Ann Robinson’s research reviews—24 September 2021

Raising urate levels in early Parkinson’s disease

The quest for better treatments for Parkinson’s disease continues. This small randomised trial of 298 people with early disease found that treatment with urate-elevating inosine didn’t fulfil its theoretical promise. The rationale is that circulating antioxidant urate may counter the oxidative damage to dopaminergic neurones that occurs in Parkinson’s disease. Unfortunately, in this study, both the inosine and placebo groups showed steady disease progression, with no difference between them. There were more serious adverse effects in the placebo group although, predictably, more kidney stones in the inosine group (7.0 per 100 patient-years v 1.4 per 100 patient-years in the placebo group). Urate-elevating treatments may still have a role, especially if given to susceptible individuals pre diagnosis, before extensive neuronal damage has occurred.

JAMA doi:10.1001/jama.2021.10207

Part time versus full time doctoring: what’s best for patients?

In this large US cross-sectional study of 392 797 Medicare patients aged over 65 years, who were admitted for emergency medical care and treated by 19 170 hospital doctors, mortality rates were significantly lower among those treated by doctors who worked full time rather than part time (adjusted 30 day mortality for physicians in the bottom quartile of days worked clinically per year versus top quartile, 10.5% v 9.6%). Readmission rates weren’t affected by how much the clinician worked. Possible explanations for the apparent association between poorer patient outcomes and lower clinical workload include the difficulties in keeping up to date, remaining skilled, maintaining good teamwork within the hospital, and balancing other non-clinical duties. But it’s an observational study with limited data, scope for confounders, no details about the reasons for doctors working part time, and no inclusion of younger or surgical patients. Conversely, some studies among outpatients have found that patients do better when cared for by part time doctors.

JAMA Intern Med doi:10.1001/jamainternmed.2021.5247

Salt substitutes and stroke reduction

Would introducing large-scale salt substitution reduce strokes and cardiovascular disease? This important, large, randomised study in 600 rural villages in China compared a salt substitute with regular salt among people who had already had a stroke (73%) and/or were at increased risk of having a stroke as a result of being over 60 years old with high blood pressure (88%). Significantly lower rates of stroke (29.14 v 33.65 events per 1000 person-years), major cardiovascular events (49.09 v 56.29 events per 1000 person-years), and death (39.28 v 44.61 events per 1000 person-years) were found in the salt substitute group compared with the regular salt group. There were no obvious adverse effects, but hyperkalaemia may have been missed in some. High salt use in food preparation is a feature of low income countries and disadvantaged populations. Salt substitution may be cost effective and help to reduce health inequalities from cardiovascular disease in those settings. Findings might not be generalisable to urban and high income areas, and other interventions may be more effective, such as reducing our seemingly insatiable appetite for salty foods.

N Engl J Med doi:10.1056/NEJMoa2105675

Covid booster jabs: early results on effectiveness

We have useful data from Israel, where they’re pressing ahead with a third Pfizer covid jab for people over 60 years old who had their second vaccine dose at least five months before the booster. Twelve days or more after the booster, rates of confirmed infection were lower in the booster group than in a matched non-booster group by a factor of 11.3 (absolute difference 86.6 infections per 100 000 person-days), and the rate of severe illness was lower by a factor of 19.5 (absolute difference 7.5 cases per 100 000 person-days). The booster was considered necessary to restore the vaccine to its previous 95% efficacy against the alpha variant now that waning immunity and increased prevalence of the delta variant have had a significant impact on its effectiveness. There were possible sources of bias; those who got the booster may be more proactive about their health than those who hadn’t yet had a third jab.

N Engl J Med doi:10.1056/NEJMoa2114255

Four into one: quadpill as initial treatment of high blood pressure

This landmark study is the first known randomised trial to show that a single pill containing quarter-dose quadruple combination (quadpill) of antihypertensive drugs given early in the treatment of patients with hypertension was more effective than starting patients on a single drug (monotherapy). The quadpill contained irbesartan (37.5 mg), amlodipine (1.25 mg), indapamide (0.625 mg), and bisoprolol (2.5 mg); and initial monotherapy was irbesartan 150 mg and placebo tablets. At 12 months, the mean blood pressure was 121/71 mm Hg in the intervention group and 128/76 mm Hg in the control group. Good control (blood pressure <140/90) was maintained at 6 and 12 months in 76% (intervention group) and 81% (control group). There was no difference in adverse events between the two groups. The covid-19 pandemic affected recruitment to the trial, which limited the precision of some subgroup analyses, and there were no data on long term cardiovascular outcomes. But the sustained, safe, and effective lowering of blood pressure that was observed with the quad pill looks compelling.

Lancet doi:10.1016/S0140-6736(21)01922-X

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