Rock. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-149 1 CASE REPORTS Metastatic Renal Cell Carcinoma Presenting as Painful Chewing Successfully Treated with Combined Nivolumab and Sunitinib

mass showed large cells with clear vesicu- lar cytoplasm. These cells were reactive to paired box gene 8 (PAX8) and pankeratin, whereas the supporting cells were reactive to smooth muscle actin. These findings were suggestive of metastatic renal cell carcinoma (RCC). Full-body positron emission to- mography (PET)-CT confirmed the above findings but also revealed masses at the infe- rior pole of the left kidney, retroperitoneal lymphadenopathy, and bilateral lung nod- ules (Figure 2A). The differential diagnosis based on the location of the mass included schwannoma, hemangiopericytoma, an- giosarcoma, lymphoma, and metastatic carcinoma, particularly lung carcinoma and RCC. Sunitinib, an inhibitor of cel- lular signaling that targets multiple recep- tor tyrosine kinases, was initiated at 50 mg Figure 2. Sagittal positron emission tomography-computed tomography (PET-CT) scan images of full body. orally daily (4 weeks on and 2 weeks off). A. Initial PET-CT clearly showing evidence of metastatic disease. B. Progression of disease on sunitinib. His pain was controlled with opioids, but C. Follow-up PET-CT scan revealing almost complete response to combined nivolumab and sunitinib. we discussed with him palliative radiation therapy to the left masticator space mass in case his pain became resistent to opioids. bulk of his disease. It was only pain while Several targeted therapies were approved Follow up PET-CT postsunitinib therapy chewing food that led to the diagnosis of as first-line for those patients who are not showed an interval progression of his disease metastatic RCC. CT scan with contrast is fit for HDIL-2, but treatment is based on (Figure 2B). Nivolumab, an anti-program the imaging modality of choice in dem- risk groups. The Memorial Sloan-Kettering death receptor 1 inhibitor, was not approved onstrating the vascularity and extent of Cancer Center prognostic score stratifies yet by the US Food and Drug Administra- the lesion.7 patients with metastatic RCC into poor, tion, but we decided to add it to sunitinib, The pathology revealed cells that are intermediate, and favorable risk catego- and the combined treatment resulted in reactive to PAX8 and pankeratin. PAX8 ries on the basis of the number of adverse almost complete response (Figure 2C). and paired box gene 2 (PAX2) are tran- clinical and laboratory parameters present.13 Table 1 illustrates a timeline of his follow- scription factors important for fetal de- Poor prognostic factors include a Karnofsky up visits, diagnostic tests, and interventions. velopment of several organs, including performance status of less than 80 (80 indi- kidney, müllerian organs, brain, and eye. cates normal activity with effort and some DISCUSSION Both are good markers for renal cell tu- signs or symptoms of disease), time from Surpassed only by breast cancer and mors. Almost all RCCs are positive for diagnosis to treatment less than 12 months, lung cancer, RCC is the third-most com- PAX8, which is frequently expressed by serum lactate dehydrogenase more than 1.5 mon cause of distant metastasis to the lymphoma (100%), nephrogenic adenoma times the upper limit of normal, corrected head and neck.7 Head-and-neck metastasis (100%), parathyroid tumors (62%), thy- serum calcium greater than 10 mg/dL, is the presenting complaint for 7.5% of roid tumors (100%), and müllerian organ- and hemoglobin less than the lower limit patients with RCC.8 However, only 1% derived tumors (92%).10,11 Tumors that of normal.13 Patients in the favorable-risk of patients with RCC have metastasis con- may be negative or infrequently positive group have no poor prognostic factors, fined to the head and neck.8 A retrospec- for PAX2, including chromophobe RCC, those in the intermediate-risk category tive chart review of 21 cases of metastasis oncocytoma, and sarcomatoid RCC, are have 1 or 2 adverse prognostic factors, and of RCC to the head and neck found that often positive for PAX8.12 patients with poor-risk RCC have more the most common sites of metastasis were Several drugs are available to treat meta- than 2 poor prognostic factors. Patients bone (n = 6), skin and subcutaneous tis- static RCC. Patients with good Karnofsky in the favorable or intermediate risk group sue (n = 6), and lymph nodes (n = 5).9 A performance status (≥ 80%) and intact are treated with sunitinib, pazopanib, or head-and-neck metastasis may occasionally organ function are treated with high-dose interferon alpha plus bevacizumab,14-16 be the presenting sign in a patient with interleukin-2 (HDIL-2) up front. HDIL-2 whereas the front-line treatment for those RCC or may follow the primary diagnosis can induce long-term remissions in approxi- in the poor risk group is temsirolimus by many years.9 Our patient did not have mately 10% of patients.12 This treatment is alone.17 Axitinib and sorafenib has been any symptoms commonly seen in RCC, associated with an approximately 4% mor- approved as second-line treatment, for use such as painless hematuria, weight loss, tality rate, so it is extremely important to after other targeted therapy or cytokine anorexia, fatigue, or anemia, despite the select patients who are fit for this therapy. therapy has failed.18

2 The Permanente Journal/Perm J 2016 Summer;20(3):15-149 CASE REPORTS Metastatic Renal Cell Carcinoma Presenting as Painful Chewing Successfully Treated with Combined Nivolumab and Sunitinib

Activating the immune system appears and nivolumab resulted in an objective escalation to 5 mg/kg intravenously every to be a promising strategy to treat meta- response rate of 61%.19 3 weeks. Objective response rate was 52% static RCC. Since 2011, 2 novel classes In a phase I trial, patients with metastatic among patients receiving nivolumab and of immunotherapy drugs have been ap- RCC received nivolumab in combination sutent and 45% among those receiving proved: the cytotoxic T lymphocyte an- with sunitinb (50 mg, 4 weeks on, 2 weeks nivolumab and pazopanib. Almost half the tigen 4 (CTLA-4) inhibitor ipilimumab off) or pazopanib (800 mg daily), until responses occurred by the first assessment, and the program death receptor 1 inhibi- progression/unacceptable toxicity. The which is week 6 of treatment. The inves- tors pembrolizumab and nivolumab.19 In starting dosage of nivolumab was 2 mg/kg tigators concluded that nivolumab plus melanoma the combination of ipilimumab intravenously every 3 weeks with planned sutent or pazopanib showed encouraging

Table 1. Timeline of the case Date Relevant past medical history and interventions April 20, 2015 Chief complaint: A 71-year-old man with no past medical history presented with painful chewing during the past 1 year. Family history: Mother died from pancreatic cancer at the age of 69. Father died from lung cancer at the age of 86. Physical examination: Mild left cheek swelling. Previous imaging: An outside-hospital, soft-tissue neck CT with contrast dated March 12, 2015 revealed a 5-cm intensely enhancing mass with extensive vascular supply in the left masticator space. Previous intervention: A CT-guided biopsy of the mass dated April 2, 2015 confirmed metastatic renal cell carcinoma (clear cell type). Current intervention: Ordered whole-body PET-CT scan to complete the staging. Summaries from initial Date and follow-up visits Diagnostic testing Interventions April 18, 2015 Follow-up visit PET-CT: At least a 3.7-cm mass within the left pterygopalatine fossa, Sunitinib 50 mg orally daily SUV 2.4. A minimum of 10 nodules are seen scattered throughout both (4 weeks on, 2 weeks off). lungs; the largest measures 33 x 28 mm, SUV 6.2. Liver: Approximately 2.1-cm focus in the posterior aspect of segment VIII, SUV 3.1. Right suprarenal fossa: approximately 9 x 6-cm mass, SUV 2.7. Left kidney, inferior pole: Approximately 9-cm mass, SUV 5.0. May 19, 2015 Tolerating medication None. Sunitinib was approved by without problems. States his insurance and shipped that he has some left to patient. Medication cheek swelling that comes started May 1, 2015. and goes July 7, 2015 Left cheek swelling that PET-CT: At least a 4.1 x 2.5-cm mass within the left pterygopalatine fossa, We decided to get comes while off Sunitinib SUV 5.5. A minimum of 10 nodules are seen scattered throughout both nivolumab off label use. We and goes away while on lungs; the largest measures 36 x 29 mm, SUV 6.3. told the patient to continue Sunitinib Liver: Approximately 5-cm focus in the posterior aspect of segment VIII, SUV taking sunitinib because 5.1. Right suprarenal fossa: Approximately 10.5 x 5.4-cm mass, SUV 5.3. he had been on it for only Left kidney, inferior pole: Approximately 6.9-cm mass, SUV 5.6. These 2 months. findings are consistent with progression of his disease. August 5 - Patient was seen every 2 None. Completed 4 cycles of September 15, 2015 weeks while on nivolumab nivolumab. September 21, 2015 PET-CT: Complete opacification of the left maxillary sinus, SUV 6.3. A Continue sunitinib and minimum of 10 nodules are seen scattered throughout both lungs, most nivolumab, restage disease of which appear slightly improved; the largest measures 28 mm, SUV 5.5. in 3 months. There is interval improvement in previously documented hypermetabolic right hepatic focus, which on today’s study has an SUV of 2.9 (prior SUV 5.1). Stable to slight morphologic and metabolic improvement in previously documented left and right renal masses. December 15, 2015 Tolerating treatment well PET-CT: Decreased extent and metabolic activity of left masticator Continue combined sunitinib with combined sunitinib space metastasis, SUV 3.7. Decreased size of the left lower pole renal and nivolumab, restage and nivolumab mass. Decrease in size, and metabolic activity of lung, right adrenal, disease in 3 months. retroperitoneal soft tissue and lymph node metastases. March 8, 2016 Tolerating treatment well PET-CT: Improving metabolic activity in the left masticator space, SUV 2.7 Continue combined sunitinib with combined sunitinib (prior SUV 3.6). Stable to slight improvement in the previously documented and nivolumab, restage and nivolumab subcentimeter right lung nodules and 1.7-cm left upper lobe mass. disease in 3 months. CT = computed tomography; PET = positron emission tomography; SUV = standardized uptake value.

The Permanente Journal/Perm J 2016 Summer;20(3):15-149 3 CASE REPORTS Metastatic Renal Cell Carcinoma Presenting as Painful Chewing Successfully Treated with Combined Nivolumab and Sunitinib

