Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by inadequate blood flow through the veins, usually in the lower limbs. It can result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Sufferers may also experience swelling and ulcers. Phlebotonics are a class of drugs that are often used to treat CVI. OBJECTIVES: To assess the efficacy of oral or topical phlebotonics. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group trials register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005), MEDLINE (January 1966 to April 2005), EMBASE (January 1980 to April 2005) and reference lists of articles. We also contacted pharmaceutical companies. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in CVI patients at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. The effects of treatment were estimated by relative risk (RR) or by standardised mean differences (SMD) by applying a random effects statistical model. Sensitivity analyses were also performed. MAIN RESULTS: Fifty-nine RCTs of oral phlebotonics were included, but only 44 trials involving 4413 participants contained quantifiable data for the efficacy analysis: 23 of rutosides, ten of hidrosmine and diosmine, six of calcium dobesilate, two of centella asiatica, one of french maritime pine bark extract, one of aminaftone and one of grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Outcomes included oedema, venous ulcers, trophic disorders, subjective symptoms (pain, cramps, restless legs, itching, heaviness, swelling and paraesthesias), global assessment measures and side effects. The results of many variables were heterogeneous. Phlebotonics showed some global benefit (i.e. oedema reduction) (relative risk 0.72, 95% confidence interval 0.65 to 0.81). The benefit for the remaining CVI signs and symptoms must be evaluated by phlebotonic group. There were no quantifiable data on quality of life. AUTHORS' CONCLUSIONS: There is not enough evidence to globally support the efficacy of phlebotonics for chronic venous insufficiency. There is a suggestion of some efficacy of phlebotonics on oedema but this is of uncertain clinical relevance. Due to the limitations of current evidence, there is a need for further randomised, controlled clinical trials with greater attention paid to methodological quality.

Neuroreflexotherapy for non-specific low-back pain.

BACKGROUND: Among the wide range of therapeutic alternatives proposed for the management of low-back pain (LBP), a less widely used technique from Spain, called neuroreflexotherapy (NRT) has claimed to show very favourable results, mainly in patients with chronic low-back pain. OBJECTIVES: The aim of this review was to systematically assess the effectiveness of NRT for the treatment of non-specific LBP in adult patients, aged 16 to 65 years. A secondary objective was to compare NRT with other conventional interventions. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to October 1, 2002. SELECTION CRITERIA: Only randomised controlled trials (RCTs) of NRT for the treatment of patients with a clinical diagnosis of non-specific LBP were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials and extracted data using pre-designed forms. Because the outcome variables were not assessed in a homogenous way, it was not possible to pool the results to obtain an estimate of global effect, as initially planned. MAIN RESULTS: Three RCT were included, with a total of 125 subjects randomised to the control groups and 148 subjects receiving active NRT. Neuroreflexotherapy was the same in all three trials, while the control groups received sham-NRT in two trials and standard care in one. Two trials studied patients with chronic LBP, the third studied patients with a mix of chronic and sub-acute LBP. Clinical outcomes were measured in the short-term (15 to 60 days) in all three trials; in one trial, resource utilization was measured after one year. Individuals who received active NRT showed statistically significantly better outcomes than the control groups for measures of pain, degree of mobility, disability, medication use, consumption of resources and costs. No significant differences were observed for quality of life measures. Side effects were more frequently reported in the control groups during short-term follow-up, with no major side effects reported by those receiving active NRT. REVIEWERS' CONCLUSIONS: NRT appears to be a safe and effective intervention for the treatment of chronic non-specific LBP. The efficacy is less clear for sub-acute LBP. However, these results are limited to three trials conducted by a small number of specifically trained and experienced clinicians, in a limited geographical location. No data are available on the ease and time-frame needed to achieve that level of expertise. RCTs by other practitioners, in other locations, that replicate the effects reported in this review are needed before recommending a broader practice.

Drugs for preventing lung cancer in healthy people.

BACKGROUND: Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta carotene and a lower risk of lung cancer. OBJECTIVES: To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people. SEARCH STRATEGY: The electronic databases MEDLINE (1966-july 2001), EMBASE (1974-july 2001) and the Cochrane Controlled Trial Register (CENTRAL, Issue 3/2001) and bibliographies were searched. In addition authors of included studies were contacted to identify potentially eligible published and unpublished trials. SELECTION CRITERIA: Included studies were randomised controlled clinical trials comparing different supplements or comparing supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Three reviewers independently selected the trials to be included in the review and assessed the methodological quality of each trial, and two extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes. MAIN RESULTS: Four studies were eligible for inclusion. All were population based trials, including a total of 109,394 participants. Two studies included smokers, one included workers exposed to asbestos and two studies were carried out in health professionals. A group of participants with no known risk factors for lung cancer was included in the study sample of two trials. Beta-carotene was evaluated in all trials, alone or combination with alpha-tocopherol or retinol, and one study tested alpha-tocopherol alone. Duration of treatment varied from 2 to 12 years and follow-up was from two to five years. All trials had a placebo group. For people with risk factors for lung cancer no reduction in lung cancer incidence or mortality was found in those taking vitamins alone compared with placebo (incidence of lung cancer: RR 0.98, 95% CI 0.81-1.19; lung cancer mortality: RR 0.93, 95% CI 0.73-1.19). For people with no known risk factors of lung cancer, none of the vitamins or their combinations appeared to have any effect. Combined data from three studies showed a non-statistically significant increased risk of lung cancer incidence (RR 1.11, 95% CI 0.94-1.33) and mortality (RR 1.05, 95% CI 0.87-1.28) for beta-carotene alone at pharmacological doses in groups with risk factors for lung cancer. When beta-carotene was combined with retinol, data from a single study showed that there was a statistically significant, increased risk of lung cancer incidence (RR 1.42, 95% CI 1.13-1.80) and mortality (RR 1.75, 95% CI 1.29-2.38) in people with risk factors for lung cancer who took both vitamins compared with those who took placebo. Data from also from one study showed that the combination of beta-carotene with alpha-tocopherol in people with risk factors for lung cancer was associated with a non-statistically significant increased risk of lung cancer incidence (RR 1.16, 95% CI 0.96-1.39) and mortality (RR 1.15, 95% CI 0.91-1.45). No effect was observed for total cancer incidence, mortality or all-cause mortality. REVIEWER'S CONCLUSIONS: There is currently no evidence to support recommending vitamins such as alpha-tocopherol, beta-carotene or retinol, alone or in combination, to prevent lung cancer. A harmful effect was found for beta-carotene with retinol at pharmacological doses in people with risk factors for lung cancer (smoking and/or occupational exposure to asbestos). More research from larger trials and with longer follow-up is needed to analyse the effectiveness of other supplements.