Ann Robinson’s research reviews—25 March 2021

Ann Robinson reviews the latest research from the top medical journals

Anticoagulation in severe covid-19

Prophylactic anticoagulation for patients with covid-19 in intensive care has been a game changer; but which dose is best? This Iranian study randomised 562 patients to intermediate dose enoxaparin (1 mg/kg/day) versus standard dose (enoxaparin 40 mg/day) with adjustment for weight and renal function. The composite outcome of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, and death within 30 days was similar (45.7% for intermediate dose v 44.1% for standard dose). Major bleeding was rare in both groups (2.5% for intermediate dose v 1.4% for standard dose), and severe thrombocytopenia occurred only in the intermediate dose group. There are some caveats, however: the most seriously ill patients weren’t included; assignment was open label; the rate of thrombosis was lower than expected (possibly because of a lack of routine screening); and results may not be fully generalisable as the number of very obese people was relatively low.

JAMA doi:10.1001/jama.2021.4152

Fish oils and vitamin D for AF?

Do fish oils (marine omega-3 fatty acids) and/or vitamin D3 prevent atrial fibrillation (AF)? Not according to this trial of more than 25 000 people aged over 50 years, followed up for a median 5.3 years, who didn’t have AF, cardiovascular disease, or cancer at the start of the study. Around 3.4% of participants developed AF whether they took the supplements or not. The idea of supplementation is based on the observation that low blood levels of fish oils and vitamin D are associated with a higher risk of AF and on experimental models showing favourable electrophysiological effects on atrial remodelling. AF may have been under-reported in this trial, the doses may have been too low, younger people or those with established heart disease may show greater benefit, and the study, though large, may have been underpowered to detect small changes. Or it might be that, although fish oils and vitamin D are part of a healthy diet, there’s no compelling case for supplementation to prevent AF.

JAMA doi:10.1001/jama.2021.1489

How effective is osteopathic treatment?

In this randomised trial of 400 participants, six fortnightly sessions of standard osteopathic manipulative treatment (OMT) didn’t have a significant impact on functional impairment caused by non-specific subacute and chronic low back pain compared with sham OMT at three months. There was no difference in pain, time off work, or consumption of analgesics between the two groups. On the plus side, OMT was safe. This trial took place in a single centre. Osteopathy techniques and practitioners vary widely, so results may not be widely applicable.

JAMA Intern Med doi:10.1001/jamainternmed.2021.0005

Azithromycin and covid—it doesn’t work

Azithromycin has potential antiviral and anti-inflammatory properties and has been my go-to antibiotic for suspected covid-19 in those at risk of complications. This UK based, primary care trial (PRINCIPLE) assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected covid-19 to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. Compared with usual care alone, azithromycin didn’t provide much benefit in terms of either time to self reported recovery (estimated benefit <1 day) or hospital admission (3% in both groups).There were no deaths in either group, and safety outcomes were similar. Several randomised trials among patients admitted to hospital have found that azithromycin isn’t an effective treatment for covid-19, and this elegant, community based study has found the same. Looks like it’s time for me to break the azithromycin habit.

Lancet doi:10.1016/S0140-6736(21)00461-X

Immediate antiretrovirals in HIV: ideal but not critical?

In an ideal world, asymptomatic people who are found to be HIV positive should start antiretroviral therapy (ART) immediately, regardless of CD4 cell count, to reduce the risk of both AIDS and non-AIDS related events. In reality, there’s often a delay, and people start ART once their CD4 count has fallen below 500 × 109 cells/L. This reassuring 10 year multinational prospective cohort study of 8318 people who were HIV positive found that delayed ART made little impact on the incidence of both AIDS defining and non–AIDS defining cancers. The 10 year risk was 2.5% for AIDS defining cancers and 2.97% for non–AIDS defining cancers in those given immediate ART—a difference of 0.12-1 percentage points compared with delayed ART.  This was a young population (median age of 36 years) in whom the baseline risk of cancer was low, and the observational nature of the study means a risk of residual confounding.

Ann Intern Med doi:10.7326/M20-5226

Neutralising antibodies for HIV prophylaxis: more work needed

In the midst of covid-19, it’s easy to forget that the 40 year old global pandemic of HIV still infects 1.7 million new people a year. Can a broadly neutralising antibody (bnAb), which acts against multiple viral strains, prevent HIV in at risk people? Two parallel proof-of-concept efficacy trials assigned at-risk HIV negative individuals to receive low or high dose bnAb (VRC01) or placebo and found that rates of HIV infection were broadly similar after 20 months. Pre-exposure prophylaxis (PrEP) was offered to all participants but uptake was low. Results were disappointing but proof of concept was demonstrated in HIV isolates that were sensitive to VRC01. Resistance is likely to become a problem with a single agent like VRC01 and further studies to look at combinations of antibodies are needed.

NEJM doi:10.1056/NEJMoa2031738

Ann Robinson is an NHS GP and health writer and broadcaster.