antitumor activity and a manageable safety Acknowledgment 11. Truong LD, Shen SS. Immunohistochemical 20 Leslie Parker, ELS, provided editorial assistance. diagnosis of renal neoplasms. Arch Pathol Lab profile in patients with metastatic RCC. Med 2011 Jan;135(1):92-109. DOI: http://dx.doi. The decision to add nivolumab (off-label org/10.1043/2010-0478-RAR.1. How to Cite this Article use) in our patient was based on the results 12. Gupta R, Balzer B, Picken M, et al. Diagnostic Mahmoud F, Abdallah AO, Arnaoutakis K, implications of transcription factor Pax 2 protein of the above phase I trial. Three months later Makhoul I. Metastatic renal cell carcinoma and transmembrane enzyme complex carbonic (November 23, 2015), the FDA approved presenting as painful chewing successfully treated anhydrase IX immunoreactivity in adult renal nivolumab on the basis of results of an open with combined nivolumab and sunitinib. Perm J epithelial neoplasms. Am J Surg Pathol 2009 Feb;33(2):241-7. DOI: http://dx.doi.org/10.1097/ label, randomized study that showed an 2016 Summer;20(3):15-149. DOI: http://dx.doi.org/ PAS.0b013e318181b828. overall survival advantage of nivolumab over 10.7812/TPP/15-149. 13. Motzer RJ, Mazumdar M, Bacik J, Berg W, everolimus in patients with metastatic RCC Amsterdam A, Ferrara J. Survival and prognostic 21 stratification of 670 patients with advanced renal cell who failed antiangiogenic agents. Those References carcinoma. J Clin Oncol 1999 Aug;17(8):2530-40. treated with nivolumab lived an average of 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 14. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib 25 months compared with 19.6 months in 2015. CA Cancer J Clin 2015 Jan-Feb;65(1):5-29. versus sunitinib in metastatic renal-cell carcinoma. N DOI: http://dx.doi.org/10.3322/caac.21254. Engl J Med 2013 Aug 22;369(8):722-31. DOI: http:// those treated with Afinitor. Additionally, 2. Hunt JD, van der Hel OL, McMillan GP, Boffetta P, dx.doi.org/10.1056/NEJMoa1303989. 21.5% of those treated with nivolumab Brennan P. Renal cell carcinoma in relation to 15. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib experienced a complete or partial shrinkage cigarette smoking: meta-analysis of 24 studies. Int J versus interferon alfa in metastatic renal-cell Cancer 2005 Mar 10;114(1):101-8. DOI: http://dx.doi. carcinoma. N Engl J Med 2007 Jan 11;356(2):115-24. of their tumors, which lasted an average of org/10.1002/ijc.20618. DOI: http://dx.doi.org/10.1056/NEJMoa065044. 23 months, compared with 3.9% of those 3. Ljungberg B, Campbell SC, Choi HY, et al. The 16. Escudier B, Pluzanska A, Koralewski P, et al; epidemiology of renal cell carcinoma. Eur Urol 2011 AVOREN Trial Investigators. Bevacizumab plus taking everolimus, lasting an average of 13.7 Oct;60(4):615-21. DOI: http://dx.doi.org/10.1016/j. 21,22 interferon alfa-2a for treatment of metastatic renal months. eururo.2011.06.049. Erratum in: Eur Urol 2011 cell carcinoma: a randomised, double-blind phase III Our patient appears to be tolerating the Dec;60(6):1317. DOI: http://dx.doi.org/10.1016/j. trial. Lancet 2007 Dec 22;370(9605):2103-11. DOI: eururo.2011.09.001. combination of nivolumab and sunitinib. http://dx.doi.org/10.1016/S0140-6736(07)61904-7. 4. Cho E, Curhan G, Hankinson SE, et al. 17. Hudes G, Carducci M, Tomczak P, et al; Global His follow-up PET-CT showed improve- Prospective evaluation of analgesic use and risk ARCC Trial. Temsirolimus, interferon alfa, or both ment in his disease (Table 1). of renal cell cancer. Arch Intern Med 2011 Sep for advanced renal-cell carcinoma. N Engl J Med 12;171(16):1487-93. DOI: http://dx.doi.org/10.1001/ 2007 May 31;356(22):2271-81. DOI: http://dx.doi. archinternmed.2011.356. org/10.1056/NEJMoa066838. CONCLUSIONS 5. Gordon SC, Moonka D, Brown KA, et al. Risk 18. Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib Metastatic cancer to the head and neck is for renal cell carcinoma in chronic hepatitis C versus sorafenib as first-line therapy in patients infection. Cancer Epidemiol Biomarkers Prev with metastatic renal-cell carcinoma: a randomised rare. Breast cancer, lung cancer, and RCC 2010 Apr;19(4):1066-73. DOI: http://dx.doi. open-label phase 3 trial. Lancet Oncol 2013 are the most common causes of distant org/10.1158/1055-9965.EPI-09-1275. Dec;14(13):1287-94. DOI: http://dx.doi.org/10.1016/ metastasis to the head and neck. In our 6. Klapper JA, Downey SG, Smith FO, et al. High-dose S1470-2045(13)70465-0. interleukin-2 for the treatment of metastatic renal 19. Postow MA, Chesney J, Pavlick AC, et al. case, pain while chewing food was the only cell carcinoma: a retrospective analysis of response Nivolumab and ipilimumab versus ipilimumab in presenting symptom of metastatic RCC. and survival in patients treated in the surgery branch untreated melanoma. N Engl J Med 2015 May Immunotherapy with interleukin-2 or at the National Cancer Institute between 1986 and 21;372(21):2006-17. DOI: http://dx.doi.org/10.1056/ 2006. Cancer 2008 Jul 15;113(2):293-301. DOI: NEJMoa1414428. interferon-alpha, biologic, or targeted ther- http://dx.doi.org/10.1002/cncr.23552. 20. Amin A, Plimack ER, Infante JR, et al. Nivolumab apy are all viable options for patients with 7. Pritchyk KM, Schiff BA, Newkirk KA, Krowiak E, (anti-PD-1; BMS-936558, ONO-4538) in combination metastatic RCC. Most recently the FDA Deeb ZE. Metastatic renal cell carcinoma to the head with sunitinib or pazopanib in patients (pts) with and neck. Laryngoscope 2002 Sep;112(9):1598-602. metastatic renal cell carcinoma (mRCC). ASCO approved nivolumab in the second-line set- DOI: http://dx.doi.org/10.1097/00005537-200209000- Annual Meeting Abstracts. J Clinical Oncol 2014 May ting after patients have failed antiangiogenic 00012. 20;32(15 Suppl):5010. agents. Our patient had an almost complete 8. Boles R, Cerny J. Head and neck metastases from 21. FDA News Release: FDA approves Opdivo to treat renal carcinomas. Mich Med 1971 Jul;70(16):616-8. advanced form of kidney cancer [Internet]. Silver response to combined nivolumab and 9. Langille G, Taylor SM, Bullock MJ. Metastatic renal Spring, MD: US Food and Drug Administration; 2015 sunitinib. Further studies should look into cell carcinoma to the head and neck: summary Nov 23 [cited 2016 Mar 9]. Available from: www.fda. the combination of targeted therapy and of 21 cases. J Otolaryngol Head Neck Surg 2008 gov/NewsEvents/Newsroom/PressAnnouncements/ Aug;37(4):515-21. ucm473971.htm. immunotherapy in the front-line setting 10. Ozcan A, Shen SS, Hamilton C, et al. PAX 8 22. Motzer RJ, Escudier B, McDermott DF, et al; among patients with metastatic RCC. v expression in non-neoplastic tissues, primary CheckMate 025 Investigators. Nivolumab versus tumors, and metastatic tumors: a comprehensive Everolimus in advanced renal-cell carcinoma. immunohistochemical study. Mod Pathol 2011 N Engl J Med 2015 Nov 5; 373(19):1803-13. DOI: Disclosure Statement Jun;24(6):751-64. DOI: http://dx.doi.org/10.1038/ http://dx.doi.org/10.1056/NEJMoa1510665. The author(s) have no conflicts of interest to modpathol.2011.3. disclose.

Flexibility

Fixity of purpose requires flexibility of method.

— Harold G Wolff, 1898-1962, American physician, neurologist, and scientist

4 The Permanente Journal/Perm J 2016 Summer;20(3):15-149 CASE REPORTS Treatment of Tracheoinnominate Fistula with Ligation of the Innominate Artery: A Case Report

Rhiana S Menen, MD; Jimmy J Pak, MD; Matthew A Dowell, PA; Ashish R Patel, MD; Simon K Ashiku, MD; Jeffrey B Velotta, MD Perm J 2016 Summer;20(3):15-166 E-pub: 06/22/2016 http://dx.doi.org/10.7812/TPP/15-166

ABSTRACT performed. Massive hemorrhage through and communicative. The patient was Introduction: Tracheoinnominate the tracheostomy occurred on day 10. transferred to the ward and is currently fistula, a rare complication of tracheos- Direct tamponade through the neck inci- doing well in a rehabilitation facility. tomy, carries high mortality regardless sion (Utley maneuver) was immediately of treatment; therefore prevention and lifesaving. Massive transfusion protocol DISCUSSION quick diagnosis is pertinent to survival. was activated and thoracic and vascular TIF is a rare but devastating complication Case Presentation: A 76-year-old surgical services were emergently con- of tracheostomy. The incidence of TIF is man who underwent emergent tra- sulted. Median sternotomy with ligation reported from 0.1% to 1%.1 There is 100% cheostomy placement presented on of the innominate artery was performed. mortality if no intervention is pursued.1 postoperative day 10 with massive The innominate artery was extremely TIF occurs within the first 3 weeks after hemorrhage concerning for tracheoin- friable, consistent with postradiation tracheostomy in 72% of the patients that nominate fistula and was treated with changes, and was ligated and divided develop this condition1 but may occur years median sternotomy and ligation of the with the addition of a pericardial patch after the surgical procedure.2 Risk factors innominate artery. and pledgeted 2-0 prolene sutures owing for TIF include tracheal infection, steroid Discussion: This presentation de- to the poor quality of the artery. The pa- use, creation of the tracheostomy below the scribes a concise diagnosis and treat- tient was stabilized and returned to the third tracheal ring, pressure necrosis caused ment plan for a rare event. The key to intensive care unit fully neurologically by overinflation of the cuff or malposition, good outcomes is quick diagnosis and intact. On postoperative day 2, with the and chest deformity leading to a high-riding urgent surgical intervention. patient medically stable in the intensive innominate artery. Surgical texts dictate im- care unit, he returned to the operating mediate repair or ligation of the innominate INTRODUCTION room for formal revision of the innomi- artery; however, there are only sporadic case Tracheoinnominate fistula (TIF) is a dev- nate stump owing to concern over its fri- reports available in the literature. astating complication of tracheostomy with ability from extensive radiation changes, 100% mortality reported in the absence as well as to prevent its constant contact Diagnosis and Management of treatment. Here we report the case of a with tracheal secretions. The stump was of Initial Hemorrhage 76-year-old man who survived ligation of debrided, ligated, and buttressed with a Bleeding from the tracheostomy site the innominate artery, and discuss diagno- pedicled left pectoralis major muscle flap is relatively common, though true TIF is sis, control of initial hemorrhage, and effi- to prevent refistulization. On postopera- rare. “Early” bleeding occurs within hours cacy of this and other approaches to repair. tive day 3, he became hypotensive longer after tracheostomy and is generally caused than 10 minutes owing to intermittent by failure of local hemostasis or underlying CASE PRESENTATION atrial fibrillation. He was later noted on coagulopathy. Incidence of TIFs, however, A 76-year-old man with a history of examination to have a left-sided hemipa- peak 1 to 2 weeks postoperatively and may recurrent papillary thyroid cancer, modi- resis. A moderate right middle cerebral manifest as a “sentinel bleed,” wherein fied radical neck dissection, and previous artery hemispheric infarct was visualized there is a brief episode of bright red, often neck radiation that was complicated by on urgent computed tomography scan pulsatile bleeding from the tracheostomy bilateral recurrent laryngeal nerve injury, of the brain. On the basis of imaging site. Unfortunately, only 35% of patients underwent emergent tracheostomy. On and timing of onset of hypotension, the with TIF exhibit this pathognomonic sign,2 postoperative day 8, less than a teaspoon cause of the stroke was determined to be making preemptive diagnosis challenging. of blood emanated from the tracheostomy ischemia from prolonged hypotension, Confirming the diagnosis of TIF can site after coughing. This was thought to rather than a direct result of decreased be difficult and may include bronchos- be related to granulation tissue around perfusion after ligation. Over time he copy, arteriography, or computed tomog- the stoma, thus bronchoscopy was not regained his strength and was fully alert raphy angiography with 3-dimensional

Rhiana S Menen, MD, is a Surgeon at the University of California San Francisco-Eastbay in Oakland. E-mail: [email protected]. Jimmy J Pak, MD, is a Vascular Surgeon at the Oakland Medical Center in CA. E-mail: [email protected]. Matthew A Dowell, PA, is a Thoracic Surgery Physician Assistant at the Oakland Medical Center in CA. E-mail: [email protected]. Ashish R Patel, MD, is a Thoracic Surgeon at the Oakland Medical Center in CA. E-mail: [email protected]. Simon K Ashiku, MD, is a Thoracic Surgeon at the Oakland Medical Center in CA. E-mail: [email protected]. Jeffrey B Velotta, MD, is a Thoracic Surgeon at the Oakland Medical Center in CA. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-166 1 CASE REPORTS Treatment of Tracheoinnominate Fistula with Ligation of the Innominate Artery: A Case Report

