Sunita Vohra

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).

The use of complementary and alternative medicine in pediatrics

The American Academy of Pediatrics is dedicated to optimizing the well-being of children and advancing family-centered health care. Related to these goals, the American Academy of Pediatrics recognizes the increasing use of complementary and alternative medicine in children and, as a result, the need to provide information and support for pediatricians. From 2000 to 2002, the American Academy of Pediatrics convened and charged the Task Force on Complementary and Alternative Medicine to address issues related to the use of complementary and alternative medicine in children and to develop resources to educate physicians, patients, and families. One of these resources is this report describing complementary and alternative medicine services, current levels of utilization and financial expenditures, and associated legal and ethical considerations. The subject of complementary and alternative medicine is large and diverse, and consequently, an in-depth discussion of each method of complementary and alternative medicine is beyond the scope of this report. Instead, this report will define terms; describe epidemiology; outline common types of complementary and alternative medicine therapies; review medicolegal, ethical, and research implications; review education and training for complementary and alternative medicine providers; provide resources for learning more about complementary and alternative medicine; and suggest communication strategies to use when discussing complementary and alternative medicine with patients and families.

Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials

Background: Antibiotic treatment is known to disturb gastrointestinal microflora, which results in a range of clinical symptoms — most notably, diarrhea. This is especially important in children, for whom antibiotics are prescribed frequently. Although meta-analyses have been conducted to evaluate the ability of probiotics to prevent antibiotic-induced diarrhea in the general population, little is known about which probiotic strains and doses might be of most benefit to children. Our objective in this study was to assess the efficacy of probiotics (of any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children and to assess adverse events associated with the use of probiotics when coadministered with antibiotics to children. Methods: A comprehensive search was performed of the major electronic databases (e.g., CENTRAL, MEDLINE, EMBASE, CINAHL, AMED) from their inception to January 2005. We also contacted experts and searched registries and meeting abstracts for additional relevant articles. Randomized controlled trials that compared probiotic treatment with placebo or no treatment, involving pediatric subjects less than 19 years of age were included. Two reviewers independently applied eligibility criteria and assessed the studies for methodological quality. Data were independently extracted by 2 reviewers and analyzed via the standard Cochrane methodology. Results: Six studies were included (total n = 707 patients). The combined results, analyzed with a per-protocol method that reported on the incidence of diarrhea during antibiotic treatment, showed significant benefit for the use of probiotics over placebo (relative risk [RR] 0.43, 95% confidence interval [CI] 0.25–0.75, Ι2 = 70.1%). In contrast, results from intention-to-treat analysis were nonsignificant overall (RR 1.01, 95% CI 0.64–1.61). Subgroup analysis on 4 studies that provided at least 5 billion single-strain colony-forming units (CFUs) daily (range 5.5–40 × 109 Lactobacillus GG, L. sporogens or Saccharomyces boulardii) showed strong evidence with narrow CIs for the preventative effects of probiotics for antibiotic-associated diarrhea (RR 0.36, 95% CI 0.25–0.53, Ι2 = 3.5%). No serious adverse events were reported. Interpretation: The potential protective effects of probiotics to prevent antibiotic-associated diarrhea in children do not withstand intention-to-treat analysis. Before routine use is recommended, further studies (with limited losses of subjects to follow-up) are merited. Trials should involve those probiotic strains and doses with the most promising evidence (i.e., Lactobacillus GG, L. sporogens or S. boulardii at 5–40 × 109 CFUs daily).

Vitamin D Receptor Polymorphisms and the Risk of Acute Lower Respiratory Tract Infection in Early Childhood

To investigate associations of 2 vitamin D receptor (VDR) gene polymorphisms and acute lower respiratory tract infection (ALRI), we compared 56 young children hospitalized with ALRI and 64 children without a history of ALRI. The FokI ff genotype was associated with an adjusted relative odds of ALRI that was approximately 7 times that of FokI FF. A weaker association with the TaqI polymorphism was also found. These data provide preliminary evidence of associations of VDR polymorphisms with the risk of ALRI (predominantly viral bronchiolitis) in young children, consistent with a potential role of vitamin D in the immune response to respiratory tract infection.

