General Internal Medicine La Revue Canadienne De Médecine Interne Générale

Volume 10, Issue 4 • 2015

Canadian Journal of General Internal Medicine La Revue Canadienne De Médecine Interne Générale

Publications Agreement Number 40025049 | 1911-1606 An Internist’s Journey with Behavioural Medicine Goldberg

An Approach to “The Social Admission” ANDREW AND POWELL www.csim.ca

Canadian Journal of General Internal Medicine

Volume 10, Issue 4 • 2015 Publications Agreement Number 40025049 EDITOR-IN-CHIEF Mitchell Levine

SENIOR ASSOCIATE EDITOR Peter Brindley Volume 10, Issue 4 • 2015 J UNIOR ASSOCIATE EDITOR CONTENTS Ben Wilson Message from the Editor-in-Chief/ 39 A Suspected Case of Endoscopic Ultra- RESIDENTS' VIEW EDITOR Andrew Appleton Message du rédacteur en chef sound Induced Pancreatitis, Without Fine Needle Aspirate EDITOR EMERITUS 4 Understanding the Biomedical - Hector Baillie Michael John Abunassar BSc, BA, MD, Loree Boyle, BN, Behavioural Continuum MD, Avijit Chaterjee, MSc, MDCM EDITORIAL BOARD Mitch Levine Ranjani Aiyar, Simona Bar, Hershl Berman, Peter Brindley, Kaberi Dasgupta, Don Echenberg, Donald Farquhar, 42 Spontaneous Four Limb Compartment Bert Govig, Luc Lanthier, Alex Leung, Suzanne Morin, 5 Pour une meilleure compréhension du Jock Murray, Kathryn Myers, Glen Pearson, Louise Pilote, Syndrome Linda Snell, Matthieu Touchette, Ben Wilson, continuum des volets biomédical et Giovanna Riolo MD, Danny Aurora MD, David Taylor MD, George Veenhuyzen comportemental Gavin CA Wood MBChB CSIM OFFICE Mitch Levine Tel: 613-422-5977; Toll-Free: 1-855-893-2746 45 Diagnostic Approaches: Images in GIM Email: [email protected] Clinical Medicine: Art and Science Acute Infectious Epiglottitis MANAGING EDITOR Jeff Shrum MD and Ben J. Wilson BJ Rose Simpson 6 An Internist’s Journey with Behavioural Medicine ARTDIRECTOR William Goldberg, MD, DSc (Hon), FRCPC, FACP 46 Deep Vein Thrombosis and Amanda Zylstra Pulmonary Embolism as a TRANSLATOR Julie Paradis 10 A Rose By Any Other Name? Complication of Traditional Richard Marlin, PhD Chinese Acupuncture and Cupping ADVERTISING John Birkby; 905-628-4309 ThucNhi T. Dang Bsc, Albert A.C. Yeung MSc, MD [email protected] 13 Seeing Wisely: The Pursuit of Clinical Expertise 50 Submucosal Lesions Presenting with CIRCULATION COORDINATOR Brenda Robinson Ben J. Wilson, MD Rectal Bleeding-Endometriosis in the [email protected] 15 Handover: The Fragile Lines of GI Tract ACCOUNTING Fahd Jowhari, MD, Pearl Behl, MD, PhD and Susan McClung Communication Sean Pritchett, MD, FRCPC GROUP PUBLISHER Andrew Smaggus MD, Adina S. Weinerman MD John D. Birkby 53 A 54 Year Old Female with Fever and ______20 An Approach to “The Social Admission” Melissa K. Andrew, MD, PhD, Ataxia Subscription Rates: Marie-Lie Cadieux-Simard MD, Laurence Green MD Colin Powell, MB, FRCP (Lond, Edin et Glas) ______Per year: $15.00; per issue: $3.75 Canadian Journal of General Internal Medicine is published 23 Acute Care SINS: Surgical Insights for the Proceedings four times a year by Andrew John Publishing Inc., with Non-surgeon Chapter 13: Spine Surgery 55 McMaster University Department offices located at 115 King Street West, Suite 220, Dundas, th ON L9H 1V1. Aaron S. Robichaud MD, David B. Clarke MDCM PhD, of Medicine 26 Annual Residents’ Cian O’Kelly MD, Martin Beed DM, Peter G. Brindley MD We welcome editorial submissions but cannot assume Research Day in Medicine responsibility or commitment for unsolicited material.Any editorial material,including photographs that are accepted from Case Reports an unsolicited contributor, will become the property of Andrew John Publishing Inc. 33 Unilateral Adrenal Hemorrhage and the The publisher and the Canadian Society of Internal Medicine Challenge of Early Recognition shall not be liable for any of the views expressed by the Resheed Alkhiari MBBS, Dana Attar MBBS, authors published in Canadian Journal of General Internal Christian Kraeker, MD Medicine,nor shall these opinions necessarily reflect those of the publisher. 36 Severe Acute Cytomegalovirus ••••• Infection Complicated by Disseminated Every effort has been made to ensure that the information provided herein is accurate and in accord with standards Intravascular Coagulation and accepted at the time of printing. However, readers are Pneumonitis in a Healthy Female advised to check the most current product information pro- Zain Chagla MD, Deborah Siegal MD, Phillippe vided by the manufacturer of each drug to verify the recom- El-Helou MD, Wendy Lim MD, Jill Rudkowski, MD mended dose, the method and duration of administration, and contraindications. It is the responsibility of the licensed prescriber to determine the dosages and best treatment for each patient. Neither the publisher nor the editor assumes any liability for any injury and/or damage to persons or property arising from this publication. ABOUT THE COVER Return undeliverable Canadian Addresses to: Photography by Dr. Hector Baillie National Gallery of Canada, Ottawa Overlooking Major’s Hill Park 2013 115 King St W., Suite 220, Dundas, ON L9H 1V1 www.andrewjohnpublishing.com For Instructions to Authors, please visit www.andrewjohnpublishing.com/pcjim.html

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 3 CSIMMessage Members from of Council the PresidentMessage from the Editor-in-Chief

Dr. Stephen Hwang President | Toronto, ON Understanding the Biomedical - Behavioural Continuum Dr. Benjamin Chen Past President | Napanee, ON Patients referred to internal medicine physicians are often unusual in their clinical Dr. Neil Gibson presentation or have multiple clinical problems and co-morbidities. The complexity Secretary-Treasurer requires that the physician have a strong understanding of both pathophysiology and Western Region Representative | Sturgeon County, AB the behavioural sciences. The further challenge is knowing how to balance both of these Dr. Amy Hendricks Western Region Representative | Yellowknife, NT disciplines when managing difficult clinical presentations. In the current issue of the Dr. David Simpson Canadian Journal of General Internal Medicine there are three articles that highlight Eastern Region Representative | Halifax, NS this dilemma. Dr. Nadine Lahoud Quebec Region Representative | LaSalle, QC In the Goldberg and the Marlin articles, we are presented with the risks of over Dr. Donald Echenberg medicalizing patient symptoms with the subsequent peril of not helping the patient Chair, CPD Subcommittee to recover and eventually regaining function and quality of life. It is critical for the Quebec Region Representative | Sherbrooke, QC clinician to recognize that invoking a biomedical model as the foundation for a Dr. Bert Govig Quebec Region Representative patient’s presentation (e.g., symptoms, illness, disability) is not always appropriate nor Vice-President, Health Promotion Committee | Amos, QC beneficial. Rather in some circumstances, after acknowledging the patient’s suffering Dr. Tom Maniatis and loss, the physician needs to adopt or integrate a behavioural model of illness in 2016 Chair, Annual Meeting Committee Quebec Region Representative | Montreal, QC order to develop the optimal management strategy and to facilitate patient recovery. Dr. William Coke In the Andrew and Powell article we are advised of the importance of not ignoring Ontario Region Representative | Toronto, ON the biomedical contributions to what might appear to be a failure of the patient’s social Dr. Céline Léger-Nolet Ontario Region Representative | New Liskeard, ON support environment. The determinants of the “social admission” are multifactorial Dr. Stephen Duke and clearly involve many aspects of the patient’s environment, from family and friends, Eastern Region Representative | Dartmouth, NS to institutions and societal policies. But often the tipping point for failure includes Dr. Ameen Patel an important contribution arising from a biomedical problem, which studies have Ontario Region Representative | Hamilton, ON suggested are commonly overlooked. Dr. John MacFadyen Ontario Region Representative | Orillia, ON With the Goldberg and Marlin articles in this issue emphasizing the relative Dr. Maria Bacchus importance of one end of the biomedical-behavioural spectrum, and the Andrew and Western Region Representative | Calgary, AB Powell article emphasizing the other end, the message might be confusing. But the Dr. Glen Drobot goal of presenting these articles together was to communicate the need for physicians Western Region Representative | Winnipeg MB to consider in all new patient encounters the potential for both biomedical and Dr. Meghan Ho Resident Representative | Vancouver, BC behavioural components underpinning the patient’s presentation, and that a skilled Dr. Michel Sauvé and knowledgeable internist will be able to provide the appropriate balance to best Representative to the CMA Council Member-at-Large | Fort McMurray, AB manage the patient’s concerns.

Other CSIM Positions Mitch Levine Dr. Pearl Behl Vice-President, Membership Affairs | Markham, ON Dr. Irfan Dhalla Vice-President, Research and Awards Committee | Toronto, ON Dr. Jim Nishikawa Vice-President, Education Committee Representative on the RCPSC Specialty Committee in Internal Medicine and to the GIM Subspecialty Committee | Ottawa, ON Dr. Mitch Levine CJGIM Editor-in-Chief l Hamilton, ON

4 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Message du rédacteur en chef CSIM Mission Statement Mission Statement The CSIM is a non-profit professional society that promotes the health and well being of Canadian patients, their communities, and their health Pour une meilleure compréhension du continuum care systems. We seek to foster leadership and excellence in the practice of General Internal Medicine (GIM) through research, education, and des volets biomédical et comportemental advocacy for health promotion and disease management. Les patients que l’on adresse à des internistes présentent souvent un tableau clinique inhabituel ou souffrent de problèmes cliniques Vision multiples et de maladies concomitantes. La complexité de ces cas exige We believe that General Internal Medicine in Canada plays a central role in the training of current and future clinicians, in clinical research, que le médecin ait une grande compréhension de la physiopathologie in patient care, in health promotion, and in health advocacy; and that ainsi que des sciences du comportement. Dans la prise en charge de it unites a body of knowledge, values, and principles of care that lay the tableaux cliniques difficiles, la pondération de ces deux disciplines foundation for excellence in the Canadian health care system. constitue un défi supplémentaire. Dans le présent numéro de la Revue canadienne de médecine interne générale trois articles mettent l’accent Values We embrace the ethical and professional standards that are common to all sur ce dilemme. healing professions, as well as the specific values of generalism, teamwork, Dans les articles de Goldberg et de Marlin on nous expose competency-based training, life-long learning, evidence-based medicine, les risques de la surmédicalisation des symptômes d’un patient, holism, and humane, patient-centered care. surmédicalisation pouvant nuire à la guérison de celui-ci et à ses possibilités de recouvrer finalement un niveau fonctionnel et une Mission qualité de vie. Il est crucial pour le clinicien de savoir reconnaître La Société canadienne de médecine interne (SCMI) est une association que d’invoquer un modèle biomédical à l’appui des manifestations professionnelle sans but lucratif qui entend promouvoir la santé et le bien- cliniques d’un patient (p. ex. : symptômes, maladie, invalidité) n’est être des patients, des collectivités et des systèmes de santé canadiens. Elle pas toujours pertinent ni bénéfique. Dans certaines circonstances, souhaite également promouvoir le leadership et l’excellence dans l’exercice tout en reconnaissant la souffrance et les pertes auxquelles le patient de la médecine interne générale en favorisant la recherche, l’éducation, la promotion de la santé et la gestion des soins thérapeutiques. est confronté, le médecin doit plutôt adopter ou intégrer un modèle comportemental de la maladie en vue d’instaurer une stratégie Vision optimale de la prise en charge et de favoriser la guérison du patient. La Société a l’intime conviction que la médecine interne générale occupe Dans l’article d’Andrew et Powell on nous avise qu’il est important une place centrale dans la formation des cliniciens aujourd’hui et à de ne pas négliger l’apport biomédical dans ce qui peut sembler être l’avenir, dans la recherche clinique, dans la prestation des soins et des services de santé et dans la promotion de la santé, et que la discipline se attribuable à une lacune dans l’environnement de soutien social fonde sur un savoir, des valeurs et des principes thérapeutiques essentiels du patient. En effet, les déterminants pour les cas d’« admission à la poursuite de l’excellence dans le système de santé canadien. pour manque de soutien social » sont multifactoriels et touchent de nombreux aspects de l’environnement du patient, autant la famille, Valeurs les amis, que les institutions et les politiques sociales. Mais souvent, La Société fait sienne les normes éthiques et professionnelles communes aux professions de la santé ainsi que les valeurs particulières du l’élément déterminant de la situation découle dans une large mesure généralisme, du travail d’équipe, de la formation axée sur les compétences, d’un problème biomédical qui, d’après certaines recherches, sont de l’éducation permanente, de la médecine factuelle, de l’holisme et des fréquemment négligés. soins et des services de santé humains, centrés sur le patient. La présentation concomitante dans le présent numéro des articles de Goldberg et de Marlin d’une part, et de celui d’Andrew et Powell d’autre part, concernant l’importance relative du continuum des volets CSIM Continuing Professional biomédical et comportemental, peut semer la confusion. Toutefois, Development Mission Statement le but visé en présentant ces articles ensemble est de sensibiliser les médecins à la nécessité d’évaluer chez un nouveau patient l’éventualité Our ultimate goal is to go beyond the simple transmission of information. de la présence de facteurs biomédicaux et comportementaux à Our goal is to make a lasting impact on the knowledge, skills and attitudes of clinicians and future clinicians; to narrow the theory to practice gap; to l’origine du tableau clinique, et de faire savoir qu’un interniste improve the health of our patients and of all Canadians. compétent et habile se doit et est en mesure de faire la part des choses dans le meilleur intérêt du patient. Mission de la SCMI sur le Mitch Levine plan du développement professionnel continu

Notre but ultime déborde du cadre de la simple transmission d’information. Il consiste à produire un effet durable sur le savoir, les compétences et les attitudes du médecin, à combler l’écart qui sépare la théorie de la pratique, à améliorer la santé de nos patients et de tous les Canadiens.

4 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 5 Clinical Medicine: Arts and Sciences

An Internist’ Journey with Behavioural Medicine W.M.Goldberg MD, DSc (Hon), FRCPC, FACP

About the Author Dr. William Goldberg was born in Hamilton, Ontario in 1925 and earned his MD from University of Western Ontario in 1949. He did his post-graduate residency at Victoria Hospital in London, Ontario and the Toronto General Hospital in 1954 and received the Honorary Doctor of Science at McMaster University in 1998. Dr. Goldberg was a clinical professor of medicine at McMaster and was Chief of Medicine at St. Joseph’s Hospital in Hamilton from 1962-1982.

his is the story of a Behavioural Medicine Unit that was statement became obvious to me in the 1960s when I began Tdeveloped in 1975 at St. Joseph’s Hospital in Hamilton seeing patients who presented with disabling symptoms but Ontario. It explains why a general internist decided to assemble had no defined disease, or whose degree of disability was far a team skilled in the principles of cognitive behavioural therapy out of proportion to that expected with their disease. These to help patients who were responding poorly to traditional patients usually had symptoms of recurrent, atypical, chest medical care. The principles that were applied at that time pain or profound fatigue and investigations failed to show continue to be as important in 2015. defined disease or disorder. I conjectured that if I could Despite the success of the program and of others that reassure them that they had no ‘organic’ disease and took the were developed over the next 40 years, these principles have time to enquire about possible emotional problems, exposure not been adequately utilized by ‘main stream’ medicine nor to excessive stress, and ask them whether they were deeply have they been emphasized sufficiently in undergraduate or concerned that they had a serious underlying disease, that they residency curricula. It is hoped that the story will stimulate would improve. I naively thought that, with reassurance and the promotion and integration of the principles of cognitive realization that their symptoms were influenced by emotional behaviour into medical education and patient care. factors, they would get better. Accordingly, I proceeded to Changing people’s behaviour can be extremely challenging counsel them in this way, but the vast majority did not improve because it usually requires changes in the management of and still believed they had some disease that had not yet deeply held beliefs. It is my thesis that nearly all human been diagnosed. behaviour results from one’s beliefs and I hope to convince To make matters worse, for those patients with chest readers that the successful application of cognitive pain, emergence of cardiac ultrasound identified mitral valve behavioural principles requires changes in the beliefs of both prolapse were referred to cardiologists. Most patients with patients and their doctors. chest pain underwent this test and many had mitral valve The journey began during my residency at Victoria Hospital prolapse because this benign condition is very common in the in London, Ontario and later at the Toronto General Hospital. general population. Affected patients were then told the mitral I was mentored by two outstanding clinicians, Dr. Frank Brien valve prolapse was the cause of their chest pain and thus, and Dr. Ray Farquharson. Part of their greatness as clinicians they were given the diagnosis of having an ‘organic’ disease. was their desire and ability to understand their patients’ This label exacerbated their problem. Some became aware of adaptations to their illness. In main stream medicine, patients’ palpitations from benign extrasystoles and presented to the responses to their illnesses often influenced their management; emergency department with their chest discomfort, where when a specific diagnosis could not be made, management was they were examined and investigated and had the diagnosis of based on the patient’s response to their illness. As I look back mitral valve prolapse confirmed. The response of the medical 65 years, I realize they were practising behavioural medicine. profession reinforced their belief that they were unwell Dr. Brien often said, “The most difficult patient to treat is the and increased their illness behaviour, and, thus their level one for whom there is no specific treatment”. The truth of his of disability.

6 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Goldberg

The chronic fatigue patients whom I saw had a condition disease, but the patient’s overall response to their symptoms that had been known to the medical profession for over 100 that caused their severe illness behaviour. The term illness years as neurasthenia. It was not until the 1990s that the behaviour refers to the response to illness (real or perceived) disorder was given the label of chronic fatigue syndrome. This as it affects the patient’s activities of daily living. This response was considered by many to be caused by chronic brucellosis mechanism had been clearly outlined in a 1961 publication by and later by the Epstein Barr virus. Both were later proved not Dr. David Mechanic2 whose title was its message, ‘Response to be causal agents. Even to this day, though no cause has been Factors in Illness, Study of Illness Behaviour.’ This message is found, it is considered by many to be a disease with an organic as pertinent today as it was in 1961. cause. Labeling these patients with a disease for which there is It was also noted that these patients demonstrated no specific treatment worsens their situation. avoidance behaviour due to a false attribution of causality. This latter term refers to the need for a person to attribute any A Better Approach event in their lives, such as illness, to a specific cause. False In the late 1960s, I thought that there must be a better approach attribution is exemplified in our patients by their belief that to manage patients who were being referred to me with they had some undiagnosed disease or a minor disorder that undiagnosed chest pain or chronic fatigue. They were being they believed was causing symptoms; the symptoms were far referred to me in what appeared to be epidemic numbers. I out of proportion to those expected with the disorder. thought I might be missing an underlying psychiatric disorder In addition, Dr. Cott then conceived the hurt/harm so I discussed my dilemma with Dr. Norman White, then the concept, which is typified by patients’ beliefs that activity Chief of Psychiatry. We decided to interview these patients would worsen their underlying condition. He felt if we could together to see if we could devise an approach that combined convince our patients that although an activity might hurt, psychiatric and internal medicine expertise. Soon, we noted a it would do them no harm, that they might cooperate with a common thread among our patients. They were very hostile to cognitive behavioural program. He also felt that if this program their doctors because they thought that they were not believed set incremental realistic goals that led to a slow increase in and that their doctors thought they were either crazy or lying. activity, with progressive success at each level, patients would In our interviews, we jumped on this belief system and devised alter their belief system. Thus, by demonstrating that carrying a plan based on convincing our patients that we thought their out a behaviour, which is incompatible with their belief that symptoms were real, that they had no mental disorder, and they have a serious underlying disease, they might change that they were not lying to us. After using this new approach in their belief. For example, he predicted that our patients with several patients, we reviewed their progress at a follow-up visit chest pain who believed they had heart disease and who were 2 to 3 weeks later and asked each patient what they thought our able to carry out an exercise program, would realize that message to them was. To our surprise, with minor variations, this activity was incompatible with their belief that they had they all felt we believed that they were crazy or lying. Thus, serious heart disease. simply telling patients what we considered to be the truth, was Our early results were promising. In 1975, we formed a not enough to change their beliefs. multidisciplinary clinical unit at St. Joseph’s Hospital called In 1974, the first Behavioural Medicine Unit was initiated the Environmental Medicine Unit because Dr. White felt that at the University of Pennsylvania.1 To try and incorporate our patients’ personal environment, which included their the principles of cognitive behavioural methodology to our family, their social life, and their work environment played clinic, we asked Dr. Arny Cott, a psychologist in cognitive an important role in reinforcing patients’ illness behaviour. behavioural therapy, to join our interviews. He concluded Eventually, it was renamed the Behavioural Medicine Unit. that the interviewed patients demonstrated what he called Dr. Cott was the Director and was responsible for planning the ‘disease-illness distinction.’ This term is best explained and implementing a cognitive behavioural program for by considering two extreme examples of a spectrum. At one each patient. Dr. White and I would participate in the initial extreme is a person with no defined disease who demonstrates assessment process and we were available to reassess patients disabling illness behaviour and is off work on disability pay, when medical or psychiatric problem arose. while at the other extreme is a paraplegic who demonstrates no The key to the success of the unit was its multidisciplinary illness behaviour because he/she works full time, is involved nature. Dr. White and I were given the responsibility of in athletics, and is only limited physically by paraplegia. ensuring that the patients’ medical and psychiatric status had Dr. Cott opined that it was not the presence of an underlying been fully investigated, and when medically necessary that

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 7 An Internist’ Journey with Behavioural Medicine

they received best available therapy. If we had doubt about litigation for accident related injuries, the clinic activity grew our diagnosis, we would seek appropriate consultation. The dramatically. The motive for the referrals from these sources main purpose of this initial phase of the program was to was related to the favourable cost-benefit outcome if we could ‘demedicalize’ the component of their illness behaviour that return patients to their work place and reduce or discontinue could not be accounted for by a known disease process. This disability payments, but the most important benefit was the left Dr. Cott with a free rein to deal with the demedicalized return of an unhappy disabled patient to a normal life style and portion of their illness behaviour by implementing a cognitive gainful employment. behavioural strategy. Each patient’s program was determined at an initial Beliefs Changed conference, chaired by Dr. Cott, where we all met and In the late 1980s, a study was carried out by Jane McCully, discussed our opinions. We also included staff that were our one of our field consultants, who was working towards her field consultants. The latter had backgrounds in psychology, PhD at McMaster University. Aware that a paper4 published nursing, or social work and underwent education and training in 1980 reinforced our experience that reassurance alone programs in cognitive behavioural principles. They assessed nearly always failed to alleviate disabling illness behaviour, the home, family and work environments as well as the social McCully based her thesis on a study of patients with chest pain milieu, to look for factors which might be exacerbating illness and no evidence of cardiac disease and an assessment of their behaviour. In addition, they liaised with family doctors and, response to cognitive behavioural reshaping. The patients were when appropriate, consultants who had evaluated the patient. initially tested for their locus of control, and were all found An important component of the field consultant’s role was to have an external locus of control. Namely, they believed to ensure that patients received a single message from all external factors over which they had little control dictated involved in their care. If they received a single message from all their behaviour. In addition, they kept a pain diary before, and concerned, they were much more likely to change their beliefs throughout, the treatment process of the cognitive behavioural to coincide with those that the program was trying to instill. reshaping program. The 43 patients who were in the treatment The planned program was implemented by the field consultant cohort all returned to a normal life style and believed they had in the patient’s home and, when necessary, their work place. no heart disease. All treated patients were retested for their In retrospect, it seems obvious that a plan, which included locus of control and, after completing the program, had all treating the patient in their home and that encouraged changed from an external to an internal locus of control. This involvement of, and reinforcement from, the family should meant that before they entered our program, they believed improve compliance and increase the likelihood of changing they were not in control of their lives, but after completing the the patient’s behaviour. The ready availability of medical and program, they believed that they were in control. Thus, two psychiatric input and its integration into the program helped major beliefs that were important factors in the production to legitimize the unit in the eyes of the patient, the referring of their illness behaviour were changed by the behavioural doctor, and the medical community. In the late 1980s, treatment program. Another significant finding was noted Drs. Cott and Anchel carried out a study3 to assess the value when we compared their pre- and post- treatment pain diaries. of field consultants. They found that 84% of field-managed This finding was that 13 of the 43 treated patients had more patients had a successful outcome compared to 61% of those frequent chest pain after completion of the program than treated solely in the office. Equally important was the much before, yet they had a normal life style. They were asked how higher dropout rate in office--treated patients. they could reconcile this paradox and their uniform answer Initially, we had difficulty in obtaining patient referrals was that they knew the pain was not caused by underlying heart because the cognitive behavioural component, which disease and they otherwise felt so well that they must have just accounted for the major portion of the cost of the program, learned to live with it. This finding exemplifies the hurt/harm was not covered by the provincial health plan. In addition, concept, in which the patient believes that a discomfort will practising doctors were not aware of cognitive behavioural do no harm even though it hurts, because of the belief that methodology nor of its potential to benefit patients. Once it is not caused by heart disease. The patient believes that he/ we demonstrated success with patients in the work place who she is in control and as a consequence demonstrates minimal were disabled and on sick leave or long term disability, or in if any illness behaviour. McCully succeeded in obtaining her

8 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Goldberg

PhD and we later published a paper that outlined her results.5 With this model, the degree of illness behaviour that A similar study was performed with patients diagnosed occurs may be appropriate to the known effects of the with chronic fatigue syndrome and the cognitive behaviour underlying disease or may be inappropriate. This is where program demonstrated a reduction in illness behaviour and a the disease/illness distinction comes into play. The patient’s high rate of return to work.6 response mechanism can be as important as the direct effects There is now evidence from PET scanning and functional of the underlying disease or disorder. Therefore the response magnetic resonance imaging of the brain that supports the mechanism should be given the same emphasis in clinical proposal that expectations of symptom improvement, long medicine, clinical investigation, and medical education that is thought to play a critical role in the placebo effect, are driven lavished on defined diseases. by the prefrontal cortical areas and the ventral striatum.7 Placebo stimulates an increase in endogenous endorpins and References dopamine production, which the authors suggested, could be 1. Kennerly RC. The Formation of the Field of Behavioural Medicine and its Roots. Medical Mind Body. Dualism,University of North Texas. Copyright the mechanism for the success of the placebo effect. I would statement and download link, 2002. propose that the findings associated with exposure to a placebo 2. Mechanic D. Response Factors in Illness: The Study of Illness Behaviour, apply to our notion that belief drives illness behaviour. To apply Social Psychiatry, 1961;1:1,11-20. 3. Cott A, Anchel H, Goldberg WM, et al. Non-institutional Treatment of those findings to our thesis, the patient must first cognitively Chronic Pain by Field Management: An outcome study with comparison believe in the projected expectation of improvement, which group. Pain 1990; 40:183-94. we contend, is then mediated through the brain resulting in 4. Ockene DS, Shay MJ, Alpert JS, et al. Unexplained Chest Pain in Patients with an increase in endorphins producing less pain. This results in Normal Coronary Arteriograms. NEJM 1980;303:1249-1252. 5. Cott A, McCully JM, Goldberg WM, Tanser P. Interdisciplinary Treatment of feeling better and so lessens illness behaviour. Morbidity in Benign Chest Pain Angiology. The Journal of Vascular Disease March 1992:195-202. Paradigm Shift Needed 6. Marlin RG, Anchel H, Gibson JC, Goldberg WM, Swinton M. An Evaluation of Multidisciplinary Intervention for the Chronic Fatigue Syndrome with Today, there is a need for a paradigm shift in clinical medicine Long-Term Follow-Up and a Comparison with Untreated Controls. AM J from a purely biomedical model to a biomedical-behavioural Med 1998 Sep 28; 105(3A):110S-114S. one. The biomedical model can be defined as follows: A disease 7. Molecular Imaging and Biology. 2007 July; Vol. 9, Issue 4:176-18. or disorder produces signs and symptoms which are the sole basis of the investigations, diagnosis and treatment.

disease->symptoms->investigation->diagnosis->therapy

The biomedical-behavioural model considers the role of the individual human behavioural response in the process of any disease or non-disease situation because this is what dictates the way in which the patient demonstrates illness behaviour. A more accurate and inclusive model is illustrated by the following: A disease or disorder produces signs and symptoms to which the patient responds resulting in some degree of illness behaviour, the extent of which must be recognized with any diagnosis and included in the diagnostic and therapeutic process.

disease->symptoms->patient response>diagnosis ->illness behaviour-> therapy

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 9 Clinical Medicine: Arts and Sciences

A Rose By Any Other Name? Richard Marlin, PhD

About the Author Dr. Richard Marlin is a clinical psychologist with more than 25 years of experience treating and consulting with industry about chronic disability problems including various chronic pain syndromes, chronic fatigue syndromes and fibromyalgia. He also treats patients with such problems as chronic depression and anxiety. Dr. Marlin is currently the director of Odyssey Health Services.

n February of this year, an expert committee of the United I agree that the suffering and impaired functioning of IStates Institute of Medicine (IOM) released a lengthy these patients should be both acknowledged and validated. I report in which its members reviewed diagnostic criteria also agree that the suffering that they experience should not be and proposed a new label for chronic fatigue syndrome, also trivialized. However, the notion that labeling their suffering historically referred to as myalgic encephalomyelitis.1 The and impaired function as a disease will actually serve to reduce committee’s proposed new label for this illness is Systemic stigmatization and improve patient care is open to discussion. Exertion Intolerance Disease. The report refers to the fact that In a broader healthcare context, we have, for some time, a sizeable population is diagnosed with this illness, which been battling the stigmatization of patients with what are causes considerable suffering and functional impairment. broadly referred to as mental health difficulties. There has been Many patients also feel stigmatized because of the label chronic a general cultural perception, which extends into the healthcare fatigue syndrome. community, that psychological, emotional or behavioural An editorial was published in The Lancet in the same difficulties are somehow less important than physical health month2 that supported the proposal for the inclusion of a difficulties. While considerable efforts have been undertaken broader array of symptoms in patients with the diagnosis, to alter this perception in recent years, the effectiveness of including: impaired day-to-day functioning secondary to these efforts themselves are often mixed. fatigue, malaise after exertion, and unrefreshing sleep as well From my perspective, efforts that directly and openly as cognitive difficulties or orthostatic intolerance, or both. validate the reality of psychological suffering and the fact The notion of including exertion intolerance is reasonable that the presence of such suffering can markedly restrict and is more inclusive than the term ‘chronic fatigue,’ but it individuals’ lives is important and needs to be emphasized. should also be acknowledged that fatigue at rest is a prominent To attribute and treat the presence of such difficulties as a symptom in the majority of patients. Of more concern is character flaw or a simplistic inadequacy on the part of the whether the use of the term ‘disease’ is valid and whether it patient is demeaning, erroneous and harmful. The fact is that will do more harm than good.3 psychological suffering can be extremely painful, provoke The Institute of Medicine’s report clearly acknowledges enormous distress and wreak havoc with people’s ability to that no underlying objectively definable disease process or carry on a meaningful life. To be fully aware of, and accept, pathology has been identified to account for the symptoms the true nature of this suffering is a necessary requirement to experienced by these patients. Indeed, consistent with earlier both provide and to receive therapeutic assistance. CDC diagnostic criteria, any known definable disease or Attempts have been made to destigmatize mental health pathology that could account for the patient’s symptoms must patients’ symptoms by proposing that they represent be ruled out before such a diagnosis can be made. neurochemical imbalances and/or diseased or pathological It appears that the utilization of the term disease is intended brain structure. This is despite the absence of convincing to both convey the severity and the reality of patients’ suffering scientific evidence that such brain pathophysiology is a cause and associated impaired functioning.4 of these health problems.

10 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Marlin

By suggesting that patients are better off if we tell them The editorial in The Lancet notes the considerable number that their difficulties are caused by brain disease, we might of ‘unfair’ criticisms directed at both the PACE trial7 as well as be worsening the stigmatization of psychological suffering the very recent Cochrane review which support the efficacy of and impairment. Instead, I feel that we should accept these graded exercise in the treatment of this illness.8 I would argue difficulties for what they are: very real human suffering in the that this is a clear manifestation of the negative stigmatization psychological realm. Such acceptance will permit patients to of psychological and behavioural issues and treatment clearly acknowledge their suffering and distress and to seek help. Such directed at such issues. help should include evidence-based psychological therapies, There is a substantive body of scientific literature including behavioural therapies and cognitive behavioural describing the role that such factors play in this and similar therapies. illnesses and, more importantly, in the degree of suffering If patients believe their difficulties to be caused by brain that patients experience and the degree of reduced function. disease, they are more likely to seek unproven medical The psychological and behavioural factors include such solutions, including medication or interventions such as fundamental processes as perceptual learning, conditioned electroconvulsive therapy or transcranial magnetic therapy, physiological responses and operant conditioning. Quite the benefits of which are uncertain and controversial. It is understandably, beliefs and fears can play an important role well established that interventions used in studies funded by in the how symptoms are perceived.9 sponsoring drug companies consistently report better efficacy If healthcare providers are hesitant to educate patients for drugs than studies with the same interventions that are about such factors and fail to strongly recommend what is an not funded by drug companies. It has also been shown that evidence-based conceptualization of the illness and treatment, when active placebos are used and the study is double-blind, they are doing patients a considerable disservice. However, it is the magnitude of effect is reduced. also essential that they validate the true degree of suffering and I believe the same applies to patients suffering from diminished function that the patient experiences. Chronic Fatigue Syndrome/Systemic Exertional Intolerance. To quote the editorial from The Lancet, “The message At the present time, cognitive behavioural therapy and of the IOM report is that CFS/ME is a serious and complex carefully graded exercise are the only treatments with a solid disorder and the authors hope that the new name could be an evidence base.5 These interventions have produced significant important step in changing perception. Further research to improvement in patient’s functional abilities, including test these new concepts with cooperation between professional improved exercise tolerance and return to gainful employment. and patient groups is now needed to improve the evidence Therefore, if appropriately addressed with evidence-based base.” treatment, we can reduce both suffering and dysfunction I concur that it is imperative that evidence be gathered to in these patients. As an aside, these interventions have been evaluate the impact of this document. One can hope that the shown to alleviate suffering even when we are dealing with net result is the removal of stigmatization with respect to this definable disease and well-defined conditions.6 Thus, there is a particular illness and the removal of the stigmatization of the considerable body of evidence that psychological, behavioural contribution of psychological and behavioural factors and and psychosocial factors play a very important role in the the stigmatization of effective behavioural treatment. Sadly, degree to which patients become impaired and disabled and I am not optimistic that incorporating the term ‘disease’ will experience secondary suffering. further that cause. The notion of attaching the label ‘disease’ to these difficulties (when there is no credible scientific evidence of References an identified disease process) carries the same risk as labeling 1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and what we typically call mental health difficulties as brain disease. study. Annals of Internal Medicine 1994; 121:953–955. Unfortunately, patients can be made to feel that their suffering 2. Lancet. February 22, 2015; 385: 663. is not real or disabling if they are offered psychological 3. See: Cott, A. The Disease-Illness Distinction: A Model for Effective and Practical Integration of Behavioural and Medical Science. In: McHugh, therapy. By labeling the condition as a disease both patients S. and Vallis, M. T. (Eds) Illness Behaviour: A Multidisciplinary Model. and healthcare practitioners are more likely to search for and Plenum Press. 1986; 71-99; and Mechanic, D. The Concept of Illness utilize unproven biomedical interventions. Such effects will Behavior. Journal of Chronic Disease 1961: 15; 189-94. neither serve patients nor healthcare providers well. 4. Whiting, P.; Bagnall, A.; Sowden, A., Cornell, J. ; Mulrow, C. and Ramirez, G. Interventions for the Treatment and Management of Chronic Fatigue Syndrome: a Systematic Review, Journal of the American Medical

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 11 A Rose By Any Other Name?