reconstruction. Taken together, these stud- because of a reporting bias in favor of suc- of endovascular stent grafting include 1) ies have only a 20% to 30% sensitivity cessful patient outcomes. inadequacy of resources and expertise at to confirm the diagnosis3 and therefore a One of the largest case series of TIF smaller community-based hospitals; 2) high clinical suspicion must be employed ligation by Furukawa and colleagues6 de- inadequate landing zones for stent place- to improve mortality. Any tracheostomal scribes excellent results seen in 7 pediatric ment, necessitating an additional surgical bleeding and/or hemoptysis beyond the patients with existing severe neurologic bypass to maintain flow; and 3) lack of first 48 postoperative hours must be con- deficits. Operative repair was approached by data because of so few cases. sidered a sentinel bleed and investigated for collar incision with partial sternotomy and TIF is a rare but devastating sequela of the possibility of TIF.2 Even with prompt innominate artery division. Cerebral blood a common surgical procedure. With early identification, surgery is associated with a flow was monitored by the blood pressure recognition, rapid control of hemorrhage, greater than 50% mortality owing to both difference in the bilateral upper extremities and prompt intervention, disruption of the perioperative hemorrhage and infectious and by near-infrared spectroscopy. Only 1 innominate artery through division and complications.4 Overall prognosis remains of 7 patients was noted to have evidence of ligation is a viable repair option that has poor, with 56% of survivors reported dead decreased cerebral perfusion after innomi- been shown to produce sustained survival within 2 months,5 probably because of the nate artery clamping, and an innominate to with minimal risk of neurologic deficit.v high prevalence of associated comorbidities right carotid artery bypass was performed. within this critically ill population. The tracheal fistula was left adherent to the Disclosure Statement innominate artery in all but 1 patient, in The author(s) have no conflicts of interest to Early Control of Hemorrhage whom a pericardial covering was placed report. When patients present with massive hem- between the trachea and innominate artery. orrhage, a stepwise progression of bedside Long-term follow-up confirmed no new Acknowledgment interventions can be rapidly applied to tem- neurologic deficits including any vascular, Mary Corrado, ELS, provided editorial assistance. porize bleeding, maintain a patent airway, tracheal, or new computed tomography How to Cite this Article and bridge patients to definitive therapy. The findings postoperatively. Overall survival Menen RS, Pak JJ, Dowell MA, Patel AR, Ashiku SK, most common site of TIF is at the level of was an impressive 84% at 37 months,7 Velotta JB. Treatment of tracheoinnominate fistula the endotracheal cuff; therefore, overinfla- compared with the reported 15% to 71% with ligation of the innominate artery: a case report. tion of the tracheostomy cuff should be at- cited elsewhere in the literature.8 Perm J 2016 Summer;20(3):15-166. DOI: http:// tempted first. This technique is successful in In the case presented in this report, dx.doi.org/10.7812/TPP/15-166. nearly 85% of cases.1 In patients in whom it ligation was accomplished via median is not, the tracheostomy should be replaced sternotomy, which allowed full exposure References 1. Grant CA, Dempsey G, Harrison J, Jones T. with a cuffed endotracheal tube distal to of the supra-aortic trunk. This was particu- Tracheo-innominate artery fistula after percutaneous the site of the bleeding.1 If hemorrhage per- larly useful in the context of an infected, tracheostomy: three case reports and a clinical review. Br J Anaesth 2006 Jan;96(1):127-31. DOI: sists, the Utley maneuver can be employed postradiation operative field. However, http://dx.doi.org/10.1093/bja/aei282. wherein a finger is placed into the airway, this approach also carries the risk of both 2. Ridley RW, Zwischenberger JB. Tracheoinnominate with or without extension of the incision, mediastinitis and wound infection. A 39% fistula: surgical management of an iatrogenic disaster. J Laryngol Otol 2006 Aug;120(8):676-80. and the innominate artery is compressed incidence of sternal wound complications DOI: http://dx.doi.org/10.1017/S0022215106001514. against the posterior sternum. Furukawa has been reported in patients with trache- 3. Sashida Y, Arashiro K. Successful management and colleagues6 describe prompt control of ostomy and median sternotomy.7 of tracheoinnominate artery fistula using a split pectoralis muscle flap with anatomical reconstruction the tracheostomy hemorrhage by insertion of Recent technologic advancements in by a synthetic graft. Scand J Plast Reconstr Surg a tracheostomy cannula with a wired silastic interventional radiology and endovascu- Hand Surg 2010 Jun;44(3):175-7. DOI: http://dx.doi. tube and an adjustable wing, and overin- lar techniques have allowed clinicians to org/10.3109/02844310801956581. 4. Allan JS, Wright CD. Tracheoinnominate fistula: flating the cuff to provide hemostasis. This pursue less invasive options to manage TIF. diagnosis and management. Chest Surg Clin N 5 resulted in control of hemorrhage in 7 of 7 Troutman et al managed to successfully Am 2003 May;13(2):331-41. DOI: http://dx.doi. patients in their case series. deploy an endovascular stent graft via the org/10.1016/S1052-3359(03)00006-1. 5. Troutman DA, Dougherty MJ, Spivack AI, Calligaro KD. right common carotid artery in addition to Stent graft placement for a tracheoinnominate artery Innominate Artery Ligation a carotid to subclavian bypass. The patient fistula. Ann Vasc Surg 2014 May;28(4):1037.e21-4. Once TIF has been identified as the survived the initial event; however, after DOI: http://dx.doi.org/10.1016/j.avsg.2013.08.021. 6. Furukawa K, Kamohara K, Itoh M, Morokuma H, cause of hemorrhage, surgical texts de- three months the patient succumbed to Morita S. Operative technique for tracheo- scribe division of the innominate artery recurrent hemoptysis and subsequent car- innominate artery fistula repair. J Vasc Surg 2014 and the separation of the oversewn ends diac arrest. Troutman et al5 concluded that Apr;59(4):1163-7. DOI: http://dx.doi.org/10.1016/j. jvs.2013.09.013. from the trachea. By ligating only the in- endovascular stent management of TIF 7. Hazarika P, Kamath SG, Balakrishnan R, Girish R, nominate artery, the subclavian and carotid offers a less invasive option and can substi- Harish K. Tracheo-innominate artery fistula: a rare circulation are left in continuity. Innomi- tute as a bridge for poor surgical candidates complication in a laryngectomized patient. J Laryngol Otol 2002 Jul;116(7):562-4. DOI: http://dx.doi. nate artery ligation has an estimated 10% with the potential for becoming better org/10.1258/002221502760132502. 6 risk of neurologic deficit. This number surgical candidates. The main advantage 8. Gelman JJ, Aro M, Weiss SM. Tracheo-innominate is roughly supported by case reports in to endovascular management of TIF is artery fistula. J Am Coll Surg 1994 Nov;179(5):626-34. the literature, although this is probably less morbidity. The limitations to the use

2 The Permanente Journal/Perm J 2016 Summer;20(3):15-166 CASE REPORTS Monoarticular Poncet Disease after Pulmonary Tuberculosis: A Rare Case Report and Review of Literature

Paritosh Garg, MD; Nikhil Gupta, MD, MBBS; Mohit Arora, MS Perm J 2016 Summer;20(3):15-199 E-pub: 07/15/2016 http://dx.doi.org/10.7812/TPP/15-199

ABSTRACT a rare and atypical presentation of Pon- Introduction: Tuberculosis is a ma- cet disease with involvement of only the jor health problem worldwide, more right knee. so in Asian countries and especially India. Being a communicable disease, CASE PRESENTATION it can affect the lives of many people. A 24-year-old woman presented with Tuberculosis has varied manifestations complaints of continuous fever for 15 and can affect almost every part of the days, which was associated with sudden- human body. Pulmonary tuberculosis onset swelling of her right knee for 5 days. is the most common form. Poncet There was a history of anorexia. There was disease (tuberculous rheumatism) is a no history of cough, burning micturition, Figure 1. Contrast-enhanced computed tomography scan of chest reveals multiple enlarged pretracheal polyarticular arthritis that occurs during vaginal discharge, abdominal complaints, lymph nodes. acute tuberculosis infection in which or trauma. There was no history of TB, no mycobacterial involvement can and the patient was sexually inactive. Re- be found or no other known cause of sults of the physical examination revealed polyarthritis is detected. swelling in the right knee, which was not Case presentation: We describe an tender. The temperature over the swelling atypical presentation of active pulmo- was normal. The remaining findings of the nary tuberculosis with monoarticular examination were normal. Poncet disease of the right knee in a The laboratory tests showed a leukocyte 24-year-old woman. count of 10.4 × 109/L (10,400/μL; 65% of Discussion: The diagnosis of Poncet segmented neutrophils), erythrocyte sedi- disease is mainly clinical with exclusion mentation rate of 32 mm/h, and C-reactive of other causes. It generally presents as protein level of 159 mg/dL. The Mantoux an acute or subacute form; however, test result was strongly positive (16 × 12 chronic forms have been described in mm). The urinalysis result was normal, the literature. and urine culture and blood culture were negative. The antinuclear antibody test INTRODUCTION result was normal, and the test results for Figure 2. X-ray film of right knee joint (at right) Tuberculous arthritis is a monoarticular, rheumatoid factor were negative. Sexually shows periarticular soft-tissue swelling. infectious, and destructive disease. How- transmitted diseases were ruled out, and ever, tuberculous rheumatism, popularly the serologic test result for human im- known as Poncet disease, is a nondestruc- munodeficiency virus was negative. The The chest x-ray film was normal. tive parainfective polyarthritis occurring serum uric acid level was 5.8 mg/dL. Fifty Contrast-enhanced computed tomogra- in patients with active tuberculosis (TB), milliliters of synovial fluid was aspirated phy scan of the chest revealed multiple which resolves completely with antitu- from the knee joint. The analysis of the enlarged lymph nodes in the pretracheal berculosis therapy.1 The diagnosis of this synovial fluid showed a leukocyte count region (Figure 1) and the prevascular and entity is largely clinical and is made by of 5 × 109/L with a differential count of precarinal regions. However, the contrast- excluding other causes of polyarthritis polymorphs being 55% and leukocytes be- enhanced computed tomography scan of in a patient with documented active TB. ing 45%. The synovial fluid was negative the abdomen was normal. The x-ray film Monoarticular involvement in tubercular for TB using polymerase chain reaction. of the right knee joint showed periarticular rheumatism has not been previously de- There were no crystals and the cultures soft-tissue swelling, and active TB with no scribed, to our knowledge. We describe were sterile. changes (Figure 2). Fine-needle aspiration

Paritosh Garg, MD, is a Pathologist at the University College of Medical Sciences and Guru Tag Bahadur Hospital in Dilshad Garden, Delhi, India. E-mail: [email protected]. Nikhil Gupta, MD, MBBS, is a Fellow in Clinical Immunology and Rheumatology at the Christian Medical College and Hospital in Vellore, Tamil Nadu, India. E-mail: [email protected]. Mohit Arora, MS, is an Orthopedician at the University College of Medical Sciences and Guru Tag Bahadur Hospital in Dilshad Garden, Delhi, India. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-199 1 CASE REPORTS Monoarticular Poncet Disease after Pulmonary Tuberculosis: A Rare Case Report and Review of Literature

The etiopathogenesis of Poncet disease is This lack of reporting may be because of proposed to be molecular mimicry and a scarcity of data and a lack of knowledge thermal shock proteins.6 about this entity called Poncet disease. Our patient had active pulmonary tu- bercular findings on a computed tomog- CONCLUSION raphy scan and swelling of the right knee, Poncet disease has been described in the which was found to be inflammatory, literature as polyarticular disease without without any evidence of organism in the any evidence of organism isolated from synovial fluid. Thus, a diagnosis of Poncet the synovial fluid. However, because of disease was made. Our patient responded a scarcity of data and lack of knowledge, to the antitubercular drugs, and her knee we may be missing quite a few cases of Figure 3. Fine-needle aspiration cytology of swelling was reduced over two weeks. monoarticular Poncet disease. Thorough pretracheal lymph nodes reveals epithelioid cell granulomas. Although Poncet disease has been research and sharing of knowledge may described as a polyarthritis, a review of be required for the discovery of such a rare the literature reveals it to be an often presentation. v cytology of the pretracheal lymph nodes pauciarticular, symmetrical arthritis pre- revealed epithelioid cell granulomas dominantly involving the large joints.1,7,8 Disclosure Statement (Figure 3). The acid-fast bacillus test The tuberculous septic monoarthritis, in The author(s) have no conflicts of interest to from the epithelioid cell granulomatous which the mycobacterium can be isolated disclose. lymph node material was positive. from the culture of the affected joint, is a The patient began antitubercular ther- known entity. However, to the best of our Acknowledgment knowledge, monoarticular Poncet disease Kathleen Louden, ELS, of Louden Health apy. On follow-up examination, she was Communications provided editorial assistance. afebrile. The joint swelling reduced after has not been described in the literature. two weeks of treatment and disappeared How to Cite this Article in about a month. In the patient’s con- Garg P, Gupta N, Arora M. Monoarticular Poncet tinuation phase of treatment, she became disease after pulmonary tuberculosis: A rare symptom-free (Figure 4). case report and review of literature. Perm J 2016 Summer;20(3):15-199. DOI: http://dx.doi.org/ DISCUSSION 10.7812/TPP/15-199. TB is a major communicable disease. According to the World Health Organiza- References tion’s 2011 report, there were an estimated 1. Isaacs AJ, Sturrock RD. Poncet’s disease—fact or fiction? A re-appraisal of tuberculous rheumatism. 8.7 million incident cases of TB (range, Tubercle 1974 Jun;55(2):135-42. DOI: http://dx.doi. 8.3 million to 9.0 million) globally.2 Be- org/10.1016/0041-3879(74)90007-5. cause of such a massive burden of TB, 2. Global tuberculosis report 2012 [Internet]. Geneva, Switzerland: World Health Organization; 2011 [cited extrapulmonary manifestations of TB, 2016 Mar 16]. Available from: www.who.int/tb/ including arthritis, are increasing. Mus- publications/global_report/gtbr12_main.pdf. culoskeletal manifestations are the most 3. Malaviya AN, Kotwal PP. Arthritis associated with tuberculosis. Best Pract Res Clin Rheumatol 2003 common form of extrapulmonary TB, Apr;17(2):319-43. DOI: http://dx.doi.org/10.1016/ accounting for 10% to 19% of cases.3-5 s1521-6942(02)00126-2. Along with septic TB arthritis, nonsuppu- 4. Hunfeld KP, Rittmeister M, Wichelhaus TA, Brade V, Enzensberger R. Two cases of chronic arthritis of the rative reactive arthritis has been described forearm due to Mycobacterium tuberculosis. Eur J in association with TB, a condition that Clin Microbiol Infect Dis 1998 May;17(5):344-8. DOI: is also known as Poncet disease.6 Because http://dx.doi.org/10.1007/s100960050079. 5. Wollheim FA. Enteropathic arthritis. In: Kelley WN, of complicated and atypical presentations, Harris ED Jr, Ruddy S, Sledge CB, editors. Textbook this entity is likely to be underdiagnosed. of rheumatology. 5th ed. Phildelphia, PA: WB Moreover, few physicians know the dis- Saunders Co; 1997 Jan 15. p 1006-14. 6. Pereira JCB. [Artropatia de Poncet—série de casos]. ease well, and the literature related to [Article in Portuguese]. Pulmão RJ 2005;14(4):321-4. this disease is scarce and restricted to case 7. Bloxham CA, Addy DP. Poncet’s disease: para- reports, which probably contributes to its infective tuberculous polyarthropathy. Br Med J 1978 Jun 17;1(6127):1590. DOI: http://dx.doi.org/10.1136/ underdiagnosis. bmj.1.6127.1590. Figure 4. Timeline of history, relevant investigations, The diagnosis of Poncet disease is 8. Arora VK, Verma R. Tuberculous rheumatism and treatment of patient with Poncet disease. mainly clinical with exclusion of other (Poncet’s disease): three case reports. Indian J AFB = acid-fast bacillus; CECT = contrast-enhanced Tuberc 1991 Jan;38:229-30. causes. It generally presents as an acute computed tomography; FNAC = fine-needle aspiration or subacute form; however, chronic forms cytology; L = leukocytes; P = polymorphs; PCR = poly- have been described in the literature.4 merase chain reaction; TB = tuberculosis.

