Covid, medical education, and a bit of RNAi: An opinionated take on NEJM highlights for June 2020

What’s your blood type?

The first report of a genome wide association study of Covid-19 severity on approximately 4000 patients and controls conducted in Spain and Italy identifies a locus on the 3rd chromosome that spans 6 potential genes for which polymorphisms appear to drive severe disease. Once the culprit gene is determined, this may help us think about drug targets. Reassuringly the study also recovers the correlation of severity with blood group that has empirically been noted in the past (on chromosome 9 although the signal is not as strong as that of the chromosome 3 locus). Genomewide Association Study of Severe Covid-19 with Respiratory Failure (open access)


Old people can be asymptomatic too

Though Covid outbreaks on cruise ships were awful for the passengers, they represent wonderful natural experiments on the history and transmission of the disease. In a letter to the editor, a Japanese team reports on asymptomatic cases about the Diamond Princess. Key lesson; although we have heard plenty about age being a major risk factor for severe disease, this does not mean that elderly individuals cannot be asymptomatic. Even worse, they tend to be carriers for longer than younger people – nursing homes beware. Natural History of Asymptomatic SARS-CoV-2 Infection (open access)


Medical education in turmoil

“Step 1”, the national exam that medical students take at the end of their 2nd year which focuses on basic science and medical knowledge rather than clinical skills is changing to pass/fail. Given that the grade for Step 1 was often a major driver of selection for residency programs this has been a source of enormous controversy: residency directors bemoaning the loss of a uniform metric to help pick candidates, whereas other stakeholders have long said that this was an obstacle to more diversity in medicine. But in the end, I think this debate a reflection of the huge stress that has been placed on the unitary perspective of what is a physician. It is increasingly clear that the triple concept of a physician as a learned scientist, a competent professional, and a servant of the community is harder and harder to integrate in a single person. Like it or not, at some point the profession will have to decide internally to split (or it will be done externally, e.g. with NPs) – between scientific medicine, technical / procedural medicine, and social medicine: each with their own set of priority talents and skills, and associated selection criteria.   Grading Changes for USMLE Step 1 — A Golden Opportunity to Recalibrate Medical Education Priorities; The Impact of a Pass/Fail Step 1 — A Residency Program Director’s View; Objective Measures Needed — Program Directors’ Perspectives on a Pass/Fail USMLE Step 1; A Test of Diversity — What USMLE Pass/Fail Scoring Means for Medicine


Echoes from Libby Zion

25 years ago, Libby Zion’s death sparked scrutiny into the very long hours associated with residency training, and reforms as well as studies on what is appropriate shift duration have continued to this day.  The latest addition is a randomized crossover trial in the ICU setting that compared a control schedule including 24 hours shifts to an intervention schedule limiting shifts to 16 hours. Unexpectedly, the control group had a smaller number of serious errors than the limited shift-duration group. The likely explanation: because their hours were less, the shorter shift group had about 25% more patients to manage when on duty. While it’s true that Libby Zion’s physicians were sleep deprived, they were also managing a huge panel of patients but for some reason that has always attracted less attention.  Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts


A treatment for acute intermittent porphyria

Patients with acute intermittent porphyria (a group of disorders of hemoglobin synthesis) are frequent flyers to the hospital with regular flare ups of their disease causing a heterogeneous set of debilitating symptoms for which there was limited treatment options. Givosiran (Givlaari, Alnylam), an RNAi was recently approved and now the full phase 3 write-up is out.  Top-line, givosiran reduced the incidence of major symptoms by about 75%. The only cloud on an otherwise glorious clinical picture, a safety signal in kidney and hepatic function which will likely not limit uptake, but may lead a number of patients not to stay on therapy. List price: 575k/yr  Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria; Givosiran — Running RNA Interference to Fight Porphyria Attacks


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.

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