N-of-1 trials in the medical literature: a systematic review.

BackgroundN-of-1 trials (multiple crossover studies conducted in single individuals) may be ideal for determining individual treatment effects and as a tool to estimate heterogeneity of treatment effects (HTE) in a population. However, comprehensive data on n-of-1 trial methodology and analysis is lacking. We performed this study to describe n-of-1 trial characteristics, examine treatment changes resulting from n-of-1 trial participation, and to determine if trial reporting is adequate for estimating HTE. MethodsWe undertook a systematic review of n-of-1 trials published between 1985 and December 2010. Included trials were those having individual treatment episodes as the unit of randomization and reporting individual-specific treatment effects. We abstracted trial characteristics, treatment change information, and analytic methods. ResultsWe included 108 trials reporting on 2154 participants. Approximately half (49%) of the trials used a statistical cutoff to determine a superior treatment, whereas the remainder used a graphical comparison (25%) or a clinical significance cutoff (20%). Sixty-seven trials, reporting on 488 people, provided treatment change information: 54% of participants had subsequent treatment decisions consistent with the results of the trial, 8% had decisions inconsistent with trial results, and 38% had ambiguous results. Less than half of the trials (45%) reported adequate information to facilitate the calculation of HTE. ConclusionN-of-1 trials are a useful tool for enhancing therapeutic precision in a range of conditions and should be conducted more often. To facilitate future meta-analysis, and the estimation of HTE, researchers reporting n-of-1 trial results should clearly describe individual data.

Adverse Events Associated With Pediatric Spinal Manipulation: A Systematic Review

BACKGROUND. Spinal manipulation is a noninvasive manual procedure applied to specific body tissues with therapeutic intent. Although spinal manipulation is commonly used in children, there is limited understanding of the pediatric risk estimates. OBJECTIVE. Our goal was to systematically identify and synthesize available data on adverse events associated with pediatric spinal manipulation. METHODS. A comprehensive search was performed of 8 major electronic databases (eg, Medline, AMED, MANTIS) from inception to June 2004 irrespective of language. Reports were included if they (1) were a primary investigation of spinal manipulation (eg, observation studies, controlled trials, surveys), (2) included a study population of children who were aged 18 years or younger, and (3) reported data on adverse events. Data were summarized to demonstrate the nature and severity of adverse events that may result rather than their incidence. RESULTS. Thirteen studies (2 randomized trials, 11 observational reports) were identified for inclusion. We identified 14 cases of direct adverse events involving neurologic or musculoskeletal events. Nine cases involved serious adverse events (eg, subarachnoidal hemorrhage, paraplegia), 2 involved moderately adverse events that required medical attention (eg, severe headache), and 3 involved minor adverse events (eg, midback soreness). Another 20 cases of indirect adverse events involved delayed diagnosis (eg, diabetes, neuroblastoma) and/or inappropriate provision of spinal manipulation for serious medical conditions (ie, meningitis, rhabdomyosarcoma). CONCLUSIONS. Serious adverse events may be associated with pediatric spinal manipulation; neither causation nor incidence rates can be inferred from observational data. Conduct of a prospective population-based active surveillance study is required to properly assess the possibility of rare, yet serious, adverse events as a result of spinal manipulation on pediatric patients.