Association, September 19, 2001, Volume 286, Number 11; Marlin, R., 8. See, for example: Nijs, J., Meeus, M., Van Oosterwijck,J., Ickmans,K., Anchel, H., Gibson, J., Goldberg, W. and Swinton, M. An evaluation of Greta Moorkens, G., Hans, G. and De Clerck, L.S. In the mind or in Multidisciplinary Intervention for Chronic Fatigue Syndrome with Long- the brain? Scientific evidence for central sensitisation in chronic fatigue Term Follow-Up and a Comparison with Untreated Controls. American syndrome. European Journal of Clinical Investigations. 2012; 42 (2): Journal of Medicine, 1998: 105.(3A, 1105-1145 and Prins, P., van der 203–212; Tanaka, M. and Watanabe, Y. A new hypothesis of chronic Meer, J. and Bleijenberg, G. Chronic fatigue syndrome. Lancet January fatigue syndrome: Co-conditioning theory. Medical Hypotheses 75 2010; 28, 2006. 244–249; Kadotaa, Y., Cooperb, G., Burtona, A.R., Lemona, J., Schallb,U., 5. ACOEM Guideline: Preventing Needless Work Disability by Helping Lloyde, A. and Vollmer-Connaa,U. Autonomic hyper-vigilance in post- People Stay Employed. Journal of Occupational and Environmental infective fatigue syndrome. Biological Psychology 85 2010; 97–103; Medicine 2006; 48, 9, 972-987. Knoopa, H., Prinsb, J.B., Moss-Morrisc, R. and Bleijenbergd, G. The 6. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare central role of cognitive processes in the perpetuation of chronic fatigue JC, et al. Comparison of adaptive pacing therapy, cognitive behaviour syndrome. Journal of Psychosomatic Research 68 2010; 489–494; Wiborg, therapy, graded exercise therapy, and specialist medical care for chronic J.F., Knoop, H., Frank, L.E. and Bleijenberg, G. Towards an evidence- fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377:823– based treatment model for cognitive behavioral interventions focusing on 36;and Bleijenberg, G. and Knoop, H. Chronic Fatigue Syndrome: Where chronic fatigue syndrome. Journal of Psychosomatic Research 72 2012; to PACE from here? Lancet. Published on-line February 18, 2011. 399–404; and Friedberg., F. Chronic Fatigue Syndrome, Fibromyalgia, 7. Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for and Related Illnesses: A Clinical Model of Assessment and Intervention. chronic fatigue syndrome. The Cochrane Library 2015, Issue 2. Journal of Clinical Psychology 2010; 66:641–665.

Canadian Journal of General Internal Medicine

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12 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Clinical Medicine: Arts and Sciences Seeing Wisely: The Pursuit of Clinical Expertise Ben J. Wilson, MD

About the Author Ben Wilson is a general internist at the Peter Lougheed Centre in Calgary, Alberta. Correspondence may be directed to [email protected].

lean white hallways. Brightness. Rooms. Rooms with eight minutes per patient. Interestingly, but not surprisingly, Cbeds. Beds lined up in series, against each wall. People in they spent 40% of their time on computers. The screen-side the beds. Patients. A person in a suit, sometimes a white coat, has largely trumped the bedside. sitting. At the bedside. Sometimes thinking. Sometimes feeling This transition, while surprising and unsettling on or listening. Always at the bedside. Always with patients. a visceral level, is not wholly negative. Indisputably, the My earliest thoughts of medicine consist of these electronic medical record, expanding diagnostic technologies, powerful, though fragmented, concrete images. At their and the ubiquity of computers have advanced the science of heart, they embody intimate human connection and healing patient care. However, if these technologies are to be used to and the profound fulfillment that inevitably results from maximally benefit our patients, they should be thought of as this combination. These endeavors – human connection adjuncts to the bedside and not as replacements for it. and healing - contribute to my life’s purpose and meaning. Indeed, there is no substitute for direct patient care. It Inevitably then, these images have become inextricably linked remains the chief source of diagnostic information. A correct to deep, visceral emotions. These images, and the emotions diagnosis can be made by the history and physical examination they invoke, have inspired my insatiable passion for medicine. alone in the majority of cases. Prior to the widespread Clinical medicine, as derived from the Greek kline, for ‘bed availability of contemporary paraclinical diagnostics, the or that on which one lies’1 refers to “the practice of medicine history and physical examination was reported to correctly based on the direct observation of patients”. 2 More simply, one diagnose approximately 90% of patient problems.5 A more expert3 has defined it as the day-to-day care of sick patients. recent report,6 which more accurately reflects our current When I had first looked this up, likely as a medical student, I access to diagnostic tests, reports a 60% true positive rate. remember being puzzled: was this not simply medicine? Why In addition, time spent with patients is fundamental to the was such a qualifier necessary? It seemed redundant. physician-patient relationship. Time is a key driver of patient Over time, during academic training, the qualifier took on satisfaction7 and education7,8 and may be associated with new meaning and became increasingly necessary. As residency improved outcomes in certain conditions.8 Furthermore, it is progressed, medicine was no longer synonymous with the interesting to note that as we spend less time with our patients, day-to-day care of sick patients. Administrative, research, and there appears to be an ever greater emphasis on the Patient educational agendas competed with the importance of clinical Safety and Quality Improvement movements. care. What I once understood to be the entirety of medicine The time is ripe for a renaissance of clinical medicine. As is became but one small part. the case with many complicated constructs, clinical expertise While these realizations dawned, candid reports detailing is easier to recognize than to define. It defies simple metrics. the evolving realities of patient care emerged. Bedside rounds, Is it measured in terms of increased patient satisfaction? Or once the paragon of inpatient care and education, have been by decreased hospital length of stay, improved diagnostic largely replaced with verbal rounds in sterile conference accuracy, or by more expert therapeutic decisions that rooms. Further, one well-designed prospective study4 reported translate into decreased morbidity and mortality? In short, that residents on an inpatient medical service spent just 12% yes- a combination of these and more. of their time directly with patients. This equated to less than

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 13 Seeing Wisely: The Pursuit of Clinical Expertise

Experience seems to be the critical ingredient. With this References in mind, at the completion of my general internal medicine 1. www.etymonline.com/index.php?allowed_in training, I intentionally immersed myself in a variety of clinical frame=0&search=clinic&searchmode=none. Accessed July 27, 2015. 2. http://dictionary.reference.com/browse/clinical+medicine. Accessed July 27, practices - academia, rural communities, outpatient practice, 2015. and intensive care medicine – to gain the experience that 3. Cassell EJ. The nature of clinical medicine: the return of the clinician. New seemed so critical to the acquisition of expertise. Although a York: Oxford University Press; 2015. 4. Block L, Habicht R, Albert WW et al. In the Wake of the 2003 and 2011 Duty better physician than when I set out, I am not as strong as I Hours Regulations, How Do Internal Medicine Interns Spend Their Time? might be, as my single-minded focus on experience came at a J Gen Intern Med 28(8):1042–7. cost; in seeing so many patients, I was never able to reflect on 5. Peterson MC, Holbrook JH, Hales D, et al. Contributions of the history, physical examination, and laboratory investigation in making medical any individual patient enough. In failing to routinely reflect, diagnoses. West J Med 1992(156):163-165. read, and discuss cases with colleagues, I squandered a large 6. Paley L, Zornitzki T, Cohen J, et al. Utility of Clinical Examination in the part of the learning from each encounter. Diagnosing and Diagnosis of Emergency Department Patients Admitted to the Department of Medicine of an Academic Hospital. Arch Intern Med. 2011;171(15):1393-1400 managing patients on existing knowledge only curbed my 7. Morell DC, Evans ME, Morris RW, et al. The “five minute” consultation: clinical progress. Experience had paradoxically undermined effect of time constraint on clinical content and patient satisfaction. Br Med J. my quest for expertise. Osler’s dictum – that “the value of 1986;292:870. 8. Dugdale DC, Epstein R, Pantilat SZ. Time and the patient–physician experience is not in seeing much but in seeing wisely” – had relationship. J Gen Intern Med. 2001;14(S1):S34–40. never wrung more true.

The Doctor by Sir Luke Fildes 1887

14 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Clinical Medicine: Arts and Sciences Handover: The Fragile Lines of Communication Andrew Smaggus MD, Adina S. Weinerman MD

About the Authors Andrew Smaggus is a staff physician in the Division of General Internal Medicine at Western University in London, Ontario. Adina S. Weinerman is a staff physician in the Division of General Internal Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario

Summary Handovers have been increasingly recognized as an important determinant of patient safety and quality of care. Changes in patterns of physician and resident work hours have increased the importance of safe handover. The current review summarizes previous literature on deficiencies in current handover practices, consequences of suboptimal handover, and barriers to effective handover. This review concludes by summarizing results of studies that used education, standardization, technology, and bundled interventions to improve handover.

Introduction What problems exist in current handover Handover is the act of transferring both the responsibility practices? for a patient’s care, and the information necessary to provide Many early studies of handover were single-centre audits care, from one healthcare professional (or team) to another. that identified content omissions in handover (summarized in Handover has increasingly been recognized as an important Table 1).5,6,7,8 Surprisingly, some of the omitted content (e.g. patient safety issue, especially as recent changes in physician and current status, active medical problems) was vital information. resident work hours have increased the need for safe handover Estimating the frequency of these omissions is difficult, as the practices.1 A study of handover frequency at an academic US goal of these studies was primarily to characterize the omitted centre found that on a one-month internal medicine clinical information. However, the nature of this omitted information teaching unit rotation, a typical intern was involved in 300 highlights the potential impact of handover on patient safety. patient handovers. In addition, a patient admitted for 5 days Unlike handover content, deficiencies of the handover had their information handed-over approximately 15 times.2 process have not been studied as often. The most in-depth The failure of duty-hour restrictions to improve measures investigation involved retrospective interviews with residents of patient safety may be due to an increase in handovers.3,4 who were asked to recall adverse events in which suboptimal When the greater demands for handover are combined with handover occurred.8 Using this method, the most commonly the growing complexity of internal medicine patients, the identified deficiency in the process was the lack of face-to- potential consequences of inadequate handover on patient face communication during handover. Other identified safety increase substantially. process deficiencies that lead to communication breakdowns This article will aim to review the current state of handover were illegible handwriting and double handovers, where between physicians in the inpatient medical setting, using a the primary team handed over to a covering physician, who quality improvement perspective. then handed over to another physician (as often occurs in

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 15 Handover: The Fragile Lines of Communication

night-float systems). One study demonstrated that While these studies implicated handover as a cause of harm 41% of handovers at one institution (which utilizes a night to patient, direct evidence of handover leading to adverse float system) did not involve a physician from the patient’s events has been difficult to demonstrate. One study that did primary team.7 investigate patient harms identified adverse events that could be attributed to handover at a rate of 7.5 per 100 patient days.5 Evidence of harm from handover issues has also been Table 1. Classification and examples of omitted handover content. Anticipatory guidance refers to instructions provided to covering physicians inferred from malpractice claims. A study of missed or delayed to be carried out if a potentially foreseeable event occurs. diagnoses identified approximately 20% and 24% of claims involved inadequate handover in ambulatory care and the Omitted Content Example(s) emergency department, respectively.12,13 Active medical problems/ - Failure to inform covering MD of active The perception of postgraduate trainees is that handover current clinical status bronchospasm requiring bronchodilator problems contribute to adverse events. When surveyed, therapy that day. Patient required residents in internal medicine and surgical specialties believed transfer to higher level of care.5 that 9.4% of patients they had cared for had suffered harm due - Failure to inform covering MD of to a handover problem and 12.3% of those harms had major elevated BPs in a patient who had consequences.6 required multiple doses of IV anti- hypertensives.8 What are the barriers to effective handover? Recent significant events - Episode of hypoglycemia in a patient with diabetes (treated with insulin) not The transfer of information is a recognized source of error 14 handed over.5 in multiple professions. From a systems perspective, the Pending events and - Failure to notify covering MD of multiple lack of standardized processes is a major barrier to efficient investigations pending consults from subspecialties.8 handover. In many institutions, handover is carried out in a 15 Rationale for desired action - Covering MD not informed of rationale haphazard manner according to the availability of physicians. for MRI (to define anatomy prior to OR The lack of a consistent, dedicated space for handover may planned for the next morning). MRI contribute to the high frequency of interruptions that affect was not performed.5 handover.16 The cognitive psychology literature suggests - Failure to include rationale for not that interruptions can have deleterious effects on tasks, like initiating antibiotics leading to handover, that have high demands on working memory.17 uncertainty.8 Time pressures may contribute to the failure of the primary Anticipatory guidance - Attempts at guidance either absent, or team to provide detailed instructions and for the covering vague (“If you are called regarding high physicians to ask questions and seek clarification. It has been 7 blood sugars, can you start insulin?”). estimated that each patient is discussed for an average of 35 seconds during handover, leaving little time for questions or clarification.7 Another systemic issue affecting handover quality is a lack of specific training regarding handover during medical school and residency. A survey of internal medicine training programs What are the consequences of deficiencies in in 2006 indicated that 60% of programs did not provide any handovers? instruction in handover.18 The potential for handover to affect the quality of patient In addition to these systems issues, there are cognitive care has been suspected for many years. A study from the aspects to handover that affect the individuals involved. 1990s suggested a link between discontinuity of physician In many academic centres, handover is often carried out coverage and adverse events.9 Years later, in a review of almost between a senior resident and a junior resident. Though other 5000 sentinel events, the Joint Commission concluded that industries have a greater appreciation of how hierarchies affect communication failures (including handover) contributed to the transfer of information these may be just as pertinent in 60-80% of preventable patient safety incidents.10,11 medicine.19 However, the one study that reported on this

16 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Smaggus and Weinerman

phenomenon found little evidence that it affected handover improve safety than education.23,24 Many centres have between interns and senior residents.7 attempted to strengthen handover through standardization.26 Another cognitive factor that may affect handover is the Handover mnemonics are a standardization attempt to ‘egocentric bias’ demonstrated in a study in which residents assist clinicians in remembering the important content of were asked to estimate the effectiveness of their handover. handover and to provide structure to the handover process. Residents who provided handover expected on-call residents A large number of handover mnemonics (e.g. SIGNOUT, to recall important pieces of information more effectively HANDOFFS, ANTICipate) have been developed, intended for than the on-call residents were able to when tested use in a variety of settings (e.g. inpatient setting, emergency (2.6 vs. 1.6, p < 0.01).20 department).27 While this overestimation of the effectiveness of Isolated studies of standardization attempts have handover may reflect an egocentric bias on the individual documented increased comfort, confidence, and satisfaction providing handover, the high complexity of the information in handover content amongst trainees.28,29 One study communicated may also affect the ability of on-call physicians also demonstrated a perception amongst trainees that the to retain salient points. Previous research has suggested that standardized handover format led to increased updates to attention and engagement vary as the complexity of a task patients and family members. More definitive evidence (i.e. increases,21,22 which may contribute to the lack of questioning beyond the perceptions of physicians) has not been measured. observed during handover sessions.7 Technology What interventions to improve handover have The use of technology has proven to be an effective method been studied? of improving handover.23,24 Multiple studies have demonstrated Many institutions have pursued quality improvement an association between the implementation of a computerized initiatives that focus on handover. The formats of these handover tool and an improvement in measures of handover attempts differ, but most include education, standardization, quality. One study demonstrated a reduction in content implementation of technology, or a combination of these (i.e. omissions following implementation of a computerized bundled interventions). sign-out tool,30 while another found that the reported accuracy of handover was higher after the implementation of Education an online signover.31 In the context of quality improvement, education is used Adverse events (defined as events that prolonged hospital to address gaps in knowledge that contribute to deficient stay or resulted in patient disability), as reported by physicians, practices. However, as an intervention, education is generally were found to be lower following the implementation of a regarded as having limited effectiveness.23,24 Educational computerized handover tool.32 interventions to improve handover quality were addressed in a systematic review that found improvements were generally Bundled Interventions limited to attitudes, knowledge, and skills and not to actual Early investigations demonstrated the potential of bundled behavior change or performance.25 interventions to improve measures of handover quality.33,34 The One educational intervention that appears promising is most impressive results from a handover intervention were teamwork training. This has been used in other industries recently reported from a study involving a bundled intervention to improve communication between team members, and to for pediatric residents. This before and after study investigated overcome barriers created by authority gradients.19 While the effect of a “handoff bundle” (teamwork training, use of the not studied on its own, teamwork training has begun to be I-PASS mnemonic and a structured sign-over tool) on errors introduced into bundled interventions to improve handover on 2 pediatric wards within a single centre. Medical errors (see below). occurred significantly less frequently in the 3-month period after the implementation of the handover bundle compared Standardization to a 3-month period before its implementation (18.3 vs. 33.8 Standardization of processes, with integration of safe medical errors per 100 admissions, p < 0.001). Fewer content practices, is regarded as a more effective intervention to omissions were noted after the bundle was implemented, and

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 17 Handover: The Fragile Lines of Communication

no differences in the time spent handing over were observed.35 12. Gandhi TK, Kachalia A, Thomas EJ, et al. Missed and delayed diagnoses in Though the study had limitations,36 it demonstrated the ambulatory setting: A study of closed malpractice claims. Ann Intern Med 2006;145:488-496. the possibility to reduce patient harm with improvements 13. Kachalia A, Gandhi TK, Puopolo AL, et al. Missed and delayed diagnoses in handover. in the emergency department: A study of closed malpractice claims from 4 liability insurers. Ann Emerg Med 2007;49:196-205. 14. Patterson ES, Roth EM, Woods DD, Chow R, Gomes JO. Handoff strategies Conclusion in settings with high consequences for failure: Lessons for health care The changing profile of physician work hours has operations. Int J Qual Health Care. 2004;16:125-132. increased the need for effective handover. As with other 15. Horwitz LI, Krumholz HM, Green ML, Huot SJ. Transfers of patient care between house staff on internal medicine wards: A national survey. Arch quality improvement initiatives, the greatest benefits have Intern Med 2006;166:1173-1177. been demonstrated following implementation of bundled 16. Estryn-Behar MR, Milanini-Magny G, Chaumon E, et al. Shift change interventions. While these findings are promising, evidence handovers and subsequent interruptions: Potential impacts on quality of care. J Patient Saf 2014;10:29-44. linking improved handover to improved patient safety is still 17. Li SYW, Magrabi F, Coiera E.A systematic review of the psychological sparse, and many barriers to effective handover remain poorly literature on interruption and its patient safety implications. J Am Med addressed. As demands for high value care increase, handover Inform Assoc 2012;19:6-12. 18. Horwitz LI, Krumholz HM, Green ML, Huot SJ. Transfers of patient care is likely to remain a key target for quality improvement between house staff on internal medicine wards: A national survey. Arch interventions. Intern Med 2006;166:1173-1177. 19. Cosby KS, Croskerry P. Profiles in patient safety: Authority gradients in medical error. Acad Emerg Med 2004;11:1341-1345. References 20. Chang VY, Arora VM, Lev-Ari S, D’Arcy M, Keysar B. Interns overestimate 1. National Steering Committee on Resident Duty Hours. 2013. Fatigue, Risk the effectiveness of their hand-off communication. Pediatrics 2010;125:491- and Excellence: Towards a Pan-Canadian Consensus on Resident Duty 496. Hours. Ottawa, Ontario: The Royal College of Physicians and Surgeons of 21. Kahneman, D. Attention and Effort Englewood Cliffs, NJ: Prentice-Hall Inc.; Canada. 1973. Available at: https://www.princeton.edu/~kahneman/docs/attention_ 2. Vidyarthi AR, Arora V, Schnipper JL, Wall SD, Wachter RM. Managing and_effort/Attention_lo_quality.pdf. Accessibility verified September 10, discontinuity in academic medical centers: Strategies for a safe and effective 2014. resident sign-out. J Hosp Med 2006;1:257-266. 22. Redelmeier DA, Shafir E. Medical decision making in situations that offer 3. Moonesinghe SR, Lowery J, Shahi N, Millen A, Beard JD. Impact of multiple alternatives. JAMA. 1995;273:302-305. reduction in working hours for doctors in training on postgraduate medical 23. Woods DM, Holl JL, Angst D, et al. Improving clinical communication education and patients’ outcomes: Systematic review. BMJ 2011;342:1580- and patient safety: clinician-recommended solutions. In: New Directions 1592. and Alternative Approaches. July 2008. Agency for Healthcare Research and 4. Pattani R, Wu PE, Dhalla IA. Resident duty hours in Canada: Past, present Quality, Rockville, MD. Available at: http://www.ahrq.gov/professionals/ and future. CMAJ 2014;186:761-765. quality-patient-safety/patient-safety-resources/resources/advances-in- 5. Horwitz LI, Moin T, Krumholz HM, Wang L, Bradley EH. Consequences of patient-safety-2/index.html. Accessibility verified September 10, 2014. inadequate sign-out for patient care. Arch Intern Med 2008;168:1755-1760. 24. Institute for Safe Medication Practices. Medication error prevention 6. Kitch BT, Cooper JB, Zapol WM, et al. Handoffs causing patient harm: “toolbox.” Medication safety alert. June 2, 1999. Available at: http://www. A survey of medical and surgical house staff. Jt Comm J Qual Patient Saf ismp.org/newsletters/acutecare/articles/19990602.asp. Accessibility verified 2008;34:563-570. September 10, 2014. 7. Horwitz LI, Moin T, Krumholz HM, Wang L, Bradley EH. What are covering 25. Gordon M, Findley R. Educational interventions to improve handover in doctors told about their patients? Analysis of sign-out among internal health care: A systematic review. Med Educ 2011;45:1081-1089. medicine house staff. Qual Saf Health Care. 2009;18:248-255. 26. DeRienzo CM, Frush K, Barfield ME, et al. Handoffs in the era of duty hours 8. Arora V, Johnson J, Lovinger D, Humphrey HJ, Meltzer DO. reform: A focused review and strategy to address changes in the accreditation Communication failures in patient sign-out and suggestions for council for graduate medical education common program requirements. improvement: A critical incident analysis. Qual Saf Health Care. Acad Med 2012;87:403-410. 2005;14:401-407. 27. Riesenberg LA, Leitzsch J, Little BW. Systematic review of handoff 9. Petersen LA, Brennan TA, O’Neil AC, Cook EF, Lee TH. Does housestaff mnemonics literature. Am J Med Qual 2009;24:196-204. discontinuity of care increase the risk for preventable adverse events? 28. Horwitz LI, Moin T, Green ML. Development and implementation of an oral Ann Intern Med 1994;121:866-872. sign-out skills curriculum. J Gen Intern Med 2007;22:1470-1474. 10. The Joint Commission. Joint Commission Center for Transforming 29. Moseley BD, Smith JH, Diaz-Medina GE, et al. Standardized sign-out Healthcare releases targeted solutions tool for hand-off communications. improves completeness and perceived accuracy of inpatient neurology Available at: http://www.jointcommission.org/assets/1/6/TST_HOC_ handoffs. Neurology. 2012;79:1060-1064. Persp_08_12.pdf. Accessibility verified September 10, 2014. 30. Flanagan ME, Patterson ES, Frankel RM, Doebbeling BN. Evaluation of a 11. The Joint Commission. Sentinel event data: root causes by event type physician informatics tool to improve patient handoffs. J Am Med Inform 2004-2013. Available at: http://www.jointcommission.org/assets/1/18/Root_ Assoc 2009;16:509-515. Causes_by_Event_Type_2004-2Q2013.pdf Accessibility verified September 10, 2014.

18 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Smaggus and Weinerman

31. Palma JP, Sharek PJ, Longhurst CA. Impact of electronic medical record integration of a handoff tool on sign-out in a newborn intensive care unit. J Perinatol 2011;31:311-317. 32. Petersen LA, Brennan TA, O’Neil AC, Cook EF, Lee TH. Does housestaff discontinuity of care increase the risk for preventable adverse events? Ann Intern Med 1994;121:866-872. 33. Boggan JC, Zhang T, Derienzo C, Frush K, Andolsek K. Standardizing and evaluating transitions of care in the era of duty hour reform: One institution’s resident-led effort. J Grad Med Educ 2013;5:652-657. 34. Graham KL, Marcantonio ER, Huang GC, Yang J, Davis RB, Smith CC. Effect of a systems intervention on the quality and safety of patient handoffs in an internal medicine residency program. J Gen Intern Med 2013;28:986- 993. 35. Starmer AJ, Sectish TC, Simon DW, et al. Rates of medical errors and preventable adverse events among hospitalized children following implementation of a resident handoff bundle. JAMA 2013;310:2262-2270. 36. Horwitz LI. Does improving handoffs reduce medical error rates? JAMA 2013;310:2255-2256.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 19 Clinical Medicine: Arts and Sciences An Approach to ‘The Social Admission’

Melissa K. Andrew, MD, PhD, Colin Powell, MB, FRCP (Lond, Edin et Glas)

About the Authors Melissa K. Andrew is an Associate Professor in the Department of Medicine, Division of Geriatric Medicine, at Dalhousie University in Halifax. Her research focuses on frailty in relation to social vulnerability and dementia, and she leads a research team on these topics within the Canadian Consortium on Neurodegeneration in Aging (CCNA). Correspondence may be directed to [email protected]. Colin Powell is Professor of Medicine (retired) at the University of Calgary, and Adjunct Professor of Geriatric Medicine at Dalhousie University. He served as Associate Editor for Ageing of the Canadian Journal of General Internal Medicine.

lthough the ‘social admission’ is no doubt a familiar causes and consequent treatments. A key difference lies in the Aoccurrence for most general internists and physicians who scope of required investigations; while investigation into most work in hospital-based practice, it is difficult to say exactly how medical conditions, as with anaemia, can generally be limited common such admissions to hospital are, or what percentage to patient-level factors (bowel lesions, bleeding, hematological of older people admitted to hospital are seen in this light. disorders etc,), unravelling the factors contributing to a social Nevertheless, this is frequent enough to merit attention to admission necessitates a broader approach. Recognizing that the underlying causes and contributing factors; this is the aim of patient is embedded in a nested social structure of families and the current article. caregivers, peer groups, institutions, and society more generally can provide a useful framework for organizing clinical thinking What is a social admission? and investigation. (Figure 1)2 Considering the factors that may There is no single accepted definition of a social admission, contribute at each level will likely be a fruitful exercise, since in and it is likely that many different situations may end up with most cases, the social admission is multifactorial in aetiology. this label or one of its numerous synonyms (some, such as ‘acopia’ and ‘bed-blocker,’ which are less appropriate than Patient Factors others).1 For the purposes of this article, a social admission Progression in previously diagnosed (or indeed new and is defined as a hospital admission for which no acute medical undiagnosed) illnesses, disabilities, poorly managed pain, issues are felt to be contributing; rather the patient’s social psychiatric conditions, cognitive decline, behavioural and circumstances are felt to be the sole cause, be it the breakdown psychological symptoms of dementia (BPSD), polypharmacy of home supports or the inability of the patient and/or family and medication adverse effects can all contribute to a nominally to cope with the demands of living at home. As we shall see, social admission. Taken together, multiple interacting physical, social admissions are heterogeneous, with many potential mental and social problems lead to a state of frailty where there contributing factors. Therefore, an organized approach to the is insufficient reserve to compensate for any additional (even patient admitted for social reasons will be helpful for busy seemingly minor) perturbations in health, functional status clinicians providing hospital care for older patients. or social conditions.3 Social admissions are thus clearly an important marker of frailty, and more generally, of vulnerability. Causes and contributing factors Similar to other geriatric syndromes like delirium and falls, Family and Informal Caregiver Fctors the social admission should be considered to be an indication Family members and other informal caregivers often play for a thorough investigation of underlying and contributing vital roles in supporting older patients. Informal caregivers causes, in order to address any reversible ones and to identify (friends and family) are distinguished from formal caregivers a management plan that may improve or alleviate the patient’s (health care workers in various roles) by their long term situation. The approach to anaemia provides a useful analogy. relationships with care recipients, and the fact that they are We would not accept a diagnosis of ‘anaemia’ as final, as unpaid and often have no formal training. Informal caregivers doing so would miss the precise identification of contributing often face many competing demands for their time and

20 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Andrew and Powell

resources, and escalating care requirements may be a source help at home. In the bigger picture of our health care system, of caregiver stress and burnout. Caregiver stress is experienced frail individuals may not be well served by the current ‘one by a family or friend caregiver related to assisting their loved thing wrong at one time’ approach to medical care, which is one, and it has important implications not only for the not generally receptive of taking the ‘big picture’ of a patient’s relationship but also for the physical and mental health of the health and functional needs into account all at once.6 caregiver.4 Caregivers may also worry about physical demands (e.g. helping their loved one transfer and mobilize), and about Societal and policy factors safety (their own or the patient’s). The social and policy environments in which people live Caregiving can also have financial ramifications, both in can greatly influence their opportunities to feel valued and seek the short term (e.g. reducing hours of work or taking a leave access to needed supports. For example, government policies to of absence as care needs escalate), and the long term (e.g. support caregivers in caring for their loved ones at home can be time away from the workforce may have retirement income instrumental; the lack of such support at a policy level can have the implications in the future). Socioeconomic considerations are opposite effect. Likewise, the presence of a generally supportive thus very important. community, which demonstrably values its senior citizens, may Lack of a viable ‘back-up plan’ in case the caregiver becomes play a vital role in supporting vulnerable older people. Ideas such ill or engages in travel is another factor that may contribute to as social capital and social cohesion are important at this level a social admission. Also important are features of the home – that is to say the overall connectedness and caring for others environment including safety, accessibility, and suitability that exists in a community.7 The built environment, or the design for meeting the patient’s care needs. To complicate matters, of buildings and communities in which people live, is another patients and families may decline assistance or supports that important factor. Accessible and age-friendly communities are are offered by health care providers; living at risk in this way is key to enabling social participation.8 the prerogative of older adults who have the capacity to make With careful attention to the above factors, in the majority personal care decisions. of cases, the social admission will be found to be multifactorial with contribution from most if not all levels. In the end, varied Peer group factors causes require varied responses. Engagement in social activities is known to be protective for health and cognition.5 For example, does the patient have Outcomes contact with friends and attend social gatherings or activities on When combined with high levels of frailty that are a regular enough basis to prevent becoming isolated? A tangible commonly present in such cases, social factors precipitating example of the benefit of such engagement would be a person admission to hospital place patients at a higher risk for poor noted to be missing from a regular social gathering, leading to outcomes. Even among the healthiest older adults who are a search of their home and the discovery that they have become community dwelling, high social vulnerability more than incapacitated and unable to seek help due to some illness or doubles the risk of mortality over 5 years, with an absolute calamity. In less fortunate cases, isolated older people have been mortality increase of 20%.9 While there is a paucity of data discovered too late, deceased in their homes or apartments, with on outcomes for hospitalized social admissions, it is clear that no one having noticed their absence or distress. Another problem these outcomes are even worse. Mortality rates worse than is that peers may stop socializing with an older person who has those of cardiac failure have been reported; one study in the dementia or other serious illness due to discomfort surrounding UK found that a diagnosis of ‘acopia’ was associated with high a stigmatizing diagnosis or awkward social interactions. levels of frailty and an in-hospital mortality rate of 22%, and that only a small minority (6 percent) of patients so labeled Institutional factors actually had no acute medical issues identified after a proper Formal supports, in the form of home care services, respite workup.10 In a Swiss study of 253 patients (mean age 81) triaged care or other assistance, may be available, but barriers to access in the Emergency Department (ED) as ‘home care impossible’, often exist. Families may have limited awareness of available acute medical problems were eventually identified in 51%, and supports and how to initiate access. Provincial Home Care 26% were found to have been undertriaged due to neurological services may have lengthy wait times and limitations in the symptoms or atypical presentations having been missed and amount of time and types of services they can provide. Families vital signs not being taken.11 This highlights the broader may face economic or geographic barriers to hiring needed problem of frail older adults often being undertriaged in ED

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 21 An Approach to “The Social Admission”

settings particularly when frailty is not formally assessed.12 A • ‘Social admissions’ are of complex aetiology Swedish study of 380 patients presenting to the ED diagnosed • Patients admitted ostensibly for social reasons often with ‘lack of community supports’ identified physical medical have underlying unrecognized medical problems causes in 85%. The vulnerability of these patients is highlighted by their finding of 34% one-year mortality.13 • A structured approach is helpful for considering the patient’s social circumstances at each level from the Suggested management patient through the family and caregiver, peer groups, Given that complex medical issues are often present and institutions and society at large that outcomes are so poor, it is important to avoid falling into • Social admissions and social vulnerability are associated the bias-laden trap of discounting a patient as ‘only a social with adverse outcomes including high mortality admission.’ To address patient-related factors, a workup for underlying medical illness, cognitive impairment and mood disorders is indicated. Given the prevalence of polypharmacy References in this patient population, careful attention to medication 1. Oliver D, ‘Acopia’ and ‘social admission’ are not diagnoses: why older people deserve better. J R Soc Med, 2008. 101(4): p. 168-74. review is also warranted. Ideally, a comprehensive geriatric 2. Andrew M and Keefe J, Social vulnerability among older adults: a social assessment and involvement of the multidisciplinary team ecology perspective from the National Population Health Survey of Canada. should be sought. The issues around a social admission are BMC Geriatrics, 2014(14): p. 90. 3. Hogan DB, MacKnight C, and Bergman H, Models, definitions, and criteria broad, and involving a social worker is essential. Nevertheless, of frailty. Aging Clinical and Experimental Research, 2003. 15(3 Suppl): p. key roles remain for physicians and other team members. 1-29. Medical expertise can contribute in important ways to both 4. Grunfeld E, Glossop R, McDowell I, et al., Caring for elderly people at home: the diagnostic investigation and the ensuing problem-solving. the consequences to caregivers. CMAJ, 1997. 157(8): p. 1101-5. 5. Fratiglioni L, Paillard-Borg S, and Winblad B, An active and socially The attending physician should therefore not simply defer care integrated lifestyle in late life might protect against dementia. Lancet to others without thinking of the situation in a critical light. Neurology, 2004. 3(6): p. 343-53. One can expect that working through the framework presented 6. Rockwood K, What would make a definition of frailty successful? Age Ageing, 2005. 34(5): p. 432-4. here to identify potential contributing factors at each level from 7. Baum FE and Ziersch AM, Social capital. J Epidemiol Community Health, the patient through the family and caregiver, peer groups, 2003. 57(5): p. 320-3. institutions and society at large will lead to the identification of 8. WHO. Age-friendly cities. [cited 2013 July 14]; Available from: http://www.who.int/ageing/age_friendly_cities/en/. some modifiable contributing factors – for example treatable 9. Andrew M, Mitnitski A, Kirkland SA, et al., The impact of social vulnerability medical issues or areas in which increased supports could be on the survival of the fittest older adults. Age and Ageing, 2012. 41(2): p. sought. At the very least, embracing the complexity that underlies 161-5. 10. Kee YY and Rippingale C, The prevalence and characteristic of patients with the (non-)diagnosis of the social admission will help to improve ‘acopia’. Age Ageing, 2009. 38(1): p. 103-5. care for this vulnerable group of patients. 11. Rutschmann OT, Chevalley T, Zumwald C, et al., Pitfalls in the emergency department triage of frail elderly patients without specific complaints. Swiss Med Wkly, 2005. 135(9-10): p. 145-50. 12. Goldstein JP, Andrew MK, and Travers A, Frailty in Older Adults Using Pre-hospital Care and the Emergency Department: A Narrative Review. Can Geriatr J, 2012. 15(1): p. 16-22. 13. Elmstahl S and Wahlfrid C, Increased medical attention needed for frail elderly initially admitted to the emergency department for lack of community support. Aging (Milano), 1999. 11(1): p. 56-60.

Figure 1. The patient is embedded in a nested social structure.2

22 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Clinical Medicine: Arts and Sciences

Acute Care SINS: Surgical Insights for the Non-surgeon Chapter 13: Spine Surgery SINS

Aaron S. Robichaud MD, David B. Clarke MDCM PhD, Cian O’Kelly MD, Martin Beed DM, Peter G. Brindley MD

Robichaud Clarke O’Kelly Beed Brindley About the Authors Aaron Robichaud is a Resident in Neurosurgery and David Clarke is Professor and Head of Neurosurgery at Dalhousie University, in Halifax, Canada. Cian O’Kelly is an Assistant Professor of Neurosurgery at the University of Alberta, in Edmonton, Canada. Martin Beed is an Honorary Assistant Professor in Anaesthesia and Consultant in Intensive Care at Nottingham University Hospital in Nottingham, UK. Peter Brindley is a Professor of Critical Care Medicine at the University of Alberta, in Edmonton, Canada. Correspondence may be directed to [email protected].

