Colchicine for primary biliary cirrhosis: a Cochrane Hepato-Biliary Group systematic review of randomized clinical trials

OBJECTIVES: Colchicine is used for patients with primary biliary cirrhosis due to its immunomodulatory and antifibrotic potential. The results from randomized clinical trials have, however, been inconsistent. We conducted a systematical review to evaluate the effect of colchicine for primary biliary cirrhosis. METHODS: We identified randomized clinical trials comparing colchicine with placebo/no intervention. We analyzed effects by fixed and random effects model. We investigated heterogeneity by subgroup and sensitivity analyses. RESULTS: We included 10 trials involving 631 patients, four of which were high-quality trials. No significant differences were detected between colchicine and placebo/no intervention regarding mortality (relative risk (RR), 1.21; 95% confidence interval (CI), 0.71-2.06), mortality or liver transplantation (RR = 1.00; 95% CI, 0.67-1.49), liver complications, liver biochemical variables, liver histology, or adverse events. Regarding mortality, an extreme case analysis favoring colchicine did not demonstrate beneficial effects of colchicine, whereas an extreme case analysis favoring placebo/no intervention demonstrated a detrimental effect of colchicine (RR = 2.28; 95% CI, 1.17-4.44). The number of patients without improvement of pruritus significantly decreased in the colchicine group (RR = 0.75; 95% CI, 0.65-0.87). However, this estimate was based on only 156 patients from three trials. CONCLUSIONS: There is insufficient evidence to support the use of colchicine for patients with primary biliary cirrhosis. As we are unable to exclude a risk of increased mortality, we recommend to use colchicine only in randomized clinical trials.     

Ribavirin monotherapy for chronic hepatitis C infection: a Cochrane Hepato-Biliary Group systematic review and meta-analysis of randomized trials

OBJECTIVES: Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C. METHODS: Randomized trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, and EMBASE (last search May 2005). The primary outcomes were sustained virological response (loss of HCV RNA) and liver-related morbidity plus all-cause mortality. Secondary outcomes included end-of-treatment virological response, biochemical response (normalization of transaminases), histological response, and adverse events. RESULTS: We included 11 randomized trials with 521 patients. Ten trials had unclear control of bias. Ribavirin had no significant effect on sustained (risk difference (RD), 0%; 95% confidence intervals (CI), -2% to 3%) or end-of-treatment virological response (RD, 0%; 95% CI, -3% to 3%). Ribavirin had no significant effect on liver-related morbidity plus mortality (RD, 0%; 95% CI, -2% to 3%). Ribavirin significantly improved histological response and end-of-treatment biochemical response, but not sustained biochemical response. Ribavirin significantly increased the risk of anemia and treatment discontinuation. CONCLUSIONS: We found no evidence to support ribavirin monotherapy for patients with chronic hepatitis C, but trials were small and type II errors cannot be excluded. Patients intolerant to interferon should not continue treatment with ribavirin alone outside randomized trials.     

Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials

OBJECTIVE: The aim of this study was to assess beneficial and harmful effects of medicinal herbs for hepatitis C virus (HCV) infection. METHODS: The databases of the Cochrane Collaboration, MEDLINE, EMBASE, and BIOSIS were searched combined with manual searches of five Chinese and one Japanese journals. We included randomized trials comparing medicinal herbs with placebo, no intervention, nonspecific treatment, other herbs, or interferon and/or ribavirin. Trials of herbs with or without other drug(s) were included. Methodological quality of the trials was evaluated by randomization, double blinding, and the Jadad scale. RESULTS: Thirteen randomized trials (n = 818) evaluated 14 medicinal herbs. Four trials had adequate methodology. Compared with placebo, none of the herbs showed effects on HCV RNA or liver enzyme, except for silybin, which showed a significant reduction of serum AST and gamma-glutamyltranspeptidase levels in one trial. Oxymatrine showed effects on clearance of HCV RNA (relative risk = 9.20, 95% CI = 1.26-67.35) compared with vitamins. The herbal mixture Bing Gan Tang plus interferon-alpha showed better effects on clearance of HCV RNA (relative risk = 2.54, 95% CI = 1.43-4.49) and on normalization of serum ALT (relative risk = 2.54, 95% CI = 1.43-4.49) than interferon-alpha alone. The herbal mixture Yi Zhu decoction showed better effects on clearance of HCV RNA and normalization of ALT compared with glycyrrhizin plus ribavirin. Yi Er Gan Tang showed effects on normalizing serum ALT compared with silymarin plus glucurolactone. The herbs were associated with adverse events. CONCLUSIONS: There is no firm evidence supporting medicinal herbs for HCV infection, and further randomized trials are justified.     

