Christopher Martyn’s research reviews—11 March 2019

Christopher Martyn reviews the latest research from the top medical journals

Annals Internal Medicine

MMR vaccine safety

Yet another study fails to find any excess risk of autism in children vaccinated with MMR. The investigators used Danish population registries to link information on vaccination, diagnosis of autism, sibling history of autism, and risk factors for autism in children born between 1999 and 2010. During more than 5 million person-years of follow-up, 6517 children were diagnosed with autism, but the risk was no higher in MMR-vaccinated children than it was in unvaccinated children. Indeed, the hazard ratio of 0.93 (95% CI, 0.85 to 1.02) shows that, if anything, MMR vaccine protects against autism. This is one of the largest studies published and, apart from adding statistical power, it refutes ideas about susceptible subgroups and clustering of cases. Whether it will change anyone’s mind is another matter.

Aspirin in prostate cancer

Pooled analyses of cardiovascular disease prevention trials found a reduced risk of cancer among people who had been allocated to aspirin use. But a registry based study from Denmark finds little evidence that  taking aspirin after a diagnosis of prostate cancer has any beneficial effect. In nearly 30 000 patients followed for a median of 5 years, neither prostate cancer specific mortality nor all cause mortality were lower in those who had received prescriptions for aspirin within a year of diagnosis. Secondary analyses give a hint that taking aspirin for more than 5 years was associated with slight reductions in mortality but it’s almost impossible to interpret these results. First, aspirin wasn’t allocated at random and second, use of aspirin was judged only from prescriptions data. No information about use of aspirin bought over the counter was available.


Multinutrients, diet, depression and obesity

Observational studies show that people who eat better diets are less likely to become depressed. Small trials suggest that improving diet reduces symptoms in people who are depressed. So, perhaps it’s not unreasonable to hope that interventions intended to improve diet and eating habits might prevent depression in overweight and obese people. Disappointingly, it turns out that they don’t. An international trial randomly allocated over 1000 people either to daily multinutrient supplements, or to therapy sessions intended to improve mood and eating behaviours, or to both these interventions, or to placebo. During a year’s observation, none of the interventions, either alone or in combination, was better than placebo in reducing episodes of major depressive disorder.

An integrated intervention for obesity and depression

Obesity and depression commonly occur together in individual patients. What’s more, the two conditions share common co-morbidities such as type 2 diabetes and cardiovascular disease, and their coexistence is associated with poorer adherence to treatment and response to therapy. A trial in 400 patients with obesity and depression tests an intervention that attempts to overcome these barriers by combining a behavioural treatment for weight loss with a problem-solving therapy for depression and, if judged necessary, antidepressant medication. Over 12 months there were statistically significant improvements in both BMI and in depressive symptoms, but the size of the changes was so small that it’s doubtful if they’re of any clinical importance.

New England Journal of Medicine

Sequelae of Ebola virus infection

No one will be surprised to learn that people who have survived Ebola virus disease complain of multiple health problems. A longitudinal study from Liberia followed nearly a thousand antibody–positive survivors comparing them with twice that number of antibody-negative close contacts. Symptoms of urinary frequency, headache, fatigue, muscle pain and memory loss were commoner in survivors, and they were also more likely to have abnormal findings, particularly uveitis, when examined. With the exception of uveitis, the prevalence of these conditions declined during 12 months follow-up.  Ebola virus RNA persisted in semen samples from around a third of the survivors.

Fluorouracil for actinic keratosis

Actinic keratoses, also known as solar keratoses, are rough patches of skin caused by damage from years of sun exposure. They’re most commonly found on the scalp, face, and forearms and hands. Although the NHS website is reassuring, saying that they aren’t usually a serious problem and may resolve spontaneously, actinic keratosis is  the most frequent premalignant skin disease in white population groups. Left untreated, actinic keratoses may develop into squamous-cell carcinoma. A trial at four hospitals in the Netherlands compared four established treatments head to head (fluorouracil cream, imiquimod cream, methyl aminolevulinate photodynamic therapy, and ingenol mebutate gel). Judged by the primary outcome of a reduction of 75% or more in the number of lesions 12 months after the end of treatment, fluorouracil cream was the most effective. Patient satisfaction and health-related quality of life were also highest in the fluorouracil group.

The Lancet

Glyceryl trinitrate after stroke

Raised blood pressure is common after stroke and predicts a poor outcome. However, it’s not clear whether treatments to lower blood pressure are helpful. A few years ago, a large trial showed no benefit from transdermal glyceryl trinitrate given within 48 hours of stroke. But 48 hours might be too late: given in the hyper-acute phase of stroke, blood pressure lowering treatment might be more effective.   This idea has been tested in a remarkable trial in which trained paramedics recruited and treated people with presumed stroke within 4 hours of onset of symptoms with transdermal glyceryl trinitrate. Over a third of patients received treatment within an hour of the onset of the stroke. The intervention successfully lowered blood pressure (by around 6mm Hg in the treatment group) but there were no differences between groups in functional outcome at 90 days.

Evacuation of intracerebral haematoma

Surgical evacuation of the haematoma after spontaneous intracerebral haemorrhage might lessen compression and distortion in the surrounding brain tissue and reduce ischaemia, but trials have failed to show benefit in terms of mortality or functional outcome. Unfortunately, the results are no better when craniotomy is replaced by a minimally invasive approach. The MISTIE trial used image guided catheters to aspirate and then irrigate the haematoma with alteplase, randomising 506 patients either to this intervention or to standard medical care. At a year there were no differences between groups in the proportion of patients who had achieved a good functional outcome.

Christopher Martyn is an associate editor, The BMJ.