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Abstract Objective: Emergence delirium is a common complication in children. Recorded mother's voice, as a non-pharmacological measure, is increasingly used to prevent the emergence of delirium in pediatric patients, but sufficient evidence is still needed to prove its efficacy. Methods: Embase, PubMed, Cochrane Library, Web of Science, CINAHL, and Sinomed databases were searched for randomized controlled trials exploring the efficacy of recorded mother's voice in preventing the emergence of delirium in pediatric patients undergoing general anesthesia. The original data were pooled for the meta-analysis with Review Manager 5.4.1. This study was conducted based on the Cochrane Review Methods. Results: Eight studies with 724 children were included in the analysis. Recorded mother's voice reduced the incidence of emergence delirium when compared with either no voice (RR: 0.45; [95 % CI, 0.34 - 0.61]; p < 0.01; I2 = 7 %) or stranger's voice (RR: 0.51; [95 % CI, 0.28 - 0.91]; p = 0.02; I2 = 38 %) without increasing other untoward reactions. In addition, it shortened the post-anesthesia care unit stay time when compared with no voice (MD = -5.64; [95 % CI, -8.43 to -2.58]; p < 0.01, I2 = 0 %), but not stranger's voice (MD = -1.23; [95 % CI, -3.08 to 0.63]; p = 0.19, I2 = 0 %). It also shortened the extubation time and reduced the incidence of postoperative rescue analgesia. Conclusion: The current analysis indicated that recorded mother's voices could reduce the incidence of emergency delirium, shorten post-anesthesia care unit stay time and extubation time, and decrease the incidence of postoperative rescue analgesia in children.
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AIMS: PCSK9 inhibition intensively lowers low density lipoprotein cholesterol and is well tolerated in adults and paediatric patients with familial hypercholesterolaemia (FH). HAUSER-RCT showed that 24 weeks of treatment with evolocumab in paediatric patients did not affect cognitive function. This study determined the effects of 80 additional weeks of evolocumab treatment on cognitive function in paediatric patients with heterozygous FH. METHODS AND RESULTS: HAUSER-OLE was an 80-week open-label extension of HAUSER-RCT, a randomized, double-blind, 24-week trial evaluating the efficacy and safety of evolocumab in paediatric patients (ages 10-17 years) with FH. During the OLE, all patients received monthly 420â mg subcutaneous evolocumab injections. Tests of psychomotor function, attention, visual learning, and executive function were administered at baseline and Weeks 24 and 80 of the OLE. Changes over time were analysed descriptively and using analysis of covariance. Cohen's d statistic was used to evaluate the magnitude of treatment effects. Analysis of covariance results indicated no decrease in performance across visits during 80 weeks of evolocumab treatment for Groton Maze Learning, One Card Learning accuracy, Identification speed, or Detection speed (all P > 0.05). Performance on all tasks was similar for those who received placebo or evolocumab in the RCT (all P > 0.05). For all tests, the least square mean differences between patients who received placebo vs. evolocumab in the parent study were trivial (all Cohen's d magnitude < 0.2). CONCLUSION: In paediatric patients with FH, 80 weeks of open-label evolocumab treatment had no negative impact on cognitive function. REGISTRATION: ClinicalTrials.gov identifier: NCT02624869.
Some children are born with a genetic disorder that causes high cholesterol, which leads to heart disease. Children with high cholesterol can be treated with evolocumab, a medication that lowers blood cholesterol. Because cholesterol is important for development and adequate function of the brain, there is a concern that lowering cholesterol in children may affect mental ability. In this study, we tested whether treating children with evolocumab for 80 weeks affected mental ability in performing several tasks. A battery of tests that measure executive function (Groton Maze Learning Test), visual learning (One Card Learning Test), visual attention (Identification Test), and psychomotor function (Detection Test) showed no decrease in performance across visits during 80 weeks of evolocumab treatment. Performance on all tasks was similar for the children who received placebo for the first 24 weeks then received evolocumab for an additional 80 weeks (placebo/evolocumab) and those who received evolocumab for 24 weeks then received evolocumab for an additional 80 weeks (evolocumab/evolocumab).
Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticolesterolemiantes , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Niño , Proproteína Convertasa 9 , Anticolesterolemiantes/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Cognición , Resultado del Tratamiento , Método Doble CiegoRESUMEN
OBJECTIVE: Emergence delirium is a common complication in children. Recorded mother's voice, as a non-pharmacological measure, is increasingly used to prevent the emergence of delirium in pediatric patients, but sufficient evidence is still needed to prove its efficacy. METHODS: Embase, PubMed, Cochrane Library, Web of Science, CINAHL, and Sinomed databases were searched for randomized controlled trials exploring the efficacy of recorded mother's voice in preventing the emergence of delirium in pediatric patients undergoing general anesthesia. The original data were pooled for the meta-analysis with Review Manager 5.4.1. This study was conducted based on the Cochrane Review Methods. RESULTS: Eight studies with 724 children were included in the analysis. Recorded mother's voice reduced the incidence of emergence delirium when compared with either no voice (RR: 0.45; [95 % CI, 0.34 - 0.61]; p < 0.01; I2 = 7 %) or stranger's voice (RR: 0.51; [95 % CI, 0.28 - 0.91]; p = 0.02; I2 = 38 %) without increasing other untoward reactions. In addition, it shortened the post-anesthesia care unit stay time when compared with no voice (MD = -5.64; [95 % CI, -8.43 to -2.58]; p < 0.01, I2 = 0 %), but not stranger's voice (MD = -1.23; [95 % CI, -3.08 to 0.63]; p = 0.19, I2 = 0 %). It also shortened the extubation time and reduced the incidence of postoperative rescue analgesia. CONCLUSION: The current analysis indicated that recorded mother's voices could reduce the incidence of emergency delirium, shorten post-anesthesia care unit stay time and extubation time, and decrease the incidence of postoperative rescue analgesia in children.
RESUMEN
BACKGROUND: The HAUSER-RCT study showed that 24 weeks of evolocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in paediatric patients with heterozygous familial hypercholesterolaemia was safe and improved lipid parameters compared to placebo. Here, we aimed to evaluate the safety and efficacy of evolocumab in this population for an additional 80 weeks. METHODS: HAUSER-OLE was an 80-week, single-arm, open-label extension of HAUSER-RCT, a randomised controlled trial, and was conducted at 46 centres in 23 countries. Paediatric patients aged 10-17 years with heterozygous familial hypercholesterolaemia who completed 24 weeks of monthly treatment with subcutaneously administered placebo or 420 mg evolocumab in HAUSER-RCT with no serious treatment-emergent adverse events were eligible to enrol in HAUSER-OLE. All patients received open-label subcutaneous evolocumab 420 mg monthly with background statins with or without ezetimibe for 80 additional weeks. The primary endpoint was treatment-emergent adverse events. Efficacy was evaluated by changes in lipids from the baseline of HAUSER-RCT to the end of HAUSER-OLE (104 weeks). This study is registered with ClinicalTrials.gov (NCT02624869) and is now completed. FINDINGS: Between Sept 10, 2016, and Nov 25, 2019, 157 patients were enrolled in HAUSER-RCT and received randomised treatment; 150 continued to HAUSER-OLE, received evolocumab treatment, and were included in the full analysis set, presented here. 146 (97%) of 150 patients completed the open-label extension. The incidence of treatment-emergent adverse events in HAUSER-OLE was 70% (105 of 150). Overall, the most common treatment-emergent adverse events were nasopharyngitis (22 [15%] of 150), headache (14 [9%]), and influenza-like illness (13 [9%]). Serious treatment-emergent adverse events occurred in four (3%) of 150 patients (perforated appendicitis and peritonitis, wrist fracture, anorexia nervosa, and headache); none was considered related to evolocumab. No treatment-emergent adverse events led to treatment discontinuation. At week 80, the mean percentage change from baseline in LDL cholesterol was -35·3% (SD 28·0). INTERPRETATION: After 80 weeks of treatment, evolocumab was safe, well tolerated, and led to sustained reductions in LDL cholesterol in paediatric patients with heterozygous familial hypercholesterolaemia. When lipid goals cannot be achieved with conventional treatments, evolocumab is an effective add-on therapy in paediatric patients. FUNDING: Amgen. TRANSLATIONS: For the French, Spanish, Spanish, Portuguese, Italian and Dutch translations of the abstract see Supplementary Materials section.