BMJ  2005;330:623-624 (19 March), doi:10.1136/bmj.330.7492.623

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What's new in the other general journals

Computerised reminder reduces venous thromboembolism in inpatients

A team from Boston has developed a computerised alerting system that improves outcomes for patients. In a large randomised trial, a computer program that reminded doctors to give their inpatients prophylaxis against venous thromboembolism reduced the risk of deep vein thrombosis or pulmonary embolism at 90 days by 41% (hazard ratio 0.59; 95% CI 0.43 to 0.81; P = 0.001).

The program, which was written from scratch, trawled through a Boston Hospital's patient database identifying patients at risk of venous thromboembolism and checking whether they were being treated. The program then randomised the 2506 who weren't being treated to an intervention group (their doctors got a reminder) or a control group. Four fifths of the patients recruited were medical inpatients; most patients recruited had cancer.

Mechanical or pharmacological prophylaxis was ordered for 421 of the 1255 patients in the intervention group (33.5%) and 182 of the 1251 patients in the control group (14.5%, P < 0.001). More importantly, patients in the intervention group were significantly less likely to get a deep vein thrombosis or pulmonary embolus during the next 90 days (figure).

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The authors were encouraged by their results, but disappointed that nearly two thirds of the doctors prompted by the program chose to ignore the reminder.

New England Journal of Medicine 2005:352: 969-77[Abstract/Full Text]

Computerised decision support helps doctors more than patients

In general there's plenty of evidence that computerised decision support can help doctors improve their clinical performance, but it's harder to find evidence that it helps patients. In a systematic review of comparative trials, 62 of 97 studies (64%) found that doctors did better with computerised decision support, reporting improvements in diagnosis, preventive care, and disease management. Fifty two trials looked at one or more patient outcomes, but only seven (13%) found improvements associated with the decision aid. Many of the studies involving patients weren't big enough to be conclusive, and none reported improvements in important outcomes such as survival.

Systems that prompted automatically seemed to work best for doctors. They improved performance in 44 of 60 trials (73%), compared with a success rate of 17/36 (47%) for systems that had to be activated by the user.

Despite a great deal of research, we have a lot to learn about computerised decision aids for doctors, say the authors. We still don't know anything about the cost effectiveness of these aids; it's unclear how best to evaluate them, and we know very little about what makes a good one.

JAMA 2005;293: 1223-38[Abstract/Full Text]

Survey shows substantial delays in childhood immunisations

We already know that fewer than one in five American children get all their immunisations on time. A new study shows that delays can stretch to months, even years. In a national survey of 14 810 children aged 2 to 3 years, three quarters had been late for at least one immunisation. These children were underimmunised for a mean of 232 days in their first two years of life—that's more than seven months. Overall, 37% of children surveyed were underimmunised for at least six months.

About a fifth of all children had severe delays in their immunisation schedule; 21% were more than six months late for four or more of the six immunisations included in the study: polio, Haemophylus influenzae type B (Hib), hepatitis B, varicella, and the combinations diphtheria, pertussis, tetanus (DTaP), and measles, mumps, rubella (MMR). Severe delay was associated with having an unmarried mother (odds rato 1.3; 95% CI 1.1 to 1.6), a poorly educated mother (2.3, 1.9 to 3.0), or siblings (1.8; 1.5 to 2.2).

The authors say their study shows substantial cracks in traditionally successful US immunisation programmes, cracks that could threaten the health of individual children and the wider public. Healthcare providers should try harder to immunise children completely and on time. Interventions that have been shown to work include good reminder systems, longer clinic hours, and teaching parents why immunisations matter.

JAMA 2005;293: 1204-11[Abstract/Full Text]

Clopidogrel looks safe for some patients with myocardial infarction

In patients with myocardial infarction, adding clopidogrel to standard treatment with fibrinolytic drugs and aspirin can improve cardiovascular outcomes, but is it safe? Clopidogrel did not increase the risk of bleeding in the latest placebo controlled trial, which included 3491 men and women with myocardial infarction and ST segment elevation—but it did significantly reduce the odds of a composite outcome combining death, further myocardial infarction, or occlusion of the infarct related artery (15% v 21.7%, a relative risk reduction of 36%, 95% CI 24% to 47%) (figure).

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Clopidogrel's early impact on the patency of the affected coronary artery led to a reduced risk of ischaemic complications, recurrent myocardial infarction, or death from cardiovascular causes after 30 days of follow-up (11.6% v 14.1%, a relative risk reduction of 20%).

These results look promising, but they won't be the final word. The patients in this trial were relatively young and fit. Only 3% of them died of their heart attack within 30 days, a very low death rate for patients with ST segment elevation. It's still unclear whether these results can be generalised to the real, unselected, world of clinical practice.

New England Journal of Medicine 2005 Mar 9 (www.nejm.org) doi:10.1056/NEJMoa050522[Abstract/Full Text]

Ribovarin may reduce bleeding in people with haemophilia and chronic hepatitis C

When five Japanese men with haemophilia and hepatitis C started combination treatment with ribovarin and interferon alfa, their requirements for clotting factors fell significantly (figure). The men, who had moderate or severe haemophilia, also reported fewer bleeding episodes during treatment. Three other men with mild haemophilia had been excluded from the analysis because they rarely needed treatment with clotting factors.

