Diagnostic utility of transcriptome sequencing for rare Mendelian diseases.

PURPOSE: We investigated the value of transcriptome sequencing (RNAseq) in ascertaining the consequence of DNA variants on RNA transcripts to improve the diagnostic rate from exome or genome sequencing for undiagnosed Mendelian diseases spanning a wide spectrum of clinical indications. METHODS: From 234 subjects referred to the Undiagnosed Diseases Network, University of California-Los Angeles clinical site between July 2014 and August 2018, 113 were enrolled for high likelihood of having rare undiagnosed, suspected genetic conditions despite thorough prior clinical evaluation. Exome or genome sequencing and RNAseq were performed, and RNAseq data was integrated with genome sequencing data for DNA variant interpretation genome-wide. RESULTS: The molecular diagnostic rate by exome or genome sequencing was 31%. Integration of RNAseq with genome sequencing resulted in an additional seven cases with clear diagnosis of a known genetic disease. Thus, the overall molecular diagnostic rate was 38%, and 18% of all genetic diagnoses returned required RNAseq to determine variant causality. CONCLUSION: In this rare disease cohort with a wide spectrum of undiagnosed, suspected genetic conditions, RNAseq analysis increased the molecular diagnostic rate above that possible with genome sequencing analysis alone even without availability of the most appropriate tissue type to assess.

Eradicating medical student mistreatment: a longitudinal study of one institution's efforts.

PURPOSE: Since 1995, the David Geffen School of Medicine at UCLA (DGSOM) has created policies to prevent medical student mistreatment, instituted safe mechanisms for reporting mistreatment, provided resources for discussion and resolution, and educated faculty and residents. In this study, the authors examined the incidence, severity, and sources of perceived mistreatment over the 13-year period during which these measures were implemented. METHOD: From 1996 to 2008, medical students at DGSOM completed an anonymous survey after their third-year clerkships and reported how often they experienced physical, verbal, sexual harassment, ethnic, and power mistreatment, and who committed it. The authors analyzed these data using descriptive statistics and the students' descriptions of these incidents qualitatively, categorizing them as "mild," "moderate," or "severe." They compared the data across four periods, delineated by milestone institutional measures to eradicate mistreatment. RESULTS: Of 2,151 eligible students, 1,946 (90%) completed the survey. More than half (1,166/1,946) experienced some form of mistreatment. Verbal and power mistreatment were most common, but 5% of students (104/1,930) reported physical mistreatment. The pattern of incidents categorized as "mild," "moderate," or "severe" remained across the four study periods. Students most frequently identified residents and clinical faculty as the sources of mistreatment. CONCLUSIONS: Despite a multipronged approach at DGSOM across a 13-year period to eradicate medical student mistreatment, it persists. Aspects of the hidden curriculum may be undermining these efforts. Thus, eliminating mistreatment requires an aggressive approach both locally at the institution level and nationally across institutions.

Numerical Versus Pass/Fail Scoring on the USMLE: What Do Medical Students and Residents Want and Why?

BACKGROUND: Although the primary purpose of the US Medical Licensing Examination (USMLE) is assessment for licensure, USMLE scores often are used for other purposes, more prominently resident selection. The Committee to Evaluate the USMLE Program currently is considering a number of substantial changes, including conversion to pass/fail scoring. METHODS: A survey was administered to third-year (MS3) and fourth-year (MS4) medical students and residents at a single institution to evaluate opinions regarding pass/fail scoring on the USMLE. RESULTS: Response rate was 59% (n  =  732 of 1249). Reported score distribution for Step 1 was 30% for <220, 38% for 220-240, and 32% for >240, with no difference between MS3s, MS4s, and residents (P  =  .89). Score distribution for Step 2 Clinical Knowledge (CK) was similar. Only 26% of respondents agreed that Step 1 should be pass/fail; 38% agreed with pass/fail scoring for Step 2 CK. Numerical scoring on Step 1 was preferred by respondents who: (1) agreed that the examination gave an accurate estimate of knowledge (odds ratio [OR], 4.23; confidence interval [CI], 2.41-7.43; P < .001); (2) scored >240 (OR, 4.0; CI, 1.92-8.33; P < .001); and (3) felt that acquisition of knowledge might decrease if the examination were pass/fail (OR, 10.15; CI, 3.32-31.02; P < .001). For Step 2 CK, numerical scoring was preferred by respondents who: (1) believed they gained a large amount of knowledge preparing for the examination (OR, 2.63; CI, 1.52-4.76; P < .001); (2) scored >240 (OR, 4.76; CI, 2.86-8.33; P < .001); (3) felt that the amount of knowledge acquired might decrease if it were pass/fail (OR, 28.16; CI, 7.31-108.43; P < .001); and (4) believed their Step 2 CK score was important when applying for residency (OR, 2.37; CI, 1.47-3.84; P < .001). CONCLUSIONS: Students and residents prefer the ongoing use of numerical scoring because they believe that scores are important in residency selection, that residency applicants are advantaged by examination scores, and that scores provide an important impetus to review and solidify medical knowledge.