SummaryBackgroundIntensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy.MethodsWe did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388.Findings3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001).InterpretationAmong patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice.FundingNational Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Background: Comparison of bolus gastric feeding (BGF) vs continuous gastric feeding (CGF) with respect to timing and delivery of energy and protein in mechanically ventilated (MV) pediatric patients has not been investigated. We hypothesized that bolus delivery would shorten time to goal nutrition and increase the percentage of goal feeds delivered.Methods: Multicenter, prospective, randomized comparative effectiveness trial conducted in seven pediatric intensive care units (PICUs). Eligibility criteria included patients aged 1 month to 12 years who were intubated within 24 h of PICU admission, with expected duration of ventilation at least 48 h, and who were eligible to begin enteral nutrition within 48 h. Exclusion criteria included patients with acute or chronic gastrointestinal pathology or acute surgery. Results:We enrolled 158 MV children between October 2015 and April 2018; 147 patients were included in the analysis (BGF = 72, CGF = 75). Children in the BGF group were slightly older than those in the CGF; otherwise, the two groups had similar demographic characteristics. There was no difference in the percentage of patients in each group who achieved goal feeds. Time to goal feeds was shorter in the BGF group (hazard ratio 1.5 [CI 1.02-2.33]; P = 0.0387). Median percentage of target kilocalories (median kcal 0.78 vs 0.59; P ≤ 0.0001) and median percentage of protein delivered (median protein 0.77 vs 0.59; P ≤ 0.0001) was higher for BGF patients. There was no difference in serial oxygen saturation index between groups. Conclusion:Our study demonstrated shorter time to achieve goal nutrition via BGF compared with CGF in MV pediatric patients. This resulted in increased delivery of target energy and nutrition. Further study is needed in other PICU populations.

To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD).DESIGN: Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. SETTING: Nine U.S. hospitals. PATIENTS:Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010TE ( -2021. MEASUREMENTS AND MAIN RESULTS:Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/Fio 2 ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) (n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/ kg/hr) (n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. CONCLUSIONS:Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

In response to the coronavirus disease 2019 (COVID-19) pandemic, state and local governments implemented mitigation strategies, including lockdowns, thereby averting the typical fall/winter 2020 bronchiolitis season and reducing the incidence of respiratory viruses, such as respiratory syncytial virus (RSV). Florida implemented a strict lockdown from April 1, 2020, to April 30, 2020. The removal of lockdown precautions on September 25, 2020, was followed by an atypical out-of-season surge of bronchiolitis in April 2021. Anecdotally, this surge appeared to be associated with both increased poly-viral coinfections and disease severity. ObjectiveTo determine if the bronchiolitis out-of-season surge differed from historical seasonal case patterns. MethodsA single-center retrospective cohort study of admissions to the pediatric intensive care unit (PICU) with International Classification of Diseases, Tenth Revision (ICD-10) codes of bronchiolitis, from December 9, 2019, to February 29, 2020 (12 weeks, pre-lockdown group or PreLD), was compared to March 29, 2021, to June 19, 2021 (12 weeks, post-lockdown group or PostLD). Variables used for comparison were gender, ethnicity, age, viral coinfections, viruses detected, PICU length of stay, hospital length of stay, mortality, maximum respiratory support needed, mechanical ventilation days, extracorporeal life support (ECLS) days, and severity of disease measured by Pediatric Logistic Organ Dysfunction-2 (PELOD-2) and Pediatric Sequential Organ Failure Assessment (pSOFA). Categorical data were analyzed using Fisher's exact test, and a t-test was used for continuous variables. A two-sided p < 0.05 was considered significant. ResultsA total of 135 subjects were analyzed from the two cohorts. More patients were admitted during the PostLD phase (87 vs. 48). The PostLD group had a higher age at admission (11.2 ± 12.3 vs. 6.6 ± 7.5, p = 0.0075), but there were no differences in gender or race/ethnicity. The PostLD group also exhibited a higher proportion of RSV infections (73 vs. 16, p < 0.0001) and poly-viral infections (p < 0.0001). Higher coronavirus OC43 (9 vs. 0, p = 0.0263) and parainfluenza types 1-4 (human parainfluenza virus (HPIV)) (19 vs. 1, p = 0.0017) detections, yet fewer human metapneumovirus (HMPV) detections (0 vs. 4, p = 0.0147), were observed PostLD. No differences were found in hospital length of stay, PICU length of stay, mortality, mechanical ventilation days, ECLS days, or severity of illness scores based on PELOD-2 or pSOFA scores. ConclusionIn the bronchiolitis out-of-season surge, there were an increased number of admissions to the PICU. Those patients were older, and more likely to have RSV, as well as a coinfection with coronavirus OC43 or HPIV, yet less likely to have HMPV. No difference in length of stay or disease severity was demonstrated.