Effect of alpha linolenic acid on cardiovascular risk markers: a systematic review.

OBJECTIVE: To determine whether dietary supplementation with alpha linolenic acid (ALA) can modify established and emerging cardiovascular risk markers. DESIGN: Systematic review and meta-analysis of randomised controlled trials identified by a search of Medline, Embase, Cochrane Controlled Trials Register (CENTRAL), and the metaRegister of Controlled Trials (mRCT). PATIENTS: All human studies were reviewed. MAIN OUTCOME MEASURES: Changes in concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglyceride, fibrinogen, and fasting plasma glucose, and changes in body mass index, weight, and systolic and diastolic blood pressure. RESULTS: 14 studies with minimum treatment duration of four weeks were reviewed. ALA had a significant effect on three of the 32 outcomes examined in these studies. Concentrations of fibrinogen (0.17 micromol/l, 95% confidence interval (CI) -0.30 to -0.04, p = 0.01) and fasting plasma glucose (0.20 mmol/l, 95% CI -0.30 to -0.10, p < 0.01) were reduced. There was a small but clinically unimportant decrease in HDL (0.01 mmol/l, 95% CI -0.02 to 0.00, p < 0.01). Treatment with ALA did not significantly modify total cholesterol, triglycerides, weight, body mass index, LDL, diastolic blood pressure, systolic blood pressure, VLDL, and apolipoprotein B. CONCLUSIONS: Although ALA supplementation may cause small decreases in fibrinogen concentrations and fasting plasma glucose, most cardiovascular risk markers do not appear to be affected. Further trials are needed, but dietary supplementation with ALA to reduce cardiovascular disease cannot be recommended.

Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-1 trials.

OBJECTIVE: To investigate the effectiveness of valerian for the management of chronic insomnia in general practice. DESIGN: Valerian versus placebo in a series of n-of-1 trials, in Queensland, Australia. RESULTS: Of 42 enrolled patients, 24 (57%) had sufficient data for inclusion into the n-of-1 analysis. Response to valerian was fair for 23 (96%) participants evaluating their "energy level in the previous day" but poor or modest for all 24 (100%) participants' response to "total sleep time" and for 23 (96%) participants' response to "number of night awakenings" and "morning refreshment". As a group, the proportion of treatment successes ranged from 0.35 (95% CI 0.23, 0.47) to 0.55 (95% CI 0.43, 0.67) for the six elicited outcome sleep variables. There was no significant difference in the number (P=0.06), distribution (P=1.00) or severity (P=0.46) of side effects between valerian and placebo treatments. CONCLUSIONS: Valerian was not shown to be appreciably better than placebo in promoting sleep or sleep-related factors for any individual patient or for all patients as a group.

How effective are treatments other than antibiotics for acute sore throat?

To estimate the benefits of treatments other than antibiotics for acute sore throat, and the differences between non-antibiotic interventions and controls in patient-perceived pain of sore throat, a systematic review of controlled trials in Medline and the Cochrane Library was carried out. Sixty-six randomised controlled trials (with or without additional antibiotics) were identified and 17 met the selection criteria. Twenty-two non-antibiotic managements for sore throat were compared. Their efficacy relative to placebo ranged from no effect to 93%. Some non-antibiotic treatments may be more effective than antibiotics; however, publication bias may have exaggerated the benefits. These treatments should be investigated further with respect to efficacy, safety, and side-effects as potential firstline management options for acute sore throat.

Screening for colorectal cancer using the faecal occult blood test, hemoccult.

