All you need to read in the other general journalsBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d7335 (Published 15 November 2011) Cite this as: BMJ 2011;343:d7335
EEG identifies possible awareness in adults in a vegetative state
Researchers have developed a new technique to probe for residual conscious awareness in people thought to be in a persistent vegetative state. Using a form of functional electroencephalography, the researchers identified three patients out of a series of 16 who were able to follow commands. The three young men, two with traumatic and one with hypoxic brain injury, altered their EEG readings consistently when asked to imagine squeezing one hand into a fist or wiggling their toes. In each set of tests they had to repeat one of the tasks 15 times in response to a series of beeps, so they had to both hear and understand verbal instructions. The EEG changes made by the three responsive men matched those made by healthy controls given the same commands and occurred in the appropriate leads for each type of motor imagery.
Others have reported similar findings using functional magnetic resonance imaging. But functional MRI is difficult, stressful, expensive, and rules out anyone who can’t keep still and trauma patients treated with metal implants such as plates or pins. The researchers hope their new technique, which is portable, cheap, and inclusive, will help identify more patients who might have been misdiagnosed using standard behavioural criteria alone.
Thirteen of the patients in this study were unable to follow commands in a way that was detectable using EEG. However, three of the 12 normal controls were also unable to produce the appropriate changes, so a negative result does not necessarily signify lack of consciousness, say the authors.
Chimney stoves cut indoor air pollution and severe pneumonia in Guatemalan children
Pneumonia is a leading cause of child deaths worldwide, and indoor air pollution from smoky cooking fires is a well established risk factor. Replacing open fires with contained stoves with chimneys can protect children from indoor air pollution and may also reduce the risk of childhood pneumonia, although a trial from Guatemala reported somewhat mixed results.
Young children in families given a new stove were no less likely to develop pneumonia than control children in families who continued using open wood fires for cooking and heating. But they were significantly less likely to develop severe pneumonia diagnosed by a doctor (rate ratio 0.67, 95% CI 0.45 to 0.98), severe pneumonia diagnosed by a field worker (0.56, 0.32 to 0.97), or severe pneumonia without a viral cause (0.54, 0.31 to 0.91).⇑
The trial was challenging, and the authors had to contend with a substantial amount of missing data, but they did find a clear link between children’s personal exposure to carbon monoxide—a proxy for particulate pollution—and a higher risk of severe pneumonia in exploratory analyses.
So, cleaning up the air inside the home probably does protect young children from pneumonia, says a linked commentary (pp 1682-4), but it is individual exposure that really counts. These stoves cut children’s carbon monoxide exposure by around half, which may not have been enough for an emphatic result. The authors suggest future trials test the impact of more efficient stoves and cleaner fuels.
Early liver transplantation for adults with severe alcoholic hepatitis?
Liver transplantation is a controversial treatment for alcoholic liver disease, and most centres insist that candidates stop drinking completely for at least six months before they can be considered for a transplant. The six month wait can be a death sentence for some patients with alcoholic hepatitis, say researchers, who report the results of a pilot offering earlier transplantation to selected patients most likely to die during the wait.
The 26 adults (fewer than 2% of admissions for alcoholic liver disease) from seven French transplant centres had been admitted for the first time, with severe alcoholic hepatitis not responding to medical treatment. All had agreed never to drink again and had close support from family members. Four separate medical teams agreed, after comprehensive assessment, that these patients were good candidates for early transplantation. Their survival was significantly better at six months than matched controls who were not offered transplants (6/26 v 20/26 mortality; estimated cumulative survival rate 77% v 23%, P<0.001). The survival advantage seemed to last for at least two years.⇑
Three of the 26 transplant patients eventually began drinking again, although none developed a dysfunctioning graft.
This small non-randomised pilot needs confirming, but at least one commentator believes the six month rule for abstinence should be reconsidered, or at least applied more selectively (pp 1836-8). Alcoholism is a disease not a lifestyle choice, he writes, and transplantation can be life saving. Patients likely to benefit should be treated early. Now we need a truly unbiased way to select them, starting with accurate tools to identify those least likely to relapse.
N-Acetylcysteine adds little to standard drugs for life threatening alcoholic hepatitis
About a third of adults with severe alcoholic hepatitis die within six months, despite recommended treatments including prednisolone. Could the antioxidant N-acetylcysteine improve this bleak outlook? Maybe, but only for a month or so, according to the latest trial.
