Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DS...Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.展开更多
Objective： To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation （TRABC） in treatment of hypertensive intracerebral hemorrhage （HICH）. Methods： This was...Objective： To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation （TRABC） in treatment of hypertensive intracerebral hemorrhage （HICH）. Methods： This was a multi-center prospective randomized open-label blinded-endpoint （PROBE） trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale （mRS）. Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale （NIHSS） scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded. Results： After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups （P〈0.01）. Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group （P=0.038）. Average Barthel scores in the treatment group after treatment was 89.11 ＋ 19.93, and in the control group 82.18 ＋ 24.02 （P=0.003）. NIHSS scores of the two groups after treatment decreased significantly compared with before treatment （P=0.001）. Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment （P〈0.05）. There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group. Conclusion： The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.展开更多
Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been es...Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.展开更多
Background： Spinocerebellar ataxia type 3 （SCA3） is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing...Background： Spinocerebellar ataxia type 3 （SCA3） is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor （NGF） may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients. Methods： We performed an open-label prospective study in genetically confirmed adult （〉18 years old） SCA3 patients. NGF was administered by intramuscular injection （18 μg once daily） fbr 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia （SARA）. Results： Twenty-one SCA3 patients （ 10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77,57 ± 2.27） were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48± 2.40 to 6.30 ± 1.87 （P 〈 0.001 ）. Subsections SARA scores also showed significant improvements in stance （P = 0.003）, speech （P = 0.023）, finger chase （P = 0.015）, fast alternating hand movements （P = 0.009）, and heel-shin slide （P = 0.001）. Conclusions： Our preliminary data suggest that NGF may be effective in treating patients with SCA3.展开更多
Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal trials.Still,clinical evidence...Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal trials.Still,clinical evidence from routine practice is needed to complement the data from the pivotal trials.Methods:OPTIPARK(NCT02847442)was a prospective,open-label,single-arm trial conducted in Germany and the UK under clinical practice conditions.Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3(Germany)or 6(UK)months in addition to their current levodopa and other antiparkinsonian treatments.The primary endpoint was the Clinician’s Global Impression of Change(CGI-C)after 3 months.Secondary assessments included Patient Global Impressions of Change(PGI-C),the Unified Parkinson’s Disease Rating Scale(UPDRS),Parkinson’s Disease Questionnaire(PDQ-8),and the Non-Motor Symptoms Scale(NMSS).Safety assessments included evaluation of treatment-emergent adverse events(TEAEs)and serious adverse events(SAEs).Results:Of the 506 patients enrolled,495(97.8%)took at least one dose of opicapone.Of these,393(79.4%)patients completed 3 months of treatment.Overall,71.3 and 76.9%of patients experienced any improvement on CGI-C and PGI-C after 3 months,respectively(full analysis set).At 6 months,for UK subgroup only(n=95),85.3%of patients were judged by investigators as improved since commencing treatment.UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF(mean±SD change from baseline:?3.0±4.6,p<0.0001)and motor scores during ON(?4.6±8.1,p<0.0001).The mean±SD improvements of?3.4±12.8 points for PDQ-8 and-6.8±19.7 points for NMSS were statistically significant versus baseline(both p<0.0001).Most of TEAEs(94.8%of events)were of mild or moderate intensity.TEAEs considered to be at least possibly related to opicapone were reported for 45.1%of patients,with dyskinesia(11.5%)and dry mouth(6.5%)being the most frequently reported.Serious TEAEs considered at least possibly related to opicapone were reported for 1.4%of patients.Conclusions:Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice.展开更多
传统机器学习方法和深度神经网络在训练模型的过程中都需要大量标记样本作为支撑,然而标记大量样本是一个耗费巨大的过程,并且真实场景变化莫测,获得所有类别的标记样本是不现实的.因此,研究者开始突破标记样本的限制,提出一种更符合现...传统机器学习方法和深度神经网络在训练模型的过程中都需要大量标记样本作为支撑,然而标记大量样本是一个耗费巨大的过程,并且真实场景变化莫测,获得所有类别的标记样本是不现实的.因此,研究者开始突破标记样本的限制,提出一种更符合现实的场景——开放集识别(Open Set Recognition,OSR).OSR要求建立的模型不仅能分类训练过程中出现的类别,还可以有效地处理未见过的类别.近年来,OSR迅速发展成为热点领域,大量的工作围绕OSR展开.对现有的OSR工作进行总结:首先,从定义上将OSR与其他相关工作进行区分;其次,按照模型建立、度量选择、增量特点对OSR算法进行总结,并介绍了OSR的两种理论;最后展望了OSR未来的发展方向.展开更多
文摘Objective: To estimate the rate of response to divalproex sodium extended release in pediatric bipolar spectrum disorder in young children age 6 - 12. Methods: This was an 8-week, open-label treatment of youth with DSM-IV bipolar disorder with divalproex sodium extended release (ER) monotherapy. Severity of mania was assessed weekly with the Young Mania Rating Scale (YMRS). Results: The sample was 8.9 ± 2.0 years of age and predominantly male (83%). At study entry the mean YMRS score was 26.3 ± 4.5. Of the 18 subjects enrolled, 7 (39%) completed the 8 week course. We failed to find a clinically or statistically significant improvement with divalproex sodium ER. Pre-post comparisons at endpoint (LOCF) indicated an average response reduction of 6.1 ± 2.6 in the YMRS to a mean of 20.3 ± 8.1. Weight increased by 1.36 ± 0.7 kg (p = 0.08) from baseline to endpoint. Conclusion. Divalproex sodium ER monotherapy was associated with poor tolerability, was associated with clinically concerning weight gain but had modest therapeutic benefits in the management of symptoms of mania and depression in children with pediatric bipolar disorder.