2 The Permanente Journal/Perm J 2016 Summer;20(3):15-199 CLINICAL MEDICINE Image Diagnosis: Encephalopathy Resulting from Dural Arteriovenous Fistula

Ana Filipa Santos, MD; Célia Machado, MD; Sara Varanda, MD; João Pinho, MD; Manuel Ribeiro, MD; Jaime Rocha, MD; Ricardo Maré, MD Perm J 2016 Summer;20(3):15-218 E-pub: 07/08/2016 http://dx.doi.org/10.7812/TPP/15-218

CASE REPORT A 69-year-old woman presented to the Neurology Department with 2 months of progressive psychomotor slowing, in- ability to concentrate, and periods of dis- orientation. Her past medical history was unremarkable, and she was taking no medi- cation. There was no history of trauma. On neurologic examination she was alert but taking a long time to answer, apathetic, distractable, and hypophonic with right visual and sensitive hemiextinction and left hemiparesis. Montreal Cognitive Assess- ment Exam score was 11/30. A computed tomography scan of the brain (Figure 1) showed possible convexity subarachnoid hemorrhage that the brain magnetic reso- Figure 1. Computed tomography scan of the brain showing possible convexity subarachnoid hemorrhage. nange imaging (MRI)/MRI angiography (Figures 2 and 3) revealed to be engorged cerebral vessels. Hyperintensity in the deep white matter of the cerebral hemispheres was also present. Cerebral angiography (Figure 4) revealed a dural arteriovenous fistula (DAVF) of the superior sagittal sinus and torcula (Cognard classification IIb1). The patient underwent endovascular embolization, with combined transarterial (n-butyl-cyanoacrylate) and transvenous (coils) approach, resulting in proximal occlusion of the superior sagital sinus, torcula, and transverse sinus (Figure 5). Posttreatment angiography revealed near complete DAVF occlusion (Figure 6). Con- trol MRI revealed a marked decrease of the deep white matter hyperintensity and no engorged cerebral veins (Figures 7 and 8). Figure 2. Coronal-view T2-weighted magnetic Figure 3. Axial-view T2-weighted magnetic resonance The patient’s mental status improved post resonance image of the brain. The white arrows image of the brain. The white crosses indicate the procedure (Montreal Cognitive Assessment indicate engorged cerebral veins visible over the increased signal that is diffusely present within the Exam score, 20/30), and she progressively surfaces of the hemispheres bilaterally. deep white matter of the cerebral hemispheres. came back to her baseline.

Ana Filipa Santos, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected] Célia Machado, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. Sara Varanda, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. João Pinho, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. Manuel Ribeiro, MD, is a Neuroradiologist at Centro Hospitalar de Vila Nova de Gaia-Espinho in Gaia, Portugal. E-mail: [email protected]. Jaime Rocha, MD, is a Neuroradiologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. Ricardo Maré, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-218 1 CLINICAL MEDICINE Image Diagnosis: Encephalopathy Resulting from Dural Arteriovenous Fistula

Figure 4. Cerebral angiography performed before Figure 5. Cerebral angiography performed after Figure 6. Posttreatment cerebral angiography endovascular embolization. The black arrowhead endovascular embolization. The black arrow shows near-complete occlusion of the dural indicates dural arteriovenous fistula of the superior indicates transvenous coils. arteriovenous fistula. sagittal sinus. The black asterisk indicates dural arteriovenous fistula of the torcula.

DISCUSSION acuity, seizures, Parkinsonism, cerebellar significant risk factors (trauma, hyperten- DAVFs are abnormal arteriovenous con- symptoms, apathy, and dementia.2-4 sion, or anticoagulation) or in possible sub- nections within the dura, usually located arachnoid hemorrhage in a nonaneurysmal within the walls of a dural sinus or an ad- CONCLUSION pattern. This should prompt imaging with jacent cortical vein, and account for 10% Our patient with DAVF presented with MRI and angiography, which are the gold to 15% of all intracranial arteriovenous encephalopathy with diffuse white matter standard for diagnosis. DAVF recognition lesions.2-4 The initiating events which lead changes related to venous ischemia. Her is essential because these patients are poten- to their development are not clear, but the symptoms partially reverted with endo- tially treatable. v literature reports association with trauma, vascular treatment. infection, recent surgery, and dural sinus DAVF should be considered in patients Disclosure Statement thrombosis.2-4 A wide variety of signs and with encephalopathy. This relatively non- The authors have no conflicts of interest to symptoms, which can vary because of lesion specific clinical picture may delay the diag- disclose. nosis and result in further deterioration. A location and pattern of venous drainage, How to Cite this Article may arise from DAVFs, namely, pulsatile high level of suspicion should be maintained Santos AF, Machado C, Varanda S, et al. Image tinnitus, ophthalmoplegia, proptosis, che- in patients who present in the context of un- diagnosis: Encephalopathy resulting from dural mosis, retro-orbital pain, decreased visual explained intracranial hemorrhage without arteriovenous fistula. Perm J 2016 Summer;20(3): 15-218. DOI: http://dx.doi.org/10.7812/TPP/15-218.

References 1. Cognard C, Gobin YP, Pierot L, et al. Cerebral dural arteriovenous fistulas: clinical and angiographic correlation with a revised classification of venous drainage. Radiology 1995 Mar;194(3):671-80. DOI: http://dx.doi.org/10.1148/radiology.194.3.7862961. 2. Gandhi D, Chen J, Pearl M, Huang J, Gemmete JJ, Kathuria S. Intracranial dural arteriovenous fistulas: classification, imaging findings, and treatment. AJNR Am J Neuroradiol 2012 Jun;33(6):1007-13. DOI: http://dx.doi.org/10.3174/ajnr.A2798. 3. Oh JT, Chung SY, Lanzino G, et al. Treatment of intracranial dural arteriovenous fistulas: clinical characteristics and management based on location and hemodynamics. J Cerebrovasc Endovasc Neurosurg 2012 Sep;14(3):192-202. DOI: http://dx.doi.org/10.7461/jcen.2012.14.3.192. 4. Vilela P, Goulão A. [Primary dural intracranial arteriovenous lesions]. [Article in Portuguese]. Figure 7. Posttreatment magnetic resonance image Figure 8. Posttreatment magnetic resonance image Acta Med Port 2003 May-Jun;16(3):171-8. of the brain showing no engorged cerebral veins. of the brain. The white cross indicates a marked decrease of the hyperintensity in the deep white matter of the cerebral hemisphere.

2 The Permanente Journal/Perm J 2016 Summer;20(3):15-218 CLINICAL MEDICINE Image Diagnosis: Pott Puffy Tumor

Diane Apostolakos, MD, MS; Ian Tang, MD Perm J 2016 Summer;20(3):15-157 E-pub: 06/24/2016 http://dx.doi.org/10.7812/TPP/15-157

CASE REPORT day 39. During hospitalization he was treated cranial surgery are the usual predisposing A 20-year-old man was admitted to with intravenous ampicillin and sulbactam factors; the majority of cases occurred in our hospital with complaints of frontal every 6 hours. At discharge, his treatment younger males. Culture results indicated headache, sinusitis, and fever for one week. was changed to oral metronidazole and the frequent pathogens were Streptococcus He had a history of allergic rhinitis and daily intravenous ceftriaxone via a central species (47%), anaerobic species (28%), recurrent sinus infections. At admission his catheter. He received a total of 3 months of and Staphylococcus aureus (22%). Almost temperature was 40˚C and his pulse rate antibiotic treatment and remained well after half of the cultures revealed mixed infec- was 140 beats per minute. On physical ex- the antibiotic treatment was completed. tions with more than one isolate. Epidural amination, the center of his forehead had a and subdural empyema were the most soft, tender, warm, swollen area that caused DISCUSSION frequently reported intracranial compli- an obvious bulge. The initial imaging Sir Percivall Pott (1714-1788), a sur- cations.5 study, a computed tomography scan, failed geon at St Bartholomew’s Hospital in Pott puffy tumor is treated with sur- to clearly show the intracranial pathology. London, first described Pott puffy tumor gery and antibiotics. Surgical treatment A magnetic resonance imaging study of the in 1760.3 It was called a tumor because includes drainage of the frontal sinus and patient’s head with intravenous contrast tumor refers to one of the four historic other areas of infection. Broad-spectrum revealed osteomyelitis of the frontal bone manifestations of inflammation noted by antibiotics that have good central nervous with localized swelling and underlying Aulus Cornelius Celsus (c 25 BC-c 50 system penetration must be started on epidural empyema (Figures 1 and 2). This AD): rubor (redness), tumor (swelling), diagnosis. Prolonged antibiotic treatment finding confirmed the diagnosis of Pott calor (warmth), and dolor (pain). Origi- is required after surgery because osteomy- puffy tumor, which is defined as forehead nally described as a complication of head elitis is usually present. v swelling, usually from the anterior exten- trauma, Pott puffy tumor typically occurs sion of frontal sinusitis, and associated as a complication of frontal sinusitis. The Disclosure Statement osteomyelitis of the frontal bone.1,2 extracranial manifestations frequently in- The author(s) have no conflicts of interest to The patient was seen by otorhinolaryn- clude subperiosteal or subgaleal abscesses. disclose. gology as well as neurosurgery; he declined Intracranial complications may include How to Cite this Article the recommended surgery and conse- epidural empyema, subdural empyema, Apostolakos D, Tang I. Image diagnosis: Pott puffy quently remained febrile with a maximum intraparenchymal abscess, cavernous sinus tumor. Perm J 2016 Summer;20(3):15-157. DOI: temperature of over 38˚C for 6 consecutive thrombosis, or meningitis.4 http://dx.doi.org/10.7812/TPP/15-157. days. He continued to have occasional fever A review of 53 cases of Pott puffy tumor5 spikes and was not discharged until hospital indicated that sinusitis, head trauma, or References 1. Bambakidis NC, Cohen AR. Intracranial complications of frontal sinusitis in children: Pott’s puffy tumor revisited. Pediatr Neurosurg 2001;35(2):82-9. DOI: http://dx.doi. org/10.1159/000050395. 2. Koch SE, Wintroub BU. Pott’s puffy tumor. A clinical marker for osteomyelitis of the skull. Arch Dermatol 1985;121(4):548-9. DOI: http://dx.doi.org/10.1001/ archderm.1985.01660040132029. 3. Pott P. Observations on the nature and consequences of wounds and contusions of the head, fractures of the skull, concussions of the brain, &c. London, England: Hitch & Hawes; 1760. p 22-58. 4. Wells RG, Sty JR, Landers AD. Radiological evaluation of Pott puffy tumor. JAMA 1986 Mar 14;255(10):1331-3. DOI: http://dx.doi.org/10.1001/ jama.1986.03370100125030. 5. Skomro R, McClean KL. Frontal osteomyelitis Figure 1. Sagittal-view magnetic resonance image Figure 2. Axial-view magnetic resonance image of (Pott’s puffy tumour) associated with Pasteurella of the cranium with intravenous contrast. The black the cranium with intravenous contrast. The black multocida—a case report and review of the literature. arrows indicate epidural empyema. The white arrow arrows indicate epidural empyema. The white arrow Can J Infect Dis 1998 Mar;9(2):115-21. indicates localized swelling. indicates localized swelling.

