Supporting early academic family medicine careers with the clinician scholar enhanced-skills program

Context: The Clinician Scholar Program (CSP) is an enhanced-skills (R3) residency program to train clinician researchers/educators/leaders for academic family practice. This article intends to share Laval University’s CSP development and evaluation strategy, and provide recommendations for similar innovations in other disciplines/settings. Methods This article uses Kern’s model to present the program development, and a program-oriented approach for program evaluation, carried from 2011 to 2017 using descriptive data. Questionnaires, reflexive texts and an Objective Structured Teaching Exam supported data collection. Results 7 CSP graduates and 14 controls participated in the program evaluation. Residents were highly satisfied with the program, nevertheless suggested allowing training later in career. The CSP enriched knowledge, skills and attitudes about academic practice. CSP increased residents’ entrustment level about academic competencies. All graduates joined an academic practice within five years of program completion. Conclusions Key recommendations to implement similar programs include academic medicine core training, project-based learning with learner-centered objectives, relevant and authentic learning and assessment, and multi-level program evaluation approach. Programs should consider concomitant graduate studies and opportunity to offer such training after a few years of clinical practice to meet other needs at a timely stage of career

Evidence summaries (decision boxes) to prepare clinicians for shared decision-making with patients: a mixed methods implementation study

Background: Decision boxes (Dboxes) provide clinicians with research evidence about management options for medical questions that have no single best answer. Dboxes fulfil a need for rapid clinical training tools to prepare clinicians for clinician-patient communication and shared decision-making. We studied the barriers and facilitators to using the Dbox information in clinical practice. Methods: We used a mixed methods study with sequential explanatory design. We recruited family physicians, residents, and nurses from six primary health-care clinics. Participants received eight Dboxes covering various questions by email (one per week). For each Dbox, they completed a web questionnaire to rate clinical relevance and cognitive impact and to assess the determinants of their intention to use what they learned from the Dbox to explain to their patients the advantages and disadvantages of the options, based on the theory of planned behaviour (TPB). Following the 8-week delivery period, we conducted focus groups with clinicians and interviews with clinic administrators to explore contextual factors influencing the use of the Dbox information. Results: One hundred clinicians completed the web surveys. In 54% of the 496 questionnaires completed, they reported that their practice would be improved after having read the Dboxes, and in 40%, they stated that they would use this information for their patients. Of those who would use the information for their patients, 89% expected it would benefit their patients, especially in that it would allow the patient to make a decision more in keeping with his/her personal circumstances, values, and preferences. They intended to use the Dboxes in practice (mean 5.6 ± 1.2, scale 1–7, with 7 being “high”), and their intention was significantly related to social norm, perceived behavioural control, and attitude according to the TPB (P < 0.0001). In focus groups, clinicians mentioned that co-interventions such as patient decision aids and training in shared decision-making would facilitate the use of the Dbox information. Some participants would have liked a clear “bottom line” statement for each Dbox and access to printed Dboxes in consultation rooms. Conclusions: Dboxes are valued by clinicians. Tailoring of Dboxes to their needs would facilitate their implementation in practic

Developing and user-testing Decision boxes to facilitate shared decision making in primary care - a study protocol

<p>Abstract</p> <p>Background</p> <p>Applying evidence is one of the most challenging steps of evidence-based clinical practice. Healthcare professionals have difficulty interpreting evidence and translating it to patients. Decision boxes are summaries of the most important benefits and harms of diagnostic, therapeutic, and preventive health interventions provided to healthcare professionals before they meet the patient. Our hypothesis is that Decision boxes will prepare clinicians to help patients make informed value-based decisions. By acting as primers, the boxes will enhance the application of evidence-based practices and increase shared decision making during the clinical encounter. The objectives of this study are to provide a framework for developing Decision boxes and testing their value to users.</p> <p>Methods/Design</p> <p>We will begin by developing Decision box prototypes for 10 clinical conditions or topics based on a review of the research on risk communication. We will present two prototypes to purposeful samples of 16 family physicians distributed in two focus groups, and 32 patients distributed in four focus groups. We will use the User Experience Model framework to explore users' perceptions of the content and format of each prototype. All discussions will be transcribed, and two researchers will independently perform a hybrid deductive/inductive thematic qualitative analysis of the data. The coding scheme will be developed a priori from the User Experience Model's seven themes (valuable, usable, credible, useful, desirable, accessible and findable), and will include new themes suggested by the data (inductive analysis). Key findings will be triangulated using additional publications on the design of tools to improve risk communication. All 10 Decision boxes will be modified in light of our findings.</p> <p>Discussion</p> <p>This study will produce a robust framework for developing and testing Decision boxes that will serve healthcare professionals and patients alike. It is the first step in the development and implementation of a new tool that should facilitate decision making in clinical practice.</p

Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

Sirtuin 3, a New Target of PGC-1α, Plays an Important Role in the Suppression of ROS and Mitochondrial Biogenesis

Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1alpha induces several key reactive oxygen species (ROS)-detoxifying enzymes, but the molecular mechanism underlying this is not well understood.Here we show that PGC-1alpha strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. Knockdown of PGC-1alpha led to decreased Sirt3 gene expression. PGC-1alpha activated the mouse SIRT3 promoter, which was mediated by an estrogen-related receptor (ERR) binding element (ERRE) (-407/-399) mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that ERRalpha bound to the identified ERRE and PGC-1alpha co-localized with ERRalpha in the mSirt3 promoter. Knockdown of ERRalpha reduced the induction of Sirt3 by PGC-1alpha in C(2)C(12) myotubes. Furthermore, Sirt3 was essential for PGC-1alpha-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. Overexpression of SIRT3 or PGC-1alpha in C(2)C(12) myotubes decreased basal ROS level. In contrast, knockdown of mSIRT3 increased basal ROS level and blocked the inhibitory effect of PGC-1alpha on cellular ROS production. Finally, SIRT3 stimulated mitochondrial biogenesis, and SIRT3 knockdown decreased the stimulatory effect of PGC-1alpha on mitochondrial biogenesis in C(2)C(12) myotubes.Our results indicate that Sirt3 functions as a downstream target gene of PGC-1alpha and mediates the PGC-1alpha effects on cellular ROS production and mitochondrial biogenesis. Thus, SIRT3 integrates cellular energy metabolism and ROS generation. The elucidation of the molecular mechanisms of SIRT3 regulation and its physiological functions may provide a novel target for treating ROS-related disease

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

On the conjecture of Langlands and Rapoport.

The conjecture of Langlands and Rapoport describes, under certain hypotheses, the set of points on the reduction of a Shimura variety at a prime of the reflex field. The description is sufficiently group theoretic in nature so as to allow comparison between automorphic L-functions and the zeta function of the Shimura variety. Langlands and Rapoport assume the group used to define the Shimura variety splits over an unramified extension at the prime in question, and that the derived group is simply connected. Their conjecture is stated in the cases where the variety has good reduction (i.e., where the variety is defined using a hyperspecial subgroup), or when it has 'mild' bad reduction (i.e., where the adjoint group is anisotropic at the prime in question, and one uses the unique special group to define the Shimura variety). This thesis generalises the conjecture: arbitrary parahoric groups are allowed. The main application of the results in the thesis is the following. Suppose the centre of the reductive group used in the definition of the Shimura variety has trivial cohomology. Then, to prove the original conjecture for Shimura varieties with mild bad reduction, it suffices to prove a sufficiently functorial version of the generalised conjecture for Shimura varieties defined using a parahoric subgroup that is the intersection of hyperspecial subgroups. The method is to embed the variety with mild bad reduction into a second Shimura variety, and then to use a descent argument.Ph.D.MathematicsPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131428/2/9909892.pd

National survey assessing knowledge and management of the drug interaction between dolutegravir and metformin by Canadian HIV practitioners

Pharmacy residents have the opportunity to complete a research project during their residency training, which provides them with skills on how to conduct and manage a research project. Projects often represent an area of interest and need that has been recognized by the host institution’s pharmacy department. Projects are presented as a poster at an annual CSHP Ontario Branch Residency Research Night, and many eventually go on to be published in a peer-reviewed journal.Background: A well-described pharmacokinetic drug interaction between dolutegravir and metformin results in increased exposure to metformin. However, no conclusive management recommendations exist. This study was conducted to examine current Canadian practice. Objectives: The study objectives were to describe Canadian practitioners’ knowledge and management of the interaction, including assessment of interprofessional or regional variations, and to identify factors that influence the decision to administer metformin and dolutegravir concomitantly. Methods: The study was an online survey of Canadian physicians, nurse practitioners, and pharmacists caring for HIV-infected patients. The survey consisted of multiple choice, short answer, and case-based questions administered via SimpleSurvey. An iterative process was used to pilot the survey electronically in French and English prior to two waves of survey dissemination. Results: The survey was distributed to 179 practitioners (response rate 36 %, completion rate 83%). The majority (93%) knew the interaction increased metformin exposure; of these, 65% correctly identified the magnitude. In clinical scenarios, 67-90% of respondents administered the medications concomitantly, with some electing to decrease the metformin dose. Closer monitoring of renal function, diabetes, and metformin tolerability, including lactic acidosis, was suggested by respondents co-administering dolutegravir and metformin. Diabetes-related factors, dolutegravir dose, and renal dysfunction commonly affected co-therapy decisions. There was minimal variation by profession, though practice in Alberta may differ slightly. Conclusion: A majority of clinicians did not consider co-administration of dolutegravir and metformin to be contraindicated. However, factors such as maximum metformin dose, renal dysfunction, and diabetes-related conditions were most likely to affect decisions to continue co-therapy

Psychiatric treatment considerations with direct acting antivirals in hepatitis C

Abstract Background Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications. Methods We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies. Results Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John’s Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized. Conclusions Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy

Psychiatric treatment considerations with direct acting antivirals in hepatitis C

Abstract Background Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications. Methods We conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies. Results Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John’s Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized. Conclusions Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy