An opinionated take on NEJM highlights for June 2018


It’s hard to quit (and E-cigs don’t help)

A large trial (6000 participants) comparing free cessation support, e-cigarettes, and a $600 cash incentive for sustained abstinence shows that none of these approaches are particularly effective with 1-3% overall success rates depending on the arm.  Prevention is where it’s at. A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation (free access)


NPs and PAs numbers are growing fast

A look back at the last 15 years and forward to the next 15 shows that the physician workforce is growing at about ~1% per year while mid-level practitioners (NPs and PAs) are growing at ~5% per year. By 2030 the combined number of NPs and PAs will be more than half that of physicians. Several trends are behind that chief among them the abandonment by docs of primary care and rural areas, as well as the cost differential: it takes a lot more money and time to produce a doc than an NP or a PA and that is reflected in their compensation. Finally as algorithmic medicine grows, the culture and expectations of mid-level practitioners are better-suited to the function of following guidelines and decision support. Growing Ranks of Advanced Practice Clinicians — Implications for the Physician Workforce (subscriber access)


Progress against refractory asthma

Dupilumab (Dupixent, Sanofi/Regeneron) is part of a slate of recently approved biologics for asthma (although the others target the IL-5 pathway whereas dupilumab targets IL-4). A pair of placebo-controlled trials of subcutaneous dupilumab every two weeks in a patient population with poorly controlled asthma showed that the treated group needed significantly less systemic steroid therapy, saw their exacerbation rate drop by half, and had objective improvement in lung function. It does not work for everyone, but for those who respond, this allows for a highly significant improvement in their health status, although at a cost of about $3000/month which will make the determination of who is a responder vs. who is not a significant a thorny question.  Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma; Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma; New Biologics for Asthma (subscriber access)


After CAR-T, CAR-V?

We all know that poliovirus has a pathogenic effect on the nervous system. It also has affinity for the CD155 receptor that is over-expressed in many solid tumor types. This has led a group of scientists at Duke (some of whom are now at recently formed Istari Oncology) to try to exploit this characteristic to address the worst form of brain cancer (glioblastoma multiforme aka GBM). In a single arm study they treated 61 patients with recurrent GBM (meaning quasi end-of-the-line cases) by instilling a modified poliovirus (PVSRIPO) directly into the tumor (through a catheter piercing the skull). They did a comparison with historical controls rigorously selected to match the studied population with some remarkable findings. First, the survival curves for the first 18 months are virtually identical but then, while the control group continues to die, a subset of about 20% of PVSRIPO treated patients seems headed for long-term survival. Second, in that subset, a number of patients had local recurrences, but treatment with standard chemotherapy agents was extraordinarily effective leading to a complete response which is hardly ever the case for GBM.  While the virus appears to kill some tumor cells, there are indications that it also stimulates an immune response to the tumor and that is a major element of the anti-tumor effect in patients who respond.  Recurrent Glioblastoma Treated with Recombinant Poliovirus; Exploiting Viruses to Treat Diseases (subscriber 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.