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.

Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

Abstract: Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

Disagreements in meta-analyses using outcomes measured on continuous or rating scales: observer agreement study.

Abstract: Objective To study the inter-observer variation related to extraction of continuous and numerical rating scale data from trial reports for use in meta-analyses. Design Observer agreement study. Data sources A random sample of 10 Cochrane reviews that presented a result as a standardised mean difference (SMD), the protocols for the reviews and the trial reports (n=45) were retrieved. Data extraction Five experienced methodologists and five PhD students independently extracted data from the trial reports for calculation of the first SMD result in each review. The observers did not have access to the reviews but to the protocols, where the relevant outcome was highlighted. The agreement was analysed at both trial and meta-analysis level, pairing the observers in all possible ways (45 pairs, yielding 2025 pairs of trials and 450 pairs of meta-analyses). Agreement was defined as SMDs that differed less than 0.1 in their point estimates or confidence intervals. Results The agreement was 53% at trial level and 31% at meta-analysis level. Including all pairs, the median disagreement was SMD=0.22 (interquartile range 0.07-0.61). The experts agreed somewhat more than the PhD students at trial level (61% v 46%), but not at meta-analysis level. Important reasons for disagreement were differences in selection of time points, scales, control groups, and type of calculations; whether to include a trial in the meta-analysis; and data extraction errors made by the observers. In 14 out of the 100 SMDs calculated at the meta-analysis level, individual observers reached different conclusions than the originally published review. Conclusions Disagreements were common and often larger than the effect of commonly used treatments. Meta-analyses using SMDs are prone to observer variation and should be interpreted with caution. The reliability of meta-analyses might be improved by having more detailed review protocols, more than one observer, and statistical expertise.

Iodised salt for preventing iodine deficiency disorders.

Abstract: Background Iodine deficiency is the main cause for potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. Objectives To assess the effects of iodised salt in comparison with other forms of iodine supplementation or placebo in the prevention of iodine deficiency disorders. Search methods We searched The Cochrane Library, MEDLINE, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database, China National knowledge Infrastructure, and searched reference lists, databases of ongoing trials and the Internet. Selection criteria We included prospective controlled studies of iodised salt versus other forms of iodine supplementation or placebo in people living in areas of iodine deficiency. Studies reported mainly goitre rates and urinary iodine excretion as outcome measures. Data collection and analysis The initial data selection and quality assessment of trials was done independently by two reviewers. Subsequently, after the scope of the review was slightly widened from including only randomised controlled trials to including non-randomised prospective comparative studies, a third reviewer repeated the trials selection and quality assessment. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. Main results We found six prospective controlled trials relating to our question. Four of these were described as randomised controlled trials, one was a prospective controlled trial that did not specify allocation to comparison groups, and one was a repeated cross-sectional study comparing different interventions. Comparison interventions included non-iodised salt, iodised water, iodised oil, and salt iodisation with potassium iodide versus potassium iodate. Numbers of participants in the trials ranged from 35 to 334; over 20,000 people were included in the cross-sectional study. Three studies were in children only, two investigated both groups of children and adults and one investigated pregnant women. There was a tendency towards goitre reduction with iodised salt, although this was not significant in all studies. There was also an improved iodine status in most studies (except in small children in one of the studies), although urinary iodine excretion did not always reach the levels recommended by the WHO. None of the studies observed any adverse effects of iodised salt. Authors' conclusions The results suggest that iodised salt is an effective means of improving iodine status. No conclusions can be made about improvements in other, more patient-oriented outcomes, such as physical and mental development in children and mortality. None of the studies specifically investigated development of iodine-induced hyperthyroidism, which can be easily overlooked if just assessed on the basis of symptoms. High quality controlled studies investigating relevant long term outcome measures are needed to address questions of dosage and best means of iodine supplementation in different population groups and settings.

