Ann Robinson’s research reviews—14 May 2021

Ann Robinson reviews the latest research from the top medical journals

Tuberculosis treatment: is four months enough?

Shortening treatment for tuberculosis from the current six months to four is an attractive idea as it’s likely to improve compliance and reduce adverse effects and costs. An open-label, phase III trial found that a 4 month rifapentine based regimen with moxifloxacin was non-inferior to the standard 6 month regimen in the treatment of newly diagnosed pulmonary tuberculosis (unfavourable outcome in 15.5% versus 14.6%) although rifapentine without moxifloxacin was not non-inferior. The safety profile was similar between the groups. The study had no placebo arm for technical reasons and 8% of participants also had HIV, which complicates comparison between the regimens. On the plus side, cure rates were high (96.9% in the control group) and participants included adolescents and a diverse population across 13 countries.

N Engl J Med doi:10.1056/NEJMoa2033400

Donanemab for dementia: disappointing results

This small and imperfect phase II study of the efficacy of donanemab in early Alzheimer’s disease produced mixed but ultimately disappointing results. Donanemab, an antibody that targets amyloid-β peptide, was compared with placebo in patients with early symptomatic Alzheimer’s disease with tau and amyloid deposits on positron emission tomography (PET) scans. The donanemab group showed slightly less cognitive and functional decline than the placebo group at 76 weeks when the integrated Alzheimer’s disease rating scale was used (-6.86 v -10.06 from baseline), but no significant difference on other scales, such as the mini mental state examination. No differences were noted in PET scan results. Donanemab appeared to be safe (no increase in serious adverse effects when compared with placebo) but ineffective. Larger, longer trials are needed as the search continues for dementia treatments that work.

N Engl J Med doi:10.1056/NEJMoa2100708

Use cardiovascular risk, not blood pressure, to guide antihypertensive treatment

Should antihypertensive medication be limited to people with high blood pressure or be considered for anyone at increased risk of cardiovascular disease? This important and relevant study suggests the latter. A meta-analysis of nearly 350000 people across 48 trials analysed individual participant level data to investigate the effects of lowering blood pressure on the risk of major cardiovascular events, according to individuals’ baseline levels of systolic blood pressure. Over an average of four years, a 5 mm Hg reduction in systolic blood pressure reduced the risk by about 10% (reductions of 13% for stroke and heart failure, 8% for ischaemic heart disease, and 5% death from cardiovascular disease). The greater the lowering of systolic blood pressure, the greater the impact on risk, regardless of baseline measurement. These treatment advantages persisted among individuals with normal baseline blood pressure, whether or not they had pre-existing cardiovascular disease. The study wasn’t designed to investigate potential harms (such as dizziness and falls) which can, in practice, limit taking blood pressure ever lower. But it looks like the end of slavish adherence to specific blood pressure thresholds to start or intensify treatment and “floor levels” for blood pressure reduction.

Lancet doi:10.1016/S0140-6736(21)00590-0

Tocilizumab improves survival in covid-19

Tocilizumab improved survival and other clinical outcomes in 4116 patients hospitalised with covid-19 in this arm of the Recovery trial, and the benefits were in addition to those of corticosteroids. Overall, 31% of the 2022 patients on tocilizumab died within 28 days compared with 35% of those who received usual carea stark reminder of how high mortality rates were this time last year. Discharge from hospital within 28 days was more likely on tocilizumab (57% versus 50%), and patients who weren’t ventilated at the start of the study were less likely to progress to needing ventilation or dying. Previous smaller trials, apart from REMAP-CAP trial in critically ill patients, had failed to show a survival benefit for tocilizumab, but this study showed a convincing benefit, in addition to the known benefits of corticosteroids. The difference is that steroids are cheap and widely available whereas tocilizumab isn’t; incorporating it into global guidelines may prove challenging.

Lancet doi:10.1016/S0140-6736(21)00676-0

Women who are doctors delay having kids

Female doctors appear to have kids later than non-doctors, especially if they’re “specialists” rather than family doctors, according to this Canadian study that followed a cohort from the age of 15 for a median of 16 years (note to the authors: family doctors are specialists too!). The women who would go on to become doctors were more likely to live in high income urban areas (39% versus 17%) and be immigrants (15% v 10%) than non-physicians. Family doctors had more children than hospital based doctors (2.83 v 2.42 per 100 person-years). By the age of 37, 62% of female doctors and non-doctors had at least one child, but the median age of first birth was significantly higher for the doctors (31.6 v 27) and higher than women from a similar income bracket. Ninety eight per cent of female doctors delay having a child until after they finish medical school, which may be similar in other professions that have long training such as law. It’s not clear to what extent women are exercising choice or being disadvantaged by a training and culture that still makes it hard to pursue a career in medicine and have and raise children. More on this, and reproductive choices of male doctors, would be very welcome.

JAMA Intern Med doi:10.1001/jamainternmed.2021.1635

Ann Robinson is an NHS GP and health writer and broadcaster