Ann Robinson’s research reviews—29 January 2019

Ann Robinson reviews the latest research from the top medical journals

Annals of Internal Medicine

Renal transplant for patients with lupus nephritis improves survival

Patients with end-stage renal disease due to lupus nephritis have high rates of premature death and these haven’t improved in the past 20 years. In the past, these patients weren’t usually offered renal transplantation because of fears of recurrence of the nephritis, complications such as thrombosis, and rejection of the transplant. But is it better to go ahead with renal transplant, despite the risks? Opinion has changed, but concerns remain and transplant is often held as a last resort. This US study shows that transplant improves survival compared to dialysis, primarily due to fewer deaths from cardiovascular disease and infection. The authors urge “timely referral” for transplant.


Levodopa—when’s the best time to start?

Levodopa remains the main treatment for symptoms of Parkinson’s disease. Traditionally, neurologists have held off using it until symptoms such as bradykinesia and rigidity become troublesome because of its unwanted effects of involuntary movements (dyskinesia), fluctuations of motor control, and because its effect starts to wear off with time. But is it better to start levodopa as early as possible? Could it have a disease-modifying effect? This double-blind, placebo-controlled, delayed-start trial, randomly assigned patients with early Parkinson’s disease to levodopa with carbidopa for 80 weeks (early start group), or placebo for 40 weeks and then levodopa and carbidopa (delayed-start group.) There was no significant difference in progression of Parkinson’s disease between the two groups, which suggests that there’s no point in starting levodopa before it’s needed to treat symptoms.

Endometrial scratching doesn’t improve success of IVF

Endometrial scratching involves making superficial scratches in the endometrium in an attempt to improve the receptivity of the uterus to embryo implantation. This open-label, randomized, controlled trial followed 1364 women undergoing in vitro fertilization. Half had endometrial scratching performed in the cycle before embryo transfer and half didn’t. 26.1% had a live birth (comparable with the 21% overall rate and 29% for under 35’s in the UK), with no difference between the groups. It’s not clear how scratching works and this study suggests that it doesn’t.

The Lancet

Early calcium doesn’t prevent pre-eclampsia

Why are pre-eclampsia and eclampsia so prevalent in low-income countries? One theory is that low levels of calcium in the diet may be part of the problem. There is evidence that calcium supplementation in the second half of pregnancy reduces the severity of pre-eclampsia. But do calcium supplements given in the first half of pregnancy have a similar protective effect? This study, conducted in South Africa, Zimbabwe, and Argentina, compared the outcome in pregnant women who had previously had pre-eclampsia and eclampsia and took 500mg calcium a day in the first half of pregnancy, compared to similar women who took placebo. All these high risk women took calcium in the second half of pregnancy as there’s already good evidence for that. This study didn’t show a similar benefit in early pregnancy though. there was no significant difference in the incidence of pre-eclampsia between the two groups (23% in the calcium group, 29% in the placebo group). The trial was only powered to detect a large effect size, so some individuals or sub-groups may benefit, but that would need a different type of study to explore further.


Daily aspirin for healthy people?

Should healthy people take an aspirin a day? Do the pros outweigh the cons? It’s a question that crops up frequently and help is at hand from this meta-analysis of 13 trials with 164 225 participants with no known cardiovascular disease. Median age was 62, minimum follow up time was 1 year, and the baseline cardiovascular risk was 9.2%. It found that aspirin was associated with a lower risk of cardiovascular events (number needed to treat of 265) and an increased risk of major bleeding (number needed to harm of 210) compared to those on placebo or no aspirin. So if 1000 healthy people take a daily aspirin, approximately four will benefit from a cardiovascular point of view and a similar number will have a major bleed. This doesn’t take into account any other possible advantages of aspirin such as cancer prevention, but on the basis of this study, it doesn’t seem worth taking a daily aspirin on spec.

JAMA Intern Med

Best practice for liver transplants

Footballer George Best generated headlines when he went on an alcohol-fuelled binge within a couple of years of a liver transplant for alcohol-associated liver disease. Alcohol-associated liver disease used to be a reason not to offer a transplant, but is now the main reason to offer a liver transplant in the US. An expert panel in 1983 recommended that a six month period of abstinence should be a requirement for transplant to see if disease would stabilise without a transplant and improve public perception that donated organs weren’t being wasted. Since then studies have shown that the chances of reverting to alcoholism after a transplant for alcohol-associated liver disease is linked to many factors, but not specifically to the period of abstinence prior to the transplant. This prospective, national (US) cohort study looked at why transplant for alcohol-associated liver disease has doubled in recent years and what the long term survival rates are. Nearly half of the increase in transplants for alcohol-associated liver disease is attributed to the decrease in liver transplants needed for hepatitis C (as other treatments have become available.) People with alcohol-associated liver disease did less well after transplant in the long term (cumulative unadjusted 10-year posttransplant survival was 63%), than people who had a transplant for other reasons (cumulative unadjusted 10-year posttransplant survival was 68%)  The excess deaths were mostly due to cancer and infections and linked to a return to alcohol abuse and lower socio-economic status. What’s not clear is whether the previous requirement to abstain from alcohol prior to transplant, for at least six months, should be reinstated and what other measures are needed to support those with alcohol-associated liver disease to improve their survival after transplant, or find ways to obviate the need for a new liver altogether.


Rheumatoid arthritis—which non-TNF drug is best?

Many people living with rheumatoid arthritis find that tumour necrosis factor (TNF) α inhibitors vastly improve their quality of life. But as many as a third of people with rheumatoid arthritis don’t respond to anti-TNF drugs. Three non-TNF targeted biologic agentsrituximab (a B lymphocyte depleting agent), abatacept (targets T cell co-stimulation), and tocilizumab (an interleukin 6 receptor inhibitor) are available for these non responders and all perform better than placebo in trials. But which of the three is safest and most effective? This population-based prospective French study followed 3162 adults who had refractory rheumatoid arthritis, but were otherwise healthy. Drug retention is used as a surrogate marker for effectiveness and safety. The assumption is that if you stay on the drug, you’re probably deriving net benefit. By that (indirect) measure, patients treated with rituximab or tocilizumab fared better at 24 months than those on abatacept.

Frying tonight?

Up to a third of Americans eat food from fast food outlets every day and most of the food is fried. It’s safe to assume that the UK is catching up fast and the consensus is that it’s a bad thing. But hard evidence of the effect of a fast food habit on mortality is thin on the ground. This prospective cohort study drawn from the estimable Women’s Health Initiative used data from nearly 2 million person years of follow up and found that frequent consumption of fried foods (especially chicken and fish/shellfish) were associated with a higher risk of all-cause and cardiovascular mortality among postmenopausal women. The underlying mechanisms are unclear and require further study. On the plus side, there was no increase in cancer mortality (the heart attack gets you first, presumably.) I would quibble with the sunny optimism of the authors who say “we have identified a risk factor for cardiovascular mortality that is readily modifiable by lifestyle and cooking choices.” Personal choices are rarely “readily modifiable” in my experience. 

Ann Robinson is an NHS GP and health writer/broadcaster. She works within her local community and is a trustee of the Anthony Nolan charity.

Competing interests: None declared.