Clinician Investigator Program Research Articles

Scientific overview: CSCI-CITAC Annual General Meeting and Young Investigator's Forum 2013.

The 2013 joint Canadian Society of Clinician Investigators (CSCI)-Clinical Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) annual general meeting(AGM) was held in Ottawa, September 2013. The symposium focused on "Applications of the 'omics' to Clinical Practice", with presentations from Drs. William T. Gibson (University of British Columbia), Julie Ho (University of Manitoba) and David Hwang (University of Toronto), discussing topics of genome, proteome and the microbiome, respectively. Other highlights from the 2013 AGM include presentations by Dr. Salim Yusuf (McMaster University, 2013 CSCI-RCPSC Henry Friesen Award winner), Dr. Gary Lewis (University of Toronto, 2013 CSCI Distinguished Scientist Award winner) and Dr. Michael Taylor (University of Toronto, 2013 Joe Doupe Award winner). The CSCI/CITAC/Friends of CIHR Joint Symposium consisted of presentations from Drs. John Bell (University of Ottawa), Dan Drucker (University of Toronto) and Heather J. Dean (University of Manitoba). Finally, the meeting ended with the presentation "The Power of an Idea to Bring Ideas to Power" by Dr. Harvey V. Fineberg (President, U.S. Institute of Medicine), the winner of the 2013 Henry Friesen International Prize. Also presented at the conference was research by clinician investigator (CI) trainees from across Canada; ie., those enrolled in MD/MSc, MD/PhD or Clinician Investigator Program(CIP) programs. Canadian trainees' research extended beyond the pillar of biomedical research, covering the spectrum between basic and clinical research, with a focus on the causes of significant morbidity and mortality for Canadians, including cancers, infectious diseases and other maladies. It is this research that we have summarized in this review.

The Clinician Investigator Program at the University of Ottawa

ABSTRACTClinician investigators play a critical role in developing new approaches and improving upon existing approaches to medical care, ultimately resulting in improved health of Canadians. Such individuals are uniquely suited to conduct research that addresses clinical observations as well as translates research findings into novel approaches to disease management and prevention. The need for such individuals has long been recognized and in 1995, the Royal College of Physician and Surgeons of Canada (RCPSC) developed the first formal training program in the country to help support the development of clinician investigators. Since its inception, over 200 trainees have completed the RCPSC Clinician Investigator Program (CIP), the details of which are communicated in a review by Cathy Hayward et al. [1] in Clinical and Investigative Medicine. Currently, the CIP is active at 15 (almost all) medical schools across the country. Dr. Andrew Badley, a clinician scientist in the Division of Infectious Disease, led the development of the application for the CIP at the University of Ottawa (U of O), which was ultimately approved in 2002. In 2003 Jonathan Angel became the Director of the CIP at U of O and in 2004, the first trainee was accepted into the program. Since then, approximately 40 trainees have enrolled in the CIP, and as of April 2014, 25 trainees have completed the program. While a few of the recent trainees have resumed clinical training following their research activities, the majority of the graduates (n=14) have gone on to assume academic positions at the University of Ottawa and elsewhere.RÉSUMÉ Les cliniciens-chercheurs jouent un rôle clé dans le développement de nouvelles méthodes et dans l’amélioration des méthodes existantes dans les soins médicaux. Le but est, ultimement, d’améliorer la santé des Canadiens et Canadiennes. Ces personnes sont bien placées pour mener des projets de recherche qui portent sur des observations cliniques et qui traduisent les résultats de recherche en approches novatrices pour la prévention et la prise en charge des maladies. Le besoin pour ces professionnels est reconnu depuis longtemps. En 1995, le Collège royal des médecins et chirurgiens du Canada (CRMCC) a créé le premier programme officiel pour appuyer le perfectionnement des cliniciens-chercheurs. Depuis sa création, plus de 200 personnes ont complété le Programme de cliniciens-chercheurs (PCC) du CRMCC. Une revue du programme a été publiée par Cathy Hayward et coll., dans la revue Clinical and Investigative Medicine. Actuellement, le PCC est offert dans 15 facultés de médecine au Canada, soit presque la totalité d’entre elles. Dr Andrew Badley, un clinicien-scientifique de la Division des maladies infectieuses, a mené l’intégration du PCC à l’Université d’Ottawa, programme qui a été approuvé ultimement en 2002. En 2003, Jonathan Angel est devenu le directeur du PCC de l’Université d’Ottawa et, en 2004, le premier stagiaire du programme était admis. Depuis cette date, environ 40 stagiaires se sont inscrits au PCC et, en avril 2014, 25 d’entre eux avaient terminé le programme. Bien que quelques-uns des plus récents stagiaires aient repris leur formation clinique après avoir achevé leur recherche, la majorité des finissants (n=14) ont accepté des fonctions universitaires à l’Université d’Ottawa ou ailleurs.

