Assessment of Usefulness of Randomized Control Trials in Child Health Research Published in 2007 and 2017.

OBJECTIVE: To examine how clinical usefulness in pediatric research with randomized controlled trials (RCTs) has changed over a 10-year period via a research usefulness tool composed of unique clinical usefulness criteria. STUDY DESIGN: We leveraged a pre-existing sample of child health RCTs published in 2007, used by our team in a previous study. Using the same methods, a research librarian executed a literature search in the Cochrane Central Register of Controlled Trials for the 2017 cohort. We included the first 300 eligible citations from the randomly ordered list for each year, creating two cohorts of 300 publications each, 1 in 2007 and 1 in 2017. Each publication was analyzed and data regarding primary and secondary outcomes, as well as 11 unique criteria of clinical usefulness, were extracted. Each publication was then graded using a tool created by our research team. After quality review, statistical analysis was then performed. RESULTS: Six hundred pediatric RCT publications were included in this review. The mean score increased from 6.07 in 2007 to 9.20 in 2017 (P < .001). Usefulness factors that saw the largest increase in reporting were context placement, funding statements, and conflict of interest statements, while patient centeredness, value for money, and raw data availability remained infrequently reported. CONCLUSION: Our results demonstrate that clinical usefulness of pediatric research improved over this 10-year period, but there are still areas that need a great deal of improvement in order to maximize clinical usefulness and reduce research waste.

A Decade of Efforts to Add Value to Child Health Research Practices.

OBJECTIVE: To identify practices that add value to improve the design, conduct, and reporting of child health research and reduce research waste. STUDY DESIGN: In order to categorize the contributions of members of Standards for Research (StaR) in Child Health network, we developed a novel Child Health Improving Research Practices (CHIRP) framework comprised of 5 domains meant to counteract avoidable child health research waste and improve quality: 1) address research questions relevant to children, their families, clinicians, and researchers; 2) apply appropriate research design, conduct and analysis; 3) ensure efficient research oversight and regulation; 4) Provide accessible research protocols and reports; and 5) develop unbiased and usable research reports, including 17 responsible research practice recommendations. All child health research relevant publications by the 48 original StaR standards' authors over the last decade were identified, and main topic areas were categorized using this framework. RESULTS: A total of 247 publications were included in the final sample: 100 publications (41%) in domain 1 (3 recommendations), 77 publications (31%) in domain 2 (3), 35 publications (14%) in domain 3 (4), 20 publications (8%) in domain 4 (4), and 15 publications (6%) in domain 5 (3). We identified readily implementable "responsible" research practices to counter child health research waste and improve quality, especially in the areas of patients and families' engagement throughout the research process, developing Core Outcome Sets, and addressing ethics and regulatory oversight issues. CONCLUSION: While most of the practices are readily implementable, increased awareness of methodological issues and wider guideline uptake is needed to improve child health research. The CHIRP Framework can be used to guide responsible research practices that add value to child health research.

Nebulised hypertonic saline solution for acute bronchiolitis in infants.

BACKGROUND: Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (≥ 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and updated in 2010, 2013, and 2017. OBJECTIVES: To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 13 January 2022. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 13 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department (ED) trials was rate of hospitalisation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics. MAIN RESULTS: We included six new trials (N = 1010) in this update, bringing the total number of included trials to 34, involving 5205 infants with acute bronchiolitis, of whom 2727 infants received hypertonic saline. Eleven trials await classification due to insufficient data for eligibility assessment. All included trials were randomised, parallel-group, controlled trials, of which 30 were double-blinded. Twelve trials were conducted in Asia, five in North America, one in South America, seven in Europe, and nine in Mediterranean and Middle East regions. The concentration of hypertonic saline was defined as 3% in all but six trials, in which 5% to 7% saline was used. Nine trials had no funding, and five trials were funded by sources from government or academic agencies. The remaining 20 trials did not provide funding sources. Hospitalised infants treated with nebulised hypertonic saline may have a shorter mean length of hospital stay compared to those treated with nebulised normal (0.9%) saline or standard care (mean difference (MD) -0.40 days, 95% confidence interval (CI) -0.69 to -0.11; 21 trials, 2479 infants; low-certainty evidence). Infants who received hypertonic saline may also have lower postinhalation clinical scores than infants who received normal saline in the first three days of treatment (day 1: MD -0.64, 95% CI -1.08 to -0.21; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 893 infants; day 2: MD -1.07, 95% CI -1.60 to -0.53; 10 trials (1 outpatient, 1 ED, 8 inpatient trials), 907 infants; day 3: MD -0.89, 95% CI -1.44 to -0.34; 10 trials (1 outpatient, 9 inpatient trials), 785 infants; low-certainty evidence). Nebulised hypertonic saline may reduce the risk of hospitalisation by 13% compared with nebulised normal saline amongst infants who were outpatients and those treated in the ED (risk ratio (RR) 0.87, 95% CI 0.78 to 0.97; 8 trials, 1760 infants; low-certainty evidence). However, hypertonic saline may not reduce the risk of readmission to hospital up to 28 days after discharge (RR 0.83, 95% CI 0.55 to 1.25; 6 trials, 1084 infants; low-certainty evidence). We are uncertain whether infants who received hypertonic saline have a lower number of days to resolution of wheezing compared to those who received normal saline (MD -1.16 days, 95% CI -1.43 to -0.89; 2 trials, 205 infants; very low-certainty evidence), cough (MD -0.87 days, 95% CI -1.31 to -0.44; 3 trials, 363 infants; very low-certainty evidence), and pulmonary moist crackles (MD -1.30 days, 95% CI -2.28 to -0.32; 2 trials, 205 infants; very low-certainty evidence). Twenty-seven trials presented safety data: 14 trials (1624 infants; 767 treated with hypertonic saline, of which 735 (96%) co-administered with bronchodilators) did not report any adverse events, and 13 trials (2792 infants; 1479 treated with hypertonic saline, of which 416 (28%) co-administered with bronchodilators and 1063 (72%) hypertonic saline alone) reported at least one adverse event such as worsening cough, agitation, bronchospasm, bradycardia, desaturation, vomiting and diarrhoea, most of which were mild and resolved spontaneously (low-certainty evidence). AUTHORS' CONCLUSIONS: Nebulised hypertonic saline may modestly reduce length of stay amongst infants hospitalised with acute bronchiolitis and may slightly improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation amongst outpatients and ED patients. Nebulised hypertonic saline seems to be a safe treatment in infants with bronchiolitis with only minor and spontaneously resolved adverse events, especially when administered in conjunction with a bronchodilator. The certainty of the evidence was low to very low for all outcomes, mainly due to inconsistency and risk of bias.

