All you need to read in the other general journals
BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2087 (Published 22 April 2010) Cite this as: BMJ 2010;340:c2087
Infliximab looks a better second line option for Crohn’s disease
Young adults who don’t respond to first line treatments for Crohn’s disease are often started on azathioprine. A new trial suggests that infliximab works better. Both drugs together work better still, although the combination carries a risk of rare but serious side effects, say the authors⇑.
The double blind double dummy trial comprised 508 adults with moderate or severe Crohn’s disease who were given infliximab, azathioprine, or both for up to 50 weeks. The chance of remission without the need for systemic steroids was 56.8% (96/169) in those given both drugs, 44.4% (75/169) in those given infliximab alone, and 30% (51/170) in controls given azathioprine. Infliximab was also better at healing mucosal ulcers than azathioprine. Again, the combination worked best. Findings were similar at 26 and 50 weeks.
These adults had had Crohn’s disease for a median of two years at randomisation. They had tried systemic steroids, budesonide, or mesalamine without success. None had received azathioprine or infliximab before the trial.
Side effect profiles were comparable in all three groups, and those given the combination had no more serious infections than others. But the trial was too small to rule out this kind of hazard. Combining azathioprine with biological agents against tumour necrosis factor (TNF) has already been linked to an excess of serious opportunistic infections and hepatosplenic T cell lymphomas.
Setback for CMV screening in newborns
Neonatal cytomegalovirus (CMV) infection is a leading cause of sensorineural deafness. Researchers looking for a rapid and reliable screening test had high hopes for the dried blood spots collected routinely for metabolic screening in many developed countries. Real time polymerase chain reaction (PCR) technology should, in theory, detect viral DNA in blood spots from infected newborns. But the test proved disappointingly inaccurate in the first large prospective study. A single primer test had a sensitivity of just 28.3% (95% CI 17.4% to 41.4%). A PCR test with two sets of primers had a sensitivity of 34.4% (18.6% to 53.2%). Viral culture of saliva, a test that is accurate but too labour intensive for mass screening, was the reference standard.
The researchers tested more than 20 000 neonates born in seven US hospitals; 92 (0.45%, 0.36% to 0.55%) had confirmed CMV infection. The PCR tests on blood spots picked up 28 and missed the rest.
The authors aren’t sure why the test performed so poorly in this study. PCR testing of peripheral blood is already used widely to detect CMV infection in immunocompromised adults. The likeliest explanation is that congenitally infected newborns aren’t always viraemic at birth. Viral DNA persists better in saliva, says one commentator (p 1425), who suggests that researchers turn their attention to PCR testing of saliva instead.
Anticonvulsant drugs linked to suicidal behaviour
Evidence of a link between some anticonvulsant drugs and suicide is mounting. The latest study implicates gabapentin, lamotrigine, oxcarbazepine, and tiagabine. All were associated with a significantly higher risk of suicide, attempted suicide, or violent death than reference drugs topiramate or carbamazepine⇑.
The study included nearly 300 000 new users of anticonvulsants over the age of 15 from a research database of medical and pharmacy claims covering 17 US states. The researchers did their best to account for the confounding effects of psychiatric and other disorders associated with both suicide and use of these drugs. In extensively adjusted analyses new users of oxcarbazepine were twice as likely to commit suicide or attempt suicide within 180 days than new users of topiramate (hazard ratio 2.07, 95% CI 1.52 to 2.80). Comparable hazard ratios were 1.42 (1.11 to 1.80) for gabapentin, 1.84 (1.43 to 2.37) for lamotrigine, and 2.41 (1.65 to 3.52) for tiagabine. Sodium valproate also seemed to be associated with higher risk than topiramate in one of the three main analyses.
It is not yet clear how or why these drugs should be associated with suicide, and residual confounding is still a possibility, say the researchers. Anticonvulsants are prescribed for a wide range of disorders including neuralgias, psychoses, and migraine so any hints of serious harm should be taken seriously. The US Food and Drug Administration issued a generic warning about anticonvulsants and suicidal behaviour in 2008.
Heavy drinking may be catching
Obesity, smoking, happiness, and sadness all cluster within social networks. So does alcohol consumption, according to a new study.
