This is another article from the National Electronic Library for Health series. See the web-based version for links.

The news that aromatherapy or light therapy may be more useful than sedatives in treating some of the symptoms of dementia was reported in the Times on 17 December, 2002. The article accurately reported an editorial in the BMJ, which discussed the findings of six trials.

The Times reported that aromatherapy or light therapy could be used as an alternative to neuroleptic (antipsychotic) drugs for the treatment of psychological symptoms and behavioural disturbances associated with dementia.

The BMJ reported the findings of six recently conducted trials of aromatherapy or light therapy in patients with dementia. Three trials found that aromatherapy (massage or inhalation of lavender or lemon balm essential oils) reduced agitation among patients with dementia and three trials of bright light therapy found that it reduced sleep disturbances and had some beneficial effects for restlessness.

The newspaper article correctly interpreted the research findings reported in the editorial. However, the authors of the editorial did not undertake a systematic review of the evidence and it is therefore unclear how reliable the overall findings are.

The editorial was an overview of six trials which examine two different interventions for the management of some of the symptoms of dementia. The authors discuss three placebo controlled trials of aromatherapy with patients suffering from severe dementia and three controlled trials of light therapy used in patients with dementia. The total number of participants included in the aromatherapy trials was 108 and 48 in the light therapy trials.

Each of the three aromatherapy trials reported a significant beneficial effect on agitation compared with placebo, with almost complete compliance and no side effects. The trials examining bright light therapy reported some benefits for restlessness, and a particular beneficial effect on sleep disturbance. Eleven patients withdrew from the bright light therapy trials.

The authors did not conduct a systematic review of the literature and did not state how they selected trials for inclusion in the editorial. This means that it is not possible to ascertain if there are any other important studies that have not been included and it cannot be assumed that the overall conclusions have not been influenced by selection bias. Very little data were presented on the individual trials and no information was given with regards to their quality. It is therefore not clear how reliable the findings of these individual trials are.

Information staff at CRD searched for systematic reviews relevant to this subject. There was one related protocol for a review (i.e. a review in preparation) identified on the Cochrane Database of Systematic Reviews (CDSR) and one related review identified on the Database of Abstracts of Reviews of Effects (DARE). There is therefore only poor evidence for the efficacy of these therapies in dementia. They probably don’t do much harm.

A recent Lancet article has shown that in 2002, 17 people died from variant CJD (vCJD) in the UK, compared with 20 in 2001 and 28 in 2000. The authors analysed data for deaths from vCJD since 1995 and estimated the underlying trend in mortality. The trend had a quadratic component (p=0·005), suggesting that the increase was not exponential, and that the previously increasing trend is slowing down. The death rate peaked in 2000. These findings are encouraging.

That mortality is no longer increasing exponentially is encouraging. However, to conclude that the epidemic is in permanent decline would be premature. Up to now, all cases of vCJD have been in individuals who are methionine homozygous at codon 129 of the PRNP gene. People with other genotypes might also be susceptible to vCJD but have longer incubation periods than those homozygous for methionine, and future epidemics of vCJD in these genotypes is possible. The polymorphism at codon 129 in PRNP could have a major effect on the incubation period in both growth-hormone related cases of CJD⁴ and in kuru.⁵ Even within the methionine homozygous population we might see more peaks in the future if subgroups of individuals have different incubation periods, as has been recorded in mice. Furthermore, although only one strain of BSE has been identified, the possibility of other strains, associated with longer incubation periods in human beings, cannot be excluded.

Finally, future cases might arise from secondary human-to-human transmission, for example by contaminated surgical instruments or blood transfusion. Continuing surveillance of CJD in the UK is needed to investigate these possibilities

This Bandolier paper looked at bias. It says that what we have lacked up to now is proof that poor study design is associated with bias. A new contribution from Holland provides the missing link.

It searched for and found 26 systematic reviews of diagnostic tests with at least five included studies. Only 11 could be used in their analysis, because 15 were either not systematic in their searching or did not report any sensitivity or specificity. Data from the remainder were subjected to mathematical analysis, to investigate whether the presence or absence of some item of proposed study quality made a difference to the perceived value of the test.

There were 218 studies, only 15 of which satisfied all eight criteria of quality for the analysis. Thirty percent fulfilled at least six of eight criteria. The relative diagnostic odds ratio used indicated the diagnostic performance of a test in studies failing to satisfy the methodological criterion relative to its performance in studies with the corresponding feature. Over-estimation of effectiveness (positive bias) of a diagnostic test was shown by a lower confidence interval for the relative diagnostic odds ratio of more than 1.

Use of different reference tests, lack of blinding and lack of a description of either the test or the population in which it was studied led to positive bias. But the largest factor leading to positive bias was evaluating a test in a group of patients already known to have the disease and a separate group of normal patients - called a case-control study here.

The amount of positive bias in poorly conducted studies of diagnostic tests is extremely worrying. Most information for most laboratory tests is only available in the form of case-control studies - those with the highest bias.

Take one example, that of the fashionable free-PSA test. The likelihood ratios from the early studies were 2 to 7. This might be useful in a population of men referred to a urology clinic with prostate cancer or BPH, but most of the studies were case-control studies. If the likelihood ratios were biased, and in truth were lower, the test may be of no use even in a high prevalence setting.

It is all very worrying. It is time someone in academe, or the NHS, or industry sat up and took notice. The problem is not just, or even, with treatment. The problem is knowing who is to be treated. The message is that we need to get back to first principles and do some large high-quality real-life studies. CARE has started that for the clinical examination, but there's absolutely no reason why similar studies could not be performed in other setting for laboratory tests and clinical examinations