Chronic Benign Neutropenia/Agranulocytosis Associated With Non-Clozapine Antipsychotics

Back to table of contents Previous article Next article Communications and UpdatesFull AccessChronic Benign Neutropenia/Agranulocytosis Associated With Non-Clozapine AntipsychoticsFidel Vila-Rodriguez, M.D., Peter Tsang, M.D., and Alasdair M. Barr, Ph.D.Fidel Vila-RodriguezSearch for more papers by this author, M.D., Peter TsangSearch for more papers by this author, M.D., and Alasdair M. BarrSearch for more papers by this author, Ph.D.Published Online:1 Oct 2013https://doi.org/10.1176/appi.ajp.2013.13020215AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Agranulocytosis (absolute neutrophil count, <500/μl) is a potentially life-threatening condition. Clozapine and other antipsychotics are associated with acute agranulocytosis (1). We report the case of a man with chronic and benign neutropenia/agranulocytosis associated with multiple non-clozapine antipsychotics (fluphenazine, olanzapine, flupenthixol, haloperidol, and paliperidone).Case Report“Mr. N,” a man in his mid-50s, was diagnosed with paranoid schizophrenia in his early 20s. He had never received clozapine, but he had been taking fluphenazine, 50 mg i.m every 2 weeks, for 20 years when he was initially noted neutropenic in 2003 (Figure 1). In 2004, the neutropenia worsened with the introduction of olanzapine, 10 mg/day, dropping to 500 neutrophils/μl. At this point, both antipsychotics were discontinued and he was started on haloperidol, 5 mg/day. In early 2006, he was switched to flupenthixol, 40 mg i.m every 2 weeks. Mr. N’s absolute neutrophil count dropped to 200/μl, and he was subsequently switched back to fluphenazine (range, 20–60 mg every 2 weeks) late in that same year. In fall 2012, he was admitted as a result of a psychosis exacerbation thought to be related to noncompliance of antipsychotic therapy. On admission, his absolute neutrophil count was noted as 2,100/μl, and this dropped to 400/μl after switching to paliperidone (156 mg every 4 weeks, maintenance dosage). Of note, this pattern had been documented on two prior admissions that were caused by noncompliance followed by acute psychotic exacerbations (Figure 1). The treatment plan included maintaining paliperidone at the lowest dosage possible that would prevent psychosis.FIGURE 1. Absolute Neutrophil Count Over Time and Correspondence to Antipsychotic Treatment and Admissions Due to NoncomplianceA bone marrow biopsy in February 2006, when Mr. N’s absolute neutrophil count was 300/μl, revealed normal cellularity on the three lines, with adequate white cell precursors and good white cell differentiation, indicating no bone marrow disorder. He was human leukocyte antigen (HLA) II genotyped, showing a DQB1*06 genotype (DRB1*15, DRB1*16, and DQB1*05 were all absent). Over 10 years of follow-up, Mr. N. has never presented with any infectious complication from low absolute neutrophil count or required treatment with granulocyte colony-stimulating factor.DiscussionThe presence of a normal bone marrow biopsy in Mr. N points to a peripheral mechanism of destruction of mature neutrophils. In addition, the patient’s HLA genotype is not associated with autoimmune agranulocytosis, and therefore the most plausible mechanism seems to be hapten mechanism, whereby binding of the drug to the membrane of granulocytes induces antibodies directed to the drug (hapten) (2). The most likely diagnosis is that of idiosyncratic drug-induced chronic benign neutropenia. In our patient, where discontinuation of the likely causative agent(s) of low absolute neutrophil count was not possible because of the extreme risk associated with discontinuation of antipsychotic therapy, a conservative course of action was decided. Lowest dosages of antipsychotics, the avoidance of drugs known to be associated with neutropenia, close and regular monitoring of WBC and absolute neutrophil count, consultation to rule out central or autoimmune mechanisms, and ongoing shared care with hematology were all essential components of excellent care in this complex clinical situation. This approach might be applicable in similar situations other clinicians may encounter.From the Departments of Psychiatry, Hematology, Anesthesiology, Pharmacology, and Therapeutics, the University of British Columbia, Vancouver.Dr. Vila-Rodriguez has received support from the UBC Clinician Investigator Program. Dr. Barr has received consulting fees from Bristol-Myers Squibb Canada, Eli Lilly, and Roche. Dr. Tsang reports no financial relationships with commercial interests.

