AIM:To investigate usefulness of adherence to gastroesophageal reflux disease(GERD) guideline established by the Spanish Association of Gastroenterology.METHODS:Prospective,observational and multicentre study of 301 p...AIM:To investigate usefulness of adherence to gastroesophageal reflux disease(GERD) guideline established by the Spanish Association of Gastroenterology.METHODS:Prospective,observational and multicentre study of 301 patients with typical symptoms of GERD who should be managed in accordance with guidelines and were attended by gastroenterologists in daily practice.Patients(aged > 18 years) were eligible for inclusion if they had typical symptoms of GERD(heartburn and/or acid regurgitation) as the major complaint in the presence or absence of accompanying atypical symptoms,such as dyspeptic symptoms and/or supraesophageal symptoms.Diagnostic and therapeutic decisions should be made based on specific recommendations of the Spanish clinical practice guideline for GERD which is a widely disseminated and well known instrument among Spanish in digestive disease specialists.RESULTS:Endoscopy was indicated in 123(41%) patients:50 with alarm symptoms,32 with age > 50 years without alarm symptom.Seventy-two patients(58.5%) had esophagitis(grade A,23,grade B,28,grade C,18,grade D,3).In the presence of alarm symptoms,endoscopy was indicated consistently with recommendations in 98% of cases.However,in the absence of alarm symptoms,endoscopy was indicated in 33% of patients > 50 years(not recommended by the guideline).Adherence for proton pump inhibitors(PPIs) therapy was 80%,but doses prescribed were lower(half) in 5% of cases and higher(double) in 15%.Adherence regarding duration of PPI therapy was 69%;duration was shorter than recommended in 1%(4 wk in esophagitis grades C-D) or longer in 30%(8 wk in esophagitis grades A-B or in patients without endoscopy).Treatment response was higher when PPI doses were consistent with guidelines,although differences were not significant(95% vs 85%).CONCLUSION:GERD guideline compliance was quite good although endoscopy was over indicated in patients > 50 years without alarm symptoms;PPIs were prescribed at higher doses and longer duration.展开更多
In recent years histone deacetylase inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. While favorable responses to HDACi’s as single agents have been shown in several hematological malignancies...In recent years histone deacetylase inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. While favorable responses to HDACi’s as single agents have been shown in several hematological malignancies, very little efficacy has been demonstrated in solid tumors. c-Myc (Myc), an oncoprotein commonly over-expressed in cancer, has been shown by several studies to play a critical role in HDACi-mediated cellular death. To expand upon these findings and determine the role that Myc plays in this process in solid tumors, we compared the effect of two HDAC inhibitors, SAHA and LAQ824, on the proliferation of solid tumor cell lines expressing high versus low levels of Myc. We found that cells expressing high levels of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cell types with prominent apoptosis in cells expressing higher levels of Myc while cell cycle arrest was more commonly observed in cells expressing lower levels of Myc. Interestingly, HDACi reduced the expression of Myc and one of its well-known oncogenic miRNA targets, miR-17~92 cluster, resulting in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel mechanism may play a role in the potent anti-proliferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression could be used as a predictive biomarker to select patients with solid tumors who may be more responsive to HDACi treatment.展开更多
Background: Daivobetis a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle. Objective: To assess the cost-effectiveness of once-daily treatme...Background: Daivobetis a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle. Objective: To assess the cost-effectiveness of once-daily treatment with Daivobet (4 weeks) followed by calcipotriol (4 weeks) compared to tacalcitol (8 weeks). Methods: Resource utilization was assessed within a double-blind 8-week clinical trial (all treatments for psoriasis, adverse events and concomitant dermatological medication), estimated from the French societal perspective. Results: Total direct medical costs for psoriasis were comparable (Daivobet: EUR 107.53 and tacalcitol EUR 113.50) despite a higher acquisition cost for Daivobet. The probability of ≥75%reduction in the Psoriasis Area and Severity Index (effectiveness criterion) was 46.6%with Daivobet and 13.9%with tacalcitol at 4 weeks, and 44.6 and 23.8%, respectively, at 8 weeks (both: p < 0.001). Over 8 weeks, Daivobet was almost twice as cost-effective as tacalcitol (EUR 241.22 per successful treatment vs. EUR 476.70); this result was robust to sensitivity assumptions. Conclusion: Daivobet is more effective and less costly than tacalcitol for treating psoriasis.展开更多
