Ann Robinson’s research reviews—31 January 2020

Ann Robinson reviews the latest research from the top medical journals

Stem cell transplants: why have outcomes improved in the past decade

This study found that a cohort of around 1100 patients who had allogeneic haematopoietic cell transplantation in 2013-17 fared significantly better than a similar cohort who had had a transplant 10 years earlier. Just over six months after the transplant (200 days), overall mortality had fallen (hazard ratio of 0.66) in the 2013-17 group. The fall in mortality was similar whether the donor was a sibling or unrelated, and in patients who underwent reduced-intensity or total ablation of their bone marrow before the transplant. Complications also fell. The results are cheering, although overall survival from stem cell transplantation remains around only 50% and disease relapse is still the main cause of death. The problem with a cohort study is that we don’t know why survival rates have improved; improved donor selection and management of transplant are likely causes, but confounding factors such as transplanting less sick patients may also have contributed.

Ann Intern Med doi:10.7326/M19-2936

The new virus in town: how will it behave?

A cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China, just one month ago. With impressive speed, this report of the isolation and identification of a novel betacoronavirus (2019-nCoV) details the results of a race to trace and identify the likely organism in three original cases. 2019-nCoV is similar to some betacoronaviruses detected in bats, which may be the zoonotic source, possibly with an intermediate vector. It is also similar to, but distinct from, the two other novel coronaviruses that have emerged over the past 20 years, SARS-CoV (2003) and MERS-CoV (2012). The authors freely admit that their analysis implicates rather than proves the link between this newly identified virus and the Wuhan outbreak. A linked editorial comments that fear played a large part in the economic and social consequences of the SARS epidemic and that specific anti-coronavirus therapies are still in development but not yet available. Strict infection control, prompt diagnosis, and quarantining in the community helped to contain transmission of SARS and MERS and hopefully will help to contain this new virus whose potential to spread and harm is not yet fully known. 

N Engl J Med doi:10.1056/NEJMoa2001017

Coronavirus: person to person spread confirmed

A key question is whether the 2019-nCoV can be transmitted from human to human. This study of a family cluster of cases suggests that person to person transmission is already happening. Five family members out of six who travelled to Wuhan had evidence of 2019-nCoV infection on their return to Shenzhen, which is over 1000 km away. None had visited an animal market, but two of them had been in Wuhan hospital. Notably, an additional family member who didn’t travel with them was subsequently infected. All developed respiratory symptoms, fever, and/or diarrhoea.

Lancet doi:10.1016/S0140-6736(20)30154-9

Low dose aspirin for the prevention of preterm delivery

Low dose aspirin (81 mg) given to nulliparous pregnant women from 6-13 weeks gestation until 36 weeks significantly reduced the risk of preterm birth, according to this trial in low and middle income countries. Preterm birth (<37 weeks) occurred in 11.6% of women who took aspirin compared with 13.1% of women who took placebo. Aspirin reduced the risk of perinatal mortality by 14% and early prematurity (<34 weeks) by 25%. The results of this large and well conducted study generally chime with previous studies. The “low cost and proven tolerability of aspirin in this population” suggests that it can be safely adopted across a range of global sites, say the authors. The optimal dose and time to start aspirin are still not certain. And it’s not clear whether these findings translate to high income countries, where rates of prematurity and perinatal mortality are lower.

Lancet doi:10.1016/S0140-6736(19)32973-3

Shining a light on sunscreens

In these bleak midwinter months, it’s hard to worry about the effects of sunscreens. This useful, if untimely, small, randomised study compared the absorption (maximum plasma concentration) of six active ingredients (primarily avobenzone) from four commercially available sunscreen lotions and sprays after maximum recommended use. Mean maximum plasma concentrations of all six active ingredients exceeded the FDA recommended threshold of 0.5 ng/mL even after a single application. Reassuringly, there were no serious adverse effects, although this study didn’t provide for long term follow-up. There are 12 active ingredients in sunscreens for which the FDA has requested additional data to determine if they are “generally recognized as safe and effective” (GRASE). It seems extraordinary that such widely used products are so poorly understood. “These findings do not indicate that individuals should refrain from the use of sunscreen,” say the authors, and, to be fair, toxicity seems to be low. But further safety information is sorely needed, preferably before the summer.

JAMA doi:10.1001/jama.2019.20747

Junk food is bad, even if it’s low fat and low carb

This cohort study of 37,233 US adults 20 years or older found that it’s not enough to follow a low carbohydrate diet and low fat diet; a healthy form of the diet (more plants, fewer saturated fats) is associated with lower mortality rates but an unhealthy version is linked to higher mortality. Overall, they cancel each other out so that there was no significant difference in mortality rates between a group who self reported that they followed an low carbohydrate diet or low fat diet and those that didn’t. The clear inference is that the quality of food matters, not just the percentage of fats and carbohydrates in the diet. Perhaps the best advice for our patients who have been flirting with Veganuary and post Xmas faddy diets, is the old maxim; “eat real food, not too much.”

JAMA doi:10.1001/jamainternmed.2019.6980

Thyroid eye disease; a new treatment 

Thyroid eye disease is debilitating and potentially sight threatening condition for which there is no FDA approved medical therapy. Treating the underlying thyroid disorder doesn’t necessarily improve eye symptoms such as proptosis, which are linked to insulin-like growth factor I receptor (IGF-IR). This small study found that teprotumumab, a targeted inhibitor of IGF-IR, improved proptosis in 83% (34 patients) vs. 10% (just 4 patients) in the placebo group. Orbital imaging in six patients showed that the reduction in proptosis was associated with a fall in extraocular muscle and orbital fat volumes. Quality of life scores were better in the teprotumumab group and accompanying photos of the results suggest why that might be. The follow up period was only 24 weeks and there’s no data on long term follow up including relapse rates and the percentage who go on to need surgical intervention. On the other hand, there’s no other effective and safe medical treatment for thyroid eye disease so this is a potentially very welcome development. 

N Engl J Med doi:10.1056/NEJMoa1910434

Ann Robinson is an NHS GP and health writer and broadcaster