Nina Buscemi

Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction : meta-analysis

Abstract 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.

The efficacy and safety of exogenous melatonin for primary sleep disorders a meta-analysis

BACKGROUND: Exogenous melatonin has been increasingly used in the management of sleep disorders.PURPOSE: To conduct a systematic review of the efficacy and safety of exogenous melatonin in the management of primary sleep disorders.DATA SOURCES: A number of electronic databases were searched. We reviewed the bibliographies of included studies and relevant reviews and conducted hand-searching.STUDY SELECTION: Randomized controlled trials (RCTs) were eligible for the efficacy review, and controlled trials were eligible for the safety review.DATA EXTRACTION: One reviewer extracted data, while the other verified data extracted. The Random Effects Model was used to analyze data.DATA SYNTHESIS: 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.CONCLUSIONS: 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).

Systematic review of biomarkers of brain injury in term neonatal encephalopathy.

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 at >36 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 (P < 0.001), first urine S100 (P < 0.0001), cord-blood interleukin-6 (P = 0.02), serum nonprotein-bound iron (P < 0.001), 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.

Systematic review data extraction: cross-sectional study showed that experience did not increase accuracy

OBJECTIVE This study assessed the impact of systematic review and data extraction experience on the accuracy and efficiency of data extraction in systematic reviews. STUDY DESIGN AND SETTING We conducted a prospective cross-sectional study from October to December 2006. Participants were classified as having minimal, moderate, or substantial experience in systematic reviews and data extraction. Three studies on insomnia treatment were extracted. Our primary outcome was the accuracy of data extraction. Data sets of each experience level were analyzed for errors in data extraction and results of meta-analyses. Additionally, the time required for completion of data extraction was compared. RESULTS Error rates were similar across the various levels of experience and ranged from 28.3% to 31.2%. Mean rates for errors of omission (11.3-16.4%) were generally lower than those for errors of inaccuracy (13.9-17.9%). There were no significant differences in error rates or accuracy of meta-analysis results between groups. Time required approached significance, with minimally experienced participants requiring the most time. CONCLUSION Overall, there were high error rates by participants at all experience levels; however, time required for extraction tended to decrease with experience. These results illustrate the need to develop strategies aimed at mastery of data extraction, rather than reliance on previous data extraction experience alone.

Comparison of meta-analytic results of indirect, direct, and combined comparisons of drugs for chronic insomnia in adults : A case study

Background:Our Center recently conducted a systematic review of the manifestations and management of chronic insomnia in adults. The efficacy and safety of benzodiazepines and nonbenzodiazepines, relative to placebo, were compared indirectly. Objectives:Determine how the results of indirect comparisons made in the review compare with the results of direct comparisons, as well as with estimates derived from Bayesian mixed treatment comparisons. Establish general appropriateness of the use of results of indirect or mixed treatment comparisons. Methods:Treatments were compared using frequentist direct, indirect, and combined methods, as well as Bayesian direct and mixed methods. Results:Estimates for comparisons tended to be clinically and statistically similar across methods. Estimates obtained through indirect comparisons were not biased and were similar to those obtained through direct analysis. Conclusions:Results of indirect comparisons made in the review, accurately reflected the current evidence. Frequentist and Bayesian methods of analysis of indirect comparisons should be considered when performing meta-analyses.