Somnath Mookherjee

Mutagenesis of dihydrofolate reductase from Plasmodium falciparum: analysis in Saccharomyces cerevisiae of triple mutant alleles resistant to pyrimethamine or WR99210.

Inhibitors of dihydrofolate reductase (DHFR) have been a mainstay of chemotherapy of falciparum malaria for >50 years. Unfortunately, point mutations in DHFR are the major cause of resistance to drugs of this class and mutations have rapidly diminished the clinical effectiveness of these drugs. We designed a simple yeast-based system to produce and analyze point mutations in the Plasmodium falciparum DHFR domain of the DHFR-thymidylate synthase gene that confers resistance to pyrimethamine (PM), the major antifolate currently used in malaria treatment, or to WR99210, an experimental antifolate. We used PCR mutagenesis, screened >1000 DHFR alleles that encoded functional enzymes and studied approximately 100 that were more resistant than a naturally occurring resistant allele (N51I and S108N). The IC(50) values for both drugs were determined for a subset of 44 alleles that carried only a single new mutation. Mutations that increased resistance to PM 10-100 fold (to >10(-4) M) were identified in three regions of the DHFR domain - around amino acids 50, 188 and 213. In contrast, mutations that caused WR-resistance were far less common and only conferred approximately 10-fold resistance (to approximately 10(-7) M). Even more interesting, only the mutations at 188 increased resistance to WR and mutations in the 213 and other regions either had no effect or actually increased sensitivity to WR. This collateral hypersensitivity raises the possibility that opposing selection for resistance/sensitivity to PM and WR might be used to slow selection of populations of P. falciparum resistant to antifolate treatment.

Physical Examination Education in Graduate Medical Education—A Systematic Review of the Literature

ABSTRACTOBJECTIVESThere is widespread recognition that physical examination (PE) should be taught in Graduate Medical Education (GME), but little is known regarding how to best teach PE to residents. Deliberate practice fosters expertise in other fields, but its utility in teaching PE is unknown. We systematically reviewed the literature to determine the effectiveness of methods to teach PE in GME, with attention to usage of deliberate practice.DATA SOURCESWe searched PubMed, ERIC, and EMBASE for English language studies regarding PE education in GME published between January 1951 and December 2012.STUDY ELIGIBILITY CRITERIASeven eligibility criteria were applied to studies of PE education: (1) English language; (2) subjects in GME; (3) description of study population; (4) description of intervention; (5) assessment of efficacy; (6) inclusion of control group; and (7) report of data analysis.STUDY APPRAISAL AND SYNTHESIS METHODSWe extracted data regarding study quality, type of PE, study population, curricular features, use of deliberate practice, outcomes and assessment methods. Tabulated summaries of studies were reviewed for narrative synthesis.RESULTSFourteen studies met inclusion criteria. The mean Medical Education Research Study Quality Instrument (MERSQI) score was 9.0 out of 18. Most studies (n = 8) included internal medicine residents. Half of the studies used resident interaction with a human examinee as the primary means of teaching PE. Three studies “definitely” and four studies “possibly” used deliberate practice; all but one of these studies demonstrated improved educational outcomes.LIMITATIONSWe used a non-validated deliberate practice assessment. Given the heterogeneity of assessment modalities, we did not perform a meta-analysis.CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGSNo single strategy for teaching PE in GME is clearly superior to another. Following the principles of deliberate practice and interaction with human examinees may be beneficial in teaching PE; controlled studies including these educational features should be performed to investigate these exploratory findings.

An innovative quality improvement curriculum for third-year medical students

Abstract Background Competence in quality improvement (QI) is a priority for medical students. We describe a self-directed QI skills curriculum for medical students in a 1-year longitudinal integrated third-year clerkship: an ideal context to learn and practice QI. Methods Two groups of four students identified a quality gap, described existing efforts to address the gap, made quantifying measures, and proposed a QI intervention. The program was assessed with knowledge and attitude surveys and a validated tool for rating trainee QI proposals. Reaction to the curriculum was assessed by survey and focus group. Results Knowledge of QI concepts did not improve (mean knowledge score±SD): pre: 5.9±1.5 vs. post: 6.6±1.3, p=0.20. There were significant improvements in attitudes (mean topic attitude score±SD) toward the value of QI (pre: 9.9±1.8 vs. post: 12.6±1.9, p=0.03) and confidence in QI skills (pre: 13.4±2.8 vs. post: 16.1±3.0, p=0.05). Proposals lacked sufficient analysis of interventions and evaluation plans. Reaction was mixed, including appreciation for the experience and frustration with finding appropriate mentorship. Conclusion Clinical-year students were able to conduct a self-directed QI project. Lack of improvement in QI knowledge suggests that self-directed learning in this domain may be insufficient without targeted didactics. Higher order skills such as developing measurement plans would benefit from explicit instruction and mentorship. Lessons from this experience will allow educators to better target QI curricula to medical students in the clinical years.