随着中国进入老龄化社会,人口生育政策逐步放开,揭示脑与行为毕生发展的一般规律和常规模式(常模)正成为公共卫生和人口健康领域的重大基础需求.本文介绍"中国彩巢计划"(Chinese Color Nest Project—CCNP)这一在全国范围内...随着中国进入老龄化社会,人口生育政策逐步放开,揭示脑与行为毕生发展的一般规律和常规模式(常模)正成为公共卫生和人口健康领域的重大基础需求.本文介绍"中国彩巢计划"(Chinese Color Nest Project—CCNP)这一在全国范围内分期分步地开展的项目规划,在10年(2013~2022年:http://zuolab.psych.ac.cn/colornest.html)内CCNP将积累毕生发展各年龄段的心理行为与脑影像样本,基于加速纵向实验设计方法建立中国人脑毕生发展的常模轨线.作为CCNP的发育项目"成长在中国"(dev CCNP:Growing Up in China)这一学龄儿童青少年脑与行为生长曲线项目,dev CCNP已经完成对重庆北碚区192名健康儿童青少年(6~18岁)的5年追踪.初步的研究结果表明,dev CCNP在实验设计、样本采集策略、数据获取和存储、初步发现和数据共享等方面具备长期实施的可行性,我国应及早部署开展儿童青少年的脑与认知生长曲线常模的大规模脑科学研究计划,提升中国在脑科学与医疗健康研究领域的国际实力和影响力,革新脑疾病临床实践.展开更多
Despite its importance and potential impact in clinical trials,central reading continues to be an under-represented topic in the literature about inflammatory bowel disease(IBD)clinical trials.Although several IBD stu...Despite its importance and potential impact in clinical trials,central reading continues to be an under-represented topic in the literature about inflammatory bowel disease(IBD)clinical trials.Although several IBD studies have incorporated central reading to date,none have fully detailed the specific methodology with which the reads were conducted.Here we outline key principles for designing an efficient central reading paradigm for an ulcerative colitis(UC)study that addresses regulatory,operational and clinical expectations.As a step towards standardization of read methodology for the growing number of multicenter phase 3 clinical trials in IBD,we have applied these principles to the design of an optimal read methodology that we call the‘2þ1 paradigm.’The 2þ1 paradigm involves the use of both site and central readers,validated scoring criteria and multiple measures for blinding readers,all of which contribute to reducing bias and generating a reliable endoscopic subscore that reflects endoscopic disease severity.The paradigm can be utilized while maintaining a practical workflow compatible with an operationally feasible clinical trial.The 2þ1 paradigm represents a logical approach to endoscopic assessment in IBD clinical trials,one that should be considered attractive to prospective sponsors,contract research organizations,key opinion leaders and regulatory authorities and be ready for implementation and further evaluation.展开更多
Celiac disease is a lifelong disorder for which there is currently only one known,effective treatment:a gluten-free diet.New treatment approaches have recently emerged;several drugs are in Phase 2 trials and results a...Celiac disease is a lifelong disorder for which there is currently only one known,effective treatment:a gluten-free diet.New treatment approaches have recently emerged;several drugs are in Phase 2 trials and results appear promising;however,discussion around regulatory endpoints is in its infancy.We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints,such as patient-reported outcomes,histology,serology,gene expression analysis and other tests.We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials,with a particular emphasis on current thinking in regulatory agencies.We conclude our paper with recommendations and a glossary of regulatory terms,to enable readers who are less familiar with regulatory language to take maximum advantage of this review.展开更多
文摘AIM:To investigate usefulness of adherence to gastroesophageal reflux disease(GERD) guideline established by the Spanish Association of Gastroenterology.METHODS:Prospective,observational and multicentre study of 301 patients with typical symptoms of GERD who should be managed in accordance with guidelines and were attended by gastroenterologists in daily practice.Patients(aged > 18 years) were eligible for inclusion if they had typical symptoms of GERD(heartburn and/or acid regurgitation) as the major complaint in the presence or absence of accompanying atypical symptoms,such as dyspeptic symptoms and/or supraesophageal symptoms.Diagnostic and therapeutic decisions should be made based on specific recommendations of the Spanish clinical practice guideline for GERD which is a widely disseminated and well known instrument among Spanish in digestive disease specialists.RESULTS:Endoscopy was indicated in 123(41%) patients:50 with alarm symptoms,32 with age > 50 years without alarm symptom.Seventy-two patients(58.5%) had esophagitis(grade A,23,grade B,28,grade C,18,grade D,3).In the presence of alarm symptoms,endoscopy was indicated consistently with recommendations in 98% of cases.However,in the absence of alarm symptoms,endoscopy was indicated in 33% of patients > 50 years(not recommended by the guideline).Adherence for proton pump inhibitors(PPIs) therapy was 80%,but doses prescribed were lower(half) in 5% of cases and higher(double) in 15%.Adherence regarding duration of PPI therapy was 69%;duration was shorter than recommended in 1%(4 wk in esophagitis grades C-D) or longer in 30%(8 wk in esophagitis grades A-B or in patients without endoscopy).Treatment response was higher when PPI doses were consistent with guidelines,although differences were not significant(95% vs 85%).CONCLUSION:GERD guideline compliance was quite good although endoscopy was over indicated in patients > 50 years without alarm symptoms;PPIs were prescribed at higher doses and longer duration.
