Medications for daytime sleepiness in individuals with idiopathic hypersomnia.

BACKGROUND: Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. OBJECTIVES: To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. SEARCH METHODS: We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. SELECTION CRITERIA: Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. MAIN RESULTS: We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. AUTHORS' CONCLUSIONS: Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.

Iron for the treatment of restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common neurologic disorder that is associated with peripheral iron deficiency in a subgroup of patients. It is unclear whether iron therapy is effective treatment for RLS. OBJECTIVES: To evaluate the efficacy and safety of oral or parenteral iron for the treatment of restless legs syndrome (RLS) when compared with placebo or other therapies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycNFO, and CINAHL for the time period January 1995 to September 2017. We searched reference lists for additional published studies. We searched Clinicaltrials.gov and other clinical trial registries (September 2017) for ongoing or unpublished studies. SELECTION CRITERIA: Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment, in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality, with discussion to reach consensus in the case of any disagreement. The primary outcome considered in this review was restlessness or unpleasant sensations, as experienced subjectively by the patient. We combined treatment/control differences in the outcomes across studies using random-effects meta-analyses. We analysed continuous data using mean differences (MDs) where possible and performed standardised mean difference (SMD) analyses when different measurements were used across studies. We calculated risk ratios (RRs) for dichotomous data using the Mantel-Haenszel method and 95% confidence intervals (CIs). We analysed study heterogeneity using the I2 statistic. We used standard methodological procedures expected by Cochrane. We performed GRADE analysis using GRADEpro. MAIN RESULTS: We identified and included 10 studies (428 total participants, followed for 2-16 weeks) in this review. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the International Restless Legs Scale (IRLS) (range, 0 to 40) in eight trials and a different RLS symptom scale in a ninth trial. Nine studies compared iron to placebo and one study compared iron to a dopamine agonist (pramipexole). The possibility for bias among the trials was variable. Three studies had a single element with high risk of bias, which was lack of blinding in two and incomplete outcome data in one. All studies had at least one feature resulting in unclear risk of bias.Combining data from the seven trials using the IRLS to compare iron and placebo, use of iron resulted in greater improvement in IRLS scores (MD -3.78, 95% CI -6.25 to -1.31; I2= 66%, 7 studies, 345 participants) measured 2 to 12 weeks after treatment. Including an eighth study, which measured restlessness using a different scale, use of iron remained beneficial compared to placebo (SMD -0.74, 95% CI -1.26 to -0.23; I2 = 80%, 8 studies, 370 participants). The GRADE assessment of certainty for this outcome was moderate.The single study comparing iron to a dopamine agonist (pramipexole) found a similar reduction in RLS severity in the two groups (MD -0.40, 95% CI -5.93 to 5.13, 30 participants).Assessment of secondary outcomes was limited by small numbers of trials assessing each outcome. Iron did not improve quality of life as a dichotomous measure (RR 2.01, 95% CI 0.54 to 7.45; I2=54%, 2 studies, 39 participants), but did improve quality of life measured on continuous scales (SMD 0.51, 95% CI 0.15 to 0.87; I2= 0%, 3 studies, 128 participants), compared to placebo. Subjective sleep quality was no different between iron and placebo groups (SMD 0.19, 95% CI -0.18 to 0.56; I2 = 9%, 3 studies, 128 participants), nor was objective sleep quality, as measured by change in sleep efficiency in a single study (-35.5 +/- 92.0 versus -41.4 +/- 98.2, 18 participants). Periodic limb movements of sleep were not significantly reduced with iron compared to placebo ( SMD -0.19, 95% CI -0.70 to 0.32; I2 = 0%, 2 studies, 60 participants). Iron did not improve sleepiness compared to placebo, as measured on the Epworth Sleepiness Scale (data not provided, 1 study, 60 participants) but did improve the daytime tiredness item of the RLS-6 compared to placebo (least squares mean difference -1.5, 95% CI -2.5 to -0.6; 1 study, 110 participants). The GRADE rating for secondary outcomes ranged from low to very low.Prespecified subgroup analyses showed more improvement with iron in those trials studying participants on dialysis. The use of low serum ferritin levels as an inclusion criteria and the use or oral versus intravenous iron did not show significant subgroup differences.Iron did not result in significantly more adverse events than placebo (RR 1.48, 95% CI 0.97 to 2.25; I2=45%, 6 studies, 298 participants). A single study reported that people treated with iron therapy experienced fewer adverse events than the active comparator pramipexole. AUTHORS' CONCLUSIONS: Iron therapy probably improves restlessness and RLS severity in comparison to placebo. Iron therapy may not increase the risk of side effects in comparison to placebo. We are uncertain whether iron therapy improves quality of life in comparison to placebo. Iron therapy may make little or no difference to pramipexole in restlessness and RLS severity, as well as in the risk of adverse events. The effect on secondary outcomes such as quality of life, daytime functioning, and sleep quality, the optimal timing and formulation of administration, and patient characteristics predicting response require additional study.

