Cochrane Collaboration

About: Cochrane Collaboration is a nonprofit organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Systematic review & Randomized controlled trial. The organization has 1995 authors who have published 3928 publications receiving 382695 citations.

Combination pharmacotherapy for the treatment of neuropathic pain in adults

Abstract: Background Pharmacotherapy remains an important modality for the treatment of neuropathic pain. However, as monotherapy current drugs are associated with limited efficacy and dose-related side effects. Combining two or more different drugs may improve analgesic efficacy and, in some situations, reduce overall side effects (e.g. if synergistic interactions allow for dose reductions of combined drugs). Objectives This review evaluated the efficacy, tolerability and safety of various drug combinations for the treatment of neuropathic pain. Search methods We identified randomised controlled trials (RCTs) of various drug combinations for neuropathic pain from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and trial registries. The most recent search was performed on 9 April 2012. Selection criteria Double-blind, randomised studies comparing combinations of two or more drugs (systemic or topical) to placebo and/or at least one other comparator for the treatment of neuropathic pain. Data collection and analysis Data extracted from each study included: proportion of participants a) reporting ≥ 30% pain reduction from baseline OR ≥ moderate pain relief OR ≥ moderate global improvement; b) dropping out of the trial due to treatment-emergent adverse effects; c) reporting each specific adverse effect (e.g. sedation, dizziness) of ≥ moderate severity. The primary comparison of interest was between study drug(s) and one or both single-agent comparators. We combined studies if they evaluated the same drug class combination at roughly similar doses and durations of treatment. We used RevMan 5 to analyse data for binary outcomes. Main results We identified 21 eligible studies: four (578 participants) evaluated the combination of an opioid with gabapentin or pregabalin; two (77 participants) evaluated an opioid with a tricyclic antidepressant; one (56 participants) of gabapentin and nortriptyline; one (120 participants) of gabapentin and alpha-lipoic acid, three (90 participants) of fluphenazine with a tricyclic antidepressant; three (90 participants) of an N-methyl-D-aspartate (NMDA) blocker with an agent from a different drug class; five (604 participants) of various topical medications; one (313 participants) of tramadol with acetaminophen; and another one (44 participants) of a cholecystokinin blocker (L-365,260) with morphine. The majority of combinations evaluated to date involve drugs, each of which share some element of central nervous system (CNS) depression (e.g. sedation, cognitive dysfunction). This aspect of side effect overlap between the combined agents was often reflected in similar or higher dropout rates for the combination and may thus substantially limit the utility of such drug combinations. Meta-analysis was possible for only one comparison of only one combination, i.e. gabapentin + opioid versus gabapentin alone. This meta-analysis involving 386 participants from two studies demonstrated modest, yet statistically significant, superiority of a gabapentin + opioid combination over gabapentin alone. However, this combination also produced significantly more frequent side effect-related trial dropouts compared to gabapentin alone. Authors' conclusions Multiple, good-quality studies demonstrate superior efficacy of two-drug combinations. However, the number of available studies for any one specific combination, as well as other study factors (e.g. limited trial size and duration), preclude the recommendation of any one specific drug combination for neuropathic pain. Demonstration of combination benefits by several studies together with reports of widespread clinical polypharmacy for neuropathic pain surely provide a rationale for additional future rigorous evaluations. In order to properly identify specific drug combinations which provide superior efficacy and/or safety, we recommend that future neuropathic pain studies of two-drug combinations include comparisons with placebo and both single-agent components. Given the apparent adverse impact of combining agents with similar adverse effect profiles (e.g. CNS depression), the anticipated development and availability of non-sedating neuropathic pain agents could lead to the identification of more favourable analgesic drug combinations in which side effects are not compounded.

General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis

Abstract: Objectives To quantify the benefits and harms of general health checks in adults with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes. Design Cochrane systematic review and meta-analysis of randomised trials. For mortality, we analysed the results with random effects meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible. Data sources Medline, EMBASE, Healthstar, Cochrane Library, Cochrane Central Register of Controlled Trials, CINAHL, EPOC register, ClinicalTrials.gov, and WHO ICTRP, supplemented by manual searches of reference lists of included studies, citation tracking (Web of Knowledge), and contacts with trialists. Selection criteria Randomised trials comparing health checks with no health checks in adult populations unselected for disease or risk factors. Health checks defined as screening general populations for more than one disease or risk factor in more than one organ system. We did not include geriatric trials. Data extraction Two observers independently assessed eligibility, extracted data, and assessed the risk of bias. We contacted authors for additional outcomes or trial details when necessary. Results We identified 16 trials, 14 of which had available outcome data (182 880 participants). Nine trials provided data on total mortality (11 940 deaths), and they gave a risk ratio of 0.99 (95% confidence interval 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (4567 deaths), risk ratio 1.03 (0.91 to 1.17), and eight on cancer mortality (3663 deaths), risk ratio 1.01 (0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings. We did not find beneficial effects of general health checks on morbidity, hospitalisation, disability, worry, additional physician visits, or absence from work, but not all trials reported on these outcomes. One trial found that health checks led to a 20% increase in the total number of new diagnoses per participant over six years compared with the control group and an increased number of people with self reported chronic conditions, and one trial found an increased prevalence of hypertension and hypercholesterolaemia. Two out of four trials found an increased use of antihypertensives. Two out of four trials found small beneficial effects on self reported health, which could be due to bias. Conclusions General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although they increased the number of new diagnoses. Important harmful outcomes were often not studied or reported. Systematic review registration Cochrane Library, doi:10.1002/14651858.CD009009.