文摘In recent years histone deacetylase inhibitors (HDACi’s) have emerged as promising therapeutics for cancer. While favorable responses to HDACi’s as single agents have been shown in several hematological malignancies, very little efficacy has been demonstrated in solid tumors. c-Myc (Myc), an oncoprotein commonly over-expressed in cancer, has been shown by several studies to play a critical role in HDACi-mediated cellular death. To expand upon these findings and determine the role that Myc plays in this process in solid tumors, we compared the effect of two HDAC inhibitors, SAHA and LAQ824, on the proliferation of solid tumor cell lines expressing high versus low levels of Myc. We found that cells expressing high levels of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cell types with prominent apoptosis in cells expressing higher levels of Myc while cell cycle arrest was more commonly observed in cells expressing lower levels of Myc. Interestingly, HDACi reduced the expression of Myc and one of its well-known oncogenic miRNA targets, miR-17~92 cluster, resulting in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel mechanism may play a role in the potent anti-proliferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression could be used as a predictive biomarker to select patients with solid tumors who may be more responsive to HDACi treatment.
文摘Background: Daivobetis a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle. Objective: To assess the cost-effectiveness of once-daily treatment with Daivobet (4 weeks) followed by calcipotriol (4 weeks) compared to tacalcitol (8 weeks). Methods: Resource utilization was assessed within a double-blind 8-week clinical trial (all treatments for psoriasis, adverse events and concomitant dermatological medication), estimated from the French societal perspective. Results: Total direct medical costs for psoriasis were comparable (Daivobet: EUR 107.53 and tacalcitol EUR 113.50) despite a higher acquisition cost for Daivobet. The probability of ≥75%reduction in the Psoriasis Area and Severity Index (effectiveness criterion) was 46.6%with Daivobet and 13.9%with tacalcitol at 4 weeks, and 44.6 and 23.8%, respectively, at 8 weeks (both: p < 0.001). Over 8 weeks, Daivobet was almost twice as cost-effective as tacalcitol (EUR 241.22 per successful treatment vs. EUR 476.70); this result was robust to sensitivity assumptions. Conclusion: Daivobet is more effective and less costly than tacalcitol for treating psoriasis.
文摘随着中国进入老龄化社会,人口生育政策逐步放开,揭示脑与行为毕生发展的一般规律和常规模式(常模)正成为公共卫生和人口健康领域的重大基础需求.本文介绍"中国彩巢计划"(Chinese Color Nest Project—CCNP)这一在全国范围内分期分步地开展的项目规划,在10年(2013~2022年:http://zuolab.psych.ac.cn/colornest.html)内CCNP将积累毕生发展各年龄段的心理行为与脑影像样本,基于加速纵向实验设计方法建立中国人脑毕生发展的常模轨线.作为CCNP的发育项目"成长在中国"(dev CCNP:Growing Up in China)这一学龄儿童青少年脑与行为生长曲线项目,dev CCNP已经完成对重庆北碚区192名健康儿童青少年(6~18岁)的5年追踪.初步的研究结果表明,dev CCNP在实验设计、样本采集策略、数据获取和存储、初步发现和数据共享等方面具备长期实施的可行性,我国应及早部署开展儿童青少年的脑与认知生长曲线常模的大规模脑科学研究计划,提升中国在脑科学与医疗健康研究领域的国际实力和影响力,革新脑疾病临床实践.
文摘Despite its importance and potential impact in clinical trials,central reading continues to be an under-represented topic in the literature about inflammatory bowel disease(IBD)clinical trials.Although several IBD studies have incorporated central reading to date,none have fully detailed the specific methodology with which the reads were conducted.Here we outline key principles for designing an efficient central reading paradigm for an ulcerative colitis(UC)study that addresses regulatory,operational and clinical expectations.As a step towards standardization of read methodology for the growing number of multicenter phase 3 clinical trials in IBD,we have applied these principles to the design of an optimal read methodology that we call the‘2þ1 paradigm.’The 2þ1 paradigm involves the use of both site and central readers,validated scoring criteria and multiple measures for blinding readers,all of which contribute to reducing bias and generating a reliable endoscopic subscore that reflects endoscopic disease severity.The paradigm can be utilized while maintaining a practical workflow compatible with an operationally feasible clinical trial.The 2þ1 paradigm represents a logical approach to endoscopic assessment in IBD clinical trials,one that should be considered attractive to prospective sponsors,contract research organizations,key opinion leaders and regulatory authorities and be ready for implementation and further evaluation.
文摘Celiac disease is a lifelong disorder for which there is currently only one known,effective treatment:a gluten-free diet.New treatment approaches have recently emerged;several drugs are in Phase 2 trials and results appear promising;however,discussion around regulatory endpoints is in its infancy.We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints,such as patient-reported outcomes,histology,serology,gene expression analysis and other tests.We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials,with a particular emphasis on current thinking in regulatory agencies.We conclude our paper with recommendations and a glossary of regulatory terms,to enable readers who are less familiar with regulatory language to take maximum advantage of this review.
