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Stunting and the microbiome Stunting (low growth for age) affects > 20% of children across the globe and has major impact on the brain, on health, and on opportunities for success in life. The precise mechanism of stunting has remained elusive. Sanitation and diet diversity play a role but targeted interventions in these areas have had less impact than hoped for. Jeff Gordon from WashU has spent the last decade exploring the relationship between stunting and the microbiome, and now his group reports on a study that shows a clear correlation between certain microbe populations in the gut and stunting… Read More

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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). Read More

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Remdesivir works… but not enough to change the public health perspective The eagerly awaited results of the remdesivir NIH trial are out, and it’s solid but not smashing, although this is a partial read since the study was interrupted before completion because of evidence of benefit (and we should get more data in the coming months).  Overall, the primary end-point of faster improvement in the treatment group was met while mortality showed a benefit that was just short of statistical significance. Also important is that remdesivir is clearly safe. But there is a lot more to digest in the data… Read More

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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… Read More

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A first Covid-19 interventional study – unfortunately negative The first of what promises to be a series of many interventional studies for acute Covid-19 disease to appear in the Journal. Lopinavir is an HIV drug that had shown in-vitro activity against SARS, another corona virus, and ritonavir is a drug that boosts lopinavir concentration by reducing its rate of metabolization – so it was worth trying the combo in sick patients with Covid-19.  The study was clearly conducted in quasi-battlefield conditions in one of Wuhan’s main hospital from mid-January to mid-February 2020. Many corners were cut for speed and efficiency,… Read More

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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… Read More

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The loneliness of the patent-less drug Colchicine is a very old drug commonly used in gout with an anti-inflammatory mechanism of action that is not well defined. It is a generic (although in the US, the story is somewhat peculiar) and therefore incentives are lacking for further development in new indications by private companies. Given a well-established (but not well-understood) connection between inflammation and cardiovascular events, some researchers have hypothesized and explored potential utility in patients with high cardiovascular risk – but this would have to be validated by a robust, large, expensive, randomized-controlled trial. Thanks to the Canadian… Read More

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A triumph for cystic fibrosis patients (and for Vertex) Phase 3 confirmation that the benefits seen in early trials from triple-combination therapy of elexacaftor, tezacaftor, and ivacaftor, are sustained and applicable to 90% of the cystic fibrosis patients.  Every metric is unambiguously better: sweat chloride concentration, forced expiration volume (FEV1), respiratory symptom questionnaire, pulmonary exacerbations (down 60%), hospitalizations (down 70%). If anything, with 400 subjects, the study was probably overpowered by at least a factor of 4 to show effect.  It is great news for CF patients most of whom are likely to live a quasi-normal life if they… Read More

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Genomic applications and scalability Two very different papers about applications of genomics, one for a very common clinical scenario, the other for an ultra-rare disease. It is well known that while clopidogrel (now available as a generic but branded as Plavix) is an excellent antiplatelet agent for a majority of patients, it works poorly in some due to individual genetic idiosyncrasies of cytochrome driven drug metabolism. Since then, other agents (tigracrelor AKA Brilinta, prasugrel AKA Effient) with a similar mechanism of action but more consistent metabolism have come on market, but they are very expensive. Given that we can now… Read More

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Best care vs. good care In wealthy countries, the recommended standard of care can often lead to complex medication regimens requiring frequent follow-ups: this can be very challenging for people who though they live in wealthy countries but are poor themselves. In developing countries, efforts have been made to prioritize simplicity and population level impact through one-size fits all polypill interventions, but that has not been tested in the US. Here the authors report on a randomized study including 303 individuals living in poverty and at risk for cardiovascular disease. The active arm was provided with a daily polypill combining… Read More