Qigong for hypertension: a systematic review of randomized clinical trials

OBJECTIVES: To assess systematically the clinical evidence of qigong for hypertension. METHODS: Databases were searched up to August 2006. All randomized clinical trials (RCTs) testing qigong in patients with hypertension of any origin and assessing clinically relevant outcomes were considered. Trials using any type of control intervention were included. The selection of studies, data extraction and quality assessment were performed independently by at least two reviewers. Methodological quality was evaluated using the Jadad score. RESULTS: A total of 121 potentially relevant articles were identified and 12 RCTs were included. Seven RCTs tested qigong in combination with antihypertensive drugs compared with antihypertensive drugs alone. The meta-analysis of two trials reporting adequate data suggested beneficial effects in favour of qigong [weighted mean difference, systolic blood pressure (SBP) -12.1 mmHg, 95% confidence interval (CI) -17.1 to -7.0; diastolic blood pressure -8.5 mmHg, 95% CI -12.6 to -4.4]. Qigong was compared with waiting list control in two RCTs and was found to reduce SBP significantly (weighted mean difference -18.5 mmHg, 95% CI -23.1 to -13.9). In three further RCTs the comparisons made were: qigong combined with conventional therapy versus muscle relaxation combined with conventional therapy; qigong as a sole treatment versus exercise. All reported positive results in at least some of the relevant outcome measures. The methodological quality of the studies was low. CONCLUSION: There is some encouraging evidence of qigong for lowering SBP, but the conclusiveness of these findings is limited. Rigorously designed trials are warranted to confirm these results.     

Interventions for the prevention of overweight and obesity in preschool children: a systematic review of randomized controlled trials

The objective of this study was to analyse interventions for the prevention of overweight and obesity in children under 5 years of age. We carried out a systematic review focusing exclusively on randomized controlled trials (RCTs). Data sources include Medline, Cochrane Library, EMBASE, CINHAL, PsychInfo and Web of Science. Data were extracted from seventeen articles describing seven RCTs identified through electronic search, screening of references in systematic reviews, own files and contact with authors. RCTs were assessed with the Jadad scale. Four trials were carried out in preschool settings, one with an exclusive educational component, two with an exclusive physical activity component and one with both. Two trials were family‐based, with education and counselling for parents and children. The remaining trial was carried out in maternity hospitals, with a training intervention on breastfeeding. None of the interventions had an effect in preventing overweight and obesity. The failure to show an effect may be due to the choice of outcomes, the quality of the RCTs, the suboptimal implementation of the interventions, the lack of focus on social and environmental determinants. More rigorous research is needed on interventions and on social and environmental factors that could impact on lifestyle.     

Interventions employing mobile technology for overweight and obesity: an early systematic review of randomized controlled trials

Obesity is a global epidemic with major healthcare implications and costs. Mobile technologies are potential interventions to promote weight loss. An early systematic review of this rapidly growing area of research was conducted. Electronic databases were searched for articles published between January 1998 and October 2011. Data sources included Medline, Embase and the Cochrane Central Register of Controlled Trials. Ongoing research was searched for using clinical trials databases and registers. Out of 174 articles retrieved, 21 met the inclusion criteria of randomized controlled trials (RCTs) on mobile technology interventions facilitating weight loss in overweight and obese adults with any other comparator. A narrative synthesis was undertaken. Seven articles were included and appraised using the Cochrane risk of bias tool: four presented a low risk of bias and three presented a high risk of bias. There is consistent strong evidence across the included multiple high‐quality RCTs that weight loss occurs in the short‐term because of mobile technology interventions, with moderate evidence for the medium‐term. Recommendations for improving the reporting and quality of future trials are made including reporting weight loss in percent to meet clinical standards, and including features such as long‐term follow‐up, cost‐effectiveness and patient acceptability.     

Yoga for low back pain: a systematic review of randomized clinical trials

It has been suggested that yoga has a positive effect on low back pain and function. The objective of this systematic review was to assess the effectiveness of yoga as a treatment option for low back pain. Seven databases were searched from their inception to March 2011. Randomized clinical trials were considered if they investigated yoga in patients with low back pain and if they assessed pain as an outcome measure. The selection of studies, data extraction and validation were performed independently by two reviewers. Seven randomized controlled clinical trials (RCTs) met the inclusion criteria. Their methodological quality ranged between 2 and 4 on the Jadad scale. Five RCTs suggested that yoga leads to a significantly greater reduction in low back pain than usual care, education or conventional therapeutic exercises. Two RCTs showed no between-group differences. It is concluded that yoga has the potential to alleviate low back pain. However, any definitive claims should be treated with caution.     

Osteopathy for musculoskeletal pain patients: a systematic review of randomized controlled trials

The objective of this systematic review was to assess the effectiveness of osteopathy as a treatment option for musculoskeletal pain. Six databases were searched from their inception to August 2010. Only randomized clinical trials (RCTs) were considered if they tested osteopathic manipulation/mobilization against any control intervention or no therapy in human with any musculoskeletal pain in any anatomical location, and if they assessed pain as an outcome measure. The selection of studies, data extraction, and validation were performed independently by two reviewers. Studies of chiropractic manipulations were excluded. Sixteen RCTs met the inclusion criteria. Their methodological quality ranged between 1 and 4 on the Jadad scale (max = 5). Five RCTs suggested that osteopathy compared to various control interventions leads to a significantly stronger reduction of musculoskeletal pain. Eleven RCTs indicated that osteopathy compared to controls generates no change in musculoskeletal pain. Collectively, these data fail to produce compelling evidence for the effectiveness of osteopathy as a treatment of musculoskeletal pain.     