Diane Apostolakos, MD, MS, is a Hospitalist at the North Sacramento Medical Center in CA. E-mail: [email protected]. Ian Tang, MD, is a Physician at Apicha Community Health Center in New York, NY. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-157 1 CLINICAL MEDICINE Image Diagnosis: Tubo-ovarian Abscess with Hydrosalpinx

Kiersten L Carter, MD; Gus M Garmel, MD, FACEP, FAAEM Perm J 2016 Fall;20(4):15-211 E-pub: 06/24/2016 http://dx.doi.org/10.7812/TPP/15-211

Tubo-ovarian abscess (TOA) and hydro- The most useful diagnostic imaging metronidazole with doxycycline) can usu- salpinx are complications, though uncom- studies include transvaginal ultrasonog- ally be initiated within 24 hours to 48 hours mon, of pelvic inflammatory disease (PID). raphy and computed tomography. Com- of clinical improvement to complete the Both TOA and hydrosalpinx can lead to sig- pared with ultrasonography, computed 14-day treatment course.4 The majority of nificant morbidity and, rarely, mortality, and tomography has increased sensitivity to small abscesses (< 9 cm in diameter) resolve both necessitate treatment to reduce short- detect thick-walled, rim-enhancing adnexal with antibiotic therapy alone.1 and long-term complications. Risk factors of masses, pyosalpinx, and mesenteric strand- The aim of therapeutic management is TOA include younger age, multiple sexual ing, as well as changes suggestive of ruptured to be as noninvasive as possible. However, partners, nonuse of barrier contraception, TOA.1 On computed tomography scan with if this approach fails to yield clinical im- and a history of PID.1 The clinical manifes- contrast, a hydrosalpinx is visualized as a provement within 3 days, reassessment of tations of TOA are similar to PID—lower dilated, fluid-filled fallopian tube without the antibiotic regimen, with consideration abdominal pain, fever, chills, and vaginal rim enhancement (Figures 1 and 2). for laparoscopy, laparotomy, adnexectomy, discharge, with the addition of pelvic mass Although TOA is a complication of PID, hysterectomy, or image-guided abscess noted on examination or imaging. Women Neisseria gonorrhoeae and Chlamydia tracho- drainage is necessary.3,4 Because of its as- with TOA present with fever and chills matis are infrequently isolated from abscess sociation with shorter hospitalization and (50%), nausea (26%), vaginal discharge fluid. Instead, these organisms weaken improved pain control, image-guided per- (28%), abnormal vaginal bleeding (21%), normal host defenses, facilitating invasion cutaneous abscess drainage is an attractive and acute lower abdominal pain (89%).2 and infection of the upper genital tract by alternative to surgical intervention in the Women with a presentation consistent the lower genital tract flora.1 Treatment for management of TOA.3 The clinician should with TOA should be evaluated with a com- TOA includes inpatient admission for in- inform, evaluate, test, and treat the patient’s plete history; pelvic examination; laboratory travenous antibiotics to target polymicrobial sexual partners. v testing for complete blood count, eryth- organisms likely to produce TOA—Esch- rocyte sedimentation rate, and C-reactive erichia coli, aerobic streptococci, Prevotella, Disclosure Statement protein; cervical testing for gonorrhea and Bacterioides fragilis, and Peptostreptococcus.3 The author(s) have no conflicts of interest to chlamydia; and pregnancy testing to guide Cephamycin or cefotetan and doxycycline disclose. antimicrobial therapy.3 In severe cases, TOA or gentamicin and clindamycin are pre- can rupture and leak, causing sepsis. This ferred, although local antibiotic resistance How to Cite this Article increases mortality and requires emergent patterns should be considered.4 Transi- Carter KL, Garmel GM. Image diagnosis: Tubo-ovarian abscess with hydrosalpinx. Perm J Fall;20(4):15-211. surgical intervention. tion to oral antibiotics (clindamycin or DOI: http://dx.doi.org/10.7812/TPP/15-211.

References 1. Lareau SM, Beigi RH. Pelvic inflammatory disease and tubo-ovarian abscess. Infect Dis Clin North Am 2008 Dec;22(4):693-708. DOI: http://dx.doi. org/10.1016/j.idc.2008.05.008. 2. Landers DV, Sweet RL. Tubo-ovarian abscess: contemporary approach to management. Review of Infectious Diseases 1983 Sep;5(5):876-84. 3. Granberg S, Gjelland K, Ekerhovd E. The management of pelvic abscess. Best Pract Res Clin Obstet Gynaecol 2009 Oct;23(5):667-78. DOI: http:// dx.doi.org/10.1016/j.bpobgyn.2009.01.010. 4. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guideline, 2015. MMWR Recomm Rep 2015 Jun 5;64(RR-03):78-83. Erratum in: Figure 1. Axial-view computed tomography scan of Figure 2. Cross-sectional computed tomography MMWR Recomm Rep 2015 Aug 28;64(33):924. the abdomen and pelvis. The long arrow indicates scan of the abdomen and pelvis. The arrow indi- left-sided hydrosalpinx. The short arrow indicates cates the left-sided tubo-ovarian abscess. the associated tubo-ovarian abscess.

Kiersten L Carter, MD, is an Emergency Medicine Resident Physician at the Stanford/Kaiser Emergency Medicine Residency Program in CA. Gus M Garmel, MD, FACEP, FAAEM, is a Senior Emergency Physician at the Santa Clara Medical Center, Co-Program Director of the Stanford/Kaiser Emergency Medicine Residency Program, and Clinical Professor (Affiliate) of Surgery (Emergency Medicine) at Stanford University in CA. He is also a Senior Editor for The Permanente Journal. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Fall;20(4):15-211 1 CLINICAL MEDICINE Image Diagnosis: Gastric Migration of Hookworms in a Patient with Anemia

Chalapathi Rao Achanta, MD Perm J 2016 Summer;20(3):15-201 E-pub: 06/24/2016 http://dx.doi.org/10.7812/TPP/15-201

CASE REPORT infected population remain asymptomatic, worm burden.8 Treatment includes either a A 65-year-old man presented to our 10% of those infected suffer from anemia,4 single dose of oral albendazole 400 mg or hospital with 4 months of fatigue and bringing them to medical attention. Infesta- oral mebendazole 100 mg twice daily for 3 weakness. He denied any bleeding mani- tion impairs the physical, intellectual, and days. Treatment success ranges from 69% festations and had pallor on examination. nutritional development of children.4 to 92% depending on the regimen used.9 Laboratory test results showed hemoglobin The adult female hookworm releases eggs, Concomitant iron therapy is necessary to of 8.2 gm/dL with microcytosis and low which are passed in stool. Rhabditiform replace lost iron stores.5 v iron stores. There was no peripheral eosin- larvae are released in soil after hatching and ophilia. Liver and renal function tests were undergo two molts before reaching an infec- Disclosure Statement normal. Upper endoscopy was ordered for tive third-stage filariform larvae. These larvae The author(s) have no conflicts of interest to evaluation of iron deficiency anemia. can survive for 3 to 4 weeks in contaminated disclose. The patient’s esophagus was normal, but soil under favorable climate conditions. They How to Cite this Article there were motile hookworms in the gas- penetrate human skin upon contact and Achanta CR. Image diagnosis: Gastric migration of tric antrum (Figure 1) and heavy loads of reach the lungs through the heart via blood hookworms in a patient with anemia. Perm J 2016 hookworms in the duodenum (Figure 2). circulation. Once these larvae penetrate the Summer;20(3):15-201. DOI: http://dx.doi.org/ His stool examination showed hookworm pulmonary alveoli, they ascend the bronchus 10.7812/TPP/15-201. eggs. The patient received 400 mg of to the pharynx. From there they are swal- oral albendazole therapy along with iron lowed and reach the small intestine, where References therapy. At 3-month follow-up, his anemia they mature to adult worms. 1. Chakma T, Rao PV, Tiwary RS. Prevalence of anaemia and worm infestation in tribal areas of Madhya was corrected, and he was symptom free. Adult hookworms inhabit the small in- Pradesh. J Indian Med Assoc 2000 Sep;98(9):567-71. testine and ingest intestinal epithelial and 2. Mahajan M, Mathur M, Talwar V, Revathi G. Prevalence DISCUSSION red blood cells, causing iron-deficiency of intestinal parasitic infestation in east Delhi. Indian J Community Med 1993 Oct-Dec;18(4):177-80. Ancylostoma duodenale and Necator anemia. On average, daily intestinal blood 3. Pal D, Chattopadhyay UK, Sengupta G. A study on americanus are the common species of loss is estimated to be between 0.01 mL to the prevalence of hookworm infection in four districts hookworm that attach to the small intes- 0.3 mL depending on the parasite species.5 of West Bengal and its linkage with anaemia. Indian J Pathol Microbiol 2007 Apr;50(2):449-52. tinal mucosa. Some 570 million to 740 Very rarely, these worms migrate and reach 4. Haburchak DR, Dhawan VK, Watson CM, million people are estimated to be infected the gastric antrum.6,7 According to Thomas Chandrasekar PH. Hookworm disease: background with hookworms worldwide, and infection et al, retrograde jejuno-duodenogastric [Internet]. New York, NY: WebMD LLC; 2014 May 12 [cited 2016 Jan 21]. Available from: http://emedicine. rates in India range from 16% to 30% of the reflux results in the gastric migration of medscape.com/article/218805-overview. population.1-3 Although the majority of the the hookworms, especially in cases of high 5. Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology/diagnosis/management. 9th ed. Philadelphia, PA: Saunders Elsevier; 2010. 6. Dumont A, Seferian V, Barbier P. Endoscopic discovery and capture of Necator americanus in the stomach. Endoscopy 1983 Mar;15(2):65-6. DOI: http://dx.doi.org/10.1055/s-2007-1021467. 7. Boopathy V, Balasubramanian P, Phansalkar M, Varghese RG. Endoscopic (video) demonstration of hookworm infestation of the stomach. BMJ Case Rep 2014 May 30;2014. DOI: http://dx.doi.org/10.1136/ bcr-2014-204065. 8. Thomas V, Jose T, Harish K, Kumar S. Hookworm infestation of antrum of stomach. Indian J Gastroenterol 2006 May-Jun;25(3):154. 9. Steinmann P, Utzinger J, Du ZW, et al. Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and Taenia spp: a randomized controlled trial. PLoS One Figure 1. Upper endoscopy of the distal gastric Figure 2. Upper endoscopy of the duodenum, 2011;6(9):e25003. DOI: http://dx.doi.org/10.1371/ antrum, showing hookworms (black arrow) close to showing hookworms attached to the duodenal journal.pone.0025003. the pylorus (white asterisk). mucosa.

