Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial.

OBJECTIVES: Doubt over the cost-effectiveness of the cholinesterase inhibitors in dementia has renewed interest in alternative treatments such as Ginkgo biloba. We aimed to determine the effectiveness and the safety profile of Ginkgo biloba for treating early stage dementia in a community setting. METHODS: We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120 mg daily) or a placebo control for 6 months. Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). RESULTS: We recruited 176 participants, mainly through general practices. In the ANCOVA model with baseline score as a co-variate (n = 176), Ginkgo did not have a significant effect on outcome at six months on either the ADAS-Cog score (p = 0.392), the participant-rated QOL-AD score (p = 0.787) nor the carer-rated QOL-AD score (p = 0.222). CONCLUSION: We found no evidence that a standard dose of high purity Ginkgo biloba confers benefit in mild-moderate dementia over 6 months.

The Hawthorne Effect: a randomised, controlled trial.

BACKGROUND: The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. METHODS: Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). RESULTS: We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life. CONCLUSION: We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. TRIAL REGISTRATION: Current controlled trials: ISRCTN45577048.

Evaluation of specific and non-specific effects in homeopathy: feasibility study for a randomised trial.

OBJECTIVE: To determine the feasibility, in terms of acceptability to patients, physicians and other staff; data return and statistical power of a study to elucidate the relative contributions of specific and non-specific effects in homeopathic treatment of dermatitis. DESIGN: Randomised, controlled 4-arm trial, 2 arms double-blind. SETTING: Outpatient clinic, Royal London Homoeopathic Hospital. PARTICIPANTS: Seventy-five adult patients with dermatitis. INTERVENTIONS: Patients were randomly allocated to: 'fast track' open verum homeopathy, 'fast track' double-blind verum homeopathy, 'fast track' double-blind placebo homeopathy or waiting list control. MAIN OUTCOME MEASURES: One hundred millimeter visual analogue scale of overall symptom severity; 10 point digital scores of sleep, itching, skin condition; weekly 5-point Likert scale of topical steroid use; Dermatology Life Quality Index at entry and completion. RESULTS: Recruitment was below target, but the study was acceptable to staff and feasible. Blinded patients were more likely to withdraw (P=0.021, chi2 test). After correction for baseline differences and multiple comparisons, no outcome measure showed statistically significant between group differences. Blindness appeared to have a negative effect, but this was confounded by differential withdrawal. CONCLUSIONS: A definitive trial of this design is unlikely to discriminate the relative contributions of the non-specific and specific effects to the outcome of homeopathic treatment of dermatitis, because of patient preference issues.

Labelling chronic illness in primary care: a good or a bad thing?

Traditionally the management of any chronic condition starts with its diagnosis. The labelling of disease can be beneficial in terms of defining appropriate treatment such as in coronary artery disease. However, sometimes it may be detrimental such as when x-rays are used to diagnose lumbar spondylosis leading to patients inappropriately limiting their activity. Chronic knee pain in the elderly is another example where applying labels is problematical. A common diagnosis in this situation is osteoarthritis, but this label can be applied in two ways: as a radiological diagnosis, or as a clinical one. The x-ray diagnosis, however, does not equate with the clinical syndrome, and vice versa. In addition, diagnosing knee pain as osteoarthritis does not necessarily help in management, since a patient's debility is more dependent upon their clinical signs and symptoms than the presence of radiographic osteoarthritis, and by the same token its clinical counterpart. GPs are consistent in their management of knee pain, but in attempting to diagnose the pain as osteoarthritis, these plans can alter and become more dependent on the actual diagnosis than the clinical picture. As a result management may well diverge from what the current best evidence supports. Diagnosis for diagnosis sake, should therefore be discouraged, and chronic knee pain gives us one example of why this is the case. GPs would be better placed to manage this condition if it was considered more as a regional pain syndrome, perhaps defining it simply as 'chronic knee pain in older people'. This example suggests that there is a pressing need in primary care to carefully consider in chronic disease when it is appropriate to be definitive in diagnosis such that when using disease specific labels, there is definite benefit for the patient and doctor.

Effectiveness gaps: a new concept for evaluating health service and research needs applied to complementary and alternative medicine.