Acupuncture for fibromyalgia--a systematic review of randomized clinical trials

OBJECTIVE: Acupuncture is often used and frequently advocated for the symptomatic treatment of fibromyalgia. A systematic review has previously demonstrated encouraging findings. As it is now outdated, we wanted to update it. METHODS: We searched seven electronic databases for relevant randomized clinical trials (RCTs). The data were extracted and validated independently by both authors. As no meta-analysis seemed possible, the results were evaluated in narrative form. RESULTS: Five RCTs met our inclusion criteria, all of which used acupuncture as an adjunct to conventional treatments. Their methodological quality was mixed and frequently low. Three RCTs suggested positive but mostly short-lived effects and two yielded negative results. There was no significant difference between the quality of the negative and the positive RCTs. All positive RCTs used electro-acupunture. CONCLUSION: The notion that acupuncture is an effective symptomatic treatment for fibromyaligia is not supported by the results from rigorous clinical trials. On the basis of this evidence, acupuncture cannot be recommended for fibromyalgia.     

Pharmacological interventions for hypertensive emergencies: a Cochrane systematic review

Hypertensive emergencies occur when high blood pressure is associated with the presence of acute end-organ damage, such as hypertensive encephalopathy. There is controversy as to when and which antihypertensive drugs to use in these situations. Using a comprehensive search strategy in electronic sources, MEDLINE, EMBASE and Cochrane clinical trial register, we conducted a systematic review to look all randomized control trials (RCTs) that compare an antihypertensive drug versus placebo, no treatment or another antihypertensive drug. Fifteen RCTs (representing 869 patients) met the inclusion criteria. Two trials included a placebo arm. All studies (except one) were open-label trials. Seven drug classes were evaluated in those trials: nitrates (nine trials), angiotensin-converting enzyme inhibitors (seven), diuretics (three), calcium channel blockers (six), alpha-1 adrenergic antagonists (four), direct vasodilators (two) and dopamine agonists (one). Mortality event data were reported in seven trials. Due to insufficient data, no meta-analysis was performed for clinical outcomes. Differences in blood pressure changes between antihypertensives were minor. There is no RCT evidence demonstrating that antihypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies. Furthermore, there is insufficient RCT evidence to determine which drug or drug class is most effective in reducing mortality and morbidity. There were some minor differences in the degree of blood pressure lowering when one class of antihypertensive drug is compared to another. However, the clinical significance is unknown. RCTs are needed to assess different drug classes to determine initial and longer-term mortality and morbidity outcomes.Journal of Human Hypertension (2008) 22, 596-607; doi:10.1038/jhh.2008.25; published online 17 April 2008.     

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials

OBJECTIVE: To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. METHODS: Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. RESULTS: Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. CONCLUSIONS: There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.     

Meta-analysis of randomized controlled trials on the effectiveness of somatostatin analogues for pancreatic surgery: a Cochrane review

Background:

The use of synthetic analogues of somatostatin following pancreatic surgery is controversial. The aim of this meta-analysis is to determine whether prophylactic somatostatin analogues (SAs) should be used routinely in pancreatic surgery.

Methods:

Randomized controlled trials were identified from the Cochrane Library Trials Register, MEDLINE, EMBASE, Science Citation Index Expanded and reference lists. Data were extracted from these trials by two independent reviewers. The risk ratio (RR), mean difference (MD) and standardized mean difference (SMD) were calculated with 95% confidence intervals (95% CIs) based on intention-to-treat or available case analysis.

Results:

Seventeen trials involving 2143 patients were identified. The overall number of patients with postoperative complications was lower in the SA group (RR 0.71, 95% CI 0.62–0.82), but there was no difference between the groups in perioperative mortality (RR 1.04, 95% CI 0.68–1.59), re-operation rate (RR 1.15, 95% CI 0.56–2.36) or hospital stay (MD −1.04 days, 95% CI −2.54 to 0.46). The incidence of pancreatic fistula was lower in the SA group (RR 0.64, 95% CI 0.53–0.78). The proportion of these fistulas that were clinically significant is not clear. Analysis of results of trials that clearly distinguished clinically significant fistulas revealed no difference between the two groups (RR 0.69, 95% CI 0.34–1.41). Subgroup analysis revealed a shorter hospital stay in the SA group than among controls for patients with malignant aetiology (MD −7.57 days, 95% CI −11.29 to −3.84).

Conclusions:

Somatostatin analogues reduce perioperative complications but do not reduce perioperative mortality. However, they do shorten hospital stay in patients undergoing pancreatic surgery for malignancy. Further adequately powered trials of low risk of bias are necessary.