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There is uncertainty as to the optimal approach for screening and diagnosis of gestational diabetes mellitus (GDM). Based on systematic reviews published in 2003 and 2008, the U.S. Preventive Services Task Force concluded that there was insufficient evidence upon which to make a recommendation regarding routine screening of all pregnant women.(1) Identify properties of screening tests for GDM, (2) evaluate benefits and harms of screening for GDM, (3) assess the effects of different screening and diagnostic thresholds on outcomes for mothers and their offspring, and (4) determine the benefits and harms of treatment for a diagnosis of GDM.We searched 15 electronic databases from 1995 to May 2012, including MEDLINE and Cochrane Central Register of Controlled Trials (which contains the Cochrane Pregnancy and Childbirth Group registry); gray literature; Web sites of relevant organizations; trial registries; and reference lists.Two reviewers independently conducted study selection and quality assessment. One reviewer extracted data, and a second reviewer verified the data. We included published randomized and nonrandomized controlled trials and prospective and retrospective cohort studies that compared any screening or diagnostic test with any other screening or diagnostic test; any screening with no screening; women who met various thresholds for GDM with those who did not meet various criteria, where women in both groups did not receive treatment; any treatment for GDM with no treatment. We conducted a descriptive analysis for all studies and meta-analyses when appropriate. Key outcomes included preeclampsia, maternal weight gain, birth injury, shoulder dystocia, neonatal hypoglycemia, macrosomia, and long-term metabolic outcomes for the child and mother.The search identified 14,398 citations and included 97 studies (6 randomized controlled trials, 63 prospective cohort studies, and 28 retrospective cohort studies). Prevalence of GDM varied across studies and diagnostic criteria: American Diabetes Association (75 g) 2 to 19 percent; Carpenter and Coustan 3.6 to 38 percent; National Diabetes Data Group 1.4 to 50 percent; and World Health Organization 2 to 24.5 percent. Lack of a gold standard for the diagnosis of GDM and little evidence about the accuracy of screening strategies for GDM remain problematic. The 50 g oral glucose challenge test with a glucose threshold of 130 mg/dL versus 140 mg/dL improves sensitivity and reduces specificity. Both thresholds have high negative predictive values (NPV) but variable positive predictive values (PPVs) across a range of prevalence. There was limited evidence for the screening of GDM diagnosed less than 24 weeks' gestation (three studies). One study compared the International Association of Diabetes in Pregnancy Study Groups' (IADPSG) diagnostic criteria with a two-step strategy. Sensitivity was 82 percent, specificity was 94 percent. Only two studies examined the effects on health outcomes from screening for GDM. One retrospective cohort study (n=1,000) showed more cesarean deliveries in the screened group. A survey within a prospective cohort study (n=93) found the same incidence of macrosomia (≥4.3 kg) in screened and unscreened groups (7 percent each group). Thirty-eight studies examined health outcomes for women who met different criteria for GDM and did not undergo treatment. Methodologically strong studies showed a continuous positive relationship between increasing glucose levels and the incidence of primary cesarean section and macrosomia. One of these studies also found significantly fewer cases of preeclampsia, cesarean section, shoulder dystocia and/or birth injury, clinical neonatal hypoglycemia, and hyperbilirubinemia for women without GDM compared with those meeting IADPSG criteria. Among the other studies, fewer cases of preeclampsia were observed for women with no GDM and women who were false positive versus those meeting Carpenter and Coustan criteria. For maternal weight gain, few comparisons showed differences. For fetal birth trauma, single studies showed no differences for women with Carpenter and Coustan GDM and World Health Organization impaired glucose tolerance versus women without GDM. Women diagnosed based on National Diabetes Data Group GDM had more fetal birth trauma compared with women without GDM. Fewer cases of macrosomia were seen in the group without GDM compared with Carpenter and Coustan GDM, Carpenter and Coustan 1 abnormal oral glucose tolerance test, National Diabetes Data Group GDM, National Diabetes Data Group false positives, and World Health Organization impaired glucose tolerance. Fewer cases of neonatal hypoglycemia were found among patient groups without GDM compared with those meeting Carpenter and Coustan criteria. There was more childhood obesity for Carpenter and Coustan GDM versus patient groups with no GDM. Eleven studies compared diet modification, glucose monitoring, and insulin as needed with no treatment. Moderate evidence showed fewer cases of preeclampsia in the treated group. The evidence was insufficient for maternal weight gain and birth injury. Moderate evidence found less shoulder dystocia with treatment for GDM. Low evidence showed no difference for neonatal hypoglycemia between treated and untreated GDM. Moderate evidence showed benefits of treatment for reduction of macrosomia (4,000 g). There was insufficient evidence for long-term metabolic outcomes among offspring. Five studies provided data on harms of treating GDM. No difference was found for cesarean delivery, induction of labor, small for gestational age, or admission to a neonatal intensive care unit. There were significantly more prenatal visits among those treated.While evidence supports a positive association with increasing plasma glucose on a 75 g or 100 g oral glucose tolerance test and macrosomia and primary cesarean section, clear thresholds for increased risk were not found. The 50 g oral glucose challenge test has high NPV but variable PPV. Treatment of GDM results in less preeclampsia and macrosomia. Current evidence does not show that treatment of GDM has an effect on neonatal hypoglycemia or future poor metabolic outcomes. There is little evidence of short-term harm from treating GDM other than an increased demand for services. Research is needed on the long-term metabolic outcome for offspring as a result of GDM and its treatment, and the "real world" effects of GDM treatment on use of care.

Many children requiring acute care receive suboptimal analgesia.To describe paediatric pain management practices and policies in emergency departments (EDs) in Alberta.A descriptive survey was distributed to each of the EDs in Alberta.A response rate of 67% (72 of 108) was obtained. Seventy-one percent (42 of 59) of EDs reported the use of a pain tool, 29.3% (17 of 58) reported mandatory pain documentation and 16.7% (10 of 60) had nurse-initiated pain protocols. Topical anesthetics were reported to be used for intravenous line insertion by 70.4% of respondents (38 of 54) and for lumbar puncture (LP) by 30.8% (12 of 39). According to respondents, infiltrated anesthetic was used for LP by 69.2% (27 of 39) of respondents, and oral sucrose was used infrequently for urinary catheterization (one of 46 [2.2%]), intravenous line insertion (zero of 54 [0%]) and LP (one of 39 [2.6%]).Few Alberta EDs use policies and protocols to manage paediatric pain. Noninvasive methods to limit procedural pain are underutilized. Canadian paediatricians must advocate for improved analgesia to narrow this knowledge-to-practice gap.De nombreux enfants qui ont besoin de soins aigus reçoivent une analgésie sous-optimale.Décrire les pratiques et politiques de gestion de la douleur en pédiatrie dans les salles d’urgence (SU) albertaines.Chaque SU de l’Alberta a reçu un sondage descriptif.Les chercheurs ont obtenu un taux de réponse de 67 % (72 sur 108). Au total, 71 % des SU (42 sur 59) ont déclaré utiliser un outil de gestion de la douleur, 29,3 % (17 sur 58) ont déclaré exiger de consigner la douleur et 16,7 % (dix sur 60) disposaient de protocoles de gestion de la douleur initiés par les infirmières. Ainsi, 70,4 % des répondants (38 sur 54) recouraient à l’anesthésie topique pour insérer un cathéter intraveineux et 30,8 % (12 sur 39), pour effectuer une ponction lombaire (PL). De plus, 69,2 % des répondants (27 sur 39) utilisaient des injections d’anesthésique pour les PL et, rarement, du saccharose par voie orale pour un cathétérisme urinaire (un cas sur 46 [2,2 %]), l’insertion d’un cathéter intraveineux (zéro sur 54 [0 %]) et une PL (un sur 39 [2,6 %]).Un petit nombre de SU albertaines sont dotées des politiques et protocoles pour gérer la douleur en pédiatrie. Les méthodes non invasives sont sous-utilisées pour limiter la douleur liée à des interventions. Les pédiatres canadiens doivent prôner une meil-leure analgésie pour réduire cet écart entre le savoir et la pratique.

We thank Drs Payne and Webb and Drs Echouffo-Tcheugui and Kengne for their letters regarding our article “Agreement Among Cardiovascular Disease Risk Calculators.”1 Drs Payne and Webb raised concern we did not explore why differences exist in the risk calculator estimations or examine how risk estimation may influence patient/clinician behavior. Those are both important issues. As mentioned in our article, our objective was to assess the consistency of a broad sample of commonly used calculators over a sample of patients with a range of cardiovascular risk factors. We wanted to describe the disagreement among calculators (if it occurred). The next but separate question is why does it occur. We explored some subgroups that might help explain the differences and found focusing on Framingham 10-year Cardiovascular Disease risk calculators improved agreement (same database, same duration, and similar outcomes). Furthermore, we also discussed some of the potential causes of disagreement in the conclusion. We focused on describing agreement primarily and stated that more research is …