Antibiotics for acute bronchitis.

BACKGROUND: The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. OBJECTIVES: To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis. SEARCH METHODS: We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017. SELECTION CRITERIA: Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease. DATA COLLECTION AND ANALYSIS: At least two review authors extracted data and assessed trial quality. MAIN RESULTS: We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 11) and were less likely to have an abnormal lung exam (5 studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB 6). Antibiotic-treated participants also had a reduction in days feeling ill (5 studies with 809 participants, MD -0.64 days, 95% CI -1.16 to -0.13) and days with impaired activity (6 studies with 767 participants, MD -0.49 days, 95% CI -0.94 to -0.04). The differences in proportions with activity limitations at follow-up did not reach statistical significance. There was a significant trend towards an increase in adverse effects in the antibiotic group (12 studies with 3496 participants, RR 1.20, 95% CI 1.05 to 1.36; NNT for an additional harmful outcome 24). AUTHORS' CONCLUSIONS: There is limited evidence of clinical benefit to support the use of antibiotics in acute bronchitis. Antibiotics may have a modest beneficial effect in some patients such as frail, elderly people with multimorbidity who may not have been included in trials to date. However, the magnitude of this benefit needs to be considered in the broader context of potential side effects, medicalisation for a self limiting condition, increased resistance to respiratory pathogens, and cost of antibiotic treatment.

Beta2-agonists for acute cough or a clinical diagnosis of acute bronchitis.

BACKGROUND: The diagnosis of acute bronchitis is made on clinical grounds and a variety of clinical definitions have been used. There are no clearly effective treatments for the cough of acute bronchitis. Beta2-agonists are often prescribed, perhaps because clinicians suspect many patients also have reversible airflow restriction (as seen in asthma or chronic obstructive pulmonary disease (COPD)) contributing to the symptoms. OBJECTIVES: To determine whether beta2-agonists improve acute bronchitis symptoms in people with no underlying pulmonary disease (such as asthma, COPD or pulmonary fibrosis). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2015, Issue 5, MEDLINE (January 1966 to May 2015), EMBASE (1974 to May 2015), Web of Science (2011 to May 2015) and LILACS (1982 to May 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) which allocated people (adults, or children over two years of age) with acute bronchitis or acute cough and without known pulmonary disease to beta2-agonist versus placebo, no treatment or alternative treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently selected outcomes and extracted data while blinded to study results. Two review authors independently assessed each trial for risk of bias. We analysed trials in children and adults separately. MAIN RESULTS: Two trials of moderate quality in children (n = 134) with no evidence of airflow restriction did not find any benefits from oral beta2-agonists. Five trials in adults (n = 418) had mixed results but overall summary statistics did not reveal any significant benefits from oral (three trials) nor from inhaled (two trials) beta2-agonists. Three studies with low-quality evidence demonstrated no significant differences in daily cough scores, nor in the percentage of adults still coughing after seven days (control group 71%; risk ratio (RR) 0.86, 95% confidence interval (CI) 0.63 to 1.18; 220 participants). In one trial, subgroups with evidence of airflow limitation had lower symptom scores if given beta2-agonists. The trials that noted quicker resolution of cough with beta2-agonists were those with a higher proportion of people wheezing at baseline. Low-quality evidence suggests that adults given beta2-agonists were more likely to report tremor, shakiness or nervousness (RR 7.94, 95% CI 1.17 to 53.94; 211 participants; number needed to treat for an additional harmful outcome (NNTH) 2). AUTHORS' CONCLUSIONS: There is no evidence to support the use of beta2-agonists in children with acute cough who do not have evidence of airflow restriction. There is also little evidence that the routine use of beta2-agonists is helpful for adults with acute cough. These agents may reduce symptoms, including cough, in people with evidence of airflow restriction. However, this potential benefit is not well supported by the available data and must be weighed against the adverse effects associated with their use.

