Ann Robinson’s research reviews—12 February 2021

Ann Robinson reviews the latest research from the top medical journals

Is becoming richer good for your heart?

This huge retrospective analysis of 3123 US counties, encompassing over 100 million individuals from 2010 to 2017, found that every 10 point increase in economic prosperity was associated with a modest 0.4% lowering of cardiovascular mortality in adults aged 40-64 years. The authors note that post-recession economic stagnation and poor social cohesion in the US have been associated with a rise in “deaths of despair” (such as drug poisoning, suicide, alcoholic liver disease). Economic stress may also have upregulated inflammatory processes and increased cardiovascular mortality. However, numerous confounders complicate the picture; not least that healthy middle-aged people may have voted with their feet and abandoned economically stagnant areas, leaving those most predisposed to cardiovascular disease behind.

JAMA doi:10.1001/jama.2020.26141

What causes cerebral palsy?

Birth asphyxia accounts for less than 10% of cases of cerebral palsy, so what explains the other 90% of this common neurodevelopmental disorder that affects up to three in every 1000 people? This cross sectional study used exome sequencing of two cohorts and found pathogenic genetic variants in 32.7% of paediatric patients and 10.5% of adult patients with cerebral palsy. The lower yield with adult patients reflected the need for narrower testing as there was much less availability of data about the parents of subjects with cerebral palsy, which was needed for comparison. The molecular diagnostic yield in this study was in line with results for other neurodevelopmental disorders which are known to co-exist with cerebral palsy such as epilepsy and autism. Using a combined cohort without details of the type and severity of cerebral palsy was a significant limitation of the study. And its observational nature means that there’s no proof that the genetic variants cause cerebral palsy. Further study to translate the results of genetic studies into clinical practice is the next vital step.

JAMA doi:10.1001/jama.2020.26148

Global surgical cancer care: levelling up

About 80% of people with cancer require some sort of surgery. How do postoperative outcomes differ across high income countries and low to middle income countries (HIC and LMICs)? Unsurprisingly, this international prospective cohort study found that patients in LMICs presented with more advanced disease than in HICs. LMICs also had higher 30 day postoperative mortality for gastric and colorectal cancer patients, but there was no difference after breast cancer surgery. Complication rates were similar globally, but more likely to cause death in LMICs and played a significant part in the disproportionate numbers of postoperative deaths in cancer patients in poorer countries. Both patient-related factors (such as poor nutrition) and health system factors (such as lack of critical care) play a role. The authors urge better perioperative interventions to reduce avoidable mortality from common surgical complications in global surgical cancer care.

Lancet doi:10.1016/S0140-6736(21)00001-5

Predisposition to breast cancer: it’s bigger than BRCA

Knowing that you carry pathogenic variants in genes that predispose you to a particular cancer (such as BRCA1 and 2 and breast cancer) is useful because the woman can choose risk-reducing surgery or drugs and enhanced screening. Existing knowledge of gene variants is based on high risk populations, but few studies have searched multigene panels across a wider population of women. This US case-control study found evidence of 12 pathogenic variants in 5% of women with breast cancer (versus 1.63% in controls) and confirmed the increased risk associated with BRCA1 and 2. The study also found that a further 16 candidate gene variants weren’t associated with an increased risk. At the moment, only women with a known family or personal history of breast and ovarian cancer are offered genetic testing. Studies such as this one pave the way to offering risk estimates for all individuals to guide tailored screening, cancer testing, prevention, and management.

N Engl J Med doi:10.1056/NEJMoa2005936

Moderna trials ongoing

A phase 3 randomised US trial among individuals at high risk of covid-19 found that two doses of the mRNA-1273 (Moderna) vaccine given 28 days apart were effective in preventing covid-19 from two weeks after the second dose compared with placebo. The vaccine showed 94.1% efficacy against covid-19. All 30 people (of >30 000 participants) who became seriously unwell with covid-19 (including one who died) were in the placebo group. Moderna is the third covid vaccine licensed in the UK. Important questions remain about longer term safety, duration of immunity (and a way of measuring it), and transmissibility. 

N Engl J Med doi:10.1056/NEJMoa2035389

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