Editorial peer review for improving the quality of reports of biomedical studies

Abstract: Background Scientific findings must withstand critical review if they are to be accepted as valid, and editorial peer review (critique, effort to disprove) is an essential element of the scientific process. We review the evidence of the editorial peer-review process of original research studies submitted for paper or electronic publication in biomedical journals. Objectives To estimate the effect of processes in editorial peer review. Search methods The following databases were searched to June 2004: CINAHL, Ovid, Cochrane Methodology Register, Dissertation abstracts, EMBASE, Evidence Based Medicine Reviews: ACP Journal Club, MEDLINE, PsycINFO, PubMed. Selection criteria We included prospective or retrospective comparative studies with two or more comparison groups, generated by random or other appropriate methods, and reporting original research, regardless of publication status. We hoped to find studies identifying good submissions on the basis of: importance of the topic dealt with, relevance of the topic to the journal, usefulness of the topic, soundness of methods, soundness of ethics, completeness and accuracy of reporting. Data collection and analysis Because of the diversity of study questions, viewpoints, methods, and outcomes, we carried out a descriptive review of included studies grouping them by broad study question. Main results We included 28 studies. We found no clear-cut evidence of effect of the well-researched practice of reviewer and/or author concealment on the outcome of the quality assessment process (9 studies). Checklists and other standardisation media have some evidence to support their use (2 studies). There is no evidence that referees' training has any effect on the quality of the outcome (1 study). Different methods of communicating with reviewers and means of dissemination do not appear to have an effect on quality (3 studies). On the basis of one study, little can be said about the ability of the peer-review process to detect bias against unconventional drugs. Validity of peer review was tested by only one small study in a specialist area. Editorial peer review appears to make papers more readable and improve the general quality of reporting (2 studies), but the evidence for this has very limited generalisability. Authors' conclusions At present, little empirical evidence is available to support the use of editorial peer review as a mechanism to ensure quality of biomedical research. However, the methodological problems in studying peer review are many and complex. At present, the absence of evidence on efficacy and effectiveness cannot be interpreted as evidence of their absence. A large, well-funded programme of research on the effects of editorial peer review should be urgently launched.

Vaccines for measles, mumps and rubella in children

Abstract: Measles, mumps and rubella (MMR) are three very dangerous infectious diseases which cause severe morbidity, disability and death in low-income countries. Based on the evidence provided by three cohort studies (3104 participants), vaccination with one dose of MMR vaccine is at least 95% effective in preventing clinical measles among preschool children; in schoolchildren and adolescents at least one dose of MMR vaccine was 98% effective in preventing laboratory-confirmed measles cases; one or two MMR doses were respectively 92% and 95% effective in preventing secondary measles cases. At least one dose of MMR vaccine is effective in preventing clinical mumps among children and adolescents when prepared with Jeryl Lynn strains (vaccine effectiveness = 69% to 81%, one cohort and one case-control study, 1656 participants), as well as when prepared with Urabe strain (vaccine effectiveness = 70% to 75%, one cohort and one case-control study, 1964 participants). Effectiveness against laboratory-confirmed mumps in children and adolescents was estimated to be between 64% to 66% for one and 83% to 88% for two doses of Jeryl Lynn MMR (two case-control studies, 1664 participants) and 87% for Urabe-containing MMR (one cohort study, 48 participants). Vaccination with Urabe MMR confers protection against secondary mumps infection (vaccine effectiveness = 73%, one cohort study, 147 participants). We identified no studies assessing the effectiveness of MMR vaccine against clinical or laboratory-confirmed rubella. Results from two very large case series studies involving about 1,500,000 children who were given the MMR vaccine containing Urabe or Leningrad-Zagreb strains show this vaccine to be associated with aseptic meningitis; whereas administration of the vaccine containing Moraten, Jeryl Lynn, Wistar RA, RIT 4385 strains is associated with febrile convulsion in children aged below five years (one person-time cohort study, 537,171 participants; two self controlled case series studies, 1001 participants). The MMR vaccine could also be associated with idiopathic thrombocytopaenic purpura (two case-controls, 2450 participants, one self controlled case series, 63 participants). We could assess no significant association between MMR immunisation and the following conditions: autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, or bacterial or viral infections. The methodological quality of many of the included studies made it difficult to generalise their results.