Coronavirus and more: An opinionated take on NEJM highlights for January/February 2020

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Keeping up with COVID-19

It’s not easy for a refereed weekly print periodical to keep up with an epidemic that evolves on a daily basis, but the NEJM is doing its best and all articles are free on-line. Most interesting beyond the description of the initial cluster in Wuhan are: (1) the first US case was quite severe and the patient received the antiviral remdesivir (was in development by Gilead for Ebola, but showing activity against coronaviruses) – it is now in testing in China; (2) the rigorous documentation of disease transmission by an asymptomatic individual to another in Germany (which will make control of spread all the more difficult).  A Novel Coronavirus from Patients with Pneumonia in China, 2019; First Case of 2019 Novel Coronavirus in the United States; Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany (all free access)

 

The limitations of hotspotting

In most populations, a small fraction (<5%) of individuals drives the majority of healthcare utilization at any given time. This is true for disadvantaged populations where beyond pathophysiology, social determinants are known to be important drivers – and this has led to the idea that if we could only engage on those drivers (housing, transportation, counseling, etc.) with high utilizers, this might result in considerable health benefits as well as overall savings. A lot of interventions have been tried and published on this, but most of them lack a true control group – the comparison is one of “before” and “after” the intervention. To their credit, the Camden Coalition and their external partners have done a rigorous job testing their care transition model targeted to poor super-utilizers with high social and medical needs and comparing it to a similar, contemporaneous control group who received no intervention. What the data show is that the intervention group improved significantly post enrollment – but so did the control group in a way that was statistically equivalent.  This illustrates how, while it is true that any given time a few individuals are super-utilizers, many of them regress toward the mean over the next few months and are replaced by others, or in other words, “super-utilizer status is not sticky”. To have full value from supportive interventions, you have to intervene earlier – and this requires predicting with some accuracy who might become a super-utilizer, which is hard to do… Health Care Hotspotting — A Randomized, Controlled Trial

 

Long(er)-term efficacy of gene therapy in hemophilia A

The hope of gene therapy in congenital genetic disease is that it is “one and done”.  Value/pricing rides on this, and also in the case of an AAV vector “one and no redosing” is probably the reality given immunogenicity concerns.  Even as this approach matures, there remains lot of interest in long term follow-up of the very first cohorts who have received gene therapy. Here, BioMarin reports on their phase 1/2 cohort 3 years from treatment, and the takeaway is that there is sustained efficacy with minimal bleeding events and need for infusion of exogenous Factor VIII. Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A

 

BTR CRISPR

An article on the implications of basic research emerging from David Liu’s lab at the Broad which has improved on CRISPR technology through what is now getting known as “prime editing”. The advance is a true single package capability that allows the insertion of DNA sequences at specific locations of the genome. This is achieved through two new elements compared to usual CRISPR technology: the RNA guide now is prolonged with (further down the sequence) an RNA complementary template for the sequence that needs to be inserted, and a reverse transcriptase is fused to Cas9.  So what happens now is that after Cas9 nicks the cellular DNA at the desired location, the reverse transcriptase creates the desired DNA sequence from the RNA template and it is inserted in the cellular DNA.  This is certainly not the last innovation in this domain but very much points the way toward a future where editing genetic code becomes completely straightforward. Prime Time for Genome Editing?

 

Arbitrary medicine

An interesting letter to the editor about an analysis of the management of patients who have a myocardial infarction 2 weeks before their 80th birthday vs. 2 weeks after. It shows a big discontinuity in clinical care when really, there is not a guideline or other evidence to warrant that. We need a way more sophisticated system of decision support than the gut feeling of clinician based on the left-most digit of the age number. Behavioral Heuristics in Coronary-Artery Bypass Graft Surgery

 

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.