Multi-sectoral health promotion and public health: the role of evidence

Abstract: Background Evidence-informed health promotion and public health is an emerging and ever-changing theme in research and practice. A collaborative approach to gathering and applying evidence is crucial to implementing effective multi-sectoral health promotion and public health interventions for improved population outcomes. This paper presents an argument for the development of multi-sector evidence and discusses both facilitators and challenges to this process. Methods Sector-specific contacts familiar with decision-making processes were selected from referrals gained through academic, government and non-government networks and interviewed (in-person or via telephone) as part of a small scale study to scope the use of evidence within non-health sectors where decisions are likely to impact on public health. Results The views gathered are preliminary, and this analysis would benefit from more extensive consultation. Nonetheless, information gathered from the interviews and literature search provide valuable insights into evidence-related decision-making paradigms which demonstrate similarities with, and differences from, those found in the health sector. Conclusions Decisions in health promotion and public may benefit from consideration of the ways in which disciplines and sectors can work

Short‐course oral steroids as an adjunct therapy for chronic rhinosinusitis

Abstract: BACKGROUND: This review is one of a suite of six Cochrane reviews looking at the primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is a common condition involving inflammation of the lining of the nose and paranasal sinuses. It is characterised by nasal blockage and nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Oral corticosteroids are used to control the inflammatory response and improve symptoms. OBJECTIVES: To assess the effects of a short course of oral corticosteroids as an adjunct ('add-on') therapy in people with chronic rhinosinusitis who are already on standard treatments. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 7); MEDLINE; EMBASE; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 11 August 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing a short course (up to 21 days) of oral corticosteroids to placebo or no treatment, where all patients were also receiving pharmacological treatment for chronic rhinosinusitis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were disease-specific health-related quality of life (HRQL), patient-reported disease severity, and the adverse event of mood or behavioural disturbances. Secondary outcomes included general HRQL, endoscopic nasal polyp score, computerised tomography (CT) scan score, and the adverse events of insomnia, gastrointestinal disturbances and osteoporosis. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: Two trials with a total of 78 participants met the inclusion criteria. Both the populations and the 'standard' treatments differed in the two studies. Oral steroids as an adjunct to intranasal corticosteroidsOne trial in adults with nasal polyps included 30 participants. All participants used intranasal corticosteroids and were randomised to either short-course oral steroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 21-day treatment course) or no additional treatment. None of the primary outcome measures of interest in this review were reported by the study. There may have been an important reduction in the size of the polyps (measured by the nasal polyps score, a secondary outcome measure) in patients receiving oral steroids and intranasal corticosteroids, compared to intranasal corticosteroids alone (mean difference (MD) -0.46, 95% confidence interval (CI) -0.87 to -0.05; 30 participants; scale 1 to 4) at the end of treatment (21 days). This corresponds to a large effect size, but we are very uncertain about this estimate as we judged the study to be at high risk of bias. Moreover, longer-term data were not available and the other outcomes of interest were not reported. Oral steroids as an adjunct to antibioticsOne trial in children (mean age of eight years) without nasal polyps included 48 participants. The trial compared oral corticosteroids (oral methylprednisolone, 1 mg/kg and reduced progressively over a 15-day treatment course) with placebo in participants who also received a 30-day course of antibiotics. This study addressed one of the primary outcome measures (disease severity) and one secondary outcome (CT score). For disease severity the four key symptoms used to define chronic rhinosinusitis in children (nasal blockage, nasal discharge, facial pressure, cough) were combined into one score. There was a greater improvement in symptom severity 30 days after the start of treatment in patients who received oral steroids and antibiotics compared with placebo and antibiotics (MD -7.10, 95% CI -9.59 to -4.61; 45 participants; scale 0 to 40). The observed mean difference corresponds to a large effect size. At the same time point there was a difference in CT scan score (MD -2.90, 95% CI -4.91 to -0.89; 45 participants; scale 0 to 24). We assessed the quality of the evidence to be low.There were no data available for the longer term (three months). AUTHORS' CONCLUSIONS: There might be an improvement in symptom severity, polyps size and condition of the sinuses when assessed using CT scans in patients taking oral corticosteroids when these are used as an adjunct therapy to antibiotics or intranasal corticosteroids, but the quality of the evidence supporting this is low orvery low (we are uncertain about the effect estimate; the true effect may be substantially different from the estimate of the effect). It is unclear whether the benefits of oral corticosteroids as an adjunct therapy are sustained beyond the short follow-up period reported (up to 30 days), as no longer-term data were available.There were no data in this review about the adverse effects associated with short courses of oral corticosteroids as an adjunct therapy.More research in this area, particularly research evaluating longer-term outcomes and adverse effects, is required.