All you need to read in the other general journalsBMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b2511 (Published 22 June 2009) Cite this as: BMJ 2009;338:b2511
Researchers criticised for stopping sepsis trial too early
Endotoxins, a feature of Gram negative sepsis, can be filtered out of the blood using a haemoperfusion column impregnated with polymyxin B. There’s some evidence that patients with the right kind of severe sepsis can benefit from this treatment, including a preliminary trial from Italy that recently reported a significant reduction in 28 day mortality in patients who underwent haemoperfusion with polymyxin B (11/34 (32%) v 16/30 (53%) in controls given conventional therapy alone; adjusted hazard ratio 0.36, 95% confidence interval 0.16 to 0.80)⇑. The 64 patients in this trial had abdominal sepsis, mostly from perforated bowel. Those given two sessions of haemoperfusion with polymyxin B had greater improvements in haemodynamics and organ function than controls given conventional therapy alone. The fall in mortality prompted an oversight board to stop the trial early.
Stopping the trial was a mistake, says a linked editorial (pp 2496-7). These data are preliminary and cannot establish benefit with any certainty, or rule out harm. The mortality results were a surprise and are insecure. Even the authors say their promising results must be confirmed in bigger trials.
Recruiting for such trials will be very difficult, says the editorial, now an oversight board has been persuaded that randomising is unethical in this setting. The available evidence simply isn’t enough to convince most regulatory authorities, nor should it. A definitive answer was possible and is now further away than ever. Evaluation could now stall, denying patients with a lethal condition access to a potentially life saving treatment. “The position taken by the oversight board . . . should be rescinded,” conclude the editorial’s authors.
Calcium supplement fails to prevent weight gain
In theory, extra dietary calcium could help sequester fat within the gut, preventing absorption and promoting weight loss (or at least preventing weight gain). Unfortunately, this concept doesn’t seem to work in practice. In the first randomised trial to test this theory, 1500 mg a day of extra calcium taken at meal times made no difference to weight change among 340 overweight and obese volunteers from the US.
Participants took the supplements or a matching placebo for 2 years and gained a mean of 1.3 kg each, regardless of their assigned treatment⇑. Compliance was reasonable and the trial had enough power to rule out any clinically meaningful benefit associated with the calcium supplements. The extra calcium had no impact on fat mass, abdominal circumference, hip circumference, or triceps skinfold thickness either.
Most of the participants were women recruited through advertising. They had a mean body mass index of 33 at baseline, and three quarters reported taking less dietary calcium than recommended by the US authorities.
Women looking to calcium supplements as a painless way to stop gaining weight are likely to be disappointed, say the authors.
Computed tomographic colonography is a reasonable screening option for some high risk adults
Colonoscopy is the gold standard screening test for adults at risk of colorectal cancer, but it’s invasive and unpleasant. A study from the US suggests that computed tomographic colonography could be a more acceptable alternative for some patient groups.
The new test picked up 151 of the 177 advanced lesions detected by colonoscopy, and thus had an overall sensitivity of 85.3% (95% CI 79.0% to 90.0%). Specificity and positive and negative predictive values were 87.8% (85.2% to 90.0%), 61.9% (55.4% to 68.0%), and 96.3% (94.6% to 97.5%), respectively. The study included 937 adults with a family history of colorectal cancer, a personal history of colorectal adenoma, or a positive faecal occult blood test. All participants had computed tomographic colonography immediately followed by colonoscopy.
Computed tomographic colonography is a reasonably accurate alternative to colonoscopy, says an editorial (pp 2498-9), although it’s too early to recommend it for all high risk adults. Computed tomography colonography is less invasive and more convenient, but there are trade offs including radiation exposure and a small chance of missing something potentially lethal. In this study, 26 of the 731 patients cleared by computed tomographic colonography actually had an advanced adenoma or cancer. Computed tomographic colonography seemed least useful for the subgroup with a positive faecal occult blood test.
Antenatal screening for group B streptococcus increases following change in policy
In 2002, US guidelines recommended screening all women in late pregnancy for colonisation with group B streptococcus, a leading cause of serious infection in young infants. Hospitals responded quickly, screening coverage increased, and the incidence of invasive disease fell, according to surveillance data from 7691 women in 10 states⇑. In 2003 and 2004, 85.0% (95% CI 83.9% to 86.0%) of eligible women in these states were screened and 85.1% (82.9% to 87.0%) of those with positive results received intrapartum antibiotics, usually penicillin. Both figures were higher than those reported by a similar study in 1998 and 1999, before the change in policy.