O06 The satellite cell in male and female, developing and adult mice: evidence for functionally distinct stem cell populations

muscle weakness. In the world literature the genetic defect for this condition has been identified in two families, having the R279W mutation in the sarcomeric protein TTN, although cases without this mutation have already been reported. Methods: Two large pedigrees and an apparently sporadic case with CBM were included in this study. Clinical characteristics and diagnostic investigations of all affected family members was collected from charts and summarised. Western blot of C-terminal TTN protein was performed. Genome-wide 1000 microsatellite analysis was performed in one of the families to identify a linkage region and shared haplotype. Exome sequencing was performed on 4 patients. Results: Onset of disease was usually in middle-age, with tibialis anterior being the earliest and most severely affected muscle. Pulmonary function tests indicated low FEV1 and FVC, with worsening when supine. Cardiac involvement was not present. Muscle pathology was nonspecific in some affected patients. Electromyography demonstrated necrotising myopathic process in the majority of patients. MRI invariably revealed signal abnormalities of semitendinosus muscle. Blot of C-terminal TTN protein was normal. A single 20 cM linkage region on chromosome 2 was identified. Exome sequencing detected the disease mutation and identified other candidates for exclusion with segregation analysis. Conclusions: We report the disease gene for these patients with CBM, and describe in detail the phenotype and diagnostic investigations from these three pedigrees. Genetic testing for these CBM genes should be performed in patients with myopathy and early respiratory failure if muscle pathology reveals cytoplasmic bodies or is nonspecific. Acknowledgements: GP is the recipient of funding from the Clinician Investigator Program from the University of British Columbia in Vancouver, Canada, and a Bisby fellowship from the Canadian Institutes of Health Research. The authors report no competing interests.

Clinician Investigator Training in Canada: A Review

The Royal College of Physicians and Surgeons of Canada undertook a review of its Clinician Investigator Program (CIP), 13 years after launching the program in response to shortages in clinical investigators. The primary study goals were to determine the outcomes, impact, strengths and weaknesses of CIP. Focus groups and telephone interviews with current and past program directors (PD) and a detailed survey of current and former trainees were conducted. Thirteen PD and 45% of current and former trainees from 10 CIP participated. Since 1995, 12 CIP have been accredited and 553 residents have enrolled in CIP, with 194 completing CIP and residency training by 2008. PD recognized CIP as an excellent program that produces highly qualified clinical investigators; important for faculty renewal. Both trainees and PD identified the need to improve CIP funding. Most (84%) CIP trainees did not have prior graduate degrees. Most alumni had completed Masters (58%) or Doctoral (39%) programs during CIP and published on their CIP research (97%). Among alumni who completed CIP and residency, many obtained an academic appointment with protected time for research, with 39% receiving an external career award. Many (60%) alumni reported no drawbacks to CIP and recognized the added values included Royal College recognition, structured training, pursuit of graduate studies, integration of clinical/research training and enhanced mentorship. Since the progam's inception, the number of CIP in Canada has grown. CIP are recognized as important mechanisms for integrating clinical and research training during residency to produce highly qualified clinician investigators.