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The men took interferon alfa and ribovarin 600 mg or 800 mg a day for six months. During treatment their mean clotting factor requirements fell from 3783 units per month to 1605 units per month (P = 0.03). Clotting factor requirements stayed low in the six months after combination therapy (1667 units per month), but the gastroenterologists who reported these findings don't say what, if anything, the men took instead. The combination of interferon alfa and ribovarin eradicated hepatitis C virus in four of the men.

Four of the five patients in this report and 43 others in the same hospital had already tried interferon alfa on its own, but this did not result in any change in their requirements for clotting factors. The authors say these results strongly suggest that ribovarin was the agent responsible. Without a control group it's impossible to say, but the authors hope their very preliminary data will be a catalyst for proper clinical trials.

JAMA 2005;293: 1190-2[Full Text]

Tobacco smoke damages fetal chromosomes

Scientists from Barcelona have found a link between smoking in pregnancy and chromosomal abnormalities in fetal epithelial cells. It wasn't easy. After interviewing 800 pregnant women they eventually found 25 long term smokers and 25 long term non-smokers without exposure to any other genotoxic substances—including tea, coffee, and alcohol. Amniotic cells from the smokers had 3.5 times more chromosomal abnormalities than amniotic cells from the non-smokers, suggesting once again that tobacco smoke is genotoxic and damages cells on both sides of the placental barrier. The abnormalities were mostly translocations and deletions. Chromosomal band 11q23, implicated in childhood leukaemia, looked the most vulnerable to tobacco damage in this study, although the data weren't completely convincing.

A linked editorial says these new findings add to almost 20 years of fairly consistent research on tobacco as a transplacental mutagen. The findings are important, but weakened slightly by technical limitations in the methods, and by the lack of urinary cotinine measurements to substantiate participants' self reported smoking habits. As usual, there's more work to be done. In the meantime, pregnant women should stop smoking. We already know it harms them and their babies.

JAMA 2005;293; 1212-22[Abstract/Full Text]

Rasagiline is an effective adjuvant treatment for Parkinson's disease

Adding rasagiline to standard treatment with levodopa can improve symptoms for patients with Parkinson's disease, according a randomised trial in 687 patients. The trial, which was double blind, compared 18 weeks of rasagiline, entacapone, or placebo in patients who had fluctuating motor function despite treatment with levodopa. Rasagiline and entacapone both improved symptoms compared with placebo, decreasing the length of time patients spent each day with poor motor function (off-time) and increasing length of time they spent each day without dyskinesia (rasagiline reduced mean daily off-time by 1.18 hours, entacapone by 1.2 hours, and placebo by 0.4 hours).

The authors say theirs is the first trial to test rasagiline as an adjunct to levodopa in advanced Parkinson's disease, and the first to compare rasagiline with entacapone, an established treatment for motor fluctuations. Since rasagiline is already licensed in Europe, doctors there can add it to their long list of adjuvant options for patients with severe Parkinson's disease. The list includes dopamine agonists such as bromocriptine; the first monoamine oxidase inhibitor, selegeline (rasageline is the second); and the catechol

O-methyltransferase inhibitors entacapone and tolcapone. The challenge now is to put the list in order, with the safest and most effective options at the top, informed by data from proper head to head trials.

Lancet 2005;365: 947-54[CrossRef][ISI][Medline]

LDL cholesterol: lower is better in stable coronary heart disease

The cardioprotective effects of low serum concentrations of low density lipoprotein (LDL) cholesterol are well known, but how low should you go in patients with established coronary heart disease? To find out, researchers randomised 10 001 men and women with stable heart disease and low serum concentrations of LDL cholesterol (mean 2.6 mmol/l) to take 10 mg or 80 mg of atorvastatin daily.

After a median follow up of 4.9 years, the mean serum concentration of LDL cholesterol in the high dose group had fallen to 2.0 mmol/l compared with a stable 2.6 mmol/l in the low dose group. The reduction was associated with significantly fewer serious cardiovascular events; during follow up 8.7% of those who took 80 mg and 10.9% of those who took 10 mg died from coronary heart disease or had a cardiac arrest, stroke, or non-fatal heart attack (figure). That's an absolute reduction in risk of 2.2%, and a relative reduction in risk of 22%, with the higher dose (hazard ratio 0.78, 95% CI 0.69 to 0.89).

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The researchers conclude that driving LDL cholesterol below currently recommended levels (2.6 mmol/l) is good for patients with stable coronary heart disease. But a linked editorial (10.1056/NEJMe058052) says these findings are not enough to change the recommendations yet. The higher dose of atorvastatin did not reduce overall mortality, and there's a suggestion that fewer cardiovascular deaths were offset by more non-cardiovascular deaths.

New England Journal of Medicine 2005 Mar 8 (www.nejm.org) doi:10.1056/NEJMoa050461[Abstract/Full Text]

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