Antibiotics for acute bronchitis.

BACKGROUND: The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. OBJECTIVES: To assess the effects of antibiotics in improving outcomes and assess adverse effects of antibiotic therapy for patients with a clinical diagnosis of acute bronchitis. SEARCH METHODS: We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to January 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in patients without underlying pulmonary disease. DATA COLLECTION AND ANALYSIS: At least two review authors extracted data and assessed trial quality. MAIN RESULTS: Seventeen trials with 3936 participants were included in the primary analysis. The quality of trials was generally good. There was limited evidence to support the use of antibiotics in acute bronchitis. At follow-up, there was no difference in participants described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15; number needed to treat for an additional beneficial outcome (NNTB) 22. Participants given antibiotics were less likely to have a cough (four studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a shorter mean cough duration (seven studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated patients were more likely to be unimproved according to clinician's global assessment (six studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB 6); have a reduction in days feeling ill (five studies with 809 participants, MD -0.64 days, 95% CI -1.16 to -0.13) and a reduction in days with limited activity (six studies with 767 participants MD -0.49 days, 95% CI -0.94 to -0.04). The differences in proportions with activity limitations at follow-up did not reach statistical significance. There was a significant trend towards an increase in adverse effects in the antibiotic group (12 studies with 3496 participants) (RR 1.20, 95% CI 1.05 to 1.36; NNT for an additional adverse effect 5). AUTHORS' CONCLUSIONS: There is limited evidence to support the use of antibiotics in acute bronchitis. Antibiotics may have a modest beneficial effect in some patients such as frail, elderly people with multimorbidity who may not have been included in trials to date. However, the magnitude of this benefit needs to be considered in the broader context of potential side effects, medicalisation for a self-limiting condition, increased resistance to respiratory pathogens and cost of antibiotic treatment.

Methods to decrease blood loss during liver resection: a network meta-analysis.

