Short Cuts

All you need to read in the other general journals

BMJ 2010; 340 doi: (Published 16 March 2010) Cite this as: BMJ 2010;340:c1476

Old treatments have a low profile in leading medical journals

Between 2008 and 2009, six leading medical journals published 328 studies evaluating drug treatments for disease. Less than a third (104/328) compared one established treatment with another, or otherwise helped doctors and patients make everyday decisions about which treatment to use, which dose to prescribe, how to avoid side effects, or how long to treat. Researchers trawled through the six journals to try and quantify a much publicised blind spot in biomedical research—comparative effectiveness studies evaluating existing treatments and informing real world choices.

Among the 104 comparative effectiveness studies they found, few compared drug treatments with non-drug treatments such as behaviour change (11/104), and even fewer included a cost effectiveness analysis (2/104). One in six (16/104) compared different dosing strategies, and only one in five (20/104) focused on drug safety.

Nearly all studies relied on non-commercial funding (90/104), because commercial organisations are necessarily more interested in evaluating new drugs against placebos, for the regulators. The US government recently pledged more than $1bn (£0.66bn; €0.73bn) for research dedicated to helping doctors and patients get the most out of existing treatments. This snapshot should help direct the money where it is needed most. Used wisely, the new money has the potential to transform health care in the US, adds one observer (p 985).

Donating a kidney looks safe in a large study from the US

Live kidney donors are one answer to the chronic shortage of kidneys for transplantation. But is it safe to donate a kidney to a relative? The most reassuring data so far come from a large cohort of more than 80 000 adult donors who had a nephrectomy between 1994 and 2009 in the US. Just 25 died within 90 days of surgery—an associated mortality of 3.1 per 10 000 donations, which is substantially lower than the mortality associated with laparoscopic cholecystectomy (18/10 000).

Long term survival was excellent. Donors were no more likely to die during six years of follow-up than matched controls from the general population. In fact, they were less likely to die, although this advantage was probably caused by residual differences in health and fitness that were unaccounted for by matching and adjustments. Donors are carefully selected after a battery of tests, say the authors. Controls were selected using basic demographic and comorbidity information from a less detailed national survey. The donors were probably healthier.

Surgery was riskier for men than for women (mortality 5.1 v 1.7 per 10 000 donors; risk ratio 3.0, 95% CI 1.3 to 6.9), and black donors had a higher surgical mortality than white or Hispanic donors (7.6 v 2.6 and 2.0 per 10 000 donors; 3.1, 1.3 to 7.1). These subgroups should be counselled accordingly, say the authors. The small minority of donors with hypertension (2%) had the highest risks of all.

An oral drug for hard to treat head lice

Head lice are becoming resistant to commonly used topical insecticides, and researchers have begun to look for alternatives. The oral drug ivermectin, which is known to be active against other ectoparasites such as scabies, cured more head lice infestations than topical malathion in a cluster randomised trial (95.2% (378/397) v 85% (352/414); P<0.001; number needed to treat 9.8, 95% CI 6.4 to 21.7). The authors randomised 376 families with persistent infestations of head lice despite at least one treatment with a topical insecticide. Affected family members had a mean age of 10 and had two treatment sessions eight days apart, in a double dummy design. The active component was either 400 µg per kg of oral ivermectin or a lotion containing 0.5% malathion, which was applied to dry hair and left in for 10-12 hours. The trial was paid for by companies with a commercial interest in ivermectin.

The ivermectin seemed to work significantly better after 15 days and caused no more side effects than the malathion lotion. One 7 year old girl had a convulsion six days after taking ivermectin. After investigation, the seizure was attributed to an eplileptogenic focus in the right centrotemporal area. She made a full recovery.

Elective coronary angiography is poorly targeted

People with suspected coronary artery disease go through a variety of tests and assessments before they get as far as coronary angiography, but selection remains poor. In one large cohort from the US, only 37.6% (149<thin739/398 978) of adults tested with angiography had clinically relevant coronary artery disease. The rest were exposed to the risks and radiation unnecessarily, say the authors.

The study looked at 398 978 adults with suspected heart disease. They had elective angiography prompted by a combination of symptoms, risk factors, and diagnostic work-up that could include any non-invasive test. More than a third (39.2%) had effectively clean coronary arteries, defined by the authors as less than 20% stenosis in all coronary vessels. The usual risk factors—including male sex, age, diabetes, smoking, dyslipidaemia, hypertension, and peripheral vascular disease—independently predicted obstructive coronary artery disease on angiography. So did typical chest pain (adjusted odds ratio relative to no symptoms 1.91, 95% CI 1.78 to 2.05).