Establishing a Trainee Section in the CIM

The Clinician Investigator Trainee Association of Canada – Association des cliniciens-chercheurs en formation du Canada (CITAC-ACCFC) is a national organization composed of MD+ trainees enrolled in MD/MSc, MD/PhD, and Clinician Investigator Programs (CIP) across Canada. In less than three years since its conception, CITAC-ACCFC has become an established organization with over 200 members from fifteen academic institutions. The mission of the CITAC-ACCFC is to organize and promote activities that support clinician investigator trainees in Canada, with the intention to improve academic and post-graduate career opportunities, expand institutional and public awareness of clinician investigator programs, and develop a nationally accessible information database of student and program development. The CITAC-ACCFC aims to improve the early-career conditions of clinician investigators in order to expand and advance innovative research initiatives within Canada. Throughout its development, CITAC-ACCFC has relied on the Canadian Society for Clinical Investigation (CSCI) for mentorship and guidance. In an exciting development, the relationship between CITAC-ACCFC and CSCI has enabled an innovative opportunity for early career development through a new collaboration- the creation of a Trainee Section in the Clinical and Investigative Medicine (CIM) journal. As a forum through which work on diverse topics can be shared with the global community, the CIM Trainee Section will create unique opportunities for professional development. Trainees in MD+ programs represent the next generation of clinical-investigators, who will integrate cutting edge research and compassionate patient care throughout their careers. Both professions require excellent communication skills, and through the Trainee Section, MD+ trainees, their supervisors, and MD+ Program Directors, will be able to focus on mentorship, academic training, financial planning, and career development, among other topics devoted to MD+ trainees. In addition to articles highlighting the research activities of trainees, the Trainee Section will feature clinical work, review articles, first chapter of theses, book reviews, and opinion pieces. This focus of the Trainee Section will complement CIM’s current focus on original research and issues of interest to the CSCI. It is therefore fitting to establish a Trainee Section that is dedicated to addressing issues arising at an earlier stage of training. As MD+ organizations are being established globally, the Trainee Section will strive to become an international forum that focuses on MD+ training. By increasing the international readership of CIM through the CITAC website, we will aim to engage MD+ trainees, program directors, university administration, and other leaders in education, to advocate for issues of national and global relevance. As trainees will be responsible for overseeing the editorial and peer-review process of the Trainee Section, we anticipate that this will provide an avenue by which to foster stronger interactions and collaborations among trainees on our Editorial Board, junior investigators, and senior faculty, while providing critical editorial experience for board members. Our team of Editors will ensure that articles are reviewed in a fair and timely manner, respecting the need to promptly publish articles of immediate relevance. We encourage all MD+ trainees to participate in the Trainee Section editorial and/or peer-review process. Additional details can be found on our website at: http://www.citac-accfc.org/portal/ As MD+ trainees, we are optimistic about the future of both basic science and clinical research. This is an exciting time to be an MD+ trainee, and we are confident that the creation of a Trainee Section will only augment this positive experience. We strongly encourage you to publish your work in the Trainee Section and become part of an emerging global community of MD+ trainees, who are keen on tackling health issues that affect us irrespective of our geographic, cultural, or racial borders. We look forward to receiving your articles.

YIF Poster Awards 2008

Award recipients from the Young Investigator Forum at the CSCI meeting in Toronto, September, 2008. The investigators were students from Canadian MD/PhD and Clinician Investigator Programs.

YIF Poster Awards 2007

The Annual Meeting of the Canadian Society for Clinical Investigation once again featured the Young Investigators Forum, an opportunity for students from Canadian MD/PhD and Clinician Investigator Programs to present their research in poster and oral format. Here are this year’s award recipients.

The Clinician Investigator Program in Companion Animal Internal Medicine at North Carolina State University

A retrospective study was conducted to describe the development and evolution of the combined internal medicine/PhD program, the Clinician Investigator (CI) Program, at North Carolina State University. Separate survey instruments were developed for individuals who had committed to completing both the residency and PhD components and for graduate advisors of individuals who were granted the PhD degree. Results are summarized here. Most CIs reported believing that each component of the program (clinical training and research training) provided mutual benefits and that their teaching skills were enhanced, particularly as a result of instructing students in the Veterinary Teaching Hospital. Opinions among both the CIs and the graduate advisors were divided about the benefits of a combined program compared with a sequential program; however, all but one of 11 CIs who completed the survey would enroll in the combined program again. The graduate advisors were overwhelming positive about the CIs they had advised and indicated that they would welcome a CI as a PhD student in their laboratory again. Suggested areas for improvement included guaranteed salary/stipend support for the average time to completion (six years) instead of for five years, as well as more emphasis on and guidance in identifying a graduate advisor earlier in the CI program so as to smooth the transition between the clinical and research training components of the program. It is hoped that other training programs will benefit from the summary of our experience with this program.