eMJA: In Other Journals, 2 June 2008

The placebo debate continues to rear its head and provoke heated discussion following the publication of a randomised controlled trial in the United Kingdom involving patients with irritable bowel syndrome.1 Researchers set out to determine if placebo effects can be separated into the responses by patients to three components of a placebo medical encounter. A total of 262 adults (76% women) with irritable bowel syndrome were randomly assigned to three groups: waiting list (observation); placebo acupuncture alone (limited); or placebo acupuncture in which the patient-practitioner relationship was accompanied by warmth and attention (augmented). After 3 weeks, participants completed a global improvement scale and symptom severity assessment. Researchers hypothesised that the factors contributing to the placebo effect can be progressively combined in a way resembling a graded dose escalation. The outcome measures showed a trend: a significant increase in the reported improvement of symptoms as the three components of the placebo effect were progressively added. Enhancing the patient-practitioner relationship component appears to be the most significant factor in the observed improvement. The authors acknowledge the limitations of their study, including the subjective nature of the outcome measures, and call for further research into the components of the placebo effect. Spirited debate among the medical community has ensued, raising interesting questions about the nature of the therapeutic relationship.2

B vitamins and the heart

Supplementation with a combination of B vitamins does not appear to reduce the risk of cardiovascular events among high-risk women, despite reducing homocysteine levels, according to the results of a US randomised controlled trial. The trial involved 5442 female health professionals with a history of cardiovascular disease (CVD) or three or more cardiovascular risk factors. Participants, who were aged 42 years or older, were allocated at random to two groups receiving either a combination pill containing folic acid, vitamin B6 and vitamin B12, or a placebo. Treatment continued for 7.3 years, and outcome measures were a composite of myocardial infarction, stroke, coronary revascularisation, or CVD mortality. The treatment group showed a significant reduction in plasma homocysteine levels, as expected with vitamin B supplementation. As the authors point out, high homocysteine levels have been associated with increased cardiovascular risk in some observational studies. Despite this effect, vitamin B supplementation did not appear to reduce the incidence of total cardiovascular events among the population of high-risk women included in the trial.

JAMA 2008; 299: 2027-2036

Hypertension — to treat or not to treat?

The benefit of treating patients with hypertension who are over 80 years of age has been unclear, with conflicting results from various studies confounding the issue. In an international randomised controlled trial involving almost 4000 people with hypertension and a mean age of 83.6 years, participants were randomly assigned to groups receiving either a diuretic or a placebo. An angiotensin-converting enzyme (ACE) inhibitor (or matching placebo) was added if necessary to achieve a target blood pressure of 150/80 mmHg. Active treatment with the diuretic, with or without the ACE inhibitor, appeared to result in a significant (30%) reduction in the rate of stroke and significant reductions in the rate of heart failure, rate of death from stroke and death from any cause. The authors discuss the differences between their findings and those from other trials and meta-analyses, concluding that there is good evidence that treatment in this subgroup with the prescribed medications is beneficial.

N Engl J Med 2008; 358: 1887-1898

Bone density in the genes

An international research group investigating the heritability of osteoporosis has identified evidence for an association between bone mineral density and certain genetic loci. In a genome-wide association study with over 8500 participants, researchers measured bone mineral density at the lumbar spine and femoral neck and identified people with osteoporosis and osteoporotic fractures. Two single nucleotide polymorphisms were identified on chromosomes 8 and 11, which showed evidence for an association with bone mineral density and osteoporotic fracture. The authors comment that the combined risk of the presence of both of these alleles was similar to or greater than that of several other osteoporotic risk factors, including low body mass index, glucocorticoid exposure, and smoking. They propose that a panel of genetic markers may eventually become available as a screening tool to identify individuals at risk for osteoporotic fractures.

Lancet 2008; 371: 1505-1512

Dr Tanya Grassi, MJA

mja.com.au | The Medical Journal of Australia