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.

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.

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.

The efficacy of nebulized budesonide in dexamethasone-treated outpatients with croup.

OBJECTIVE: To determine the added clinical benefit of nebulized budesonide in children with mild to moderate croup treated with 0.6 mg/kg oral dexamethasone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Emergency department of a tertiary-care pediatric hospital with 47,000 visits per year. PARTICIPANTS: Children 3 months to 5 years of age with a syndrome consisting of hoarseness, inspiratory stridor, and barking cough and a croup score of 3 or greater after at least 15 minutes of mist therapy. Patients were excluded from the study if they had diagnoses of epiglottitis, chronic upper or lower airway disease (not including asthma), or severe croup or had received corticosteroids within the preceding 2 weeks. INTERVENTION: All patients received 0.6 mg/kg oral dexamethasone and were randomly assigned to receive 4 mL (2 mg) of budesonide solution (n=25) or 4 mL of 0.9% saline solution (n=25) by updraft nebulizer with a continuous flow of oxygen at 5 to 6 L/min. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients in each group who had clinically important changes (two points) in the croup score during the 4 hours after treatment. RESULTS: Eighty-four percent (n=21) of the patients who received budesonide had clinically important responses, compared with 56% (n=14) in the placebo group. The number of patients who would need to be treated with nebulized budesonide for one patient to have a clinically important response is four patients. CONCLUSIONS: Despite receiving simultaneous oral dexamethasone, pediatric outpatients with mild to moderate croup have added, clinically important improvement in respiratory symptoms after treatment with budesonide.

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.

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.

Efficacy of ipratropium bromide in acute childhood asthma: a meta-analysis.

PURPOSE: To determine whether inhaled ipratropium bromide provides an additive, clinically important improvement in children with acute asthma who are being treated with beta 2-agonists. METHODS: An English-language literature search was conducted employing MEDLINE (1966 to 1992), Science Citation Index (1986 to 1992) using key citations, bibliographic reviews of primary research and review articles, and correspondence with authors of recent articles. After independent review by two observers, six studies were selected on the basis of prespecified selection criteria. Two observers independently assessed the selected papers by using explicit methodologic criteria for evaluating the quality of studies dealing with therapeutic intervention. RESULTS: None of the six studies found a significant difference in clinical rating score, admission rate, or length of stay in hospital between the ipratropium bromide and the control groups. The three studies with the highest methodologic validity measured the change in percentage predicted forced expiratory volume in 1 second (FEV1) from baseline to 60 minutes. The pooled effect size (95% CI) for these studies was 0.88 (0.42-1.34), which translates to an improvement in percentage predicted FEV1 over the control group of 12.5% (95% CI, 6.6-18.4). In a subset of 23 children who had severe airway obstruction, peak expiratory flow rate (PEFR) responded better to a beta 2-agonist alone (p = 0.007). CONCLUSION: The existing evidence reveals that the addition of ipratropium bromide to a beta 2-agonist offers a statistically significant improvement in percentage predicted FEV1 but no clinical improvement. As it may cause deterioration in PEFR in severely asthmatic children, ipratropium bromide should not be used universally for acute childhood asthma until further research determines the clinical significance of these spirometric changes.

Agreement in the interpretation of extremity radiographs of injured children and adolescents.

OBJECTIVES: To measure agreement beyond chance (kappa) for comparison interpretations of extremity radiographs by pediatric radiologists and emergency physicians (EPs) and to identify factors associated with disagreement. METHODS: A random sample of 205 radiographs was selected from 1,016 patients having x-rays of their extremities in the emergency and radiology departments of a tertiary care pediatric hospital. Interpretations by the "official" reporting pediatric radiologist (ORPR), the treating EP, and a pediatric radiologist blinded to all clinical information (BPR) were compared for three categories: "abnormal" (one or more of fracture, dislocation, or effusion); "possibly abnormal"; and "normal." RESULTS: The overall weighted kappa (Kw) for the ORPRs and the EPs was 0.55. For fractures alone, the Kw for the ORPRs vs the EPs was 0.77; and for effusions alone, the value was 0.34. The Kw for the ORPRs vs the BPR was 0.63 (range 0.43-0.83 for individual ORPRs). The main areas of disagreement were in the identification of joint effusions and of nondisplaced fractures of the phalanges, elbow joint, tarsals, or metatarsals. CONCLUSIONS: There is good agreement between EPs and pediatric radiologists in interpreting extremity radiographs of injured children and adolescents. Disagreement occurs mainly for effusions or minor fractures and for the elbow region. Because of the importance of recognizing abnormalities in this region, an educational intervention to improve this area of deficiency is recommended.

The use of antibiotics to prevent serious sequelae in children at risk for occult bacteremia: a meta-analysis.

