药品风险管理贯穿于药品整个生命周期,药品风险效益评估是药品上市前审评与上市后评价的核心内容,积极深入地开展药物警戒活动是提高药品监管水平保障公众用药安全有效的重要环节。国际药物警戒学会(International Society of Pharmacov...药品风险管理贯穿于药品整个生命周期,药品风险效益评估是药品上市前审评与上市后评价的核心内容,积极深入地开展药物警戒活动是提高药品监管水平保障公众用药安全有效的重要环节。国际药物警戒学会(International Society of Pharmacovigilance,ISoP)是权威、独立、非营利性的国际性学术组织,是国际范围内公开、中立分享经验和知识的专业学术平台,旨在提升全球药物警戒的科学性,促进药物警戒和风险管理技术的发展。本文介绍了其组建发展、任务和学术交流方式等内容,提出ISoP为中国药品评价及药物警戒专业人员开启了一扇了解国际药物警戒技术和风险管理策略发展前沿的窗口,值得中国药品评价、药物警戒和药品安全领域科研、学术及医疗机构、药品生产经营企业及政府监管人员的充分关注与积极参与。展开更多
BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions ...BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.展开更多
Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of...Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.展开更多
BACKGROUND Gastrointestinal bleeding(GIB)is a common and potentially life-threatening clinical event.To date,the literature on the long-term global epidemiology of GIB has not been systematically reviewed.AIM To syste...BACKGROUND Gastrointestinal bleeding(GIB)is a common and potentially life-threatening clinical event.To date,the literature on the long-term global epidemiology of GIB has not been systematically reviewed.AIM To systematically review the published literature on the worldwide epidemiology of upper and lower GIB.METHODS EMBASE®and MEDLINE were queried from 01 January 1965 to September 17,2019 to identify population-based studies reporting incidence,mortality,or casefatality rates of upper GIB(UGIB)or lower GIB(LGIB)in the general adult population,worldwide.Relevant outcome data were extracted and summarized(including data on rebleeding following initial occurrence of GIB when available).All included studies were assessed for risk of bias based upon reporting guidelines.RESULTS Of 4203 retrieved database hits,41 studies were included,comprising a total of around 4.1 million patients with GIB worldwide from 1980–2012.Thirty-three studies reported rates for UGIB,four for LGIB,and four presented data on both.Incidence rates ranged from 15.0 to 172.0/100000 person-years for UGIB,and from 20.5 to 87.0/100000 person-years for LGIB.Thirteen studies reported on temporal trends,generally showing an overall decline in UGIB incidence over time,although a slight increase between 2003 and 2005 followed by a decline was shown in 5/13 studies.GIB-related mortality data were available from six studies for UGIB,with rates ranging from 0.9 to 9.8/100000 person-years,and from three studies for LGIB,with rates ranging from 0.8 to 3.5/100000 person-years.Casefatality rate ranged from 0.7%to 4.8%for UGIB and 0.5%to 8.0%for LGIB.Rates of rebleeding ranged from 7.3%to 32.5%for UGIB and from 6.7%to 13.5%for LGIB.Two main areas of potential bias were the differences in the operational GIB definition used and inadequate information on how missing data were handled.CONCLUSION Wide variation was seen in estimates of GIB epidemiology,likely due to high heterogeneity between studies however,UGIB showed a decreasing trend over the years.Epidemiological data were more widely available for UGIB than for LGIB.展开更多
The western flower thrips, Frankliniella occidentalis, is one of the most destructive sucking pests of vegetables, fruits and ornamental crops in China. Spinosad is one of the most commonly used insecticides to manage...The western flower thrips, Frankliniella occidentalis, is one of the most destructive sucking pests of vegetables, fruits and ornamental crops in China. Spinosad is one of the most commonly used insecticides to manage thrips. To assess the incidence of spinosad resistance in F. occidentalis field populations in eastern China, survival rates for 24 different populations were compared with those of a susceptible laboratory strain. All populations showed significantly higher resistance to spinosad compared with the control as determined by comparing median lethal concentrations. Two populations from Shouguang and Liaocheng in Shandong Province were classified as having moderate and high levels of resistance to spinosad with a mean resistance ratio of 17.0 and 89.2, respectively. Our research indicates a widespread reduction in spinosad efficacy for controlling F. occidentalis field populations, and that resistance management strategies should be implemented as soon as practicable, to reduce the potential of progressive resistance development and loss of efficacy.展开更多
The burden of maternal mortality (MM) and morbidity is especially high in Asia.However,China has made significant progress in reducing MM over the past two decades,and hence maternal death rate has declined considerab...The burden of maternal mortality (MM) and morbidity is especially high in Asia.However,China has made significant progress in reducing MM over the past two decades,and hence maternal death rate has declined considerably in last decade,To analyze availability and quality of emergency obstetric care (EmOC) received by women at Tongji Hospital,Wuhan,China,this study retrospectively analyzed various pregnancy-related complications at the hospital from 2000 to 2009.Two baseline periods of equal length were used for the comparison of variables.A total of 11 223 obstetric complications leading to MM were identified on a total of 15 730 hospitalizations,either 71.35％ of all activities.No maternal death was recorded.Mean age of women was 29.31 years with a wide range of 14-52 years.About 96.26％ of women had higher levels of schooling,university