StaR Child Health: developing evidence-based guidance for the design, conduct, and reporting of pediatric trials.

Standards for Research in (StaR) Child Health was founded in 2009 to address the paucity and shortcomings of pediatric clinical trials. This initiative involves international experts who are dedicated to developing practical, evidence-based standards to enhance the reliability and relevance of pediatric clinical research. Through a systematic "knowledge to action" plan, StaR Child Health will make efforts to improve and expand the evidence base for child health across the world.

Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children.

BACKGROUND: Dehydration associated with gastroenteritis is a serious complication. Oral rehydration is an effective and inexpensive treatment, but some physicians prefer intravenous methods. OBJECTIVES: To compare oral with intravenous therapy for treating dehydration due to acute gastroenteritis in children. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists. We also contacted researchers, pharmaceutical companies, and relevant organizations. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing intravenous rehydration therapy (IVT) with oral rehydration therapy (ORT) in children up to 18 years of age with acute gastroenteritis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed quality using the Jadad score. We expressed dichotomous data as a risk difference (RD) and number needed to treat (NNT), and continuous data as a weighted mean difference (WMD). We used meta-regression for subgroup analyses. MAIN RESULTS: Seventeen trials (1811 participants), of poor to moderate quality, were included. There were more treatment failures with ORT (RD 4%, 95% confidence interval (CI) 1 to 7, random-effects model; 1811 participants, 18 trials; NNT = 25). Six deaths occurred in the IVT group and two in the ORT groups (4 trials). There were no significant differences in weight gain (369 participants, 6 trials), hyponatremia (248 participants, 2 trials) or hypernatremia (1062 participants, 10 trials), duration of diarrhea (960 participants, 8 trials), or total fluid intake at six hours (985 participants, 8 trials) and 24 hours (835 participants, 7 trials). Shorter hospital stays were reported for the ORT group (WMD -1.20 days, 95% CI -2.38 to -0.02 days; 526 participants, 6 trials). Phlebitis occurred more often in the IVT group (NNT 50, 95% CI 25 to 100) and paralytic ileus more often in the ORT group (NNT 33, 95% CI 20 to 100, fixed-effect model), but there was no significant difference between ORT using the low osmolarity solutions recommended by the World Health Organization and IVT (729 participants, 6 trials). AUTHORS' CONCLUSIONS: Although no clinically important differences between ORT and IVT, the ORT group did have a higher risk of paralytic ileus, and the IVT group was exposed to risks of intravenous therapy. For every 25 children (95% CI 14 to 100) treated with ORT one would fail and require IVT.

Acyclovir for treating varicella in otherwise healthy children and adolescents.

BACKGROUND: Acyclovir has the potential to shorten the course of illness which may result in reduced costs and morbidity associated with chickenpox. OBJECTIVES: 1) To examine the evidence evaluating the efficacy of acyclovir in alleviating symptoms of chickenpox and shortening the duration of illness. 2) To examine complications of chickenpox and adverse effects associated with acyclovir as reported in the relevant trials. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2005), MEDLINE (January 1966 to June 2005), and EMBASE (1988 to June 2005). The reference lists of all relevant articles were reviewed. The primary author of relevant studies and the pharmaceutical company that manufactures acyclovir were contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated otherwise healthy children zero to 18 years of age, with chickenpox. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the studies for eligibility. Two authors independently assessed methodological quality of the relevant studies using the Jadad scale and allocation concealment. Differences were resolved by consensus. Data were extracted by one author using a structured form and checked by a second. Continuous data were converted to the weighted mean difference (WMD). Weighted mean differences were combined into an overall estimate using random effects. There were too few studies to consider exploring statistical heterogeneity between studies (i.e., differences in reported effects), formally, or to assess for publication bias. MAIN RESULTS: Three studies were included. Study quality was three (n = 2) and four (n = 1) on the Jadad scale. Acyclovir was associated with a reduction in the number of days with fever (-1.1 days, 95% CI -1.3 to -0.9) and in reducing the maximum number of lesions (-76 lesions, -145 to -8). Results were less supportive with respect to the number of days to no new lesions and the number of days to the relief of itching. There were no clinically important differences between acyclovir and placebo with respect to complications associated with chickenpox or adverse effects associated with the treatment. AUTHORS' CONCLUSIONS: Acyclovir appears to be effective in reducing the number of days with fever and the maximum number of lesions among otherwise healthy children with chickenpox. The results were less convincing with respect to the number of days to no new lesions and relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains uncertain.