BACKGROUND The effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose is unclear. PURPOSE To systematically review the effectiveness of lifestyle interventions on minimizing progression to diabetes in high-risk patients or progression to clinical outcomes (such as cardiovascular disease and death) in patients with type 2 diabetes. DATA SOURCES 5 electronic databases (1980 to June 2013), reference lists, and gray literature. STUDY SELECTION Two reviewers independently identified randomized, controlled trials of lifestyle interventions (≥3 months' duration) that included exercise, diet, and at least 1 other component; the comparator was standard care. DATA EXTRACTION One reviewer extracted and a second verified data. Two reviewers independently assessed methodological quality. DATA SYNTHESIS Nine randomized, controlled trials with patients who were at risk for diabetes and 11 with patients who had diabetes were included. Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up. LIMITATION Most trials focused on surrogate measures (such as weight change, blood pressure, and lipids) for which clinical relevance was unclear. CONCLUSION Comprehensive lifestyle interventions effectively decrease the incidence of type 2 diabetes in high-risk patients. In patients who already have type 2 diabetes, there is no evidence of reduced all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Background Croup is a common childhood illness characterized by barky cough, stridor, hoarseness and respiratory distress. Children with severe croup are at risk for intubation. Nebulized epinephrine may prevent intubation. Objectives To assess the efficacy (measured by croup scores, rate of intubation and health care utilization such as rate of hospitalization) and safety (frequency and severity of side effects) of nebulized epinephrine versus placebo in children with croup, evaluated in an emergency department (ED) or hospital setting. Search methods We searched CENTRAL 2013, Issue 6, MEDLINE (1966 to June week 3, 2013), EMBASE (1980 to July 2013), Web of Science (1974 to July 2013), CINAHL (1982 to July 2013) and Scopus (1996 to July 2013). Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs of children with croup evaluated in an ED or admitted to hospital. Comparisons were: nebulized epinephrine versus placebo, racemic nebulized epinephrine versus L-epinephrine (an isomer) and nebulized epinephrine delivered by intermittent positive pressure breathing (IPPB) versus nebulized epinephrine without IPPB. Primary outcome was change in croup score post-treatment. Secondary outcomes were rate and duration of intubation and hospitalization, croup return visit, parental anxiety and side effects. Data collection and analysis Two authors independently identified potentially relevant studies by title and abstract (when available) and examined relevant studies using a priori inclusion criteria, followed by methodological quality assessment. One author extracted data while the second checked accuracy. We use the standard methodological procedures expected by the Cochrane Collaboration. Main results Eight studies (225 participants) were included. In general, children included in the studies were young (average age less than two years in the majority of included studies). Severity of croup was described as moderate to severe in all included studies. Six studies took place in the inpatient setting, one in the ED and one setting was not specified. Six of the eight studies were deemed to have a low risk of bias and the risk of bias was unclear in the remaining two studies. Nebulized epinephrine was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I2 statistic = 0%). This effect was not significant two and six hours post-treatment. Nebulized epinephrine was associated with significantly shorter hospital stay than placebo (one RCT, MD -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L-epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of nebulized epinephrine via IPPB versus nebulization alone at 30 minutes (one RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to 0.42). None of the studies sought or reported data on adverse effects. Authors' conclusions Nebulized epinephrine is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment. Evidence does not favor racemic epinephrine or L-epinephrine, or IPPB over simple nebulization. The authors note that data and analyses were limited by the small number of relevant studies and total number of participants and thus most outcomes contained data from very few or even single studies.

Background Pediatric osteomyelitis is a bacterial infection of bones requiring prolonged antibiotic treatment using parenteral followed by enteral agents. Major complications of pediatric osteomyelitis include transition to chronic osteomyelitis, formation of subperiosteal abscesses, extension of infection into the joint, and permanent bony deformity or limb shortening. Historically, osteomyelitis has been treated with long durations of antibiotics to avoid these complications. However, with improvements in management and antibiotic treatment, standard of care is moving towards short durations of intravenous antibiotics prior to enteral antibiotics. Methods/Design The authors will perform a systematic review based on PRISMA guidelines in order to evaluate the literature, looking for evidence to support the optimal duration of parenteral and enteral therapy. The main goals are to see if literature supports shorter durations of either parenteral antibiotics and/or enteral antibiotics. Multiple databases will be investigated using a thorough search strategy. Databases include Medline, Cochrane, EMBASE, SCOPUS, Dissertation Abstracts, CINAHL, Web of Science, African Index Medicus and LILACS. Search stream will include medical subject heading for pediatric patients with osteomyelitis and antibiotic therapy. We will search for published or unpublished randomized and quasi-randomized controlled trials. Two authors will independently select articles, extract data and assess risk of bias by standard Cochrane methodologies. We will analyze comparisons between dichotomous outcomes using risk ratios and continuous outcomes using mean differences. 95% confidence intervals will be computed. Discussion One of the major dilemmas of management of this disease is the duration of parenteral therapy. Long parenteral therapy has increased risk of serious complications and the necessity for long therapy has been called into question. Our study aims to review the currently available evidence from randomized trials regarding duration of both parenteral and oral therapy for pediatric acute osteomyelitis. Trial registration CRD42013002320

A 50-g oral glucose challenge test (OGCT) is a widely accepted screening method for gestational diabetes mellitus (GDM), but other options are being considered.To systematically review the test characteristics of various screening methods for GDM across a range of recommended diagnostic glucose thresholds.15 electronic databases from 1995 to May 2012, reference lists, Web sites of relevant organizations, and gray literature.Two reviewers independently identified English-language prospective studies that compared any screening test for GDM with any reference standard.One reviewer extracted and a second reviewer verified data from 51 cohort studies. Two reviewers independently assessed methodological quality.The sensitivity, specificity, and positive and negative likelihood ratios for the OGCT at a threshold of 7.8 mmol/L (140 mg/dL) were 70% to 88%, 69% to 89%, 2.6 to 6.5, and 0.16 to 0.33, respectively. At a threshold of 7.2 mmol/L (130 mg/dL), the test characteristics were 88% to 99%, 66% to 77%, 2.7 to 4.2, and 0.02 to 0.14, respectively. For a fasting plasma glucose threshold of 4.7 mmol/L (85 mg/dL), they were 87%, 52%, 1.8, and 0.25, respectively. Glycated hemoglobin level had poorer test characteristics than fasting plasma glucose level or the OGCT. No studies compared the OGCT with International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria.The lack of a gold standard for confirming GDM limits comparisons. Few data exist for screening tests before 24 weeks' gestation.The OGCT and fasting plasma glucose level (at a threshold of 4.7 mmol/L [85 mg/dL]) by 24 weeks' gestation are good at identifying women who do not have GDM. The OGCT is better at identifying women who have GDM. The OGCT has not been validated for the IADPSG diagnostic criteria.

OBJECTIVE: Brief intervention (BI) is recommended for use with youth who use alcohol and other drugs. Emergency departments (EDs) can provide BIs at a time directly linked to harmful and hazardous use. The objective of this systematic review was to determine the effectiveness of ED-based BIs. METHODS: We searched 14 electronic databases, a clinical trial registry, conference proceedings, and study references. We included randomized controlled trials with youth 21 years or younger. Two reviewers independently selected studies and assessed methodological quality. One reviewer extracted and a second verified data. We summarized findings qualitatively. RESULTS: Two trials with low risk of bias, 2 trials with unclear risk of bias, and 5 trials with high risk of bias were included. Trials evaluated targeted BIs for alcohol-positive (n = 3) and alcohol/other drug-positive youth (n = 1) and universal BIs for youth reporting recent alcohol (n = 4) or cannabis use (n = 1). Few differences were found in favor of ED-based BIs, and variation in outcome measurement and poor study quality precluded firm conclusions for many comparisons. Universal and targeted BIs did not significantly reduce alcohol use more than other care. In one targeted BI trial with high risk of bias, motivational interviewing (MI) that involved parents reduced drinking quantity per occasion and high-volume alcohol use compared with MI that was delivered to youth only. Another trial with high risk of bias reported an increase in abstinence and reduction in physical altercations when youth received peer-delivered universal MI for cannabis use. In 2 trials with unclear risk of bias, MI reduced drinking and driving and alcohol-related injuries after the ED visit. Computer-based MI delivered universally in 1 trial with low risk of bias reduced alcohol-related consequences 6 months after the ED visit. CONCLUSIONS: Clear benefits of using ED-based BI to reduce alcohol and other drug use and associated injuries or high-risk behaviours remain inconclusive because of variation in assessing outcomes and poor study quality. Language: en

To determine whether the three commonly used measures of critical thinking correlate with academic success of medical professionals in training.The search for English-language articles (from 1980 to 2011) used Medline, Embase, Scopus, Cochrane Library on Ovid, Proquest Dissertations, Health and Psychosocial Instruments, PsychINFO, and references of included articles. Studies comparing critical thinking with academic success among medical professionals were included. Two authors performed study selection independently, with disagreement resolved by consensus. Two authors independently abstracted data on study characteristics, quality, and outcomes, with disagreement resolved by a third author. Critical thinking tests studied were the California Critical Thinking Skills Test (CCTST), California Critical Thinking Disposition Inventory (CCTDI), and Watson-Glaser Critical Thinking Appraisal. Correlation coefficients were pooled in meta-analysis.The search identified 557 studies: 52 met inclusion for systematic review, 41 of which were meta-analyzed. Critical thinking was positively correlated with academic success, r=0.31 (95% confidence intervals [CI] 0.26, 0.35), with a moderate statistical heterogeneity (I=67%). In subgroup analysis, only student type had statistical significance for correlation, although bias was likely due to low numbers for some student types. In direct comparison, using studies that employed two critical thinking tests, the CCTDI (r=0.23, 95% CI 0.15, 0.30) was significantly inferior (P.001) to the CCTST (r=0.39, 95% CI 0.33, 0.45).Critical thinking was moderately correlated with academic success of medical professionals in training. The CCTDI was inferior to the CCTST in correlating with academic success.