Summary “Surgical Insights for the Non-surgeon,” or SINS, is composed of several short chapters intended to cover fundamental surgical knowledge for non-surgeons. The authors focus on surgical pearls, operative insights, and applied anatomy. In Chapter 13 of this series, the authors address the brain and neurosurgery Part Two.

Résumé L’ouvrage « Surgical Insights for the Non-surgeon » (aperçu de la chirurgie à l’intention du non-chirurgien) se compose de courts chapitres couvrant les connaissances fondamentales en chirurgie. Les auteurs se concentrent sur des enseignements tirés de leur expérience, des aspects opératoires et l’anatomie appliquée. Dans le chapitre 13 de cet ouvrage, les auteurs abordent le cerveau et la deuxième partie de neurochirurgie.

“The definition of minor surgery: surgery which is done on someone else” ––Old surgical maxim . . . and a useful caution.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 23 Spinal SINS

Anatomy nerve exits beneath the L4 pedicle. It follows that a typical postero- Although the spinal cord constitutes only about 2% of the lateral disc herniation in the cervical spine will affect the nerve central nervous system, it has a vital function: it connects the root that corresponds to the vertebra below that disc space. For body to the brain and vice versa. Without it you would quite example, a C5/6 disc herniation affects the C6 nerve root (Figure literally lose your head! Continuing from the medulla, the spinal 3). Similarly, in the lumbar spine, a typical L4/5 paracentral disc cord extends from the foramen magnum and ends as the conus herniation will affect the L5 nerve root. The uncommon far medullaris at the level of the first or second lumbar vertebra lateral lumbar disc herniations affect the same-level nerve root: for (Figure 1). example, a far lateral L4/5 herniation affects the L4 nerve. Below that, the nerves fan out like a horse’s tail: appropriately In transverse section, the spinal cord has a central H-shaped termed the “cauda equina.” Each nerve is composed of a area of grey matter which contains the cell bodies of the ventral ventral root containing efferent motor fibres and a dorsal (motor) horn and dorsal (sensory) horn. The white matter root containing afferent sensory fibres. These combine in the tracts surround the “H.” These tracts include ascending sensory spinal canal and pass through the vertebral column via the tracts, such as the posteriorly located dorsal columns, which are intervertebral foramina. There are 31 such paired spinal nerves: responsible for ipsilateral light touch and joint position sense. 8 cervical (C), 12 thoracic (T), 5 lumbar (L), 5 sacral (S), and 1 These tracts also include the spinothalamic tracts, which are coccygeal nerve. Each spinal cord segment innervates a sensory responsible for contralateral pain and temperature. Laterally, dermatome (Figure 2) and a motor myotome. The spinal roots the white matter contains the descending motor tract, called may also contain preganglionic sympathetic and parasympathetic the corticospinal tract. This is responsible for ipsilateral limb fibres, depending on the level. movement. This tract crosses (decussates) in the medulla, which The spinal cord is a cylindrical tube 40–50 cm long and is why left brain injury affects the right body and vice versa. 1–1.5 cm in diameter. It has a cervical enlargement between The C1 vertebra, known as the atlas, has large lateral masses to C3–T1 providing innervation to the upper limbs; and a lumbar allow head flexion and extension. The C2 vertebra, known as the enlargement, between L1-S2, providing innervation to the lower axis, has a large anterior projection called the dens, or odontoid. limbs. The C1 nerve exits the spinal canal between C1 and the This articulates closely with C1 to allow rotational head movement. occiput of the skull; the C2–C7 nerves exit above their pedicles Figure 3 shows a typical cervical vertebra below C2. Cervical (for example, C5 exits between C4 and C5, above the pedicle of vertebrae can be distinguished by their bifid spinous processes C5). Remember that there is no C8 vertebra. and the transverse foramina through which the vertebral arteries Below the cervical spine, each nerve leaves the spinal canal below (C3-6) and veins (C3-7) pass. Figure 1 also shows shows a typical the pedicle of its corresponding vertebra. For example, the L4 thoracic vertebra, and a typical lumbar vertebra. Thoracic vertebrae

C1 (Atlas) Cervical vertebrae

Dens (odontoid process of C2)

C2 (Axis) Vertebra prominens (C7 spinous process) Thoracic vertebrae T1

Spinal cord

L1 Lumbar vertebrae

Conus medullaris

Cauda equina

Sacral promontory

Coccyx Figure 1. Mid-sagittal section of the spinal cord and the bony spine column, with typical cervical, thoracic and lumbar vertebrae

6 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Robichaud et al.

are notable for their heart-shaped bodies and the costal facets that Trauma articulate with the ribs. The lumbar vertebrae are broader, have Spine Fractures larger pedicles, and more horizontally oriented facet joints. Enough Cervical spine (C-spine) prose: it is time to match (anatomic) form with (spinal) function. • Separated into atlanto-axial (C1–2) fractures and sub-axial fractures (C3–C7) • Need to determine:

C3 º Mechanism of injury C3 C3 C4 C4 ■ Strong association between head injury and C-spine C3 C4 C3 C4 C4 C3 C4 T1 C4 injury T2 T1 T2 C4 T2 T2 T3 T3 T4 C5 T3T4 T3 T4T5 ■ A high index of suspicion is required after polytrauma C5 T4 T5 T5 T6 C5 T5T6 T6T7 C5 (for example motor-vehicle injuries, or falls from T6 T7 T7 T8 T7T8 T8T9 T9 T10 T2 T8 T9 T2 height) T10T9 T10T11 T10 T11 T12 C6 T11 T1 T12 C6 º Neurologic status (spinal cord and nerve root function) C6 T12T11 T1 L1 C6 T12 L1 L2 º Presence/absence of disruption to the discoligamentous L1 L2 L1 C8 C8 complex L2 S3 L2 S3 • Incomplete spinal cord injury has much better prognosis C8 L3 S2C8 than complete injury L3 S2 C7 S1 C7 C7 L3 S1 L3 • Non-operative management means fracture reduction and C7 L3 S2 L3 S2 S4 immobilization S4 S5 S5 L4 º Reduction, if required, equals traction with a halo ring, L4 L5 L4 L5 L5 L4 L5 provided the patient can participate in serial assessments of their neurologic status

S1 L5 º Once the halo is secured to the skull S1 L5 S1 Weight is added using a traction system S1 ■ ■ General rule is 5 lbs for the head Figure 2. Map of dermatomes relating to cervical through to sacral nerve roots ■ Plus 2.5 lbs for each cervical spine level above the fracture ■ Before adding additional weight: Nerve roots • Confirm no change in the neurologic exam Nerve roots C1 • Review a lateral X-ray to check for reduction vs. C1 AtlasAtlas over-distraction º Once reduction is achieved, some patients can be C8 C7 C7 C8 T1 T1 T1 T1 immobilized using the halo-vest attachment • Indications for operative reduction and stabilization include: º Failure of non-operative management A A º Fractures deemed unstable A A º Surgery may also be required to decompress the nerve roots or the spinal cord (i.e. the neural elements) • Common C-spine fractures T12T12 º Jefferson’s: fracture of anterior and posterior arches of C1 Conus L1 L1 Conus ■ Axial compression or hyperextension medullarismedullaris B ■ Lateral displacement of C1’s lateral masses Cauda B Cauda ■ Often unstable L5 equinaequina L5 º Hangman’s: fracture of both pedicles of C2 FilumFilum ■ Neck hyperextension terminale terminale Type I: pedicles only C C ■ Type II: also into the body of C2 Figure 3. Coronal view of the spinal cord demonstrating: A. Cervical nerve root ■ compression (8 cervical nerves but 7 cervical vertebrae. Therefore, C6/7 disc ■ Type III: includes facet dislocation; unstable herniation affects C7 nerve root, whilst T1/2 herniation affects T1 nerve root); B. º Clay Shoveler’s: spinous process fracture of C6, C7, or T1 Lumbar nerve root compression from a paracentral disc herniation (Paracentral ■ Hyperflexion of neck; avulsion of the spinous process disc herniations do not impinge on the nerve root exiting, but on the nerve root º Odontoid fractures: fracture of the dens of C2 entering the lateral recess- which exits at the level below. Therefore, L4/5 disc ■ Type I in the upper odontoid affects L5 nerve root); C. Far lateral disc herniation (therefore L4/5 disc affects • Rare, but potentially unstable L4 nerve root)

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 25 Spinal SINS

■ Type II in the base of the odontoid ■ Disc space narrowing or widening • Unstable and with a high risk of non-union • MRI if there is remaining doubt ■ Type III through the odontoid and into the body of C2 º Therefore, CT is required in most trauma • Most likely to heal due to this fracture’s large surface º MRI can identify any spinal cord compression or injury, area and can assess ligamentous injury ■ BUT can be avoided Thoracolumbar (TL) Spine • If no concern of bony/ligamentous disruption • Principles of TL surgery • If the patient is clinically intact º Fracture reduction if necessary (open or closed) • Clinical clearance º Decompression if there is compromise of neural elements º Patient must be awake, able to follow commands, free of º Certain fractures are amenable to non-operative distracting injuries stabilization º Full neurological exam should be done º Surgical fusion for instability and failed non-operative ■ This includes motor and sensory function stabilization ■ Includes both the upper and lower extremities • Fractures are considered unstable if more than two of three ■ Includes rectal tone/sensation columns are affected • “If you don’t put your finger in it; you’ll put your º Anterior column includes the anterior longitudinal foot in it” (old surgical [and medical]) maxim ligament and anterior two-thirds of the vertebral body º Any physician is capable of clinically clearing the spine º Middle column contains the posterior longitudinal º Consultation with spine surgeon not always required ligament and posterior one-third of the vertebral body ■ But appropriate for those with documented/highly º Posterior column contains the pedicles, facets, laminae, suspected spine fracture or neurologic injury and spinous processes Spinal Cord Injury (SCI) ‘Clearing’ the Spine Definitions • To fully clear the spine • Level of injury º Attend to both the radiological and clinical components º Described as being the most caudal spinal cord segment º Must be no radiographic evidence of bony or ligamentous with motor function at least 3/5 disruption ■ Also with pain and temperature sensation preserved º Must be no clinical evidence of spinal cord or nerve root ■ For example, quadriplegia with preserved bicep injury function is called a C5 injury • Spine precautions • Incomplete injury º Cervical collar, flat patient, and bed rest/log-roll º Residual motor or sensory function four or more ■ Maintain until the spine is cleared segments below the level of injury º Back board is not necessary • Complete injury ■ Should be removed on Emergency Department arrival º No motor or sensory function four or more segments • Because it predisposes to the development of sacral below the level of injury ulcers • Neurogenic shock • Radiographic clearance º Hypotension/hypoperfusion following spinal cord or º In awake and cooperative patient with no distracting brain injury injury, complete and adequate plain X-rays (seeing down º Loss of vascular tone due to disrupted sympathetics to C7–T1 and including flexion/extension views) are ■ In spinal cord injury, involves the cervical or high adequate for c-spine clearance thoracic cord º However, CT scan is the gold standard when looking for • At or above the level where the vascular sympathetics spinal fractures leave the spinal cord (T1–T12) º Also, CT is required to º Unopposed activity from the cardiac parasympathetics ■ Better elucidate fractures seen on X-ray (vagal nerve) ■ When the X-rays are inadequate or incomplete ■ Causes an inappropriate bradycardia ■ Or when there is a high index of suspicion of severe º Loss of muscle tone from skeletal paralysis below the level injury of injury º Evidence of ligamentous disruption may be picked up by ■ Causes decreased venous return CT ■ Further exacerbates hypotension ■ Widening of the facet joints • Spinal shock

26 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Robichaud et al.

º NOT the same thing as neurogenic shock º Bilateral motor paralysis below level of injury º Transient loss of all neurologic function (voluntary and º Painful dysesthesia in the upper extremities reflex) below level of injury º Bilateral loss of pain and temperature (spinothalamic º Flaccid paralysis and areflexia tract) ■ Lasts 1–2 weeks º Sparing of two-point discrimination, vibration and º Probably due to potassium loss in injured cells proprioception ■ Extracellular potassium accumulation and axonal ■ This would imply preservation of the dorsal columns inhibition • Brown-Séquard syndrome ■ Once potassium equilibrates, spinal shock ceases º Results from spinal cord hemi-section º Paralysis may persist after spinal shock resolves º Rarely a traumatic injury, but could occur in penetrating ■ But with the emergence of upper motor neuron signs trauma • Spasticity and hyper-reflexia ■ Can also follow a large space-occupying lesion or focal º Bulbocavernosus (BC) reflex demyelination ■ Typically one of first reflexes to return after spinal • Including paracentral disc herniation shock º Ipsilateral loss of motor function below the level ■ Absence of motor and sensation BUT presence of BC (corticospinal tract) reflex º Ipsilateral loss of proprioception/vibration (dorsal • Indicates complete spinal cord injury columns) • Namely, loss of function is no longer due to spinal º Contralateral loss of pain and temperature (spinothalamic shock tract) ■ Preserved light-touch due to representation in both Incomplete SCI Syndromes spinothalamic tracts (crude touch) and dorsal columns • Central cord syndrome (fine touch) º Most common syndrome º Classically follows acute neck hyperextension injury in an Acute Management of SCI elderly patient • Initial stabilization of the airway, breathing, and circulation º Patient typically has pre-existing spinal canal stenosis º Do not forget your ABCs º Central portion of cord is a watershed zone ■ See Trauma SINS chapter ■ Most susceptible to injury from edema caused by • Spinal cord decompression may be indicated transient compression º Reduction and operative decompression º Weakness of upper extremities with lesser effect on lower º Urgent in cases of incomplete injury extremities • Management of bony or ligamentous injury ■ Reverse of what you would expect in other SCI º As outlined above ■ Injury pattern is because cervical fibres run more • Maintain mean arterial pressure (MAP) ≥ 85 mmHg for 7 medially within the corticospinal (i.e. motor) tracts days post-injury • Anterior cord syndrome º To maintain adequate spinal cord perfusion º Occlusion of the anterior spinal artery º To give greatest chance of recovery in ischemic but not ■ Results in cord infarction in the distribution of this infarcted cord vessel ■ Also known as the “spinal penumbra” • i.e. the anterior two-thirds of the cord • Steroid treatment of SCI is no longer recommended

Table 1. ASIA Impairment Scale • Classification system for SCI • Based on the American Spinal Injury Association (ASIA) motor scoring system

Class A Complete: no motor or sensory function below neurologic level Class B Incomplete: sensory but no motor function below neurologic level Class C Incomplete: motor function below neurological level, with more than half of key muscle groups below with strength < 3 Class D Incomplete: motor function preserved below neurological level, with more than half of key muscle groups below having strength ≥ 3 Class E Normal – sensory and motor function normal

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 27 Spinal SINS

• ASIA assessment (see Table 1) should be completed at • Definition: where one vertebral body slips forward on another admission and at 48 hours • Can be fixed or dynamic º This aids with prognostication ■ Back pain from dynamic spondylolisthesis may • In patients with paralysis: improve with spinal fusion º Deep vein thrombosis (DVT) prophylaxis with low molecular weight heparin +/- pneumatic compression Radiculopathy stockings Pathophysiology º DVT/pulmonary embolus (PE) is a leading cause of • By definition, this means pathology of the nerve root morbidity/mortality in SCI patients • Most commonly caused by compression of a single nerve • Frequent repositioning and pneumatic beds root by a disc herniation º To minimize the development of pressure ulcers • Radiculopathy can involve both motor and sensory • Bladder catheterization will likely be necessary as retention components of the nerve root is common º Loss of muscle bulk, weakness º And overflow incontinence can further predispose to º Decreased sensation in distribution of affected nerve root sacral ulcers º Diminished or absent relevant reflex º Indwelling catheter initially, then in-and-out • Compression can also result from neoplastic or infectious catheterization if bladder does not recover processes • May have initial bowel incontinence with need for rectal • Could also be non-compressive catheterization for hygiene º i.e. inflammatory or metabolic º Later constipation becomes an issue, requiring aggressive bowel regimens Presentation • Once the spine is stabilized • Most common radiculopathies: C5, C6, C7 (neck); L5, S1 º The focus moves to aggressive physiotherapy, (lower back) occupational therapy assessments, and long-term spine • Symptoms include pain (most common), numbness, rehabilitation weakness in distribution of the affected nerve root

Degenerative Spine Disease Evaluation Mechanical Back Pain • Always perform a thorough neurologic examination • Very common: lifetime prevalence as high as 90% º Looking at motor, sensory, and reflexes from the affected • Also one of the most common causes of disability in young nerve root persons º Look for other potential causes of the neurologic • Multifactorial etiology: presentation º Combination of degenerative disc disease, facet joint ■ Elevated reflexes or involvement of both the upper sclerosis/osteoarthritis, and muscular/ligamentous strain and lower extremity suggests myelopathy • For most, conservative management suffices ■ Multifocal changes may suggest an inflammatory/ º Over the counter pain or anti-inflammatory medications metabolic problem º Plus core-strengthening exercise/return to normal • In the upper extremity, patients may have a positive activities after a very brief period of rest Spurling test • Further workup in the setting of “red flags” º Flex the head laterally towards the affected side º Cancer: age > 50 yrs, history of cancer, unexplained ■ If painful, then test is positive (and over) weight loss ■ If no pain, then the physician applies further pressure º Compression fracture: advanced age (> 70), trauma, (laterally and downwards) to the top of the patient's history of osteoporosis, steroid use, substance abuse head º Infection: fever/chills, recent infection, ■ Pain radiates in the direction of the corresponding immunosuppression, use of intravenous drugs dermatome • Consultation to a spine surgeon is not indicated for isolated • In the lower extremity, straight leg raise test may be positive acute or chronic low back pain without radicular or other º Supine patient; flex the extended leg at the hip (done by neurologic symptoms/signs MD not patient) º Because there are no surgical solutions to this ■ Look for radiating pain towards the L5 or S1 º Spondylolisthesis may be an exception dermatomes ■ Spondylolisthesis ■ Record the angle at which pain is elicited

28 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Robichaud et al.

º Confirmed with a cross-leg straight raise • May involve the cervical, thoracic, and upper lumbar regions ■ Lift the non-affected leg; expect pain in the affected leg of the spinal cord º Remembering that the cord ends at the L1/L2 level Management • Natural history of acute disc herniation-related Presentation radiculopathy: • Upper motor neuron findings º Spontaneous improvement occurs in 80–90% of patients º Spasticity, increased tone, hyperreflexia, clonus ■ Generally within 3–6 months (cervical radiculopathies • Patients most often first notice problems with their gait often take longer than lumbar radiculopathies to • In cervical myelopathy, increasing difficulty with fine motor recover) movements in the hands • Analgesia º Difficulty with handwriting, buttons/zippers, unable to º Over the counter pain and anti-inflammatory medications manipulate objects for most º Narcotics tend to be less effective; if used, very short term Evaluation (days) only • Hyperreflexia on examination º Medication targeting neuropathic pain may be added º Upper extremities: bilateral Hoffman’s ■ e.g. pregabalin, gabapentin, or nortriptyline (helps with º Lower extremities: bilateral Babinski’s sleep) • Non-dermatomal sensory loss: look for sensory level • Nerve root blocks • MRI identifies the source of myelopathy and the extent of º Local anaesthetic and/or steroid injections cord injury º An option for short-term relief • Severe cord compression causes MRI signal change in the º No proven long-term benefit spinal cord º Can also aid in identifying the spinal level responsible for º Hyperintensity on an unenhanced T2 MRI image symptoms • Remainder of work-up dictated by the presumed etiology of • Significant radicular pain that persists the myelopathy º Imaging studies are indicated ■ CT scans can demonstrate disc pathology Management ■ However, MRI is the preferred test for diagnosis and • Typically, compressive myelopathy needs surgical surgical planning decompression and fusion in selected cases • Nerve conduction studies º May help isolate the affected nerve root in unclear cases Cauda Equina Syndrome (CES) º Or distinguish active radiculopathy from chronic changes Pathophysiology Surgery is indicated for patients: • • Usually secondary to a large acute lumbar disc herniation º Who fail to respond to conservative management • Large herniation can compress the entire cauda equina º For progressive or severe motor deficit • Results in a combination of bilateral motor and sensory º For bowel or bladder involvement (cauda equina symptoms syndrome) • Results in bowel and bladder dysfunction º Microscope-assisted discectomy is the most common • If not a disc, often a cancerous tumour, both primary and procedure in the lumbar spine metastatic • Cervical spine disc herniations most commonly treated with anterior cervical decompression and fusion Presentation Posterior foraminotomy is also used in selected cases • • Signs and symptoms usually bilateral • Acute presentation is severe back pain Myelopathy º +/- Radicular pain, often down back of legs Pathophysiology º Or worsening of pre-existing back/radicular pain • Clinical syndrome manifesting as spinal cord dysfunction • Motor weakness • Can be the result of compression º Often involves more than a single nerve root; can progress º Chronic degenerative changes (cervical stenosis), acute to paraplegia central disc herniation, neoplastic, infectious process, etc. • Saddle anesthesia (numbness in the perineal region) • Can be the result of intrinsic pathology º A very concerning sign º Syringomyelia, neoplastic process, inflammatory lesions º The result of compression of the sacral nerve roots (multiple sclerosis) • Urinary retention

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 29 Spinal SINS

º From compression of parasympathetics running in nerve Lumbar Spinal Stenosis roots S2–S4 Pathophysiology º Results in an atonic bladder and unopposed sphincter • Usually from hypertrophy of facet joints and spinal tone ligaments º Caution: pain alone is common cause of urinary • Often underlying degenerative disc disease retention º Degenerative changes are more likely to become • Patients can also experience urinary incontinence symptomatic when superimposed on a congenitally º Due to overflow and leakage from a distended bladder narrowed canal º Needs to be distinguished from urge or stress incontinence Presentation º Voluntary retention and associated overflow can occur • Most common presenting symptom is neurogenic when there is profound dysuria claudication ■ Overflow secondary to cauda equina syndrome • Progressive low back/posterior thigh pain that occurs with typically has associated painless retention standing or walking • Fecal incontinence can occur secondary to loss of rectal tone º When severe- and in contrast to vascular claudication- patients experience pain immediately on standing upright Evaluation and pain is relieved quickly by sitting • A thorough neurologic exam of the lower extremities plus º Walking in a flexed position, such as leaning on a rectal tone/sensation shopping cart, can increase a patient’s range • A post-void residual should be obtained º Differentiate from vascular claudication º Either by in-and-out catheterization or bladder scan after ■ WHICH IS also brought on by activity and relieved by the patient has voided rest º Any post-void volume over 100 mL is abnormal and ■ BUT is independent of position supports the diagnosis ■ AND stopping to stand alleviates vascular º However, patients in pain, elderly, multiparous women, claudication; sitting is not necessary and elderly men with urinary retention from prostatic ■ Associated with trophic changes and diminished or hypertrophy can have high residuals absent pedal pulses seen in peripheral vascular disease • If the exam supports CES º MRI is needed to confirm and to identify the level of Evaluation compression • Decreased reflexes and positional pain (especially with back º CT is less useful extension) are not uncommon ■ As the disc is not well-seen in this modality • BUT exam may be normal

Management Management • CES is a surgical emergency! • Non-surgical treatment is preferred º Urgent decompression to avoid irreversible paraplegia º NSAIDs/acetaminophen and physiotherapy ■ And loss of bowel/bladder/sexual function • MRI is the pre-surgical test of choice • Discectomy is performed to remove herniated disc material º Demonstrates canal stenosis and compression of neural • Wider laminectomy may be required for surgical access structures º Many patients can recover, provided there is timely • Surgery is indicated for patients who have severe intervention impairment despite a trial of conservative management º Unfortunately, long-term bladder and sexual dysfunction º Most cases can be treated with a simple decompressive can occur laminectomy º Fusion may be indicated if there is associated instability

30 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Robichaud et al.

Surgical Pearl #1 Surgical Pearl #2 Lumbar Puncture Lumbar Drain Insertion Indications Common Indications • Presumed infection (bacterial; viral; fungal) • Relief of pressure in the setting of CSF leak after surgery • Guillain Barré (increased protein but not increased WBCs) º In order to facilitate dural healing • Multiple Sclerosis (oligoclonal bands) • If multiple diagnostic or therapeutic LPs required • Subarachnoid hemorrhage (red blood cells/xanthochromia in º A lumbar drain can minimize patient discomfort CT negative thunderclap headache) • Prophylactically • Leptomeningeal carcinomatosis (abnormal cytology) º To reduce ICP by drainage of CSF during some intracranial procedures Contraindications • Signs of cerebral herniation Procedure • Signs of raised intracranial pressure 1. Same as for lumbar puncture º With focal deficit or known space-occupying lesion 2. In addition • Cardiorespiratory compromise preventing appropriate º Insert Tuohy needle with bevel parallel to sagittal plane positioning º Access the thecal sac • Coagulopathy (risk of spinal epidural hematoma) º Then rotate the bevel toward the head • Infection at the site of insertion ■ Be careful to avoid too much CSF drainage once the • Spina bifida may represent a relative contraindication, as stylet is removed tethering of the spinal cord may be present 3. Thread lumbar drain catheter through Tuohy needle º To approximately the 15-cm mark (but can vary, Procedure depending on the depth of needle penetration required) 1. Position the patient 4. Remove the needle over the catheter º Either sitting up, or in lateral decubitus º Cap the catheter º Back flexed, knees tucked in toward chest, chin on chest º Securing the cap in place with a silk tie or suture º Approximate the L4/L5 space ■ Be careful to avoid withdrawing or cutting the catheter ■ Midline at the height of the superior iliac spines while removing needle ■ Palpate the space between spinous processes 5. Secure the drain in place and connect to drain collection 2. Under sterile conditions and after local anesthetic system º Insert spinal needle between spinous processes º Observe for flow of CSF ■ Typically spinal needles are 20 gauge or smaller • To minimize the risk of dural puncture headache ■ Larger needles may be used for specific indications • i.e. to measure CSF pressure º Angle superiorly ~ 15–30 degrees, with the bevel of the needle parallel to the sagittal plane (aim toward the umbilicus) º Advance through subcutaneous tissue and ligamentum flavum º Feel “pop” as needle goes through dura º Periodically withdraw the stylet to observe for CSF flow 3. Once CSF is obtained º Withdraw the needle and place a sterile bandage º In certain cases an opening pressure may be recorded as an approximation of intracranial pressure (supine position only)

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 31 Spinal SINS

Surgical Pearl #3 Surgical Pearl #4 Halo Vest (to be performed by neurosurgical or Cervical Spine Traction (to be performed by orthopedic service) neurosurgical or orthopedic service)

Common Indication Common Indications • Immobilization of cervical spine fractures/dislocations, • Reduction of fractures/dislocations provided there is satisfactory reduction • Decompression of spinal cord/nerve roots

Contraindications Contraindications • Skull defects or fracture at the pin sites • Atlanto-occipital dislocation, type IIA and III hangman’s • Infection at the pin sites fractures • Congenital bone defects • A separate rostral lesion (higher in the cervical spine) • Children aged under 3 years • Skull defects or fracture at the pin sites • Elderly patients with bone demineralization • Infection at the pin sites • Movement disorders where pin erosion is likely to occur • Congenital bone defects, children aged under 3 years, elderly patients with bone demineralization, or movement disorders Procedure where pin erosion is likely to occur 1. Shave and sterilize the pin sites on the skull • Obtunded patient unable to notify clinician of new deficits 2. Inject local anesthetic into the pin sites (anesthetize down during reduction to bone) 3. Position the ring just below the widest part of the skull: Procedure approximately mid-forehead, 1 cm above orbital bar and 1 1. Attach halo ring as previously outlined cm above pinna 2. Apply traction to reduce fracture: typically 5 lbs for the 4. Hold the ring in place temporarily with the suction cups as head, then 2.5 lbs for each spinal level above the fracture you advance the pins and screw them into the skull 3. Obtain a C-spine X-ray a half-hour after traction to check 5. Insert anterior pins above the lateral orbit to ensure that the for reduction frontal sinus, supra-trochlear, and supra-orbital nerves are 4. Add more weight as necessary until reduction is achieved not injured; ensure patients eyes are closed to avoid pinning or if over-distraction is demonstrated (widening of the disc eyes opened spaces) 6. Insert posterior pins just behind the pinna, avoiding 5. Must stop if any new neurologic deficits occur mastoid air cells 6. Once fracture is reduced, can decrease some of the weight 7. Tighten the pins sequentially, opposite one another; use to avoid over-distraction and maintain alignment torque wrench to ensure complete tightening 8. Attach halo ring to the vest for stabilization 9. Re-torque the pins on the following day and ensure they are cleaned regularly

32 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Case Report

Unilateral Adrenal Hemorrhage and the Challenge Of Early Recognition Resheed Alkhiari MBBS, Dana Attar MBBS, Christian Kraeker, MD

About the Author Resheed Alkhiari is a PGY4 in Gastroenterology at McMaster University and Teaching Assistant at Qassim University, Saudi Arabia. Dana Attar is a PGY4 Endocrinology at McGill University, Montreal, Québec, Canada and Christian Kraeker is an Assistant professor in General Internal Medicine at McMaster University, in Hamilton, Ontario, Canada. Correspondence may be directed to [email protected]. Alkhiari Attar Kraeker

Summary Adrenal hemorrhage (AH) is a rare condition with an estimated prevalence of 1% among hospital-based autopsies. It is usually discovered incidentally on computed tomography.1 Most cases are associated with the use of anticoagulation, especially in the setting of heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome, trauma, metastatic disease, sepsis, and critical illness.5-7 We report a case of acute unilateral adrenal hemorrhage associated with Escherichia coli pyelonephritis in the context of recent prolonged steroid use.

Résumé L’hémorragie surrénalienne (adrenal hemorrhage ou AH) est une pathologie rare dont la prévalence est estimée à 1 % sur les autopsies réalisées en milieu hospitalier. Elle est habituellement remarquée de manière accidentelle lors d’une tomodensitométrie1. La plupart des cas sont associés à l’usage d’anticoagulants, en particulier en situation de thrombocytopénie induite par l’héparine, de syndrome d’anticorps antiphospholipides, de trauma, de maladie métastatique, de septicémie ou de maladie grave5-7. Nous décrivons ici un cas d’hémorragie surrénalienne unilatérale aiguë associée à une pyélonéphrite due à Escherichia coli dans un contexte d’usage prolongé récent de stéroïdes.

Case Report 125 g/L, a leukocyte count of 30.2 x103/L, and a platelet count An 87-year-old woman presented to the emergency department of 203 x109/L. Serum sodium was 135 mmol/L, potassium 5 with a four-day history of generalized weakness, dysuria, and mmol/L, blood urea nitrogen 26 mmol/L, and creatinine 388 fever. Her past medical history was significant for osteoarthritis, μmol/L. Urinalysis was positive for nitrites and showed more osteoporosis, and polymyalgia rheumatica, for which she was than 30 leukocytes per high power field, and urine culture treated with prednisone that had been reduced gradually over revealed the presence of a pan-sensitive Escherichia coli. Also, two years and completely discontinued four months prior to two peripheral blood cultures were negative. presentation. Her medications included vitamin D, calcium, The working diagnosis of a complicated urinary tract and naproxen. On examination, she was alert and oriented. infection was made and intravenous ceftriaxone and fluids were Her body temperature was 37.7 C, pulse rate was 107 beats/ started immediately, in addition to venous thromboembolism min, and blood pressure was 139/69 mm Hg without any (VTE) prophylaxis with unfractionated heparin 5000 IU postural change. Her abdomen was soft to palpation with BID subcutaneously. Unfortunately there was no significant mild tenderness in the right upper quadrant. There was no improvement in her condition over the first three days despite skin discoloration. Initial workup revealed a hemoglobin of appropriate antibiotic therapy.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 33 Unilateral adrenal hemorrhage and the challenge of early recognition Alkhiari et al.

Figure 1.

To investigate potential complications, abdominal and identified adrenal hematoma. Prior to discharge, her renal ultrasounds were performed, and both showed no hemoglobin concentration was 92 g/L, leukocyte count was 10 evidence of pyelonephritis. On the fourth day, she started to X 103/L, and platelet count was 240 x109/L. Serum sodium was have severe right-sided abdominal pain, nausea and vomiting, 139 mmol/L, potassium was 4 mmol/L, blood urea nitrogen with an unexpected drop in hemoglobin from 125 to 92 g/L. was 9.8 mmol/L, and creatinine was 159 μmol/L. Abdominal computed tomography (CT) scan was arranged A follow-up morning cortisol 6 weeks later (collected after which revealed a right-sided pyelonephritis complicated by an withholding the evening dose of hydrocortisone the night acute right-sided adrenal hemorrhage (Figure 1). The patient before) was 148 nmol/L. A decision was made, in consultation was immediately started on dexamethasone after obtaining a with an endocrinologist, to continue hydrocortisone therapy baseline ACTH level of 7.6 pmol/L at 2 p.m. (normal level less for another 6 months and to reassess whether it should be than 10.3 pmol/L according to local lab values). The following continued at that time. morning at 8 a.m. a 250 mcg adrenocorticotropic hormone (ACTH) stimulation test was performed, followed by magnetic Discussion resonance imaging of the pituitary which demonstrated The adrenal glands are crucial to homeostasis and survival. no abnormality. The diagnosis of adrenal insufficiency was They play a major role in stress response, maintenance of confirmed by an inadequate response to ACTH serum cortisol blood pressure, and electrolyte balance. They receive a rich levels 137, 350, and 433 nmol/L, at 0, 30, and 60 minutes, blood supply, thus rendering them susceptible to vascular respectively). injury, hemorrhage, and metastatic deposits.2 Accordingly, glucocorticoid replacement with AH is a rare condition found in 0.14% to 1.8% of hospital- hydrocortisone 15 mg orally in the morning and 10 mg in the based autopsies.1 It is often picked up incidentally on CT evening, was started. Within 24 hours, her condition improved imaging when patients present with non-specific symptoms dramatically in terms of fatigue, dizziness, vomiting, weakness and is therefore believed to be under-recognized. It can be and anorexia. Her fever subsided and her blood work results bilateral or unilateral. Over a period of 25 years, the Mayo returned to baseline. Follow-up imaging with abdominal CT Clinic recorded 141 cases of AH; 78 (55%) were bilateral, and one week later showed a decrease in the size of the previously 63 (45%) were unilateral. Clinical features are usually vague

34 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Alkhiari et al.

and included abdominal pain, nausea, vomiting, fatigue, steroid exposure and the acute hemorrhage in the setting of weakness, fever, and hypotension. Of these, the most common pyelonephritis while being on unfractionated heparin for VTE was abdominal pain. Possible laboratory abnormalities include prophylaxis resulted in a decompensated hypocortisolemic state. hyponatremia, hyperkalemia, leukocytosis, and a drop in The described report reflects the challenge of early recognition hemoglobin level, especially with acute AH and retroperitoneal and treatment of AH, and reminds the physician to consider this hemorrhage. Clinical manifestations and biochemical diagnosis in the appropriate clinical setting. To our knowledge, abnormalities, however, are largely related to the underlying this is the first case identifying unilateral AH in the context of etiology of AH.3-7 previous steroid use and Escherichia coli pyelonephritis. Causes of adrenal hemorrhage can be classified as traumatic and non-traumatic. Major risk factors for non-trauma References related include: anticoagulant drugs especially in the setting 1. Xarli VP, Steele AA, Davis PJ, et al. Adrenal hemorrhage in the adult. Medicine (Baltimore) 1978; 57(3):211-221. of heparin-induced thrombocytopenia, anti-phospholipid 2. Longo DL, Fauci AS, Kasper DL, et al.editors. Harrison’s principles of antibody syndrome, metastatic disease, sepsis, surgery, critical internal medicine.18th ed. New York: McGraw Hill; 2010:2940-2944. illness, and pre-existent adrenal mass. Traumatic causes are 3. Swift DE, Overholt EL, Travelli R. Methods of diagnosis of acute adrenal 6, 7 hemorrhage complicating anticoagulant therapy-abdominal CAT scanning. usually related to motor vehicle accidents or blunt trauma. Wis Med J 1981;80(11):25-28. Of note, Waterhouse-Friderichsen syndrome is a well- 4. Albert SG, Wolverson MK, Johnson FE. Bilateral adrenal hemorrhage in an recognized cause of adrenal hemorrhage in the setting of severe adult: demonstration by computed tomography. JAMA1982;247(12):1737- bacterial infection, typically with meningococcemia. This 1739. 5. Rosenberger LH, Smith PW, Sawyer RG, et al. Bilateral adrenal hemorrhage: syndrome is characterized by petechial rash, coagulopathy, the unrecognized cause of hemodynamic collapse associated with heparin- shock, and adrenal hemorrhage. Less commonly, it may induced thrombocytopenia. Crit Care Med 2011; 39(4):833-838. result from infection due to Escherichia coli, Streptococcus 6. Caron P, Chabannier MH, Cambus JP, et al. Definitive adrenal insufficiency due to bilateral adrenal hemorrhage and primary antiphospholipid pneumoniae, Neisseria gonorrhoeae, Haemophilus influenza, syndrome. J Clin Endocrinol Metab 1998; 83(5):1437-1439. and Staphylococcus aureus.8 7. Vella A, Nippoldt TB, Morris JC 3rd. Adrenal hemorrhage: a 25-year A CT scan of the abdomen is usually the investigation experience at the Mayo Clinic. Mayo Clin Proc Feb 2001;76(2):161-8. 8. Adem PV, Montgomery CP, Husain AN, et al. Staphylococcus aureus sepsis of choice in diagnosing AH in the absence of overt signs of and the Waterhouse-Friderichsen syndrome in children. N Engl J Med. Sep bleeding. It usually shows asymmetric enlargement with a 22 2005;353(12):1245-1251. round or oval shaped gland with high attenuation compared 9. Shah HR, Love L, Williamson MR, et al. Hemorrhagic adrenal metastases: CT findings. J Comput Assist Tomogr. Jan-Feb 1989;13(1):77-81. to soft tissues. A streaky appearance of the perirenal fat may 10. Sacerdote MG, Johnson PT, Fishman EK. CT of the adrenal gland: the also be present.9-11 many faces of adrenal hemorrhage. Emerg Radiol. 2012 Jan;19 (1): 53-6111. The mainstay of treatment in AH is to treat the precipitant Sinelnikov AO, Abujudeh HH, Chan D, et al. CT manifestations of adrenal trauma: experience with 73 cases. Emerg Radiol. Mar 2007;13(6):313- 318. factor and to give steroid replacement if accompanied by 12. Jahangir-Hekmat M, Taylor HC, Levin H, et al. Adrenal insufficiency evidence of adrenal insufficiency. While most reports point attributable to adrenal hemorrhage: long-term follow-up with reference to towards survival benefit with corticosteroids in AH in the glucocorticoid and mineralocorticoid function and replacement. Endocr Pract Jan-Feb 2004;10(1):55-61. setting of anti-phospholipid antibody syndrome and after postoperative hemorrhage, steroids only provided minimal survival benefit in the setting of severe sepsis or sepsis and adrenal hemorrhage. Case reports have suggested that mineralocorticoid replacement may not necessarily be required in the absence of hypotension or electrolyte abnormalities. As for glucocorticoids, their use should be case-specific and patients should be screened by baseline cortisol levels and formal evaluation with cosyntropin-stimulation tests.7,12 In this case report, we describe a unique presentation of unilateral adrenal hemorrhage in association with Escherichia coli pyelonephritis and recent prolonged steroid use. Subnormal cortisol level with inadequate response to ACTH stimulation test is probably multifactorial; it is likely that the patient had pre-existent, bilateral adrenal atrophy from prolonged

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 35 Case Report Chagla et al.

