Category: NEJM Highlights

Recon takes an analytical look behind select developments in healthcare

A slow summer: An opinionated take on NEJM highlights for August 2020

A cheap, low tech intervention for a common Achilles’ heel When I am out and about, for instance at the grocery store, I am always surprised at the number of people I see with swollen legs. About half a million times a year in the US, these folks end-up in a hospital bed with cellulitis (a skin and subcutaneous infection) of the leg. In a single center randomized trial with 84 patients who had an episode of cellulitis, an Australian group tested whether compressive stockings would make a difference in

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An opinionated take on NEJM highlights for July 2020

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

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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

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Covid, iPSCs, and ADCs: An opinionated take on NEJM highlights for May 2020

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

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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

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The infectiologists have the floor: An opinionated take on NEJM highlights for March 2020

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

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

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

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Tax dollars doing good work: An opinionated take on NEJM highlights for December 2019

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

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An opinionated take on NEJM highlights for November 2019

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

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An opinionated take on NEJM highlights for October 2019

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,

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An opinionated take on NEJM highlights for September 2019

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.

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Busy summer: An opinionated take on NEJM highlights for July/August 2019

Is the lack of new (non-viral) antibiotics a market failure? A lament about the lack of success in getting the biopharma industry to invest sustainably in the development of new antibiotics against highly-resistant organisms, and a recommendation “it is time to seriously consider the establishment of nonprofit organizations for developing these lifesavings drugs”.  Let’s be clear; the reason economic viability of this therapeutic area is problematic is due to three confluent factors: (1) treatment is curative – i.e. does not provide recurrent revenues (2) the targeted population is small (3)

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Fishing for nucleic acids: An opinionated take on NEJM highlights for June 2019

Huntington’s disease: light at the end of the tunnel? The awful thing about Huntington’s is that in most cases, people know they are going progressively lose their mind at an early age, but there is absolutely nothing they can do about it.  Recently there has been tremendous excitement around suppressing toxic huntingtin production in the brain by using antisense oligonucleotides (ASOs) administered intrathecally (i.e. in the cerebrospinal fluid through the spine). Two ASOs are in full blown clinical testing: HTTRx (Ionis and Roche) which does not discriminate between mutant and

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An opinionated take on NEJM highlights for May 2019

TAVR for all? TAVR has become the standard of care for patients who need an aortic value replacement but are at high/medium surgical risk.  But what about those at low-risk? Two studies answer that question, one with the Edwards device and the other with Medtronics. Both show that TAVR is superior along a number of end-points (stroke, hospitalization duration, atrial fibrillation) both at 30 days and at 1-2 year. Long-term outcomes remain a question though. Low-risk patients are younger (mean age 73-74) and will live with their valves longer, which

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It’s in the brain: An opinionated take on NEJM highlights for April 2019

He’s dead, Jim As previously widely advertised, the BACE-1 inhibitor verubecestat (Merck) (and in journal correspondence atabecestat, Janssen) has now failed in a population with very early signs of cognitive impairment (this after a failure of those agents in mild-moderate Alzheimer’s). Target engagement clearly occurred with a decline of the amyloid detected through PET imaging in the treatment arms and an increase in the placebo arm. However, if anything, cognition declined more in the treatment arm than in the placebo arm after 2 years on study. A silver lining is

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An opinionated take on NEJM highlights for March 2019

Target assessment with genetic polymorphisms Please bear with me for a long (but interesting!) story. Bempedoic acid (Esperion) is an inhibitor of ATP citrate lyase (ACLY), an enzyme in the cholesterol synthesis pathway (upstream of HMG-CoA reductase, the target of statins). In a study of 2,230 patients at high risk for cardiovascular events, on maximum statin therapy, and LDL > 70 (basically the PCSK9 target population), bempedoic acid was well tolerated and lowered the LDL by around 16% – a substantial effect. This would potentially position bempedoic acid, an oral

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February was short and cold: An opinionated take on NEJM highlights for February 2019

Targeted conjugated cancer therapeutics – so few, but may be more soon The idea that one could combine the precision of a targeted biologic with the potency of a traditional cytotoxic to demolish a tumor has been around for decades, but with very rare exceptions, has not had the level of traction one would have expected.  But this month, the journal has two studies reporting on these types of therapies, both in breast cancer. One shows that in a group of heavily pre-treated triple-negative breast cancer patients, sacituzumab govitecan-hziy (Immunomedics)

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Methods towards better care: An opinionated take on NEJM highlights for January 2019

The bundle Unlike many other CMMI experiments, the Comprehensive Care for Joint Replacement (CJR) program was a true randomized control trial in that participation was mandatory in a selection of metropolitan areas and not allowed anywhere else, which allows for an analysis untainted by self-selection bias. In brief the question to be answered was does a 90-day bundled payment for a joint replacement (knee/hip) get better value (improved care and/or lower costs) than the traditional FFS approach? A differences of differences analysis comparing the bundled vs. control arms before and

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On the uses of genetic information in disease: An opinionated take on NEJM highlights for December 2018

Genetic trade secrets In 2012, the US Supreme Court decided a case known as “Prometheus” establishing that therapeutic methods based on biomarkers were not patentable – this essentially blocked one of the two main avenues to monetizing intellectual property from the very hard clinical work of figuring out personalized medicine, i.e. what works for whom. The other avenue that would remain is that of trade secrets, and I for one, have been waiting for the other shoe to drop.  A hint comes from a study on ovarian cancer just published

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Eating your way out of disease: An opinionated take on NEJM highlights for November 2018

Peanut medicine that won’t cost peanuts Allergy to peanuts is a major issue and though prevention is now possible in infants there is a huge population for whom actual survival is connected to vigilance in what they consume and availability of epi-pens. Desensitization to allergens is a well-established method to overcome an allergy, but it is typically done through injections, and it requires well calibrated micro-doses of the allergen.  Aimmune has been pursuing an oral approach with progressive dosing with peanut protein (AR101) and in a phase 3 trial, two

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