Alex Nowbar reviews the latest research from the top medical journals

Clots with the AstraZeneca vaccine

On one hand, this clot news is an open-shut case because the benefits of the vaccine so gigantically outweigh the risks. On the other hand, there is more to this than a PR war about vaccine uptake. What is the mechanism of thrombosis and thrombocytopenia? These reports from Germany, Austria, and Norway conclude that the thrombotic events represent immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against platelet factor as a result of the ChAdOx1 nCov-19 vaccine. The syndrome was reported to be similar to heparin induced thrombocytopenia, but the patients had never received heparin to explain this. This syndrome has been triggered non-pharmacologically before—for example, after viral or bacterial infection or knee replacement surgery. The onset was 5-16 days after vaccination. Understandably, people who have had the vaccine will be worried about this, but they shouldn’t because the rates are so low. If you’re wondering why clots form when there are fewer platelets, it’s because the platelet factor 4-antibody immune complexes activate platelets to produce platelet derived microparticles that promote excess thrombin generation.

N Engl J Med doi:10.1056/NEJMoa2104840

N Engl J Med doi:10.1056/NEJMoa2104882

Covid-19: previous infection and future protection

I am proud that I am personally contributing as a participant in this study. But more than that, I’m proud that the SIREN investigators designed a study to properly answer important questions about covid-19 by prospective paired antibody and PCR testing. Everyone hopes that previous infection will protect against future infection. Intensive follow-up of a prospective cohort can give us a lot more information about this question than a case-control approach. It’s a wonderful testament to the UK research scene. Study participants with a previous SARS-CoV-2 infection had an 84% lower risk of infection. The authors conclude: “previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals.” Unfortunately, these data cover June to December 2020. Now that we have variants, does previous infection still protect you? Lucky for us, the SIREN study continues, so we’ll be able to find out.

Lancet doi:10.1016/S0140-6736(21)00675-9

Walking for peripheral artery disease

People with peripheral artery disease are more likely to walk at a comfortable pace than at speed, but McDermott and colleagues found that low intensity exercise (which did not induce ischaemic leg symptoms) did not carry the benefits of high intensity exercise (which caused ischaemic leg symptoms). A year after randomisation, the 6-minute walk distance was improved in the high intensity group, but not in the low intensity and non-exercise groups. The exercise groups weren’t just given advice to go exercise and sent on their way. They wore accelerometers recording the amount and intensity of exercise. A coach reviewed this data and telephoned them weekly to help them to adhere to the prescribed exercise. Interestingly, patients in both exercise groups reported similar benefits compared with the non-exercise group, but the
patients were not blinded to study arm. Overall it seems worth pushing through the pain and it appeared safe.

JAMA doi:10.1001/jama.2021.2536

Diagnostic reasoning

Are we good at diagnostic reasoning? It’s a large portion of our jobs, so one would hope so. The US practitioners who answered this survey about scenarios relating to common conditions, such as pneumonia and breast cancer, overestimated the probability of disease both before and after testing. “Correct” answers to the scenarios were based on expert review of scientific evidence. I’m going to be generous and infer that this overestimation stems from a sincere desire to offer patients answers and solutions rather than from an educational deficit. Practitioners are aware of pretest probability and how to interpret positive and negative results, but they just don’t seem to use this knowledge in everyday practice. This almost certainly leads to overdiagnosis. This reflects a culture of both over-testing and over-reliance on test results, which is driven by patients and clinicians in a vicious cycle. The authors state: “Medical decisions, like other human decisions, may not be rational and are prone to errors associated with poor knowledge of the base rate of disease or other errors associated with probability.”

JAMA Intern Med doi:10.1001/jamainternmed.2021.0269

Help for substance use disorders

The NavSTAR trial randomised 400 people hospitalised with substance use disorders (be it alcohol, opioids, or cocaine) to Navigation Services to Avoid Rehospitalization or usual care. Navigation Services reduced readmission to hospital, which was the primary outcome. This is promising. It is reassuring to know that readmissions aren’t inevitable and there is something that can be done. Unfortunately, this was conducted only at one hospital site in Baltimore, which limits generalisability of the results in two ways. First, the intervention might be less effective with a different geographic population, as their needs may differ. Second, the intervention may not be deliverable elsewhere because it seems to heavily rely on the study’s patient navigators (social workers), who in turn were supervised by a senior social worker in addition to having weekly in-depth multidisciplinary meetings to review cases. However, it is plausible that their methods could be learnt—that is, use of motivational interviewing techniques to address ambivalence and facilitate behaviour change coupled with proactive service delivery after discharge. Other elements of the intervention were linking participants to community resources and access to a modest support fund for transport to appointments, medication copayments, etc. This intervention seems worth pursuing.

Ann Intern Med doi:10.7326/M20-5475

Alex Nowbar is a clinical research fellow at Imperial College London