Long term effects of a home visit to prevent childhood injury: three year follow up of a randomized trial.

OBJECTIVE: To assess the long term effect of a home safety visit on the rate of home injury. DESIGN: Telephone survey conducted 36 months after participation in a randomized controlled trial of a home safety intervention. A structured interview assessed participant knowledge, beliefs, or practices around injury prevention and the number of injuries requiring medical attention. SETTING: Five pediatric teaching hospitals in four Canadian urban centres. PARTICIPANTS: Children less than 8 years of age presenting to an emergency department with a targeted home injury (fall, scald, burn, poisoning or ingestion, choking, or head injury while riding a bicycle), a non-targeted injury, or a medical illness. RESULTS: We contacted 774 (66%) of the 1172 original participants. A higher proportion of participants in the intervention group (63%) reported that home visits changed their knowledge, beliefs, or practices around the prevention of home injuries compared with those in the non-intervention group (43%; p<0.001). Over the 36 month follow up period the rate of injury visits to the doctor was significantly less for the intervention group (rate ratio = 0.74; 95% CI 0.63 to 0.87), consistent with the original (12 month) study results (rate ratio = 0.69; 95% CI 0.54 to 0.88). However, the effectiveness of the intervention appears to be diminishing with time (rate ratio for the 12-36 month study interval = 0.80; 95% CI 0.64 to 1.00). CONCLUSIONS: A home safety visit was able to demonstrate sustained, but modest, effectiveness of an intervention aimed at improving home safety and reducing injury. This study reinforces the need of home safety programs to focus on passive intervention and a simple well defined message.

Intravenous immunoglobulin for presumed viral myocarditis in children and adults.

BACKGROUND: Case reports and case series have described dramatic responses to IVIG in adults and children with presumed viral myocarditis. Administration of IVIG has become commonplace in the management of this condition. OBJECTIVES: To compare the outcome of patients with presumed viral myocarditis treated with IVIG to patients who did not receive IVIG. SEARCH STRATEGY: We searched CENTRAL (Issue 2, 2003), MEDLINE/PubMed (1966-2003), EMBASE (1988-2003), CINAHL (1982-2003), Web of Science (1975-2003), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers. SELECTION CRITERIA: Studies were included if: (1) patients had a clinical diagnosis of acute myocarditis with either a left ventricular ejection fraction (LVEF) <= 0.45, LVEDD of >2 SDs above the norm, or a shortening fraction (SF) >2 SDs below the mean and the duration of cardiac symptoms was less than six months; (2) patients had no evidence of non-infectious or bacterial cardiac disease; and, (3) patients were randomised to receive at least 1 gm/kg of IVIG versus no IVIG or placebo. Studies were excluded if: (1) patients had received immunosuppression prior to outcome assessment; or, (2) onset of myocarditis was less than six months postpartum. DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted independently by two reviewers. Meta-analysis was not possible because only one relevant study was found. MAIN RESULTS: The relevant study involved 62 adults with acute myocarditis randomized to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The incidence of death or requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (OR for event-free survival was 0.52 ,95% CI 0.12 to 2.30). Follow-up at six and 12 months showed equivalent improvement in LVEF (mean difference 0.00, 95% CI -0.07 to 0.07 at six months, mean difference 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (mean difference -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all appeared to be mild (OR 30.16, 95% CI 1.69 to 539.42). AUTHORS' CONCLUSIONS: Evidence from one trial does not support the use of IVIG for the management of adults with presumed viral myocarditis. There are no randomized paediatric trials. Further studies of the pathophysiology of this entity would lead to improved diagnostic criteria which would facilitate future research.

Epidemiology of electrical and lightning related deaths and injuries among Canadian children and youth.

