Ann Robinson’s journal review—23 October 2019

Ann Robinson reviews the latest research from the top medical journals


Tranexamic acid for trauma: a no brainer?

The CRASH-3 trial into the effects of tranexamic acid in acute traumatic brain injury showed a substantial reduction in head injury related deaths (18.5% in tranexamic acid group v 19.8% in the placebo group), with no increase in disability among survivors or vascular occlusive events. Tranexamic acid, an antifibrinolytic drug that slows the breakdown of clots and reduces intracranial bleeding, was most effective if given promptly within a three hour window and among those with mild or moderate, rather than severe, traumatic brain injury. Since the CRASH-2 study reported in 2010, current trauma guidelines recommend prompt administration of tranexamic acid as part of pre-hospital care, but cases of isolated  traumatic brain injury were excluded as evidence of safety and efficacy had to wait for this study. With 60 million new cases of traumatic brain injury a year across the world, the prompt use of this cheap and widely available drug at the scene could have a major impact, although not as great as measures to improve road safety and reduce falls, which are the two major causes of traumatic brain injury. 


Low calorie Mediterranean diets

An intervention that included a low calorie Mediterranean diet, exercise plan, and behavioural support (compared with an unrestricted Mediterranean diet) led to a lasting dietary change over 12 months in overweight people with no cardiovascular disease, according to this preliminary analysis of an ongoing large, Spanish randomised trial. The mean calorie intake was around 2300 kcal/day in both groups at the outset of the trial, and after 12 months the intervention group’s mean intake was 102 kcal/day less than that of the control group.  Whether people continue to stick to the lower calorie diet and, importantly, whether they derive any cardiovascular benefits, remains to be seen as the trial continues. All participants received free extra virgin olive oil and nuts, but the high cost of these foods may preclude rolling out this diet out to the population at large. The dietary intervention was multifaceted and, if lasting benefit is shown, there’s no way of knowing which components made the difference. Previous studies have suggested that it’s the combination, rather than individual foods, that make up the Mediterranean diet that confers the benefit. Let’s hope that this trial is spared the indignities of its predecessor; the original landmark study into Mediterranean diets (PREDIMED) had to be retracted because of “irregularities in randomisation procedures” although subsequent reanalysis by the authors appeared to confirm its benefits. 

JAMA Internal Medicine

Collaborative medication reviews for elderly people

This Norwegian study asked whether clinical geriatric assessments and medication reviews by a geriatrician and family doctor yield positive results for elderly people taking lots of drugs. How can it not? I asked myself. And, indeed, this cluster randomised clinical trial including 70 GPs and 174 patients found significant improvements in health related quality of life scores after 16 weeks, compared with a control group who received “usual care.” All the interventions were carried out by a single physician, and a less competent individual may be less effective. The main outcome of the geriatric assessment was around medication review, with occasional recommendations to the GP to refer or request further investigations. The question is whether similar benefits would flow from an assessment and medication review that is carried out, as it often is in the UK, by a GP, pharmacist, or other healthcare worker. 


Treatment of advanced melanoma: a triumph

The past decade has seen huge progress in the treatment of advanced melanoma, thanks to the advent of new systemic therapies such as ipilimumab and nivolumab. The CheckMate 067 trial has already shown a substantially higher response rate and longer progression-free survival and overall survival with nivolumab plus ipilimumab or nivolumab alone than with ipilimumab alone (overall survival 52%, 44%, and 26% respectively). This update of CheckMate 067 confirms those findings, with greater long term overall survival at five years in patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone. There was no apparent deterioration in quality of life between the different groups and no new cases of late toxicity. I can remember when the diagnosis of advanced melanoma was a death sentence and five year survival rates of over 50% would have seemed fanciful. It’s one of the triumphs of modern medicine.  

Closed loop control in type 1 diabetes

This multicentre, randomised trial of people with type 1 diabetes showed a sustained improvement in glycaemic control in those who used a closed loop system (“artificial pancreas”) compared with the control group who used a continuous glucose monitor and an insulin pump. The closed loop system uses an algorithm that turns off the insulin pump in the event of hypoglycaemia and gives automated correction boluses and overnight boosts of basal insulin delivery to achieve near-normal glycaemia each morning. The mean percentage of time in the target range of glycaemic control was 11 percentage points higher with the closed loop system than in the control group, an improvement that was sustained over the six month trial period. There were more adverse events in the closed loop group; primarily hyperglycaemia with ketosis from pump infusion set failure. The authors speculate that this may merely reflect a lower bar for reporting adverse events because the closed loop system is an investigational advice (to back this up, they point out that blood ketone levels were similar in both groups). 

Ann Robinson is an NHS GP and health writer and broadcaster