Ann Robinson’s research reviews—12 December 2020

Ann Robinson reviews the latest research from the top medical journals

Malaria: a far greater threat to children in Africa than covid-19

Large scale seasonal malaria chemoprevention (SMC) given to children under 5 years old, was effective in reducing morbidity and mortality from malaria in west and central Africa, according to this important observational evaluation of the ACCESS-SMC project. Serious adverse reactions were rare or rarely reported. Despite challenges of supply and distribution, 90% of children received at least one treatment, more than 50% of children received all four treatments per year, and the death rate from malaria fell by 42-57% in areas of SMC intervention. Resistance to sulfadoxine-pyrimethamine and amodiaquine were uncommon, but ongoing monitoring is needed as malaria remains a major threat in sub-Saharan Africa, where it will kill far more people, many of them children, than covid-19 will this year. Recruitment has started for human trials of a transmission-blocking malaria vaccine developed by the Oxford team behind one of the covid-19 vaccines. But even if a vaccine is found, it will not be a substitute for SMC.

Lancet doi:10.1016/S0140-6736(20)32227-3

Flu jabs: high dose trivalent no better than standard dose quadrivalent

Reducing flu in a high risk population over 65 years old leads to fewer hospitalisations and deaths from cardiovascular and respiratory illness. But is a high dose trivalent flu vaccine better than the standard dose quadrivalent one? This pragmatic, randomised trial of individuals at high cardiovascular risk (recent myocardial infarction or admission with heart failure) enrolled over three flu seasons found that high dose trivalent inactivated influenza vaccine did not significantly reduce the composite end point of all-cause death or hospitalisations for cardiac or pulmonary causes compared with standard dose quadrivalent inactivated influenza vaccine. The high dose vaccine unsurprisingly caused more vaccine related adverse effects, although severe events were rare and similar in both groups. An important caveat is that there was no laboratory confirmation of flu in this pragmatic trial, so whether it was reduced in this population remains unknown. There was also no unvaccinated control group as flu vaccination is strongly recommended in this high risk group, so not offering vaccination at all would be considered unethical. 

JAMA doi:10.1001/jama.2020.23649

“Payment delinquency” precedes dementia diagnosis by up to six years

People who live on their own start to have problems managing their financial affairs—including keeping up with bill payments—for several years before a diagnosis of Alzheimer’s disease and related dementias (ADRD) is made. This large, retrospective, secondary data analysis of consumer credit report outcomes from 1999 to 2018 linked to Medicare claims data found a small but significantly higher risk of “payment delinquency” (missed payments) among those who went on to develop ADRD within the next six years compared with matched controls who didn’t. The difference increased in the quarter after diagnosis. I’m not sure what this study adds to the sum of human knowledge; the difference is small, and most people who care for or about an older relative will already be aware of the risk of financial vulnerability.

JAMA Intern Med doi:10.1001/jamainternmed.2020.6432

Covid-19 solidarity: the ongoing quest for better treatments

Remdesivir, hydroxychloroquine, lopinavir, and interferon had no significant effect on overall mortality, initiation of ventilation, or duration of hospital stay in hospitalised patients with covid-19 according to the open-label interim WHO Solidarity trial. The results are disappointing, but the organisation of this global study is awe inspiring: 11330 patients in 405 hospitals in 30 countries were enrolled from March to October of this year. And its efficient factorial design and recruitment of 2000 patients per month mean that the Solidarity trial is well set up to assess further treatments such as immunomodulators and monoclonal antibodies to SARS-CoV-2 virus. The overall risk of death to day 28 was 11.8%, with no significant impact attributable to any of the drugs studied. Results could be honed by using narrower confidence intervals, especially for remdesivir. But, the authors say, the main need is for better treatments.

N Engl J Med doi:10.1056/NEJMoa2023184

Steroids in rheumatoid arthritis associated with severe infection

A large retrospective cohort study has shown that long term, low dose glucocorticoids were associated with an increased risk of hospitalisation due to serious infection in patients with rheumatoid arthritis who had been taking disease modifying antirheumatic drugs for more than six months. The increased risk was dose dependent and apparent even at low doses of 5mg a day. Two major limitations of this study are the possibility of misclassification of the dose of glucocorticoids and the risk of residual confounding in this type of study. Consensus on the role of glucocorticoids in rheumatoid arthritis remains elusive, although there is general agreement that the aim is to give the lowest possible dose for the shortest possible time.

Ann Intern Med doi:10.7326/M20-1594

Ann Robinson is an NHS GP and health writer and broadcaster