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd., Background: Previous systematic reviews have not shown clear benefit of glucocorticoids for acute viral bronchiolitis, but their use remains considerable. Recent large trials add substantially to current evidence and suggest novel glucocorticoid-including treatment approaches. Objectives: To review the efficacy and safety of systemic and inhaled glucocorticoids in children with acute viral bronchiolitis. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 12), MEDLINE (1950 to January week 2, 2013), EMBASE (1980 to January 2013), LILACS (1982 to January 2013), Scopus® (1823 to January 2013) and IRAN MedEx (1998 to November 2009). Selection criteria: Randomised controlled trials (RCTs) comparing short-term systemic or inhaled glucocorticoids versus placebo or another intervention in children under 24 months with acute bronchiolitis (first episode with wheezing). Our primary outcomes were: admissions by days 1 and 7 for outpatient studies; and length of stay (LOS) for inpatient studies. Secondary outcomes included clinical severity parameters, healthcare use, pulmonary function, symptoms, quality of life and harms. Data collection and analysis: Two authors independently extracted data on study and participant characteristics, interventions and outcomes. We assessed risk of bias and graded strength of evidence. We meta-analysed inpatient and outpatient results separately using random-effects models. We pre-specified subgroup analyses, including the combined use of bronchodilators used in a protocol. Main results: We included 17 trials (2596 participants); three had low overall risk of bias. Baseline severity, glucocorticoid schemes, comparators and outcomes were heterogeneous. Glucocorticoids did not significantly reduce outpatient admissions by days 1 and 7 when compared to placebo (pooled risk ratios (RRs) 0.92; 95% confidence interval (CI) 0.78 to 1.08 and 0.86; 95% CI 0.7 to 1.06, respectively). There was no benefit in LOS for inpatients (mean difference -0.18 days; 95% CI -0.39 to 0.04). Unadjusted results from a large factorial low risk of bias RCT found combined high-dose systemic dexamethasone and inhaled epinephrine reduced admissions by day 7 (baseline risk of admission 26%; RR 0.65; 95% CI 0.44 to 0.95; number needed to treat 11; 95% CI 7 to 76), with no differences in short-term adverse effects. No other comparisons showed relevant differences in primary outcomes. Authors' conclusions: Current evidence does not support a clinically relevant effect of systemic or inhaled glucocorticoids on admissions or length of hospitalisation. Combined dexamethasone and epinephrine may reduce outpatient admissions, but results are exploratory and safety data limited. Future research should further assess the efficacy, harms and applicability of combined therapy.

Background Controversies are common in medicine. Some arise when the conclusions of research publications directly contradict each other, creating uncertainty for frontline clinicians. Discussion In this paper, we review how researchers can look at very similar data yet have completely different conclusions based purely on an over-reliance of statistical significance and an unclear understanding of confidence intervals. The dogmatic adherence to statistical significant thresholds can lead authors to write dichotomized absolute conclusions while ignoring the broader interpretations of very consistent findings. We describe three examples of controversy around the potential benefit of a medication, a comparison between new medications, and a medication with a potential harm. The examples include the highest levels of evidence, both meta-analyses and randomized controlled trials. We will show how in each case the confidence intervals and point estimates were very similar. The only identifiable differences to account for the contrasting conclusions arise from the serendipitous finding of confidence intervals that either marginally cross or just fail to cross the line of statistical significance. Summary These opposing conclusions are false disagreements that create unnecessary clinical uncertainty. We provide helpful recommendations in approaching conflicting conclusions when they are associated with remarkably similar results.

There is growing interest in the use of ω-3 fatty acid (n-3FA) lipid emulsions to prevent complications associated with parenteral nutrition. The authors systematically reviewed the evidence on the benefits and safety of n-3FA compared with standard lipid emulsions in children with intestinal disease, critical illness, trauma, or postoperative complications.The authors searched 4 bibliographic databases from their inception to March 2011, conference proceedings, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodological quality, and rated the strength of the evidence. One reviewer extracted and a second reviewer verified data. The authors summarized findings qualitatively and conducted meta-analysis when appropriate.Five randomized controlled trials with unclear risk of bias and 3 high-quality prospective cohort studies were included. The studies examined premature, low birth weight infants (n = 6) and children with heart disease (n = 1) or intestinal failure (n = 1). The strength of evidence was consistently low or very low across all lipid emulsion comparisons and outcomes. In young children, n-3FA emulsions resulted in improvement in some biochemical outcomes of intestinal failure-associated liver disease but no difference in mortality. Few studies examined patient-important outcomes, such as length of hospital and intensive care stay; need for transplantation, growth, and cognitive development; or the long-term effects and potential harms associated with these therapies.Currently, there is a lack of sufficient high-quality data to support the use of parenteral n-3FA lipid emulsions in children. Future trials examining long-term clinical outcomes and harms are needed.

BackgroundGRADE was developed to address shortcomings of tools to rate the quality of a body of evidence. While much has been published about GRADE, there are few empirical and systematic evaluations.ObjectiveTo assess GRADE for systematic reviews (SRs) in terms of inter-rater agreement and identify areas of uncertainty.DesignCross-sectional, descriptive study.MethodsWe applied GRADE to three SRs (n = 48, 66, and 75 studies, respectively) with 29 comparisons and 12 outcomes overall. Two reviewers graded evidence independently for outcomes deemed clinically important a priori. Inter-rater reliability was assessed using kappas for four main domains (risk of bias, consistency, directness, and precision) and overall quality of evidence.ResultsFOR THE FIRST REVIEW, RELIABILITY WAS: κ = 0.41 for risk of bias; 0.84 consistency; 0.18 precision; and 0.44 overall quality. Kappa could not be calculated for directness as one rater assessed all items as direct; assessors agreed in 41% of cases. For the second review reliability was: 0.37 consistency and 0.19 precision. Kappa could not be assessed for other items; assessors agreed in 33% of cases for risk of bias; 100% directness; and 58% overall quality. For the third review, reliability was: 0.06 risk of bias; 0.79 consistency; 0.21 precision; and 0.18 overall quality. Assessors agreed in 100% of cases for directness. Precision created the most uncertainty due to difficulties in identifying "optimal" information size and "clinical decision threshold", as well as making assessments when there was no meta-analysis. The risk of bias domain created uncertainty, particularly for nonrandomized studies.ConclusionsAs researchers with varied levels of training and experience use GRADE, there is risk for variability in interpretation and application. This study shows variable agreement across the GRADE domains, reflecting areas where further guidance is required.

BACKGROUND AND OBJECTIVE: Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial due to uncertainty of their relative benefits and safety. We systematically reviewed the effectiveness and safety of first- (FGA) and second-generation antipsychotics (SGA) for patients aged ≤24 years with psychiatric and behavioral conditions. METHODS: We searched 10 databases from January 1987 to February 2011, gray literature, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodologic quality, and graded the evidence. One reviewer extracted, and a second verified, data. We summarized findings qualitatively and conducted meta-analyses when appropriate. RESULTS: Sixty-four trials and 17 cohort studies were included. Most trials had a high risk of bias; cohort studies had moderate quality. All comparisons of FGAs versus SGAs, FGAs versus FGAs, and FGAs versus placebo had low or insufficient strength of evidence. There was moderate strength of evidence for the following comparisons. Olanzapine caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone. Olanzapine caused more weight gain than quetiapine. Compared with placebo, SGAs improved clinical global impressions (schizophrenia, bipolar and disruptive behavior disorders) and diminished positive and negative symptoms (schizophrenia), behavior symptoms (disruptive behavior disorders), and tics (Tourette syndrome). CONCLUSIONS: This is the first comprehensive review comparing the effectiveness and safety across the range of antipsychotics for children and young adults. The evidence on the comparative benefits and harms of antipsychotics is limited. Some SGAs have a better side effect profile than other SGAs. Additional studies using head-to-head comparisons are needed. * Abbreviations: ADHD — : attention-deficit/hyperactivity disorder AHRQ — : Agency for Healthcare Research and Quality CI — : confidence interval FDA — : Food and Drug Administration FGA — : first-generation antipsychotic CGI — : Clinical Global Impressions DSM — : Diagnostic and Statistical Manual of Mental Disorders MD — : mean difference NRCT — : nonrandomized controlled trial RCT — : randomized controlled trial SGA — : second-generation antipsychotic SOE — : strength of evidence

To assess inter-rater reliability and validity of the Newcastle Ottawa Scale (NOS) used for methodological quality assessment of cohort studies included in systematic reviews.Two reviewers independently applied the NOS to 131 cohort studies included in eight meta-analyses. Inter-rater reliability was calculated using kappa (κ) statistics. To assess validity, within each meta-analysis, we generated a ratio of pooled estimates for each quality domain. Using a random-effects model, the ratios of odds ratios for each meta-analysis were combined to give an overall estimate of differences in effect estimates.Inter-rater reliability varied from substantial for length of follow-up (κ = 0.68, 95% confidence interval [CI] = 0.47, 0.89) to poor for selection of the nonexposed cohort and demonstration that the outcome was not present at the outset of the study (κ = -0.03, 95% CI = -0.06, 0.00; κ = -0.06, 95% CI = -0.20, 0.07). Reliability for overall score was fair (κ = 0.29, 95% CI = 0.10, 0.47). In general, reviewers found the tool difficult to use and the decision rules vague even with additional information provided as part of this study. We found no association between individual items or overall score and effect estimates.Variable agreement and lack of evidence that the NOS can identify studies with biased results underscore the need for revisions and more detailed guidance for systematic reviewers using the NOS.

