BMJ  2006;332:1025-1026 (29 April), doi:10.1136/bmj.332.7548.1025

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What's new in the other general journals

Amalgam fillings seem safe for children in the short term

Dental amalgam is half mercury, a well known neurotoxin. A vigorous debate has run for years about whether amalgam fillings poison children, mostly without the benefit of decent prospective evidence. The first two randomised trials to consider this indicate that amalgam is safe, at least in the short term. Both studies failed to find any indication of neurological damage in children whose back teeth were filled with amalgam. Controls had their back teeth filled with a resin composite instead. The trials were relatively small, however, given that many millions of children worldwide have amalgam fillings, and a linked editorial remains somewhat sceptical (pp 1835-6). Neither trial was powerful enough to detect subtle neuropsychological changes in children given amalgam fillings. Even if these changes occurred with an incidence of only 1%, they would still affect about 500 000 children worldwide. In both trials, children treated with amalgam had significantly higher urinary concentrations of mercury than children treated with composite resin. They were followed up for seven years or less, so longer term effects cannot be ruled out. The editorial concludes that it's too early to end the debate (or the research) on the safety of amalgam fillings for children.

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JAMA 2006;295: 1775-83 and 1784-92[Abstract/Full Text]

Rare but lethal complication follows ablation procedure for atrial fibrillation

Radiofrequency ablation around the pulmonary vein is an effective treatment for some patients with atrial fibrillation. Most of the time it's safe. But reports are emerging of a rare and catastrophic complication—the formation of a fistula between the oesophagus and the left atrium. Twelve cases have been reported, and only one patient has survived.

The most recent case series included nine patients who presented between 10 and 16 days after their ablation procedure. They had non-specific symptoms at first; most had a fever and felt generally unwell. All nine developed septicaemia, eight developed neurological symptoms characteristic of cerebral air embolism (multiple strokes), and three had overt gastrointestinal bleeding. The patients died of sepsis and cardiovascular collapse soon afterwards. In five patients, the fistula was discovered only at autopsy.

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The authors uncovered these cases by asking around a small but unspecified number of hospitals in the United States and in Brazil. There are likely to be more. Fever, malaise, leucocytosis, dysphagia, and neurological symptoms in patients with a recent catheter ablation procedure should ring warning bells, say the authors. Delay seems to be universally fatal.

Ann Intern Med 2006;144: 572-4[Abstract/Full Text]

Candesartan remains unproved as a prophylactic against hypertension

Prehypertension, is defined as a systolic blood pressure of 120-139 mm Hg or a diastolic blood pressure of 80-89 mm Hg, It's already a problem in the developed world, affecting an estimated 70 million people in the United States alone, where prevalence continues to rise. Treatment with drugs is one option, and the angiotensin converting enzyme inhibitor candesartan seemed to prevent or delay hypertension in a recent placebo controlled trial. Participants took candesartan or a placebo for two years. A further two years after the end of treatment, in which all 772 participants took a placebo, 208/391 (53%) in the candesartan group and 240/381 (63%) controls had developed hypertension, a significant relative reduction of 16%.

But the drug may not be as effective as it looks, says a linked editorial (pp 1742-4). At least some of the apparent benefit may be an artefact of the trial's design. Even with the most optimistic interpretation, more than half of the participants ended up with hypertension, regardless of their study treatment. For now, people with prehypertension should concentrate on the recommended lifestyle changes—sodium restriction, enhanced physical activity, weight loss, and moderation of alcohol intake.

New Engl J Med 2006;354: 1685-97[Abstract/Full Text]

European plans for bird flu are full of holes

To find out if Europe is ready for a human pandemic of avian influenza, researchers examined 21 national plans across the region, marking them for completeness and quality against the World Health Organization's latest recommendations. Although most countries have made an excellent start on the broad implications of a pandemic and how to manage it, the detail contains some notable gaps, write the authors. The plans were strong on strategic areas, such as surveillance and communication, but much weaker on specifics, including the politically sensitive question of who will get antiviral drugs and why; whether or not there will be enough; and how the chosen will get hold of them. Detail is also lacking on the development, production, distribution, and administration of vaccines (perhaps because there aren't any). Many countries still don't know how they will maintain essential services, including hospitals, and where all the extra medical equipment, such as protective clothing, is going to come from. Stockpiling of drugs and equipment has been left largely to local authorities, which may struggle without clear guidance from governments. One of the biggest problems is that most European countries are not coordinating their plans with neighbouring countries, despite directions to that effect from the European Commission.

