BACKGROUND: Sleep deprivation resulting from night shifts, is a major cause of burnout among physicians. Exogenous melatonin may improve sleep quality in night-shift workers. The study aims to compare the effectivenes...BACKGROUND: Sleep deprivation resulting from night shifts, is a major cause of burnout among physicians. Exogenous melatonin may improve sleep quality in night-shift workers. The study aims to compare the effectiveness of melatonin versus placebo on sleep effi ciency in emergency medicine(EM) residents. METHODS: A randomized, double-blind, replicated crossover trial was performed on EM residents. This study consisted of 4 phases within a month with intervention periods of 2 nights and washouts of 6 days. In our study, EM residents had nine-hour shifts on 6 consecutive days, 2 mornings, 2 evenings and 2 nights and then 2 days off. At the end of shifts' cycle, 24 EM residents were given 3 mg melatonin or placebo(12 in each arm of the study) for 2 consecutive nights after the second night shift with crossover to the other arm after a six-day off drug. This crossover intervention was repeated for two more another time. Finally, we created 48 cases and comparisons in each arm. Different items related to sleep quality were assessed and compared both within the same group and between the two groups. RESULTS: In the melatonin group, daytime sleepiness(calculated by Karolinska Sleep Scale) had a signifi cant reduction after taking the second dose of drug(P=0.003) but the same result was not observed when comparing the 2 groups. Mood status(calculated by Profile of Mood States) showed no remarkable difference between the 2 groups. CONCLUSION: Melatonin might have a limited benefi t on sleep quality in EM residents working night shifts.展开更多
Background Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression.Microglia activation can lead to an increase in the levels of proinflammatory cytokines,includ...Background Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression.Microglia activation can lead to an increase in the levels of proinflammatory cytokines,including TNF-α,which leads to neuronal apoptosis in the specific neural circuits of some brain regions,abnormal cognition and treatment-resistant depression(TRD).Protein kinase C(PKC)is a key regulator of the microglia activation process.We assume that the abnormality in PKC might result in abnormal microglia activation,neuronal apoptosis,significant changes in emotional and cognitive neural circuits,and TRD.In the current study,we plan to target at the PKC signal pathway to improve the TRD treatment outcome.Methods and analysis This is a 12-week,ongoing,randomised,placebo-controlled trial.Patients with TRD(N=180)were recruited from Shanghai Mental Health Center,Shanghai Jiao Tong University.Healthy control volunteers(N=60)were recruited by advertisement.Patients with TRD were randomly assigned to‘escitalopram+golimumab(TNF-αinhibitor)’,‘escitalopram+calcium tablet+vitamin D(PKC activator)’or‘escitalopram+placebo’groups.We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale(HAMD-17).The secondary outcome is defined as changes in anti-inflammatory effects,cognitive function and quality of life.Discussion This study might be the first randomised,placebo-controlled trial to target at the PKC signal pathway in patients with TRD.Our study might help to propose individualised treatment strategies for depression.Trial registration number The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.展开更多
Background:A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic.We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019.Methods:This ongoing phase 2...Background:A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic.We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019.Methods:This ongoing phase 2 and 3 double-blind,placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition,at 31 sites in five countries(Belgium,Brazil,Colombia,Philippines.展开更多
Background:Dupilumab,a fully human monoclonal antibody,blocks interleukin-4 and interleukin-13 signaling,which have key roles in eosinophilic esophagitis.Methods:We conducted a three-part,phase 3 trial in which patien...Background:Dupilumab,a fully human monoclonal antibody,blocks interleukin-4 and interleukin-13 signaling,which have key roles in eosinophilic esophagitis.Methods:We conducted a three-part,phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo(Part A)or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo(Part B)up to week 24.展开更多
Background:Severe coronavirus disease 2019(Covid-19)is associated with dysregulated inflammation.The effects of combination treatment with baricitinib,a Janus kinase inhibitor,plus remdesivir are not known.Methods:We ...Background:Severe coronavirus disease 2019(Covid-19)is associated with dysregulated inflammation.The effects of combination treatment with baricitinib,a Janus kinase inhibitor,plus remdesivir are not known.Methods:We conducted a double-blind,randomized,placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19.All the patients received remdesivir(≤10 days)and either baricitinib(≤14 days)or placebo(control).The primary outcome was the time to recovery.The key secondary outcome was clinical status at day 15.展开更多