Chalapathi Rao Achanta, MD, is a Gastroenterologist at Queen’s NRI Hospital in Visakhapatnam, India. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-201 1 CLINICAL MEDICINE Image Diagnosis: Encephalopathy Resulting from Dural Arteriovenous Fistula

Ana Filipa Santos, MD; Célia Machado, MD; Sara Varanda, MD; João Pinho, MD; Manuel Ribeiro, MD; Jaime Rocha, MD; Ricardo Maré, MD Perm J 2016 Summer;20(3):15-218 E-pub: 07/08/2016 http://dx.doi.org/10.7812/TPP/15-218

CASE REPORT A 69-year-old woman presented to the Neurology Department with 2 months of progressive psychomotor slowing, in- ability to concentrate, and periods of dis- orientation. Her past medical history was unremarkable, and she was taking no medi- cation. There was no history of trauma. On neurologic examination she was alert but taking a long time to answer, apathetic, distractable, and hypophonic with right visual and sensitive hemiextinction and left hemiparesis. Montreal Cognitive Assess- ment Exam score was 11/30. A computed tomography scan of the brain (Figure 1) showed possible convexity subarachnoid hemorrhage that the brain magnetic reso- Figure 1. Computed tomography scan of the brain showing possible convexity subarachnoid hemorrhage. nange imaging (MRI)/MRI angiography (Figures 2 and 3) revealed to be engorged cerebral vessels. Hyperintensity in the deep white matter of the cerebral hemispheres was also present. Cerebral angiography (Figure 4) revealed a dural arteriovenous fistula (DAVF) of the superior sagittal sinus and torcula (Cognard classification IIb1). The patient underwent endovascular embolization, with combined transarterial (n-butyl-cyanoacrylate) and transvenous (coils) approach, resulting in proximal occlusion of the superior sagital sinus, torcula, and transverse sinus (Figure 5). Posttreatment angiography revealed near complete DAVF occlusion (Figure 6). Con- trol MRI revealed a marked decrease of the deep white matter hyperintensity and no engorged cerebral veins (Figures 7 and 8). Figure 2. Coronal-view T2-weighted magnetic Figure 3. Axial-view T2-weighted magnetic resonance The patient’s mental status improved post resonance image of the brain. The white arrows image of the brain. The white crosses indicate the procedure (Montreal Cognitive Assessment indicate engorged cerebral veins visible over the increased signal that is diffusely present within the Exam score, 20/30), and she progressively surfaces of the hemispheres bilaterally. deep white matter of the cerebral hemispheres. came back to her baseline.

Ana Filipa Santos, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected] Célia Machado, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. Sara Varanda, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. João Pinho, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. Manuel Ribeiro, MD, is a Neuroradiologist at Centro Hospitalar de Vila Nova de Gaia-Espinho in Gaia, Portugal. E-mail: [email protected]. Jaime Rocha, MD, is a Neuroradiologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected]. Ricardo Maré, MD, is a Neurologist at Hospital de Braga in Braga, Portugal. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-218 1 CLINICAL MEDICINE Image Diagnosis: Encephalopathy Resulting from Dural Arteriovenous Fistula

Figure 4. Cerebral angiography performed before Figure 5. Cerebral angiography performed after Figure 6. Posttreatment cerebral angiography endovascular embolization. The black arrowhead endovascular embolization. The black arrow shows near-complete occlusion of the dural indicates dural arteriovenous fistula of the superior indicates transvenous coils. arteriovenous fistula. sagittal sinus. The black asterisk indicates dural arteriovenous fistula of the torcula.

DISCUSSION acuity, seizures, Parkinsonism, cerebellar significant risk factors (trauma, hyperten- DAVFs are abnormal arteriovenous con- symptoms, apathy, and dementia.2-4 sion, or anticoagulation) or in possible sub- nections within the dura, usually located arachnoid hemorrhage in a nonaneurysmal within the walls of a dural sinus or an ad- CONCLUSION pattern. This should prompt imaging with jacent cortical vein, and account for 10% Our patient with DAVF presented with MRI and angiography, which are the gold to 15% of all intracranial arteriovenous encephalopathy with diffuse white matter standard for diagnosis. DAVF recognition lesions.2-4 The initiating events which lead changes related to venous ischemia. Her is essential because these patients are poten- to their development are not clear, but the symptoms partially reverted with endo- tially treatable. v literature reports association with trauma, vascular treatment. infection, recent surgery, and dural sinus DAVF should be considered in patients Disclosure Statement thrombosis.2-4 A wide variety of signs and with encephalopathy. This relatively non- The authors have no conflicts of interest to symptoms, which can vary because of lesion specific clinical picture may delay the diag- disclose. nosis and result in further deterioration. A location and pattern of venous drainage, How to Cite this Article may arise from DAVFs, namely, pulsatile high level of suspicion should be maintained Santos AF, Machado C, Varanda S, et al. Image tinnitus, ophthalmoplegia, proptosis, che- in patients who present in the context of un- diagnosis: Encephalopathy resulting from dural mosis, retro-orbital pain, decreased visual explained intracranial hemorrhage without arteriovenous fistula. Perm J 2016 Summer;20(3): 15-218. DOI: http://dx.doi.org/10.7812/TPP/15-218.

References 1. Cognard C, Gobin YP, Pierot L, et al. Cerebral dural arteriovenous fistulas: clinical and angiographic correlation with a revised classification of venous drainage. Radiology 1995 Mar;194(3):671-80. DOI: http://dx.doi.org/10.1148/radiology.194.3.7862961. 2. Gandhi D, Chen J, Pearl M, Huang J, Gemmete JJ, Kathuria S. Intracranial dural arteriovenous fistulas: classification, imaging findings, and treatment. AJNR Am J Neuroradiol 2012 Jun;33(6):1007-13. DOI: http://dx.doi.org/10.3174/ajnr.A2798. 3. Oh JT, Chung SY, Lanzino G, et al. Treatment of intracranial dural arteriovenous fistulas: clinical characteristics and management based on location and hemodynamics. J Cerebrovasc Endovasc Neurosurg 2012 Sep;14(3):192-202. DOI: http://dx.doi.org/10.7461/jcen.2012.14.3.192. 4. Vilela P, Goulão A. [Primary dural intracranial arteriovenous lesions]. [Article in Portuguese]. Figure 7. Posttreatment magnetic resonance image Figure 8. Posttreatment magnetic resonance image Acta Med Port 2003 May-Jun;16(3):171-8. of the brain showing no engorged cerebral veins. of the brain. The white cross indicates a marked decrease of the hyperintensity in the deep white matter of the cerebral hemisphere.

2 The Permanente Journal/Perm J 2016 Summer;20(3):15-218 NURSING RESEARCH & PRACTICE Future Challenges of Robotics and Artificial Intelligence in Nursing: What Can We Learn from Monsters in Popular Culture?

Henrik Erikson, RNT, PhD; Martin Salzmann-Erikson, RN, MHN, PhD Perm J 2016 Summer;20(3):15-243 E-pub: 07/15/2016 http://dx.doi.org/10.7812/TPP/15-243

ABSTRACT cyborgs (empathic protocols). From It is highly likely that artificial intelligence (AI) will be implemented in nursing robotics this perspective, we ask the question of in various forms, both in medical and surgical robotic instruments, but also as different whether monsters can help us relate to types of droids and humanoids, physical reinforcements, and also animal/pet robots. AI and to nursing robots. Exploring and discussing AI and robotics in nursing and health care before these tools become commonplace is of great importance. We propose that monsters in popular LINK BETWEEN MONSTERS AND culture might be studied with the hope of learning about situations and relationships ARTIFICIAL INTELLIGENCE that generate empathic capacities in their monstrous existences. The aim of the article Monsters do relate to robotics and some- is to introduce the theoretical framework and assumptions behind this idea. Both robots times to “evil” machines that combine the and monsters are posthuman creations. The knowledge we present here gives ideas two into one appearance. One example in about how nursing science can address the postmodern, technologic, and global world popular culture is found in the Termina- to come. Monsters therefore serve as an entrance to explore technologic innovations tor film series, in which machines have such as AI. Analyzing when and why monsters step out of character can provide im- reached far beyond the point that is often portant insights into the conceptualization of caring and nursing as a science, which is referred to as technologic singularity.13,14 important for discussing these empathic protocols, as well as more general insight into Technologic singularity is a critical mo- human knowledge. The relationship between caring, monsters, robotics, and AI is not ment, a point when AI surpasses biological as farfetched as it might seem at first glance. intelligence. In the Terminator series, the machines develop, improve, and reproduce INTRODUCTION relating to empathic abilities in posthu- themselves without human involvement, It is highly likely that artificial intelli- man creations. Cataloging and analyzing and their goal is to drive their creators— gence (AI) will be implemented in medi- situations in which monster characters the humans—to extinction. cal technologic equipment for clinical actually become nurturing and caring However, in the 1940s, Isaac Asimov15 monitoring and decision making.1,2 This can be important for understanding how wrote Runaround, in which he developed change will probably happen rapidly and humans care as well as for understanding the Laws of Robotics: on a global scale, because digitalization care in relation to posthuman venues. Are 1. A robot may not injure a human being, and globalization are intensely connected these situations of protection, sheltering, or through inaction, allow a human be- via the Internet.3,4 For this reason, the or friendship? Questions about empathy ing to come to harm ethics of robotics and AI must be well in relation to robotics and AI have been 2. A robot must obey the orders given it by developed for these posthuman creations addressed by researchers. Usually, this re- human beings, except where such orders to make decisions within the frame of lationship is presented from the perspec- would conflict with the First Law acceptable human ethics and values of tive of humans’ empathy for robots.11,12 3. A robot must protect its own existence as nursing.5 One paradox is the question of However, the dimension we are interested long as such protection does not conflict how we can understand and explore these in is the reverse: the empathic capacities with the First or Second Law 15p44-5 AIs before we must embrace them as facts that robotics and AI can demonstrate for 4. (Added later, known as the zeroth law): in everyday health care services.6-9 humans. The knowledge generated will No robot may harm humanity or, Monsters in popular culture could be bring clues as to what the relationship is through inaction, allow humanity to scrutinized with the hope of learning between empathy and AI and will con- come to harm.16 about situations that generate empathic tribute to our understanding so that it We are entering an era when the vast capacities.10 If everyone who encounters will be useful for a future where the im- digitalization of health care in everyday a fictional monster—in a book, play, pact of digitalization has to be taken into life and the fictional Laws of Robotics just motion picture, or video game—and account in nursing/caring theories. This presented are discussed as reality.17 Health who engages in caring activities reported is one attempt to capture understanding care institutions and the nursing discipline their observations, together these obser- about empathic intelligences in virtual face paradigmatic changes that are related vations might show important patterns creations, that is, robots, machines, and to digital technology. For the discipline of

Henrik Erikson, RNT, PhD, is a Professor in Nursing at the Department of Nursing and Care at The Swedish Red Cross University College in Stockholm, Sweden. E-mail: [email protected]. Martin Salzmann-Erikson, RN, MHN, PhD, is an Associate Professor in Nursing of Health and Occupational Studies in the Department of Health and Caring Sciences at the University of Gävle in Sweden. E-mail: [email protected].

The Permanente Journal/Perm J 2016 Summer;20(3):15-243 1 NURSING RESEARCH & PRACTICE Future Challenges of Robotics and Artificial Intelligence in Nursing: What Can We Learn from Monsters in Popular Culture?