基金Supported by the Beijing Committee on Science and Technology,Project on Research on Two Standards of Traditional Chinese Medicine Treatment for Stroke(No.D101107049310003)
文摘Objective： To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation （TRABC） in treatment of hypertensive intracerebral hemorrhage （HICH）. Methods： This was a multi-center prospective randomized open-label blinded-endpoint （PROBE） trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale （mRS）. Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale （NIHSS） scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded. Results： After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups （P〈0.01）. Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group （P=0.038）. Average Barthel scores in the treatment group after treatment was 89.11 ＋ 19.93, and in the control group 82.18 ＋ 24.02 （P=0.003）. NIHSS scores of the two groups after treatment decreased significantly compared with before treatment （P=0.001）. Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment （P〈0.05）. There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group. Conclusion： The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.
基金This study was supported by the National Key Basic Research Program of China(973 Program No.2015CB553902)
文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.
基金This study was supported by grants from the National Natural Science Foundation of China grant，The Innovation Team Fund of the First Affiliated Hospital of Zhengzhou University and the National Natural Science Foundation of China
文摘Background： Spinocerebellar ataxia type 3 （SCA3） is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor （NGF） may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients. Methods： We performed an open-label prospective study in genetically confirmed adult （〉18 years old） SCA3 patients. NGF was administered by intramuscular injection （18 μg once daily） fbr 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia （SARA）. Results： Twenty-one SCA3 patients （ 10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77,57 ± 2.27） were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48± 2.40 to 6.30 ± 1.87 （P 〈 0.001 ）. Subsections SARA scores also showed significant improvements in stance （P = 0.003）, speech （P = 0.023）, finger chase （P = 0.015）, fast alternating hand movements （P = 0.009）, and heel-shin slide （P = 0.001）. Conclusions： Our preliminary data suggest that NGF may be effective in treating patients with SCA3.
基金The study was funded by BIALThree authors(JFR,DM and PSS)were employed by the funder and participated in the study design,data collection,data management,and data analysis+1 种基金The funder of the study had no other role in data interpretation or in the decision to submit the manuscript for publicationBIAL also supported reporting of study results by procuring medical writing support.
文摘Background:The efficacy and safety of opicapone,a once-daily catechol-O-methyltransferase inhibitor,have been established in two large randomized,placebo-controlled,multinational pivotal trials.Still,clinical evidence from routine practice is needed to complement the data from the pivotal trials.Methods:OPTIPARK(NCT02847442)was a prospective,open-label,single-arm trial conducted in Germany and the UK under clinical practice conditions.Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3(Germany)or 6(UK)months in addition to their current levodopa and other antiparkinsonian treatments.The primary endpoint was the Clinician’s Global Impression of Change(CGI-C)after 3 months.Secondary assessments included Patient Global Impressions of Change(PGI-C),the Unified Parkinson’s Disease Rating Scale(UPDRS),Parkinson’s Disease Questionnaire(PDQ-8),and the Non-Motor Symptoms Scale(NMSS).Safety assessments included evaluation of treatment-emergent adverse events(TEAEs)and serious adverse events(SAEs).Results:Of the 506 patients enrolled,495(97.8%)took at least one dose of opicapone.Of these,393(79.4%)patients completed 3 months of treatment.Overall,71.3 and 76.9%of patients experienced any improvement on CGI-C and PGI-C after 3 months,respectively(full analysis set).At 6 months,for UK subgroup only(n=95),85.3%of patients were judged by investigators as improved since commencing treatment.UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF(mean±SD change from baseline:?3.0±4.6,p<0.0001)and motor scores during ON(?4.6±8.1,p<0.0001).The mean±SD improvements of?3.4±12.8 points for PDQ-8 and-6.8±19.7 points for NMSS were statistically significant versus baseline(both p<0.0001).Most of TEAEs(94.8%of events)were of mild or moderate intensity.TEAEs considered to be at least possibly related to opicapone were reported for 45.1%of patients,with dyskinesia(11.5%)and dry mouth(6.5%)being the most frequently reported.Serious TEAEs considered at least possibly related to opicapone were reported for 1.4%of patients.Conclusions:Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice.
文摘传统机器学习方法和深度神经网络在训练模型的过程中都需要大量标记样本作为支撑,然而标记大量样本是一个耗费巨大的过程,并且真实场景变化莫测,获得所有类别的标记样本是不现实的.因此,研究者开始突破标记样本的限制,提出一种更符合现实的场景——开放集识别(Open Set Recognition,OSR).OSR要求建立的模型不仅能分类训练过程中出现的类别,还可以有效地处理未见过的类别.近年来,OSR迅速发展成为热点领域,大量的工作围绕OSR展开.对现有的OSR工作进行总结:首先,从定义上将OSR与其他相关工作进行区分;其次,按照模型建立、度量选择、增量特点对OSR算法进行总结,并介绍了OSR的两种理论;最后展望了OSR未来的发展方向.