degrees and above and received the education of secondary school or college.About 3.74％ received primary education at period two (P2) from 2005 to 2009,which was significantly higher than that of period one (P1) from 2000 to 2004 (P＜0.05) (OR:0.586; 95％ CI:0.442 to 0.776).About 65.69％ were employed as skilled or professional workers at P2,which was significantly higher than that of P1 (P＜0.05).About 34.31％ were unskilled workers at P2,which was significantly higher than that of P1 (P＜0.05).Caesarean section was performed for 9,930 women (88.48％) and the percentage of the procedure increased significantly from 19.25％ at P1 to 69.23％ at P2 (P＜0.05).We were led to conclude that,despite the progress,significant gaps in the performance of maternal health services between rural and urban areas remain.However,MM reduction can be achieved in China.Priorities must include,but not limited to the following:secondary healthcare development,health policy and management,strengthening primary healthcare services.展开更多
An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchan...An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16<sup>ink4a</sup>, are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.展开更多
To evaluate prospectively 4 selected serum fibrosis markers （tenascin, hyaluronan, collagen Ⅵ, TIMP-1） before, during and 12 mo after IFN treatment of children with chronic hepatitis B. METHODS： Forty-seven consec...To evaluate prospectively 4 selected serum fibrosis markers （tenascin, hyaluronan, collagen Ⅵ, TIMP-1） before, during and 12 mo after IFN treatment of children with chronic hepatitis B. METHODS： Forty-seven consecutive patients with chronic hepatitis B （range 4-16 years, mean 8 years） underwent IFN treatment （3 MU tiw for 20 wk）. Fibrosis stage and inflammation grade were assessed in a blinded fashion before and 12 mo after end of treatment. Serum fibrosis markers were determined using automated assays.RESULTS： IFN treatment improved histological inflammation but did not change fibrosis in the whole group or in subgroups. Only hyaluronan correlated significantly with histological fibrosis（r = 0.3383, P = 0.022）. Basal fibrosis markers did not differ between responders （42.5%） and nonresponders（57.5%）. During IFN treatment only serum tenascin decreased significantly in the whole group and in nonresponders. When pretreatment values were compared to values 12 mo after therapy, TIMP-1 increased in all patients and in nonresponders, and hyaluronan decreased in all patients and in responders.CONCLUSION： Tenascin reflects hepatic fibrogenesis and inflammation which decreases during IFN treatment of children with chronic hepatitis B. TIMP-1 correlates with nonresponse and hyaluronan with histological fibrosis.展开更多
文摘药品风险管理贯穿于药品整个生命周期,药品风险效益评估是药品上市前审评与上市后评价的核心内容,积极深入地开展药物警戒活动是提高药品监管水平保障公众用药安全有效的重要环节。国际药物警戒学会(International Society of Pharmacovigilance,ISoP)是权威、独立、非营利性的国际性学术组织,是国际范围内公开、中立分享经验和知识的专业学术平台,旨在提升全球药物警戒的科学性,促进药物警戒和风险管理技术的发展。本文介绍了其组建发展、任务和学术交流方式等内容,提出ISoP为中国药品评价及药物警戒专业人员开启了一扇了解国际药物警戒技术和风险管理策略发展前沿的窗口,值得中国药品评价、药物警戒和药品安全领域科研、学术及医疗机构、药品生产经营企业及政府监管人员的充分关注与积极参与。
基金supported by a grant from Bayer HealthCare/Bayer Schering Pharma AG
文摘BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.
文摘Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.
文摘BACKGROUND Gastrointestinal bleeding(GIB)is a common and potentially life-threatening clinical event.To date,the literature on the long-term global epidemiology of GIB has not been systematically reviewed.AIM To systematically review the published literature on the worldwide epidemiology of upper and lower GIB.METHODS EMBASE®and MEDLINE were queried from 01 January 1965 to September 17,2019 to identify population-based studies reporting incidence,mortality,or casefatality rates of upper GIB(UGIB)or lower GIB(LGIB)in the general adult population,worldwide.Relevant outcome data were extracted and summarized(including data on rebleeding following initial occurrence of GIB when available).All included studies were assessed for risk of bias based upon reporting guidelines.RESULTS Of 4203 retrieved database hits,41 studies were included,comprising a total of around 4.1 million patients with GIB worldwide from 1980–2012.Thirty-three studies reported rates for UGIB,four for LGIB,and four presented data on both.Incidence rates ranged from 15.0 to 172.0/100000 person-years for UGIB,and from 20.5 to 87.0/100000 person-years for LGIB.Thirteen studies reported on temporal trends,generally showing an overall decline in UGIB incidence over time,although a slight increase between 2003 and 2005 followed by a decline was shown in 5/13 studies.GIB-related mortality data were available from six studies for UGIB,with rates ranging from 0.9 to 9.8/100000 person-years,and from three studies for LGIB,with rates ranging from 0.8 to 3.5/100000 person-years.Casefatality rate ranged from 0.7%to 4.8%for UGIB and 0.5%to 8.0%for LGIB.Rates of rebleeding ranged from 7.3%to 32.5%for UGIB and from 6.7%to 13.5%for LGIB.Two main areas of potential bias were the differences in the operational GIB definition used and inadequate information on how missing data were handled.CONCLUSION Wide variation was seen in estimates of GIB epidemiology,likely due to high heterogeneity between studies however,UGIB showed a decreasing trend over the years.Epidemiological data were more widely available for UGIB than for LGIB.