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Lancet 2006 April 20 doi: 10.1016/S0140-6736(06)68511-5

Short or long gaps between pregnancies are bad for babies

Having babies too close together or too far apart is associated with risky neonatal outcomes. A thorough and systematic search found more than 60 observational studies from all over the world that together show that women should aim to leave at least 18 months but no more than 60 months between one pregnancy and the next. In a meta-analysis of the 26 cross sectional and cohort studies getting pregnant less than six months after giving birth was associated with an increased risk of preterm birth (odds ratio compared with intervals of 18 to 24 months 1.40, 95% CI 1.24 to 1.58), low birth weight (1.61, 1.39 to 1.86), and small size for gestational age (1.26, 1.18 to 1.33). Women who left more than five years between pregnancies were between 20% and 43% more likely to have these outcomes. The data on fetal and neonatal deaths were less clear cut, but the highest risks were in women with gaps shorter than six months or longer than 50 months. The analysis is not perfect, say the authors, but should be good enough to inform some robust policy making on family planning in both rich and poor countries. An editorial (pp 1837-8) goes further: "clinicians should counsel all women to space pregnancies at least 12 months apart, if at all possible."

JAMA 2006;295: 1809-23[Abstract/Full Text]

Green tea may protect against type 2 diabetes

Drinking a lot of coffee is associated with a reduced risk of type 2 diabetes in citizens of the United States and Europe. A large cohort study from Japan confirms this link and reports that green tea is also associated with a lower risk of type 2 diabetes, particularly in women. The cohort included 17 413 healthy Japanese adults aged between 40 and 65 who were originally recruited for a study of incident cancer. People who said that they drank more than six cups of green tea a day at baseline were a third less likely to develop type 2 diabetes than participants who drank less than one cup a week (odds ratio adjusted for age, body mass index, and other confounders 0.67, 95% CI 0.47 to 0.94). The association was dose dependent—as green tea consumption went up, risk of diabetes went down—and was confined to women.

The authors think that green tea protects against diabetes because, like coffee, it contains caffeine. Japanese men and women get about half their daily caffeine from green tea. If so, why should green tea protect women but not men? It's impossible to say for certain but the authors speculate that men who drink little or no green tea drink caffeinated cola instead, which could mask any association between green tea and diabetes. The authors had no data on consumption of cola in this cohort.

Ann Int Med 2006;144: 554-62[Abstract/Full Text]

Ondansetron helps prevent vomiting in dehydrated children with gastroenteritis

Children with diarrhoea and vomiting can quickly dehydrate, and rehydrating them is difficult if they are still vomiting. The antiemetic ondansetron may help, one placebo controlled trial has found. Children given a single 4 mg dose as a tablet that disintegrates on the tongue vomited less during the next hour than controls given an identical placebo (15/107 v 37/107; P < 0.001). They also drank more oral rehydration solution (239 v 196 ml; P = 0.001), needed a smaller volume of intravenous fluids (38 v 46 ml/kg; P = 0.002), and went home sooner than controls (after 106 v 120 minutes; P = 0.02). The only notable side effect was an increase in the number of episodes of diarrhoea in the hour after treatment with ondansetron (1.4 v 0.5; P < 0.001). The authors, who were familiar with this problem, say that it was clinically insignificant.

The trial was independent of the drug's manufacturers and included children between 6 months and 10 years old who presented to the emergency department of a single US hospital with diarrhoea and vomiting from gastroenteritis, accompanied by mild or moderate dehydration. The authors estimate that to prevent one child vomiting, five children would need treatment with ondansetron in this setting.

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New Engl J Med 2006;354: 1698-1705[Abstract/Full Text]

Link between education and heart disease remains unexplained

Getting better educated by staying at school or college is one way of staying healthy. The longer you stay in full time education, the lower your risk of cardiovascular disease, for example. Although the link is well established, researchers still don't fully understand it. We know that education helps people access health care when they need it; navigate through complicated healthcare systems; and stick to their treatment. We also know that education helps people avoid disease by managing risk factors such as smoking and body mass index. But neither of these could fully explain the clear association between education and subclinical coronary artery disease in a cohort study of 2913 asymptomatic middle aged US citizens. Participants who had failed to graduate from high school were four times more likely to have calcium in their coronary arteries than those who had stayed in full time education beyond college (odds ratio 4.14, 95% CI 2.33 to 7.35). Risk factors such as smoking, waist circumference, blood pressure, and exercise explained only half the association. This means that there is still more work to do on the other half.

JAMA 2006;295: 1793-1800[Abstract/Full Text]

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Rapid Responses:

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candesartan NEJM

Adrian Verrinder
bmj.com, 28 Apr 2006 [Full text]

candesartan

Thomas Simonson
bmj.com, 28 Apr 2006 [Full text]