Among burn injuries, electrical injuries constitute a small but devastating fraction. To describe the epidemiology of electrical injuries in Canadian children, data on deaths and emergency department visits related to electrical injuries, including lightning strikes, were obtained from provincial coroners' offices and the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) respectively, for the years 1991-96. Twenty one deaths and 606 emergency visits highlight that electrical related deaths, more frequent among school age children, are more likely the result of high voltage and lightning strike, while emergency department visits, more frequent among younger children, are more likely the result of low voltage. While the introduction of legislated standards for child safe outlets and educational programs for parents, children, and youth are recommended strategies toward reducing the frequency of these incidents, these strategies require further evaluation before their effectiveness can be estimated.

Acyclovir for treating varicella in otherwise healthy children and adolescents.

BACKGROUND: Acyclovir has the potential to shorten the course of illness which may result in reduced costs and morbidity associated with chickenpox. OBJECTIVES: 1) To examine the evidence evaluating the efficacy of acyclovir in alleviating symptoms of chickenpox and shortening the duration of illness. 2) To examine complications of chickenpox and adverse effects associated with acyclovir as reported in the relevant trials. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (1988 to April 2003). The reference lists of all relevant articles were reviewed. The primary author of relevant studies and the pharmaceutical company that manufactures acyclovir were contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated otherwise healthy children zero to 18 years of age, with chickenpox. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the studies for eligibility. Two reviewers independently assessed methodological quality of the relevant studies using the Jadad scale and allocation concealment. Differences were resolved by consensus. Data were extracted by one reviewer using a structured form and checked by a second.Continuous data were converted to the weighted mean difference (WMD). Weighted mean differences were combined into an overall estimate using random effects. There were too few studies to consider exploring statistical heterogeneity between studies (i.e., differences in reported effects), formally, or to assess for publication bias. MAIN RESULTS: Three studies were included. Study quality was three (n = 2) and four (n = 1) on the Jadad scale. Acyclovir was associated with a reduction in the number of days with fever (-1.1 days, 95% CI -1.3 to -0.9) and in reducing the maximum number of lesions (-76 lesions, -145 to -8). Results were less supportive with respect to the number of days to no new lesions and the number of days to the relief of itching. There were no clinically important differences between acyclovir and placebo with respect to complications associated with chickenpox or adverse effects associated with the treatment. REVIEWERS' CONCLUSIONS: Acyclovir appears to be effective in reducing the number of days with fever and the maximum number of lesions among otherwise healthy children with chickenpox. The results were less convincing with respect to the number of days to no new lesions and relief of itchiness. The clinical importance of acyclovir treatment in otherwise healthy children remains controversial.

Graduated driver licensing for reducing motor vehicle crashes among young drivers.

BACKGROUND: Graduated driver licensing (GDL) has been proposed as a means of reducing crash rates among novice drivers by gradually introducing them to higher risk driving situations. OBJECTIVES: To examine the effectiveness of GDL systems in reducing crash rates of young drivers. SEARCH STRATEGY: Studies were identified through searches of MEDLINE, EMBASE, CINAHL, Healthstar, Web of Science, NTIS Bibliographic Database, TRIS Online, SIGLE, the World Wide Web, relevant conference proceedings, consultation with experts and authors, and reference lists. The search was not restricted by language or publication status. SELECTION CRITERIA: Studies were included if: 1) they compared outcomes pre- and post-implementation of a GDL program within the same jurisdiction, 2) comparisons were made between jurisdictions with and without GDL, or 3) both. Studies had to report at least one objective, quantified outcome. Two reviewers independently screened searches and assessed the full text of potentially relevant studies for inclusion using a standard form. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by a second. Additional data were requested from authors. Results were not pooled due to substantial heterogeneity between studies. Percentage change was calculated for each year after the intervention, using one year prior to the intervention as the baseline rate. Results were adjusted by internal controls. Analyses were stratified by different denominators (population, licensed drivers). Results were calculated for the different crash types (overall, injury, fatal, night-time, alcohol, and those resulting in hospitalization). Results were presented for 16 year-olds alone and all teenage drivers combined. MAIN RESULTS: We included 13 studies evaluating 12 GDL programs that were implemented between 1979 and 1998 in the US (n=7), Canada (3), New Zealand (1), and Australia (1). Programs varied in their restrictions during the intermediate stage: e.g. night curfews (8); limitations of extra passengers (2); roadway restrictions (1). Based on the Insurance Institute for Highway Safety classification scheme, no programs were good, six were acceptable, five were marginal, and one was poor. Reductions in crash rates were seen in all jurisdictions and for all crash types. Among 16 year-old drivers, the median decrease in per population overall crash rates during the first year was 31% (range 26-41%). Per population injury crash rates were similar (median 28%, range 4-43%). Results for all teenage drivers, rates per licensed driver, and rates adjusting for internal controls were generally reduced when comparing within jurisdictions. REVIEWERS' CONCLUSIONS: The existing evidence shows that GDL is effective in reducing the crash rates of young drivers, although the magnitude of the effect is unclear. The conclusions are supported by consistent direction of the findings, and the temporal relationship and plausibility of the association. The reviewers have made recommendations for primary research on GDL (e.g. study methods, standardized reporting of outcomes and results, long-term follow-up). The project has also shown what is needed to carry out systematic reviews of observational studies (e.g. quality assessment instruments).

Glucocorticoids for croup.

BACKGROUND: Since the initial version of this systematic review in 1997, a number of randomised trials examining the benefit of glucocorticoids have been published, reflecting a continued interest in the use of glucocorticoids to treat patients with croup. The objective of this review was to provide evidence to guide clinicians in their treatment of patients with croup by determining the effectiveness of glucocorticoids and to identify areas of uncertainty for future research. OBJECTIVES: To determine the effect of glucocorticoids for children with croup. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to April 2003) and Excerpta Medica/EMBASE (January 1974 to August 2003). We also contacted authors of identified croup trials published in the last ten years to inquire about additional published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials that examine children with croup and objectively measure the effectiveness of glucocorticoid treatment. DATA COLLECTION AND ANALYSIS: Based on review of the title and abstract (when available), two researchers identified studies for potential relevance. The complete text was retrieved and using a priori inclusion criteria, the studies were independently reviewed for relevance by two reviewers. Two observers independently assessed quality. Differences with respect to inclusion status and quality assessment were resolved by consensus. Data were extracted using a structured form by one reviewer and checked for accuracy by a second reviewer. Standard statistical analyses were performed. MAIN RESULTS: Thirty-one studies were deemed relevant for inclusion (N = 3736). Glucocorticoid treatment was associated with an improvement in the Westley score at six hours with a weighted mean difference of -1.2 (95% confidence interval -1.6 to -0.8) and at 12 hours -1.9 (-2.4 to -1.3); at 24 hours this improvement was no longer significant (-1.3, -2.7 to 0.2). Fewer return visits and/or (re)admissions occurred in patients treated with glucocorticoids (relative risk 0.50; 0.36 to 0.70). Length of time spent in accident and emergency or hospital (weighted mean difference 12 hours, five to 19 hours) was significantly decreased for patients treated with glucocorticoids. Use of epinephrine decreased for children treated with a glucocorticoid (risk difference 10%; 1 to 20). No other decreases in additional treatments were found in the primary analysis. Publication bias does not impact results importantly. No between-trial significant differences were found between populations with mild and moderate croup. Oral dexamethasone may be superior to intramuscular dexamethasone. REVIEWER'S CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as six hours after treatment. Fewer return visits and/or (re)admissions are required and the length of time spent in hospital is decreased in inpatients. Dexamethasone is also effective in mild croup populations. Research is required to examine the most beneficial method for disseminating croup practice guidelines and to increase the uptake of evidence to improve outcomes.

Epinephrine for bronchiolitis.

BACKGROUND: Bronchodilators are commonly used in the management of bronchiolitis. A recent systematic review showed that bronchodilators produce modest short-term benefit among patients with mild or moderate bronchiolitis. OBJECTIVES: To compare epinephrine versus placebo and other bronchodilators in infants less than 2 years of age with bronchiolitis. SEARCH STRATEGY: Electronic searches were conducted on the following bibliographic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (January 1988 to May 2003). The reference lists of all selected articles were examined for relevant studies. Primary authors were contacted for information on additional trials. SELECTION CRITERIA: Studies were included if they: 1) were RCTs comparing epinephrine with placebo or other bronchodilator; 2) involved children less than two years with bronchiolitis; 3) presented at least one quantitative outcome. DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted by one reviewer using a structured form and checked by a second. Separate analyses were conducted for the two types of control groups (placebo, non-epinephrine bronchodilators) and for patient status (inpatient, outpatient). MAIN RESULTS: Fourteen studies were included. Quality ranged from one to five (Jadad scale) with a median of three (inter-quartile range: two to three). Allocation concealment was adequate in six trials and unclear in eight. Among inpatient studies comparing epinephrine and placebo (n = five), there was one significant outcome favouring epinephrine: change in clinical score at 60 minutes post-treatment (SMD -0.52; 95% CI -1.00,-0.03). For outpatient studies (n = three), change in clinical score at 60 minutes (SMD -0.81; -1.56,-0.07), change in oxygen saturation at 30 minutes (WMD 2.79;1.50,4.08), respiratory rate at 30 minutes (WMD -4.54;-8.89-0.19), and "improvement" (OR 25.06; 4.95,126.91) favoured epinephrine. Heart rate at 60 minutes post-treatment favoured placebo (WMD 11.80; 5.20,18.40). Admission rates and change in oxygen saturation at 60 minutes post-treatment were not significantly different. For inpatient studies comparing epinephrine and salbutamol (n = four), only one of the seven outcomes was statistically significant: respiratory rate at 30 minutes favoured epinephrine (WMD -5.12; -6.83;-3.41). Among outpatient studies (n = four), change in oxygen saturation at 60 minutes (WMD 1.91; 0.38,3.44), heart rate at 90 minutes (WMD -14.00; -22.95;-5.05), respiratory rate at 60 minutes (WMD -7.76; -11.35,-4.17) post-treatment and "improvement" (OR 4.51; 1.93,10.53) favoured epinephrine. Admission rates were not significantly different (OR 0.40; 0.12,1.33). Pallor at 30 minutes post-treatment was significantly higher in the epinephrine group (OR 6.00; 1.33,27.00). REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among inpatients. There is some evidence to suggest that epinephrine may be favourable to salbutamol and placebo among outpatients. A number of large, multi-centered trials are required to examine the effectiveness of epinephrine compared to placebo and salbutamol for infants presenting to outpatient settings. There is a need to develop a validated, reliable scoring system that is sensitive to important clinical changes in patients with bronchiolitis.

The inclusion of reports of randomised trials published in languages other than English in systematic reviews.

OBJECTIVE: To assemble a large dataset of language restricted and language inclusive systematic reviews, including both conventional medicinal (CM) and complementary and alternative medicine (CAM) interventions. To then assess the quality of these reports by considering and comparing different types of systematic reviews and their associated RCTs; CM and CAM interventions; the effect of language restrictions compared with language inclusions, and whether these results are influenced by other issues, including statistical heterogeneity and publication bias, in the systematic review process. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Centralised Information Service for Complementary Medicine. REVIEW METHODS: Three types of systematic reviews were included: language restricted; language inclusive/English language (EL) reviews that searched RCTs in languages other than English (LOE) but did not find any and, hence, could not include any, in the quantitative data synthesis; and systematic reviews that searched for RCTs in LOE and included them in the quantitative data synthesis. Fisher's exact test was applied to compare the three different types of systematic reviews with respect to their reporting characteristics and the systematic review quality assessment tool. The odds ratio of LOE trials versus EL trials was computed for each review and this information was pooled across the reviews to examine the influence that language of publication and type of intervention (CM, CAM) have on the estimates of intervention effect. Several sensitivity analyses were performed. RESULTS: The LOE RCTs were predominantly in French and German. Language inclusive/LOE systematic reviews were of the highest quality compared with the other types of reviews. The CAM reviews were of higher quality compared with the CM reviews. There were only minor differences in the quality of reports of EL RCTs compared with the eight other languages considered. However, there are inconsistent differences in the quality of LOE reports depending on the intervention type. The results, and those reported previously, suggest that excluding reports of RCTs in LOE from the analytical part of a systematic review is reasonable. Because the present research and previous efforts have not included every type of CM RCT and the resulting possibility of the uncertainty as to when bias will be present by excluding LOE, it is always prudent to perform a comprehensive search for all evidence. This result only applies to reviews investigating the benefits of CM interventions. This does not imply that systematic reviewers should neglect reports in LOE. We recommend that systematic reviewers search for reports regardless of the language. There may be merit in including them in some aspects of the review process although this decision is likely to depend on several factors, including fiscal and other resources being available. Language restrictions significantly shift the estimates of an intervention's effectiveness when the intervention is CAM. Here, excluding trials reported in LOE, compared with their inclusion, resulted in a reduced intervention effect. The present results do not appear to be influenced by statistical heterogeneity and publication bias. CONCLUSIONS: With the exception of CAM systematic reviews, the quality of recently published systematic reviews is less than optimal. Language inclusive/LOE systematic reviews appear to be a marker for a better quality systematic review. Language restrictions do not appear to bias the estimates of a conventional intervention's effectiveness. However, there is substantial bias in the results of a CAM systematic review if LOE reports are excluded from it.