BACKGROUND: Liver resection is a major surgery with significant mortality and morbidity. Various methods have been attempted to decrease blood loss and morbidity during elective liver resection. These methods include different methods of vascular occlusion, parenchymal transection, and management of the cut surface of the liver. A surgeon typically uses only one of the methods from each of these three categories. Together, one can consider this combination as a treatment strategy. The optimal treatment strategy for liver resection is unknown. OBJECTIVES: To assess the comparative benefits and harms of different treatment strategies that aim to decrease blood loss during elective liver resection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded to July 2012 to identify randomised clinical trials. We also handsearched the references lists of identified trials. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) where the method of vascular occlusion, parenchymal transection, and management of the cut surface were clearly reported, and where people were randomly assigned to different treatment strategies based on different combinations of the three categories (vascular occlusion, parenchymal transection, cut surface). DATA COLLECTION AND ANALYSIS: Two review authors identified trials and collected data independently. We assessed the risk of bias using The Cochrane Collaboration's methodology. We conducted a Bayesian network meta-analysis using the Markov chain Monte Carlo method in WinBUGS 1.4 following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit guidance documents. We calculated the odds ratios (OR) with 95% credible intervals (CrI) (which are similar to confidence intervals in the frequentist approach for meta-analysis) for the binary outcomes and mean differences (MD) with 95% CrI for continuous outcomes using a fixed-effect model or random-effects model according to model-fit. MAIN RESULTS: We identified nine trials with 617 participants that met our inclusion criteria. Interventions in the trials included three different options for vascular occlusion, four for parenchymal transection, and two for management of the cut liver surface. These interventions were combined in different ways in the trials giving 11 different treatment strategies. However, we were only able to include 496 participants randomised to seven different treatment strategies from seven trials in our network meta-analysis, because the treatment strategies from the trials that used fibrin sealant for management of the raw liver surface could not be connected to the network for any outcomes. Thus, the trials included in the network meta-analysis varied only in their approaches to vascular exclusion and parenchymal transection and none used fibrin sealant. All the trials were of high risk of bias and the quality of evidence was very low for all the outcomes. The differences in mortality between the different strategies was imprecise (seven trials; seven treatment strategies; 496 participants). Five trials (six strategies; 406 participants) reported serious adverse events. There was an increase in the proportion of people with serious adverse events when surgery was performed using radiofrequency dissecting sealer compared with the standard clamp-crush method in the absence of vascular occlusion and fibrin sealant. The OR for the difference in proportion was 7.13 (95% CrI 1.77 to 28.65; 15/49 (adjusted proportion 24.9%) in radiofrequency dissecting sealer group compared with 6/89 (6.7%) in the clamp-crush method). The differences in serious adverse events between the other groups were imprecise. There was a high probability that 'no vascular occlusion with clamp-crush method and no fibrin' and 'intermittent vascular occlusion with Cavitron ultrasonic surgical aspirator and no fibrin' are better than other treatments with regards to serious adverse events. Quality of life was not reported in any of the trials.The differences in the proportion of people requiring blood transfusion was imprecise (six trials; seven treatments; 446 participants). Two trials (three treatments; 155 participants) provided data for quantity of blood transfused. People undergoing liver resection by intermittent vascular occlusion had higher amounts of blood transfused than people with continuous vascular occlusion when the parenchymal transection was carried out with the clamp-crush method and no fibrin sealant was used for the cut surface (MD 1.2 units; 95% CrI 0.08 to 2.32). The differences in the other comparisons were imprecise (very low quality evidence). Three trials (four treatments; 281 participants) provided data for operative blood loss. People undergoing liver resection using continuous vascular occlusion had lower blood loss than people with no vascular occlusion when the parenchymal transection was carried out with clamp-crush method and no fibrin sealant was used for the cut surface (MD -130.9 mL; 95% CrI -255.9 to -5.9). None of the trials reported the proportion of people with major blood loss.The differences in the length of hospital stay (six trials; seven treatments; 446 participants) and intensive therapy unit stay (four trials; six treatments; 261 participants) were imprecise. Four trials (four treatments; 245 participants) provided data for operating time. Liver resection by intermittent vascular occlusion took longer than liver resection performed with no vascular occlusion when the parenchymal transection was carried out with Cavitron ultrasonic surgical aspirator and no fibrin sealant was used for the cut surface (MD 49.6 minutes; 95% CrI 29.8 to 69.4). The differences in the operating time between the other comparisons were imprecise. None of the trials reported the time needed to return to work. AUTHORS' CONCLUSIONS: Very low quality evidence suggested that liver resection using a radiofrequency dissecting sealer without vascular occlusion or fibrin sealant may increase serious adverse events and this should be evaluated in further randomised clinical trials. The risk of serious adverse events with liver resection using no special equipment compared with more complex methods requiring special equipment was uncertain due to the very low quality of the evidence. The credible intervals were wide and considerable benefit or harm with a specific method of liver resection cannot be ruled out.