There were 254 cases of invasive group B streptococcus in the 10 states in 2003 and 2004, an incidence of 0.32 per 1000 live births. Incidence was higher among babies born before 37 weeks, and the study’s authors identified women at risk of preterm delivery as one target area for improvement. Only half the women who delivered preterm in this study were screened.
False negative screening cultures also remain a problem. One hundred and sixteen of the 189 term babies with invasive streptococcal disease (61.4%) were born to mothers who had negative cultures before delivery.
Red yeast rice still unproved as an alternative to statins
Rice that has been fermented with red yeast brings down serum concentrations of low density lipoprotein cholesterol. Could it be a useful alternative treatment for people who can’t tolerate statins? One small trial suggests red yeast rice can work for adults with statin induced myalgia. The 62 adults in this study took red yeast rice or a matching placebo for six months alongside a 12 week programme of education, diet, exercise, and relaxation commissioned by one suburban cardiology practice in the US. Both groups lost weight, but low density lipoprotein cholesterol concentrations fell further in the group taking red yeast rice (from 4.2 mmol/l to 3.3 mmol/l compared with 4.3 mmol/l to 3.9 mmol/l in those on placebo; P=0.011). The supplement, which contained active ingredients including a small amount of lovastatin, caused no more myalgia than the placebo.
These results look promising, but doctors shouldn’t prescribe red yeast rice without more rigorous evaluation, says an editorial (pp 885-6). Red yeast rice is still “an unapproved, unstandardized form of lovastatin labeled as a nutraceutical.” We know it can cause rhabdomyolysis, and the US Food and Drug Administration has already issued warnings about inconsistent, possibly toxic formulations. This small trial can’t rule out serious side effects such as muscle toxicity.
Advancing age, chronic illness, and polypectomy increase the risks associated with colonoscopy
More and more older people need colonoscopy for screening, diagnosis, or polypectomy. To find out about the risks in this age group, US researchers analysed claims data from Medicare, publicly funded health care for people over 65. They looked specifically for complications within 30 days of a colonoscopy, including perforations and bleeding (serious gastrointestinal events); nausea, vomiting, and abdominal pain (other gastrointestinal events); and cardiovascular events such as heart attacks, angina, and arrhythmias.
The 53 220 adults in the analysis had a higher risk of all three types of complication than age matched controls who did not have a colonoscopy (6.9 v 1.8 events per 1000 persons, 12.0 v 6.3 events per 1000 persons, and 19.4 v 16.6 events per 1000 persons, respectively). The difference was most marked for patients having a polypectomy.
Absolute risks of gastrointestinal complications including perforation were relatively low, but went up with age. The adjusted risk of a serious gastrointestinal event after colonoscopy was 12.1 per 1000 persons for adults over 85, compared with 5.0 per 1000 persons for adults aged 66 to 69. Risks were also higher for people with pre-existing illnesses, in particular diabetes, heart failure, atrial fibrillation, stroke, and chronic obstructive pulmonary disease.
The link between colonoscopy and cardiovascular events was less clear. Risks went up with age in both the colonoscopy cohort and the control cohort.
Quality of life data support lower haemoglobin targets for people with chronic kidney disease
Agents that stimulate erythropoiesis, such as epoetin alfa and darbepoetin alfa, have revolutionised the treatment of anaemia in people with chronic kidney disease. A target haemoglobin concentration of no more than 120 g/l seems to be associated with the right balance of risks and benefits, although most of the research so far has focused on clinical outcomes such as heart disease and death.
Researchers have now done a systematic review to find out how use of these agents affects patients’ quality of life. They found 11 head to head trials comparing lower (90-120 mg/l) with higher (more than 120 g/l) targets for haemoglobin in people with chronic kidney disease who were treated with erythropoietin stimulating agents. Nine of the trials used the short form 36 questionnaire to assess quality of life. Reporting was generally patchy, but after contacting trial investigators for more data the researchers had enough to combine in a meta-analysis. Any differences in quality of life between people treated to lower haemoglobin targets and those treated to higher targets were small and clinically unimportant for all domains studied, including social functioning and physical, emotional, and mental health. The higher target was associated with slightly improved quality of life scores in four of eight domains, but the difference from the lower target was never more than 3 points on scales running from 1 to 100.
These findings add to growing evidence that doctors should use these agents with care, says an editorial (pp 1100-1). We know that pushing haemoglobin concentrations beyond 120 g/l doesn’t help patients live longer; it probably doesn’t help them feel better either. Doctors should stick to current recommendations and aim for haemoglobin concentrations between 110 g/l and 120 g/l.
Cite this as: BMJ 2009;338:b2511