Severe Acute Cytomegalovirus Infection Complicated by Disseminated Intravascular Coagulation and Pneumonitis in a Healthy Female Zain Chagla MD, Deborah Siegal MD, Phillippe El-Helou MD, Wendy Lim MD, Jill Rudkowski MD

Chagla Siegal El-Helou Lim Rudkowski

About the Authors Zain Chagla is an Assistant Professor of in the Department of Medicine at McMaster University. Deborah Siegal is a Clinical Scholar in the Department of Hematology and Thromboembolism at McMaster University. Phillippe El-Helou is an Associate Professor in the Department of Medicine at McMaster University. Wendy Lim is an Associate Professor in the Department of Medicine at McMaster University. Jill Rudkowski is an Associate Professor in the Department of Medicine at McMaster University. Correspondence may be directed to [email protected].

Abstract Cytomegalovirus (CMV) is an endemic infection worldwide. Among healthy individuals, infections are usually asymptomatic. An infectious mononucleosis-type syndrome is classically described. More serious manifestations, such as pneumonitis, hepatitis, and meningoencephalitis have been described in otherwise healthy populations. Disseminated intravascular coagulation is a life-threatening complication that is extremely rare in competent hosts. We describe a case of pneumonitis and DIC associated with acute CMV infection that resolved with antiviral therapy.

Résumé Les infections à cytomégalovirus (CMV) sont présentes de façon endémique partout dans le monde. Chez les individus en bonne santé, l’infection est habituellement asymptomatique. Sa présentation classique est celle d’un syndrome infectieux de type mononucléosique. Certaines manifestations plus sérieuses, comme la pneumonie, l’hépatite et la méningoencéphalite sont toutefois signalées dans des populations par ailleurs en santé. La coagulation intravasculaire disséminée (C.I.D.) en est une complication délétère extrêmement rare observée chez certains sujets. Nous décrivons ici un cas de pneumonite et de C.I.D. associé à une CMV aiguë qui fut guéri par l’administration d’agents antiviraux.

36 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Chagla et al.

Case Report The patient had detectable cytomegalovirus (CMV) IgG and A 39-year-old African-Canadian female presented to the IgM serology and strongly positive CMV polymerase chain

emergency room for assessment of a nonspecific febrile illness. reaction (PCR) from serum (5.5 log10 copies/mL, normal Her past medical history was significant for celiac disease. She undetectable). Given the atypical lymphocytosis and the was compliant to her diet. She had a 25-pack/year smoking concern of a malignant hematologic process, flow cytometry history. She was on no medications and had no allergies. She was performed revealed a predominant CD8 population reported one sexual partner without condom use, but no without evidence of clonality, in keeping with an inflammatory history of sexually transmitted infections. A family member in process. her household had a recent, self-resolving, flu-like illness. She Two days after admission, she developed hypoxic denied recent travel, intravenous or illicit drug use, or alcohol respiratory failure requiring endotracheal intubation. Her abuse. She had one healthy pet dog at home. coagulopathy worsened with evidence of schistocytosis on The patient initially presented with fevers, chills, and repeated blood smears, and she was treated with fresh frozen sweats of 10 days duration. This was associated with exertional plasma and cryoprecipitate. Her hepatic transaminases and dyspnea, a non-productive cough, nausea, vomiting, LDH remained elevated but stable. A bronchoalvelolar lavage

myalgias, intermittent abdominal pain, and mild diarrhea. specimen was positive for CMV by PCR testing (4.67 log10 On examination in the emergency room, her temperature copies/mL, normal undetectable) without evidence of other was 38.3 degrees Celsius, blood pressure 106/70 mmHg, pulse bacterial, viral, or fungal organisms. A CT scan of the chest 105 beats/minute, respiratory rate 20/minute, pulse oximetry revealed bilateral mediastinal adenopathy, central and upper 92% on 3 liters of oxygen by nasal prongs. Her abdomen was lobe predominant ground glass opacities, without evidence of tender to palpation in all 4 quadrants, with no peritoneal pulmonary embolism, in keeping with a viral pneumonitis, signs. Her pulmonary examination revealed decreased breath and no evidence of specific lobar infiltrate. sounds and inspiratory crackles in the right lower lung zone on Given the severity and organ dysfunction from her auscultation. The rest of her examination was unremarkable. underlying viremia, the patient was started on gancyclovir Her initial complete blood count revealed anemia at 5 mg/kg every 12 hours for 2 weeks. She also empirically (hemoglobin 105 g/L, normal 115-165 g/L), thrombocytopenia received a pulse dose of 1 gram of methylprednisolone (107x109 cells/L, normal 150-450x109 cells/L) , and leukocytosis because of impending respiratory demise. She improved (leukocyte count of 26.6x109 cells/L, normal 4-11x109 cells/L) rapidly over the next 2 days with resolution of her respiratory with lymphocytosis (11.9x109 cells/L, normal 1.5-4.0x109 failure, disseminated intravascular coagulation (DIC), hepatic cells/L) and monocytosis (3.2x109 cells/L, normal 0.2-0.8x109 transaminases, LDH, and atypical lymphocytosis. Repeat cells/L). A blood film showed atypical lymphocytosis. There CMV PCR after 2 weeks was entirely negative. The patient was was evidence of coagulopathy with elevated international discharged home on day 14 without further therapy, and at normalized ratio and partial thromboplastin time at 1.7 1-month follow-up was back to baseline function. (normal 0.8 – 1.2) and 59 seconds (normal 22-35 seconds), respectively. Fibrinogen was low at 0.6 g/L (normal 1.6- Discussion 4.2 g/L), and a coombs test was negative. Her C-reactive Cytomegalovirus, a member of a B herpesviridae family, is an protein was 19.4 mg/L (normal <= 5.0 mg/L). Her alanine endemic infection worldwide. Seroprevalence studies in the aminotransferase was elevated at 56 U/L (normal <=28 U/L). United States have shown rates up to 50.4%, with socioeconomic Lactate dehydrogenase was 1041 U/L (normal 100-220 U/L). status and ethnicity tied to higher rates.1 Among those The remainder of her electrolytes and chemistry were within infected, most are asymptomatic or have self-limited illnesses. normal limits. A chest radiograph revealed a right lower lobe However, acute infection in the immunocompromised, as well infiltrate. Computerized tomography (CT) of the abdomen as viral latency and reactivation, cause a significant burden revealed resolving non-specific colitis in the sigmoid and of disease. Severe manifestations may be seen among bone rectum with a diagnostic consideration of inflammatory bowel marrow and solid organ transplant patients, those on chronic disease or infectious colitis. glucocorticoids and/or other immunosuppressants, and those An extensive infectious workup including blood and with HIV infection.2 sputum bacterial cultures, Epstein-Barr Virus (EBV) serology, A number of manifestations can be seen in and Human Immunodeficiency Virus (HIV) enzyme-linked immunocompetent individuals. While most infections are immunosorbent assay (ELISA) and p24 antigen were negative. asymptomatic, an infectious mononucleosis-type syndrome

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 37 Severe Acute Cytomegalovirus Infection Complicated by Disseminated Intravascular Coagulation and Pneumonitis in a Healthy Female is classically described and acute CMV infection can mimic against the benefit, particularly in those who present with acute EBV infection. More serious manifestations, such as mild to moderate manifestations. Orasch and Conen describe pneumonitis, hepatitis, and meningoencephalitis have been 3 immunocompetent patients with multiorgan dysfunction described in otherwise healthy populations.2 Severe disease in treated with antiviral therapy9 with clinical improvement and immunocompetent individuals is rare, although significant discharge from hospital. In another review of healthy patients morbidity and mortality has been described. A recent case with severe disease, 6 of 7 patients (85.7%) treated with CMV series reviewed 290 patients with severe disease. Manifestations specific antiviral therapy survived. Of the untreated patients, 13 included the gastrointestinal tract, portal vein thrombosis, of 27 (48.1%) survived.10 Therapies described in the literature meningoencephalitis, pneumonitis, hepatitis, myocarditis, include gancyclovir, valgancyclovir, and foscarnet,3 although the pericarditis, and ocular manifestations such as retinitis. ideal dose, parameters for monitoring therapeutic response, and Hematologic manifestations such as thrombocytopenia and need for induction and maintenance therapy are unknown. hemolytic anemia were also described.3 In conclusion, this case of primary cytomegalovirus The hallmark finding in this patient was the presence of infection in an immunocompetent female complicated by DIC reactive lymphocytosis. A differential diagnosis includes and pneumonitis causing respiratory failure demonstrated infections, acute physiologic stress, hypersensitivity (Drug clinical and microbiologic response following treatment with Reaction with Eosinophila and Systemic Symptoms), and gancyclovir. Given the seroprevalence of this infection in the malignancy. Although CMV and EBV are common causes, general population, clinicians should consider this diagnosis acute infections such as HIV, Herpes Simplex Virus II, Rubella, in unexplained viral syndromes, particularly with hematologic Toxoplasma gondii, Adenovirus, Dengue, Human Herpes Virus abnormalities. 6 and 8, Varicella Zoster Virus, and Bordatella pertussis have been associated with reactive lymphocytosis. Other chronic References infections such as Leishmaniasis, Leprosy, and Strongyloidiasis 1. Bate S, Dollard S, Cannon M. Cytomegalovirus seroprevalence in the United 4 States: the national health and nutrition examination surveys, 1988-2004. have also been described. Clinicians encountering atypical Clin Infect Dis 2010;50(11):1439-47. lymphocytosis on blood smear should consider a broad 2. Crumpacker C, Zhang J. Cytomegalovirus. In: Mandell GL, Bennett, JE, differential diagnosis and consider serologic testing based on & Dolin R, editors. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingston; 2009. p. 1971-87. clinical symptoms. 3. Rafailidis P, Mourtzoukou E, Varbobitis I, et al. Severe cytomegalovirus The development of DIC in this otherwise infection in apparently immunocompetent patients: a systematic review. immunocompetent patient was a potentially life-threatening Virol J 2008; 27(5):47. complication of her viremia. DIC is a known consequence of 4. Kipps TJ. Chapter 81. Lymphocytosis and Lymphocytopenia. In: Prchal JT, Kaushansky K, Lichtman MA, Kipps TJ, Seligsohn U, eds. Williams CMV among immunocompromised hosts, however, only two Hematology. 8th ed. New York: McGraw-Hill; 2010. previous healthy patients developing DIC with documented 5. Niewold T,Bundrick J. Disseminated Intravascular Coagulation due to acute CMV infection have been reported in the literature. A Cytomegalovirus Infection in an Immunocompetent Adult Treated with Plasma Exchange. Am J Hematol 2006;81:454–457. 63-year-old healthy female, who was diagnosed based on IgM 6. Tiula E, Leinikki P. Fatal cytomegalovirus infection in a previously healthy and IgG, presented with severe DIC and acute respiratory boy with myocarditis and consumption coagulopathy as presenting signs. distress syndrome (ARDS), and was subsequently treated Scand J Infect Dis 1972; 4(1):57-60. 7. Persoons M, Stals F, Van Dam-Mieras M et al. Multiple organ involvement 5 with plasmapheresis alone with clinical response. Another during experimental cytomegalovirus infection is associated with pediatric patient did not respond to supportive management disseminated vascular pathology. J Pathol 1998; 184(1):103-9. and ultimately died.6 The mechanism of DIC may be related to 8. Van Dam-Mieras M, Muller A, van Hinsbergh V, et al. The procoagulant response of cytomegalovirus infected endothelial cells. Thromb Haemost viral pathogenesis. Rat models of CMV indicate the presence 1992; 68(3):364-70. of extensive vascular and endothelial damage and demonstrate 9. Orasch C,Conen A. Severe primary cytomegalovirus infection in the hematologic parameters compatible with DIC.7 In vitro CMV immunocompetent adult patient: a case series. Scand J Infect Dis 2012;44(12):987-91. infection of human umbilical vein endothelial cells causes 10. Eddleston M, Peacock S, Juniper M, et al. Severe cytomegalovirus infection a procoagulant response more rapid than the tissue factor in immunocompetent patients. Clin Infect Dis 1997; 24(1):52-6. response through the usual inflammatory pathway.8 The use of antiviral therapy and corticosteroids in our patient was based on the deterioration in her clinical status. However, it is unclear whether antiviral therapy alters the natural history of disease or complications. Furthermore, the potential toxicity associated with treatment must be weighed

38 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Case Report

A Suspected Case Of Endoscopic Ultrasound Induced Pancreatitis, Without Fine Needle Aspirate Michael John Abunassar BSc, BA, MD, Loree Boyle, BN, MD, FRCPC, Avijit Chaterjee, MSc, MDCM. FRCPC

About the Author Dr. Michael John Abunassar is currently a Gastroenterology Fellow at The Ottawa Hospital – University of Ottawa. Dr. Loree Boyle is an Internist and Clinician Teacher with Internal Medicine who practices at the Ottawa Hospital (General Campus). Dr. Avijit Chaterjee is a Clinical Gastroenterologist, researcher, and program director of the Therapeutic Endoscopy Fellowship Program at The Ottawa Hospital – University of Ottawa. Correspondence may be Abunassar Boyle Chaterjee directed to [email protected].

Summary A 78-year-old male developed nausea and epigastric pain 8 hours following an endoscopic ultrasound (EUS) procedure. The patient had a history of recurrent pancreatitis, and underwent the EUS procedure with the aim of aspirating a pancreatic cyst. The cyst had regressed in size, in keeping with a pseuodocyst, and was not biopsied. The patient tolerated the procedure well with no immediate complications, and was discharged home in stable condition. Eight hours later, the patient developed acute pancreatitis.

Résumé Huit heures après avoir subi une endo-échographie, un homme âgé de 78 ans ressent des nausées et une douleur épigastrique. Le patient a des antécédents de pancréatites récurrentes et l’endo échographie a été effectuée en prévision de l’aspiration d’un kyste du pancréas. Le kyste s’étant avéré avoir régressé à l’état de pseudokyste, on n’effectua pas de biopsie. Le patient, ayant bien toléré l’examen, ne présentant pas de complications immédiates et ayant un état stable, a reçu son congé. Huit heures plus tard, il développait une pancréatite aiguë.

Introduction our patient was significantly older than the patients in these Endoscopic ultrasound (EUS) and (EUS)-guided fine needle previous studies. aspiration (EUS-FNA) are recognized as accurate and safe methods for diagnosing and staging gastrointestinal and Case non-GI malignancies. EUS-FNA can also be used to aspirate A 78-year old male was seen for review of chronic, recurrent fluid from cystic lesions, pseudocysts, and fluid collections for pancreatitis and a septated mass at the head of the pancreas. His both diagnostic and therapeutic purposes. Rates of pancreatitis medical history was complicated by (a) rheumatic heart disease associated with pancreatic EUS-FNA range from 0% to 2%.1 leading to bio-prosthetic aortic valve replacement and mitral In a pooled analysis of 4909 EUS cases in the USA, acute annulus ring (2003) (b) psoriatic arthritis treated with chronic pancreatitis secondary to EUS-guided FNA biopsy of pancreatic low dose steroids (c) recurrent E. Coli bacteremia, source masses, pancreatitis resulted in 0.29% or 14 cases.2 Therefore, unknown (d) hypo-gammaglobinemia (e) chronic obstructive the likelihood of pancreatitis occurring without direct biopsy pulmonary disease (COPD) due to remote smoking habit (f) of the pancreas is even lower, and has been reported twice, duodenal diverticulum. He had no current or prior alcohol based on our review of the literature.3,4 Noteworthy is that consumption. He underwent EUS of the pancreatic mass

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 39 A Suspected Case Of Endoscopic Ultrasound Induced Pancreatitis, Without Fine Needle Aspirate Abunassar et al. in October 2013. The mass had regressed in size, and it was calcium 2.3 mmol/L (normal range 2.12-2.52 mmol/L), lipase thought to be most likely a pseudocyst. Therefore, it was not 5632 U/L (normal range 73-393 U/L), liver function tests biopsied. The patient was asymptomatic post-procedure, and were normal. Blood cultures were negative. There was no he was discharged home feeling well. The diagnosis post-EUS laboratory evidence of hypertriglyceridemia. His initial chest was chronic pancreatitis, complex pancreatic head cyst, and x-ray showed a right middle lobe consolidation/atelectasis. unilocular pancreatic body/tail cyst. (Figure 1) Repeat imaging A subsequent x-ray suggested a left-lower lobe pneumonia/ was scheduled 6 months hence. atelectasis, which resolved with therapy. He was admitted to the medicine service for acute Figure 1: EUS REPORT monitoring, IV fluid resuscitation and empiric IV Piperacilin- Celiac Lymph Nodes: None Tazobactam 3.375g q6 hours therapy. This was changed after 48 hours to a 7 day course of oral Amoxacillin/Clavulanate. Pancreas: Diffuse lobularity suggesting chronic The patient’s epigastric pain and nausea resolved quickly with pancreatitis. Complex multi-septated lesion in the head bowel rest, IV fluids and supportive care. of the pancreas measuring 2.7 x 1.6 with solid internal components (presumably debris). Secondary unilocular Discussion cyst in the body of the pancreas measuring 1 x 1 cm with We present a suspected case of EUS-induced pancreatitis in a no suspicious features. The ampulla was unremarkable patient attending outpatient endoscopy in a Canadian tertiary and both the pancreatic duct ‘and’ common bile duct endoscopy centre. (CBD) could be seen coursing into the ampulla with no After an extensive literature search, we found 2 cases of evidence of stones or sludge. post-diagnostic EUS pancreatitis. The first case report was of a CBD: Unremarkable (not well seen as it crosses the area 22-year-old woman with recurrent pancreatitis who sustained of the pancreatic head cyst). diagnostic EUS-induced acute pancreatitis. This condition The endoscopic ultrasound images did not reveal a may have been induced by mechanical irritation of the concerning solid pancreatic mass. No pancreatic calculus. patient’s pancreatic gland. Alternatively, it could have been Cystic structures within the pancreas were in keeping due to ‘ansa pancreatica’3 a communication between the main with post-pancreatitis pseudocysts. Imaging surveillance pancreatic duct (Wirsung) and the accessory pancreatic duct is suggested. (Santorini).5 Ansa pancreatica is an uncommon anatomical variant predisposing pancreatitis.3 That evening, the patient developed nausea, followed The second case report described a 33-year-old male with by chills and worsening epigastric pain radiating to his 12 episodes of recurrent pancreatitis. He was found to have back. Overnight his pain worsened, and he presented to the had changes of chronic pancreatitis and an echogenic polypoid emergency department. The Gastroenterology service reviewed lesion was seen. A biopsy was not performed. He had nausea his condition, and a diagnosis of post-procedural pancreatitis post-procedure, but was discharged 4 hours later only to return was made. to hospital 10 hours later with increasing abdominal pain and On examination, he appeared unwell. His blood pressure nausea. His lipase was 6100 IU/L (normal range 166-292IU/L). was 90/55, his heart rate was 80 beats per minute (regular), his He was diagnosed with EUS-induced pancreatitis.4 respiratory rate of 16 breaths per minute, his oxygen saturation Erikson (2002) suggests that EUS may be more prone to o of 93% on room air, and his temperature 39 C. His jugular inducing pancreatitis than standard endoscopy for at least venous pulsation (JVP) was at the angle of the jaw. No jaundice three reasons. 1) High risk patients with recurrent pancreatitis or scleral icterus was seen. Heart sounds were normal, and a are often undergoing diagnostic EUS as part of their evaluation. 2/6 aortic flow murmur was present. Pulmonary exam was 2) Much more time is typically spent in the duodenum during normal except for occasional crackles at the right lung base. EUS than with standard endoscopy since it is there that the The epigastrium was tender to palpation, but there was no pancreatic head, ampullary region and extra-hepatic biliary rebound and bowel sounds were present. Extremities were tree is examined. 3) The water-filled balloon used for acoustic warm and well perfused. Laboratory tests showed a white coupling may also result in additional mechanical trauma to 9 blood cell count of 24.6 x 10 /L (normal range 3.5-10.5 x the ampullary region through compression or rubbing.4 9 10 /L), hemoglobin of 104 g/L (normal range 125-170 g/L), In our case, no balloon was used and the EUS transducer 9 9 platelets 319 x 10 /L (normal range 130-380 x 10 /L). Corrected was positioned directly in contact with the ampulla. Hence,

40 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Abunassar et al.

the mechanical stress of the EUS probe in the region of the References pancreas (in a patient who has a ‘sensitive’ pancreas, prone to 1. Adler DG, Jacobson BC, Davila RE, et al. ASGE guideline: Complications of recurrent acute inflammation) is suspected to have been the EUS. Gastrointest Endosc 2005. 61(1) : 8-12. 2. Eloubeidi MA, Gress FG, Thomas JS, et al. Acute pancreatitis after EUS cause of pancreatitis. guided FNA of solid pancreatic masses: a pooled analysis from EUS centers in Comparison between the 2 cases found in the literature the United States. Gastroint Endosc 2004. 60(3) : 385-389. (Kulling et al. (1998)3 and Erikson 20024 with our case 3. Kulling D, Sahai AV, Knapple WL. et al. Diagnostic endoscopic ultrasound of the pancreas may cause acute pancreatitis. Endoscopy 1998. 30(1): 7-8. reveals a clear age difference. Our patient was significantly 4. Erickson R. Acute pancreatitis complicating diagnostic endosonography. older (78-years-old) than their patients. Noteworthy, each VHJOE. 2002. 1(3): 2-3. patient had a history of recurrent pancreatitis. None of these 5. Jarrar M, Khenissi A, Ghrissi R. et al. Surgical and Radiologic Anatomy. 2013. 35(8): 745-748. patients had previously undergone an endoscopic retrograde pancreaticography (ERCP). None of these patients had a history of alcohol abuse. The patient in Erickson (2002) did have a family history of heavy alcohol use, recurrent pancreatitis, and subsequent pancreatic cancer in his father.4 The Kulling et al. patient developed symptoms of acute pancreatitis 30 minutes post-EUS,3 Erikson’s patient appeared to develop nausea very soon post-procedure.4 Our patient developed symptoms 8 hours later. We present a suspected case of a very rare complication of a procedure that caused patient morbidity. Clinicians should consider acute pancreatitis in the differential diagnosis of patients who present unwell post-EUS investigations, with or without biopsy. This potential complication should also be added to the informed consent discussion prior to the procedure.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 41 Case Report Riolo et al.

Spontaneous Four Limb Compartment Syndrome

Giovanna Riolo MD, Danny Arora MD, David Taylor MD, Gavin CA Wood MBChB, FRCS

About the Authors David Taylor, MD is a general internist at Queen’s University. Giovanna Riolo MD, FRCPC is a respirologist and cystic fibrosis specialist at University of Toronto, Toronto. Danny Arora MD, MSc (c), FRCSC - Orthopaedic Surgery Clinical Fellow, University of Toronto. Gavin Wood MBChB, FRCS is an orthopedic Taylor Riolo Arora Wood surgeon at Queen’s University. Correspondence may be directed to [email protected].

Summary We present a unique case of atraumatic rhabdomyolysis and four-limb compartment syndrome. Edema and inflammation associated with rhabdomyolysis, was further exacerbated by aggressive saline resuscitation. This resulted in raised compartment pressures and necessitated four-limb fasciotomy. The cause of rhabdomyolysis was most likely multifactorial including systemic capillary leak syndrome seizure, illicit drug use (crack cocaine and methamphetamine) and the prescription medication, mirtazapine.

Résumé Nous présentons ici un cas exceptionnel de rhabdomyolyse atraumatique accompagnée d’un syndrome des loges aux quatre membres. L’œdème et l’inflammation associés à la rhabdomyolyse ayant été exacerbés par une réanimation liquidienne agressive, il en est résulté une augmentation de la pression dans les loges et il a fallu procéder à une aponévrotomie aux quatre membres. La rhabdomyolyse a été très probablement causée par plusieurs facteurs, dont une crise systémique d’un syndrome de fuite capillaire et l’usage illicite de drogues (cocaïne épurée ou crack, méthamphétamine) jumelé au médicament prescrit, la mirtazapine.

42 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Riolo et al.

Case using a transducer, were as follows: right forearm 68mmHg A 49-year-old female presented to a community hospital on dorsal side and 58mmHg on volar side; her anterior lower- emergency department after awaking with bilateral hand and leg pressures measured 40mmHg on the left and 48mmHg on forearm swelling and diffuse myalgias that restricted motion. the right. The myalgias were not limited to pressure areas. She denied She underwent urgent four-limb fasciotomy: bilateral recent exercise or trauma. Although an epileptic, she denied forearms (volar and dorsal), bilateral carpal tunnel releases, recent seizures. She admitted to smoking crack cocaine and bilateral legs (anterior, lateral, superficial and deep posterior) marijuana daily and injecting crystal methamphetamine five with irrigation and debridement. Intraoperatively, there were days prior. signs of poor muscle perfusion (delayed contraction and Past history included hepatitis B, chronic hepatitis C and palor), but no necrosis. This resolved with surgical release. (untreated) epilepsy. She took Mirtazepine for depression. For The extreme swelling meant that full skin closure could not be 5 months, she had taken Isoniazide, Rifampin and Pyridoxine achieved until day 4. Muscle biopsy did not identify an etiology for pulmonary tuberculosis therapy. Five months prior, she for the rhabdomyolysis. consumed approximately 6 beers per day, twice weekly. Post-operatively, CK normalized within a week. She On examination, she was normothermic, pulse was was able to have normal mobility in 4 limbs. She had mild 110 beats per minute and blood pressure 150/90 mmHg. paresthesia in the median nerve distribution of the left hand Cardiac, pulmonary, abdominal, and neurologic exams were and preserved function of the radial and ulnar distribution. unremarkable. She had bilateral edema of hands and forearms but preserved distal pulses, and slightly limited motion Discussion of wrists and metacarpal phalangeal joints. Urine output was This case describes atraumatic rhabdomyolysis complicated 50 cc/hr. by four-limb compartment syndrome, and associated most She had an elevated creatinine kinase (CK) at 23,480 U/L likely with aggressive hydration. Rhabdomyolysis can cause (normal (N): 35-155), aspartate aminotransferase at 3211 U/L (and be further worsened by) compartment syndrome.1 (N: 5-40) and alanine aminotransferase at 543 U/L (N: 0-35). However, atraumatic rhabdomyolysis complicated by Complete blood count, alkaline phosphatase, total bilirubin, four-limb compartment syndrome has not been previously troponin, renal function, lactate, blood cultures and thyroid- reported. Ninety-seven percent of cases are associated with stimulating hormone were normal. Myoglobin was detected either a fracture (69%) or a traumatic soft-tissue injury in the urine. A urine toxicology screen was positive for opiates (28%). This leaves a small minority from spontaneous or and cannabinoids. atraumatic causes.2 The cause of our patient’s rhabdomyolysis Work-up included serum HIV, Epstein-Barr virus was likely multifactorial, such as recreational drugs (cocaine and cytomegalovirus testing, which were negative. Given and methamphetamine), prescription drugs (Mirtazepine and elevated liver enzymes, HCV RNA viral load was sent, but Isoniazide) and/or due to a rare syndrome called systemic was undetectable along with a normal abdominal ultrasound. capillary leak syndrome. Anti-nuclear antibody showed a positive homogenous pattern Cocaine-induced3 and alcohol-induced rhabdomyolysis4 with a low titer of 1:160 and smooth muscle antibodies were have been widely reported. Like cocaine, methamphetamine5,6 negative. can cause violent behavior and excessive isometric motor A working diagnosis of atraumatic rhabdomyolysis and movement. This along with increased adenotriphosphate myositis was assumed. During hospitalization, she had (ATP) demand can cause rhabdomyolysis.5 Methamphetamine episodes of hypovolemia and low jugular venous pressure. users also under hydrate and therefore present with a higher In response to these hemodynamic changes, a total of seven mean initial CK than non-methamphetamine patients.5 liters of 0.9% normal saline was infused over 18 hours from Although our patient denied alcohol use, alcohol withdrawal admission. The following morning after admission, her upper- resulting in delirium tremens, can also elevate CK.4 extremity myalgia was worse, as was ambulation. All limbs Prescription drugs such as isoniazid and mirtazapine were very edematous, and tender to palpation and movement. may have contributed. Isoniazid has been associated with Urine was now tea-coloured; though output was still adequate rhabdomyolysis,7 but is unlikely in our case given that it had (70cc/hr). CK-total peaked at 186,913 U/L. been tolerated for 5 months prior without complications. Concern of acute compartment syndrome led to urgent Our patient was taking Mirtazapine. Mirtazipine lowers transfer for surgical consultation. Compartment pressures, seizure-threshold- especially when combined with alcohol-

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 43 Spontaneous Four Limb Compartment Syndrome

withdrawal and benzodiazepines- and seizures can result in References rhabdomyolysis. Concurrent use with inhibitors or inducers 1. Khan FY. Rhabdomyolysis: a review of the literature. Neth J Med. 2009 of CYP1A2, CYP2D6, or CYP3A4 may result in higher or lower Oct;67:272–83. 2. McQueen MM, Gaston P, Court-Brown CM. Acute compartment syndrome, 8,9 concentrations of mirtazapine, respectively. Who is at Risk? J Bone Joint Surg Br. 2000 Mar; 82(2):200-3. Systemic capillary leak syndrome (SCLS) is a severe and rare 3. Horowitz BZ, Panacek EA, Jourites, NJ. Severe rhabdomyolysis with renal disease caused by increased capillary permeability. The cause failure after intranasal cocaine use. J Emerg Med. 1997 Nov-Dec;15(6):833-7. 4. Curry SC, Chang D, Connor D. Drug- and Toxin-Induced Rhabdomyolysis. is unknown and characterized by episodes of hypotension, Ann Emerg Med. 1989 Oct;18(10):1068-84. edema and hypovolemia. This results in a massive shift of fluid 5. Richards JR, Johnson EB, Stark RW, Derlet RW. Methamphetamine Abuse into the extravascular space and compartment syndrome.10 and Rhabdomyolysis in the ED: 5 year study. Am J Emerg Med. 1999 Nov;17(7):681-5. Less than 100 cases have been described since 1960, with only 6. Knochel JP. Mechanisms of rhabdomyolysis. Curr Opin Rheumatol. 1993 one case of four-limb compartment syndrome.10 Intravenous Nov;5(6):725-31. fluids increase the risk of vascular overload without providing 7. Cronkright PJ, Szymaniak G. Isoniazid and Rhabdomyolysis. Annals of 10 Internal Medicine. 1989 Jun1;110(11):945. an increase arterial pressure. 8. Khandat AB, Nurnberger JI Jr, Shekhar A. Possible mirtazapine-induced In our case, in addition to 7 liters of crystalloid fluid in rhabdomyolysis. Ann Pharmacother. 2004 Jul-Aug;38(7-8):1321. less than 24 hours, intramuscular inflammation, such as 9. Kuliwaba A. Non-lethal mirtazapine overdose with rhabdomyolysis. Aust N Z J Psychiatry. 2005 April;39(4):312-3. occurs with rhabdomyolysis, can mean even more interstitial 10. Simon DA, Taylor TL, Bayley G, Lalonde KA. Four-limb compartment edema.2,11 This along with possible SCLS, plus recreational syndrome associated with the systemic capillary leak syndrome. J Bone Joint and prescription drugs, could have worsened the edema. This Surg Br. 2010 Dec;92(12):1700-2. 11. Poels PJE, Gabreels FJM. Rhabdomyolysis: a review of the literature. Clin in turn makes compartment syndrome more likely through Neurol Neurosurg. 1993 Sep;95(3):175-92. further swelling, ischemia and fluid sequestration. All of this can cause a vicious cycle of ongoing muscle damage, and further CK elevation. Continuous monitoring of intra- compartmental pressure can help to help reduce complications (including the threat of limb-loss). Surgical fasciotomy was performed to break this medical vicious cycle.

44 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Case Report

Diagnostic Approaches: Images in GIM Acute Infectious Epiglottitis Jeff Shrum MD and Ben J. Wilson BJ

About the Author Jeff Shrum is a 5th-year general internal medicine subspecialty resident at the University of Calgary. Ben Wilson is a general internist at the Peter Lougheed Centre in Calgary, Alberta. Correspondence may be directed to [email protected].

Shrum Wilson

Case Report A 36-year-old man presented to the emergency department with 1 week of sore throat, odynophagia, change in voice and inability to swallow saliva. His oropharynx was unremarkable with no palpable cervical lymphadenopathy, but his anterior neck was tender to light palpation. Lateral cervical radiograph showed substantial epiglottal swelling manifesting as the ‘thumb sign’ (Figure 1). Bedside flexible nasal laryngoscopy revealed an erythematous edematous epiglottis, with preserved vocal cord structure and function. Acute infectious epiglottitis was diagnosed, and improved with intravenous antibiotics. The thumb sign, as seen on lateral cervical radiograph, results from pathological enlargement of the epiglottis.1 Accurate data regarding the sensitivity of this sign is lacking. However, a retrospective review of 47 adult patients who presented at the emergency department with acute infectious epiglottitis found that 68% had the thumb sign.2 Direct visualization of an inflamed, edematous epiglottis is required for the definitive diagnosis of epiglottitis. Prior to widespread vaccination, acute infectious epiglottis was almost exclusively caused by Haemophilus influenza.3 Streptococcal species are now the most commonly isolated bacterial pathogen in adults.4

References 1. Podgore JK. The “thumb sign” and “little finger sign” in acute epiglottitis. J Pediatr 1976;88:154-155. 2. Qazi IM, Jafar AM, Hadi KA, et al. Acute epiglottitis: a retrospective review of 47 patients in Kuwait. Indian J Otolaryngol Head Neck Surg 2009;61:301–305. 3. Mayo-Smith MF, Spinale JW, Donskey CJ, et al. Acute epiglottitis: an 18-year experience in Rhode Island. Chest 1995;108:1640-47. 4. Briem B, Thorvardsson O, Petersen H. Acute epiglottitis in Iceland 1983–2005. Auris Nasus Larynx 2009; 36:46–52.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 45 Case Report Yeung and Dang

Deep Vein Thrombosis and Pulmonary Embolism as a Complication of Traditional Chinese Acupuncture and Cupping

ThucNhi T. Dang Bsc, Albert A.C. Yeung MSc, MD

About the Authors ThucNhi T. Dang is a 2nd year medical student at the University of Alberta Hospital, Edmonton. Albert Yeung is a staff internist at the Royal Alexandra Hospital in Edmonton, Alberta, and adjunct professor of pharmacology and medicine, University of Alberta. Correspondence may be directed to [email protected].