Iron for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common neurologic syndrome and is associated with iron deficiency in many patients. It is unclear whether iron therapy is effective treatment for RLS. OBJECTIVES: The objective of this review was to assess the effects of iron supplementation (oral or intravenous) for patients with RLS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Jan 1995 to April 2011); EMBASE (Jan 1995 to April 2011); PsycINFO (Jan 1995 to April 2011); and CINAHL (Jan 1995 to April 2011). Corresponding authors of included trials and additional members of the International Restless Legs Syndrome Study Group were contacted to locate additional published or unpublished trials. SELECTION CRITERIA: Controlled trials comparing any formulation of iron with placebo, other medications, or no treatment in adults diagnosed with RLS according to expert clinical interview or explicit diagnostic criteria. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and at least two authors assessed trial quality. We contacted trial authors for missing data. MAIN RESULTS: Six studies (192 total subjects) were identified and included in this analysis. The quality of trials was variable. Our primary outcome was restlessness or uncomfortable leg sensations, which was quantified using the IRLS severity scale in four trials and another RLS symptom scale in a fifth trial. Combining data from the four trials using the IRLS severity scale, there was no clear benefit from iron therapy (mean difference in IRLS severity scores of -3.79, 95% CI: -7.68 to 0.10, p = 0.06). However, the fifth trial did find iron therapy to be beneficial (median decrease of 3 points in the iron group and no change in the placebo group on a 10 point scale of RLS symptoms, p = 0.01). Quality of life was improved in the iron group relative to placebo in some studies but not others. Changes in periodic limb movements were not different between groups (measured in two studies). Objective sleep quality, subjective sleep quality and daytime functioning were not different between treatment groups in the studies that assessed them. The single study of subjects with end stage renal disease did show a benefit of therapy. Most trials did not require subjects to have co-morbid iron deficiency and several excluded patients with severe anemia. The single study that was limited to iron deficient subjects did not show clear benefit of iron supplementation on RLS symptoms. There was no clear superiority of oral or intravenous delivery of iron. Iron therapy did not result in significantly more side effects than placebo (RR 1.39, 95% CI 0.85 to 2.27). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether iron therapy is beneficial for the treatment of RLS. Further research to determine whether some or all types of RLS patients may benefit from iron therapy, as well as the best route of iron administration, is needed.

Beta2-agonists for acute bronchitis.

BACKGROUND: There are no clearly effective treatments for the cough of acute bronchitis. Beta2-agonists are often prescribed, perhaps because clinicians suspect many patients also have reversible airflow restriction contributing to the symptoms. OBJECTIVES: To determine whether beta2-agonists improve acute bronchitis symptoms in patients with no underlying pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2011, issue 1 which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to February week 1, 2011) and EMBASE (1974 to February 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) in which patients (adults, or children over two years of age) with acute bronchitis or acute cough and without known pulmonary disease were allocated to beta2-agonist versus placebo, no treatment or alternative treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently selected outcomes and extracted data while blinded to study results. Two review authors independently assessed each trial for risk of bias. We analysed trials in children and adults separately. MAIN RESULTS: Two trials in children (n = 109) with no evidence of airway obstruction did not find any benefits from oral beta2-agonists. Five trials in adults (n = 418) had mixed results but overall summary statistics did not reveal any significant benefits from oral (three trials) nor inhaled (two trials) beta2-agonists. There were no significant differences in daily cough scores nor in the percentage of adults still coughing after seven days (control group 73%; risk ratio (RR) 0.77, 95% confidence interval (CI) 0.54 to 1.09). in one trial, subgroups with evidence of airflow limitation had lower symptom scores if given beta2-agonists. The trials that noted quicker resolution of cough with beta2-agonists were those with a higher proportion of wheezing patients at baseline. Adults given beta2-agonists were more likely to report tremor, shakiness or nervousness (RR 7.94, 95% CI 1.17 to 53.94; number needed to treat to harm (NNTH) 2.3). AUTHORS' CONCLUSIONS: There is no evidence to support the use of beta2-agonists in children with acute cough who do not have evidence of airflow obstruction. There is also little evidence that the routine use of beta2-agonists is helpful for adults with acute cough. These agents may reduce symptoms, including cough, in people with evidence of airflow obstruction. However, this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with their use.

Cochrane's Linked Data Project: How it Can Advance our Understanding of Surrogate Endpoints.

Cochrane has developed a linked data infrastructure to make the evidence and data from its rich repositories more discoverable to facilitate evidence-based health decision-making. These annotated resources can enhance the study and understanding of biomarkers and surrogate endpoints.

What guidance is available for researchers conducting overviews of reviews of healthcare interventions? A scoping review and qualitative metasummary.