How to develop a competency-based examination blueprint for longitudinal standardized patient clinical skills assessments

Background: Objective Structured Clinical Exams (OSCEs) with standardized patients (SPs) are commonly used in medical education to assess learners’ clinical skills. However, assessments are often discrete rather than intentionally developmentally sequenced. Aims: We developed an examination blueprint to optimize assessment and feedback to learners with purposeful sequence as a series of longitudinally integrated assessments based on performance milestones. Integrated and progressive clinical skills assessments offer several benefits: assessment of skill development over time, systematic identification of learning needs, data for individualized feedback and learning plans, and baseline reference points for reassessment. Methods: Using a competency-based medical education (CBME) framework, we translated pre-determined competency milestones for medical students’ patient encounters into a four-year SP-based OSCE examination blueprint. Results: Initial evaluation of cases using the blueprint revealed opportunities to target less frequently assessed competencies and to align assessments with milestones for each year. Conclusions: The examination blueprint can guide ongoing SP-based OSCE case design. Future iterations of examination blueprints can incorporate lessons learnt from evaluation data and student feedback.

Potential Unintended Consequences Due to Medicare’s “No Pay for Errors Rule”? A Randomized Controlled Trial of an Educational Intervention with Internal Medicine Residents

BACKGROUNDMedicare has selected 10 hospital-acquired conditions for which it will not reimburse hospitals unless the condition was documented as “present on admission.” This “no pay for errors” rule may have a profound effect on the clinical practice of physicians.OBJECTIVETo determine how physicians might change their behavior after learning about the Medicare rule.DESIGNWe conducted a randomized trial of a brief educational intervention embedded in an online survey, using clinical vignettes to estimate behavioral changes.PARTICIPANTSAt a university-based internal medicine residency program, 168 internal medicine residents were eligible to participate.INTERVENTIONResidents were randomized to receive a one-page description of Medicare’s “no pay for errors” rule with pre-vignette reminders (intervention group) or no information (control group). Residents responded to five clinical vignettes in which “no pay for errors” conditions might be present on admission.MAIN MEASURESPrimary outcome was selection of the single most clinically appropriate option from three clinical practice choices presented for each clinical vignette.KEY RESULTSSurvey administered from December 2008 to March 2009. There were 119 responses (71%). In four of five vignettes, the intervention group was less likely to select the most clinically appropriate response. This was statistically significant in two of the cases. Most residents were aware of the rule but not its impact and specifics. Residents acknowledged responsibility to know Medicare documentation rules but felt poorly trained to do so. Residents educated about the Medicare’s “no pay for errors” were less likely to select the most clinically appropriate responses to clinical vignettes. Such choices, if implemented in practice, have the potential for causing patient harm through unnecessary tests, procedures, and other interventions.