Dang Yeung

Summary We provide the first reported case of deep vein thrombosis with pulmonary embolism following acupuncture and cupping. This is a reminder that although serious adverse events associated with acupuncture and cupping are reportedly rare when performed by qualified practitioners, life-threatening complications can still arise.

Résumé Nous présentons ici le premier cas signalé de thrombose veineuse profonde accompagnée d’une embolie pulmonaire par suite d’un traitement d’acupuncture et de l’application de ventouses. Ceci vient nous rappeler que même si les effets indésirables graves découlant de traitements d’acupuncture et de l’application de ventouses seraient plutôt rares lorsque réalisés par des praticiens qualifiés, il n’en demeure pas moins que des complications extrêmement graves peuvent survenir.

Case Report acupuncture and cupping from an established practitioner of A 72-year-old Caucasian man presented to the emergency traditional Chinese medicine (TCM). department with a 1 day history of right-sided anterior pleuritic Before his presentation, he received a total of 10 electro- chest pain. He had accompanying mild dyspnea but no dizziness enhanced acupuncture sessions spanning over a 2 month or syncope. He did not have hemoptysis, leg swelling, or leg period. For his last 2 sessions, which were separated by a pain at the time. His past medical history included a remote 1 week interval, he received acupuncture followed by cupping uncomplicated myocardial infarction, localized prostate cancer over his right popliteal fossa – specifically at the denoted which was successfully treated by prostatectomy 10 years acupuncture point “bladder forty” (BL-40) (Figure 1), the before, and longstanding non-progressive idiopathic sensory typical treatment site for peripheral neuropathy of the lower peripheral neuropathy characterized by persistent paraesthesia limbs. Negative pressure in the cup was achieved by means of and discomfort in his feet for which he received treatment with a mechanical hand-pump connected to the cup. He received

46 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Yeung and Dang

Figure 2. Enhanced computed tomography pulmonary angiogram showing a single right lower lobe pulmonary artery embolus (arrow)

Figure 1. Acupressure point denoted BL-40 in relation to the venous anatomy of the right posterior leg and popliteal fossa.

his last treatment 6 days prior to the onset of chest pain, and he commented that the acupuncture and cupping session on that day went smoothly without local bleeding or undue discomfort. The following day, he felt mild discomfort behind his Figure 3. Doppler ultrasound showing residual thrombus of the intramuscular right knee associated with a circular bruise over his popliteal branch of the anterior thigh which feeds into the superficial femoral vein fossa. Two days later, he complained of erythematous, tender (arrow) swelling over the medial aspect of his right thigh, but he had no difficulty bending his knee or walking. Five days following the was no jugular venous distention. He had reduced air entry last treatment, his thigh pain and swelling had spontaneously due to shallow inspiration. No pleural rub was heard. Leg resolved. examination showed no asymmetry, no swelling, nor bruising. He denied prolonged stasis or recent trauma to his right leg. Palpation along the popliteal vein did not elicit any tenderness. He had no personal history of thromboembolism. There was Initial investigations revealed a normal complete blood no family history of thromboembolism or thrombophilia. His count, creatinine, and coagulation panel. Serum troponin only prescribed medication was atorvastatin 40 mg/day. He was not elevated, but the D-dimer assay was elevated at 1.4 was not taking any antiplatelet drug. He also regularly took a mg/L (fibrinogen equivalent units). Serum prostatic specific multivitamin tablet, fish oil, and coenzyme Q10 supplements. antigen was less than 0.1 ug/L. Serum protein electrophoresis On examination, he was in acute distress. Blood pressure showed no monoclonal band. Thrombophilia testing for factor 133/82 mmHg, heart rate 66 per minute, respiratory rate V Leiden and prothrombin G20210A mutations, activated 23 per minute, oxygen saturation 89% on room air. There protein C resistance, presence of antiphospholipid antibodies,

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 47 Deep Vein Thrombosis and Pulmonary Embolism as a Complication of Traditional Chinese Acupuncture and Cupping Yeung and Dang and deficiencies in protein C, protein S, and antithrombin III over 1 million acupuncture treatments estimated the risk were unremarkable. An enhanced computed tomography scan of serious adverse events to be 0.05/10,000 treatments, or of the chest revealed a single segmental pulmonary embolus in 0.55/10,000 patients.7 The most common complications were the right anterolateral basal lobe (Figure 2). pneumothorax, injury to the central nervous system, and Doppler ultrasound of his right lower limb showed a infections, mostly hepatitis B. The commonest local infection definite thrombus a few centimeters long within the lumen of was that of the external ear after auricular acupuncture. a large intramuscular branch of the anterior thigh which drains Complications were largely dependent on the treatment into the superficial femoral vein (Figure 3). The common site, the depth of needle insertion, and the technical skill of femoral and popliteal veins were patent. the practitioner. A review of acupuncture experience in the He was treated with low molecular weight heparin United Kingdom, reported to the National Patient Safety subcutaneously followed by rivaroxaban orally. Eight weeks Agency, found 95% of incidents to be inconsequential or of later, a repeat right leg ultrasound showed complete resolution low clinical importance.11 The most serious adverse events of the deep vein thrombosis (DVT). included retained needles, dizziness, and fainting episodes. However, there has never been record of any instances of Discussion thromboembolism. TCM practitioners fundamentally believe that many diseases A careful 6 year survey of 62,482 acupuncture and are caused by stagnant or blocked qi (pronounced chi) the vital moxibustion treatments performed at a national acupuncture energy or life force that normally flows along defined pathways clinic in Japan reported an adverse event rate of 14/10,000 in the body. Acupuncture and cupping are techniques believed treatment sessions.12 Failure to remove needles, ecchymosis, to relieve blockages and correct imbalances in the flow of qi and burn injuries were among the most common complications. in order to restore health.1,2 Both acupuncture and cupping The authors expressed concern about the under-reporting are becoming increasingly popular worldwide.3 The World of adverse events by acupuncture practitioners, especially in Health Organization had identified acupuncture as an effective English language journals. Nevertheless, they concluded that alternative therapy for 28 different disorders, although their severe or serious adverse events were rare in standard practice recommendations were not evidence-based.4 by trained practitioners. We describe the first reported case of venous Remarkably, acupuncture-induced vascular injuries thromboembolism following acupuncture and cupping. A have been singularly rare despite the widespread and causal relationship is suggested by the temporality of events increasing use of acupuncture worldwide.8,13,14 In 1991, and the absence of any other identifiable risk factors for venous the first case of acupuncture-induced DVT was reported.15 thromboembolism. The patient had not taken low dose ASA Furthermore, Bergquist’s systematic review of the literature or alternative antiplatelet drug for over a year; however, he on vascular injuries caused by acupuncture found only was on atorvastatin which has been reported to have some 2 cases with venous thrombosis – one calf DVT and a left protective effect against DVT and pulmonary embolism.5,6 crural vein thrombophlebitis.8,13 Traumatic bleeding and His heart rate had been relatively slow since his previous pseudoaneurysm formation were among the commonest myocardial infarction; this could account for the absence of vascular complications.13,14 tachycardia on admission. Cupping, in contrast, is a TCM technique in which a Virchow’s triad of vascular thrombosis includes vacuum is created over specific sites on the skin with a cup, hypercoagulability, hemostasis, and endothelial injury. In this sucking underlying tissue part way into the cup. The vacuum patient, the last factor was likely operative. Electroacupuncture can be induced by heating enclosed air under the cup with a needling may cause direct trauma to an underlying vein. In flame and allowing it to cool, or mechanically with a hand contrast, electroacupuncture in combination with cupping pump attached to the cup. The high tensile stress induced in may additionally induce tissue edema or inflammation around the skin layer under the cup rim and stretched skin can cause veins. In our case, the absence of immediate bleeding from the capillary breakage with resulting erythema and ecchymosis in acupuncture needling site or popliteal fossa swelling argues a characteristic circular pattern. The transmission of tension against direct venous puncture. downwards becomes progressively reduced.16 Bruising caused The overall risk of serious adverse events following by cupping may take days to weeks to dissipate. acupuncture is reported to be very low.7-12 For instance, a Of the 7 major types of cupping used in China, our review of 12 surveys of approximately 100,000 patients and patient received “needle cupping.” This consists of applying

48 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Yeung and Dang

acupuncture needling first, followed by cupping for several minutes. Cupping is considered very safe, although the methodological quality of published reports attesting to its clinical efficacy and safety is weak.17 An unexplained D-Dimer elevation in the absence of thromboembolism was reported in a one report;18 another case report discussed the possible link between cupping to the cervical area and subsequent stroke from intracerebral hemorrhage in a non-hypertensive individual.19

Conclusion Our case highlights the uncommon but potentially life- threatening complication of venous thromboembolism following needle cupping. This is a reminder that although serious adverse events associated with acupuncture and cupping are reportedly rare, particularly when performed by qualified practitioners, life-threatening complications can still arise.

Acknowledgments We would like to thank Dr. Steven K.H. Aung, MD for kindly helping us with his expert knowledge of acupuncture in the practice of Traditional Chinese Medicine, especially for Figure 1.

References 1. Chang, S., The meridian system and mechanism of acupuncture-a comparative review. Part 1: the meridian system. Taiwan J Obstet Gynecol, 2012. 51(4): p. 506-14. 2. Chang, S., The meridian system and mechanism of acupuncture--a comparative review. Part 2: mechanism of acupuncture analgesia. Taiwan J Obstet Gynecol, 2013. 52(1): p. 14-24.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 49 Case Report Jowhari et al.

Submucosal Lesions Presenting With Rectal Bleeding-Endometriosis in the GI Tract Fahd Jowhari, MD, Pearl Behl, MD, PhD and Sean Pritchett, MD, FRCPC

About the Authors Fahd Jowhari is a Gastroenterology fellow at Queen’s University, Kingston Ontario. Pearl Behl is a General Internist at Trillium Health Partners, Ontario. Sean Pritchett is the Head, Division of Gastroenterology, and Chief, Department of Medicine & Critical Care, Quinte Health Care, Belleville, Ontario.. Correspondence may be directed to [email protected]. Jowhari Behl Pritchett

Summary Endometriosis is typically marked by the implantation and proliferation of foci of endometrial stroma and glands outside the endometrial cavity and uterine musculature. Extra-gonadal seeding has been observed in sites like the small and large bowel, peritoneum, appendix, pleura, umbilicus, old wound scars, subarachnoid space, inguinal canal, heart and lungs.14,7 The gastrointestinal tract is the third most common localization of endometriosis after the ovaries and the peritoneum, with intestinal involvement being reported in about 12 to 37% of individuals.1,2,5-7 Establishing a diagnosis of intestinal endometriosis can often be a diagnostic challenge. We present an interesting case of sigmoidal endometriosis in a 46-year-old female, whose initial presentation was irregular bowel movements with rectal bleeding.

Résumé L’endométriose se caractérise habituellement par l’implantation et la prolifération de foyers du stroma et des glandes de l’endomètre à l’extérieur de la cavité endométriale et de la musculature utérine. Un ensemencement extra-gonadique a déjà été observé dans des sites comme le petit et le gros intestin, le péritoine, l’appendice, la plèvre, l’ombilic, de vieilles cicatrices de blessures, l’espace sous-arachnoïdien, le canal inguinal, le cœur et les poumons14,7. Le tube digestif vient au troisième rang en termes de localisation de l’endométriose, après les ovaires et le péritoine, avec des atteintes intestinales relevées dans 12 à 37 % des cas1,2,5-7. Il peut souvent être difficile d’établir un diagnostic d’endométriose intestinale. Nous présentons ici un cas intéressant d’endométriose sigmoïdienne chez une femme de 46 ans et dont les premières manifestations consistaient en selles irrégulières accompagnées de saignements au niveau du rectum.

50 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Jowhari et al.

Case large submucosal lesions were found (30 cm and 40 cm from A 46-year-old female presented with a 4-week history of the rectum respectively) that were firmer than a typical lipoma irregular bowel movements (increased frequency and looser and appearances were most in keeping with GIST tumors than baseline), and rectal bleeding (both outside and mixed (Figure 1 and 2). Deep biopsies were taken. The transverse within stool). There was no associated abdominal pain, nausea/ colon appeared mildly edematous, with appearances suggestive vomiting, hematemesis, coffee ground emesis, or melena. of melanosis coli. Some internal hemorrhoids (not bleeding) There were no fevers, chills, or weight loss (some weight gain). were noted upon retroflexion. No history of travel or sick contacts. Review of symptoms was Pathologies from the attempted deep biopsies revealed unremarkable. Family history was negative for colon cancer or normal colonic mucosa, muscularis mucosa and superficial any GI conditions including celiac disease or inflammatory bowel submucosa, with no significant abnormalities and no disease (IBD). She had never received a colonoscopy in the past. neoplastic spindle cell lesions present. Her past medical history was unremarkable with no prior A CT scan of the abdomen/pelvis showed unremarkable surgeries. She was on no medications including no over the bowel loops, and the submucosal masses visualized during counter medications. She had been a non-smoker and non- colonoscopy could not be appreciated on imaging. The spleen, drinker all her life and had no drug allergies. pancreas, adrenals, kidneys, ovaries, bone, and soft tissue were Examination was unremarkable with no palpable masses or all unremarkable. areas of tenderness in the abdomen. DRE was unremarkable. Given the persistent GI symptoms with focally identified Laboratory investigations including CBC, electrolytes, lesions on colonoscopy that looked characteristic of GIST creatinine, urea, metabolic panel, and inflammatory markers tumors, and no evidence of metastatic disease on imaging, our were all within normal limits. patient underwent a repeat colonoscopy where the submucosal Given the rectal bleeding and history of irregular bowel lesions were tattooed; and subsequently a laparotomy for movements, with no biochemical abnormalities or physical resection of the lesions, with left hemi-colectomy and end exam findings, an elective colonoscopy was performed. Two anastomosis. Intraoperatively, there was no evidence of metastatic disease in the abdomen; however she did have a large uterine fibroid, enlarged appendix (resected), and evidence of endometriosis on both ovaries. Pathologies from the resected recto-sigmoid specimen interestingly revealed extensive endometriosis characterized by variably sized columnar-lined glands cuffed by endometrial- type stroma, extending from the sub-mucosa to the mesentery. The diagnosis was supported by immunohistochemistry (positive ER immunostain with CD10 reactivity). The appendix showed evidence of endometriosis as well, and the anastomotic margins were histologically normal. The patient did very well post-operatively. Her bowel Fig 1. First submucosal lesion seen at ~30 cm from the rectum. movements became regular and formed, with no evidence of lower GI bleeds.

Discussion Endometriosis occurs in 6 to 10% of the general female population.12 Its presence in the gastrointestinal tract has been reported in several case reports with the sigmoid colon and rectum being the two most common sites, followed by the ileum, ileocecal area, appendix and anterior rectal wall.3 Establishing a diagnosis of intestinal endometriosis is often a diagnostic challenge as none of its symptoms are pathognomonic, and even though the symptoms should Fig 2. Second submucosal lesion seen at 35-40 cm from the rectum. physiologically be worse cyclically with menses, this is

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 51 Submucosal Lesions Presenting With Rectal Bleeding-Endometriosis in the GI Tract

not always the case.8 The disease is primarily diagnosed dyspareunia should point one in the direction of intestinal in premenopausal women, but can also cause symptoms seeding; however, the absence of these should not deter one in postmenopausal women as endometrial implants may from considering the diagnosis. continue to induce a fibrotic reaction in the muscle of the Including Endometriosis in the differential diagnoses of affected bowel wall even after cessation of ovarian function.13 undiagnosed submucosal lesions in the GI tract could thereby Presenting symptoms are often non-specific and can include help guide patient management and allow for timely referrals unexplained digestive problems, tenesmus, per-rectal as needed. bleeding, bloating, constipation, diarrhea, and pain. Pain can be epigastric, abdominal, pelvic or rectal with the symptoms References varying depending on the location, depth of invasion, adnexal 1. Scarmato VJ, Levine MS, Herlinger H, Wickstrom M, Furth EE, Tureck RW. 9 Ileal endometriosis: radiographic findings in five cases. Radiology. 2000; adhesions, and the presence of a consequential partial or 214:509 – 512. complete bowel obstruction.3,15 2. Jenkinsson EL, Brown WH. endometriosis: a study of 117 cases with special Endoscopic diagnosis of intestinal endometriosis is reference to constricting lesions of the sigmoid and colon. JAMA. 1943; 122:349–354. challenging, as most lesions do not infiltrate the gastrointestinal 3. Martimbeau PW, Pratt JH, Gaffey TA. Small bowel obstruction secondary to mucosa; and therefore radiological modalities such as CT scans, endometriosis. Mayo Clin. Proc. 1975; 50:239–243. MRI or trans-vaginal ultrasonography may help with making 4. Orbuch I, Reich H, Orbuch M, Orbuch L. Laparoscopic treatment of the diagnosis. Based on case reports and observational studies, recurrent small bowel obstruction secondary to ileal endometriosis. Journal of minimally invasive gynecology. 2007; 14(1): 113--115. luminal findings suggestive of endometriosis range from 5. Weed JC, Ray JE. Endometriosis of the bowel. Obstetrics and Gynecology eccentric wall thickenings, polypoid lesions, endometrioid 1987; 69:727–30. heterotopias of the mucosa, and gross surface nodularities/ 6. Jerby B, Kessler H, Falcone T, Milsom J. Laparoscopic management of colorectal endometriosis. Surgical endoscopy. 1999; 13(11): 1125--1128. 16,17 ulcerations. Rates of histological confirmation of the 7. Olive DL, Schwartz LB. Endometriosis. New England Journal of Medicine diagnosis seem to be highest in cases with surface nodularities, 1993; 128:1759–69. with inconclusive results seen in most other cases.17 8. Slesser A, Sultan S, Kubba F, Sellu D. Acute small bowel obstruction secondary to intestinal endometriosis, an elusive condition: a case report. Management involves symptom control and maintaining World J Emerg. Surg.2010; 5:27. fertility. This is achieved primarily from surgical resection of 9. Chapron C, Fauconnier A, Dubuisson J-B, et al. Deep infiltration all visible endometriosis. Hormonal therapies may improve endometriosis: relation between severity of dysmenorrhea and extent of disease. Hum Reprod. 2003; 18:760–6. symptoms in the short term but they do not improve 10. Varol N, Maher P, Healey M, et al. Rectal surgery for endometriosis — fertility.10,11 Patients with intestinal endometriosis achieve should we be aggressive? J Am. Assoc. Gynecol. Laparosc. 2003; 10:182–9. disease control with either laparoscopic bowel resection, or 11. Abbott JA, Hawe J, Clayton RD, Garry R. The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year segmental bowel resection (via laparotomy and primary end follow-up. Hum Reprod. 2003; 18:1915 –7. anastomosis) depending on the extent of disease.4 12. Giudice LC, Kao LC. Endometriosis. Lancet. 2004; 364(9447): 789–99. In our patient, recto-sigmoidal endometriosis presented 13. Teunen A, Ooms EC, Tytgat, GN. Endometriosis of the small and large bowel. Study of 18 patients and survey of the literature. Neth. J Med. 1982; endoscopically with what looked like classic GIST lesions. 25(5): 142-50. Radiological imaging and biopsies did not help us make the 14. Offodile A, Hidgin JB, Arnell T. Asymptomatic intussusception of the diagnosis. Even though the ultimate management of our appendix secondary to endometriosis. The American Surgeon 2007. 73(3) 299-301. patient in either case would have been identical, the take- 15. Yantiss R, Clement P, Young R. Endometriosis of the intestinal tract. A home learning point from the case was that the differential study of 44 cases of a disease that may cause diverse challenges in clinical diagnoses for sub-mucosal GI lesions in the recto-sigmoidal and pathologic evaluation. Am. J Surg. Pathol. 2001; 25:445–54. region, amongst other known benign and malignant etiologies, 16. Kim K, Jung S, Yang S et al. Colonoscopic findings and histologic diagnostic yield of colorectal endometriosis. Journal of clinical gastroenterology. 2011; must also include Endometriosis. 45(6): 536--541. In summary, the diagnosis of intestinal endometriosis 17. Matronitskii, RB, Mel’nikov, MV, Chuprynin, VD. et. al. Endoscopic can be challenging. However, it is prudent to consider this diagnostics of colorectal endometriosis. Eksp. Klin. Gastroenterol. (3): 11-4, 2013. in the differential diagnosis, especially in a premenopausal patient presenting with vague abdominal symptoms including unexplained digestive problems, pain, changes in bowel movements or bleeding from the GI tract. Cyclical bowel symptoms with menstruation along with concurrent findings on history including menometroharragia, infertility and

52 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Case Report

A 54-Year-Old Female With Fever and Ataxia

Marie-Lie Cadieux-Simard MD, Laurence Green MD

About the Author Marie-Li Cadieux-Simard is a 4th year resident in general internal medicine at McGill University. Dr Green is an Associate Professor of Medicine at McGill University and an attending physician at the MUHC. He is the Associate Director for the MUHC Division of General Internal Medicine, and the Department of Medicine Site Director at the Montreal General Hospital. He currently is the Director of the 15 West clinical teaching unit. His interests are in hypertension, pre-operative medicine, tropical medicine and clinical teaching. Correspondence may be directed to Cadieux-Simard Green [email protected].

Case Report positive for cocaine. Her haemoglobin, white blood cell count We present the case of a 54-year-old female known for (6,2 x 109/L), and electrolytes were unremarkable. Aggressive hypertension, alcoholism and occasional cocaine intake. She fluid resuscitation with isotonic fluids was provided to treat was brought to the emergency department because of new the rhabdomyolysis. onset confusion and decreased level of consciousness. The next day, she was admitted to the internal medicine The history was taken from a family member. The patient ward. The admitting diagnosis was delirium secondary to recent had increased shortness of breath with a cough that started 48 intoxication, substance withdrawal, aspiration pneumonia and hours prior to her visit. The night prior to presentation, she was a possible stroke. intoxicated with cocaine and alcohol and was then found to Her mental status improved quickly and a complete have slurred speech, gait disturbance and urinary incontinence. neurological assessment was performed. The patient was The next morning, she was found obtunded, which prompted found to have significant cerebellar findings including gait her family members to seek medical attention. ataxia, dysarthria, dysmetria and dysdiadochokinesis. Her In the emergency department, the patient was found to be main complaint at that time was profuse diarrhea. Given the lethargic and unable to answer question appropriately. Her association of gastrointestinal symptoms with pneumonia, we blood pressure was 140/65, her pulse was 105 and regular, her considered the possibility of Legionnaire’s disease. A positive temperature was 39oC and her Oxygen saturation was 93% on urine assay for legionella antigen confirmed the diagnosis. room air. There were no signs of respiratory distress. A magnetic resonance imaging was negative but did confirm Given the patient’s drowsiness and altered mental status, a that the stroke was not acute. computed tomography of her head was done which revealed Legionella is one of the leading cause of community- an age-indeterminate lacunar infarct in the corona radiate. The acquired pneumonia and, is also an important pathogen in patient was started on antibiotics to cover for possible bacterial hospital-acquired pneumonia. It is an important respiratory and viral meningitis but these were stopped shortly thereafter pathogen, which may have a multisystemic presentation because of a normal lumbar puncture. in addition to pneumonia. The classical presentation of As part of basic investigations, a chest x-ray was obtained Legionnaire’s disease includes pneumonia (90 % of the cases)1 which showed bilateral basal infiltrates. Ceftriaxone and associated with gastrointestinal manifestations, but it has azithromycin were initiated for presumed aspiration or been associated with neurological symptoms in up to 43%.2 community acquired pneumonia. The most common symptoms are altered mental status and Her initial laboratory blood work was significant for headache. It has also been described in association with liver thrombocytopenia at 77 x 109/L, a creatinine of 204 μmol/L and dysfunction,3 hyponatremia and elevated creatine kinase a creatine kinase of 17 000 U/L. Her transaminases were three leading to acute renal failure.4 Retrospectively, the patient times the upper limit of normal and a toxicology screen was presented with many features that are known to be associated

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 53 A 54 Year Old Female With Fever and Ataxia

with Legionella but the predominance of cerebellar dysfunction References as the primary neurologic manifestation is unusual and noted 1. Marston BJ, Lipman HB, Breiman RF. Surveillance for Legionnaire’s disease: on few case reports. In a computer-based search5 including Risk factors for morbidity and mortality. Arch Intern Med 1994; 19: 1130- 1132. 29 patients with cerebellar dysfunction in the context of 2. Johnson JD, Raff MJ, Arsdall JA. Neurological manifestations of Legionnaire’s legionella, dysarthria and ataxia were the two most common disease. Medicine 1984; 63: 303-310. findings. Most of the patients were young otherwise healthy 3. Atypical Presentation of Legionnaire’s Disease: A Case Report and Review. New York Medical Journal. adults. Some had persistent deficits. Computed tomography, 4. Johnson DA, Elter HS. Legionnaire’s disease with rhabdomyolysis and acute magnetic resonance imaging and lumbar puncture are often reversible myoglobinuric renal failure. South Med J 1984; 77: 777-779. normal. Treatment is the same as for other Legionellosis cases. 5. Southern Medical Journal. Cerebellar Involvement in Legionellosis. Shelburne, Samuel A. MD, Kielhofner, Marcia A. MD, Tiwari, Pinky S. MD In our case, the antibiotics were tailored to azithromycin South Med J. 2004;97(1). alone and the patient’s pneumonia improved. Her renal failure, thrombocytopenia and liver dysfunction normalized. Her gait ataxia and dysarthria were still significant at the time of discharge but completely resolved over the following 6 months. Cigarette smoking and chronic lung disease are known risk factor amongst other for Legionella. There is conflicting data about alcohol and its potential association with the disease and its severity. It would certainly be interesting to better know the risk factor associated with severe disease to identify patients at high risk. Legionnaire’s disease is a disease that may present with a variety of symptoms. In our case, the cerebellar symptoms were striking and suggested a primary neurological disease or complication. It is important to consider Legionella infection in patients with pneumonia and neurological findings.

54 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine Proceedings

ORAL PRESENTATION

McMaster University 26th Annual Gold Medal: Ashraf Alazzoni, Cardiology PGY6 ABSTRACT 3-O Residents’ Research Day in Medicine A Randomized Controlled Trial of RADIATION McMaster Resident Research Day is an annual event hosted PROTECTion with a Patient Lead Shield and by the Department of Medicine at McMaster University a Novel, Non-Lead Surgical Cap for Operators where residents from the core Internal Medicine Training Performing Coronary Angiography or Intervention Program (PGY1 – 3) and residents from medicine subspecialty programs (PGY4 -6) can present their research to peers and Background: Interventional Cardiologists receive one of the highest levels of annual occupational radiation exposure. faculty members. Further measures to protect healthcare workers are needed.

Residents submit abstracts related to projects completed Methods and Results: We aimed to evaluate the efficacy during residency training for consideration for poster or of a pelvic lead shield and a novel surgical cap in reducing oral presentation. Abstracts are designated by the resident interventional cardiologists’ radiation exposure. Patients (author) as either (1) Clinical, relating to a patient case or undergoing coronary angiography or percutaneous coronary intervention (PCI) (n=230) were randomized to have their cases, or (2) Scientific, relating to an original hypothesis procedure with or without a lead shield placed over the testing or hypothesis generating research project. Three patient designed for either radial or femoral access. During abstract reviewers independently rank clinical and scientific all procedures, the interventional cardiologist wore the abstract, then meet to determine the final rank order list by “No Brainer” surgical cap (Worldwide Innovations and consensus. Clinical abstracts are evaluated based the novelty Technology, Kansas City, Kansas) designed to protect the head from radiation exposure. The co-primary outcomes for of the clinical case, depth of case presentation, completeness the lead shield comparison were i) operator dose (µSv) and of background information and description of implications ii) operator dose indexed for Air Kerma (µSv/mGy). For the cap and conclusions. Scientific abstracts are evaluated based on comparison, the primary outcome was the difference between the novelty of the research, the contribution of the resident, total radiation dose (µSv) (internal and external to cap). appropriateness of methods, completeness of background The lead shield use resulted in a 76% reduction in operator dose (mean dose 3.07; 95% CI 2.00-4.71 µSv lead shield group information, and description of implications and conclusions. vs. 12.57; 95% CI 8.14-19.40 µSv control group, p<0.001). The Abstracts are then selected for poster presentation, oral mean dose indexed for air kerma was reduced by 71% (0.005; presentation or rejected. Only abstracts from the first two 95% CI 0.004-0.006 µSv/mGy lead shield group vs. 0.017; 95% groups have been accepted for publication in CJGIM. CI 0.014-0.020 µSv/mGy control group, p<0.001). The cap use resulted in an 81% reduction in operator head radiation During the event, 3 judges for the clinical posters and exposure (mean external dose 6.47; 95% CI 5.56-7.50 µSv vs. mean internal dose 1.25; 95% CI 1.01-1.53 µSv, p<0.001). 3 judges for the scientific posters and oral sessions evaluate each presentation. For poster sessions, the resident author Conclusions: The use of a pelvic lead shield and the cap presents a verbal summary of their research followed by a reduced operator radiation exposure each independently by brief question and answer session with the judges. Resident more than 75%. These protective measures can be incorporated presentation skills and resident knowledge are considered into clinical practice and increase operators’ safety. in the judges’ evaluation. The judges select the top 3 clinical Supervisor: Dr. Sanjit Jolly posters, the top 3 scientific posters and the top 3 oral abstracts which are announced at the end of Resident Research Day.

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 55 McMaster University 26th Annual Residents’ Research Day in Medicine

ORAL PRESENTATION ORAL PRESENTATION

Silver Medal: Mary Salib, PGY3 Bronze Medal: Tahseen Rahman, PGY2 ABSTRACT 1-O ABSTRACT 4-O The Epidemiology of Immune Thrombocytopenia Comparative Effectiveness of Transitional Care (ITP): Validation of an ITP Registry Services in Patients Discharged from Hospital with Heart Failure: a Meta-Analysis Introduction: Understanding of the epidemiology of immune thrombocytopenia (ITP) requires large prospective cohort Background: Patients are at increased risk of death and studies with prolonged follow up. The objectives of this study readmissions following heart failure (HF) hospitalization. were to (a) describe the prevalence, clinical features and Services that support patients transitioning from hospital to treatments received from consecutive patients with ITP from home can improve clinical outcomes, but their comparative a newly-established registry, and (b) ensure the accuracy of effectiveness is unclear. data collection. Purpose: To compare the effectiveness of transitional care Methods: The McMaster ITP Registry (MIR) enrolls services in decreasing all-cause mortality and readmissions consecutive patients with thrombocytopenia from a tertiary following HF hospitalization. hematology clinic. Patient data collected includes: diagnosis at most recent visit, platelet count trends, bleeding events, Methods: We searched Pubmed, Embase, CINAHL, and and treatments. Accuracy of data capture was evaluated for Cochrane for articles published between 2000-2014. We 50 registry patients chosen at random by comparing the data included RCTs that recruited hospitalized patients with a main in the registry with data abstracted from patients’ charts by diagnosis of HF, tested the efficacy of a transitional care service 2 independent assessors. Agreement was calculated using intervention, provided >1 month of follow-up, and reported Cohen’s kappa (k). the outcomes of all-cause mortality or readmissions. Two authors independently reviewed each study and extracted data. Results: From January 2010 to February 2014, 465 thrombocytopenic patients were enrolled in the MIR: 258 Results: We included 45 RCTs with 9571 HF patients. (55.5%) with ITP. Median age at diagnosis of ITP was 41 years Interventions included education alone, telephone support, [IQR, 32 – 58], 62.8% were female and patients had received telemonitoring, pharmacist interventions, nurse home visits, a median of 2 (IQR, 0 – 4) treatments. 33.3% of patients case management, or disease management clinics (DMCs). had splenectomy, 15.4% had received rituximab and 20.5% Overall, transitional care services significantly decreased had received thrombopoietin receptor agonists. Of patients all-cause mortality (RR 0.83, 95% CI 0.77-0.88) and readmissions with a documented platelet count at diagnosis (n=155), 70% (RR 0.80, 95% CI 0.72-0.90). Among services that decreased presented with a platelet count <30 x109/L and of those, 6.9% all-cause mortality, DMCs (RR 0.65, 95% CI 0.53-0.81) were were refractory to treatment at their most recent follow up. most effective, followed by telephone support (RR 0.78, 95% Accuracy of data collection was excellent (k>0.8). CI 0.61-0.99); home visits (RR 0.84, 95% CI 0.72-0.99); and case management (RR 0.85, 95% CI 0.77-0.94). Services that Conclusion: In the setting of a tertiary hematology clinic, 55% decreased all-cause readmissions include case management (RR of patients presenting with thrombocytopenia had ITP. 6.9% 0.75, 95% CI 0.57-0.99), and multidisciplinary DMCs (RR 0.79, of ITP patients who presented with severely reduced platelets 95% CI 0.68-0.92). The other interventions did not improve all- (<30 x109/L) became refractory to treatment. The MIR can cause mortality or readmissions. help identify clinical and laboratory features of ITP patients to better understand natural history and treatment responses. Conclusion: Case management, home visits, telephone support and DMCs decreased all-cause mortality or readmissions after Supervisor: Dr. Donald Arnold HF hospitalization. These strategies should be considered following HF admission.

Supervisor: Dr. Harriette Van Spall

56 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

ORAL PRESENTATION ORAL PRESENTATION

Kimia Honarmand PGY2, Diana Ulic PGY3, Roochi Arora PGY1 Abubaker Khalifa PGY2, Andrew Gibson Critical Care Fellow, ABSTRACT 5-O Fayez Alshamsi Critical Care Fellow, Resident Assessment of Faculty: Erick Duan Critical Care Fellow Residents’ Perceptions of Utility ABSTRACT 2-O The Deferred Consent Model in A Low Risk Study Introduction: Resident written assessments of faculty Evaluating Myocardial Injury in the ICU physicians are used to provide feedback on clinical teaching in performance reviews. Previous studies have identified Background: Informed consent is a hallmark of ethical clinical barriers that may prevent residents from providing honest, research. An inherent challenge in critical care research is useful feedback. This study sought to determine if residents: obtaining consent in the intensive care unit (ICU) when feel confident in the anonymity of online feedback to patients lack decision-making capacity. The objective of this faculty physicians, believe their feedback is used to modify research ethics sub-study is to describe a deferred consent clinical teaching, and are aware of the process by which their model in a low-risk, minimally invasive study in the ICU. assessments are delivered to faculty.

Methods: PRO-TROPICS was a prospective, pilot Methods: We designed an anonymous, online survey for observational study of adult critically ill patients in Internal Medicine residents using the above objectives. 60/99 3 Hamilton ICUs, involving serial electrocardiograms and residents completed it. cardiac biomarkers during the ICU stay. Newly admitted ICU patients were enrolled over one month. When possible, Results: Only 44% of respondents were confident their online informed consent was obtained a priori, but largely consent feedback is anonymous. Although 100% of respondents was deferred until investigators could approach the patient felt honest feedback was important, only 54% admitted to or their substitute decision-makers (SDMs), as per Research providing it. Main barriers to providing honest feedback were Ethics Board approval. concerns regarding anonymity, and the belief that assessments would not modify clinical teaching. Although 70% of residents Results: Of 266 patients approached, consent encounters believed faculty deem resident feedback honest and fair, and were with patients (n=140, 52.6%) more often than SDMs 79% believed faculty view resident feedback as integral to (n=126, 47.4%), led mostly by residents following a brief professional development, only 8% thought faculty would training session. Consent encounters were in person (n=221, modify behaviours based on resident feedback “often”; 66% 83.1%) or by telephone (n=45, 16.9%). The overall consent felt they would do so “sometimes” and 26% felt they would do rate was 80.1% (84.5% at St. Joseph’s Healthcare, 84.4% at so “rarely”. 60% of residents had minimal or no understanding the Juravinski Hospital, and 72.6% at the Hamilton General of the feedback process. Presently, resident feedback is collated Hospital; p=0.07). The median interval between enrollment and distributed to faculty annually to preserve anonymity. and the consent encounter was 1 day (IQR=1-2). There was Residents suggested their comments be synthesized into no difference in consent rates between patients and SDMs general feedback, and delivered to faculty sooner to effect (84.3% vs. 75.4%; p=0.09). Of 53 persons declining consent, timely changes. 37 (69.8%) agreed to the use of data collected to that point. Conclusions: Residents desire reassurance that their feedback Conclusions. While informed consent should be obtained is anonymous and are skeptical that it modifies clinical as early as possible, the deferred consent model facilitates teaching. Future directions include resident education on the timely protocol implementation until the consent encounter feedback process. is possible. The deferred consent model appears to be an acceptable and feasible alternative to exclusively a priori Supervisor: Dr. Parveen Wasi consent in low-risk ICU studies.

Supervisor: Dr. Deborah Cook

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 57 McMaster University 26th Annual Residents’ Research Day in Medicine

ORAL PRESENTATION ORAL PRESENTATION

Diana Ulic PGY3, Kimia Honarmand PGY2, Abubaker Khalifa Neal Manning, Hematology PGY5 PGY2, Andrew Gibson Critical Care Fellow, Fayez Alshamsi ABSTRACT 7-O Critical Care Fellow, Erick Duan Critical Care Fellow Interventions to Reduce Blood Loss from ABSTRACT 6-O Laboratory Testing in Critically Ill Patients and Scholars and Collaborators on the Frontline: Impact on Transfusion: A Systematic Review Resident-led Research in a Prospective, Observational Study in Critically Ill Patients Background: Blood loss for laboratory testing contributes to anemia, which is a common complication of critical illness Background: Conducting clinical research represents an and is associated with poor outcomes. Reduction of diagnostic important academic opportunity and a training program phlebotomy volume may reduce transfusions and improve expectation during residency. However, residents are rarely outcomes in critically ill patients. Study aims are to identify involved in all stages of a study. Highlighting the CanMEDS strategies for reducing blood loss from diagnostic phlebotomy roles of ‘Collaborator’ and ‘Scholar’, our objective is to describe and assess their impact on volume of blood loss, transfusion and a novel, resident-driven approach to clinical research in a clinical outcomes. multicenter prospective pilot observational study. Methods: Systematic review of published English-language Methods: Over 10 months, 7 residents collaborated on the studies using standard methodology. PROTROPICS Pilot Study, which aimed to evaluate the feasibility of a larger study to assess the prognostic importance of troponin Results: A search (Medline and Embase) yielded 3045 studies. elevations in ICU patients. As Principal Investigator, a research After review by 2 independent assessors, 7 studies including fellow completed the literature review and initial protocol. 3 randomized controlled trials and 4 controlled cohort studies Results: Full resident involvement occurred from initial protocol were included. Interventions included indwelling catheter refinement to ethics board approval and implementation. devices that reduce discarded blood (n=4), small-volume Preparatory work included building and piloting case report blood collection tubes (n=2) and avoidance of arterial catheters forms, an inter-rater reliability study, and training to obtain (n=1). All 3 RCTs reported reduced phlebotomy volumes valid research consent. During the 1-month recruitment and using arterial catheter blood conservation devices compared 4-month follow-up in 3 Hamilton ICUs, resident-investigators to standard practice (mean/day 35 vs. 69 mL, p<0.01; median/ worked daily, outside their clinical duties, screening 304 patient day 8 vs. 40 mL, p<0.001; median/day 63 vs. 133 mL, p=0.001). admissions (representing 280 eligible patients), procuring Two RCTs reported transfusion data, 1 showed a statistically deferred consent for 213 patients, collecting and entering significant decrease in transfusions with the arterial catheter patient-level data. Consistent, longitudinal involvement resulted device intervention vs. control (21% vs. 38%, p=0.01). In 2 of in a deeper understanding of research methodology and research 3 cohort studies interventions reduced phlebotomy volumes ethics than usual for resident research, and facilitated early compared to standard practice (mean/day 63.6 vs. 114.7 mL, identification and resolution of barriers to recruitment. p<0.001; median/day 5.1 vs. 19.9 mL, p<0.001; mean/day 32.2 vs. 55.6 mL, p-value not specified, respectively). ICU length Conclusion: High-intensity resident-led research was possible of stay was not different between groups. for the PROTROPICS Pilot Study. The ‘Collaborator’ role was developed through interaction of resident-investigators with Conclusion: Diagnostic phlebotomy volume reduction one another in dividing study responsibilities across sites, and techniques appear to reduce blood loss and may reduce with ICU staff while in-servicing and addressing study concerns. transfusion rates in critically ill patients. High quality randomized The ‘Scholar’ role was developed through hands-on experience studies evaluating patient-important clinical outcomes are in research methodology. Immersion of residents in so many needed to evaluate the efficacy and possible harms associated aspects of this study fostered project ownership, represented with interventions that reduce blood loss for laboratory testing. unique experiential research education, and encouraged academic leadership. Supervisor: Dr. Deborah Siegal

Supervisor: Dr. Deborah Cook

58 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

ORAL PRESENTATION SCIENTIFIC POSTER PRESENTATIONS

Nazanin Montazeri PGY2 First Prize: Bishoy Deif, PGY2 ABSTRACT 8-O ABSTRACT 9-S Longer Length of Initial Prescription Post-STEMI Application of Syncope Guidelines in the is Associated with Higher Medication Adherence: Emergency Department does not Reduce a Post-Hoc Sub-Study of the DERLA-STEMI Trial Admission Rates and Syncope Admissions are not Associated with Less Adverse Cardiovascular Background: Discontinuation of guideline-recommended Outcomes: A Retrospective Cohort Study cardiac medications post-ST-elevation myocardial infarction (STEMI) is common and associated with increased mortality. Background: Syncope comprises 1.5% of all emergency Previous observational studies have suggested an association department (ED) visits and approximately 2-billion dollars between longer initial prescription length and improved (USD) in related hospitalizations. Syncope guidelines are long-term adherence. This study aimed to further evaluate intended to identify high-risk patients and streamline admissions the relationship between prescription length and medication and investigations. Our aim was to determine if application of adherence post-STEMI. syncope guidelines would reduce the number of admissions.

Methods: Observational sub-study of the DERLA-STEMI cluster- Methods: A retrospective chart review was conducted in randomized controlled trial (REB number: 11-191). Discharge all syncope presentations to the ED, spanning 1 year at two prescriptions of DERLA-STEMI participants were reviewed on an tertiary care institutions. Three different guidelines, Canadian electronic health records management system. Medication classes, Cardiovascular Society (CCS), American College of Emergency duration of prescription and repeats were recorded. Medication Physicians (ACEP) and European Society of Cardiology (ECS), use at 12 months post-STEMI was studied in relation to the initial were applied to determine the effect on admission rates. prescription duration. Adherence data was collected through structured phone calls to the patients by a blinded research Results: A total of 1228 syncope presentations to the ED coordinator as per a previously published protocol. were identified, 505 patients (41%) were admitted and 723 The main outcome of interest was the proportion of (59%) were discharged. Five hundred charts were randomly patients taking all 4 cardiac medication classes (acetylsalicylic reviewed to date, 174 (40%) were admitted and 261 (60%) acid, angiotensin blocker, statin, and beta-blocker) at were discharged from the ED. The admitted group had higher 12 months in each prescription group (≤2 months versus rates of Congestive Heart Failure 13% vs. 6%, Coronary Artery >2 months). Disease 34% vs. 15%, and Structural Heart Disease 11% vs. 5% (p<0.01), respectively. Medical records were reviewed Results: Out of 390 participants reviewed, 315 had prescriptions 1 year following syncope presentations in both admitted and for 4/4 medications with available follow-up. A total of 170 were non-admitted groups and adverse cardiovascular events were prescribed 4/4 medications for greater than 2 months while 145 9% vs. 3% (p<0.01), respectively. When compared to 174 had one or more medication that was prescribed for less than or (40%) deemed necessary admissions by the deciding physician, equal to 2 months. The results showed a statistically significant CCS guidelines warranted for 263 (60%, p<0.01), ACEP 189 increase in cardiac medication persistence at 12 months in the (43%, p=0.28), and ESC 220 (50%, p=0.004) admissions. group with longer initial prescriptions (OR 2.87, 95% CI 1.77- 4.66, p<0.0001). Conclusion: Our study suggests that the current admitted Conclusions: In post-STEMI patients, longer duration of syncope population is older and has a higher comorbidity discharge prescriptions was associated with higher adherence burden, possibly explaining why adverse cardiovascular events at 12 months. The results are limited by the small sample size are higher in this group. Finally, our data shows that application and the observational design of this study. Nevertheless, giving of syncope guidelines is unlikely to reduce admission rates, and longer prescriptions at discharge is a simple intervention that that a lack of agreement exists among the different guidelines could increase long-term medication adherence. resulting in significant variation between warranted admissions.

Supervisor: Dr. JD Schwalm Supervisor: Dr. Carlos Morillo

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 59 McMaster University 26th Annual Residents’ Research Day in Medicine

SCIENTIFIC POSTER PRESENTATION SCIENTIFIC POSTER PRESENTATION

Second Prize: Matthew Lanktree, PGY3 Benjamin Tam PGY3 ABSTRACT 2-S ABSTRACT 1-S IronSeq: Improving Genetic Testing in Are Critical Events Predictable? The Patterns of Hemochromatosis with Next Generation Decline Reflected in the Hamilton Early Warning Sequencing Score (HEWS) Prior to Inpatient Death, Arrest or Unplanned ICU Transfer Background: The genetic test for hemochromatosis currently implemented in clinical practice involves the genotyping of 2 Background: The Hamilton Early Warning Score (HEWS) single nucleotide polymorphisms (HFE C282Y and H63D). was implemented to be a safety net for deteriorating However, low penetrance and sensitivity yield a test of little ward patients. The objective of this study was to improve clinical value despite wide clinical use. Improvements in understanding of the score by outlining patterns of decline technology have reduced the cost of DNA sequencing creating prior to critical events. the opportunity for an improved genetic test. We hypothesized that deep resequencing of iron metabolism genes would Methods: We identified 7138 patients admitted to medical uncover additional mutations. or surgical wards at two academic hospitals. One centre had already implemented HEWS while the other was in the process Methods: A targeted next generation sequencing panel was of implementation. Charts were reviewed retrospectively for constructed to allow for the high-throughput evaluation of a critical event defined as an inpatient death, arrest and/or 16 genes with known roles in iron metabolism. After ethics unplanned ICU transfer. The highest HEWS was documented approval, the DNA of 96 patients with elevated ferritin at time of admission and at 72, 48 and 24 hour intervals (>400 pmol/L) or transferrin saturation (>55%) were sequenced. before a critical event. The relationships between those with and without a predictive pattern of decline were examined. Results: A total of 36 mutations in 10 different genes were Discrete variables were compared with Chi-square tests and observed. These included: a complete deletion of hemojuvelin continuous variables with ANOVA. (HJV, HFE2), a complete duplication of beta-2-microglobulin (B2M), a frameshift mutation in ferritin light chain (FTL), Results: Overall, 519 critical events occurred. Patients who had a nonsense mutation in cerruloplasmin (CP), as well as critical events were admitted with a higher median HEWS than 6 mutations previously reported as deleterious. Eighteen those who did not. Furthermore, the median HEWS rose above patients had heterozygous mutations in multiple different triggered care thresholds 24 hours prior to a critical event. A iron metabolism genes. Of 96 patients sequenced, 21 were total of 55% of patients had a pattern of HEWS that predicted HFE 282Y homozygotes and an additional 11 were compound a critical outcome. However, there were no differences in 282Y/63D heterozygotes, which was 100% concordant with patient characteristics or outcomes in those with or without a previous genotyping results. No additional HFE mutations predictive pattern of decline. were identified and no patients had homozygous mutations consistent with a diagnosis of juvenile hemochromatosis. Conclusions: Physiologic disturbances reflected by HEWS can be detected in ward patients at the time of admission and Conclusions: The clinical significance of iron metabolism gene prior to critical events. As such, HEWS creates a safety net by mutations requires further evaluation before implementation providing the backbone to monitor, triage and communicate in clinical practice. However, next generation sequencing is the a patient’s status throughout the hospital. Future work will inevitable evolution of genetic testing in hemochromatosis. optimize care for patients who have a predictive pattern of deterioration and outline factors associated with a non- Supervisor: Dr. Mark Crowther predictive decline.

Supervisor: Dr. Alison Fox-Robichaud

60 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

SCIENTIFIC POSTER PRESENTATION SCIENTIFIC POSTER PRESENTATION

Andrew Smyth, Nephrology PGY5 Abubaker Khalifa PGY2 ABSTRACT 3-S ABSTRACT 4-S Diet and Major Renal Outcomes: Home Administered Lasix Therapy in Patients The NIH-AARP Diet and Health Study with Heart Failure and Chronic Congestion ( HALT)

Introduction: Chronic kidney disease (CKD) is increasingly Background: Healthcare costs related to hospitalization prevalent and associated with significant morbidity and for heart failure (HF) continue to rise. Some patients mortality. Diet modification may be a low-cost, simple approach become unresponsive to oral diuretic therapy and require to reducing CKD burden. In this study, we aimed to evaluate the hospitalization for adequate intravenous (IV) diuresis. To our association between diet quality, sodium and potassium intake knowledge, home-administered IV Lasix therapy (H-IVL) is a and major renal outcomes. novel regimen to relieve the chronic congestion and transition patients to oral diuretic therapy while avoiding unnecessary Methods: The NIH-AARP Diet and Health Study is a prospective hospitalizations. The purpose of this study is to report patient cohort study of community-dwelling adults living in 6 states and clinical outcomes over the 6-month period following initiation 2 urban areas in the USA. Using a food frequency questionnaire, of H-IVL in the HF clinic. we assessed diet quality (Alternate Healthy Eating Index (AHEI), Healthy Eating Index (HEI), Mediterranean Diet Score (MDS) Methods: We conducted a retrospective chart review of and Recommended Food Score (RFS)), sodium and potassium 55 patients who received H-IVL between January 2011 and intake. Multivariable adjusted competing risks regression was September 2012. Clinical events (transition to oral diuretic used to calculate sub-hazard ratios (sHR) for a composite of therapy, hospitalization, death), number of clinic visits, dialysis OR death due to a renal cause, with death from a non- duration of time receiving H-IVL were collected for the first renal cause as the competing event. 6 months after initiation of H-IVL.

Results: Of the 544,635 participants included, mean follow-up Results: Patients had a median (25th, 75th percentile) age of 75 was 14.3 years and 4,848 participants initiated dialysis or died (69, 82) years. LVEF 35 (22, 53)%, NYHA III-IV symptoms from a renal cause. Three diet quality scores (AHEI, HEI and (100%), and 72% had been hospitalized (all cause) in the MDS) were significantly associated with outcomes; the RFS was previous 6 months. The median starting total daily dose of not. The strongest association was seen with AHEI. Compared H-IVL therapy was 160 (90,160) mg and median duration of to the lowest diet quintile, the highest quintile of AHEI H-IVL was 54 (18,78) days. In the 6-month period following (sHR 0.71; 95% CI 0.65-0.79), HEI (sHR 0.82; 95% initiation of H-IVL, 75% (n=41) transitioned to oral diuretics, CI 0.74-0.91), and MDS (sHR 0.84; 95% CI 0.74-0.95) were while 31% (n=17) transitioned to oral therapy without associated with a reduced hazard of the composite. The highest hospitalization or death. Thirty-three patients (60%) were sodium quintile (sHR 1.17; 95% CI 1.02-1.33 for sodium intake hospitalized (HF) with a median LOS of 5 (0,14) days and 22% >3.6g/day) was associated with an increased hazard while (n=12) died (all cause). the highest potassium quintile (sHR 0.83 (0.73-0.95)) with a reduced hazard. Conclusion: This novel H-IVL therapy allows these advanced HF patients to avoid prolonged HF-related hospitalizations Conclusion: Our findings support an association between in an attempt to improve quality of life. Future studies need healthy dietary patterns and reduced risk of renal outcomes to include patient reported outcomes such as quality of life, caregiver burden, and the economic analysis of this program. Supervisors: Drs. Martin O’Donnell & Salim Yusuf Supervisor: Dr. Robert McKelvie

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 61 McMaster University 26th Annual Residents’ Research Day in Medicine

SCIENTIFIC POSTER PRESENTATION SCIENTIFIC POSTER PRESENTATION

Diana Ulic PGY3, Rebecca Mathew PGY3, Katrina Piggott PGY2, Arthur Wong PGY3, Serena Gundy PGY4 Leslie Martin PGY3, Alexandra Patel, ABSTRACT 5-S Matthew Patel, Yudong Liu Reduced Resident Duty Hours – A Change for ABSTRACT 6-S the Better? A Qualitative Analysis of a Reduced Important Barriers to Goals of Care Discussions Duty Hour Model for Senior Internal Medicine with Patients and Families from the Perspective Residents at McMaster University of Oncologists and Oncology Nurses

Background: A night float (NF) model for senior medical Background: Cancer is the leading cause of death in Canada, residents (SMRs) was introduced at McMaster, substituting and yet only a minority of hospitalized cancer patients have 26-hour call with 13-hour night shifts by dedicated NF SMRs, discussions with their healthcare providers about goals of thereby eliminating post-call absences for SMRs on the Clinical care (GoC). Decision-making about GoC has been defined Teaching Unit (CTU). No Canadian study has assessed the as a process that occurs between healthcare providers and a effects of reduced duty hours on efficiency of healthcare patient to establish a plan of care in an institutionalized setting. delivery by residents for medicine patients. The purpose of This process includes decisions about the use or non-use of this study is to evaluate the impact of McMaster’s NF model life-sustaining treatments. We sought to identify barriers to on markers of healthcare efficiency, specifically investigating GoC discussions from the perspectives of staff oncologists, whether uninterrupted CTU SMR daytime presence decreased oncology residents, and oncology nurses. length of stay (LOS) and whether nighttime presence of day-rested NF SMRs resulted in shorter wait times between Methods: Juravinski Cancer Center staff oncologists, oncology initial medicine consultation and admission. residents, and registered nurses working on oncology wards were surveyed. Barriers to GoC discussions were assessed on a Methods: Data were collected across 2 McMaster sites for 10 7-point Likert scale (1=extremely unimportant; 7=extremely months before and after NF implementation in July 2013. The important). ED-based primary outcome was timing between consultation and admission, while the CTU-based outcome consisted of LOS. Results: Between July 2013 and May 2014, 30 staff physicians, Statistical analysis involved calculating means and standard 10 residents, and 28 nurses returned surveys (response rate of deviations of primary outcomes, using an independent sample 37%). The most important barriers to GoC discussions were t-test to assess for statistical significance (p<0.05). patient and family member factors. They included difficulty accepting poor prognoses (mean [SD] score, 5.9 + 1.0), lack Results: There was no statistically significant difference in time of family agreement in the goals of care (5.8 + 1.1), difficulty elapsed between consultation and medicine admission in the understanding the limitations of life-sustaining treatments ED before and after the implementation of NF, nor was there (5.8 + 1.0), lack of patients’ capacity to make goals of care a significant difference in CTU LOS. decisions (5.7 + 1.1), and language barriers (5.7 + 1.0). Participants viewed system factors and healthcare provider Conclusions: The implementation of an SMR NF model did factors as less important barriers. not lead to changes in healthcare efficiency either on the CTU or ED – findings at odds with our initial hypotheses. However, Conclusions: Oncology caregivers perceive patient and family ED wait times and CTU LOS are affected by multiple variables factors as the most limiting barriers to GoC discussions. Our that may have confounded our results. Overall, a NF model is findings highlight the high levels of anxiety or even denial faced feasible and does not compromise efficient healthcare delivery by patients with advanced cancer and underscore the need for for medicine patients, which may have positive implications oncology clinicians to be equipped with strong communication for patient safety. skills to help patients and families navigate GoC discussions.

Supervisors: Drs. Shariq Haider, Parveen Wasi Supervisor: Dr. John You

62 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

SCIENTIFIC POSTER PRESENTATION SCIENTIFIC POSTER PRESENTATION

Elvira Bangert PGY2 Arastoo Mokhtari PGY2 ABSTRACT 7-S ABSTRACT 8-S The Prognostic Utility of Stress Myocardial Utilization of Anticoagulation and Antiplatelet Perfusion Imaging in Patients with Evidence of Therapies at Discharge in Patients with Atrial Myocardial Injury After Non-Cardiac Surgery Fibrillation and Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Although patients with myocardial injury after non-cardiac surgery (MINS) are at increased risk of adverse CV events Background: Guidelines recommend use of oral following surgery, non-invasive risk stratification tools to better anticoagulants (OAC) for stroke prevention in patients with risk stratify these individuals has not been evaluated. atrial fibrillation (AF), and dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) with stent Objective: Our study evaluated the prognostic relevance implantation. The antithrombotic management of patients of SPECT-MPI in patients with MINS. The primary with coexistent AF and stent implantation is more complex objective was to examine the association between coronary and less defined. In this study we intended to assess local artery disease (CAD) identified on SPECT-MPI and major practice patterns in this unique group of patients. cardiovascular events (MCVE, defined as myocardial infarction, death, heart failure or coronary revascularization) Methods: Clinical characteristics and discharge antithrombotic at 6 months following surgery. regimens were collected through chart review of consecutive patients undergoing PCI admitted to three local academic Methods: We conducted a retrospective chart review at the hospitals from January to December 2014. Inclusion criteria Hamilton Health Sciences from 2009 to 2013. Patients with were: admission with acute coronary syndrome (ACS); known MINS, defined as an abnormal troponin within 30 days following or new onset AF with CHADS2 ≥ 1, 70% stenosis in at least one surgery who also underwent SPECT-MPI were included in this coronary artery, successful stent implantation, and being alive study. Outcomes were examined up to 6 months following at the time of discharge. surgery. CAD on SPECT-MPI was defined as a sum stress score (SSS) > 4, and its association with clinical events was examined. Results: After considering the selection criteria, fifty-three patients were included in the analysis. Median age was 76 years Results: 77 participants were included in the study. The SSS old; median CHADS2 and ATRIA bleeding risk score were was abnormal (>4) in 27 (35%). The rate of MCVE was 6.0% 2 and 3 respectively. Sixteen patients (30.2%) were discharged in patients with a normal SSS, compared to 14.8% with an on both OAC and DAPT defined as Triple therapy (TT). abnormal SSS. A SSS > 4 was associated with a 2.69 (95% CI The CHADS2 score was significantly higher in the TT group, 0.42-19.86) increase in the odds of a major cardiovascular event. compared to DAPT group (3.06 vs. 2.11, p=0.004). None of Each unit increase in the SSS was associated with a 1.13 (95% CI the other clinical or process variables predicted use of TT. The 1.00-1.29) increase in risk. thrombosis service was consulted in 22.6% of patients and this was associated with a higher use of TT (p=0.002). Conclusion: Although this study was underpowered to evaluate the relationship between the extent of CAD Conclusion: TT was used in one-third of patients with AF and identified on SPECT and events, large differences in both the ACS undergoing PCI with stent implantation. Patients treated cardiovascular event rate and odds ratios suggest that SPECT with TT had significantly higher CHADS2 scores and were may be an effective risk stratifying tool for patients suffering more likely seen by the thrombosis service; however, there MINS. Larger studies are needed. appeared to be no association between treatment regimen and variables that predict bleeding. Supervisor: Dr. Philip Joseph Supervisor: Dr. Madhu Natarajan

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 63 McMaster University 26th Annual Residents’ Research Day in Medicine

SCIENTIFIC POSTER PRESENTATION SCIENTIFIC POSTER PRESENTATION

Omair Sarfaraz, Medical Biochemistry PGY2 Mary Salib PGY3 ABSTRACT 10-S ABSTRACT 11-S A Quantitative Metabolomics Profiling Approach Difficulties in Establishing the Cause of For the Noninvasive Assessment of Liver Thrombocytopenia Among Ambulatory Patients Histology in Patients with Chronic Hepatitis C Referred to Hematology: An Agreement Study

Background: High-throughput technologies have the potential Introduction: The diagnosis of thrombocytopenia can be to identify biomarkers of liver pathology and improve our challenging as common diseases specific or easily identifiable understanding of basic mechanisms of liver injury and repair. diagnostic markers. The reliability of the diagnosis is uncertain, A metabolomics profiling approach was employed to determine which has implications for patient management and eligibility associations between alterations in serum metabolites and liver for clinical trials. The objective of this study was to determine histology in patients with chronic hepatitis C (HCV). the reliability of the diagnosis of thrombocytopenia in the outpatient setting among 3 independent hematologists. Methods: Sera from 45 non-diabetic patients with chronic HCV were analyzed using 1H-NMR spectroscopy, and Methods: We selected 20 patients referred to a tertiary concentrations of metabolites were quantitatively determined. hematology clinic with thrombocytopenia, previously A metabolite profile of advanced fibrosis (METAVIR F3-4) enrolled into the McMaster ITP Registry. Three hematologists was established using orthogonal partial least squares independently reviewed all source documentation blinded discriminant analysis modeling and validated using seven-fold to the chart diagnosis, and were asked to make their own cross-validation and permutation testing. Bioprofiles of diagnosis. Agreement was calculated using Fleiss’s kappa (k). moderate to severe steatosis (≥ 33%) and necroinflammation Following the initial adjudication, reviewers met face-to-face (METAVIR A2-3) were also derived. The classification to resolve disagreements. accuracy of these profiles was determined using areas under the receiver operator curves (AUROCSs) measuring against Results: Overall agreement among the reviewers for the liver biopsy as the gold standard. diagnosis of thrombocytopenia was moderate (k=0.51, 95% confidence interval, 0.39 to 0.63), with reviewers demonstrating Results: In total 63 spectral features were profiled, of which a perfect agreement in 10 of 20 patients with primary ITP (n=5), highly significant subset of 21 metabolites were associated with secondary ITP (n=3), and MDS (n=2). Agreement among advanced fibrosis (variable importance score > 1 in multivariate reviewers for the diagnosis of ITP was associated with lower modeling; R2=0.673 and Q2=0.285). For the identification platelet count nadirs (median=4x109/L vs. 20x109/L; p=0.04) of F3-4 fibrosis, the metabolite bioprofile had an AUROC of and response to steroids or intravenous immune globulin 0.86 (95% CI 0.74-0.97). The AUROCs for the bioprofiles for (IVIG). During the consensus meeting, 5 disagreements were moderate to severe steatosis were 0.87 (95% CI 0.76-0.97) and resolved. The remaining disagreements were primarily due to for grade A2-3 inflammation were 0.73 (0.57-0.89). ambiguity of ‘liver disease’ and ‘hypersplenism’ As a result, these categories have been combined in the McMaster ITP Conclusion: This proof-of-principle study demonstrates the Registry. utility of a metabolomics profiling approach to non-invasively identify biomarkers of liver pathology in patients with chronic Conclusion: Inter-rater reliability for the diagnosis of HCV. Future cohorts are necessary to validate these findings. thrombocytopenia was moderate. Agreement was highest for patients with ITP and MDS. Lower nadir platelet counts and Supervisor: Dr. Andrew Don-Wauchope response to corticosteroids or IVIG were indicative of ITP. Patients with hypersplenism or liver disease were generally indistinguishable. Our classification scheme can help establish the cause of thrombocytopenia.

Supervisor: Dr. Donald Arnold

64 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Nima Zamiri PGY1 Michael Fine PGY2 ABSTRACT 12-S ABSTRACT 13-S Efficacy and Safety of Dabigatran vs. Warfarin Systematic Review: Sequential Rescue Therapy According to CHA2DS2-VASc Score: in Severe Ulcerative Colitis: Do the Benefits A Subgroup Analysis of RE-LY Trial Outweigh the Risks?

Introduction: RE-LY demonstrated the effects of dabigatran Background: The options for medical management of acute compared with warfarin in patients with atrial fibrillation. we severe steroid-refractory ulcerative colitis (UC) are limited. investigated the efficacy and safety of dabigatran versus warfarin Recent guidelines caution against use of sequential rescue therapy with respect to CHA2DS2-VASc and HAS-BLED scores. in the setting of failed medical management with an initial salvage therapy. A systematic review and meta-analysis were Methods: Based on CHA2DS2-VASc score, patients were conducted to assess the outcomes of sequential rescue therapy categorized into low (0-1), medium (2 to 4) and high risk with infliximab and calcineurin inhibitors like cyclosporine or (5 to 9) subgroups. We conducted a subgroup analysis of tacrolimus in patients with steroid refractory UC. RE-LY database with regards to primary efficacy (risk of stroke and systemic embolism) and safety (risk of major bleeding) Methods: A literature search identified studies that investigated outcomes according to CHA2DS2-VASc subgroups. treatment with infliximab and cyclosporine or tacrolimus in acute severe UC. The primary outcome was short term Results: The effects of Dabigatran 110mg BID compared symptomatic response to treatment. Secondary outcomes to warfarin were consistent according to CHA2DS2-VASc included adverse drug reactions, serious infections, mortality, subgroup for all efficacy and safety outcomes. The effects of rates of remission, and colectomy at 3 months and 12 months. dabigatran 150mg BID were consistent across risk groups for Response rates with 95% confidence intervals are reported. stroke and systemic embolism, and intra-cranial hemorrhage. However, for major bleeding there was a significant Results: Overall, 10 studies with 314 participants were eligible interaction (p<0.001) with a reduction in major bleeding with for inclusion. After sequential treatment patients achieved dabigatran 150mg BID in lower risk patients (HR 0.77; 95%CI short-term treatment response in 62.4% (95% CI 57.0- 0.65-0.92) and an increase in major bleeding in higher risk 67.8%) of cases and remission in 38.9% (95% CI 33.5-44.3%). patients ( HR1.34; 95%CI 1.06-1.69). There was some evidence Colectomy was required in 28.3% (95% CI 21.7-34.5%) of interaction for dabigatran 150mg BID versus warfarin for of patients at 3 months and 42.3% (95% CI 36.0-48.6) at mortality (p=0.03) with lower mortality in lower risk patients 12 months. Adverse events were encountered by 23.0% and similar mortality in higher risk patients. (95% CI 17.7-28.3%) of patients, including serious infections in 6.7% (95% CI 3.6-9.8%) and mortality in 1% (95% CI 0-2.1%). Conclusion: The effects of dabigatran 110mg BID versus warfarin are consistent across CHA2DS2-VASc risk groups. Conclusion: Our data summarizing experience from The effects of dabigatran 150mg BID on major bleeding vary observational studies suggest that the risk-benefit ratio of significantly according to risk. The lower dose of dabigatran sequential rescue therapy in acute severe UC seems acceptable. may be a better choice for some higher risk patients (such as In the setting of failed corticosteroids and an initial rescue CHA2DS2-VASc score 5 or more). therapy for acute severe UC, consideration can be given to use of another salvage agent based on patient preferences and the Supervisor: Dr. Stuart Connolly safety of this experience from observational data.

Supervisor: Dr. John Marshall

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Hassan Mir PGY3 Leslie Martin PGY3, Katrina Piggott PGY2, ABSTRACT 14-S Arthur Wong PGY3, Alexandra Patel, Tobacco Control: Analyzing Compliance of Matthew Patel, Yudong Liu Labelling on Tobacco Packets in Six Middle ABSTRACT 15-S Eastern Countries Goals of Care Discussions with Hospitalized Patients: the Role of Allied Health Providers in Introduction: Despite its positive impact, implementation of these Discussions and Perceived Barriers the World Health Organization’s Framework Convention on Tobacco Control (FCTC) remains a tremendous challenge. Background: Allied health professionals (AHPs) can contribute Monitoring compliance allows objective evidence and meaningfully to end-of-life goals of care (GoC) discussions specific feedback for the Ministries of Health to rectify their with seriously ill hospitalized patients and their families. limitations. In this study, we assess compliance of labelling on However, the perspective of AHPs about their participation in tobacco packets from 6 Middle Eastern countries with national GoC discussions is largely unknown. legislation and Article 11 of the FCTC. Methods: In this study, we sought to explore the perspective Methods: Investigators from 6 Middle Eastern Countries of hospital based AHPs on their role in GoC discussions and – Bahrain, Jordan, Oman, Qatar, Saudi Arabia, and United to identify barriers. We distributed a questionnaire to AHP Arab Emirates - collected at least 10 unique packets of the on general medicine, radiation and medical oncology at two most commonly consumed and cheapest brands of cigarettes hospital sites in Hamilton Ontario. Items were assessed on a between June 2013 and November 2014. A total of 81 packets 7-point Likert scale (1=extremely unimportant/unacceptable; were inspected using a structured data collection tool; all labels 7=extremely important/acceptable). were assessed for content, size, and location. Results: Questionnaires were completed by 32 AHPs Results: Health warnings were present on the Principal Display (9 physiotherapists, 7 social workers, 6 occupational therapists, Area (PDA - front and back panel) of all packets. There were 4 registered dieticians, 3 pharmacists, 2 speech language an average of 2 health warnings per pack and graphic pictorial pathologists, 1 unknown; response rate 68.1%). From AHPs’ warnings were present on 80% of all packs examined. All perspectives, the greatest barriers preventing them from countries met or exceeded the minimum requirement of engaging in GoC discussions with patients and families the FCTC recommendations. However, only Bahrain and were: lack of patient capacity (5.9+1.5, mean+SD), lack of Qatar met or exceeded their own legislation relating to health awareness of what other team members had told the patient/ warning labelling on tobacco packets in their country family (5.7+1.4), and family members’ difficulty accepting a Promotional labels were present on all packages. Deceptive poor prognosis for their loved one (5.6+1.4). AHPs believed terms such as ‘light’ and ‘blue’ were found on 67% of all it was most acceptable for staff physicians, residents, fellows packs. Legislative and ingredient labels were also present on (6.8+0.5) and advanced practice nurses (6.7+0.5) to initiate all packages. GoC discussions and reach a final decision, but also believed it was acceptable for a range of AHPs (5.3-6.1) to act as a Conclusion: All countries were compliant with FCTC decision coach with patients/families. Overall, AHPs did not recommendations on health warning labelling. However, there feel strongly supported to participate in GoC discussions is poor compliance and implementation of their own national (4.3+1.6). legislation. Promotional and deceptive labelling was present in all countries despite their ban according to the FCTC and Conclusion: AHPs are willing to be active participants in GoC national legislation. discussions with hospitalized patients and families by acting as a decision coach. By improving interprofessional collaboration Supervisor: Dr. Salim Yusuf we can engage the entire health care team in establishing GoC with patients and their families.