BACKGROUND: Overviews of reviews (overviews) compile data from multiple systematic reviews to provide a single synthesis of relevant evidence for decision-making. Despite their increasing popularity, there is limited methodological guidance available for researchers wishing to conduct overviews. The objective of this scoping review is to identify and collate all published and unpublished documents containing guidance for conducting overviews examining the efficacy, effectiveness, and/or safety of healthcare interventions. Our aims were to provide a map of existing guidance documents; identify similarities, differences, and gaps in the guidance contained within these documents; and identify common challenges involved in conducting overviews. METHODS: We conducted an iterative and extensive search to ensure breadth and comprehensiveness of coverage. The search involved reference tracking, database and web searches (MEDLINE, EMBASE, DARE, Scopus, Cochrane Methods Studies Database, Google Scholar), handsearching of websites and conference proceedings, and contacting overview producers. Relevant guidance statements and challenges encountered were extracted, edited, grouped, abstracted, and presented using a qualitative metasummary approach. RESULTS: We identified 52 guidance documents produced by 19 research groups. Relatively consistent guidance was available for the first stages of the overview process (deciding when and why to conduct an overview, specifying the scope, and searching for and including systematic reviews). In contrast, there was limited or conflicting guidance for the latter stages of the overview process (quality assessment of systematic reviews and their primary studies, collecting and analyzing data, and assessing quality of evidence), and many of the challenges identified were also related to these stages. An additional, overarching challenge identified was that overviews are limited by the methods, reporting, and coverage of their included systematic reviews. CONCLUSIONS: This compilation of methodological guidance for conducting overviews of healthcare interventions will facilitate the production of future overviews and can help authors address key challenges they are likely to encounter. The results of this project have been used to identify areas where future methodological research is required to generate empirical evidence for overview methods. Additionally, these results have been used to update the chapter on overviews in the next edition of the Cochrane Handbook for Systematic Reviews of Interventions.

A Cochrane systematic review and network meta-analysis comparing treatment strategies aiming to decrease blood loss during liver resection.

INTRODUCTION: Intraoperative haemorrhage remains one of the major risks during liver resection, and perioperative blood loss and blood transfusion are important factors affecting perioperative morbidity and mortality. The aim of this study is to compare treatment strategies aiming to decrease blood loss during hepatectomy. METHODS: A systematic review of the literature was performed to identify randomised controlled trials reporting on the method of vascular occlusion, parenchymal transection, and management of the cut surface during liver resection. A Bayesian network meta-analysis was performed using WinBUGS. RESULTS: Seven trials reporting on 496 participants randomised to seven treatment strategies were analysed. Continuous vascular occlusion resulted in lower blood loss compared to no vascular occlusion when parenchymal transection was performed with clamp-crush and no fibrin sealant was used for the cut surface. People undergoing liver resection by continuous vascular occlusion had decreased amounts of blood transfused than people with intermittent vascular occlusion when parenchymal transection was performed with clamp-crush and no fibrin sealant. There was no significant difference in proportion of people transfused, mortality, or hospital stay between the different strategies. There were significantly more serious adverse events when surgery was performed using radiofrequency dissecting sealer compared with standard clamp-crush method in the absence of vascular occlusion and fibrin sealant. CONCLUSIONS: Continuous vascular occlusion during hepatectomy results in decreased blood loss and decreased blood transfusion requirements. Further studies are needed to compare treatment strategies aiming to decrease blood loss, defined by their method of vascular occlusion, parenchymal transection, and management of the cut surface.

How the philosophies, styles, and methods of family medicine affect the research agenda.

Family physicians provide person-centered, continuous, comprehensive care that is accessible and available at the time of need. Although this core philosophy is shared around the world, its translation into actual practice can vary greatly with time and from place to place as family physicians adapt to local constraints and conditions. Factors driving these local variations include entrenched habits and patterns of care, funding systems, patient expectations, public policy, and the availability and quality of other critical health system components. This diversity provides both an opportunity and a challenge for family medicine research. The potential for fruitful comparisons and contrasts arising from natural experiments may require investigators to use multiple research methods capable of evaluating complex interventions and comparisons. Family medicine has the capacity to be an excellent laboratory in which research in representative populations can offer the pragmatic answers needed by practicing physicians. The nature of the research questions and interventions require the involvement of clinicians in the formulation of research questions and evaluation of the applicability of research results. The variations in implementation of the family medicine philosophy can be a potential asset because of the research opportunities they provide.