Core Outcome Measures in Effectiveness Trials (COMET) initiative: protocol for an international Delphi study to achieve consensus on how to select outcome measurement instruments for outcomes included in a ‘core outcome set’

BackgroundThe Core Outcome Measures in Effectiveness Trials (COMET) initiative aims to facilitate the development and application of ‘core outcome sets’ (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The overall aim of the Core Outcome Measurement Instrument Selection (COMIS) project is to develop a guideline on how to select outcome measurement instruments for outcomes included in a COS. As part of this project, we describe our current efforts to achieve a consensus on the methods for selecting outcome measurement instruments for outcomes to be included in a COS.Methods/DesignA Delphi study is being performed by a panel of international experts representing diverse stakeholders with the intention that this will result in a guideline for outcome measurement instrument selection. Informed by a literature review, a Delphi questionnaire was developed to identify potentially relevant tasks on instrument selection. The Delphi study takes place in a series of rounds. In the first round, panelists were asked to rate the importance of different tasks in the selection of outcome measurement instruments. They were encouraged to justify their choices and to add other relevant tasks. Consensus was reached if at least 70% of the panelists considered a task ‘highly recommended’ or ‘desirable’ and if no opposing arguments were provided. These tasks will be included in the guideline. Tasks that at least 50% of the panelists considered ‘not relevant’ will be excluded from the guideline. Tasks that were indeterminate will be taken to the second round. All responses of the first round are currently being aggregated and will be fed back to panelists in the second round. A third round will only be performed if the results of the second round require it.DiscussionSince the Delphi method allows a large group of international experts to participate, we consider it to be the preferred consensus-based method for our study. Based upon this consultation process, a guideline will be developed on instrument selection for outcomes to be included in a COS.

The Safety of Pediatric Acupuncture: A Systematic Review

CONTEXT: Acupuncture is increasingly used in children; however, the safety of pediatric acupuncture has yet to be reported from systematic review. OBJECTIVE: To identify adverse events (AEs) associated with needle acupuncture in children. METHODS: Eighteen databases were searched, from inception to September 2010, irrespective of language. Inclusion criteria were that the study (1) was original peer-reviewed research, (2) included children from birth to 17 years, inclusively, (3) involved needle acupuncture, and (4) included assessment of AEs in a child. Safety data were extracted from all included studies. RESULTS: Of 9537 references identified, 450 were assessed for inclusion. Twenty-eight reports were included, and searches of reference lists identified 9 additional reports (total: 37). A total of 279 AEs were identified, 146 from randomized controlled trials, 95 from cohort studies, and 38 from case reports/series. Of the AEs, 25 were serious (12 cases of thumb deformity, 5 infections, and 1 case each of cardiac rupture, pneumothorax, nerve impairment, subarachnoid hemorrhage, intestinal obstruction, hemoptysis, reversible coma, and overnight hospitalization), 1 was moderate (infection), and 253 were mild. The mild AEs included pain, bruising, bleeding, and worsening of symptoms. We calculated a mild AE incidence per patient of 168 in 1422 patients (11.8% [95% confidence interval: 10.1–13.5]). CONCLUSIONS: Of the AEs associated with pediatric needle acupuncture, a majority of them were mild in severity. Many of the serious AEs might have been caused by substandard practice. Our results support those from adult studies, which have found that acupuncture is safe when performed by appropriately trained practitioners.

Heat Loss Prevention: A Systematic Review of Occlusive Skin Wrap for Premature Neonates

OBJECTIVE:To systematically identify and synthesize investigations of the effectiveness of occlusive skin wrap for reducing heat loss in premature infants born at less than 36 weeks gestations.STUDY DESIGN:Systematic review.RESULTS:Three randomized controlled trials (RCT) and five historical controlled trials (HCT) were included. Meta-analysis shows wrapped infants had significantly higher admission temperatures than unwrapped infants (RCTs WMD 0.63°C, 95% confidence interval (CI) 0.38, 0.87; HCTs WMD 0.96°C, 95% CI 0.66, 1.27). A statistically significant difference in mortality was not found between wrapped and unwrapped infants in the RCTs (RR 0.72, 95% CI 0.36, 1.45) or the HCTs (RR 0.76, 95% CI 0.51, 1.13).CONCLUSIONS:The findings suggest that occlusive skin wrap prevents heat loss in premature infants. The meta-analysis lacked the power to provide definitive results regarding the effect of wrap on mortality.