nursing, the relationship to technology and expression.26 More generally, monsters ask ourselves and improving our understand- AI is sparse, so these changes will represent us why we created them.26 Maybe for that ing of AI and robotics. a giant leap. We argue that it is also highly reason, popular culture is full of monsters What we can see in our project Car- relevant and timely for nursing science to in TV series, books, and movies. ing Monsters34 so far is that monsters are monitor and to debate AI and Robotics in the same fashion as other areas, such as medicine. Monsters represent our fears, and they stand on the threshold The International Robot Fair16 con- of human becoming, always representing “the other.” These cluded with a World Robot Declaration representations suggest that monsters ask us how we perceive proposition that next-generation robots the world; they ask us to reevaluate our cultural assumptions will 1) be partners that coexist with hu- about ethnicity, gender and sexuality, our perception of man beings, 2) assist human beings both difference, and our tolerance toward expression physically and psychologically, and 3) contribute to the realization of a safe and peaceful society. Even though robots These representations in popular cul- not doomed to uphold their monstrous equipped with AI in popular culture often ture have the potential to contribute characters. They reshape their existence are portrayed as embodied monsters, this to scholarly knowledge in relation to and meaning over time. A monster as might not be the reality in the near future. the challenges we are facing in nursing “the other” is not a fixed position, nor However, and more importantly, AI is because of digitalization. Autonomous is the position unchangeable in relation developing rapidly, and several research personal robots for private use are enter- to humans. For example, our fear of projects predict that technologic singu- ing the general market in 2016.27 Au- the power of science, as represented by larity is no more than 30 years away.18 tonomous personal robots will have the Frankenstein’s monster, has shifted over Today’s robots are starting to be imple- capability to recognize faces, take part nearly 200 years from being the epitome mented in health care facilities, in forms in conversations, adapt to new environ- of all monsters to the superhero.35 Our such as surgical robots19 and in nursing ments, and make their own decisions on fear of technology and AI as represented homes.20 As posited in the World Robot the basis of their own AI. AI has taken a in the Terminator film-series shows an Declaration, next-generation robots assist giant leap compared with mobile personal evolution from killing machine to con- humans physically. One important aspect assistants such as Siri (Apple, Cupertino, scientious protector.13 Fear of the col- of AI and robotics for nursing is that CA) and Assistant (Speaktoit Inc, Palo lapse of a given society, as represented by nurses might be firsthand partners, work- Alto, CA) or similar tools. Although the zombies in current popular culture, has ing in nursing in institutions with robots robot may seem impressive and appears shifted in just a few decades from being in the near future. Nurses might interact to create safety, the robot is not in itself the problem to representing the solution with household robots in patients’ homes particularly intelligent, which is why we for humanity, as represented in the book rather than with the patients themselves. must distinguish between the robot as a and film “Warm Bodies” and the British technical tool and its ability to make its TV series “In the Flesh.”36 The ability to CHALLENGES OF ROBOTICS AND own decisions.28,29 Exploring and elabo- doubt is visualized and highlighted as ARTIFICIAL INTELLIGENCE IN NURSING rating on robots and AI is highly relevant crucial when monsters step out of char- Even if there is a connection between and timely for nursing research. acter in popular culture. The ability to monsters and robots, one does not ordi- doubt seems to be a cornerstone when narily think of monsters and nursing in IMPLICATIONS FOR NURSING PRACTICE giving caring attributes to the monsters. the same framework, nor of robotics and When various nursing robots become We therefore assume that monsters do empathy. The relationship between car- common practice in institutional settings, not exist as separate entities in nature; ing monsters, robotics, and AI is not as they will have a major impact on nursing rather, they are socially constructed in, farfetched as it might seem at first glance. work, the nursing profession, and health for example, colloquial speech in everyday Both robots and monsters are posthuman care in general.30,31 Nursing robots will conversations and manifested throughout creations.21 Just like the robot, monsters redefine ideas about nurses in general as popular culture, where they are narrated are also connected to cultural and historic well as ideas about nursing attributes and in texts or depicted in movies. contexts.22 Monsters represent our fears, conceptual frameworks of comfort and In the future of nursing robotics, ques- and they stand on the threshold of hu- safety in particular.32,33 Staying abreast tions of empathic protocols should be man becoming, always representing “the of developments regarding redefinitions explored further. Analyzing when and in- other.”23-25 These representations suggest of nursing and its underlying beliefs, val- terpreting why monsters step out of char- that monsters ask us how we perceive ues, and assumptions is relevant to also acter can provide important insight into the world; they ask us to reevaluate our understanding the implications of AI the conceptualization of caring and nurs- cultural assumptions about ethnicity, and robots in health care. We therefore ing as a science, insight that is important gender and sexuality, our perception state that we can turn to monsters and for discussing these empathic protocols of difference, and our tolerance toward their evolutionary existence for preparing and, more generally, human knowledge.20

2 The Permanente Journal/Perm J 2016 Summer;20(3):15-243 NURSING RESEARCH & PRACTICE Future Challenges of Robotics and Artificial Intelligence in Nursing: What Can We Learn from Monsters in Popular Culture?

It is important to address the issue that 6. Nejat G, Nies MA, Sexton TR. An interdisciplinary Int J Soc Robot 2014 Nov;6(4):575-91. DOI: http:// team for the design and integration of assistive dx.doi.org/10.1007/s12369-014-0242-2. monsters are creations of storytellers and robots in health care applications. Home Health Care 21. Duffy BR. Anthropomorphism and the social writers who have their own ideas and mes- Manag Pract 2010 Feb;22(2):104-10. DOI: http:// robot. Robotics and Autonomous Systems sages about AI and robotics. However, the dx.doi.org/10.1177/1084822309331575. 2003 Mar 31;42(3-4):177-90. DOI: http://dx.doi. 7. Lupton D. M-health and health promotion: the digital org/10.1016/s0921-8890(02)00374-3. storytellers’ motivations are not necessar- cyborg and surveillance society. Soc Theory Health 22. Hutton I, Joy F, MacDonald MR, Sherman J, Smith S, ily the same as the readers’ and viewers’ 2012;10:229-44. DOI: http://dx.doi.org/10.1057/ de Vos G. Introduction. In: Sherman J, editor. ideas, nor the larger social interpretations sth.2012.6. Storytelling: an encyclopedia of mythology and 8. Huang Z, Katayama T, Kanai-Pak M, et al. Design folklore. New York, NY: M.E. Sharpe; 2008. that the monster itself creates. In other and evaluation of robot patient for nursing skill p xvii-xxix. words, the writers’ and creators’ motiva- training in patient transfer. Adv Robot 2015; 23. Haraway D. The promises of monsters: a tions do not always match with the ideas 29(19):1269-85. DOI: http://dx.doi.org/10.1080/ regenerative politics for inappropriate/d others. In: 01691864.2015.1052012. Grossberg L, Nelson C, Treichler P, editors. Cultural their work provokes. We can apply this 9. Lattanzio F, Abbatecola AM, Bevilacqua R, et al. studies. New York, NY: Routledge; 1992. p 295-337. logic in the context of AI; the motivation Advanced technology care innovation for older 24. Haraway DJ. Primate visions: gender, race, and behind researchers creating AI might not people in Italy: necessity and opportunity to promote nature in the world of modern science. New York, NY: health and wellbeing. J Am Med Dir Assoc 2014 Routledge, Chapman & Hall, Inc; 1989. be the same as the interpretation of the Jul;15(7):457-66. DOI: http://dx.doi.org/10.1016/j. 25. Haraway DJ. Simians, cyborgs, and women: the resulting AI itself. Monsters exist outside jamda.2014.04.003. reinvention of nature. New York, NY: Routledge; and beyond storytellers’ and writers’ mo- 10. Monster [Internet]. Springfield, MA: Merriam-Webster, 1991. Incorporated; c2015 [cited 2015 Oct 2]. Available 26. Cohen JJ. Monster culture (seven theses). In: tivations. For this reason, we have chosen from: www.merriam-webster.com/dictionary/monster. Cohen JJ, editor. Monster theory: reading culture. to look at the monsters themselves, not 11. Riek LD, Rabinowitch TC, Chakrabarti B, Robinson P. Minneapolis, MN: University of Minnesota Press; the creators’ motivations and intentions. Empathizing with robots: fellow feeling along the 1996. p 3-25. anthropomorphic spectrum. In: 2009 3rd International 27. Tobe F. 2016 will be a pivotal year for social robots By stating this, we recognize the under- Conference on Affective Computing and Intelligent [Internet]. Santa Barbara, CA: The Robot Report; standing of reality as the projection of an Interaction and Workshops; 2009 Sep 10-12; 2015 Dec 13 [cited 2016 Apr 20]. Available from: ongoing construction and reconstruction Amsterdam, The Netherlands. Piscataway, NJ: www.therobotreport.com/news/2016-will-be-a-big- Institute of Electrical and Electronics Engineers; year-for-social-robots. from the points of reference that we ex- 2009. p 1-6. DOI: http://dx.doi.org/10.1109/ 28. Sandry E. Re-evaluating the form and communication perience through life and that doubt and ACII.2009.5349423. of social robots: the benefits of collaborating self-negotiation are vital human values 12. Riek LD, Rabinowitch TC, Chakrabarti B, with machinelike robots. Int J Soc Robot 2015 Robinson P. How anthropomorphism affects empathy Jun;7(3):335-46. DOI: http://dx.doi.org/10.1007/ that also seem to be crucial in the evolu- toward robots. In: Proceedings of the 4th ACM/ s12369-014-0278-3. tionary history of monsters. v IEEE International Conference on Human Robot 29. Haring KS, Matsumoto Y, Watanabe K. How Interaction; 2009 Mar 10-13; New York, NY. New do people perceive and trust a lifelike robot? York, NY: ACM; 2009. p 245-6. Proceedings of the International Conference on Disclosure Statement 13. Bennett E. Deus ex machina: AI apocalypticism Intelligent Automation and Robotics (ICIAR’13); 2013 The author(s) have no conflicts of interest to in Terminator: The Sarah Connor Chronicles. The Oct 23-25; San Francisco, CA. Hong Kong, China: disclose. Journal of Popular Television 2014 Apr 1;2(1):3-19. World Congress on Engineering and Computer DOI: http://dx.doi.org/10.1386/jptv.2.1.3_1. Science; 2013. 14. Vinge V. The coming technological singularity: How to Cite this Article 30. Sandelowski M. Troubling distinctions: a semiotics of how to survive in the post-human era [Internet]. the nursing/technology relationship. Nurs Inq 1999 Erikson H, Salzmann-Erikson M. Future challenges Proceeding of Vision-21: Interdisciplinary Science Sep;6(3):198-207. DOI: http://dx.doi.org/10.1046/ of robotics and artificial intelligence in nursing: and Engineering in the Era of Cyberspace; 1993 j.1440-1800.1999.00030.x. What can we learn from monsters in popular Mar 30-31; Westlake, OH. Cleveland, OH: NASA 31. Sandelowski M. Visible humans, vanishing culture? Perm J 2016 Summer;20(3):15-243. Lewis Research Center; 1993 Dec 1 [cited 2015 bodies, and virtual nursing: complications of life, Sep 16]. Available from: http://ntrs.nasa.gov/search. DOI: http://dx.doi.org/10.7812/TPP/15-243. presence, place, and identity. ANS Adv Nurs jsp?R=19940022855. Sci 2002 Mar;24(3):58-70. DOI: http://dx.doi. 15. Asimov I. Runaround. Astounding Science Fiction org/10.1097/00012272-200203000-00007. 1942 Mar. 32. Sandelowski M. Culture, conceptive technology, and References 16. Veruggio G. Euron roboethics roadmap [Internet]. 1. Hanson CW 3rd, Marshall BE. Artificial intelligence nursing. Int J Nurs Stud 1999 Feb;36(1):13-20. DOI: Proceedings of the EURON Roboethics Atelier; 2006 http://dx.doi.org/10.1016/s0020-7489(98)00048-0. applications in the intensive care unit. Crit Care Feb 27-Mar 3; Genoa, Italy. Heverlee, Belgium: Med 2001 Feb;29(2):427-35. DOI: http://dx.doi. 33. Salzmann-Erikson M, Eriksson H. The rise of EURON; 2006 [cited 2015 Sep 16]. Available the avatar: virtual dimensions of ‘the human’ org/10.1097/00003246-200102000-00038. from: www.roboethics.org/atelier2006/docs/ 2. Schweikard A, Ernst F. Medical robotics. Cham, in nursing science. Nordic Journal of Nursing ROBOETHICS%20ROADMAP%20Rel2.1.1.pdf. Research 2015 Sep;35(3):158-64. DOI: http://dx.doi. Switzerland: Springer International Publishing; 2015. 17. Iosa M, Morone G, Cherubini A, Paolucci S. The DOI: http://dx.doi.org/10.1007/978-3-319-22891-4. org/10.1177/0107408315589462. three laws of neurorobotics: a review on what 34. www.caringmonsters.com [Internet]. Stockholm, 3. Parks JA. Lifting the burden of women’s care work: neurorehabilitation robots should do for patients and should robots replace the “human touch”? Hypatia Sweden: CaringMonsters.com; 2015 May 27 [cited 2016 clinicians. J Med Biol Eng 2016;36:1-11. Apr 20]. Available from: www.caringmonsters.com. 2010 Winter;25(1):100-20. DOI: http://dx.doi. 18. Kurzweil R. The singularity is near: when humans org/10.1111/j.1527-2001.2009.01086.x. 35. Shelly M. Frankenstein; or, the modern Prometheus. transcend biology. New York, NY: Penguin Group; Berkshire, United Kingdom: Cox & Wyman; 1994. 4. Pfadenhauer M, Dukat C. Robot caregiver or robot- 2005. 36. Mitchell D. In the Flesh. [television series]. London, supported caregiving? The performative deployment 19. Ashford H, Hunter A, Phung C, Coustasse A. Use of the social robot PARO in demetia care. Int J Soc United Kingdom: BBC Drama Productions; 2013 Mar of robots on cardiac surgery [Internet]. Proceedings 17-2014 Jun 8. Robot 2015 Jun;7(3):393-406. DOI: http://dx.doi. of the AABRI International Conference; 2015 org/10.1007/s12369-015-0284-0. Jan 1-3; Orlando, FL. Huntington, WV: Marshall 5. Fleming G. Nurses will be replaced by evil robots— University; 2015 [cited 2015 Oct 19]. Available you have been warned [Internet]. London, England: from: http://mds.marshall.edu/cgi/viewcontent. Nursing Times; 2009 Oct 30 [cited 2016 Apr 5]. cgi?article=1119&context=mgmt_faculty. Available from: www.nursingtimes.net/nurses- 20. Robinson H, MacDonald B, Broadbent E. The role of will-be-replaced-by-evil-robots-you-have-been- healthcare robots for older people at home: a review. warned/5007966.fullarticle.

