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Aim: Pain associated with immunisations can result in distress and/or anxiety for children and parents. We assessed the feasibility and acceptability of two novel devices; Coolsense (cold) and Buzzy (vibration ± cooling pads) versus standard care to minimise pain during immunisations. We also evaluated compliance to the devices and parent's perception of the effectiveness of the devices/standard care for minimising pain during immunisation.Design: Open label, pilot, randomised controlled trial (RCT).Methods: Forty children aged 3.5 to 6 years attending an Immunisation Centre at The Royal Children's Hospital in Melbourne, Australia, were randomised (1:1:1:1) into four groups: (i) Coolsense plus standard care; (ii) Buzzy with cold plus standard care; (iii) Buzzy without cold plus standard care; and (iv) Standard care alone (distraction with bubbles).Results and Analysis: Recruitment was completed in 12 days. Seventy percent were compliant with Buzzy (±cold), 82% with Coolsense, and 60% with standard care. Buzzy (with cold) was identified as effective by 70% of parents, Coolsense by 64%, Buzzy without cold by 50% and standard care by 60%.Conclusions: This pilot study demonstrated feasibility. A larger RCT is needed to provide definitive evidence to inform best practice for minimising immunisation pain in young children. [ABSTRACT FROM AUTHOR]

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain.Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD).Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020.Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met.Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately.Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group.Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded.Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943. [ABSTRACT FROM AUTHOR]

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain.Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders.Design, Setting, and Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017.Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks.Main Outcomes and Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables.Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21).Conclusions and Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference.Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392. [ABSTRACT FROM AUTHOR]

Aim: To compare diazepam use, muscle spasm, analgesia, and side effects when clonidine or fentanyl are added to epidural bupivacaine in children with cerebral palsy after multilevel orthopaedic surgery.Method: Fifty children were prospectively randomized to receive clonidine (n=24, mean age 10y 10mo [SD 2y 11mo]) or fentanyl (n=26, mean age 10y 11mo [SD 2y 10mo]).Results: There was no difference in primary outcome measures: median diazepam use (fentanyl 0, interquartile range [IQR] 0-0; clonidine 0, IQR 0-0; p=0.46), any muscle spasm (no muscle spasms in: fentanyl, 36%; clonidine, 62%; p=0.11), painful muscle spasm (fentanyl 40%; clonidine 25%; p=0.46), or pain score ≥6 (none: fentanyl 44%; clonidine 42%; p=0.29). There were differences in secondary outcome measures: no vomiting (clonidine 63%; fentanyl 20%); vomiting occurred more frequently with fentanyl (32% vomited more than three times; clonidine none; p=0.001). Fentanyl resulted in more oxygen desaturation (at least two episodes: fentanyl 20%; clonidine 0; p<0.001). Clonidine resulted in lower mean (SD) area under the curve for systolic blood pressure (fentanyl 106.5 [11.0]; clonidine 95.7mmHg [7.9]) and heart rate (fentanyl 104.9 beats per minute [13.6]; clonidine 85.3 [11.5]; p<0.001).Interpretation: Clonidine and fentanyl provide adequate analgesia with low rates of muscle spasm, resulting in low diazepam use. The choice of epidural additive should be based upon the most tolerable side-effect profile. [ABSTRACT FROM AUTHOR]

Background: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities.Methods: Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years.Results: For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day.Conclusions: Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years. [ABSTRACT FROM AUTHOR]