Adults with life threatening hepatitis given five days of intravenous N-acetylcysteine in addition to 40 mg a day of oral prednisolone were more likely to live for one month than controls given just prednisolone (7/85 (8%) v 21/89 (24%) mortality; hazard ratio for combination therapy 0.58, 95% CI 0.14 to 0.76). But they were no more likely to live for six months (23/85 (27%) v 34/89 (38%); 0.62, 0.37 to 1.06). Results at three months were hard to interpret: there were fewer deaths in the group given N-acetylcysteine, but the difference wasn’t statistically significant.⇑
Oxidative stress is an important factor in alcoholic hepatitis and N-acetylcysteine should improve outcomes, say the authors. They are reluctant to abandon the drug completely and suggest that more powerful trials, perhaps testing longer treatment with N-acetylcysteine, are still justified. In this trial the antioxidant reduced the risk of infections and seemed to prevent deaths from hepatorenal syndrome (20/89 (22%) with prednisolone only v 8/85 (9%) with prednisolone + N-acetylcysteine, odds ratio 2.79, 1.08 to 7.42).
(Mostly) reassuring safety data on TNF antagonists
Careful analysis of data from four large US health databases suggests that widely used biological agents acting against tumour necrosis factor (TNF) do not increase the risk of serious infections, at least not in the first year of treatment. The analysis, which is part of a larger national project monitoring the safety of these drugs, included more than 30 000 adults with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis.
Overall, new users of biological agents were no more likely to be admitted to hospital with a serious infection during the next year than closely matched controls who started treatment with a non-biological disease modifying drug instead. Fear of infections has always accompanied anti-TNF agents infliximab, etanercept, and adalimumab, says a linked editorial (doi:10.1001/jama.2011.1705). Randomised trials and large surveillance studies have tended to confirm a risk, so why is this study different?
Residual confounding is one possibility, and an unusually high rate of infections among controls is another, writes the author. Both would disguise any real differences between the two types of agent. The study was also characterised by large losses to follow-up, particularly among patients taking non-biological comparators.
So, while generally reassuring, these results are not the final word, says the editorial. Regulatory agencies need to stay vigilant.
Bone marrow cells fail to improve cardiac function late after a heart attack
Intracoronary infusions of bone marrow cells are an emerging treatment for myocardial infarction, and research is currently focused on which cell type (or combination of cell types) to infuse and when. Two to three weeks after the event is probably too late, according to a trial evaluating intracoronary infusions of autologous mononuclear cells from bone marrow. The infusions had no effect on any measure of left ventricular function or repair (including left ventricular ejection fraction, left ventricular volume, wall motion, or infarct size) during six months of follow-up.
This double blind, placebo controlled trial recruited 87 patients a median of 17 days after a first myocardial infarction. They had all been treated with an early percutaneous coronary intervention, and had a left ventricular ejection fraction of 45% or less.
The authors were a little surprised by the negative result, since earlier trials hinted that infusions of bone marrow mononuclear cells can make a difference when given in the first week after a myocardial infarction. Their trial was small, but reasonably well powered. A linked editorial suggests future studies explore intramyocardial delivery instead this late after cardiac injury (pp 2156-7). Meanwhile, trials are already under way testing a variety of other cell types including mesenchymal stem cells, mesenchymal precursor cells, and cardiac stem cells.
Cognitive behaviour therapy and exercise both good for chronic widespread pain
Cognitive behaviour therapy, exercise, or both together worked significantly better than treatment as usual for adults with unexplained widespread pain (fibromyalgia) in a recent trial from the UK. When asked to gauge how much they had improved after six months of treatment, 30% (26/87) of those treated with cognitive therapy, 35% (32/92) of those given an exercise regimen, and 37% (35/94) of those treated with both reported feeling much better or very much better than they had at the start of the trial. Just 8% (7/88) of controls reported the same magnitude of improvement; the other 92% reported minimal improvement or worse.
Cognitive therapy was delivered by telephone, eight times over six months. Exercise sessions were delivered once a month by a trained instructor, who recommended at least two visits to the gym each week coupled with brisk walking between visits. Both treatments had a limited impact on a large number of secondary outcomes including quality of life, and cost effectiveness analyses were equally hard to interpret. Even so, a linked editorial is confident that cognitive therapy and exercise look like good options for the large numbers of primary care patients currently taking opioid drugs for chronic widespread pain or fibromyalgia (doi:10.1001/archinternmed.2011.547). Both treatments are less risky than drugs and encourage patients to take control of their own illness. Around a fifth of all primary care visits in the US currently end in a prescription for opioid pain killers, says the editorial.
Cite this as: BMJ 2011;343:d7335