STICKLAND, M. K., B. H. ROWE, C. H. SPOONER, B. VANDERMEER, and D. M. DRYDEN. Effect of Warm-Up Exercise on Exercise-Induced Bronchoconstriction. Med. Sci. Sports Exerc., Vol. 44, No. 3, pp. 383–391, 2012. Purpose: Exercise-induced bronchoconstriction (EIB) occurs when vigorous exercise induces bronchoconstriction. Preexercise warm-up routines are frequently used to elicit a refractory period and thus reduce or prevent EIB. This study aimed to conduct a systematic review to evaluate the effectiveness of preexercise routines to attenuate EIB. Methods: A comprehensive literature search was performed, with steps taken to avoid publication and selection bias. Preexercise warm-up routines were classified into four groups: interval high intensity, continuous low intensity, continuous high intensity, and variable intensity (i.e., a combination of low intensity up to very high intensity). The EIB response was measured by the percent fall in the forced expiratory volume in 1 s (FEV1) after exercise, and the mean differences (MDs) and 95% confidence intervals (CI) are reported. Results: Seven randomized studies met the inclusion criteria. The pooled results showed that high intensity (MD = j10.6%, 95% CI = j14.7% to j6.5%) and variable intensity (MD = j10.9%, 95% CI = j14.37% to j7.5%) exercise warm-up attenuated the fall in FEV1. However, continuous low-intensity warm-up (MD = j12.6%, 95% CI = j26.7% to 1.5%) and continuous high-intensity warm-up (MD = j9.8%, 95% CI = j26.0% to 6.4%) failed to result in a statistically significant reduction in bronchoconstriction. Conclusions: The most consistent and effective attenuation of EIB was observed with high-intensity interval and variable intensity preexercise warm-ups. These findings indicate that an appropriate warm-up strategy that includes at least some high

Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg-IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg-IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost-effectiveness of granulocyte colony-stimulating factor (G-CSF) versus Peg-IFN dose reduction for HCV therapy-associated neutropenia in treatment naive adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost-effectiveness and cost-utility analyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction. The remaining studies were case series or retrospective cohorts and provided weak evidence for the relationship between SVR and G-CSF. The risk of adverse events, including infection, associated with G-CSF was low (13.1%; 95% CI: 8.0-20.8) and clinically insignificant. G-CSF had an incremental cost-effectiveness ratio of $41,701 per SVR achieved in genotype 1, and $16,115 per SVR achieved in genotype 2 or 3. Estimates were robust under a variety of resource and intervention scenarios. While administration of G-CSF may enable patients to remain on or resume optimal HCV therapy, there was weak evidence that this improves the likelihood of SVR compared with dose reduction. Adverse effects of G-CSF are mild. The economic evaluation was inconclusive.

Background Bronchodilators are commonly used for acute bronchiolitis, despite uncertain effectiveness. Objectives To examine the efficacy and safety of epinephrine in children less than two with acute viral bronchiolitis. Search methods We searched CENTRAL (2010, Issue 3) which contains the Acute Respiratory Infections Group's Specialized Register, MEDLINE (1950 to September Week 2, 2010), EMBASE (1980 to September 2010), Scopus (1823 to September 2010), PubMed (March 2010), LILACS (1985 to September 2010) and Iran MedEx (1998 to September 2010). Selection criteria We included randomized controlled trials comparing epinephrine to placebo or another intervention involving children less than two years with acute viral bronchiolitis. Studies were included if the trials presented data for at least one quantitative outcome of interest. We selected primary outcomes a priori, based on clinical relevance: rate of admission by days one and seven of presentation for outpatients, and length of stay (LOS) for inpatients. Secondary outcomes included clinical severity scores, pulmonary function, symptoms, quality of life and adverse events. Data collection and analysis Two review authors independently screened the searches, applied inclusion criteria, assessed risk of bias and graded the evidence. We conducted separate analyses for different comparison groups (placebo, non-epinephrine bronchodilators, glucocorticoids) and for clinical setting (inpatient, outpatient). Main results We included 19 studies (2256 participants). Epinephrine versus placebo among outpatients showed a significant reduction in admissions at Day 1 (risk ratio (RR) 0.67; 95% confidence interval (CI) 0.50 to 0.89) but not at Day 7 post-emergency department visit. There was no difference in LOS for inpatients. Epinephrine versus salbutamol showed no differences among outpatients for admissions at Day 1 or 7. Inpatients receiving epinephrine had a significantly shorter LOS compared to salbutamol (mean difference -0.28; 95% CI -0.46 to -0.09). One large RCT showed a significantly shorter admission rate at Day 7 for epinephrine and steroid combined versus placebo (RR 0.65; 95% CI 0.44 to 0.95). There were no important differences in adverse events. Authors' conclusions This review demonstrates the superiority of epinephrine compared to placebo for short-term outcomes for outpatients, particularly in the first 24 hours of care. Exploratory evidence from a single study suggests benefits of epinephrine and steroid combined for later time points. More research is required to confirm the benefits of combined epinephrine and steroids among outpatients. There is no evidence of effectiveness for repeated dose or prolonged use of epinephrine or epinephrine and dexamethasone combined among inpatients.

To evaluate and compare the efficacy and safety of bronchodilators and steroids, alone or combined, for the acute management of bronchiolitis in children aged less than 2 years.Systematic review and meta-analysis.Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx, conference proceedings, and trial registers. Inclusion criteria Randomised controlled trials of children aged 24 months or less with a first episode of bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or combined, with placebo or another intervention (other bronchodilator, other steroid, standard care).Two reviewers assessed studies for inclusion and risk of bias and extracted data. Primary outcomes were selected by clinicians a priori based on clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and length of stay for inpatients. Direct meta-analyses were carried out using random effects models. A mixed treatment comparison using a Bayesian network model was used to compare all interventions simultaneously.48 trials (4897 patients, 13 comparisons) were included. Risk of bias was low in 17% (n = 8), unclear in 52% (n = 25), and high in 31% (n = 15). Only adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo: pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920 patients). Unadjusted results from a single large trial with low risk of bias showed that combined dexamethasone and adrenaline reduced admissions on day 7 (risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline alone or combined with steroids as the preferred treatments for outpatients (probability of being the best treatment based on admissions at day 1 were 45% and 39%, respectively). The incidence of reported harms did not differ. None of the interventions examined showed clear efficacy for length of stay among inpatients.Evidence shows the effectiveness and superiority of adrenaline for outcomes of most clinical relevance among outpatients with acute bronchiolitis, and evidence from a single precise trial for combined adrenaline and dexamethasone.

Croup is a common childhood illness characterized by barky cough, stridor, hoarseness and respiratory distress. Children with severe croup are at risk for intubation. Nebulized epinephrine (NE) may prevent intubation.To evaluate the efficacy and safety of NE in children presenting to emergency department (ED) or admitted to hospital with croup.We searched CENTRAL (The Cochrane Library 2010, Issue 4), containing the Cochrane Acute Respiratory Infections Group's Specialized Register, MEDLINE (1966 to November Week 1, 2010), EMBASE (1980 to November 2010), Web of Science (1974 to November 2010), CINAHL (1982 to November 2010) and Scopus (1996 to November 2010).Randomized controlled trials (RCTs) or quasi-RCTs of children with croup evaluated in an ED or admitted to hospital. Comparisons were: NE versus placebo, racemic NE versus L-epinephrine (an isomer), and NE delivered by intermittent positive pressure breathing (IPPB) versus NE without IPPB. Primary outcome was change in croup score post-treatment. Secondary outcomes were rate and duration of intubation and hospitalization, croup return visit, parental anxiety and side effects.Two authors independently identified potentially relevant studies by title and abstract (when available) and examined relevant studies using a priori inclusion criteria, followed by methodologic quality assessment. One author extracted data while the second checked accuracy. We performed standard statistical analyses.Eight studies (225 participants) were included. NE was associated with croup score improvement 30 minutes post-treatment (three RCTs, standardized mean difference (SMD) -0.94; 95% confidence interval (CI) -1.37 to -0.51; I(2) statistic = 0%). This effect was not significant two and six hours post-treatment. NE was associated with significantly shorter hospital stay than placebo (one RCT, mean difference -32.0 hours; 95% CI -59.1 to -4.9). Comparing racemic and L-epinephrine, no difference in croup score was found after 30 minutes (SMD 0.33; 95% CI -0.42 to 1.08). After two hours, L-epinephrine showed significant reduction compared with racemic epinephrine (one RCT, SMD 0.87; 95% CI 0.09 to 1.65). There was no significant difference in croup score between administration of NE via IPPB versus nebulization alone at 30 minutes (one RCT, SMD -0.14; 95% CI -1.24 to 0.95) or two hours (SMD -0.72; 95% CI -1.86 to 0.42).NE is associated with clinically and statistically significant transient reduction of symptoms of croup 30 minutes post-treatment. Evidence does not favor racemic epinephrine or LE, or IPPB over simple nebulization.

Background Randomized controlled trials (RCTs) are the gold standard for trials assessing the effects of therapeutic interventions; therefore it is important to understand how they are conducted. Our objectives were to provide an overview of a representative sample of pediatric RCTs published in 2007 and assess the validity of their results. Methods We searched Cochrane Central Register of Controlled Trials using a pediatric filter and randomly selected 300 RCTs published in 2007. We extracted data on trial characteristics; outcomes; methodological quality; reporting; and registration and protocol characteristics. Trial registration and protocol availability were determined for each study based on the publication, an Internet search and an author survey. Results Most studies (83%) were efficacy trials, 40% evaluated drugs, and 30% were placebo-controlled. Primary outcomes were specified in 41%; 43% reported on adverse events. At least one statistically significant outcome was reported in 77% of trials; 63% favored the treatment group. Trial registration was declared in 12% of publications and 23% were found through an Internet search. Risk of bias (ROB) was high in 59% of trials, unclear in 33%, and low in 8%. Registered trials were more likely to have low ROB than non-registered trials (16% vs. 5%; p = 0.008). Effect sizes tended to be larger for trials at high vs. low ROB (0.28, 95% CI 0.21,0.35 vs. 0.16, 95% CI 0.07,0.25). Among survey respondents (50% response rate), the most common reason for trial registration was a publication requirement and for non-registration, a lack of familiarity with the process. Conclusions More than half of this random sample of pediatric RCTs published in 2007 was at high ROB and three quarters of trials were not registered. There is an urgent need to improve the design, conduct, and reporting of child health research.