Acyclovir for treating varicella in otherwise healthy children and adolescents.

BACKGROUND: Acyclovir has the potential to shorten the course of illness which may result in reduced costs and morbidity. OBJECTIVES: 1) To examine the evidence evaluating the efficacy of acyclovir in alleviating symptoms and shortening the duration of illness. 2) To examine complications of chickenpox and adverse effects associated with acyclovir as reported in the relevant trials. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (2002, Issue 2), MEDLINE (January 1966 to October 2001), EMBASE (1988 to September 2001). The reference lists of all relevant articles were reviewed. The primary author of relevant studies and the pharmaceutical company that manufactures acyclovir were contacted. SELECTION CRITERIA: Randomized controlled trials that evaluated otherwise healthy children 0-18 years of age with chickenpox. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the studies for eligibility. Two reviewers independently assessed methodological quality of the relevant studies using the Jadad scale and allocation concealment. Differences were resolved by consensus. Data were extracted by one reviewer using a structured form and checked by a second. Continuous data were converted to the weighted mean difference (WMD). Weighted mean differences were not combined into an overall estimate due to the varied age groups between studies. There were too few studies to consider statistical heterogeneity between studies (i.e., differences in reported effects), to perform subgroup or sensitivity analyses, or to assess for publication bias. MAIN RESULTS: Three studies were included. Study quality was three (n=2) and four (n=1) on the Jadad scale. Acyclovir was associated with a reduction in the number of days with fever, from -1.0 (95% CI -1.5,-0.5) to -1.3 (95% CI -2.0,-0.6). Results were inconsistent with respect to the number of days to no new lesions, the maximum number of lesions and the number of days to the relief of itching. There were no clinically important differences between acyclovir and placebo with respect to complications associated with chickenpox or adverse effects associated with the drug. REVIEWER'S CONCLUSIONS: Acyclovir appears to be effective in reducing the number of days with fever among otherwise healthy children with chickenpox. The results were inconsistent with respect to the number of days to no new lesions, relief of itchiness and maximum number of lesions. The clinical importance of acyclovir treatment in otherwise healthy children remains controversial.

The effectiveness of a home visit to prevent childhood injury.

OBJECTIVE: To examine the effectiveness of a home visit program to improve home safety and decrease the frequency of injury in children. We examined the effects of the program on 1) parental injury awareness and knowledge; 2) the extent that families used home safety measures; 3) the rate of injury; and 4) the cost effectiveness of the intervention. DESIGN: A randomized, controlled trial. SETTING: A multicenter trial conducted at 5 hospitals in 4 Canadian urban centers. PARTICIPANTS: Children <8 years old, initially enrolled in an injury case-control study, were eligible to participate. Intervention. Subsequent to a home inspection conducted to determine baseline hazard rates for both groups, participants in the intervention group received a single home visit that included the provision of an information package, discount coupons, and specific instruction regarding home safety measures. MAIN RESULTS: The median age was 2 years, with males comprising ~60% of participants. The experimental groups were comparable at outset in terms of case-control status, age, gender, and socioeconomic status. Parental injury awareness and knowledge was high; 73% correctly identified injury as the leading cause of death in children, and an intervention effect was not demonstrated. The adjusted odds ratios (ORs) for the home inspection items indicated that significant safety modifications only occurred in the number of homes having hot water not exceeding 54 degrees C (OR: 1.31, 95% confidence interval [CI]: 1.14, 1.50) or the presence of a smoke detector (OR: 1.45, 95% CI: 0.94, 2.22). However, the intervention group reported home safety modifications of 62% at 4 months and significantly less injury visits to the doctor compared with the nonintervention group (rate ratio: 0.75; 95% CI: 0.58, 0.96). The total costs of care for injuries were significantly lower in the intervention group compared with the nonintervention group with a cost of $372 per injury prevented. CONCLUSIONS: An intervention using a single home visit to improve the extent to which families use safety measures was found to be insufficient to influence the long-term adoption of home safety measures, but was effective to decrease the overall occurrence of injuries. Future programs should target a few, well-focused, evidence-based areas including the evaluation of high-risk groups and the effect of repeated visits on outcome.