Bedside teaching of clinical reasoning and evidence‐based physical examination

Context and setting Medical school physical examination (PE) education focuses on the acquisition of skills in three domains: psychomotor (motor skills); affective (interaction with examinees), and cognitive (interpretation). To reinforce learning in the cognitive domain, we currently offer an advanced physical diagnosis elective to senior medical students to teach the principles of evidence-based physical examination (EBPE). Why the idea was necessary Recent studies have emphasised a ‘synthetic’ domain: practising doctors must not only recognise findings and understand their evidence-based utility, but must also make optimal management decisions based on these findings. ‘Synthesis’ is rarely taught; rather, students are expected to become adept simply with experience. Consequently, as they make the transition to internship, students may be ill-prepared to apply EBPE in practice. What was done The existing elective includes an introduction to the principles of EBPE. We developed a 3-hour structured bedside rounding session to reinforce key EBPE skills, including: estimation of pre-test probability; recognition of PE findings; evidence-based estimation of post-test probability of the disease, and decision making based on this assessment. For example, in a patient with dyspnoea, elevated neck veins, S3 heart sound and abdominojugular reflux, students decide whether to prescribe diuretics or to order an echocardiogram. Each session is structured as follows: faculty staff preselect two to four patients to examine at the bedside; small groups of three or four students examine the patients and are given feedback by the faculty staff about their examination technique and findings; the students commit to a next step in management, and the faculty staff provide feedback on the students’ decision making. Students answered preand post-elective questionnaires that measured their confidence in their ability to perform EBPE, the perceived utility of PE, and the usefulness of elective activities. Clinical vignettes presenting practice choices were used to assess clinical reasoning. Evaluation of results and impact Three 2-week electives were offered between November 2009 and March 2010. Twenty-one students participated. On a Likert scale of 1–5 (1 = not at all confident, 5 = very confident), students showed increased confidence in: (i) their PE skills in general (mean ± standard deviation [SD] score: retrospective pre-elective 3.38 ± 0.50, post-elective 4.19 ± 0.40; p < 0.05); (ii) understanding the significance of findings (mean ± SD: retrospective pre-elective 2.86 ± 0.57, post-elective 4.23 ± 0.44; p < 0.05), and (iii) making management decisions based on findings (mean ± SD: retrospective pre-elective 2.90 ± 0.87, post-elective 4.57 ± 0.60; p < 0.05). Most students requested that more bedside rounds be included in the elective. Vignettes designed to assess clinical reasoning won high pre-elective scores that did not change appreciably in post-elective testing. Our pilot of structured bedside rounds to teach senior medical students to recognise findings, understand their evidence-based utility and use assessments to make optimal management decisions was well received and valued by students. Students reported increased confidence in making management decisions based on PE findings at the end of the elective. However, improvement in clinical reasoning could not be detected using our assessments, indicating that better calibrated instruments to measure the synthetic domain must be developed.

Twelve tips for teaching evidence-based physical examination

Abstract Background: Practicing evidence-based physical examination (EBPE) requires clinicians to apply the diagnostic accuracy of PE findings in relation to a suspected disease. Though it is important to effectively teach EBPE, clinicians often find the topic challenging. Aims: There are few resources available to guide clinicians on strategies to teach EBPE. We seek to fill that need by presenting tips for effectively teaching EBPE in the clinical context. Methods: This report is based primarily on the authors’ experience and is supported by the available literature. Results: We present 12 practical tips targeting the clinician educator. The first six tips condense key preparatory steps for the teacher, including basic statistics underpinning EBPE. The final six tips provide specific guidance on how to teach EBPE in the clinical environment. Conclusions: By practicing the 12 tips provided, clinicians will develop the confidence needed to effectively teach EBPE in inpatient or outpatient settings.

An advanced quality improvement and patient safety elective

Background:  Practising doctors must be competent in quality improvement (QI) and patient safety (PS). Despite this need, QI and PS have yet to be fully integrated into the undergraduate medical curriculum. Furthermore, there are few resources available for motivated senior medical students to receive advanced training prior to starting residency. To address these needs, we piloted an elective in QI/PS for senior medical students.

Three hospital admissions in 9 days to diagnose azathioprine hypersensitivity in a patient with Crohn's disease.

Azathioprine (AZA) is commonly used as a steroid-sparing immunosuppressive medication for the treatment of immune-mediated disorders including Crohns disease. There is ample awareness of the more common adverse effects of this drug, including myelosuppression and risk of malignancy. We present a case of a 57-year-old man with fistulizing Crohns disease who underwent 3 hospital admissions for recurrent fever with an extensive work-up for infection before the diagnosis of AZA hypersensitivity was made. Clinicians should be vigilant for AZA hypersensitivity as a cause of otherwise unexplained fever. Furthermore, in patients with inflammatory bowel disease (IBD), the signs and symptoms of AZA hypersensitivity may overlap with typical findings of inflammatory bowel disease flare.

Observing bedside rounds for faculty development

Bedside rounds are an ideal opportunity for clinical teaching. We previously offered faculty development on balancing learner autonomy, patient care and teaching. We noticed that participants often asked whether attending physicians and learners shared the same perceptions of the key elements (patient‐centredness, efficiency and educational value) of bedside rounds. Understanding these perceptions and identifying areas of discordance would inform faculty development for optimal bedside rounds.