On the Pulse - 30th January 2009

Genetic determinants of response to clopidogrel
Only last week, this column suggested that personalized genetic medicine was still a long way off, despite the hype a few years ago. However, a French study in the NEJM has just brought it a step closer. The investigators followed up 2000 people being treated with clopidogrel after acute myocardial infarction and genotyped them for variants of some of the many genes modulating absorption, metabolic activation and biological activity of the drug. The most striking finding was that people carrying two CYP2C19 loss-of-function alleles had a substantially (~3.5 times) higher rate of subsequent cardiovascular events. Another study, also in the NEJM, shows that this genetic variant is associated with lower levels of the active metabolite of clopidogrel, and confirms the increased risk of vascular events.

No steroids for wheezing kids
Intermittent wheezing is common in pre-school children, although its cause is uncertain. A paper in the NEJM debunks the frequent treatment of such cases with prednisolone, showing that in 687 children presenting to three hospitals in England, it was no more effective than placebo in terms of duration of hospitalization or a number of secondary measures. This is no doubt because the great majority of such children do not have atopic conditions. An accompanying Editorial assesses the evidence from this and a related paper on pre-emptive fluticasone for wheeze prevention, and concludes that we have been treating pre-school children as miniature adults for far too long.

Clinical detection of pleural effusion
New diagnostic tests are, quite rightly, evaluated in terms of sensitivities, specificities and predictive values before they are put into clinical practice. But it’s rare for the techniques of clinical examination to be scrutinized in the same way. A systematic review in JAMA identified only five prospective studies of the usefulness of physical findings in the diagnosis of pleural effusions; dullness to percussion and asymmetric chest expansion turned out to be the most accurate signs. Even so, a chest radiograph is still recommended to confirm the diagnosis.

Better therapy for prostate cancer
In advanced prostate cancer, it has been known for several years that radiotherapy plus endocrine therapy has benefits over radiotherapy alone. A study in the Lancet shows that the converse is also true: when 875 men from 47 Scandinavian centres were openly randomized to anti-androgens alone or anti-androgens plus radiotherapy, overall 10-year mortality was 39.8% in the former group, but only 29.6% in the latter. The effect was even stronger when only deaths from prostate cancer were considered. There was a small increase in adverse effects in the combined-therapy group, and perhaps a slightly greater decline in social function, but it seems safe to assume that most patients will think that this is a small price to pay for a reduction in mortality.

Escitalopram in older people with anxiety disorder
A placebo-controlled RCT in JAMA claims short-term benefit from the SSRI escitalopram in people aged over 60 with generalized anxiety disorder. The most commonly reported adverse effects were fatigue and somnolence, but the drug was generally well tolerated, and the drop-out rate from adverse effects was only 3%. However, the overall drop-out rate was higher; of 179 patients randomized, only 144 completed the 12-week trial period. If the data are analysed conservatively, assuming that people who dropped out did so because the treatment didn’t work, the difference in response rate between escitalopram and placebo disappears.

Acute geriatric units
Data on the effectiveness of acute geriatric units are scanty, and systematic reviews have often lumped them in with geriatric evaluation and maintenance units, which are more concerned with care after an acute problem has stabilized. A meta-analysis in the BMJ surveys 11 studies, including 5 RCTs, and concludes that compared with those admitted to convention care, elderly patients admitted to an acute geriatric unit had less risk of functional decline at discharge, and were more likely to continue living at home. A trend towards reduced case fatality was not quite significant, but even so, the findings suggest that these units are worthwhile.

Neurofibromatosis
Type 1 neurofibromatosis (NF1), also called von Recklinghausen disease, is one of the commonest autosomal dominant disorders, and is caused by a defect in a tumour-suppressing gene on the long arm of chromosome 17. People with the condition develop disseminated cutaneous and subcutaneous neurofibromas of varying size, and multiple café-au-lait skin patches. The clinical manifestations are variable, and many patients with mild neurofibromatosis have little disability. But a report in the Canadian Medical Association Journal of a man with visual loss caused by an optic nerve glioma is a reminder of the increased risk of tumours of the central nervous system. Children with this diagnosis need regular specialist monitoring, and all people with NF1 should be encouraged to seek review of any unusual symptoms.

Carers or abusers?
People with dementia are notoriously difficult to look after, for many reasons. But how often does the frustration experienced by family carers slip over into behaviour that would be considered abusive by the law? A study in the BMJ attempts to find out – simply by asking a sample of carers. About 50% reported abusive behaviour (defined as causing harm or distress) at some time, with 33% saying it happened ‘sometimes’ or more often. Given the possibilities of recruitment and recall bias, these data may understate the true picture.