Ann Robinson’s research reviews—4 June 2021

Ann Robinson reviews the latest research from the top medical journals

ADHD: children as young as 5 years old on medication

In the US, around 2.4% of preschool children (under 6 years old) are diagnosed with attention-deficit/hyperactivity disorder (ADHD). The standard treatment is behavioural modification, followed by medication with stimulants (methylphenidate) or, in around 25% of cases, α-2 adrenergic agonists (guanfacine or clonidine), for which there’s not much evidence of efficacy or safety. This retrospective review of health records of 497 children with a median age of just 5 years old found improvement in 66% of those receiving α-2 adrenergic agonists versus 78% of those taking stimulants and flagged up differences in adverse effect profiles. Daytime sleepiness was a more common side effect of α2 adrenergic agonists (38% v 3%), whereas appetite suppression was a more common reported effect of stimulants (38% v 7%). Alarmingly, over a third of the children were put straight on to medication with no record of a behavioural intervention.

JAMA doi:10.1001/jama.2021.6118

Access to a liver transplant

Most people who need a liver transplant die before they get one. The main reason is a lack of donor organs, but delays in referral are also to blame according to this large US cohort study of 34 494 veterans with cirrhosis. Only 1.6% of the cohort received a transplant within three years; 95% were never referred, and 40% weren’t put on the waiting list despite being eligible. Inequity of access occurred primarily at the initial referral stage. Those with comorbidities, aged over 70 years, on lower income, African American, or with alcohol related liver damage were less likely to be referred. The study was observational, so causality can’t be demonstrated and there may have been other factors affecting clinicians’ decisions. Tracking the whole process would be a good start in addressing these grim statistics.

JAMA Intern Med doi:10.1001/jamainternmed.2021.2051

Aspirin: less is more

What’s the best dose of aspirin to reduce the risk of death, myocardial infarction, and stroke in people with known cardiovascular disease, while keeping the risk of major bleeds to a minimum? This pragmatic trial found that a higher dose of 325 mg aspirin was no better or safer than 81 mg, and patients were more likely to continue taking the lower dose. In both groups, death or hospitalisation for stroke or myocardial infarction occurred in around 7%, and major bleeds in a reassuringly low 0.6% of patients. Results could have been skewed by the open-label design, which meant that patients often switched doses—usually from 325 mg to 81 mg—and many patients had already been taking 81 mg aspirin before the study. But generally the lower dose seems  to be as effective and safe as the higher dose, as well as being more acceptable to patients.

N Engl J Med doi:10.1056/NEJMoa2102137

Kangaroo style parenting

Should human mothers behave more like kangaroos? “Kangaroo mother care” is the delightful name for keeping newborn infants in continuous contact with the mother’s chest and exclusively breast feeding the baby. Apparently, it’s one of the most effective ways of preventing death in low birthweight infants. The WHO currently recommends short bursts of kangaroo mothering once the baby’s condition is stable. But this large study across several low-resource hospitals found that starting continuous kangaroo mother care immediately after birth in low birthweight infants (1.0 to 1.799 kg) improved neonatal mortality by 25% compared with waiting for stabilisation (28 day mortality 12% v 16%) and reduced sepsis and hypothermia. There’s no way of knowing whether the benefit was due to the simple presence of the mother or whether having the baby clamped to her chest for a minimum 17 hours a day made a difference. The study may not be widely generalisable, as around 20% of the low birthweight babies couldn’t be enrolled because either the baby or mother was too unwell.

N Engl J Med doi:10.1056/NEJMoa2026486

New radiotracer improves prostate cancer outcome

In this open-label, phase II/III trial, men who had recurrent or persistent prostate cancer despite a radical prostatectomy, showed a 12% improvement in event-free survival at three years when advanced molecular imaging using a new PET radiotracer, 18F-fluciclovine, was used to guide decisions about final radiotherapy treatment compared with standard imaging. There was no significant increase in toxicity. Randomised trials of imaging tests with endpoints of primary cancer control are few and far between. Most focus on diagnostics and decision making. Longer follow-up would be useful to see whether the survival advantage is maintained.

Lancet doi:10.1016/S0140-6736(21)00581-X

Ann Robinson is an NHS GP and health writer and broadcaster