Is there a "best" way to detect and minimize publication bias? An empirical evaluation.

Using 14 meta-analyses that included both published (n = 199) and unpublished (n = 50) randomized trials, we evaluated the utility of different analytical approaches to detect, assess robustness, and minimize publication bias in meta-analysis. The rank correlation and graphical tests indicated funnel plot asymmetry in 3 and 7 of the 14 meta-analyses, respectively. The file drawer number estimates using Iyengar-Greenhouse method were between 1.5 and 4.7 times smaller compared to Rosenthal's estimates. The median difference between the Trim and Fill estimates and the actual number of missing studies was 1 (range -4, 6). Weighted estimation methods adjusted for publication bias and provided estimates of intervention effect close to the reference standard, on average. We showed there are differences in the conclusions one would reach clinically based on the different analytical approaches dealing with publication bias. Our results also suggest that the appropriate use of these methods improves the reliability and accuracy of meta-analysis.

The efficacy of nebulized racemic epinephrine in children with acute asthma: a randomized, double-blind trial.

OBJECTIVES: Recent work in bronchiolitis has demonstrated a significant clinical improvement in children treated with epinephrine over nebulized salbutamol. The objective of this study was to determine whether nebulized epinephrine, as compared with nebulized salbutamol, causes a greater clinical improvement in children with acute asthma. METHODS: Children, aged 1 to 17 years, with acute asthma presenting to the emergency department (ED) were eligible. In this double-blind study, patients were randomly allocated to receive either salbutamol or racemic epinephrine by nebulization at 0, 20, and 40 minutes. All patients received oral steroids. The primary outcome measure was a change in pulmonary index score (PIS). RESULTS: One hundred twenty patients were randomized. The groups were comparable in terms of age, gender, asthma severity, previous treatments, and use of inhaled steroids. There was no significant difference between treatments in the change in PIS, length of stay, admission to hospital, or relapse rate. The epinephrine-treated group had significantly more minor side effects (such as excess or brownish nasal discharge). CONCLUSIONS: There is no significant clinical benefit of nebulized epinephrine over salbutamol in children 1-17 years old with mild to moderate acute asthma. Salbutamol remains the treatment of choice in children with known asthma.

What contributions do languages other than English make on the results of meta-analyses?

Including only a portion of all available evidence may introduce systematic errors into the meta-analytic process and threaten its validity. We set out to examine whether language restricted meta-analyses, compared to language inclusive meta-analyses, provide different estimates of the effectiveness of interventions evaluated in randomized trials. We identified and retrieved all 79 meta-analyses from several disease areas in which explicit eligibility criteria regarding trial selection were reported. General characteristics and quality of reporting of the meta-analyses were assessed using a validated instrument. We explored the effects of language of publication of the randomized trials on the quantitative results using logistic regression analyses. Language restricted meta-analyses, compared to language inclusive meta-analyses, did not differ with respect to the estimate of benefit of the effectiveness of an intervention (ROR = 0.98; 95% CI: 0.81-1.17). These results were also robust after a series of sensitivity analyses. This study provides no evidence that language restricted meta-analyses lead to biased estimates of intervention effectiveness. We encourage others to replicate this study using different sampling frames, clinical topics and interventions.

Variation in utilization of computed tomography scanning for the investigation of minor head trauma in children: a Canadian experience.

