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CARPHOLOGY by Rajendra

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Immunisation in Alzheimer’s disease

Although immunisation with Abeta(42) resulted in clearance of amyloid plaques in patients with Alzheimer’s disease, this did not prevent progressive neurodegeneration. This was what researchers found in a randomised, placebo-controlled phase I trial which looked at the long-term effects of Abeta42 immunisation in Alzheimer’s disease. The follow-up study of this trial which they began in 2000 was completed in September, 2006. Plaques were assessed in terms of the percentage area of the cortex with Abeta immunostaining and by the histological features reflecting removal of plaque.

Lancet 2008;372:216–23.

Dimebon in Alzheimer’s disease

Dimebon, an antihistaminic, was safe, well tolerated, and significantly improved the clinical course of patients with mild-to-moderate Alzheimer’s disease, say researchers from Russia. They conducted a multicentre, randomised, double-blind, placebo-controlled study on 183 patients, which looked at cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease. Treatment with dimebon resulted in significant benefits in the cognitive subscale of the Alzheimer’s disease assessment scale compared with placebo at week 26 (mean drug-placebo difference −4.0 (95% CI −5.73 to −2.28). Dry mouth and depressed mood or depression were the most common adverse events.

Lancet 2008;372:207–15.

Backache in primary care

Patients with acute low back pain in primary care in Australia do not do as well as is claimed in clinical practice guidelines. This is the conclusion reached by researchers who studied an inception cohort of 973 consecutive patients with non-specific low back pain of less than two weeks’ duration. The patients were recruited from the clinics of 170 general practitioners, physiotherapists and chiropractors. Recovery was slow for most patients and nearly a third of patients did not recover from the backache within a year. Older age, compensation cases, higher pain intensity, longer duration of low back pain before consultation, more days of reduced activity because of lower back pain before consultation, feelings of depression and a perceived risk of persistence were each associated with a longer time to recovery.

BMJ 2008;337:a171.

Laquinimod in multiple sclerosis

In patients with relapsing-remitting multiple sclerosis 0.6 mg per day laquinimod, an immune modulator, significantly reduced MRI-measured disease activity, finds a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Laquinimod was well tolerated, with some transient and dose-dependent increases in liver enzymes. A thrombotic venous outflow obstruction of the liver (Budd-Chiari syndrome) occurred after one month of exposure in a patient with underlying hypercoagulability.

Lancet 2008;371:2085–92.

Statin induced myopathy

Researchers in Oxford have identified common variants in SLCO1B1 gene on chromosome 12 that are strongly associated with an increased risk of statin-induced myopathy. They carried out a genome-wide association study using approximately 300 000 markers in 85 subjects with definite or incipient myopathy and 90 controls, all of whom were taking 80 mg of simvastatin daily as part of a trial involving 12 000 participants. Genotyping these variants may help to achieve the benefits of statin therapy more safely and effectively, say the authors.

N Engl J Med 2008; doi: 10.1056/NEJMe0801936.

Light, melatonin and dementia

Light has a modest benefit in improving some cognitive and non-cognitive symptoms of dementia, according to the results of a long-term, double-blind, placebo-controlled, randomised trial. The participants were 189 residents of 12 group care facilities in The Netherlands whose mean age was 85.8 years. Of these, 90% were women and 87% had dementia. The intervention consisted of long-term daily treatment with whole-day bright or dim light and evening melatonin (2.5 mg) or placebo for a mean of 15 months (maximum period of 3.5 years). Melatonin shortened sleep onset latency by 8.2 minutes (95% CI 1.08 to 15.38) or 19% and increased sleep duration by 27 minutes (95% CI 9 to 46) or 6%. It affected mood adversely, but this was counteracted by the effect of light. The authors advice that melatonin should only be used in combination with light.

JAMA 2008;299:2642–55.

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