文摘BACKGROUND: Sleep deprivation resulting from night shifts, is a major cause of burnout among physicians. Exogenous melatonin may improve sleep quality in night-shift workers. The study aims to compare the effectiveness of melatonin versus placebo on sleep effi ciency in emergency medicine(EM) residents. METHODS: A randomized, double-blind, replicated crossover trial was performed on EM residents. This study consisted of 4 phases within a month with intervention periods of 2 nights and washouts of 6 days. In our study, EM residents had nine-hour shifts on 6 consecutive days, 2 mornings, 2 evenings and 2 nights and then 2 days off. At the end of shifts' cycle, 24 EM residents were given 3 mg melatonin or placebo(12 in each arm of the study) for 2 consecutive nights after the second night shift with crossover to the other arm after a six-day off drug. This crossover intervention was repeated for two more another time. Finally, we created 48 cases and comparisons in each arm. Different items related to sleep quality were assessed and compared both within the same group and between the two groups. RESULTS: In the melatonin group, daytime sleepiness(calculated by Karolinska Sleep Scale) had a signifi cant reduction after taking the second dose of drug(P=0.003) but the same result was not observed when comparing the 2 groups. Mood status(calculated by Profile of Mood States) showed no remarkable difference between the 2 groups. CONCLUSION: Melatonin might have a limited benefi t on sleep quality in EM residents working night shifts.
基金This work was supported by the National Key R&D Program of China(2016YFC1307100)the National Natural Science Foundation of China(81930033,81771465,81201057)+2 种基金the Shanghai Key Project of Science&Technology(2018SHZDZX05)the National Key Technologies R&D Program of China(2012BAI01B04)the Innovative Research Team of High-level Local Universities in Shanghai.
文摘Background Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression.Microglia activation can lead to an increase in the levels of proinflammatory cytokines,including TNF-α,which leads to neuronal apoptosis in the specific neural circuits of some brain regions,abnormal cognition and treatment-resistant depression(TRD).Protein kinase C(PKC)is a key regulator of the microglia activation process.We assume that the abnormality in PKC might result in abnormal microglia activation,neuronal apoptosis,significant changes in emotional and cognitive neural circuits,and TRD.In the current study,we plan to target at the PKC signal pathway to improve the TRD treatment outcome.Methods and analysis This is a 12-week,ongoing,randomised,placebo-controlled trial.Patients with TRD(N=180)were recruited from Shanghai Mental Health Center,Shanghai Jiao Tong University.Healthy control volunteers(N=60)were recruited by advertisement.Patients with TRD were randomly assigned to‘escitalopram+golimumab(TNF-αinhibitor)’,‘escitalopram+calcium tablet+vitamin D(PKC activator)’or‘escitalopram+placebo’groups.We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale(HAMD-17).The secondary outcome is defined as changes in anti-inflammatory effects,cognitive function and quality of life.Discussion This study might be the first randomised,placebo-controlled trial to target at the PKC signal pathway in patients with TRD.Our study might help to propose individualised treatment strategies for depression.Trial registration number The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.
文摘Background:A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic.We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019.Methods:This ongoing phase 2 and 3 double-blind,placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition,at 31 sites in five countries(Belgium,Brazil,Colombia,Philippines.
文摘Background:Dupilumab,a fully human monoclonal antibody,blocks interleukin-4 and interleukin-13 signaling,which have key roles in eosinophilic esophagitis.Methods:We conducted a three-part,phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo(Part A)or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo(Part B)up to week 24.
文摘Background:Severe coronavirus disease 2019(Covid-19)is associated with dysregulated inflammation.The effects of combination treatment with baricitinib,a Janus kinase inhibitor,plus remdesivir are not known.Methods:We conducted a double-blind,randomized,placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19.All the patients received remdesivir(≤10 days)and either baricitinib(≤14 days)or placebo(control).The primary outcome was the time to recovery.The key secondary outcome was clinical status at day 15.
