Alex Nowbar reviews the latest research from the top medical journals

The business of bundles in sepsis

A new study from the US looked at the effect of a sepsis management bundle on treatment and patient outcomes. The longitudinal study of repeated cross-sectional cohorts within 11 hospitals in one integrated US healthcare system looked at data from two years before adherence to the sepsis bundle had to be reported to Medicare to two years after. These are observational data with a historical comparison rather than a contemporaneous control group, so changes cannot be attributed to reporting of bundle adherence. However, the finding was that rates of early lactate measurement and, somewhat more moderately, antibiotic administration increased over time, but rates of death and discharge to home didn’t change. The authors suggest revising the sepsis bundle measure, but I am not hopeful for that being more effective. There may not be scope to improve outcomes further using a bundle because outcomes may be limited by other factors—such as staffing levels or the fact that, even when all elements of a bundle are adhered to, sepsis still causes adverse outcomes.

Ann Intern Med doi:10.7326/M20-5043

Hospital at home for people over 65 with frailty

I don’t think I’ve ever said this before, but I’m in love with a trial. It’s a large randomised trial, set in the UK. The study population is a critical one—older people. The primary outcome is a relevant one—living at home six months down the line. And the intervention is something that does get used, but hadn’t been properly tested until now. Now we can be confident that “admission avoidance hospital at home” (provision of hospital level care with comprehensive geriatric assessment) had similar outcomes to hospital admission. This shows there is an alternative option to admission in these patients. The problem possibly requiring admission was usually infection, but falls and COPD were also common, and most of the participants had a degree of cognitive impairment.

Ann Intern Med doi:10.7326/M20-5688

Magic mushrooms for depression?

Psilocybin was compared with escitalopram (a selective serotonin reuptake inhibitor) in a six-week double-blind randomised trial of 59 people with moderate to severe depression. It was intended to be exploratory and look at efficacy and mechanisms, but I’m not sure it provided much evidence of either. The functional MRI data were not reported here. Patients were highly selected (no comorbid psychiatric conditions, no immediate family or personal history of psychosis, and no history of serious suicide attempts). They had to have not used escitalopram before, but more than a quarter of participants had used psilocybin before. The study found similar reductions in depression scores in both groups. With no placebo group, it’s impossible to know if these effects were placebo effects in both groups (or simply the effect of the psychological support both groups received). This trial was short—the natural course of depression means we should be looking for sustained response, and six weeks doesn’t give escitalopram time to work. Blinding was also an issue: the psychedelic effect of psilocybin and the known side effects of escitalopram meant that patients could easily guess which group they were in, thus biasing the outcome measure (guessing the treatment arm could also have affected the clinician-rated assessment of depression).

N Engl J Med doi:10.1056/NEJMoa2032994

Covid-19: single dose vaccine effective

The Ad26.COV2.S vaccine (Johnson & Johnson vaccine) was found to prevent moderate to severe covid-19 with onset at least 14 days after administration with 67% efficacy, and up to 77% for severe infection alone in the double-blinded randomised Ensemble trial. It was conducted in eight countries worldwide, including Brazil, US, and South Africa. A reasonable level of efficacy was seen against the South Africa variant of SARS-CoV-2. Aside from needing only a single dose for vaccination, the vaccine can be stored in a standard freezer for up to two years and up to three months in a fridge, making it more accessible. And efficacy against symptomatic disease was demonstrated across age groups.

N Engl J Med doi:10.1056/NEJMoa2101544

Treating vaso-occlusive episodes in sickle cell disease

Casella and colleagues performed a randomised trial in 388 children and adults across 66 hospitals comparing intravenous poloxamer 188 (a nonionic block polymer surfactant, whatever that is) with placebo in a double-blind fashion. The aim was to shorten the duration of vaso-occlusive episodes, supposedly by reducing blood viscosity and improving microvascular blood flow. The effect was judged by the time to the last dose of parenteral opioids. There was no evidence of benefit with poloxamer 188. This contradicts findings from an earlier trial that suggested the drug might be beneficial (which used the more subjective “time to resolution of the episode” as an endpoint and had a lot of incomplete data). The authors, and the journal, should be congratulated on their persistence in ensuring this negative trial from 2016 saw the light of day.

JAMA doi:10.1001/jama.2021.3414

Alex Nowbar is a clinical research fellow at Imperial College London