BACKGROUND: An effectiveness gap (EG) is an area of clinical practice in which available treatments are not fully effective. EGs have not been previously researched. Complementary and alternative medicine (CAM) interventions, by definition, are not generally available through normal health care channels. Therefore, if effective, they have the potential to increase achieved community effectiveness. AIMS: A pilot study to determine whether EGs exist, and if so to provide initial data on their nature, frequency, and causes. To obtain preliminary data on whether CAM may offer effective interventions in these clinical areas. DESIGN: Semistructured telephone interviews; literature search. SETTING: Twenty-two (22) general practitioners (GPs) in London, U.K. METHOD: One hundred and fifty-two (152) doctors who had responded to an earlier survey on attitudes to CAM were approached. Respondents were asked to specify EGs and to give reasons why available treatment is unsatisfactory and to estimate the frequency and severity of clinical problems relating to EGs. Sampling was continued to redundancy. A bibliometric study examined the volume and type of published evidence on the effectiveness of CAM interventions in the identified clinical areas. RESULTS: There was good concordance among respondents on EGs encountered in general/family practice. Seventy-eight (78) clinical problems were cited. EGs are encountered quite frequently: 68 of 78 (85%) of EGs were encountered at least once per month. Musculoskeletal problems were cited by 20 of 22 (90%) of respondents as being affected by EGs. Depression, eczema, chronic pain, and irritable bowel syndrome were also frequently mentioned. Systematic reviews and meta-analyses conclude that there is evidence for the effectiveness of various CAM interventions in most of these areas. CONCLUSIONS: EGs, mapped against evidence, have the potential to inform service development and research policy. Further study should be undertaken: it should incorporate improved sampling and data collection methodology. Specifically, where effective CAM interventions exist but are not being applied, EGs form part of the "avoidable burden of illness" identified by early work on evidence-based medicine. Practice guidelines should incorporate CAM interventions where there is evidence. The CAM research agenda should focus on areas affected by EGs.

Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial.

OBJECTIVE: To determine the effects of a policy of "use acupuncture" on headache, health status, days off sick, and use of resources in patients with chronic headache compared with a policy of "avoid acupuncture." DESIGN: Randomised, controlled trial. SETTING: General practices in England and Wales. PARTICIPANTS: 401 patients with chronic headache, predominantly migraine. Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months or to a control intervention offering usual care. MAIN OUTCOME MEASURES: Headache score, SF-36 health status, and use of medication were assessed at baseline, three, and 12 months. Use of resources was assessed every three months. RESULTS: Headache score at 12 months, the primary end point, was lower in the acupuncture group (16.2, SD 13.7, n = 161, 34% reduction from baseline) than in controls (22.3, SD 17.0, n = 140, 16% reduction from baseline). The adjusted difference between means is 4.6 (95% confidence interval 2.2 to 7.0; P = 0.0002). This result is robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year (8 to 38). SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy, and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication (P = 0.02), made 25% fewer visits to general practitioners (P = 0.10), and took 15% fewer days off sick (P = 0.2). CONCLUSIONS: Acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. Expansion of NHS acupuncture services should be considered.

Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care.

OBJECTIVE: To evaluate the cost effectiveness of acupuncture in the management of chronic headache. DESIGN: Cost effectiveness analysis of a randomised controlled trial. SETTING: General practices in England and Wales. PARTICIPANTS: 401 patients with chronic headache, predominantly migraine. Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists, or to usual care alone. MAIN OUTCOME MEASURE: Incremental cost per quality adjusted life year (QALY) gained. RESULTS: Total costs during the one year period of the study were on average higher for the acupuncture group (403 pounds sterling; 768 dollars; 598 euros) than for controls (217 pounds sterling) because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years (QALYs), leading to a base case estimate of 9180 pounds sterling per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial. CONCLUSIONS: Acupuncture for chronic headache improves health related quality of life at a small additional cost; it is relatively cost effective compared with a number of other interventions provided by the NHS.

Use of a single global assessment to reduce missing data in a clinical trial with follow-up at one year.

We conducted a randomized controlled trial (ISRCTN96537534) to assess the effects of acupuncture on migraine and chronic tension headache. Patients (n=401) completed a diary of headache severity four times a day for 4 weeks at baseline, immediately following a 3-month treatment period and 1 year after randomization. During the trial, it appeared that dropout might be higher than expected. We therefore obtained a rapid global assessment of headache from participants to aid imputation of missing data. Patients were contacted by telephone and asked to rate current and baseline headache on a 0-10 scale. Use of global assessment reduced the number of patients from whom we obtained no follow-up headache data from 69 (17%) to 24 (6%). Analysis of patients who provided both a diary and a global assessment demonstrated excellent properties of global assessment, with very similar results to the full diary. We therefore used the global assessment to help impute missing 1-year diary scores. Rapid global assessment can be easily implemented in any trial and aids imputation of missing data, though it should not be used instead of more intensive methods of assessment. Further research might usefully examine the value of global assessment for imputation of missing data in a variety of different settings.