Researchers constructed a network of social contacts from participants in the Framingham offspring cohort, recruited in 1971. More than 30 years of data on alcohol consumption for people within the network showed clear clusters of both heavy drinkers and abstainers. Further analysis suggested that the clusters were the result of direct social influence, rather than shared environment, or the natural tendency for drinkers to stick together. The more heavy drinking social contacts a person had at one follow-up, the more they drank themselves by the next. The same pattern emerged for abstainers. Drinking habits seemed to spread, particularly between friends and relatives, and less so between neighbours and work colleagues.
In this study, female contacts had more influence on people than male contacts, and wives had a particularly powerful effect on husbands. Heavy drinking by a wife increased her husband’s chance of heavy drinking by 196% (95% CI 91% to 329%).
The authors admit that this kind of study can never establish cause and effect. But it is at least plausible that both good and bad health behaviours can spread through social networks. Public health interventions may work better when targeted at socially connected groups, rather than individuals.
Robotic rehabilitation still on trial
Rehabilitation after a stroke is an inexact science that often involves some kind of movement training of affected limbs⇑. Robotic devices can help patients make many hundreds of movements precisely and consistently. They never tire or wear out, and they can measure performance during treatment. At least one expert thinks robotic therapy has great potential (doi:10.1056/NEJMoa1003399).
He was commenting on a preliminary trial comparing three months of intensive movement training with and without robotic assistance in 99 adults—mostly men—with upper limb impairment for at least six months after a stroke. Another 28 had usual care. The three groups had comparable arm function at the end of the treatment period. Six months later, the group given robotic assistance had edged ahead of controls given usual care, with small but significant improvements in motor function.
Long term outcomes were essentially the same for men treated intensively with and without the robotic devices. Both groups got slightly better, which means that improvements look possible even for people with longstanding severe impairments, say the authors. These participants started the trial with low (poor) scores on a scale measuring motor and sensory impairment of the upper limbs. They had multiple comorbidities, and around a third had had more than one stroke. Quality of life scores were around 50 out of a possible 100.
Long term survival is the same after open or endovascular repair of aortic aneurysms
Endovascular repair of abdominal aortic aneurysms is less invasive than open repair and operative mortality is lower. Many patients prefer the endovascular option, given the choice. Long term results looked much less attractive in the latest analysis from a randomised trial. After the first few years, the early advantages of endovascular repair had all but disappeared under a significant excess of complications, reinterventions, and graft ruptures, many of which were fatal. In the end, the long term risk of death from any cause was the same for both groups (260/626 v 264/626; adjusted hazard ratio 1.03 (0.86 to 1.23)⇑.
Endografts have moved on since this trial stopped recruiting in 2004, and the new designs may be more durable. Even so, late complications, particularly ruptures, remain a worry that could change patients’ preferences and the cost effectiveness of endovascular repair, say the authors. The 1252 participants were mostly men and all had aneurysms measuring at least 5.5 cm in diameter.
In a sister trial, researchers compared endovascular repair with no repair in 404 patients who were not eligible for open surgery. Long term survival was almost identical (adjusted hazard ratio for all cause death 0.99; 95% CI 0.78 to 1.27), despite a lower risk of aneurysm related death associated with endovascular repair. Again, complication rates were high after endovascular repair (48% of survivors). A quarter needed some sort of reintervention within six years.
The world’s youngest and poorest children need a vaccine against RSV
Respiratory syncytial virus (RSV) is an important cause of death in children under 5 years, say researchers. Close to 34 million young children worldwide (33.8 (95% CI 19.3 to 46.2) had an acute lower respiratory illness caused by the virus in 2005, and between 66 000 and 199 000 of them died, according to best estimates from a systematic review of published and unpublished studies. Most of the infections and almost all of the deaths (99%) occurred in developing countries.
RSV causes bronchiolitis and pneumonia. In 2005, it was responsible for roughly a fifth of all acute lower respiratory infections in under 5s, and between 3% and 9% of all deaths from acute lower respiratory infections. This study suggests it is particularly lethal in children under 2 years.
Global incidence and mortality data are patchy and inaccurate, but these estimates are a good start, says a linked comment (doi:10.1016/S0140-6736(10)60401-1). They should help focus minds, funds, and research activity where they are needed most. The world’s youngest and poorest children bear the burden of illness and death caused by RSV. It is the third most important respiratory pathogen after Streptococcus pneumoniae and Haemophilus influenzae, and the only one for which we still have no vaccine.
Notes
Cite this as: BMJ 2010;340:c2087