Most of the cohort (84%) had non-invasive tests before their angiography. Two thirds had positive results, but non-invasive tests didn’t add much to prediction models using just risk factors and symptoms.

Improving the diagnostic performance of preliminary investigations such as computed tomography, echocardiography, and stress tests may help target angiography better, say the authors. Clinicians should also think carefully before recommending angiography for people without symptoms (30% of this cohort). Relief of symptoms is the main goal of treatments for coronary artery disease.

Variations in blood pressure matter too

Chronically unstable blood pressure is a bad sign for people with treated hypertension or a previous transient ischaemic attack (TIA). A series of analyses has confirmed that long term variability is associated with an increased risk of stroke, and that the excess risk is independent of average systolic blood pressure.

Four cohorts of people with TIA or minor stroke and one cohort of people with treated hypertension contributed to the analyses. All the cohorts came from large published randomised trials. The authors focused on variation in blood pressure between clinic visits. Adults with TIA who were in the top 10th of variability were six times more likely to have a stroke than those in the bottom 10th (hazard ratio 6.22, 95% CI 4.16 to 9.29). The corresponding hazard ratio for people with treated hypertension was 3.25 (2.32 to 4.54).

A commentary says these data could explain why some antihypertensive drugs are better than others at preventing stroke (p 867). In a linked systematic review, calcium channel blockers and non-loop diuretics were significantly better at controlling variations in blood pressure than other drug classes. They were also better at preventing strokes. Because none of the trials recorded variation in blood pressure within individuals, the authors used variation between individuals as a proxy.

A link between variable blood pressure and stroke is not new, says the commentary, but these analyses make it clear that we should be thinking beyond “usual” or average blood pressure when making treatment decisions. Peak systolic blood pressure also predicted stroke in the TIA cohorts. Again, the effect was independent of mean systolic blood pressure.

Light drinking linked to slower weight gain for middle aged women

Middle aged women who reported a light or moderate alcohol intake were less likely than non-drinkers to become overweight or obese during a 13 year study. Nearly 20 000 female healthcare workers had a normal body weight when recruited to the Women’s Health Study in the early 1990s. The cohort gradually gained weight over the next 13 years—41.3% (7942/19 220) became overweight and 3.8% (732/19 220) became obese. The authors modelled their self reported drinking habits against risk of weight gain and found a clear and significant trend—those who drank most gained least, up to a threshold of around 30-40 g of alcohol a day (three half pints of beer or three small glasses of wine). After extensive adjustments to account for the different lifestyles and diets of women who drink more or less alcohol, the relative risks for becoming overweight or obese fell from 1.00 for non-drinkers (reference) to a low of 0.78 (95% CI 0.67 to 0.90) for the small number of women who drank at least 30 g alcohol a day. The link survived sensitivity analyses and seemed the same for women of all ages.

The authors can’t confidently explain their findings, although others have reported similar associations in female nurses. The evidence so far points to a distinct difference between the sexes. Alcohol is generally associated with weight gain in men, possibly because they drink on top of their usual dietary intake. In this study, as in others, women who drank more tended to eat less.

Smart tax incentives could improve a nation’s diet

Pizza and sugary drinks are getting cheaper in real terms, and a growing number of experts think policy makers should tax unhealthy food and drink in an attempt to reduce consumption. One team of researchers recently calculated that an 18% surcharge on pizza and soda would reduce overall daily energy intake by 56 kcal (234 kJ) a person, causing an average weight loss of 2.25 kg for each person each year.

These final estimates came from a study that modelled the changing price of various foods, both healthy and unhealthy, with the diet and body metrics of 5115 US adults who were surveyed at regular intervals over 20 years. A $1 (£0.66; €0.73) increase in the price of both pizza and soda was associated with significantly lower consumption, lower daily energy intake, and lower body weight.

The data weren’t perfect, and the results for hamburgers were unconvincing, but a linked comment (p 405) says this study adds to other evidence supporting the case for taxing unhealthy food and drink, particularly sweet fizzy drinks such as cola. The extra revenue could pay for subsidies to cut the price of fruit and vegetables, tax incentives to encourage good retailers to open in low income communities, and measures to freshen up the nation’s frozen and well travelled school dinners.


Cite this as: BMJ 2010;340:c1476