The objectives are: (1) To assess diagnostic test characteristics of six alternative index tests compared with the selected reference standard-a standardized exercise challenge test (ECT) in patients with suspected exercise-induced bronchoconstriction or asthma (EIB/EIA); (2) to determine the efficacy of a single prophylactic dose of four pharmacologic and one nonpharmacologic interventions vs. placebo to attenuate EIB/EIA in patients with diagnosed EIB/EIA; and (3) to determine if regular daily treatment with short-acting or long-acting beta-agonists (SABA or LABA) causes patients with EIA to develop tachyphylaxis when additional prophylactic doses are used pre-exercise.A systematic and comprehensive literature search was conducted in 14 electronic databases (Diagnosis) and the Cochrane Airways Register (Therapy).Study selection, quality assessment, and data extraction were conducted independently by two reviewers. The primary outcome was the maximum percent fall in the post-exercise forced expiratory volume in 1 second (percent fall FEV1). The diagnostic threshold for a positive ECT was a percent fall FEV1 of 10% or more. Sensitivity (SN) and specificity (SP) were calculated. For therapy, mean differences (MD) in the percent fall FEV1 and 95% confidence intervals (CI) (random effects model) were calculated. A positive MD indicates the intervention works better than the control.For the diagnostic reviews, 5,318 citations yielded 28 relevant studies; for the therapy reviews, 1,634 citations yielded 109 relevant RCTs. Diagnostic test results versus ECT: self-reported history (2 studies) SN=36-8 percent; SP=85-86 percent; sport specific challenges (5 studies) SN=0-100 percent, SP=0-100 percent; eucapnic voluntary hyperpnea (7 studies) SN=25-90 percent, SP=0-71 percent; free running asthma screening test (3 studies) SN=60-67 percent, SP=47-67 percent; mannitol (3 studies) SN=58-96 percent, SP=65-78 percent. All SN and SP calculations indicated substantial heterogeneity that could not be explained by sensitivity or subgroup analyses. Therapy results: SABA offered greater protection than mast cell stabilizers (MCS) (12 studies); MD=6.8 (95 percent CI: 4.5, 9.2) but combining them offered no additional benefit; SABA versus MCS plus SABA (5 studies) MD=1.3 (95 percent CI: -6.3, 8.9). Leukotriene receptor antagonists (LTRA), MCS, ipratropium bromide, and interval warmup routines provided statistically significant attenuation of EIA when compared with placebo; inhaled corticosteroids (ICS) and other warmup routines did not. Single-dose intervention versus placebo results are: LTRA (9 studies) MD=8.9 (95 percent CI: 6.9, 11.0); MCS (nedocromil sodium) (17 studies) MD=15.6 (95 percent CI: 13.2, 18.2); interval warmup versus no warmup (4 studies) MD=10.6 (95 percent CI: 6.5, 14.7); ICS (4 studies) MD=5.0 (95 percent CI: 0.0, 9.9); continuous low intensity warmup versus no warmup (3 studies) MD=12.6 (95 percent CI: -1.5, 26.7); continuous high intensity warmup versus no warmup (2 studies) MD=9.8 (95 percent CI: -6.4, 26.0). After daily LABA (salmeterol) use for 3 to 4 weeks (4 studies), the percent fall FEV1 following an ECT at 2 and 4 weeks was greater than at day 1 in the LABA arm indicating that tachyphylaxis to prophylactic LABA use occurred. Daily SABA use for 1 week (1 study) also indicated development of tachyphylaxis. However, both LABA and SABA continued to have an attenuating effect on EIA.Given the small number of studies comparing EIB/EIA diagnostic tests, the heterogeneity of the study populations, and the varied study methodologies, there is no clear evidence that any of the index tests are a suitable replacement for a standardized ECT to diagnose EIB/EIA in the general population. All bronchodilator agents and most anti-inflammatory agents when used as pretreatment are somewhat effective in attenuating the percent fall FEV1 associated with EIA.

Many approaches exist for managing rotator cuff tears.To compare the benefits and harms of nonoperative and operative interventions on clinically important outcomes in adults with rotator cuff tears.12 electronic databases (1990 to September 2009), gray literature, trial registries, and reference lists were searched.Controlled and uncontrolled studies that assessed nonoperative or operative treatments or postoperative rehabilitation for adults with confirmed rotator cuff tears were included. Operative studies in English-language publications and nonoperative and postoperative rehabilitation studies in English, French, or German were considered. Studies were assessed in duplicate.2 reviewers assessed risk for bias by using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. One reviewer rated the evidence by using a modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Data were extracted by one reviewer and verified by another.137 studies met eligibility criteria. All trials had high risk for bias. Cohort and uncontrolled studies were of moderate quality. Reported functional outcomes did not differ between open versus mini-open repair, mini-open versus arthroscopic repair, arthroscopic repair with versus without acromioplasty, or single-row versus double-row fixation. Earlier return to work was reported for mini-open repair versus open repair and for continuous passive motion with physical therapy versus physical therapy alone. Open repairs showed greater improvement in function than did arthroscopic debridement. Complication rates were low across all interventions.Limited evidence, which was often of low quality, precluded conclusions for most comparisons. Language restrictions may have excluded some relevant studies, and selective outcome reporting may have introduced bias.Evidence on the comparative effectiveness and harms of various operative and nonoperative treatments for rotator cuff tears is limited and inconclusive.Agency for Healthcare Research and Quality.

Background The objective of this study was to describe randomized controlled trials (RCTs) and controlled clinical trials (CCTs) in child health published between 1948 and 2006, in terms of quantity, methodological quality, and publication and trial characteristics. We used the Trials Register of the Cochrane Child Health Field for overall trends and a sample from this to explore trial characteristics in more detail. Methodology/Principal Findings We extracted descriptive data on a random sample of 578 trials. Ninety-six percent of the trials were published in English; the percentage of child-only trials was 90.5%. The most frequent diagnostic categories were infectious diseases (13.2%), behavioural and psychiatric disorders (11.6%), neonatal critical care (11.4%), respiratory disorders (8.9%), non-critical neonatology (7.9%), and anaesthesia (6.5%). There were significantly fewer child-only studies (i.e., more mixed child and adult studies) over time (P = 0.0460). The proportion of RCTs to CCTs increased significantly over time (P

BACKGROUND: Healthcare costs, particularly pharmaceutical costs, are a dominant issue for most healthcare organizations, but it is unclear if randomized controlled trials (RCTs) routinely discuss costs. Our objective was to assess the frequency and factors associated with the inclusion of costs in RCTs. METHODS AND FINDINGS: We randomly sampled 188 RCTs spanning three years (2003-2005) from six high impact journals. The sample size for RCTs was based on a calculation to estimate the inclusion of actual drug costs with a precision of +/-3%. Two reviewers independently extracted cost data and study characteristics. Frequencies were calculated and potential characteristics associated with the inclusion of costs were explored. Actual drug costs were included in 4.7% (9/188) of RCTs; any actual costs were included in 7.4% (14/188) of RCTs; and any mention of costs was included in 27.7% (52/188) of RCTs. As the amount of industry funding increased across RCTs, from non-profit to mixed to fully industry funded RCTs, there was a statistically significant reduction in the number of RCTs with any actual costs (Cochran-Armitage test, p = 0.005) and any mention of costs (Cochran-Armitage test, p = 0.02). Logistic regression analysis also indicated funding was associated with the inclusion of any actual cost (OR = 0.34, p = 0.009) or any mention of costs (OR = 0.63, p = 0.02). Journal, study conclusions, study location, primary author's country and product age were not associated with inclusion of cost information. CONCLUSION: While physicians are encouraged to consider costs when prescribing drugs for their patients, actual drug costs were provided in only 5% of RCTs and were not mentioned at all in 72% of RCTs. Industry funded trials were less likely to include cost information. No other factors were associated with the inclusion of cost information.

