Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of ...Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including （1） bisphosphonates such as zoledronic acid, which directly target osteoclasts, （2） denosumab, a receptor activator of nuclear factor-kappa B （RANK） ligand inhibitor, which targets a key component of bone stromal interaction, and （3） radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer （mCRPC）. Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.展开更多
The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen de...The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.展开更多
Objective:To investigate the risk factors and protective measures of COVID-19 among policemen in an eastern state of India.Methods:This case-control study was conducted in Bihar,located in the eastern part of India.In...Objective:To investigate the risk factors and protective measures of COVID-19 among policemen in an eastern state of India.Methods:This case-control study was conducted in Bihar,located in the eastern part of India.In total,6 confirmed COVID-19 cases(the case group)and 11 negative contacts of these cases(the control group)of Bihar Military Police participated in the study.Results:All subjects were male with a median age of 51(range:23-60)years.Among these 6 confirmed cases,5 cases were asymptomatic.One third(33.3%)of the case group and the majority(90.9%)of the control group reported maintenance of physical distance of at least 1 meter with others all the time,which was significantly different(P=0.028).There was no other statistically significant difference between the case group and the control group.Conclusions:Physical distancing is the most effective public health measure to control contagious diseases like COVID-19,especially in the absence of an effective vaccine in police settings.展开更多
1|NATIO NAL DIGITAL HEALTH MISSION(NDHM):THE BEGINNING Ever since the National Health Policy,2017 was released,the drive to digitalize the Indian healthcare system has been given more importance,in line with the Unite...1|NATIO NAL DIGITAL HEALTH MISSION(NDHM):THE BEGINNING Ever since the National Health Policy,2017 was released,the drive to digitalize the Indian healthcare system has been given more importance,in line with the United Nations'Sustainable Development Goals(SDGs).The Policy empha-sizes the implementation of digital health in all levels of care—primary,secondary,and tertiary—to maintain the continuity of patient care.The application of digital technology tools and their integration in all facets of healthcare services is expected to improve the functional efficiency and outcomes of the Indian healthcare system[1].展开更多
文摘Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including （1） bisphosphonates such as zoledronic acid, which directly target osteoclasts, （2） denosumab, a receptor activator of nuclear factor-kappa B （RANK） ligand inhibitor, which targets a key component of bone stromal interaction, and （3） radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer （mCRPC）. Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
基金The study was funded by Janssen Pharmaceutical Ltd.Writing assistance was provided by Katherine A Lyseng-Williamson and Kerry Dechant,ISMPP CMPP^(TM),on behalf of Content Ed Net,and was funded by Janssen Pharmaceutical Ltd.Janssen Pharmaceutical Ltd.is not involved in the process of experimental design,results,or discussion,and has no competing interests with this study.
文摘The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.
文摘Objective:To investigate the risk factors and protective measures of COVID-19 among policemen in an eastern state of India.Methods:This case-control study was conducted in Bihar,located in the eastern part of India.In total,6 confirmed COVID-19 cases(the case group)and 11 negative contacts of these cases(the control group)of Bihar Military Police participated in the study.Results:All subjects were male with a median age of 51(range:23-60)years.Among these 6 confirmed cases,5 cases were asymptomatic.One third(33.3%)of the case group and the majority(90.9%)of the control group reported maintenance of physical distance of at least 1 meter with others all the time,which was significantly different(P=0.028).There was no other statistically significant difference between the case group and the control group.Conclusions:Physical distancing is the most effective public health measure to control contagious diseases like COVID-19,especially in the absence of an effective vaccine in police settings.
文摘1|NATIO NAL DIGITAL HEALTH MISSION(NDHM):THE BEGINNING Ever since the National Health Policy,2017 was released,the drive to digitalize the Indian healthcare system has been given more importance,in line with the United Nations'Sustainable Development Goals(SDGs).The Policy empha-sizes the implementation of digital health in all levels of care—primary,secondary,and tertiary—to maintain the continuity of patient care.The application of digital technology tools and their integration in all facets of healthcare services is expected to improve the functional efficiency and outcomes of the Indian healthcare system[1].
