Objective:Treatment options for metastatic castration resistant prostate cancer(mCRPC)have expanded rapidly in recent years.Given the significant economic burden,we sought perform a cost-effectiveness analysis(CEA)of ...Objective:Treatment options for metastatic castration resistant prostate cancer(mCRPC)have expanded rapidly in recent years.Given the significant economic burden,we sought perform a cost-effectiveness analysis(CEA)of the contemporary treatment paradigm for mCRPC.Methods:We devised a treatment protocol consisting of sipuleucel-T,enzalutamide,abiraterone,docetaxel,radium-223,and cabazitaxel.We estimated number and length of treatments for each therapy using dosing schedules or progression free survival data from published clinical trials.We estimated treatment cost using billing data and Medicare reimbursement values and performed a CEA.Our analysis assumed US$100,000 per life year saved(LYS)as the threshold societal willingness to pay.Results:Incremental cost-effectiveness ratios(ICER)for strategies incorporating sipuleucel-T that were not eliminated by extended dominance exceeded the societal threshold willingnessto-pay of US$100,000 per LYS,the lowest of which was sipuleucel-T+enzalutamide+abiraterone+docetaxel at US$207,714 per LYS.Enzalutamide+abiraterone+docetaxel exhibited the most favorable ICER among strategies without sipuleucel-T at US$165,460 per LYS.Conclusion:Based on the available survival data and current costs of treatment,all treatment strategies greatly exceed a commonly assumed societal willingness-to-pay threshold of US$100,000 per LYS.Improvements in this regard can only comewith a reduction in pricing,better tailoring of treatment or significant enhancements in survival with clinical use of treatment combinations or sequences.展开更多
To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology. METHODSPati...To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology. METHODSPatients with a rectal neoplasm who underwent flexible endoscopy and biopsies were included. In case of benign biopsies rigid rectoscopy and macrobiopsies were employed. If this failed to prove malignancy, transanal endoscopic microsurgery (TEM) was used in a final effort to establish a certain preoperative diagnosis. The preoperative results were compared with the findings after surgical excision and follow up to calculate the reliability of this algorithm. RESULTSOne hundred and thirty-two patients were included. One hundred and ten patients with a carcinoma and 22 with an adenoma. Seventy-five of 110 carcinomas were proven malignant after flexible endoscopy. With the addition of rigid endoscopy and taking of macrobiopsies, this number increased to 89. Performing TEM excision biopsies further enlarged the number of proven malignancies to 100. CONCLUSIONThe step-up approach includes taking macrobiopsies through the rigid rectoscope and performing excision biopsies using transanal endoscopic microsurgery in addition to flexible endoscopy. This approach, reduced the number of missed preoperative malignant diagnoses from 32% to 9%.展开更多
Introduction: It is not known whether prone position of newborns with umbilical catheters increases the complication risk. Purpose: Analysing complications of umbilical catheters in newborns during prone positioning a...Introduction: It is not known whether prone position of newborns with umbilical catheters increases the complication risk. Purpose: Analysing complications of umbilical catheters in newborns during prone positioning and analysing if local complications as a wet or red rim increase severe complications. Subjects: Newborns (展开更多
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integr...Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.展开更多
文摘Objective:Treatment options for metastatic castration resistant prostate cancer(mCRPC)have expanded rapidly in recent years.Given the significant economic burden,we sought perform a cost-effectiveness analysis(CEA)of the contemporary treatment paradigm for mCRPC.Methods:We devised a treatment protocol consisting of sipuleucel-T,enzalutamide,abiraterone,docetaxel,radium-223,and cabazitaxel.We estimated number and length of treatments for each therapy using dosing schedules or progression free survival data from published clinical trials.We estimated treatment cost using billing data and Medicare reimbursement values and performed a CEA.Our analysis assumed US$100,000 per life year saved(LYS)as the threshold societal willingness to pay.Results:Incremental cost-effectiveness ratios(ICER)for strategies incorporating sipuleucel-T that were not eliminated by extended dominance exceeded the societal threshold willingnessto-pay of US$100,000 per LYS,the lowest of which was sipuleucel-T+enzalutamide+abiraterone+docetaxel at US$207,714 per LYS.Enzalutamide+abiraterone+docetaxel exhibited the most favorable ICER among strategies without sipuleucel-T at US$165,460 per LYS.Conclusion:Based on the available survival data and current costs of treatment,all treatment strategies greatly exceed a commonly assumed societal willingness-to-pay threshold of US$100,000 per LYS.Improvements in this regard can only comewith a reduction in pricing,better tailoring of treatment or significant enhancements in survival with clinical use of treatment combinations or sequences.
文摘To evaluate a step up approach: Taking macrobiopsies and performing excision biopsies in patients with suspected rectal cancer in which biopsies taken though the flexible endoscope showed benign histology. METHODSPatients with a rectal neoplasm who underwent flexible endoscopy and biopsies were included. In case of benign biopsies rigid rectoscopy and macrobiopsies were employed. If this failed to prove malignancy, transanal endoscopic microsurgery (TEM) was used in a final effort to establish a certain preoperative diagnosis. The preoperative results were compared with the findings after surgical excision and follow up to calculate the reliability of this algorithm. RESULTSOne hundred and thirty-two patients were included. One hundred and ten patients with a carcinoma and 22 with an adenoma. Seventy-five of 110 carcinomas were proven malignant after flexible endoscopy. With the addition of rigid endoscopy and taking of macrobiopsies, this number increased to 89. Performing TEM excision biopsies further enlarged the number of proven malignancies to 100. CONCLUSIONThe step-up approach includes taking macrobiopsies through the rigid rectoscope and performing excision biopsies using transanal endoscopic microsurgery in addition to flexible endoscopy. This approach, reduced the number of missed preoperative malignant diagnoses from 32% to 9%.
文摘Introduction: It is not known whether prone position of newborns with umbilical catheters increases the complication risk. Purpose: Analysing complications of umbilical catheters in newborns during prone positioning and analysing if local complications as a wet or red rim increase severe complications. Subjects: Newborns (
基金the Key International(Regional)Cooperative Research Project(No.81820108028)the National Natural Science Foundation of China(Nos.81521004,81922061,81973123,and 81803306)+2 种基金the Science Foundation for Distinguished Young Scholars of Jiangsu(No.BK20160046)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).the National Cancer Institute,National Institutes of Health of USA through grants U01-CA063673,UM1-CA167462,and U01-CA167462.
文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