Impact of hypertonic saline on hospitalization rate in infants with acute bronchiolitis: A meta-analysis.

AIM: This meta-analysis aimed to assess the efficacy of nebulized hypertonic saline (HS) on the rate of hospitalization in infants with acute bronchiolitis in the Emergency Department (ED) setting. METHOD: We searched PubMed, Virtual Health Library-BVS and Cochrane CENTRAL from inception until January 31, 2018. We selected randomized trials that compared nebulized HS with normal saline (NS) or standard care in children up to 24 months of age with acute bronchiolitis in the ED setting. We conducted random-effects meta-analyses to estimate the risk ratio (RR) and 95% confidence interval (CI). RESULTS: A total of 293 records were screened and 8 trials involving 1708 patients were included. The meta-analysis showed a 16% reduction in the risk of hospitalization among patients treated with HS compared to NS (risk ratio [RR]: 0.84, 95% confidence interval [CI]: 0.71-0.98, P = 0.03). A significant effect of HS in reducing the risk of hospitalization was found only in the subgroup analyses of trials in which HS was mixed with bronchodilators, multiple doses (≥3) were given, and risk of bias was low. CONCLUSIONS: Nebulized hypertonic saline may potentially reduce the risk of hospitalization in infants with acute bronchiolitis in the ED setting. Quality of evidence is moderate due to substantial clinical heterogeneity between studies and large multicenter trials are still warranted.

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.

OBJECTIVES: For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size. STUDY DESIGN: For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We assessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisher exact test. We tested for associations between design and reporting characteristics and overall RoB and registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by RoB using the χ2 test for subgroups in meta-analysis. RESULTS: The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007 to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was associated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were not often reported, and selective reporting was prevalent. Measures to increase trialists' awareness and application of existing reporting guidance, and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field.

Nebulised hypertonic saline solution for acute bronchiolitis in infants.

BACKGROUND: Airway oedema and mucus plugging are the predominant pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution may reduce these pathological changes and decrease airway obstruction. OBJECTIVES: To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute viral bronchiolitis. SEARCH METHODS: We searched CENTRAL 2013, Issue 4, OLDMEDLINE (1951 to 1965), MEDLINE (1966 to April week 4, 2013), EMBASE (1974 to May 2013), LILACS (1985 to May 2013) and Web of Science (1955 to May 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline as a comparator in infants up to 24 months of age with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2. We used the random-effects model for meta-analyses. We used mean difference (MD) and risk ratio (RR) as effect size metrics. MAIN RESULTS: We included 11 trials involving 1090 infants with mild to moderate acute viral bronchiolitis (500 inpatients, five trials; 65 outpatients, one trial; and 525 emergency department patients, four trials). All but one of the included trials were of high quality with a low risk of bias. A total of 560 patients received hypertonic saline (3% saline n = 503; 5% saline n = 57). Patients treated with nebulised 3% saline had a significantly shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD -1.15 days, 95% confidence interval (CI) -1.49 to -0.82, P < 0.00001). The hypertonic saline group also had a significantly lower post-inhalation clinical score than the 0.9% saline group in the first three days of treatment (day 1: MD -0.88, 95% CI -1.36 to -0.39, P = 0.0004; day 2: MD -1.32, 95% CI -2.00 to -0.64, P = 0.001; day 3: MD -1.51, 95% CI -1.88 to -1.14, P < 0.00001). The effects of improving clinical score were observed in both outpatients and inpatients. Four emergency department-based trials did not show any significant short-term effects (30 to 120 minutes) of up to three doses of nebulised 3% saline in improving clinical score and oxygen saturation. No significant adverse events related to hypertonic saline inhalation were reported. AUTHORS' CONCLUSIONS: Current evidence suggests nebulised 3% saline may significantly reduce the length of hospital stay among infants hospitalised with non-severe acute viral bronchiolitis and improve the clinical severity score in both outpatient and inpatient populations.