On The Pulse - 15th June 2012

Dizziness
People with vestibular dysfunction who get dizzy when they shake their heads or change their posture naturally try to avoid movements that precipitate symptoms. Unfortunately, this only perpetuates the condition; instead they need to stimulate their inner ears and allow the brain to accommodate to the abnormal sensory input, much as seasoned sailors stop feeling seasick. A trial in the BMJ shows that providing patients with a booklet that teaches them how to do this is highly effective, and highly cost effective too. There’s no link to the booklet in the article, but you can download it here.

When metformin is not enough
Two studies in the Lancet address the question of how to treat people with type 2 diabetes who are inadequately controlled on metformin. The EUREXA trial randomises 1000 such patients to the GLP-1 receptor agonist exenatide vs the sulphonylurea glimepiride. At 3 years, HbA_1c and hypoglycaemia were lower in the exenatide group, albeit with some gastrointestinal adverse effects. The EASIE trial randomises 500 patients to insulin glargine or the DPP-4 inhibitor sitagliptin: insulin glargine achieved lower HbA_1c at 26 weeks, but increased hypoglycaemia and adverse events. An accompanying Editorial thinks only evidence of long-term benefit can justify the additional treatment burden of insulin.

Fat taxes
In the past year, Denmark has introduced a fat tax, Hungary a junk food tax, and France a tax on sweetened drinks. Many doctors think that the UK should follow suit, and a recent article in the BMJ advocates a tax of at least 20% on a wide range of unhealthy foods. A rapid response points out that no politician who imposed such a tax would get re-elected, and even at 20%, it would have very little effect. Better for a government to change its agricultural policy, practice what it preaches (the government is Britain’s largest caterer) and name and shame companies that charge higher prices for healthier foods.

Insulin glargine and n–3 fatty acids in dysglycaemia
Two papers in the NEJM report the results of the ORIGIN trial, which randomises 12,500 patients at high risk for cardiovascular events, and with impaired fasting glucose, impaired glucose tolerance or diabetes, to insulin glargine or usual care, both with and without n–3 fatty acid supplementation, in a 2×2 factorial design. Neither intervention made any difference to the rate of cardiovascular events (or cancer) over 6 years. Insulin glargine did reduce the rate of new-onset diabetes compared to usual care, but at the cost of more hypoglycaemia and some weight gain.

Psychotherapy by telephone
Although many depressed patients in primary care say that they would prefer psychotherapy to antidepressant medication, a large proportion drop out of treatment, even when it’s provided promptly. One explanation is that finding time and getting transport make it too hard for depressed people to attend regular face-to-face sessions. A trial in JAMA shows that providing therapy by telephone helps, reducing drop-outs from around 30% to 20% at the cost of a small reduction in effectiveness. At 6 months, patients receiving face-to-face therapy were less depressed than those treated over the telephone.

Delamanid for multidrug-resistant tuberculosis
Treatments for multidrug-resistant tuberculosis are badly needed, with some 440,000 cases annually worldwide. A study in the NEJM randomises 481 patients to two doses of delamanid, a new drug that inhibits mycolic acid synthesis, or placebo, plus a drug regimen based on WHO guidelines. At 2 months, 40–45% of those receiving delamanid became sputum-negative vs 30% of those receiving placebo (p=0.008).  An accompanying Editorial reviews the rise of multidrug-resistant tuberculosis, and points out that the next problem is to find the best way to use novel drugs such as delamanid.

Aspirin and bleeding
To what extent are the modest benefits of low-dose aspirin in the primary prevention of cardiovascular disease offset by the risk of bleeding? A population-based study in JAMA identifies nearly 200,000 people starting low dose aspirin and tracks them for hospitalisation for gastrointestinal or intracranial bleeding. Over 6 years of follow up, aspirin use carried a 55% relative risk increase in major bleeding which, in absolute terms, means 2 excess cases for every 1000 patients each year – about the same as the number of cardiovascular events prevented.

Citicoline for acute ischaemic stroke
Citicoline, an exogenous form of cytidine-5’-diphosphocholine, is thought to protect neurons in the ischaemic penumbra from hypoxia during stroke, but while trials have suggested it is safe and well tolerated, its efficacy is disputed. The ICTUS trial, published in the Lancet, randomises 2300 patients with moderate-to-severe ischaemic stroke of < 24 h onset to citicoline or placebo for 6 weeks. No overall difference in outcomes was seen between groups, and the trial was stopped early for futility. An accompanying Comment discusses the possible reasons for heterogeneity among the existing trials, but concludes that this result is likely to be correct.