The Permanente Journal/Perm J 2016 Summer;20(3):15-243 3 Perm J 2016 Summer;20(3) Physicians may earn up to 1 AMA PRA Category 1 CreditTM per article for reading and analyzing the designated CME ar- ticles published in each edition of TPJ. Each edition has four articles available for review. Other clinicians for whom CME is acceptable in meeting educational requirements may report up to four hours of participation. The CME evaluation form may be completed online or via mobile Web at www.tpjcme.org. The Certification of Credit will be e-mailed immediately This form is also available online: www.thepermanentejournal.org upon successful completion. Alternatively, this paper form may be completed and returned via fax or mail to the address listed below. All Sections must be completed to receive credit. Certification of Credit will be mailed within two months of Summer 2016 receipt of the paper form. Completed forms will be accepted until November 2017. To earn CME for reading each article designated for AMA PRA Category 1 Credit, you must: • Score at least 50% in the posttest CME Evaluation Program • Complete the evaluation and provide your contact information

Section A. Article 1. (page 18) A Pharmacist-Staffed, Virtual Gout Management Clinic Article 3. (page 57) Evidence-Based Workflows for Thyroid and Parathyroid Surgery for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial What is the recommended goal for urate-lowering therapy in patients with chronic, When considering the risk stratification of a thyroid nodule by ultrasound, which nodule recurrent gout? should undergo a biopsy? a. a serum uric acid level < 7.0 mg/dL a. purely cystic or spongiform b. an allopurinol dose of 300 mg/d b. < 1.5 cm nodule that is not suspicious c. a serum uric acid level < 6.8 mg/dL c. < 1 cm nodule that is suspicious and no high risk factors d. a serum uric acid level < 6.0 mg/dL d. > 1 cm nodule that is suspicious or any nodule > 1.5 cm Which of the following statements is false about urate-lowering therapy in patients with gout? When performing a preoperative voice assessment on a patient undergoing thyroid a. adherence rates to urate-lowering therapy are low compared with many other or parathyroid surgery, in which of the following situations is documenting the quality chronic conditions of the voice by using the diagnosis “Voice evaluation, normal” before surgery sufficient? b. physicians often fail to monitor and to appropriately escalate urate-lowering therapy a. no previous neck surgery c. most gout patients are on appropriate urate-lowering therapy b. previous neck surgery d. flare prophylaxis with colchicine or a nonsteroidal anti-inflammatory drug is appropriate c. previous chest surgery in the first several months even after achieving the target level with allopurinol or other d. patient with voice issues urate-lowering treatments Article 4. (page 107) You Are Not Alone: Article 2. (page 51) Improving Care in Older Patients with Diabetes: Ten Strategies for Surviving a Malpractice Lawsuit A Focus on Glycemic Control Which of the following statements is true? What is the first-line therapy for treatment of glycemic control in older adults a. our response to stress is hardwired and cannot be changed with diabetes (assuming no contraindications to the medication)? b. you should never talk to anyone about how the lawsuit is affecting you a. glipizide c. prescribing some diazepam for yourself is a good way to manage lawsuit-related stress b. glyburide d. you can increase your resilience by writing down three good things that happen each day c. metformin Which of the following is a characteristic that does not help a physician manage d. insulin the stress of a lawsuit? e. pioglitazone a. self-compassion

What is an appropriate hemoglobin A1c range in a 74-year-old patient on glipizide b. practicing mindfulness and metformin with comorbidities of hypertension and hyperlipidemia? c. being a perfectionist a. 5.5 to 5.9 d. practicing gratitude b. 6.0 to 6.4 c. 6.5 to 6.9 d. 7.0 to 7.9

Section B. Section C. Referring to the CME articles, how likely is it that you will implement this learning to improve your practice within the next 3 months? What other changes, if any, do you plan to make in your practice as a result of reading these articles? Objective 1 Objective 2 Objective 3 Integrate learned Lead in further developing “Patient- Implement changes and Key knowledge and Centered Care” activities by acquiring apply updates in services and ______5 = highly likely increase competence/ new skills and methods to overcome practice/policy guidelines, 4 = likely ______3 = unsure confidence to support barriers, improve physician/patient incorporate systems and 2 = unlikely improvement and relationships, better identify diagnosis quality improvements, and ______1 = highly unlikely change in specific and treatment of clinical conditions, effectively utilize evidence- 0 = I already did this practices, behaviors, as well as, efficiently stratify health based medicine to produce and performance. needs of varying patient populations. better patient outcomes. Section D. (Please print)

Article 1 5 4 3 2 1 0 5 4 3 2 1 0 5 4 3 2 1 0 Name ______Physician Non-Physician Article 2 5 4 3 2 1 0 5 4 3 2 1 0 5 4 3 2 1 0 Title ______Article 3 5 4 3 2 1 0 5 4 3 2 1 0 5 4 3 2 1 0

Article 4 5 4 3 2 1 0 5 4 3 2 1 0 5 4 3 2 1 0 E-mail ______

Address ______The Kaiser Permanente National CME Program is accredited by the Mail or fax completed form to: Accreditation Council for Continuing Medical Education (ACCME) to provide The Permanente Journal ______continuing medical education for physicians. 500 NE Multnomah St, Suite 100 The Kaiser Permanente National CME Program designates this journal-based Portland, Oregon 97232 Signature ______CME activity for 4 AMA PRA Category 1 Credits™. Physicians should claim Phone: 503-813-3286 only the credit commensurate with the extent of their participation in the activity. Fax: 503-813-2348 Date ______

112 The Permanente Journal/Perm J 2016 Summer;20(3)

BOOKS PUBLISHED BY Summer 2016/ Volume 20 No. 3 PERMANENTE AUTHORS: The PermanenteJournal ORIGINAL RESEARCH able feedback, 4) lack of timeliness in the & CONTRIBUTIONS delivery of feedback, 5) unclear benefit of Sponsored by the National Permanente patient experience survey data as a tool for Your Guy’s Guide to Gynecology: 4 Weight Loss and the Prevention of providing resident feedback, and 6) lack of A Reference for Men and Women Medical Groups Bruce Bekkar, MD; Uda Wahn, MD Weight Regain: Evaluation of a Treat- individualized feedback. ment Model of Exercise Self-Regulation ISBN-10: 0965506746 Mission: The Permanente Journal advances Generalizing to Controlled Eating. 31 Physicians Experiencing Intense ISBN-13: 978-0965506748 knowledge in scientific research, clinical James J Annesi, PhD, FAAHB, FTOS, Emotions While Seeing Their Patients: FAPA; Ping H Johnson, PhD; East Sandwich, MA: North Star Publications medicine, and innovative health care delivery. What Happens? Joana Vilela da Silva, (Ant Hill Press); 2000. Gisèle A Tennant, PhD; Kandice J Porter, MD; Irene Carvalho, PhD Hardcover: 325 pages PhD; Kristin L McEwen $24.95 Circulation: 25,000 print readers per A self-report survey was completed by 127 For decades behavioral weight-loss treat- quarter, 6900 eTOC readers, and in 2015, physicians, with 52 (43%) reporting experi- ments have been unsuccessful beyond encing intense emotions frequently. Coping 1.4 million page views on TPJ articles the short term. In this study, women with strategies to deal with the emotion at the in PubMed from a broad international obesity were randomized into either a moment included behavioral and cognitive readership. comparison treatment that incorporated approaches. Choking-up/crying, touch- a print manual plus telephone follow-ups ing, smiling, and providing support were (n = 55) or into an experimental treatment significantly associated with an immediate Picking up the Pieces: of The Coach Approach exercise-support positive impact on the physician-patient What Everyone Needs to protocol followed after 2 months by group relationship. Withdrawing from the situa- Know When a Child Dies nutrition sessions focused on generalizing tion, imposing, and defending oneself were Adrienne L Burnell, RN, MS, PhD; self-regulatory skills from an exercise associated with a negative impact. George M Burnell, MD support to a controlled eating context ISBN-10: 1516859405 (n = 55). Improvements in all psychological 38 Difference in Effectiveness of ISBN-13: 978-1516859405 Medication Adherence Intervention ON THE COVER: measures, physical activity, and fruit and by Health Literacy Level. Ashli A createspace.com; 2015 Roman Stonemason vegetable intake were significantly greater Owen-Smith, PhD, SM; David H Smith, Paperback: 206 pages by Tom Janisse, MD, MBA in the experimental group. Change in $26.45 self-regulation best predicted weight loss, PhD, RPh; Cynthia S Rand, PhD; Jeffrey A Roman stonemason whereas change in self-efficacy best pre- O Tom, MD, MS; Reesa Laws; Amy works to repair the vulner- dicted maintenance of lost weight. Waterbury, MPH; Andrew Williams, able corner of a 1000-year- PhD; William M Vollmer, PhD 18 A Pharmacist-Staffed, Virtual Gout old structure. He stands Promoting Adherence to Improve Effective- If you are a Permanente author and would like your book cited here, Management Clinic for Achieving sturdy in his fashionably ness of Cardiovascular Disease Therapies send an e-mail to [email protected]. Target Serum Uric Acid Levels: buckled black boots, blue (PATIENT) was a randomized clinical trial A Randomized Clinical Trial. jeans with plaster-clouded designed to test the impact, compared Robert Goldfien, MD; Alice Pressman, knees, and traditional with usual care, of two technology-based PhD, MS; Alice Jacobson, MS; Michele Ng, blue work coat with lapels. interventions that leveraged interactive PharmD; Andrew Avins, MD, MPH Kneepads wait to support voice recognition to promote medication his delicate work close to the ground, hammering The authors conducted a parallel-group, adherence. The differences in intervention additional bits of marble, variously sized, to fit all filling randomized, 26-week, controlled trial of a effects for high vs low health literacy in this defects. He restores a historic work of masonry 30 pharmacist-staffed, telephone-based pro- exploratory analysis are consistent with generations after its construction and reconstruction, gram for managing hyperuricemia vs usual the hypothesis that individuals with lower done just like this in just this way, in a process first care. Among 37 participants randomized health literacy may derive greater benefit learned during the transition from wood to stone. to the intervention group, 13 (35%) had a from this type of intervention compared serum uric acid level (sUA) ≤ 6.0 mg/dL at with individuals with higher health literacy. Some hours into mixing mud, his dextrous hands with 26 weeks vs 5 of 40 participants (13%) in precision and artistry carefully prep the faces for a final the control group (p = 0.03). A structured 45 Lifestyle and Self-Management by Those fresh surface coat, smooth to the touch. When he is pharmacist-staffed program was more ef- Who Live It: Patients Engaging Patients done, the pads, hammer, slab, and bits all fit into his fective than usual care for achieving target in a Chronic Disease Model. Michelle T metal pail, then into his bicycle basket for a ride home sUA levels. These results suggest that Jesse, PhD; Elizabeth Rubinstein; Anne through Roman traffic. He looks back to view with a structured program could significantly Eshelman, PhD, ABPP; Corinne Wee; pleasure and a sure sense of contribution his master improve gout management. Mrunalini Tankasala; Jia Li, PhD; Marwan work of art. Abouljoud, MD, CPE, MMM, FACS 24 Exploring the Reality of Using Patient Of 1862 patient satisfaction surveys, 823 Dr Janisse is the Editor-in-Chief of The Permanente Experience Data to Provide Resident were returned (44.2%). Patients and their Journal and Publisher of The Permanente Press. Feedback: A Qualitative Study of supports appreciated that the program Attending Physician Perspectives. volunteer was a transplant recipient and Steffanie Campbell, MD; Heather noted gratitude for the lifestyle information. Honoré Goltz, PhD, LMSW, MEd; Sarah Five areas were associated with the suc- Njue, MPH; Bich Ngoc Dang, MD cess of Transplant Living Community: 1) 112 CME EVALUATION FORM From 7/2013 to 8/2013, in-depth, face- a “champion”; 2) a receptive health care to-face, semistructured interviews were environment; 3) a high level of visibility conducted with 9 attending physicians to physicians and staff; 4) a lifestyle plan who precept residents in internal medicine (“Play Your ACES” [Attitude, Compliance, at 2 continuity clinics (75% of eligible at- Support, and Exercise]), and 5) a strong The Permanente Journal tendings). Content analysis identified 6 volunteer structure. It is feasible to inte- 500 NE Multnomah St, Suite 100 potential barriers in using patient experi- grate a sustainable patient-led lifestyle and ence survey data: 1) perceived inability self-management educational group into Portland, Oregon 97232 of residents to learn or to incorporate a busy tertiary care clinic for patients with www.thepermanentejournal.org feedback, 2) punitive nature of feedback, complex chronic illnesses. ISSN 1552-5767 3) lack of training in the delivery of action-

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