Folic acid supplementation
Folic acid supplements reduce neural tube defects and may reduce premature labour too. For these reasons, many countries (although not the UK) have legislated to mandate folic acid fortification of flour. But interventions imposed on people who can’t opt out need to be safe – especially for those unlikely to derive any benefit – and a report from Norway in JAMA contains worrying findings. The people in the study had all taken part in RCTs of folate and B vitamin supplements several years ago when it was still hoped that these vitamins had beneficial cardiovascular effects. Follow-up after the trials ended shows a small but statistically significant increase in cancer incidence, cancer mortality, and all-cause mortality in those treated with folate relative to the control group.
Can patients manage their own blood pressure?
Blood pressure control in patients with hypertension is typically poor, but a study in Annals of Internal Medicine promotes greater patient involvement. The authors randomised 636 hypertensive patients to either a behavioural self-management intervention every 2 months, home blood pressure self-monitoring, both interventions, or usual care. At 2 years, neither intervention alone significantly improved on usual care, but the combined group had 11% more patients under control, and an estimated systolic BP reduction of about 4 mmHg. Most patients already had reasonable control at entry, so investigation in a less cooperative group would be interesting.
Teenage pregnancies
A systematic review in the BMJ reports that the most important things associated with early parenthood are dislike of school, poor material circumstances, an unhappy childhood and low expectations for the future. No great surprises there, you may think, but accurate identification of causes can lead to effective interventions. In the second half of the paper, pooled results from 10 controlled trials show that early childhood interventions and youth development programmes can reduce teenage pregnancy rates by ~40%. Wouldn’t it be better to invest in interventions that target social disadvantage, instead of flogging the dead horse of sex education?
Erythropoietins and stroke in chronic kidney disease
Correcting the anaemia of chronic kidney disease using erythropoietins is often assumed to be beneficial, and placebo-controlled trials argued to be unethical. However, results of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) published in the NEJM, suggest otherwise. In 4038 patients with diabetes, chronic kidney disease and anaemia, those treated with darbepoetin alfa showed no improvement in cardiovascular outcomes, and almost double the risk of stroke. An accompanying Editorial raises questions regarding between-group differences in baseline characteristics, but there seems little doubt that old assumptions must be discarded.
Legius syndrome
Neurofibromatosis type 1, which older readers will remember as von Recklinghausen’s disease, is one of the commoner autosomal dominant disorders. The clinical features are variable, but typically include multiple café-au-lait spots, skin-fold freckling, cutaneous neurofibromata and other tumours of the nervous system such as optic nerve gliomas and astrocytomas. It’s caused by a mutation in the NF1 gene, a tumour suppressor gene, on the long arm of chromosome 17.A report of two surveys of people with the clinical characteristics of neurofibromatosis in JAMA describes the almost indistinguishable Legius syndrome, where the defect lies in the SPRED1 rather than the NF1 gene: the phenotype is similar but the potential risk of malignancy may be lower.
B16 genotype and asthma treatment
Studies have suggested that genetic variation in ADRB2, the gene encoding the β2 receptor, could underlie variation in response to β2 agonists in asthma, although results are mixed. A study in the Lancet investigates the influence of a single nucleotide polymorphism (B16 Gly/Gly vs Arg/Arg) on response to salmeterol against a background of inhaled corticosteroid. Although a previous retrospective analysis of trial data by these authors predicted lower response in Arg/Arg patients, no such effect was found. An accompanying Comment recommends genome-wide studies as the way forward, and cautions against regarding post-hoc subset analyses as anything more than hypothesis-generating.
Depression after CABG
Depression following coronary artery bypass grafting is common, although the mechanism remains mysterious. A study in JAMA treats patients who screened positive for depression 2 weeks after discharge from hospital with a ‘collaborative care’ strategy combining education, antidepressant pharmacotherapy and regular telephone follow-up. Patients receiving the intervention had better mental HRQL, physical functioning and mood symptoms at 8 months, compared to those receiving usual care, with men appearing to benefit more. However, as the authors admit, while a multi-pronged approach is more likely to succeed, it sheds little light on which components are important.
Inadequate information about trial participants
An important but easily overlooked question regarding clinical trials is how far the findings can be extrapolated. If the people taking part were mostly middle-aged and elderly men, can one reasonably expect similar results from the same intervention in women or younger people? It’s a particular problem in surgical trials because the people who get recruited and the surgeons who operate are both often unrepresentative of normal practice. An assessment in the BMJ of trials of orthopaedic surgical procedures finds that information on participants and the context in which they received care is often so deficient that it’s not possible to judge whether the trial findings are generalisable.