An opinionated take on NEJM highlights for the second quarter of 2023

Preparing for the next pandemic: don’t waste the value of waste

During the Covid-19 pandemic, I got in the habit of checking weekly the Boston sewage report, as a reliable, unbiased way of monitoring trends of infectious activity. There is clearly much more information to extract from waste monitoring and a recent report from the National Academies of Sciences, Engineering, and Medicine makes a number or recommendations. The CDC is implementing some of them, but in the end, exploiting this source of information will depend on 100s of local actors (public health departments, water utilities etc.) and orchestrating that is no small endeavor. Mainstreaming Wastewater Surveillance for Infectious Disease


Preventing RSV in infants

RSV has been a hot topic recently with the approval of several vaccines for older adults. However RSV is also a huge burden in children.  Many young children end up hospitalized with RSV each winter, but it is for infants (<1 year old), especially those with other health issues like prematurity, that consequences may be especially dire.   Since we do not have a pediatric vaccine, the protective alternative is antibody infusions which have been effective but are expensive and cumbersome. An alternative presented here is to immunize the mother during gestation so that she will pass on antibodies to the fetus and generate protective immunity for the first months of life. And it works! In a blinded placebo-controlled randomized study of the Pfizer vaccine (same as recently approved for older adults), vaccination reduced the risk of RSV-related hospitalization by a factor of 3.  An Advisory Committee gave a positive review last May and we are now waiting for the FDA decision which will hinge on whether a non-statistically excess of premature birth in the vaccinated is a cause for concern that outweighs the benefit.  Given the short lifetime of maternally transmitted antibodies, this is not likely to be a replacement for antibody prophylaxis in high-risk newborns, but will hopefully decrease the burden of RSV in the general infant population. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants


PD-1 in autoimmune disease

Stimulating anti-cancer immune responses through the blockade of the PD-1 pathway was arguably the biggest breakthrough in therapeutic oncology in the 2010s (though CAR-Ts would be a close second).  Now some are trying to flip the concept on its head in the context of autoimmune disease by stimulating that same pathway to down-regulate T-cell activation. A small (N=98) 12-week trial in rheumatoid arthritis (RA) of Peresolimab (Eli Lilly), a mAb agonist of PD-1, shown a significant reduction of symptoms in the treated arm relative to placebo.  The concept is intriguing, but long-term studies are clearly going to be key – the story of RA and other autoimmune diseases is littered with agents that were great short term, but had serious long-term consequences, and in this case, oncogenesis is an obvious concern. A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis


The ED is a mess

Most issues of the NEJM include an interesting case report, this one goes like this: “The patient was deemed to be high risk for harm… Transfer to an inpatient psychiatric hospital was requested, but no beds were available at any facility in the region… On day 41(!) in the acute psychiatric service of the emergency department, agitation developed…” This is illustrative of the fact that most EDs in the US are now swamped with boarders. It is not a reflection of increased inflow (Urgent Care centers are now an established destination for patients with minor issues), it is a reflection of decrease outflows with staffing shortages across the inpatient healthcare system (acute hospitals, psychiatric hospitals, skilled nursing facilities), and of all inpatient components, the ED is the one and only element that by law cannot say “no”, therefore it is where patients pile up.  If you’d like to read more, I recommend this plea to president Biden from a variety of professional societies. Case 16-2023: A 13-Year-Old Boy with Depression and Hypotension


An alternative for accelerated treatment of major depression

Major depression is a truly horrible state of being; standard pharmacological therapy takes weeks for effect, and when the first round of therapy fails, and it is on to the second round, we are now talking months spent feeling awful. There is an effective and safe alternative in the form of electroconvulsive therapy (ECT), but it comes with a heavy overlay of stigma, and occasional side-effects of some memory loss. Over the last decade, ketamine, a dissociative (and at high dose psychedelic) anesthetic has been explored as a rapid treatment including the recent approval of intranasal esketamine (Spravato, Janssen). At the same time a number of ketamine infusion clinics have sprung up but until now, we did not have a clear comparison: what works better: 3 weeks of ketamine infusions or 3 weeks of ECT therapy? Thanks to a randomized study sponsored by our own PCORI, we now have the answer: it’s about the same with a slight edge to ketamine infusions. But possibly, the most interesting data point of the study is this: of the 200 patients randomized to ketamine, 4 did not show up for their infusions; of the 203 patients randomized to ECT, 31 did not show up for treatment. Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression


The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this series we offer an opinionated perspective on selected highlights that might be of interest to our clients and others.

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