基金financially supported by the National Natural Science Foundation of China (31371942)the National Key Research and Development Program,China (2016YFC1200600)the Ministry of Science and Technology,China
文摘The western flower thrips, Frankliniella occidentalis, is one of the most destructive sucking pests of vegetables, fruits and ornamental crops in China. Spinosad is one of the most commonly used insecticides to manage thrips. To assess the incidence of spinosad resistance in F. occidentalis field populations in eastern China, survival rates for 24 different populations were compared with those of a susceptible laboratory strain. All populations showed significantly higher resistance to spinosad compared with the control as determined by comparing median lethal concentrations. Two populations from Shouguang and Liaocheng in Shandong Province were classified as having moderate and high levels of resistance to spinosad with a mean resistance ratio of 17.0 and 89.2, respectively. Our research indicates a widespread reduction in spinosad efficacy for controlling F. occidentalis field populations, and that resistance management strategies should be implemented as soon as practicable, to reduce the potential of progressive resistance development and loss of efficacy.
基金supported by agrant of Key Research Center for Humanities and Social Sciences in Hubei Province
文摘The burden of maternal mortality (MM) and morbidity is especially high in Asia.However,China has made significant progress in reducing MM over the past two decades,and hence maternal death rate has declined considerably in last decade,To analyze availability and quality of emergency obstetric care (EmOC) received by women at Tongji Hospital,Wuhan,China,this study retrospectively analyzed various pregnancy-related complications at the hospital from 2000 to 2009.Two baseline periods of equal length were used for the comparison of variables.A total of 11 223 obstetric complications leading to MM were identified on a total of 15 730 hospitalizations,either 71.35％ of all activities.No maternal death was recorded.Mean age of women was 29.31 years with a wide range of 14-52 years.About 96.26％ of women had higher levels of schooling,university degrees and above and received the education of secondary school or college.About 3.74％ received primary education at period two (P2) from 2005 to 2009,which was significantly higher than that of period one (P1) from 2000 to 2004 (P＜0.05) (OR:0.586; 95％ CI:0.442 to 0.776).About 65.69％ were employed as skilled or professional workers at P2,which was significantly higher than that of P1 (P＜0.05).About 34.31％ were unskilled workers at P2,which was significantly higher than that of P1 (P＜0.05).Caesarean section was performed for 9,930 women (88.48％) and the percentage of the procedure increased significantly from 19.25％ at P1 to 69.23％ at P2 (P＜0.05).We were led to conclude that,despite the progress,significant gaps in the performance of maternal health services between rural and urban areas remain.However,MM reduction can be achieved in China.Priorities must include,but not limited to the following:secondary healthcare development,health policy and management,strengthening primary healthcare services.
文摘An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16<sup>ink4a</sup>, are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.
基金Supported by the Interdisciplinary Center for Clinical Research(IZKF) of the University of Erlangen-Nuernberg, Germany
文摘To evaluate prospectively 4 selected serum fibrosis markers （tenascin, hyaluronan, collagen Ⅵ, TIMP-1） before, during and 12 mo after IFN treatment of children with chronic hepatitis B. METHODS： Forty-seven consecutive patients with chronic hepatitis B （range 4-16 years, mean 8 years） underwent IFN treatment （3 MU tiw for 20 wk）. Fibrosis stage and inflammation grade were assessed in a blinded fashion before and 12 mo after end of treatment. Serum fibrosis markers were determined using automated assays.RESULTS： IFN treatment improved histological inflammation but did not change fibrosis in the whole group or in subgroups. Only hyaluronan correlated significantly with histological fibrosis（r = 0.3383, P = 0.022）. Basal fibrosis markers did not differ between responders （42.5%） and nonresponders（57.5%）. During IFN treatment only serum tenascin decreased significantly in the whole group and in nonresponders. When pretreatment values were compared to values 12 mo after therapy, TIMP-1 increased in all patients and in nonresponders, and hyaluronan decreased in all patients and in responders.CONCLUSION： Tenascin reflects hepatic fibrogenesis and inflammation which decreases during IFN treatment of children with chronic hepatitis B. TIMP-1 correlates with nonresponse and hyaluronan with histological fibrosis.
