An opinionated take on NEJM highlights for September 2016


Taking a page from HIV to build a response to opioid abuse

A couple of perspectives on the challenges of treating individuals who suffer from opioid dependence. The first highlights the importance of integrating medication assisted treatment (e.g. methadone or buprenorphine) into hospital and post-hospital care – plausibly an ED visit or a hospital stay for an event triggered by opioid abuse (such as an overdose) is a significant opportunity to go beyond treating the acute issue and starting patients on long term treatments. In the second, the author recalls the tremendous progress in treating HIV/AIDS in the early 90s contemporaneous to the creation of what essentially became an HIV subspecialty within medicine, and proposes doing the same in the field of opioid abuse. Those pleas ring true and will help if heeded, but one can still be somewhat skeptical of what amounts to the aggressive medicalization of an issue that is after all highly correlated with social determinants.  Social work and public health have always been the poorer cousins of clinical medicine.  Is the time ripe for the birth of a true discipline of “social medicine”, with standardized training, certification requirements, and rigorous published body of evidence like it happened for clinical medicine, more than a century ago with the Flexner Report?  Putting Parity into Practice — Integrating Opioid-Use Disorder Treatment into the Hospital Setting (subscription access); From AIDS to Opioids — How to Combat an Epidemic (free access)


Hospitalists and the fragmentation of care

It is almost hard to remember that there was a day when your doctor would come to the hospital, examine you, and write orders – in the US at least, times have changed. Two perspectives on the rise of hospitalists analyze the impact of this shift, one celebrating the improvement in efficiency and objective quality metrics, the other ruing the loss of longitudinal continuity in patient care.  The trend is showing no sign of slowing with the patient-physician relationship gradually morphing into a purely transactional experience. Does this have an impact on long term health outcomes? – I am not so sure; but psychologically, it’s the difference between eating at McDonald’s or at the local family owned restaurant. Zero to 50,000 — The 20th Anniversary of the Hospitalist; Hospitalists and the Decline of Comprehensive Care (free access)


Evidence that CPAP does not prevent cardiovascular events

In tandem with obesity, obstructive sleep apnea (OSA) prevalence has been increasing. Numerous observational studies have shown a correlation between OSA and a higher rate of vascular events (e.g. MI, stroke), as well as a reduction of events in patients with OSA treated with CPAP (continuous positive airway pressure).  Correlation is not causation but nevertheless, millions of patients have been prescribed CPAP at least partially on the grounds that it could prevent heart attacks and strokes.   To explore this, the SAVE study randomized 2700 patients with OSA and with diagnosed cardiovascular or cerebrovascular disease to CPAP vs. usual care, and followed them for about 4 years.  There was no difference in vascular events between the groups. Given the amount of money spent on a veritable industry of sleep-labs and durable medical equipment providers of CPAP machines, this is a highly valuable study for the health system. CPAP may be useful in decreasing daytime sleepiness and quality of life, but what this study tells us is that a person with OSA and minimal day-time symptoms does not need CPAP.  Will providers change their approach? – One hopes so.  CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea; Cardiovascular Events in Obstructive Sleep Apnea — Can CPAP Therapy SAVE Lives? (subscription access)


Factor Xa inhibitors get their reversal agent too

The advent of a new generation of effective fixed dose oral anticoagulants to replace warfarin was tempered by the fact that it was not possible to rapidly reverse their effect in situations where there was bleeding.  Last year, an antidote to the thrombin inhibitor dabigatran (Pradaxa Boehringer Ingelheim – BI) came to market, but the several Factor Xa inhibitor agents (Xarelto, Eliquis, and others) were left out in the cold. No more, in a study of 67 patients with bleeding, Portola Pharmaceuticals was able to show good efficacy of their agent Andexanet Alfa, which should secure approval. An interesting angle is that in the case of the thrombin inhibitor, both the anticoagulant and the antidote are owned by BI, whereas for Factor Xa inhibitors, anticoagulants and the antidote are owned by different companies. I’ll be curious to see how this plays out in the pricing.  Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors; Engineering Reversal — Finding an Antidote for Direct Oral Anticoagulants (subscription access)


An example of an EHR-based pragmatic trial

COPD patients are typically managed in primary care, and so trials which are conducted through specialized centers don’t reflect real life. In this study of the combined inhaler Relvar/Breo (GSK) vs. usual care, about 4000 patients in the area south of Manchester were enrolled, randomized, and followed by their primary care practices with data largely collected through the EHR system.  It’s an appealing model and the implementation as presented in the Journal is convincing. The combined inhaler improved outcomes in a statistically and clinically significant way. The only missing piece of information about which I am really curious is how much did this study cost, and how does the cost compare to that of a more traditional trial.  Effectiveness of Fluticasone Furoate–Vilanterol for COPD in Clinical Practice (subscription access)


Sometime all you need are the bear necessities

Drug eluting coronary stents were hallowed as a major advance when they came on the market on the basis of short term clinical studies, but the question has remained open on their longer term impact compared to the previous standard of bare metal stents. A 5-year Norwegian study provides the answer and it is “not much”. Death and myocardial infarction occurred at indistinguishable rates between the drug-eluting stent group and the bare stent group, but there was a difference in the rate of “redo” procedures needed (10% vs. 5%). More interesting was the study process which tried to enroll EVERY Norwegian patient in need of a coronary stent (enrollment achieved 72.5%) and followed them through the Norway health system. This shows the investigative power of a comprehensive health system in which there is a relatively minimal patient flow in and out. Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease; Balancing the Evidence Base on Coronary Stents (subscription access)


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.