OBJECTIVE: To determine whether antibiotics prevent serious bacterial infections in children at risk for occult bacteremia. METHODS: Meta-analysis of randomized controlled trials involving children aged 3 months to 36 months without a focus of infection and randomized into 2 treatment groups: 1) no antibiotic vs antibiotic or 2) IM ceftriaxone vs oral antibiotic. RESULTS: The use of either an oral antibiotic or IM ceftriaxone did trend toward a reduced risk of serious infection, although neither reached statistical significance (OR = 0.60; 95% CI 0.10, 3.49; and OR = 0.38; 95% CI 0.12, 1.17, respectively). It would be necessary to treat 414 patients to prevent 1 serious bacterial infection. When only children with proven occult bacteremia were analyzed, the use of IM ceftriaxone was statistically significant in preventing serious bacterial infections (OR = 0.25; 95% CI 0.07, 0.89). CONCLUSIONS: Clinical judgment should not be replaced by widespread antibiotic use in the approach to a child with fever. If rapid methods to identify children with occult bacteremia, such as polymerase chain reaction, could be improved and become widely available, then antibiotics could be used judiciously on initial visits. Antibiotic use in all children at risk for occult bacteremia implies the treatment of many children unlikely to benefit from such therapy.

Randomized, controlled trial of inhaled budesonide as an adjunct to oral prednisone in acute asthma.

OBJECTIVE: To compare the clinical effect of nebulized budesonide with placebo in acute pediatric asthma. METHODS: A randomized, controlled, double-blind trial with parallel design was used in the ED of a tertiary care children's hospital. Children aged 6 months to 18 years with a moderate to severe exacerbation of asthma [Pulmonary Index Score (PIS) > or = 5 or < or = 11 after a salbutamol nebulization of 0.15 mg/kg] were eligible. All patients received prednisone 1 mg/kg orally and nebulized salbutamol (0.15 mg/kg) every 30 minutes for 3 doses and then every hour for 4 hours. The intervention was 2 mg (4 mL) of nebulized budesonide or 4 mL of nebulized normal saline. RESULTS: Baseline characteristics were comparable in the budesonide group (n = 24) and in the placebo group (n = 20). There were no significant differences in the primary outcome measure (PIS) between the 2 groups. However, the PIS at 1 hour had a tendency to be lower in the budesonide group (median = 5) as compared with the placebo group (median = 6; p = 0.07). Survival analysis of release/discharge from the ED/hospital showed a more rapid rate in the budesonide group as compared with the placebo group (p = 0.02). No adverse effects were seen. CONCLUSION: Although these preliminary results suggest that nebulized budesonide may be an effective adjunct to oral prednisone in the management of moderate to severe asthma exacerbations, a larger trial will be required before the widespread use of inhaled budesonide in acute asthma can be advocated.

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.

A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate in the management of selected pediatric facial lacerations.

OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children. METHODS: This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months. RESULTS: Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores. CONCLUSIONS: In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.

Validation of the Ottawa Ankle Rules in children with ankle injuries.

OBJECTIVES: The Ottawa Ankle Rules (OAR) have been found to be 100% sensitive in adult patients with ankle injuries, and application of the OAR has resulted in a 28% reduction in the number of x-rays ordered. The objectives of this study were to determine the sensitivity and specificity of the OAR in children and to determine the potential change in x-ray utilization. METHODS: Children, aged 2-16 years, presenting to the EDs of two children's hospitals, with an ankle injury in the previous 48 hours, were enrolled. All patients were assessed by either staff physicians or fellows. X-rays were ordered according to standard clinical practice. Prior to reviewing x-rays, the physical examination was recorded on a standardized form. Positive outcomes (clinically significant) were defined as fractures with fragments > or =3 mm. Patients not x-rayed and asymptomatic at five to seven days postinjury were considered to have no significant fracture. RESULTS: Six hundred seventy patients were enrolled. The OAR were 100% sensitive (95% CI = 95% to 100%) for significant ankle fractures, with a specificity of 24% (95% CI = 20% to 28%). The OAR were 100% sensitive (95% CI = 82% to 100%) for the midfoot, with a specificity of 36% (95% CI = 29% to 43%). If the OAR had been followed, there would have been a reduction of ankle x-rays by 16% and foot x-rays by 29% without missing any clinically significant fracture. However, analysis of the two hospitals showed that if the rules had been applied, one would have a reduction in x-rays, while the other center would have an increase. CONCLUSIONS: This study demonstrates the OAR to be sensitive for detecting clinically significant (> or =3 mm) ankle and midfoot fractures in children. The application of these rules may reduce the number of x-rays ordered. A further study is required to determine the effect of using the OAR in clinical practice.

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.

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.

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.

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.

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.

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).

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.