Objective: To determine whether nebulized 3% hypertonic saline with epinephrine is more effective than nebulized 0.9% saline with epinephrine in the treatment of bronchiolitis in the emergency department. Design: Randomized, double-blind, controlled trial. Setting: Single-center urban pediatric emergency department. Participants: Infants younger than 12 months with mild to moderate bronchiolitis. Interventions: Patients were randomized to receive nebulized racemic epinephrine in either hypertonic or normal saline. Outcome Measures: The primary outcome measure was the change in respiratory distress, as measured by the Respiratory Assessment Change Score (RACS) from baseline to 120 minutes. The change in oxygen saturation was also determined. Secondary outcome measures included the rates of hospital admission and return to the emergency department. Results: Forty-six patients were enrolled and evaluated. The 2 study groups had similar baseline characteristics. The RACS from baseline to 120 minutes demonstrated no improvement in respiratory distress in the hypertonic saline group compared with the normal saline control group. The change in oxygen saturation in the hypertonic saline group was not significant when compared with the control group. Rates of admission and return to the emergency department were not different between the 2 groups. Conclusions: In the treatment of acute bronchiolitis, hypertonic saline and epinephrine did not improve clinical outcome any more than normal saline and epinephrine in the emergency setting. This differs from previously published results of outpatient and inpatient populations and merits further evaluation. Trial Registration : isrctn.org Identifier: ISRCTN66632312

Background Methotrexate, a folate antagonist, is an immunosuppressant drug that is effective for treating several inflammatory disorders including Crohn's disease. Ulcerative colitis, a related chronic inflammatory bowel disease, can be challenging to treat. T his updated systematic review summarizes the current evidence on the use of methotrexate for induction maintenance of remission in ulcerative colitis. Objectives The objectives of this review were to assess the efficacy and safety of methotrexate for maintenance of remission in patients with ulcerative colitis. Search methods We searched MEDLINE, EMBASE, CENTRAL and the Cochrane IBD/FBD group specialized trials register from inception to June 26, 2014. Study references and review papers were also searched for additional trials. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. Selection criteria Randomized controlled trials in which methotrexate was compared to placebo or an active comparator in patients with quiescent ulcerative were considered for inclusion. Data collection and analysis Two authors independently extracted data and assessed the risk of bias for each study. The primary outcome was the occurrence of clinical or endoscopic relapse as defined by the primary studies. Secondary outcomes included frequency and nature of adverse events, change of disease activity score and steroid-sparing effect. We calculated the risk ratio and corresponding 95% confidence interval for dichotomous outcomes. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Main results Three trials (165 patients) fulfilled the inclusion criteria. One study compared oral methotrexate (12.5 mg/week) to placebo, another compared oral methotrexate (15 mg/week) to 6-mercaptopurine (6-MP, 1.5 mg/kg/day) or 5-aminosalicylic acid (5-ASA, 3 g/day) and the other compared methotrexate (15 mg/week) in combination sulfasalazine (3 g/day) to sulfasalazine. The placebo-controlled study was rated as low risk of bias. The study comparing methotrexate to 6-MP and 5-ASA was rated as high risk of bias and the study assessing methotrexate and sulfasalazine was rated as unclear risk of bias for sequence generation, allocation concealment and blinding. The placebo-controlled study found no statistically significant differences in the proportion of patients who maintained remission. At nine months, 36% (5/14) of methotrexate patients maintained remission compared to 54% (10/18) of placebo patients (RR 0.64, 95% CI 0.28 to 1.45). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (15 events). The study comparing combination therapy to sulfasalazine found no statistically significant difference in the proportion of patients who maintained remission. At 12 months, 100% (14/14) of patients in the combination group maintained remission compared to 75% (9/12) of sulfasalazine patients (RR 1.32, 95% CI 0.94 to 0.86), A GRADE analysis indicated that the overall quality of the evidence for this outcome was very low due to unknown risk of bias and very sparse data (23 events). There were no statistically significant differences in maintenance of remission rates between methotrexate and 6-MP or between methotrexate and 5-ASA. At 76 weeks, 14% (1/7) of methotrexate patients maintained remission compared to 64% (7/11) of 6-MP patients (RR 0.22, 95% CI 0.03 to 1.45) and 0% (0/2) of 5-ASA patients (RR 1.13, 95% CI 0.06 to 20.71). A GRADE analysis indicated that the overall quality of the evidence from this study was very low due to high risk of bias and very sparse data. Adverse events reported in these studies included transient leucopenia, migraine, nausea and dyspepsia, mild alopecia, mild increase in aspartate aminotransferase levels, peritoneal abscess, hypoalbuminemia, severe rash and atypical pneumonia Authors' conclusions The results for efficacy and safety outcomes between methotrexate and placebo, methotrexate and sulfasalazine, methotrexate and 6-mercaptopurine and methotrexate and 5-aminosalicylic acid were uncertain. Whether a higher dose or parenteral administration of methotrexate would be effective in quiescent ulcerative colitis is unknown. At present there is no evidence supporting the use of methotrexate for maintenance of remission in ulcerative colitis. More studies are needed to determine the efficacy and safety of methotrexate maintenance therapy in patients with quiescent ulcerative colitis. Large scale methodologically rigorous randomized controlled trials are needed. These studies should investigate higher doses of methotrexate (e.g. 15 to 25 mg/week) and parenteral administration.

In the view of small sample sizes of the studies published so far, the value of video capsule endoscopy (VCE) in diagnosing celiac disease (CD) is yet to be determined. The aim of this work was to systemically determine the overall diagnostic characteristics of VCE in diagnosing noncomplicated CD, compared to the gold standard, using meta-analysis.An extensive literature search was performed looking for prospective, controlled trials, with investigators blinded to results of the pathology of small-bowel biopsies. Two independent authors performed data extraction and assessment of the methodologic quality of each trial. Diagnostic characteristics of each trial were collected, and pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios were computed. Description of complications and costs was included, if reported.A total of three studies met the inclusion criteria (n = 107; 63 with CD and 44 without). The overall pooled VCE sensitivity was 83% (95% confidence interval [CI] = 71-90%) and specificity was 98% (95% CI = 88-99.6%). No major complications were reported. The costs were mentioned only in one study.The overall diagnostic characteristics of VCE, when used to diagnose celiac disease, though good with an experienced eye, could not justify the routine use of VCE as an alternative to the pathology of small-bowel biopsies. More studies are needed with proper cost-benefit analysis.

Background Nutritional support in the critically ill child has not been well investigated and is a controversial topic within paediatric intensive care. There are no clear guidelines as to the best form or timing of nutrition in critically ill infants and children. This is an update of a review that was originally published in 2009. . Objectives The objective of this review was to assess the impact of enteral and parenteral nutrition given in the first week of illness on clinically important outcomes in critically ill children. There were two primary hypotheses: 1. the mortality rate of critically ill children fed enterally or parenterally is different to that of children who are given no nutrition; 2. the mortality rate of critically ill children fed enterally is different to that of children fed parenterally. We planned to conduct subgroup analyses, pending available data, to examine whether the treatment effect was altered by: a. age (infants less than one year versus children greater than or equal to one year old); b. type of patient (medical, where purpose of admission to intensive care unit (ICU) is for medical illness (without surgical intervention immediately prior to admission), versus surgical, where purpose of admission to ICU is for postoperative care or care after trauma). We also proposed the following secondary hypotheses (a priori), pending other clinical trials becoming available, to examine nutrition more distinctly: 3. the mortality rate is different in children who are given enteral nutrition alone versus enteral and parenteral combined; 4. the mortality rate is different in children who are given both enteral feeds and parenteral nutrition versus no nutrition. Search methods In this updated review we searched: the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2); Ovid MEDLINE (1966 to February 2016); Ovid EMBASE (1988 to February 2016); OVID Evidence-Based Medicine Reviews; ISI Web of Science - Science Citation Index Expanded (1965 to February 2016); WebSPIRS Biological Abstracts (1969 to February 2016); and WebSPIRS CAB Abstracts (1972 to February 2016). We also searched trial registries, reviewed reference lists of all potentially relevant studies, handsearched relevant conference proceedings, and contacted experts in the area and manufacturers of enteral and parenteral nutrition products. We did not limit the search by language or publication status. Selection criteria We included studies if they were randomized controlled trials; involved paediatric patients, aged one day to 18 years of age, who were cared for in a paediatric intensive care unit setting (PICU) and had received nutrition within the first seven days of admission; and reported data for at least one of the pre-specified outcomes (30-day or PICU mortality; length of stay in PICU or hospital; number of ventilator days; and morbid complications, such as nosocomial infections). We excluded studies if they only reported nutritional outcomes, quality of life assessments, or economic implications. Furthermore, we did not address other areas of paediatric nutrition, such as immunonutrition and different routes of delivering enteral nutrition, in this review. Data collection and analysis Two authors independently screened the searches, applied the inclusion criteria, and performed 'Risk of bias' assessments. We resolved discrepancies through discussion and consensus. One author extracted data and a second checked data for accuracy and completeness. We graded the evidence based on the following domains: study limitations, consistency of effect, imprecision, indirectness, and publication bias. Main results We identified only one trial as relevant. Seventy-seven children in intensive care with burns involving more than 25% of the total body surface area were randomized to either enteral nutrition within 24 hours or after at least 48 hours. No statistically significant differences were observed for mortality, sepsis, ventilator days, length of stay, unexpected adverse events, resting energy expenditure, nitrogen balance, or albumin levels. We assessed the trial as having unclear risk of bias. We consider the quality of the evidence to be very low due to there being only one small trial. In the most recent search update we identified a protocol for a relevant randomized controlled trial examining the impact of withholding early parenteral nutrition completing enteral nutrition in pediatric critically ill patients; no results have been published. Authors' conclusions There was only one randomized trial relevant to the review question. Research is urgently needed to identify best practices regarding the timing and forms of nutrition for critically ill infants and children.

Although neonatal hypoxic-ischemic encephalopathy is a common cause of childhood developmental disability, its timing, duration, and outcomes are poorly defined. Biomarkers serve as surrogates for disease injury, evolution, and outcome, but no tissue biomarker in routine clinical use can help predict outcomes in term newborn encephalopathy. We reviewed biomarkers in human term neonatal encephalopathy, to determine if current biomarkers are strong enough for clinical use as predictors of outcomes. A comprehensive search of databases identified 110 publications that met our inclusion criteria, i.e., (1) newborns at36 weeks; (2) neonatal encephalopathy as defined by the American College of Obstetrics and Gynecology; (3) the use of a serum, urine, or cerebrospinal fluid biomarker; and (4) reported outcomes beyond age 12 months. Of those 110 publications, 22 reported outcomes beyond age 12 months. In single reports, urine lactate (P0.001), first urine S100 (P0.0001), cord-blood interleukin-6 (P = 0.02), serum nonprotein-bound iron (P0.001), serum CD14 cell NFkappaB activation (P = 0.014), serum interleukin-8 (P = 0.03), and serum ionized calcium (P = 0.001) were potential predictors of death or abnormal outcomes. A meta-analysis identified serum interleukin-1b (P = 0.04, n = 3), serum interleukin-6 (P = 0.04, n = 2), cerebrospinal fluid neuron-specific enolase (P = 0.03, n = 3), and cerebrospinal fluid interleukin-1b (P = 0.003, n = 2) as putative predictors of abnormal outcomes in survivors, when measured before age 96 hours. Several serum, urine, and cerebrospinal fluid biomarkers of term neonatal encephalopathy may provide important information regarding long-term outcomes. None, however, were studied extensively enough to warrant routine clinical use. Validation of these markers, either alone or in combination, is required in the development of viable therapeutic interventions.