BACKGROUND: Colorectal cancer is a leading cause of illness and death in the Western world. In Australia, the United Kingdom and the United States, it is the second commonest cancer for women after breast cancer (age-standardised incidence 22-33 per 100,000), and men after prostate or lung cancer (age-standardised incidence 31-47 per 100,000) (Jeffs et al, 1996; Parkin et al, 1992). Just under half of all persons affected will die from their disease (Jeffs et al, 1996; Parkin et al, 1992) The human and financial costs of this disease have prompted considerable research efforts to evaluate the ability of screening tests to detect the cancer at an early curable stage. Tests which have been considered for screening include faecal occult blood tests, sigmoidoscopy and colonoscopy. OBJECTIVES: To determine whether screening for colorectal cancer using the faecal occult blood test, Hemoccult reduces colorectal cancer mortality and to consider the benefits and harms of screening. SEARCH STRATEGY: Published and unpublished data for this review were identified by: * retrieving studies included in a systematic review conducted by some of the authors in 1995, * searches of MEDLINE, Current Contents and the Cochrane Controlled Trials Register, * writing to trial lists. SELECTION CRITERIA: All controlled trials of screening for colorectal cancer using Hemoccult were eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data from the trials were independently extracted by two authors. Data analysis was performed using the group subjects were randomised to ('intention to screen'), whether or not they were ever screened. To estimate the effect of Hemoccult screening on colorectal cancer mortality, we calculated relative risks and risk differences for each trial, and then overall, using fixed and random effects models and tested for heterogeneity of effects. We calculated summary measures of effect including all trials and also for just the randomised controlled trials. We also calculated a summary measure of effect, adjusted for attendance at screening in each trial (not shown in Meta-view). MAIN RESULTS: Meta-analysis of mortality results from the randomised controlled trials shows that those allocated to screening had a reduction in colorectal cancer mortality of 16% (RR 0.84, CI: 0.77-0.93). When adjusted for screening attendance in the individual studies, the mortality reduction is 23% (RR 0.77, CI: 0.57-0.89). Overall, if 10 000 people were offered a biennial Hemoccult screening program and two-thirds attended for at least one Hemoccult test, there would be 8.5 deaths (CI: 3.6-13.5) from colorectal cancer prevented over 10 years. However, the screening program would also result in 2 800 participants having at least one colonoscopy, if screening harms from the Minnesota trial are considered, and there would be 3.4 colonoscopy complications (perforation or haemorrhage). If screening harms from the Gothenburg trial are considered, approximately 600 participants would need at least one sigmoidoscopy and double contrast barium enema, resulting in 1.8 perforations or haemorrhages. REVIEWER'S CONCLUSIONS: Screening benefits include reduction in colorectal cancer mortality, possible reduction in cancer incidence through detection and removal of colorectal adenomas and potentially, treatment of early colorectal cancers may involve less invasive surgery. Harmful effects of screening include the physical complications of colonoscopy, disruption to lifestyle, stress and discomfort of testing and investigations, and the anxiety caused by falsely positive screening tests. Although screening benefits are likely to outweigh harms for populations at increased risk of colorectal cancer, we need more information about the harmful effects of screening, the community's responses to screening and screening costs for different health care systems before widespread screening can be recommended.

Quality adjusted survival analysis with repeated quality of life measures.

One way of examining trade-offs between quantity and quality of life (QOL) is to combine them into a single measure such as quality-adjusted life year (QALY). If censoring occurs, then estimation presents some difficulties. One approach, known as Q-TWiST, is to define a series of health states, use a 'partitioned' survival analysis to calculate the average time in each state, and then weight each state according to its quality of life to calculate QALYs. Such health-state models, however, are unhelpful when the transitions between health states are unclear or if they do not adequately reflect variations in quality of life. We therefore examine an alternative analysis to be used when repeated measures of quality of life are available from individual patients in a clinical trial. The method proceeds by separating quality of life and survival, that is, dQALY/dt = S(t)Q(t), where S(t) is the survival curve, estimated from the standard Kaplan-Meier method, and Q(t) is the quality of life function, derived from individual repeated measures of quality of life. We derive single health-state (QALY) and multiple health-state (Q-TWiST) models and illustrate the approach by comparing different durations of adjuvant chemotherapy for breast cancer.

Vitamin A supplementation in infectious diseases: a meta-analysis.

OBJECTIVE: To study the effect of vitamin A supplementation on morbidity and mortality from infectious disease. DESIGN: A meta-analysis aimed at identifying and combining mortality and morbidity data from all randomised controlled trials of vitamin A. RESULTS: Of 20 controlled trials identified, 12 trials were randomised trials and provided "intention to treat" data: six community trials in developing countries, three in children admitted to hospital with measles, and three in very low birth weight infants. Combined results for community studies suggest a reduction of 30% (95% confidence interval 21% to 38%; two tailed p < 0.0000001) in all cause mortality. Analysis of cause specific mortality showed a reduction in deaths from diarrhoeal disease (in community studies) by 39% (24% to 50%; two tailed p < 0.00001); from respiratory disease (in measles studies) by 70% (15% to 90%; two tailed p = 0.02); and from other causes of death (in community studies) by 34% (15% to 48%; two tailed p = 0.001). Reductions in morbidity were consistent with the findings for mortality, but fewer data were available. CONCLUSIONS: Adequate supply of vitamin A, either through supplementation or adequate diet, has a major role in preventing morbidity and mortality in children in developing countries. In developed countries vitamin A may also have a role in those with life threatening infections such as measles and those who may have a relative deficiency, such as premature infants.