Supervisor: Dr. Ameen Patel

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Payam Yazdan-Ashoori PGY3 Rebecca Mathew PGY3, Diana Ulic PGY3, Serena Gundy PGY4 ABSTRACT 16-S ABSTRACT 17-S The LACE Index Predicts 30-day Readmission or Reduced Resident Duty Hours – A Change for Death in Patients Discharged from Hospital with the Better? A Qualitative Analysis of a Reduced Heart Failure Duty Hour Model for Senior Internal Medicine Residents at McMaster University Background: Heart failure (HF) is the most common reason for hospitalization and readmission in older adults. There are Background: The traditional 24-hour call system has been currently no bedside tools to predict readmissions in HF. The associated with numerous negative consequences for residents LACE index (Length of stay; Acuity of admission; Comorbidities; and patients, including impaired working memory, increased Emergency department use) is a simple tool validated in general frequency of motor vehicle accidents and higher rates of medical and surgical patients to predict early readmission or serious medical errors. Despite initial optimism, reduced duty death in high-risk patients (scores ≥10). We assessed whether hour models in the United States and Europe have shown the LACE index can predict 30-day readmission or death in inconsistent findings on improvements in resident quality of patients hospitalized with HF. life and patient safety. The purpose of this study is to assess the impact of a reduced duty hour model for senior internal Methods: We prospectively obtained demographic and clinical medicine residents at McMaster University on resident quality data by chart review in patients admitted with HF at HGH. We of life, attainment of educational goals and patient safety in the confirmed HF diagnosis using Boston criteria and calculated Emergency Department and Clinical Teaching Unit (CTU). LACE scores for each patient. We obtained outcomes data using electronic databases. We fit a logistic regression model with Methods: Qualitative data was collected through resident tertiles of LACE score as the predictor and 30-day readmission, focus groups that were completed prior to the introduction 30-day mortality, or composite 30-day readmission or mortality of night float, and 10 months following its implementation. as the outcome. We assessed model discrimination (C statistic), We used deductive analyses guided by grounded theory to and model calibration (Hosmer-Lemeshow test). complete qualitative analyses. Transcripts were coded, and codes collapsed into themes. Results: From March 2012 to July 2013, we included 378 patients. Within 30 days of discharge, 28% were readmitted Results: Our qualitative analyses revealed 4 themes in or died. The majority of patients (91%) had LACE scores ≥10. residents’ experience: increased frequency of handover, often The risk of outcomes increased with the LACE score, and accompanied by inaccurate and incomplete communication of became significant for scores ≥14 for the composite of 30-day patient issues; a resident reported urgency to sleep in the post- readmission or death and 30-day readmission alone. call period; an improvement in the experience of the SMR on CTU with the attending physician and junior house staff; and Conclusions: Incremental increases in LACE scores predicted improved short-term but worsened long-term fatigue for the incremental risk in 30-day readmission or mortality in HF SMRs on night float. patients. A threshold of 10 appears impractical to define high-risk in this population. Scores ≥14 may be more suitable Conclusions: A reduced duty hour model has the potential to capture high-risk HF patients who could benefit most from to improve residents’ perceived fatigue on call and provide transitional care interventions in a resource-conscientious better continuity of care for patients on the CTU, but must be manner. weighed against increased frequency of handover and the loss of the ‘post call’ experience for residents which can negatively Supervisor: Dr. Harriette Van Spall impact both patient care and resident quality of life.

Supervisor: Dr. Parveen Wasi

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Elvira Bangert PGY2 Nazanin Montazeri PGY2 ABSTRACT 18-S ABSTRACT 19-S An Exploration for a Minimum CD34+ Dosage for Impact of Prescription Errors on Medication Multiple Myeloma Patients Aged 65 To 71 Based Adherence Post-STEMI: a Post-Hoc Sub-Study of on an Association Between CD34+ Dosage and the DERLA-STEMI Trial Long Term Platelet Counts Following High Dose Therapy and Autologous CD34+ Reinfusion Background: Premature discontinuation of guideline- recommended cardiac medications post-ST-elevation Establishing an appropriate CD34+ dosage for Multiple myocardial infarction (STEMI) is common and associated Myeloma (MM) patients 65 and older is crucial given that the with increased mortality. This study evaluates the impact of median age of diagnosis for MM falls in the 65 to 70 year range. prescription errors at discharge post- STEMI on long-term medication adherence. Objective: To establish a correlation between the CD34+ dose and time to platelet engraftment (PE), the number of platelet Methods: Post-hoc observational sub-study of the DERLA- transfusions (PT), and platelet counts (PC) at 30, 180, and 360 STEMI cluster-randomized controlled trial (REB number: days from CD34+ reinfusion in MM patients under and over 11-191). Original handwritten discharge prescriptions of the age of 65 years. DERLA-STEMI participants were reviewed on an electronic health records management system from 2 Hamilton hospitals. Methods: A retrospective study of MM patients at the Medication use at 12 months was collected through structured Juravinski Hospital was conducted from 2008 to 2013. The phone calls to the patients by a blinded research coordinator patients were divided into two age groups: 155 patients under as per a previously published protocol. The main outcome 65 years and 46 patients over 65. Data was collected on PC of interest was the proportion of patients taking all 4 cardiac at 30, 180, and 360 days from CD34+ reinfusion. The time medication classes (acetylsalicylic acid, angiotensin blocker, of PE and the number of PT prior to PE were also recorded. statin, and beta-blocker) at 12 months in patients with and Linear regressions were performed to correlate the predictor in without prescription errors. Other outcomes included the CD34+ dose with the responses time to platelet data. nature and frequency of the errors.

Results: In MM patients under 65, CD34+ dosage correlates Results: 390 participants were reviewed, 101 errors were found with time to PE, the number of PT before PE, and PC at in 72 prescriptions. The errors included missing medication 30 days from CD34+ reinfusion, but not with PC at 180 days or name (n=1%), date (n= 26%), route (n=3%), signature (n=4%), 360 days from CD34+ reinfusion. In MM patients 65 years and duration (n=31%) or repeats (n=30%). Incorrect dose (n=1%) older CD34+ dosage correlates with the number of PT before or frequency (n=5%) were also noted. 12-month medication use PE, and PC at 30 days, 180 days, and 360 days from CD34+ was available for 67 patients. There was no statistical difference reinfusion, but not with time to PE. in medication use at 12 months post-STEMI in patients with error containing discharge scripts as compared to no errors (OR Conclusion: The minimum CD34+ dose is inadequate for 0.80, 95% CI 0.45-1.39, p-value 0.4244). The results were the maintaining normal PC 30 days from reinfusion, and most same even when adjusted for in-hospital blood transfusions and likely inadequate for maintaining normal PC 360 days from renal dysfunction (OR 0.82, 95% CI 0.46-1.46, p-value 0.4994). reinfusion in MM patients 65 years and older, although larger studies are necessary. Conclusions: In post-STEMI patients, prescription errors had no significant impact on medication adherence at 12 months. Supervisor: Dr. Ronan Foley Our results are limited by the small sample size.

Supervisor: Dr. JD Schwalm

68 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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First Prize: Diana Ulic, PGY3 Second Prize: Haroon Yousuf PGY2, Derek Chu PGY1 ABSTRACT 2-C (First author is Derek Chu, who was unable to present on that day) An Incompatible Element: A Case of Cesium ABSTRACT 8-C Toxicity Leading to Torsades de Pointes in a Drowning in Eosinophils Patient With Renal Cell Carcinoma Background: Chronic cough is a common presenting symptom Background: Alternative medicines are commonly used by and often due to asthma, GERD, or upper airway cough cancer patients, despite their unregulated production. Cesium syndrome (previously known as post-nasal drip). However, chloride (CsCl), an alkali metal and potassium-channel blocker, chronic cough with marked eosinophilia necessitates a wide- is advertised as a natural remedy for multiple malignancies. ranging differential diagnosis and can present a diagnostic CsCl usage persists among cancer patients despite association challenge. with ventricular arrhythmias in case reports. Toxicity may go unrecognized given the lack of familiarity with this compound. Case: After 9 months of outpatient workup for chronic cough of unknown etiology, a previously healthy 38-year-old Case Presentation: An 84-year-old female with renal cell non-smoking woman presented to the emergency room carcinoma and no cardiac history. She had self-prescribed with fever, dyspnea, and cough. Her total leukocyte count 9 9 CsCl 3grams daily for 2 months, having refused surgery and was 44.2x10 cells/L (eosinophils 80% or 35.4x10 cells/L, chemotherapy. Her ECG revealed sinus bradycardia, a QT neutrophils 14%) and her chest x-ray contained bilateral interval of 560 and no ischemic features. Her magnesium was ill-defined peripheral opacities with upper and middle zone 3 0.75, potassium 3.9, and calcium 2.61. Telemetry revealed predominance. CRP was 14.3 mg/L, ESR 20 mm/h, IgE 4588x10 polymorphic ventricular tachycardia suggestive of torsades U/L. Bronchoalveolar lavage contained >70% eosinophils. The de pointes, associated with reduced level of consciousness. patient was investigated for myeloproliferative, infectious, Her rhythm normalized with magnesium but QT remained autoimmune, allergic, and metabolic causes of eosinophilia. prolonged and torsades recurred. She was commenced on During this time, she developed non-palpable retrosternal isoproterenol, with no further torsades. Cesium toxicity was chest pain radiating to her left arm, increasing oxygen concluded to have caused torsades, given a toxic plasma requirements and elevated troponin I of 220 ng/L. Initiation cesium level of 650528 nmol/L. The half-life of CsCl is of prednisone therapy rapidly reduced peripheral eosinophil 3 weeks, prompting a 6-week course of Prussian Blue to facilitate counts to an undetectable level, without evidence of tumor lysis elimination, with subsequent QT interval normalization and syndrome. Cardiac MRI showed no evidence of myocarditis. hospital discharge. The opacities on CXR resolved over the subsequent weeks. To date, the patient continues on prednisone therapy, struggling Conclusions: The unregulated industry of alternative medicines with episodes of relapse and remission. is a public health issue, particularly in vulnerable cancer patients. This case highlights the need for clinicians to remain vigilant Conclusions: Here, we review an uncommon, but remarkable about alternative medicine usage by extending their knowledge cause of cough. We discuss the clinical manifestations, base beyond traditional toxidromes to include potentially differential diagnosis, investigations and important high-risk presentations associated with these unconventional considerations during in-patient management of chronic therapies. Clinicians must also be mindful of concentration eosinophilic pneumonia. Lastly, we present an approach to variability across the numerous formulations of alternative eosinophilia and discuss current and emerging therapies for medicines available commercially. This case was particularly eosinophilic diseases. severe given the procurement of higher-concentration CsCl from a chemical facility, rather than a commercial vendor. Supervisor: Dr. Rebecca Kruisselbrink

Supervisor: Dr. Sonny Kohli

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Lonnie Pyne PGY2 Kimia Honarmand PGY2, Hussain Alzayer PGY3, ABSTRACT 1-C Zeeshan Ahmed PGY2, Jane Turner PGY2 A Fruit a Day Keeps the Transfusion Away ABSTRACT 3-C Primary Nocardia Brain Abscess in an Background: Scurvy may have a variety of clinical Immunocompetent Patient presentations. These occur primarily as a manifestation of impaired collagen synthesis. One such presentation is anemia. Background: Nocardia species are gram-positive bacilli, which are rare causes of respiratory tract infection. Infection of the Case Presentation: A 43-year-old male was referred from the central nervous system by nocardia is far more uncommon ER for anemia and weakness. The patient had a past medical and has been described predominantly in case reports of history of schizophrenia. His diet was limited to pasta, sardines immunocompromised hosts in the context of spread of the and eggs. He had not owned a refrigerator for 20 years and could disease from the respiratory tract. We present a case of a not recall the last time he had fresh food. The patient noted Nocardia farcinica brain abscess in an immunocompetent 1 month of progressive weakness, peripheral edema and lower patient without preceding respiratory infection, with emphasis limb bruising. Physical exam was notable for pallor with mild on the diagnostic and therapeutic challenges of this rare but scleral icterus. Lower limbs had pitting edema and dependent aggressive disease. ecchymoses to the shins. Thighs had signs of perifollicular hemorrhages and corkscrew hairs. Gingival bleeding was present. Case Presentation: An 81-year-old man presented to hospital Investigations showed a hemoglobin of 60 g/L and total bilirubin with left-sided weakness. CT head showed a right frontal lobe of 47 micromol/L (conjugated 17.6). All other investigations space-occupying mass suspicious for malignancy. Image- were within normal limits. A presumptive diagnosis of scurvy guided needle biopsy subsequently determined this mass to was made. The patient was started on oral ascorbic acid. The be a Nocardia farcinica abscess. There was no evidence of a initial ascorbic acid level was below the limit of detection respiratory infection at the time. Treatment was initiated (<5 μmol/L). The patient was transfused to a hemoglobin in the with Septra, which was later discontinued due to profound mid 70’s which steadily rose to 94 prior to discharge. thrombocytopenia. The patient was then started on amikacin and imipenem. Based on a previous case report, moxifloxacin Conclusion: At a follow-up visit 3 weeks after the initial was later added as adjunctive therapy. He subsequently presentation the patient’s hemoglobin was 141 g/L. The developed radiographic features to suggest a new respiratory dependent ecchymoses and perifollicular hemorrhages had infection, highly suspicious for dissemination of nocardia. resolved. Despite aggressive therapy, his hemodynamic status continued There are a number of proposed mechanisms for anemia in to deteriorate and he passed away 55 days following hospital scurvy including impaired iron incorporation into porphyrin admission. and hemorrhage into tissues and blood loss via the GI tract as a result of impaired collagen synthesis. This case highlights the Conclusions: This case illustrates an uncommon presentation importance of a detailed physical exam and dietary history in of primary nocardia brain abscess in an immunocompetent detecting rare conditions. host in the absence of evidence of preceding respiratory infection. Diagnosis can be delayed, as clinical presentation and Supervisor: Dr. John Neary initial diagnostic testing are often suggestive of malignancy. Timely biopsy to rule out alternative etiologies is of utmost importance, particularly given the aggressive nature of the disease and the potential for cure.

Supervisor: Dr. Christian Kraeker

70 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Shazmeen Manji PGY2, Janet Simons PGY3, Raman Rai, Suneet Sekhon, Stephen Giilck PGY3 Sankalp Bhavsar: Rheumatology PGY5 ABSTRACT 4-C ABSTRACT 5-C A Recipe for Disaster: Hyponatremia-induced Inflammatory Pseudotumour of the Skull Base: Seizure Following Excess Flaxseed Ingestion A Case Report and Review of the Literature

Background: Hyponatremia is a common electrolyte Background: Inflammatory pseudotumours (IPTs) are non- disturbance which has multiple etiologies, including malignancy, malignant collections of mixed inflammatory and fibroblastic drugs, and volume contraction. Seizures are a rare complication cells caused an unknown etiology. IPTs have been most of hyponatremia which are caused by a rapid decrease in serum commonly described in the gastrointestinal and respiratory sodium leading to cerebral edema. Identifying the cause of severe tract, but can occur anywhere in the body. The diagnosis of hyponatremia is paramount to rapidly correcting the electrolyte IPT is one of exclusion and rheumatologists are often asked to disturbance and preventing devastating complications. assess for entities such as GPA or IgG-4 related disease.

Case Presentation: A previously healthy 24-year-old woman Case Presentation: A 27-year-old female presented with presented with a sudden onset of vomiting and profuse diarrhea. several month of right sided temporal headache and new She had consumed a pancake made with 3 cups of raw flaxseeds dysarthria, dysphagia and rightward tongue deviation. She approximately 1-2 hours before the onset of her symptoms, was found to have a mass at the base of the skull with cranial and had no other identifiable provoking cause. While being nerve 9-12 involvement. She did not have any other features assessed, the patient had a 7-minute tonic clonic seizure, which of small vessel vasculitis and negative ANCA studies. The mass ended spontaneously. Laboratory investigations revealed severe was biopsied and found to be consistent with IPT, without hyponatremia with a sodium of 119 mmol/L, and a non-anion any features of vasculitis, malignancy, sarcoid, infection or gap metabolic acidosis consistent with a recent seizure (lactate IgG-4 related disease. She was treated with high dose steroids 12.9 mmol/L, pH 6.82). Serum sodium corrected rapidly with with initial improvement for several weeks but then relapsed. minimal intervention, and two hours later was 123 mmol/L. Cyclophosphamide and later Rituximab were added to her The patient was diagnosed with hyponatremia-induced treatment with improvement of her neurologic symptoms. seizure secondary to excess ingestion of flaxseed. Two A literature review found 7 articles detailing 10 patients mechanisms have been hypothesized. Animal studies have with skull base IPTs. All patients had biopsies performed shown flaxseed overdose can cause neurologic abnormalities for definitive diagnosis. Treatment of IPT varied; some including seizure, possibly due to an excess of linoleic acid were managed with surgery alone, others had variable doses causing an imbalance when there is a pre-existing linoleic acid of glucocorticoids, and 4 patients received concomitant deficiency. The second mechanism is profuse diarrhea causing cyclophosphamide therapy. The outcomes were generally water and solute loss due to flaxseed’s laxative properties. favourable with resolution of symptoms and improvement of neurologic deficits in most. Clinical Pearls - Taking a detailed history is important in identifying the cause of hyponatremia, particularly when it is Conclusions: IPTs have diverse presentations that may mimic rapid and severe. This case also demonstrates the importance of other rheumatologic conditions. Rheumatologists are often being aware of trends in patient diets and using this to educate asked to rule out other diseases as well as aid in management our patients. with immunosuppressive medication.

Supervisor: Dr. Akbar Panju Supervisor: Dr. Nader Khalidi

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Sunita Narang PGY2, Vanessa Ocampo PGY2 Rinu Pazhekattu PGY1, Katrina Piggott PGY2 ABSTRACT 6-C ABSTRACT 7-C A Case of Cutaneous Lupus Diabetes Insipidus: Not So Insipid

Background: The incidence of Cutaneous Lupus Erythematosus Mrs. I.S. is a 55-year-old female with a uterine mass who (CLE) is comparable to the incidence of Systemic Lupus was assessed in the preoperative general medicine clinic. Erythematosus (SLE). CLE may occur in association with SLE, Complaints of excessive thirst, blurred vision, diplopia and may portend SLE, or may occur independently as a skin-limited peripheral neuropathy were elicited. Sequential laboratory disease. The variations in clinical presentation pose a diagnostic work revealed hypernatremia and MRI of her brain showed a challenge for physicians. Regardless of the particular context, nodule anterior to the pituitary stalk, partially empty sella, and CLE is often associated with significant morbidity for patients. leptomeningeal enchancement. It is important to recognize CLE, so that it can be managed appropriately. Her Ghanaian ethnicity and the MRI pattern raised serious concern for Tuberculin exposure. Failure to establish an Case Presentation: A previously healthy 27-year-old female alternate diagnosis led to initial treatment with quadruple- presented to her family physician’s office with a 3-day history drug therapy as a case of extra-pulmonary tuberculosis of what appeared to be infectious changes involving the nose, (TB) with CNS involvement. After minimal clinical nasolabial folds and philtrum, shortly after popping a vesicle-like improvement, extensive investigations were performed, lesion at the base of her nose. Despite treatment with multiple including a paraneoplastic screen in light of her pelvic mass, courses of oral and intravenous antibiotics, in concert with and evaluation for sarcoidosis. Pathology of the uterine mass Infectious Disease specialists’ opinion, the lesion evolved into an was consistent with leiomyoma, eliminating malignancy as area of induration and chronic inflammation, and she was sent a possible etiology. Multiple lumbar punctures were more to an immunodermatology clinic for evaluation. Suspicion for consistent with an inflammatory process and ruled out a autoimmune etiology prompted sending off of immune markers viral or bacterial infection. Her autoimmune history of both which revealed positive ANA Screen (+), and anti-Ro (+). Punch rheumatoid arthritis and Sjogren’s disease combined with the biopsy was also performed. She was started on empiric treatment LP results prompted a diagnosis of presumed CNS vasculitis with topical corticosteroid with minimal effect, eventually and posterior pituitary hypophysitis. She was initiated on only responding to oral Prednisone and Plaquenil. Two weeks treatment with high-dose corticosteroids. Withdrawal of TB later, the biopsy results demonstrated Cutaneous Lupus. She therapy and improvement of her neurological deficits were had no other signs or symptoms suggestive of systemic lupus supportive of the vasculitis diagnosis. Sodium levels stabilized erythematosus. on oral DDAVP, and a repeat MRI scan showed complete resolution of the previous leptomeningeal enhancement. Conclusions: This case highlights the important of keeping a broad differential diagnosis when approaching a patient with This fascinating case emphasizes the need to keep a wide facial erythema, particularly a young woman in this age group. differential, and consider rare etiologies of central DI, Cutaneous lupus needs to be considered in the differential particularly in the context of a patient with multiple risk diagnosis in order to be able to make the diagnosis, and to factors and a non-diagnostic lumbar puncture. Furthermore, initiate the appropriate therapy. it highlights the need to recognize the broad, multisystem manifestations of autoimmune diseases and their widely Supervisor: Dr. Shariq Haider variable presentations.

Supervisor: Dr. Ameen Patel

72 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Derek Chu PGY1, David Harris, Infectious Diseases PGY4 Conor Cox PGY1 ABSTRACT 9-C ABSTRACT 10-C Pedicure Endocarditis Acute Onset Hemiballismus

Background: Infective endocarditis (IE) is often a life- Aims: Movement disorders are uncommon and difficult to threatening disease that presents in patients with a history of diagnose with broad differentials. Hemiballismus is a rare old age, intravenous drug use, immunocompromise, indwelling clinical finding associated with basal ganglia lesions, frequently catheters, and/or artificial/abnormal heart valves. Emerging in the subthalamic nucleus. The most common cause is lacunar evidence has led to changes in guidelines for short- and long- infarction (10-15% of strokes), resulting in several stroke term antibiotic and surgical management of IE. syndromes.

Case presentation: A previously healthy 29-year-old female Methods: A comprehensive chart review was undertaken, non-IV drug user presented to the ER after 72 hours of focusing on clinical examination and radiographic results with fever, headache, nausea/vomiting, meningismus, and severe a subsequent literature review. myalgias. She had returned from Africa 1 month earlier. She also had a pedicure one week prior, and was cut in the process. Results: A 73-year-old female presented with a 1 week history On presentation, she was febrile, tachycardic, hypotensive, of acute onset right-sided involuntary movements. She denied leukopenic at 3.2x109/L, with marked left shift (30% bands/ any other neurological, constitutional or infective symptoms. metamyelocytes) and toxic granulation/Döhle bodies. Thick/ Medical history included chronic kidney disease, hypertension, thin smears were negative for malaria. Empiric dexamethasone, T2DM, CHF and dyslipidemia. A meningioma resection ceftriaxone, vancomyocin and acyclovir was started for in 2001 resulted in right-sided weakness and foot drop. On meningitis. Lumbar puncture CSF was neutrophilic (53x106/L neurological examination she was alert and oriented with nucleated, 79% neutrophils) with normal glucose and protein. involuntary, large-amplitude, stereotypical and repetitive The next day, Janeway lesions, Osler’s nodes, and Roth spots movements, more pronounced in her right upper than lower were identified. Blood cultures grew MSSA by 8 hours and limb, sparing her face. These were present at rest and more antibiotics were switched to cloxacillin and gentamycin. Despite prominent with action. She was unable to suppress these except this, repeat blood cultures grew MSSA at a faster rate, and repeat with sleep. Her examination was negative for upper motor TTE revealed MR with enlarging mitral vegetation. No murmur neuron, cortical or sensory deficits. CT scan was inconclusive. was ever appreciated on auscultation. On day 6 of admission, MRI showed lacunar infarction of the posterior limb of the left she was transferred to cardiac surgery. A mitral annulus abscess internal capsule, chronic microangiopathic changes and stable was excised and replaced with a mechanical valve. Time to blood right-sided meningiomas. Biochemical workup and carotid sterility post-operatively was 3 days with daptomycin, rifampin, ultrasound were normal. and continuous-infusion cloxacillin. The patient has since rehabilitated successfully. Conclusions: The differential included stroke, neoplasm, metabolic, and medications/toxins. Clinical examination Conclusions: Here, we present a remarkable etiology localized the lesion as subcortical and in the subthalamic and presentation of IE. We discuss potential public health nucleus. CT head is a mandatory investigation for patients with implications of this case, as well as recent guideline changes to stroke symptoms, however the sensitivity for lacunar infarcts is medical and surgical management of IE. between 30-44%. MRI is more sensitive and better delineates anatomic lesions. This case is unique as lacunar infarction Supervisor: Dr. Irene Cybulsky presenting as purely hemiballismus is very rare. Our patient was treated with Quetiapine and rehabilitation with notable symptom improvement.

Supervisor: Dr. Amitabha Chakroborty

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Diana Ulic PGY3 Nazanin Montazeri PGY2, Hala Kufaishi PGY1 ABSTRACT 11-C ABSTRACT 12-C An Old Foe Re-emerges: A Case of Fatal Oropharyngeal Dysphagia Requiring Percutaneous Postpartum Group A Streptococcal Toxic Shock Enteral Feeding Secondary to Dermatomyositis in Syndrome a Hepatitis B Carrier: A Case Report

Background: Group A streptococcus (GAS) has been historically Background: Dermatomyositis (DM) is an autoimmune recognized as a common cause of maternal mortality. Thought inflammatory myopathy characterized by complement- to be now rare in developed countries, postpartum GAS mediated microangiopathy affecting the skin and muscles. infections are nonetheless increasing in prevalence, and result While dysphagia is common, there is limited data on the in significant mortality in otherwise-healthy women. Given incidence of severe oropharyngeal dysphagia requiring the erroneous assumption that GAS is a rare cause of maternal percutaneous enteral feeding. Studies have reported an shock in modern medicine, appropriate antibiotic treatment incidence of 12-18% when inflammatory myopathies (DM, and source control with hysterectomy may be delayed with polymyositis and inclusion body myositis) are combined. Here devastating results. we present an atypical case of DM with severe oropharyngeal dysphagia in a Hepatitis B carrier requiring percutaneous Case Presentation: A 37-year-old healthy female underwent an gastrostomy (PEG) tube feeding. uncomplicated vaginal delivery without instrumentation. She developed abdominal pain, SIRS criteria, thrombocytopenia, Case Presentation: A 42-year-old female of Chinese descent and diffuse mottling, prompting ICU admission for presumed presented with severe oropharyngeal dysphagia. Two months sepsis. It was revealed that her husband had recently suffered prior to presentation, she had noticed an erythematous rash from streptococcal pharyngitis. Despite fluids and Tazocin, she spreading to her face, back, abdomen, arms and thighs. She rapidly deteriorated over 12 hours, developing multiple organ reported significant myalgia. Three days prior to admission, dysfunction syndrome (MODS), widespread desquamation, she experienced throat discomfort and required multiple and disseminated intravascular coagulation. She fulfilled attempts to swallow. On the day of presentation, she was all criteria for TSS. Four out of 4 blood cultures revealed unable to swallow her saliva. gram-positive-cocci in chains, later speciated to GAS. She had extensive skin findings suggestive of Clindamycin, penicillin G, and IVIG were started. She underwent dermatomyositis. However, CK was only mildly elevated and emergent hysterectomy 3 days into her sepsis syndrome but the initial EMG study was negative. Due to the strong pretest unfortunately died on day 6 from overwhelming MODS. probability of dermatomyositis, MRI using myositis protocol was done showing widespread muscle inflammation. The Conclusions: Postpartum GAS infections are increasing in diagnosis was confirmed by a muscle biopsy. prevalence and may have devastating outcomes. The clinician Inpatient malignancy workup was negative. Considering must strongly consider GAS in the presence of rapidly progressing the patient’s hepatitis B carrier status, treatment with IVIG sepsis and recent strep exposure in postpartum patients. In this and glucocorticoids was initiated. A PEG tube was inserted case, timelier acknowledgment of strep exposure combined with for enteric nutrition due to prolonged dysphagia refractory to initial gram stain morphology interpretation even in the absence initial treatment. of speciation could have led to earlier consideration of GAS and prompter commencement of clindamycin and IVIG as adjuncts. Conclusions: The exact prevalence of oropharyngeal dysphagia Earlier consideration of hysterectomy – emergently indicated if requiring percutaneous enteral feeding in patients with DM is not anticipated mortality is greater than 60% - may have resulted in known. We present a unique case with extensive dermatologic timelier source control and better outcomes. findings, normal initial EMG, mildly elevated CK and severe dysphagia (requiring PEG tube). Furthermore, the patient was a Supervisor: Dr. Sonny Kohli Hepatitis B carrier which limited the treatment options.

Supervisors: Drs. Rajendar Hanmiah & Nader Khalidi

74 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Jane Turner PGY2 Christine Orr, Endocrinology PGY5 ABSTRACT 13-C ABSTRACT 14-C Pulmonary Langerhans Cell Histiocytosis - Thyrotoxicosis in a Critically Ill Patient The Smoking Zebra Treated with Lithium

Langerhans cell histiocytosis (LCH) is a disorder usually seen Case: A 70-year-old female was admitted to ICU following in children, characterized by clonal histiocyte proliferation a lobectomy for NSCLC. History was positive for diabetes in various tissues. Isolated pulmonary LCH (PLCH) is and multi-nodular goiter. Post-op day one, she suffered an an uncommon variant that presents in adults as a diffuse NSTEMI; day 2 she suffered respiratory distress requiring infiltrating lung disease. This disease typically occurs between BiPAP and rapid atrial fibrillation (AF) and was treated 20 and 40 years of age and is extremely rare, with a prevalence of with amiodarone. Antibiotics were initiated for possible 0.07 per 100 000. Although its etiology is unknown, an almost sepsis. She was intubated on day 3 for respiratory failure; exclusive association with cigarette smoking strongly implies a and remained tachycardic despite antiarrhythmics. causative role. Onset is usually insidious; nonspecific symptoms Labs were significant for AST 734 U/L (<35 U/L), of dry cough and dyspnea can make diagnosis challenging. This ALT 359 U/L (< 35 U/L), TSH < 0.01 mU/L and case focuses on PLCH as an orphan disease, emphasizing its FT4 23.3pmol/L (9-19 pmol/L). The diagnostic score for diagnostic features. thyroid storm using the Burch Wartofsky system was 65, with values > 45 suggestive of the diagnosis. Thionamide was not A 49-year-old woman with a 35 pack-year smoking history prescribed due to liver injury. Hydrocortisone was initiated presented with dyspnea and unintentional weight loss of 35 lb. and metoprolol changed to propranolol. Despite this, she Chest X-rays revealed interstitial fibrotic changes in the upper remained tachycardic; lithium was started. The AF terminated zones, prompting high resolution computed tomography, within 48 hours; FT4 fell to 12.2 pmol/L. Despite stabilization which identified diffuse pulmonary thin-walled cysts within the of her thyrotoxicosis, she died of pulmonary complications. upper lobes, sparing of the lower lobes, and small centrilobular nodules throughout – a combination characteristic of PLCH. Discussion: Recognition of thyrotoxicosis during concurrent Bronchoalveolar lavage showed a marked predominance of critical illness is challenging. Here, iodine exposure marcophages (78%). A high macrophage count, while not (amiodarone) aggravated the hyperthyroidism. Management diagnostic, is typical. When found in a young smoker, the included inhibition of synthesis of thyroid hormone, aforementioned features are sufficient to diagnose PLCH. The prevention of peripheral T4-T3 conversion, release of stored patient was managed conservatively, with smoking cessation as hormone, and control of symptoms. Hydrocortisone was used the critical first step. Annual lung function tests and imaging are to achieve vasomotor stability, to treat possible relative adrenal indicated to assess disease progression, as the course of PLCH insufficiency and to decrease peripheral T4-T3 conversion. is variable. Propranolol was used to decrease adrenergic symptoms, control AF and decrease peripheral T4-T3 conversion. PLCH is a rare interstitial lung disease with characteristic clinical Thionamides are associated with hepatotoxicity and must and radiographic features. Recognition of these features can be avoided in liver injury. Lithium is an alternative therapy; mitigate the need for lung biopsy. Clinicians should consider effects include inhibition of thyroid hormone synthesis and this disease when assessing young patients with nonspecific release. This patient had an excellent response to lithium. respiratory symptoms in a context of heavy smoking. Conclusion: When liver injury prevents the use of thioamides Supervisor: Dr. Andrew McIvor use of lithium as an alternate agent is effective.

Supervisor: Dr. Manoela Braga

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Resheed Alkhiari PGY3 Kalpa Shah PGY3, Omair Sarfaraz PGY2, ABSTRACT 15-C Nicole Sitzer PGY3 Late Presentation of Bicuspid Aortic Valve ABSTRACT 16-C Stenosis with Aortopathy Persistent Hypokalemia in a Patient with Lupus Treated with Cyclophosphamide Background: Bicuspid aortic valve (BAV) is one of the most common congenital cardiac defect in adult, affects around 1% of Background: Hypokalemia reflects total body potassium the population. Although most cases are familial as autosomal depletion secondary to renal or gastrointestinal losses, dominant and has been linked to different chromosomal or redistribution of potassium from the extracellular to mutations, some are sporadic. It is usually asymptomatic intracellular fluid compartment. Renal potassium wasting in early in life and detected on routine physical exam. It can adults has a broad differential diagnosis including diuretic use, also presented as aortic stenosis, aortic incompetence, or with hyperaldosteronism and congenital or acquired renal tubular infective endocarditis or aortopathy; mainly ascending aortic disorders. Early diagnosis and treatment are crucial as severe aneurysm. The pathophysiology behind aortopathy is related hypokalemia can result in paralysis, arrhythmias and death. to cystic medial degeneration in addition to disturbance of hemodynamics due to abnormal structure of the valve. Case Presentation: We describe a case of life-threatening hypokalemia secondary to renal tubular dysfunction in a Case Presentation: An 85-year-old woman presented with 41-year-old woman with systemic lupus erythematous (SLE) history of exertional shortness of breath with chest discomfort for that developed after treatment with cyclophosphamide to one month associated with hoarseness of voice. Her past medical control refractory disease. 24-hour urine collections confirmed history was significant for hypertension and atrial fibrillation, renal potassium wasting. Her hypokalemia persisted for which she was treated with rivaroxaban, metoprolol and despite treatment with potassium replacement, potassium- candesartan. She presented initially to a peripheral hospital sparing diuretics and NSAIDs. A trial of pulse steroids was where she had a chest computed tomography with angiogram to associated with transient normokalemia. Trials of intravenous rule out pulmonary embolism which surprisingly showed a large immunoglobulin (IVIG) and plasma exchange (PLEX) did not ascending aortic aneurysm measuring 6.8 cm, and transferred improve the hypokalemia. During her 8th month of hospital to our hospital for urgent cardiac surgery consultation. On admission her hypokalemia improved and she was able to examination, she was hemodynamically stable with soft first maintain normokalemia on enteral potassium replacement. heart sound and systolic ejection murmur at the left sternal There are case reports of persistent of hypokalemia associated border as well as at base. All blood work was within the normal with ifofosfamide exposure and we propose that the patient’s limit, selective percutaneous coronary angiography showed severe hypokalemia is related to cyclophosphamide exposure. mild coronary disease. Echocardiogram showed moderate BAV stenosis with dilated aortic valve root. Accordingly, Conclusions: We present a case of hypokalemia in a she successfully underwent aortic valve replacement with patient with SLE that developed following exposure to replacement of the ascending aorta and hemiarch. cyclophosphamide. To date, there are no reports in the literature of cyclophosphamide-associated hypokalemia. It is Conclusion: This case describes a late presentation of BAV important to report this case to increase awareness about this stenosis with ascending aortic aneurysm which has presented potentially life-threatening complication. initially with recurrent laryngeal nerve compression (hoarseness of voice). Supervisor: Dr. Scott Brimble

Supervisor: Dr. Tej Sheth

76 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Tooba Ali PGY1, Gennie Wang PGY1 Kimia Honarmand PGY2 ABSTRACT 17-C ABSTRACT 18-C Intermittent Hemoglobinuria: A Lesson in Pyoderma Gangrenosum as the Presenting Sign Mechanical Mitral Valve Dysfunction of Myelodysplastic Syndrome

Background: Subclinical hemolysis is common among patients Background: Pyoderma gangrenosum is a form of with mechanical prosthetic valves; however, decompensated neutrophilic dermatosis that is often associated with anemia due to such intravascular hemolysis is rare with some underlying systemic disease, particularly inflammatory bowel studies reporting a 0% incidence. We present a case of severe disease and hematologic malignancies. Previous case reports hemolytic anemia resulting from a paravalvular leak around a have described the development of pyoderma gangrenosum mechanical mitral valve. in patients with known myelodysplastic syndrome. We report a case where the development of pyoderma gangrenosum Case: A 77-year-old female presented to the emergency preceded the diagnosis of myelodysplastic syndrome. department with 1 week of fatigue, exertional dyspnea, and 2 days of intermittent, “bloody” urine. She was initially referred Case Presentation: A 54-year-old woman with a 4 year to urology for hematuria. history of pyoderma gangrenosum formally diagnosed 2 years Her past medical history was significant for rheumatic ago was referred for new onset of anemia in the absence of heart disease, which required multiple mitral valve surgeries other cytopenias. This was initially attributed to anemia of and replacements. Her last mechanical mitral valve inserted chronic disease and previous cyclophosphamide therapy. in 1986 required a minimally invasive redo in 2011 due to a Discontinuation of cyclophosphamide did not resolve paravalvular leak. The patient was on warfarin therapy due her anemia. Bone marrow biopsy, 4 years following her to her mechanical valve. The patient was hemodynamically presentation with pyoderma gangrenosum, was diagnostic of stable, with a hemoglobin of 69 g/L. She was mildly jaundiced. myelodysplastic syndrome. Her INR was 3.1 and urine microscopy revealed 3+ blood but only 3-5 erythrocytes per high-power field. Other significant Conclusions: This is the first reported case of recurrent laboratory values included total bilirubin 54 umol/L, direct pyoderma gangrenosum long preceding the clinical bilirubin 8.9 umol/L, and LDH 1985 U/L. Haptoglobin was presentation of classical cytopenias that often prompt absent and the peripheral smear revealed mild fragments. investigation for myelodysplastic syndrome. The case Coombs test was negative. highlights the variable temporal association between the two A trans-esophageal echocardiogram revealed significant conditions and suggests that pyoderma gangrenosum may be new paravalvular jets of mitral regurgitation. This was felt the primary presenting sign of myelodysplastic syndrome. This to be the cause of her hemolysis and ensuing anemia. Given case cautions against dismissing the possibility of hematologic her previous paravalvular leak with identical presentation, malignancy and underscores the need for increased surveillance the patient was subsequently referred to cardiac surgery for of patients with pyoderma gangrenosum even in the absence of consideration of another mitral valve repair. peripheral cytopenias.