The objectives of this study were to establish and describe a database of Cochrane and non-Cochrane meta-analyses of safety data and to determine under what conditions exact methods differ from asymptotic methods in meta-analyses of safety data. A sample of Cochrane ( n = 500) and non-Cochrane ( n = 200) systematic reviews was randomly selected and a database of safety meta-analyses established. Point estimates and confidence intervals for each meta-analysis were recalculated using exact methods and compared to the results of asymptotic methods. Cochrane reviews were nearly four times as likely as non-Cochrane reviews to contain meta-analyses of safety data (35% compared to 9%). More than 50% of safety meta-analyses contained an outcome with a rare event rate (

To determine the efficacy, effectiveness, and safety of cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillators (ICD) in patients with left ventricular systolic dysfunction (LVSD).A systematic and comprehensive literature search was conducted to identify randomized controlled trials (RCTs) evaluating efficacy and observational studies evaluating effectiveness or safety of CRT and/or ICD in patients with LVSD.Study selection, quality assessment, and data extraction were completed by several investigators in duplicate and independently. Random-effects models were used for analyses.From 11,340 citations, we identified 14 RCTs (4,420 patients) for the CRT efficacy review, 106 studies (9,209 patients) for the CRT effectiveness review, 89 studies (9,677 patients) for the CRT safety review, 12 RCTs (8,516 patients) for the ICD efficacy review, 48 studies (15,097 patients) for the ICD effectiveness review, and 49 studies (12,592 patients) for the ICD safety review-all studies enrolled only patients with LVSD. An additional 12 studies (68,848 patients) were included for an analysis of peri-implant outcomes for all patients with ICD (i.e., not only LVSD patients). All patients in the CRT studies had LVSD (mean LVEF from 21 to 30 percent) and prolonged QRS duration (mean from 155 to 209 msec), and 91 percent had New York Heart Association (NYHA) class III or IV symptoms. In patients with LVSD and heart failure symptoms, CRT improved ejection fraction (weighted mean difference 3.0 percent [95% CI, 0.9 to 5.1]), quality of life (weighted mean reduction in Minnesota Living with Heart Failure Questionnaire 8.0 points [95% CI, 5.6 to 10.4 points]), and function (59 percent of CRT recipients vs. 37 percent of controls improved by at least one NYHA class in the RCTs and between 63 percent and 82 percent of CRT recipients improved by at least one NYHA class in observational studies). The proportion of patients hospitalized for HF was reduced by 37 percent (95% CI, 7 to 57 percent) and all-cause mortality was reduced by 22 percent (95% CI, 9 to 33 percent; NNT=29 over 6 months). Implant success rate was 93 percent, 0.3 percent of patients with LVSD died during implantation. Over a median 11-month followup, 6.6 percent of CRT devices exhibited lead problems and 5 percent malfunctioned. In patients with LVSD, ICD reduced all-cause mortality by 20 percent (95% CI, 10 to 29 percent; NNT=20 over 35 months). ICD implant success rate was 99 percent and peri-implant deaths occurred in 1.2 percent of LVSD patients and 1.3 percent of all implantees. The frequency of post-implantation complications in LVSD patients per 100 patient years included 1.4 (95% CI, 1.2 to 1.6) device malfunctions, 1.5 (95% CI, 1.3 to 1.8) lead problems, 0.6 (95% CI, 0.5 to 0.8) implant site infections, and 19.1 (95% CI, 16.5 to 22.0) inappropriate discharges in RCT participants and 4.7 (95% CI, 4.3 to 5.1) inappropriate discharges in patients enrolled in observational studies.ICD and CRT reduce all-cause mortality in patients with LVSD meeting RCT entry criteria. The incremental benefit of CRT plus ICD over CRT alone in patients with LVSD remains uncertain. None of the trials reported differences in the efficacy of CRT or ICD across patient subgroups, nor did our meta-regression detect any subgroup effects; however, subgroup analyses and meta-regression using aggregate trial data are post-hoc analyses and were underpowered to detect such effects. Examination of individual patient trial data is urgently needed to define which clinical subgroups are most likely to benefit from these devices.

Patients with left ventricular (LV) systolic dysfunction have an increased risk for ventricular arrhythmias.To summarize the evidence about benefits and harms of implantable cardioverter defibrillators (ICDs) in adult patients with LV systolic dysfunction.A search of electronic databases (including MEDLINE, EMBASE, Cochrane Central, and U.S. Food and Drug Administration reports) from 1980 through April 2007, not limited by language of publication, was supplemented by hand searches and contact with study authors and device manufacturers.Two reviewers independently selected studies on the basis of prespecified criteria. They selected 12 randomized, controlled trials (RCTs) (8516 patients) that reported on mortality and 76 observational studies (96 951 patients) that examined safety or effectiveness.Data were extracted in duplicate and independently by 2 reviewers.In adult patients with LV systolic dysfunction, 86% of whom had New York Heart Association class II or III symptoms, ICDs reduced all-cause mortality by 20% (95% CI, 10% to 29%) in the RCTs and by 46% (CI, 32% to 57%) in the observational studies. Death associated with implantation of ICDs occurred during 1.2% (CI, 0.9% to 1.5%) of procedures. The frequency of postimplantation complications per 100 patient-years included 1.4 (CI, 1.2 to 1.6) device malfunctions, 1.5 (CI, 1.3 to 1.8) lead problems, and 0.6 (CI, 0.5 to 0.8) site infection. Rates of inappropriate discharges per 100 patient-years ranged from 19.1 (CI, 16.5 to 22.0) in RCTs to 4.9 (CI, 4.5 to 5.3) in observational studies.Studies were of short duration and infrequently reported nonfatal outcomes. Few studies evaluated dual-chamber ICDs. Lack of individual-patient data prevents identification of subgroup-specific effects.Implantable cardioverter defibrillators are efficacious in reducing mortality for adult patients with LV systolic dysfunction, and this benefit extends to nontrial populations. Improved risk stratification tools to identify patients who are most likely to benefit from ICD are needed.

Background The aim of this study was to determine which programme characteristics influence the effectiveness of secondary prevention programmes for Coronary Heart Disease. Design The study follows a meta-regression design. Methods We conducted a meta-regression within a systematic review of randomized trials comparing secondary prevention programmes versus usual care. The primary outcome was all-cause mortality. Studies were identified by searching multiple electronic databases, bibliographies of published studies, contact with experts, and references provided by the United States Centers for Medicare and Medicaid Services. Primary authors of all relevant trials were surveyed for detailed information on programme characteristics. Forty-six unique trials were identified (18 821 patients). The pooled all-cause mortality risk ratio (RR) for programmes was 0.87 [95% confidence interval (CI) 0.79-0.97]. Programmes containing less than 10 h of patient contact with health professionals reduced all-cause mortality (RR 0.80, 95% CI 0.68-0.95) as effectively as programmes with more contact time. Programmes provided in general practice settings were effective at reducing all-cause mortality (RR 0.76, 95% CI 0.63-0.92) and compared favourably with the effectiveness of hospital-based programmes. Other characteristics, including specialist versus generalist provision, did not appreciably impact programme effectiveness. Conclusions Shorter secondary prevention programmes, those based in general practice, and those staffed by generalists are at least as effective in reducing all cause mortality in patients with coronary heart disease as longer programmes, hospital-based programmes, and programmes staffed by specialists.

The objective of this review was to evaluate the efficacy and safety of rifampin, opioid antagonists, or bile acid binding agents in the treatment of cholestasis-related pruritus (CAP) from available randomized controlled trial evidence.In addition to a comprehensive gray literature search, the Cochrane Library, MEDLINE, EMBASE, PubMed, and Web of Science were searched. Only full-text RCTs in participants (75% adult) with CAP on at least one of the three medications were included. The primary outcome was change in pruritus score, recorded as a continuous or dichotomous outcome. Two independent reviewers performed trial selection and quality assessment.From 487 citations, 12 RCTs were included. Rifampin (standardized mean difference [SMD]-1.62, 95% CI -3.05 to -0.18) and opioid antagonists (SMD -0.68, 95% CI -1.19 to -0.17) significantly reduced CAP. The two cholestyramine studies were too heterogeneous to pool. Although cholestyramine (P= 0.35) and rifampin (P= 0.96) were not associated with greater side effects compared with placebo, opioid antagonists were (number needed to harm = 2.6, 95% CI 1.4-25).The available RCTs are small, few in number, and use varying scales for measuring pruritus. Although both opioid antagonists and rifampin demonstrated a reduction in pruritus, there were insufficient data to judge the efficacy of cholestyramine. Opioid antagonists were associated with transient side effects in a significant proportion of patients. A longer well-designed randomized controlled trial is needed to confirm the efficacy of bile acid binding agents and accurately assess adverse events.

