Covid and the rest: An opinionated take on NEJM highlights for April 2020


Hydroxychloroquine does not seem to help much in Covid-19 (with caveat)

There has been significant attention to the use of the antimalarial hydroxychloroquine in Covid-19, but data on impact has been scarce. In the absence of clarity, New York Presbyterian Hospital left the use of this drug to the discretion of individual treating physicians from mid-March to early April. This has led to two cohorts of Covid-19 patients which can be compared in retrospective analysis: patients treated with hydroxychloroquine (N=811) and those who did not receive the drug (N=565).   The challenge is that since there is no randomization, there is selection bias: patients treated with hydroxychloroquine tended on average to be somewhat sicker at presentation that those who were not so that the fact that that the treatment group had a 32% risk of intubation or death vs. 15% in the other group is not at all dispositive.  But there are statistical tools to correct this result for illness severity – and using them shows little difference between treatment and no treatment (i.e. the hazard ratio is close to 1). The final answer will require the results of a prospective randomized trial, but with what we have so far, the benefit of hydroxychloroquine in Covid-19, if there is any, is not likely to be large. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 (free access)


Cloak-and-dagger for face masks

An interesting read on the efforts of an executive to secure PPE for his health system. Involves a warehouse meeting, disguised trucks, and the FBI.  In Pursuit of PPE (free access)


A drug with promise for the negative symptoms of schizophrenia

Antipsychotics used in schizophrenia have a tremendous impact on positive symptoms of the disease: hallucinations and delusions. However, they do not improve the so-called negative symptoms: apathy, anhedonia, and cognitive deficits. This is why it is so exciting that for the first time, an investigational drug is showing an effect (SEP-363856, Sunovion) on positive and negative symptoms in a placebo-controlled trial of 4 weeks duration. Promising, but still early days – an on-going 1-year phase 3 trial with active control will tell us more.  The other interesting feature of this particular drug is the strategy that led to its identification. Essentially all antipsychotic drugs are active at dopamine D2 receptors with a variety of additional characteristics on top – but instead Psychogenics / Sunovion performed a screen looking for compounds with the requirement that they should have D2 blocking like effects in vivo and in vitro without interaction with the D2 receptor – in effect, screening for phenotypic effects that approximate the known target without actually engaging that target. That search identified SEP-363856 and further analysis shows that it acts at TAAR1, a receptor upstream of dopaminergic pathways, and has luck has it, seems to have impact on the negative symptoms which would be a clear differentiator from existing D2 drugs.   It’s a clever approach and one that could potentially be replicated for a number of validated targets to find new targets with a higher benefit / risk ratio: A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia; Promising Evidence of Antipsychotic Efficacy without Dopamine D2-Receptor Binding


PT for OA

For many musculoskeletal afflictions, optimal treatment is unclear and tends to be swayed by individual practitioner preference and incentives rather than hard data. Here a study comparing intra-articular steroid injections to physical therapy (PT) for a painful knee with radiographic evidence of osteoarthritis (OA) showed that doing PT first was superior from 1 month to 12 months of presentation. What I found striking is that there is not a single orthopod or even MD among the 10 authors of the study paper and the accompanying commentary (they are all PT trained).  But it is probable that they will be well represented among letters to the editor pointing out limitations of this work… Physical Therapy versus Glucocorticoid Injection for Osteoarthritis of the Knee; Physical Therapy before the Needle for Osteoarthritis of the Knee


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.