Alex Nowbar’s journal reviews—19 February 2021

Alex Nowbar reviews the latest research from the top medical journals

Weight loss wonder drug

Glucagon-like peptide-1 (GLP-1) receptor agonists are an established treatment for type 2 diabetes. However, the STEP 1 trial tested semaglutide in people who were obese but without diabetes. This double-blind randomised trial showed a dramatic reduction in weight with once weekly injectable semaglutide (15% reduction) compared with placebo (3% reduction) at one year. The word “gamechanger” has been used to describe this result, and, for once, it probably is. This is because lifestyle intervention and existing drugs such as orlistat haven’t really helped much. Bariatric surgery is effective but is a serious undertaking. This drug may truly offer hope. It’s not terribly pleasant though; three quarters of those in the treatment group had gastrointestinal disorders, compared with just under half of those in the placebo group. But these side effects led to only 5% of people stopping the treatment (compared with 1% of those in the placebo group).

N Engl J Med doi:10.1056/NEJMoa2032183

A hospital covid-19 outbreak

Even though there is still so much we don’t know about covid-19, it is hard to maintain an appetite for covid research. This study, set in Brigham and Women’s Hospital in the US, has a very important message though: “SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies.” The cluster studied consisted of 52 infections (14 patients and 38 members of staff) in September 2020. 

The infection control policies in place included universal masking of all employees, eye protection for all encounters, encouraging inpatients to wear masks whenever providers enter their rooms, visitor restrictions, screening patients on admission and daily thereafter for symptoms, nasopharyngeal polymerase chain reaction (PCR) testing of all patients on admission, cohorting patients with confirmed covid-19 wards with negative pressure airflow rooms, free PCR testing for all symptomatic employees, and paid leave for all employees with confirmed covid-19. All the usual things. 

And what happened was totally run of the mill. A patient had a negative admission swab and tested positive four days in after spiking a fever. (Side note: “the patient was frequently coughing, did not tolerate a mask, and had indistinct speech that led many providers to come near to understand her.”) By the time the positive test was known, several staff members were already symptomatic. Whole-genome sequencing was used to test whether infections could be related to the cluster. 

Then comes the most interesting aspect of the investigation – a case-control assessment of factors associated with infection, in this case: being present while patients used nebulisers, caring for patients with breathlessness or cough, interacting with staff members who tested positive, not wearing eye protection. Unfortunately it is not possible to establish these factors as contributory to infection because they are susceptible to confounding and also recall and ascertainment biases, not mention it’s only an analysis of a single cluster, albeit a fascinating and detailed one.

Ann Intern Med doi:10.7326/M20-7567

Null result for exercise for HFpEF

Heart failure with preserved ejection fraction (HFpEF) is notoriously lacking in effective therapies. This is often attributed to the syndrome not being well understood and having a range of definitions. This well designed and well conducted randomised trial of 180 patients tested whether high intensity interval training or moderate continuous exercise improved exercise capacity compared with guideline-recommended exercise (standard care) at three months. Neither type of exercise helped substantially. This is disappointing but useful evidence to have.

JAMA doi:10.1001/jama.2020.26812

Bicuspid valves and associated aortic disease

Sillesen and colleagues found a 0.77% prevalence of bicuspid valves (with a third of these also having aortopathy) based on transthoracic echo in over 25 000 newborns in Denmark. The size of the sample and the fact that there was no bias in who got scanned (all newborns were systematically scanned rather than scanning only those felt to be at risk) adds weight to the findings. Given the high rate of concomitant aortic abnormalities, it is likely that the aortopathy is a fetal abnormality rather than dilatation subsequent to the bicuspid valve.

JAMA doi:10.1001/jama.2020.27205

Prediabetes downgrade in older adults

In medicine, people can sometimes be reduced to a collection of diagnoses. It’s not really a great way to live, defined by your disease. So it makes sense to default to avoiding overdiagnosis. Overdiagnosis, or creating new “diseases” such as prediabetes to add to the collection, is always done with good intentions, but it might be better to wait until it’s shown that diagnosing something is helpful for preventing unwanted outcomes. Rooney and colleagues’ cohort study showed that people aged 70-90 years with prediabetes (almost a third of the 3412 older adults) were more likely to revert to normoglycaemia, or die, than progress to diabetes six years later. This suggests that prediabetes isn’t an important mediator of issues in older adults and so may not be useful to diagnose. Unfortunately, these data are limited by incomplete follow-up, meaning that the risk of diabetes at follow-up could have been underestimated. Also, participants may have received lifestyle modification in a way that may differ from the general population.

JAMA Intern Med doi:10.1001/jamainternmed.2020.8774

Alex Nowbar is a clinical research fellow at Imperial College London.