OBJECTIVES: To compare the utilization rates of CT scans in investigating minor head trauma in children in Canada, to identify the injuries determined by these scans, and to identify clinical findings that are highly associated with its diagnosis and the injury itself. METHODS: A retrospective cohort study involving nine pediatric hospitals in Canada was conducted. A structured data collection method was used. Inclusion criteria included age 16 years or less, history of blunt head trauma, and a Glasgow Coma Scale score (GCS) greater than or equal to 13. Data collected included demographic information, type of injury, relevant clinical information, computed tomography (CT) scan data, and clinical outcome. Clinical findings associated with CT scan and positive CT scan were identified using logistic regression. RESULTS: One thousand one hundred sixty-four children were included in the study. One hundred seventy-one (15%) had a CT scan, of which 60 (35%) were abnormal. There was a significant difference in the rate of ordering of CT scans among the participating hospitals, but no significant difference in the rate of abnormal CT scans. Mechanism of injury, GCS, and loss of consciousness were significantly related to the presence of an abnormal CT scan. CONCLUSIONS: Although there is a significant difference in the utilization of CT scans to investigate minor head trauma in children across Canada, there is no significant difference in the frequency of head injuries in these patients. This suggests that it may be possible to determine clinical criteria that are predictive of a head injury in these patients.

Community-based injury prevention interventions.

Community-based interventions offer a promising solution for reducing child and adolescent unintentional injuries. By focusing on altering behavior, promoting environmental change within the community, or passing and enforcing legislation, these interventions seek to change social norms about acceptable safety behaviors. This article systematically reviews 32 studies that evaluated the impact of community-based injury prevention efforts on childhood injuries, safety behaviors, and the adoption of safety devices. Interventions targeted schools, municipalities, and cities. Most relied on an educational approach, sometimes in combination with legislation or subsidies, to reduce the cost of safety devices such as bicycle helmets. Results indicate that community-based approaches are effective at increasing some safety practices, such as bicycle helmet use and car seat use among children. The evidence is less compelling that such interventions increase child pedestrian safety, increase adolescent vehicle safety by reducing drinking and driving behaviors, or reduce rates of several categories of childhood injuries. Strong evidence supporting the effectiveness of community-based interventions is lacking, in part because few studies used randomized controlled designs or examined injury rates among children and youths as outcome measures. Nonetheless, this review identifies common elements of successful community-based approaches that should be replicated in future studies. First, the use of multiple strategies grounded in a theory of behavior change is critical. Second, to maximize success, interventions should be integrated into the community and approaches should be tailored to meet unique community needs. Third, community stakeholders should be included in the development of community-based strategies. This community involvement and ownership of the intervention increases the likelihood of modeling and peer pressure, leading to widespread adoption of a safety behavior. Finally, when possible, a randomized controlled design should be used to maximize the trustworthiness of reported findings and aid decisions about where to invest resources in community-based approaches to injury prevention.

Short course antibiotics for acute otitis media.

BACKGROUND: Otitis media is a common pediatric problem, for which antibiotics are frequently prescribed. OBJECTIVES: To determine the effectiveness of a short course of antibiotics (less than seven days) in comparison to a longer course (seven days or greater) for the treatment of acute otitis media in children. SEARCH STRATEGY: The medical literature was searched for randomized controlled studies of the treatment of ear infections in children with antibiotics published from January 1966 to July 1997. Search last updated March 1998. SELECTION CRITERIA: Studies were included if they met the following criteria: subjects one month to 18 years of age, clinical diagnosis of ear infection, no previous antimicrobial therapy and randomization to treatment with less than seven days versus seven days or more of antibiotics. DATA COLLECTION AND ANALYSIS: Data on treatment outcomes were extracted from individual studies, and combined in the form of a summary odds ratio. A summary odds ratio (OR) equivalent to one indicated that the treatment failure rate following less than seven days of antibiotic treatment was similar to the failure rate following seven days or more of antibiotic. MAIN RESULTS: The summary OR for treatment outcomes at eight to 19 days in 1,524 children treated with short-acting antibiotics for five days versus eight to 10 days was 1.52, 95% CI: 1.17-1.98, but by 20 to 30 days outcomes between treatment groups (n=2,115) were comparable (OR=1.22, 95% CI:0.98-1.54). The absolute difference in treatment failure (Random effects model RD=2.9%, 95%CI:-0.3% to 6.1%) at 20 to 30 days suggests that at minimum 17 children would need to be treated with the long course of short-acting antibiotics to avoid one treatment failure. Similarity in outcomes was observed for up to three months following therapy (OR=1.16,95% CI=0.9-1.5). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and more than seven days of other antibiotics. REVIEWER'S CONCLUSIONS: This review suggests that five days of short-acting antibiotic is effective treatment for uncomplicated ear infections in children.