Objective To determine the most accurate, noninvasive method of assessing dehydration. Study design The following data sources were searched: electronic databases, gray literature, scientific meetings, reference lists, and authors of unpublished studies. Eligible studies were comparative outpatient evaluations that used an accepted reference standard and were conducted in developed countries in children aged Results Nine studies that included 1039 participants were identified. The 4-item Clinical Dehydration Scale (CDS), the "Gorelick" score, and unstructured physician assessment were evaluated in 3, 2, and 5 studies, respectively. Bedside ultrasound, capillary digital videography, and urinary measurements were each evaluated in one study. The CDS had a positive likelihood ratio (LR) range of 1.87-11.79 and a negative LR range of 0.30-0.71 to predict 6% dehydration. When combined with the 4-item Gorelick Score, the positive LR was 1.93 (95% CI 1.07-3.49) and negative LR was of 0.40 (95% CI 0.24-0.68). Unstructured dehydration assessment had a pooled positive LR of 2.13 (95% CI 1.33-3.44) and negative LR of 0.48 (95% CI 0.28-0.82) to detect ≥5% dehydration. Conclusions Overall, the clinical scales evaluated provide some improved diagnostic accuracy. However, test characteristics indicate that their ability to identify children both with and without dehydration is suboptimal. Current evidence does not support the routine use of ultrasound or urinalysis to determine dehydration severity.

Health care workers in our facility were surveyed, and their pagers were cultured before and after disinfection with various agents. All pagers were contaminated with bacteria, including the pathogens Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. and methicillin-resistant S. aureus. Disinfection reduced bacterial contamination. No risk factors for pager contamination with pathogens were identified.

To evaluate the effect of intentional delivery versus expectant management in women with preterm prelabor rupture of membranes (PPROM).We searched electronic databases and trials registries, contacted experts, and checked reference lists of relevant studies. Studies were included if they were randomized controlled trials comparing intentional delivery versus expectant management after PPROM, the gestational age of participants was between 30 and 36 weeks, and the study reported one of several pre-determined outcomes.Four studies were included in the meta-analysis. No difference was found between intentional delivery and expectant management in neonatal intensive care unit (NICU) length of stay (LOS) (weighted mean difference (WMD) -0.81 day, 95% confidence interval (CI) -1.66, 0.04), respiratory distress syndrome (risk difference (RD) -0.01, 95% CI -0.07, 0.06), and confirmed neonatal sepsis (RD -0.01, 95% CI -0.05, 0.04). One study found a significantly lower incidence of suspected neonatal sepsis among the intentional delivery group (RD -0.31, 95% CI -0.50, -0.12; number needed to treat (NNT) 3, 95% CI 2, 8). Maternal LOS was significantly shorter for the intentional delivery group (WMD -1.39 day, 95% CI -2.03, -0.75). There was a significant difference in the incidence of clinical chorioamnionitis favoring intentional delivery (RD -0.16, 95% CI -0.23, -0.10; NNT 6, 95% CI 5, 11). There was no significant difference in the incidence of other maternal outcomes, including cesarean section (RD 0.05, 95% CI -0.01, 0.11).Intentional delivery may be favorable to expectant management for some maternal outcomes (chorioamnionitis and LOS). There is insufficient evidence to suggest that either strategy is beneficial or harmful for the baby. Large multicenter trials with primary neonatal outcomes are required to assess whether intentional delivery is associated with less neonatal morbidity.

Hypnotics have a role in the management of acute insomnia; however, the efficacy and safety of pharmacological interventions in the management of chronic insomnia is unclear.The objective of this paper is to conduct a systematic review of the efficacy and safety of drug treatments for chronic insomnia in adults.Twenty-one electronic databases were searched, up to July 2006.Randomized double-blind, placebo-controlled trials were eligible. Quality was assessed using the Jadad scale. Data were pooled using the random effects model.One hundred and five studies were included in the review. Sleep onset latency, as measured by polysomnography, was significantly decreased for benzodiazepines (BDZ), (weighted mean difference: -10.0 minutes; 95% CI: -16.6, -3.4), non-benzodiazepines (non-BDZ) (-12.8 minutes; 95% CI: -16.9, -8.8) and antidepressants (ADP) (-7.0 minutes; 95% CI: -10.7, -3.3). Sleep onset latency assessed by sleep diaries was also improved (BDZ: -19.6 minutes; 95% CI: -23.9, -15.3; non-BDZ: -17.0 minutes; 95% CI: -20.0, -14.0; ADP: -12.2 minutes; 95% CI: -22.3, -2.2). Indirect comparisons between drug categories suggest BDZ and non-BDZ have a similar effect. All drug groups had a statistically significant higher risk of harm compared to placebo (BDZ: risk difference [RD]: 0.15; non-BDZ RD: 0.07; and ADP RD: 0.09), although the most commonly reported adverse events were minor. Indirect comparisons suggest that non-BDZ are safer than BDZ.Benzodiazepines and non-benzodiazepines are effective treatments in the management of chronic insomnia, although they pose a risk of harm. There is also some evidence that antidepressants are effective and that they pose a risk of harm.

ContextNot all research presented at scientific meetings is subsequently published and, even when it is, there may be inconsistencies between these results and what is ultimately printed. Although late-breaking trials sessions are now integrated into several major scientific meetings and the results are often promptly and prominently communicated, no studies have examined the publication fate and degree of consistency between meeting abstracts or presentations and subsequent full-length article publications for randomized controlled trials (RCTs) presented at these sessions.ObjectiveTo compare RCT abstracts presented in the late-breaking trials session vs other sessions at a major scientific meeting and subsequent full-length publications.DesignRCTs were identified by hand searching abstract proceedings booklets and related Web sites for the American College of Cardiology scientific meetings (1999-2002). Subsequent full-length articles were identified via electronic databases.Main Outcome MeasuresPublication fate and degree of consistency between meeting abstract results and subsequent full-length publication results.ResultsThe 86 late-breaking RCTs were significantly larger (median, 2737 patients vs 896; P

Objective To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. Data sources 13 electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999 to 2003). Study selection The efficacy review included randomised controlled trials; the safety review included randomised and non-randomised controlled trials. Quality assessment Randomised controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al, and non-randomised controlled trials by the Downs and Black checklist. Data extraction and synthesis One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weight studies and the random effects model was used to analyse data. Main results Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference −13.2 (95% confidence interval −27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction (−1.0 (−2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less). Conclusions There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short term use.

Background: It is not clear how physicians currently use clinical practice guidelines (CPGs).Objectives: The objective was to describe how Canadian pediatric residents and pediatricians use CPGs and to identify barriers to CPG use.Methods: Pediatric emergency physicians and general pediatricians in Edmonton and Ottawa and all Canadian pediatric residents were surveyed regarding patterns of use for CPGs and barriers to use. Results: Response rate was 178/847 (21%). The majority of responding residents (62%), emergency physicians (54%) and general pediatricians teaching more than 6 weeks annually on a clinical teaching unit (CTU) use CPGs at least monthly (55%) with less frequent use by pediatricians who teach 1 to 6 weeks on CTU (14%) or rarely/never teach on CTU (21%) (p

Exogenous melatonin has been increasingly used in the management of sleep disorders.To conduct a systematic review of the efficacy and safety of exogenous melatonin in the management of primary sleep disorders.A number of electronic databases were searched. We reviewed the bibliographies of included studies and relevant reviews and conducted hand-searching.Randomized controlled trials (RCTs) were eligible for the efficacy review, and controlled trials were eligible for the safety review.One reviewer extracted data, while the other verified data extracted. The Random Effects Model was used to analyze data.Melatonin decreased sleep onset latency (weighted mean difference [WMD]: -11.7 minutes; 95% confidence interval [CI]: -18.2, -5.2)); it was decreased to a greater extent in people with delayed sleep phase syndrome (WMD: -38.8 minutes; 95% CI: -50.3, -27.3; n=2) compared with people with insomnia (WMD: -7.2 minutes; 95% CI: -12.0, -2.4; n=12). The former result appears to be clinically important. There was no evidence of adverse effects of melatonin.There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less); however, additional large-scale RCTs are needed before firm conclusions can be drawn. There is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. There is evidence to suggest that melatonin is safe with short-term use (3 months or less).

Background Intravenous gamma globulin (IVGG) is commonly used in the management of acute myocarditis. The objective of this study was to systematically review the literature evaluating this practice. Methods We conducted a comprehensive search (electronic databases, trials registries, conference proceedings, reference lists, contact with authors) to identify studies evaluating the use of IVGG in adults and children with a clinical or histologically proven diagnosis of myocarditis of possible viral etiology and symptoms of less than six months duration. Two reviewers independently screened the searches, applied inclusion criteria, and graded the evidence. Results Results were described qualitatively; data were not pooled because only one randomized controlled trial (RCT) with 62 patients was identified. The RCT showed no benefit with respect to cardiac function, functional outcome, or event-free survival. A small, uncontrolled trial (n = 10) showed significant improvement in LVEF from a mean of 24% to 41% 12 months after IVGG in nine survivors. A retrospective cohort study of pediatric patients showed improvement in cardiac function and a trend towards improved survival in patients receiving IVGG (n = 21) versus historic controls (n = 25). Ten case reports and two case series (total n = 21) described improvement in cardiac function after administration of IVGG; two case reports showed no benefit of IVGG. One case of hemolytic anemia was attributed to IVGG. Conclusion There is insufficient data from methodologically strong studies to recommend routine use of IVGG for acute myocarditis. Future randomized studies that take into account the etiology of acute myocarditis will be required to determine the efficacy of IVGG.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To describe and assess the evidence from controlled trials on the efficacy and tolerability of pharmacological interventions by any route of administration versus placebo or other drug treatments for acute attacks of migraine in children.