Frontiers

Epidemiology

MRSA spreads among gay men

Ann Intern Med 2008 Feb 19 www.annals.org/cgi/content/full/0000605-200802190-00204v1

A new clone of methicillin resistant Staphylococcus aureus (MRSA) has recently emerged in the United States, and researchers suspect it is being sexually transmitted between men who have sex with men. The clone is community acquired and resistant to multiple classes of antibiotics, including recommended treatments for regular community acquired MRSA, such as clindamycin and tetracycline.¹

Incidence of new resistant clone in San Francisco by zip code

Researchers studying the epidemiology of the multidrug resistant USA300 strain in San Francisco found the highest incidences in areas where men who have sex with men tend to live. Male-male sex was an independent risk factor for infection in populations from San Francisco and Boston. A considerable number of infections with the new clone affected the buttocks, genitals, and perineum.

The epicentre of new infections seems to be the Castro district of San Francisco, where more than a quarter of all couples are male, say the researchers. Here, the incidence of infections caused by the new clone is 170 cases per 100,000 people (95% CI 41 to 299), compared with only 4 cases per 100,000 people (0 to 8) in districts with the lowest proportion of all male couples. (This item was first published in the BMJ, 2008;336:182-3; doi: 10.1136/bmj.39465.409051.80.)

Psychiatry

Selective reporting of antidepressant trials

N Engl J Med 2008;358:252-60

Publication bias is a well known problem. Trials with positive results are more likely to be published than trials with negative results, so that treatments sometimes look better in the published literature than they really are. When researchers from the US looked for publication bias in trials of antidepressants they found that the published data overestimated the efficacy of these drugs by nearly a third.

The researchers started with all antidepressant trials registered with the Food and Drug Administration for licensing purposes, then they looked carefully for published reports of the same trials. Nearly a third of the trials were not published (23/74). All but one of the unpublished trials were negative or equivocal. Ninety four per cent of published trials reported positive results compared with only half of all trials registered with the FDA.

All 12 drugs included in the study looked more effective in published trials than in trials registered with the FDA. The difference varied from 11% to 69%, with a median of 32%.

This kind of selective reporting biases the evidence base in favour of new drugs and is unfair to trial participants who have put themselves in harm’s way to test them, say the researchers. It also drives doctors to make the wrong treatment decisions, and it harms individual patients and the wider public health. (This item was first published in the BMJ, 2008;336:182-3; doi: 10.1136/bmj.39465.409051.80.)

Cardiology

Immunological treatment for heart failure

Lancet 2008;371:228-36

Heart failure triggers the immune system in a way that may cause further myocardial damage. One way to suppress this is to give patients small samples of their own blood that has been treated to induce apoptosis. The result is a non-specific rebalancing of proinflammatory and anti-inflammatory mediators, but does it have a detectable effect on survival?

The first large trial reported mixed results. Overall, patients with chronic severe heart failure given monthly intramuscular injections of their own treated blood were no less likely to die or be admitted to hospital than controls given matching placebo injections (hazard ratio 0.92, 95% CI 0.80 to 1.05). The treatment did work, however, in two subgroups of patients with less severe heart failure than the rest—those without a previous history of heart attack (0.74, 0.57 to 0.95), and those with NYHA (New York Heart Association) class II disease (0.61, 0.46 to 0.80). Both results are preliminary.

The researchers were disappointed. There is good evidence that chronic inflammation exacerbates heart failure, and the new treatment looked promising in smaller trials. Scientists pursuing this line of research will have to watch for cancer and infections—unintended consequences of immune manipulation—says a linked comment. Both could be slow to emerge. (This item was first published in the BMJ, 2008;336:182-3; doi: 10.1136/bmj.39465.409051.80.)

Neurology

Understanding Parkinson’s disease

Nature Medicine 2007;14:75-80

Deep brain stimulation is widely used as a neurosurgical treatment for tremors and several movement disorders, including Parkinson’s disease. In addition, clinical trials are underway to test its effectiveness in treating psychiatric conditions such as obsessive-compulsive disorder and depression. Despite the rise in the number of people having electrodes implanted in their brain tissue, it is not known how deep brain stimulation works, certainly at the molecular level. Researchers think that adenosine, the catabolic product of ATP, may play an important part.

The researchers first triggered symptoms of Parkinson’s disease in mice using drugs and then showed that infusion of adenosine dampened the tremors. This, they were able to show, was a result of activation of the adenosine A1 receptor in the thalamus of the mice. What’s more, subsequent intrathalamic infusion of specific A1 receptor antagonists exacerbated the tremors. This suggests a new avenue for the pharmacological treatment of Parkinson’s disease, they say. An important additional finding is that caffeine, a non-selective adenosine receptor antagonist, can also trigger or exacerbate tremors.

Immunology

A fertility modulating molecule

Proc Nat Acad Sci USA 2007;104:19357

Nature 2007;450:721

Leukaemia inhibitory factor, a secretory glycoprotein, was identified because of its role in leukaemic cell differentiation. Its role as a cytokine in the female reproductive tract is now thought more important. In mice it is one of the few molecules known to be required for implantation of the blastocyst. It has been hypothesised that depending on the mode of action, drugs that target this factor could be used to increase fertility by promoting implantation or as contraceptives to prevent pregnancy.

Two independent research groups have reported progress on both fronts. One group has chemically modified the factor so that it acts as a ligand for the corresponding receptor but fails to activate it, preventing all the activities that usually follow. Systemically administered, this molecule was capable of completely blocking implantation of blastocysts in mice.

Another group, meanwhile, has found that expression of leukaemia inhibitory factor in mice in uteri is positively regulated by—that is, its expression is increased by—the well studied p53 tumour suppressor gene. This raises the possibility that drugs designed to activate p53 might be used to increase fertility.

Competing interests: None declared.

Provenance and peer review: Commissioned; not peer reviewed.