Conclusion: Hemoglobinuria can be deceiving and Supervisor: Dr. Irwin Walker misdiagnosed as hematuria without examining microscopy results. In the context of a mechanical valve, evidence of hemolysis in the setting of hemoglobinuria should prompt investigations to rule out valvular dysfunction.

Supervisor: Dr. Jason Cheung

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Gennie Wang PGY1, Kimia Honarmand PGY2 Diana Ulic PGY3 ABSTRACT 19-C ABSTRACT 20-C A Rare Case of Multi-Dermatomal Varicella Zoster A Case of Superior Mesenteric Artery Encephalitis in an Immunocompetent Patient Aneurysm Rupture and Hemorrhagic Shock in Rubenstein-Taybi Syndrome Background: Varicella zoster virus (VZV) rarely causes viral encephalitis. The majority of cases of VZV encephalitis are Background: Rubenstein-Taybi Syndrome (RTS) is an reported in immunosuppressed patients, particularly those extremely rare autosomal dominant condition, caused by with advanced HIV, hematologic malignancies undergoing a chromosome 16 deletion and characterized by growth chemotherapy and those receiving immunosuppressive restriction and intellectual disability. Much about RTS remains medications. In addition, VZV lesions usually appear in unknown in terms of genotype-phenotype correlations. one dermatomal distribution, and multi-dermatomal Greater than 90% of these patients live into adulthood, making presentations or disseminated VZV infection have only been this a relevant disease for internists but challenging to treat reported in immunosuppressed patients. We report a case of comprehensively given its low prevalence and still-uncertain an immunocompetent patient with VZV encephalitis with associations. multi-dermatomal involvement. Case Presentation: A 28-year-old female with RTS presented Case Presentation: An 88-year-old man was brought to with a 3-day history of vomiting and an unwitnessed fall with the emergency department with bilateral leg weakness, new subsequent intermittent periods of unresponsiveness. On headache and delirium on a background of mild dementia. He presentation, she was in shock requiring levophed. Urosepsis was noted to have a new vesicular rash in the L5 dermatome. was the presumed etiology, based on a leukocytosis of 25.1 Head CT was unremarkable. He was admitted to hospital and and a positive urine dip. Chest x-ray, ECG, and CT Head were treated empirically for meningitis and viral encephalitis with all unremarkable, as was her initial examination. The patient ceftriaxone, vancomycin, ampicillin, and acyclovir. Over the subsequently developed significant abdominal distention, course of his hospital stay, he was noted to develop new smaller with a profound drop in her hemoglobin from 102 to 18 and lesions in the V2, C4, and S2 distributions. Lumbar puncture a lactate of 17. Massive transfusion protocol was initiated. An was positive for VZV DNA. The patient tested negative for HIV, urgent CT Chest/Abdomen was performed, revealing active hepatitis B and C, ANA, rheumatoid factor and p-ANCA. There bleeding from an SMA aneurysm. Coiling was attempted but is no known history or evidence of malignancy. The patient was the patient had multiple episodes of PEA arrest before and continued on intravenous acyclovir for a 3 week course and he during the procedure, and unfortunately died after multiple has shown gradual clinical improvement. and prolonged resuscitative efforts.

Conclusions: This is a case of multi-dermatomal VZV Conclusions: Although there are case reports of cerebral and encephalitis in an immunocompetent patient. While VZV cervical artery aneurysm dissections in RTS, as well as one encephalitis has been reported in immunocompromised hosts, report of a ruptured intracranial aneurysm, there is no previous this case highlights the importance of considering this diagnosis report in the literature detailing an association between RTS even amongst those with no evidence of immunocompromise and visceral arterial aneurysm formation. The potential and highlights the importance of timely and appropriate empiric association of this syndrome with aneurysm formation and management. rupture has important implications in the acute management of patients with RTS who present with undifferentiated shock, Supervisor: Dr. Punginathn Dorasamy compelling the clinician to suspect hemorrhage at the top of the differential.

Supervisor: Dr. Sonny Kohli

78 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Anne Hu PGY1, Rebecca Mathew PGY3, Mary Salib PGY3 Siraj Mithoowani PGY2, Bahareh Ghadaki ID Fellow Direct-acting Oral Anticoagulants in the Real ABSTRACT 21-C World: Insights Into Health Care Providers’ Significant Elevations in Liver Enzymes: Understanding of Medication Dosing and Use An Approach for Human Immunodeficiency Virus (HIV) Patients Background: Direct-acting oral anticoagulant (DOAC) use is increasing in Canada. All DOACs require dose adjustment for Background: The evaluation of persistent liver enzyme renal function, and in some cases, for age as well. Manufacturers elevations in patients with Human Immunodeficiency Virus also provide instructions on DOAC administration. Dabigatran (HIV) presents a unique diagnostic challenge. It is important should not be exposed to moisture or crushed. Higher doses to differentiate primary hepatic from secondary infectious or of rivaroxaban should be taken with meals. Ideally, health care drug-related causes. We present the case of a 53-year-old HIV- providers (HCPs) should counsel patients about appropriate positive patient with Disseminated Mycobacterium Avium DOAC use, but their understanding of these issues is unknown. Complex (DMAC) infection and marked elevation in alkaline Our objective was to assess HCP understanding of DOAC phosphatase (ALP). dosing and administration.

Case: A 53-year-old HIV-positive male with CD4+ lymphocyte Methods: An electronic survey was distributed to HCPs at our count of 70 cells/µL and undetectable viral load presented to tertiary care hospital, with questions on DOAC administration, hospital with persistent fevers, diaphoresis and generalized dose adjustment, patient counselling and comfort level with weakness. His medications included raltegravir, emtricitabine DOACs. and tenofovir. He was recently diagnosed with biopsy-proven DMAC and started on ethambutol and clarithromycin. During Results: A total of 59 responses were received –10 from nurses, his 4-week hospital stay, his blood was sterilized but liver 1 from a pharmacist, 23 from staff physicians, and 25 from enzymes rose in a cholestatic pattern with Gamma-glutamyl residents. Only 10% of respondents correctly specified the Transpeptidase (GGT) and ALP rising from110 U/L to 374 U/L approved indications for all three DOACs available in Canada. and 856 U/L to 1885 U/L, respectively. Preliminary investigations 32% felt comfortable or very comfortable prescribing DOACs. for drug-induced, viral and metabolic causes were negative. Liver When counselling, 95% discussed bleeding, 47% discussed ultrasound showed “starry sky” appearance classically in keeping adherence strategies, and 64% discussed when/how to take with hepatitis. A liver biopsy was performed and pathology the drug. 31% knew dabigatran should not be exposed to confirmed a diagnosis of MAC with liver involvement. moisture, 52% that it should not be crushed. A total of 29% knew higher dose rivaroxaban should be taken with food; 81%, Discussion: We present a case of DMAC in an HIV-positive 69% and 76% adjusted dabigatran, rivaroxaban and apixaban, patient on appropriate MAC therapy and sterilization of blood respectively, for renal function. However only 61% calculated cultures but persistent marked elevations in serum ALP. While renal function with an accepted formula. A total of 61% and isolated elevations in serum ALP can occur in up to 53% of 54% adjusted dabigatran and apixaban, respectively, for age. patients with DMAC, the differential diagnosis for an HIV patient includes HIV cholangiopathy, acalculous cholecystitis, Conclusion: HCP understanding of DOACs is variable. medication-induced hepatoxicity, opportunistic infections, Though they express comfort with DOACs, their self-reported vanishing bile duct syndrome and viral hepatitis. Ultimately a knowledge of dosing, administration and patient counselling liver biopsy remains the gold standard in diagnosing DMAC is incomplete. HCPs have a unique opportunity to improve associated liver disease. patients’ medication literacy; strategies are needed to improve their knowledge base. Supervisor: Dr. Parveen Wasi Supervisor: Dr. Menaka Pai

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 79 McMaster University 26th Annual Residents’ Research Day in Medicine

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Derek Chu PGY1 Suneet Sekhon PGY5, Raman Rai PGY5 Therapeutic Potential of Anti-IL-6 Therapies for Patient Perspectives on the Introduction of Granulocytic Airway Inflammation in Asthma Subsequent Entry Biologics in Canada

Background: Determining the cellular and molecular Background: Biologic medications have revolutionized phenotypes of inflammation in asthma can identify patient the treatment of inflammatory arthritis. Subsequent entry populations that may best benefit from targeted therapies. biologics (SEBs) are similar but not identical to the innovator Although elevated IL-6 and polymorphisms in IL-6 signalling biologics, and are poised to enter the Canadian market. We are associated with lung dysfunction in asthma, it remains conducted a survey of Canadian arthritis patients on innovator unknown if elevated IL-6 levels are associated with a specific biologics to understand their perspectives on SEBs. cellular inflammatory phenotype, and how IL-6 blockade might impact such inflammatory responses. Methods: A survey consisting of 15 questions was administered sequentially to 208 patients at a biologic infusion clinic. Methods: Patients undergoing exacerbations of asthma Patients were asked about their understanding of SEBs, and were phenotyped according to their airway inflammatory after providing a definition were asked about factors that characteristics (normal cell count, eosinophilic, neutrophilic, might influence them switching to one. Survey results were mixed granulocytic), sputum cytokine profiles, and lung analyzed using SAS version 9.3. function. Mice were exposed to the common allergen, house dust-mite (HDM), in the presence or absence of IL-6. Results: Of the patients surveyed, mean age was 56 years and The intensity and nature of lung inflammation, and levels of 67% were female. Most patients had rheumatoid arthritis (76%) pro-granulocytic cytokines and chemokines under these and had been on their current biologic for 1-5 years (55%). conditions were analyzed. When asked about the definition of a SEB, 58% indicated they did not know, 26% chose correctly, and 16% chose incorrectly. Results: Elevated IL-6 was associated with a lower FEV1 in When asked about interest in using a SEB, 30% were neutral, patients with mixed eosinophilic-neutrophilic bronchitis. 40% were interested, and 30% were opposed to it. Potential In mice, allergen exposure increased lung IL-6 and IL-6 lower cost of a SEB did not influence this decision, though if was produced by dendritic cells and alveolar macrophages. an insurance company mandated use due to lower cost most Loss-of-function of IL-6 signalling (knockout or antibody- opposed this (54%). The lack of testing in North American mediated neutralization) abrogated elevations of eosinophil patients led to 79% of patients being opposed to SEBs. Most and neutrophil recruiting cytokines/chemokines and were interested in continuing to use the innovator biologic allergen-induced airway inflammation in mice. if there was no additional cost (70%) and felt their doctor’s opinion would influence their decision (85%). Conclusions: We demonstrate the association of pleiotropic cellular airway inflammation with IL-6 using human and Conclusion: This survey identifies a lack of patient animal data. These data suggest that exacerbations of asthma, understanding of SEBs and highlights a need for further particularly those with a combined eosinophilic and neutrophilic education. Open dialogue is needed between patients, bronchitis, may respond to therapies targeting the IL-6 pathway physicians, industry and regulatory bodies to safely introduce and therefore, provide a rational basis for initiation of clinical SEBs into practice. trials to evaluate this. Supervisor: Dr. William Bensen Supervisor: Dr. Manel Jordana

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Kim Lewis PGY1, Christopher Sheasgreen PGY4 Janet Simons PGY3 Cement Ingestions: A Case Report Successful Reintroduction of Statin Therapy Following Statin-Associated Rhabdomyolysis Background: Caustic ingestions in adults often occur in the context of attempting suicide and the resultant injuries tend to Background: Statin associated rhabdomyolysis is a serious be more severe than accidental caustic ingestion by children. adverse event with a very low incidence and is considered the The extent of tissue injury depends on the concentration and pH most severe of the muscle related side effects of the statins. of the substance, premorbid state of tissue, contact duration, and The mechanism of statins causing rhabdomyolysis are unclear, amount of substance ingested. Esophagogastroduodenoscopy but may be a combination of pharmacokinetic factors, genetic (EGD) is the gold standard tool in assessing the extent of injury. factors, and direct statin effects such as depletion of intracellular cholesterol. Re-challenge with statins is not a recommended Case: A 49-year-old woman was admitted after a suicide practice following rhabdomyolysis, and guidelines provide no attempt. She had ingested handfuls of cement powder. The recommendations on the topic. This case report demonstrates physical exam revealed an apathic patient with cement powder the successful use of an alternative statin following a statin around her mouth. The initial investigations were normal related episode of rhabdomyolysis. apart from a leukocytosis and an elevated creatnine. A chest radiograph appeared unchanged from baseline. Case Presentation: The patient was started on atorvastatin The poison control center recommended performing 20 mg daily at the age of 43 for dyslipidemia in the context an EGD to rule out caustic damage. The EGD revealed of family history significant for early cardiovascular disease. erythematous mucosa with small abrasions in the stomach, The episode of rhabdomyolysis occurred three months after grade 1A esophagitis, and copious amounts of grey-brown the initiation of therapy. At the time, the atorvastatin was sludge-like material that was thought to be the cement his only medication. The statin was stopped, and the patient product. The patient was admitted to the psychiatry ward suffered a NSTEMI 1 year later. He then used alternative lipid for observation, started on a proton pump inhibitor, and had lowering therapy for 2 years. His LDL-cholesterol was not serial abdominal radiographs to watch for obstruction. meeting typical secondary prevention targets. An alternative A repeat EGD 4 days later showed short scabs in a linear statin was introduced and the patient has been followed for 4 configuration along the greater curvature of the stomach similar years without recurrence of the rhabdomyolysis. to what was seen on the previous EGD, and friable esophageal mucosa. There were no remnants of cement observed. After Conclusion: This case suggests it may be time to reconsider in-hospital management of psychotic depression, the patient the accepted practice of permanently avoiding statin therapy was discharged home. following rhabdomyolysis. Careful consideration of the risks and benefits of reinitiating therapy is important. There is a Conclusion: Caustic ingestion can result in potentially fatal need for further research into this area. outcomes. Cement, an alkaline substance, has the potential to result in serious injuries to the gastrointestinal tract but this Supervisor: Dr. Andrew Don-Wauchope clinical case proves the possibility of a benign outcome.

Supervisor: Dr. Waleed Al-Hazzani

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PUBLISHED ABSTRACT PUBLISHED ABSTRACT

Chenchen Hou PGY1 Alex Meadley PGY3, Mohan Cooray Gastroenterology Pilot Study of Online Learning Modules in Long-Term Colectomy Rates in Patients with Hemoglobinopathies for Canadian Hematology Ulcerative Colitis Treated with Infliximab: A Single Training Programs Canadian Tertiary Care Centre’s Experience

The number of patients in Canada with hemoglobinopathies, Background: Prior to introduction of biologic agents in 2005, such as sickle cell disease, and thalassemia continues to increase rates of colectomy for severe Ulcerative Colitis were estimated due to high rates of immigration from countries with high disease to be approximately 20%. It has not been clearly demonstrated prevalence and improved survival into adulthood with modern how Infliximab affects long-term colectomy rates and there has medical care. Hematologists completing training will require the been limited Canadian data. knowledge and expertise to manage these medically complex Our aim was to assess the rates of colectomy at our patients. This study builds on a needs assessment of Canadian institution in patients treated with Infliximab for severe hematology training programs completed by Dr. Verhovsek Ulcerative Colitis. and colleagues (https://ash.confex.com/ash/2014/webprogram/ Paper71742.html) which found a wide variability in exposure Methods: Charts of patients with Ulcerative Colitis on to hemoglobinopathy cases among training programs and Infliximab were retrospectively reviewed. Inclusion criteria a paucity of case-based learning tools to help address gaps in consisted of Infliximab initiation between January, 2005 and case mix. Across Canada, both training program directors and January, 2012. Charts were reviewed to January, 2014 for residents alike expressed strong interest in access to online study outcomes. learning modules for hemoglobinopathy learning. As such, Crohn’s colitis, indeterminate colitis or age less than we are designing 12 – 18 online modules to teach hematology 18 years by January, 2012 were exclusions. An additional residents core content that relates to hemoglobinopathies to 10 exclusions were due to a colectomy prior to the first dose of allow learners to apply clinical and laboratory-based knowledge infliximab or insufficient records. in an interactive web-based format. We will administer and A t-test was used to analyze eligible information. analyze the results of resident focus groups and questionnaires for resident satisfaction, self-reported knowledge gains, and Results: A total of 7 (10.6%) patients required a colectomy usability of the modules. In addition, the National Hematology for refractory ulcerative colitis. The mean number of months Online Practice Exam administered yearly to all hematology from the initiation of Infliximab to colectomy was 10.7 trainees will be analyzed with respect to whether or not (95% CI 4.14 to 17.29). The mean duration of disease prior to completion of the online cased-based learning curriculum starting Infliximab between the colectomy and non-colectomy correlated with knowledge gains. Following completion of the groups were 9.4 and 72.2 months respectively (p = 0.046). The study, if our results show that the intervention is well received mean number of hospitalizations before and after Infliximab and successful in enhancing resident learning, the modules will were 1.1 and 0.4 respectively (p < 0.001). In January 2014, be made available for use by all Canadian Hematology trainees 72% of patients were still receiving Infliximab. as well as medical learners in other specialties. The online cases could also be adapted for use as accredited CME activities for Conclusion: Our findings suggest comparable long-term practicing physicians across Canada and beyond. rates of colectomy to the current literature. The frequency of hospitalizations was significantly reduced, representing the Supervisor: Dr. Madeline Verhovsek efficacy of Infliximab. Our small sample size limits our ability to make strong inferences; however, our data supports the long-term use of Infliximab in Ulcerative Colitis.

Supervisor: Dr. Smita Haider

82 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

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Conor Cox PGY1 Zeeshan Ahmed PGY2 A Multi-Dimensional Approach to the Spontaneous Pneumomediastinum in a Severe Management of Severe Asthma Asthma Exacerbation

Aims: Approximately 8.5% of Canadians will be diagnosed Background: Spontaneous pneumomediastinum (SPM) is with asthma during their lifetime, 20% of these with severe defined as air within the mediastinum and often occurs without disease. These patients pose management challenges and here a clear precipitant. Patients with SPM present commonly we describe the utility of a multi-dimensional approach to severe with chest pain, dyspnea and subcutaneous emphysema. On asthma management. auscultation of the heart, a crunching sound during systole (termed Hamman’s sign) may be heard, and while present in Results: A 41-year-old male was referred with persistent severe only 20% of cases, is pathognomonic for SPM. SPM is due to asthma, refractory to treatment with Ventolin, Symbicort, acutely increased intrathoracic pressure resulting in alveolar Spiriva, theophylline, N-acetylcysteine and daily prednisone. He rupture into the pulmonary parenchyma and tracking of air had high illness-burden with daily symptoms (dyspnea, cough along the bronchivascular sheath and into the mediastinum. and sputum). Despite medication compliance and regular This can also result in subcutaneous emphysema if the air clinic appointments, he had unscheduled ER visits and at least travels along the fascial planes into the neck, face and limbs. 4 exacerbations per year requiring higher doses of prednisone. He was an ex-smoker (5 pack-year history). On examination Case: A 27-year-old male with asthma presented to the ER he was not in distress and breathing quietly, with a BMI of with a productive cough, dyspnea and wheezing. His physical 38kg/m2. Cardiopulmonary, HEENT, and neurological exam demonstrated diminished breath sounds throughout all examinations were non-remarkable. There was no clinical, lung fields with marked crepitus on palpation of his neck and radiological or biochemical evidence suggesting secondary precordium. A chest X-ray revealed pneumomediastinum and etiology for asthma. Spirometry showed moderately- subcutaneous emphysema but no focal area of consolidation or severe airflow obstruction [post-bronchodilator FEV1 2.4L evidence of pneumothorax. In the absence of any penetrating (54%), FVC 5.3L (97%), ratio 46%], and severe airway thoracic or esophageal trauma, and no history of cocaine use, hyperresponsiveness (PC20 methacholine 0.1mg/mL). Sputum these findings were attributed solely to the severity of the analysis demonstrated neutrophilic bronchitis and sputum cell patient’s asthma exacerbation. He was treated with antibiotics, counts allowed steroid tapering. Anti-microbial therapy was bronchonchodilators and steroids. His respiratory status and guided by molecular microbiology which identified an abnormal subcutaneous emphysema improved over the next 4 days with airway microbiome with anaerobic organisms. Further control oxygen and analgesia. His nasopharyngeal swab later revealed was obtained from targeting airway hyperresponsiveness with rhinovirus and the patient was discharged home on regular bronchial thermoplasty. There was both objective and subjective inhaled fluticasone/salmetrol. improvement (FEV1 3L, 65%L; FVC 5.7L, 98%, ratio 53%, PC20 of 0.4mg/mL), with a reduction in yearly exacerbations, Clinical Pearls: SPM is a rare entity that is benign and self- less daily symptoms, improved exercise tolerance, and decreased limited in nature and requires supportive, non-surgical medication requirements (currently on Symbicort 4 puffs daily therapy. Very rarely, patients may develop life threatening and Oxeze prn). complications such as pneumorachis or pneumopericardium which require surgical intervention. Conclusions: This experience illustrates the value of measuring the pathogenetic elements in severe asthma with quantitative Supervisor: Dr. Shariq Haider sputum cell analysis, molecular microbiology, and airway challenge in order to target specific elements with focused, effective therapies.

Supervisor: Dr. Parameswaran Nair

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 83 McMaster University 26th Annual Residents’ Research Day in Medicine

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Zeeshan Ahmed PGY2, Haroon Yousuf PGY2 Faizan Amin PGY5 Indolent T-Cell Lymphoproliferative Disorder of The Kounis Syndrome the GI Tract Causing Chronic Diarrhea

Background: Kounis syndrome (KS) is an eponymous Background: Indolent T-Cell Lymphoproliferative Disease term referring to acute coronary syndrome in the context of (LPD) of the GI-tract is a relatively rare lymphoproliferative anaphylaxis. First described in 1991 by Kounis et al., KS manifests disorder of the GI tract that has just recently been defined as in three recognized ways: vasospastic allergic angina (Type I), a clinical entity in 2013. It generally presents as diarrhoea, allergic myocardial infarction (Type II) and stent thrombosis abdominal pain, and or nausea/vomiting. Given the rarity of (Type III). KS appears to be due to coronary vasospasm, this clinical entity and its similarity on pathology with diseases inflammatory mediator release and platelet aggregation resulting such as enteropathy associated T-Cell Lymphoma, celiac in coronary artery thrombosis. disease or inflammatory bowel disease it is often misdiagnosed.

Case: A 69-year-old male with a history of hypertension, Case: We present the case of an 82-year-old woman with a dyslipidemia and coronary artery disease presented to the ER 4-week history of diffuse abdominal pain, diarrhea with with dyspnea after suffering a bee sting on his lower lip. He clay coloured stool up to 15 times per day and decreased received therapy for anaphylaxis with histamine blockade, oral intake due to nausea without vomiting. She was treated intravenous steroids and IM epinephrine. Thereafter, he with intravenous fluids. An infectious workup including developed typical cardiac chest pain. An EKG revealed an inferior stool cultures, ova and parasite, norovirus and C. difficile STEMI and the patient underwent an urgent angiogram which was negative. An EGD showed diffuse erosive changes in revealed dominant right coronary system with 100% occlusion the duodenum with biopsies showing villous blunting and of his circumflex with 70% stenosis of his LAD. He received a increased intra-epithelial lymphocytes suggestive of celiac bare metal stent to the culprit circumflex lesion. He remained disease. The diarrhea persisted despite a gluten free diet and hypotensive even after primary PCI and was transferred to the total parenteral nutrition was started. The pathology and CCU and placed on an epinephrine infusion maintain a stable immunohistochemistry was reviewed by a hematopathologist blood pressure. Two days after PCI for his inferior STEMI he resulting in a new diagnosis of indolent T-cell LPD of the developed sudden onset abdominal pain. An abdominal CT GI tract. A trail of intravenous methylprednisolone resulted in scan revealed a ruptured infrarenal abdominal aortic aneurysm improvement of symptoms. She was discharged on a slow oral and required urgent endovascular repair with a bifurcated stent prednisone taper with no symptom recurrance. graft. The remainder of his stay in hospital was unremarkable and he was discharged home. Conclusions: In cases of chronic diarrhea that is not responsive to typical treatment regimens, clinicians should consider the Clinical Pearls: KS and epinephrine induced coronary diagnosis of indolent T-Cell LPD of the GI-tract. This disorder vasospasm is a rare phenomenon with only one other case does not require chemotherapy like other peripheral T-cell described in the literature. Furthermore, this is the first report lymphomas and symptoms can often be self-limited in nature. of aortic aneurysmal rupture in the setting of KS and myocardial To our knowledge this is the first case report in which indolent infarction. T-cell LPD of the GI tract has been treated with prednisone.

Supervisor: Dr. Hisham Dokainish Supervisor: Dr. Irwin Walker

84 Volume 10, Issue 4, 2015 Canadian Journal of General Internal Medicine McMaster University 26th Annual Residents’ Research Day in Medicine

PUBLISHED ABSTRACT PUBLISHED ABSTRACT

Bishoy Deif PGY2, Ashraf Al-Azzoni PGY6 Shannon Riley PGY2, Nicole Sitzer PGY3, Acute Severe Mitral Regurgitation Uncovered by Sophie Corriveau Respirology PGY4 Treatment of Concomitant Septic Shock: A Case Teaching Residents How to Effectively Prescribe Report Nicotine Replacement Therapy on the Clinical Teaching Unit Background: Acute mitral regurgitation (MR) complicates a significant proportion of myocardial infarction and patients are Introduction: Despite evidence that smoking cessation is often critically ill, with mortality as high as 50% despite surgical best achieved through the combination of counselling and intervention. Furthermore, the diagnosis of acute MR can be pharmacotherapy, residents perceive barriers to providing this challenging and non-specific clinical manifestations may delay standard of care. In a recently distributed survey at McMaster, time to definitive treatment. 57% of residents identified a lack of knowledge regarding Nicotine Replacement Therapy (NRT) as a common barrier Case Presentation: Our case is that of a 67-year-old female to smoking cessation counselling. We hypothesized that a who initially presented with an NSTEMI but subsequently teaching intervention promoting the role of NRT in smoking developed high-grade fevers, hypotension, and hemoptysis cessation would bridge an identified gap in medical education during her admission. A Chest X-ray (CXR) revealed diffuse and promote health advocacy amongst residents. right side air-space disease and despite antibiotic treatment of her underlying pneumosepsis, the patient further deteriorated Methods: A teaching intervention directed towards housestaff with worsening hypotension and hypoxia. The patient was on the CTU at St. Joseph’s Hospital, Hamilton took place on ultimately admitted to the Coronary Care Unit, intubated, and week 4 of an 8-week rotation. Electronic pharmacy records underwent Pulmonary Artery (PA) catheterization. were retrospectively extracted from the hospital database to An echocardiogram performed shortly after admission determine NRT prescribing behaviour. The amount of NRT reported severe MR with a flail posterior mitral leaflet; however, prescribed during the 4-weeks pre-intervention was used to the patient was only minimally symptomatic at that time. establish a control rate amongst the current housestaff. PA catheter readings were initially suggestive of septic shock with a Cardiac Index (CI) of 2.75 L/min/m2 and a Systemic Results: During the 4-week pre-intervention period, 15 Vascular Resistance Index (SVRI) of 1200 dynes-sec/cm-5/m2. prescriptions were written for NRT for 13 unique patients The severity of the patient’s MR became more apparent after providing an average of 3.75 prescriptions per a week. 24-hours of antibiotic treatment when her CI dropped to 1.2L/ Preliminary data from the 2-week period post-intervention min/m2 and she progressed to cardiogenic shock. confirms 17 prescriptions were written for 16 unique patients providing an average of 8.5 prescriptions per a week- a 2.27 Conclusion: Our case demonstrates how septic shock can fold increase. ameliorate the severity of acute MR by reducing afterload and increasing forward flow. Acute MR can be difficult to diagnose as Conclusion: Providing an innovative strategy to promote clinical manifestations often mimic an acute respiratory process. smoking cessation at McMaster has demonstrated an overall Murmurs can be absent in 50% of cases and the CXR may show trend towards improved rates of NRT prescribing in active unilateral pulmonary edema. In our case, the diagnosis was even smokers. Educating residents on the delivery of effective more challenging to make due to the presence of concomitant smoking cessation counselling may target previously identified septic shock. barriers. Although limited by a small sample size, this data suggests that integrating formal education on NRT into the Supervisor: Dr. Omid Salehian residency curriculum can alter resident prescribing behavior.

Supervisor: Dr. Jill Rudkowski

Canadian Journal of General Internal Medicine Volume 10, Issue 4, 2015 85 The only GLP-1 receptor agonist for chronic weight management in people with obesity or overweight with ≥1 weight-related comorbidity1* CONGRATULATIONS TO THE 2015 WINNERS!

DR. DAVID SACKETT SENIOR INVESTIGATOR AWARD RESEARCH POSTERS Dr. Stephen Hwang 1st - Dr. Christopher Yarnell 2nd - Dr. Michael Fralick NEW INVESTIGATOR AWARD WITH OBESITY 3rd - Dr. Theophile Theriault Dr. Todd Lee QUALITY IMPROVEMENT ORALS THE CSIM OSLER AWARD Dr. Andrea Blotsky Dr. Amy Hendricks QUALITY IMPROVEMENT POSTERS THE OSLER LECTURER 1st - Dr. Kate Colizza Dr. James Nishikawa 2nd - Dr. Maude Phaneuf rd HUI LEE HEALTH PROMOTION SCHOLARSHIP 3 - (tie) - Dr. Shaan Chugh In a 56-week study, 3731 patients with obesity or overweight Dr. Gurpreet Jaswal 3rd - (tie) V- isitDr. Joséecsim. Sylvainca to register and with ≥1 weight-related comorbidity (without diabetes) achieved: view the Preliminary Program. Signiﬁ cant weight loss with Saxenda® vs. placebo1†‡ THE DR. MAHESH RAJU AWARD FOR TED GILES CLINICAL VIGNETTES • 64% lost 5% of initial body weight vs. 27% of patients RESIDENT MENTORSHIP 1st - Dr. Peter Wu ≥ Reserve your hotel room at the on placebo (P<0.0001) Dr. Joffre Munro 2nd - Dr. Vincent Larouche 3rd - (tie)special - Dr. Adam con fMazzettierence rate at the • 33% lost >10% of initial body weight vs. 10% of patients CSIM/PROFESSORS OF MEDICINE RESEARCH ORALS 3rd - (tie) - Dr. Erin DSpicerelta Prince Edward on placebo (P<0.0001) st 1 - Dr. Michael Fralick in Charlottetown. 2nd - Dr. Penny Yin EDUCATION AND RESEARCH FUND 3rd - Dr. Lauren Lapointe-Shaw Dr. Rahul Mehta

Indications and clinical use: Other relevant warnings and precautions: For more information: Saxenda® (liraglutide) is indicated as an adjunct to a • Combination use with other weight loss products Please consult the product monograph at http://www. reduced calorie diet and increased physical activity for has not been established novonordisk.ca/content/dam/Canada/AFFILIATE/ The Canadian Society of Internal Medicine gratefully acknowledges chronic weight management in adult patients with an • Should not be administered intravenously www-novonordisk-ca/OurProducts/PDF/Saxenda_PM_ initial body mass index (BMI) of:1 or intramuscularly English.pdf for more information relating to adverse support of its 2015 annual meeting from: • 30 kg/m2 or greater (obese), or • Risk of increase in heart rate and PR interval reactions, drug interactions, and dosing information GOLD SPONSORS • 27 kg/m2 or greater (overweight) in the presence prolongation; monitor consistent with usual which have not been discussed in this piece. of at least one weight-related comorbidity (e.g., clinical practice The product monograph is also available by calling hypertension, type 2 diabetes, or dyslipidemia) and • Risk of hypoglycemia in patients with type 2 diabetes Novo Nordisk at 1-800-465-4334. who have failed a previous weight management mellitus; should not be used together with insulin Reference: ® intervention. • Observe patients carefully for signs and symptoms 1. Saxenda Product Monograph, Novo Nordisk Canada Inc., 2015. of acute pancreatitis *Clinical signifi cance has not been established. Limited effi cacy and safety data in overweight patients † • Acute gallbladder disease A multicentre, randomized, double-blind, placebo-controlled trial with at least one weight-related comorbidity. The evaluating once-daily Saxenda® (n=2437) compared to placebo ® • Risk of hypersensitivity and angioedema (n=1225), in conjunction with a reduced food intake and increased long-term safety of Saxenda is unknown. Patients ≥65 2 • Breast neoplasms physical activity, in patients without diabetes and with a BMI ≥30 kg/m , years may experience more gastrointestinal side effects. or 27–29.9 kg/m2 with at least one weight-related comorbid condition. • Avoid use in patients with a history of suicidal Saxenda® was titrated to 3 mg daily during a 4-week period. The Contraindications: attempts or active suicidal ideation primary endpoints were mean percent change in body weight and the • Personal or family history of medullary thyroid • Caution in patients with recent myocardial infarction, proportion of patients achieving ≥5% and >10% weight loss from carcinoma (MTC) or in patients with Multiple baseline to week 56. Mean baseline weight: 106.3 kg for both groups. unstable angina and congestive heart failure ‡ Treatment with Saxenda® should be discontinued after 12 weeks on Endocrine Neoplasia syndrome type 2 (MEN 2) • Not recommended in patients with hepatic insuffi ciency the 3.0 mg/day dose if a patient has not lost at least 5% of their initial • Pregnant or breast-feeding women • Caution when initiating or escalating doses in body weight. Most serious warnings and precautions: patients with renal insuffi ciency; not recommended Fictitious case. May not be representative of all patients. Risk of Thyroid C-Cell Tumours: Liraglutide causes in patients with severe renal insuffi ciency JOIN THE CSIM dose-dependent and treatment-duration-dependent • Should not be used by patients with infl ammatory thyroid C-cell tumours in both genders of rats and mice. It is bowel disease or diabetic gastroparesis unknown whether liraglutide causes thyroid C-cell tumours,

Visit www.csim.ca for a list of membership including MTC, in humans. Patients should be counselled CA/SA/0615/0032E regarding the risk and symptoms of thyroid tumours. benefits - including eligibility for awards and Watch www.csim.ca and join us on scholarships, discounted CSIM Meeting registration Twitter and Facebook All trademarks owned by Novo Nordisk A/S and used by Novo Nordisk Canada Inc. fees, access to CPD events and more. Novo Nordisk Canada Inc., 300-2680 Skymark Avenue, Mississauga, Ontario L4W 5L6. for updates! Tel: (905) 629-4222 or 1-800-465-4334. www.novonordisk.ca Residents and medical students JOIN FREE! © 09/2015 Novo Nordisk Canada Inc.

Canadian Journal of General Internal Medicine Volume 10, Issue 2, 2015 86

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CSIM Journal Ad Build: E1 Date: Aug 19, 2015 Docket: NOV14SA006 Production Artist(s): MH Client: Novo Nordisk/Saxenda Studio Manager: GB ______Type Safety: .25" all around Art Director: ME ______LAST ROUND REVIEWED ON Trim Area: 8.125" x 10.75" Medical Writer: UK/KK ______Date: Bleed: 0.125” Prod. Manager: BF Build: Colour(s): 4C Account Manager: KF/ES ______Notes: Assoc. Creative Dir: MB ______Proofreader: SF ______The only GLP-1 receptor agonist for chronic weight management in people with obesity or overweight with ≥1 weight-related comorbidity1* CONGRATULATIONS TO THE 2015 WINNERS!

47043 NOV14SA006_CSIM_JournalAD_E1.indd 1 2015-08-20 8:36 PM