The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years ...The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-展开更多
Introduction Canadian academic centres and children’s hospitals have had a longstanding interest in the improvement of drug therapy for children through research conducted across the four pillars of activity identifi...Introduction Canadian academic centres and children’s hospitals have had a longstanding interest in the improvement of drug therapy for children through research conducted across the four pillars of activity identified as being of展开更多
BACKGROUND Crohn’s disease(CD)is complicated by perianal fistulas in approximately 20%of patients.Achieving permanent fistula closure remains a challenge for physicians.An association between serum anti-tumor necrosi...BACKGROUND Crohn’s disease(CD)is complicated by perianal fistulas in approximately 20%of patients.Achieving permanent fistula closure remains a challenge for physicians.An association between serum anti-tumor necrosis factor-αconcentrations and clinical outcomes in patients with CD has been demonstrated;however,little information is available on serum adalimumab(ADA)concentrations and remission of perianal fistulas in such patients.AIM To study the relationship between serum ADA concentrations and clinical remission of CDassociated perianal fistulas.METHODS This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018.At the time of each serum ADA concentration measurement,we collected information about the patients and their fistulas.The primary study endpoint was clinical remission of fistulas defined as the absence of drainage(in accordance with Present’s criteria),with a PDAI≤4,absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center.We also assessed fistula healing[defined as being in clinical and radiological(magnetic resonance imaging,MRI)remission]and adverse events.RESULTS The study cohort comprised 34 patients who underwent 56 evaluations(patients had between one and four evaluations).Fifteen patients had clinical remissions(44%),four of whom had healed fistulas on MRI.Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not[14(10-16)vs 10(2-15)μg/mL,P=0.01].Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas[11(7-14)vs 10(4-16)μg/mL,P=0.69].The adverse event rate did not differ between different serum ADA concentrations.CONCLUSION We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.展开更多
Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception eme...Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.展开更多
文摘The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-
文摘Introduction Canadian academic centres and children’s hospitals have had a longstanding interest in the improvement of drug therapy for children through research conducted across the four pillars of activity identified as being of
基金Supported by the Assistance Publique des H?pitaux de Paris and AbbVie (North Chicago, Illinois, United States)
文摘BACKGROUND Crohn’s disease(CD)is complicated by perianal fistulas in approximately 20%of patients.Achieving permanent fistula closure remains a challenge for physicians.An association between serum anti-tumor necrosis factor-αconcentrations and clinical outcomes in patients with CD has been demonstrated;however,little information is available on serum adalimumab(ADA)concentrations and remission of perianal fistulas in such patients.AIM To study the relationship between serum ADA concentrations and clinical remission of CDassociated perianal fistulas.METHODS This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018.At the time of each serum ADA concentration measurement,we collected information about the patients and their fistulas.The primary study endpoint was clinical remission of fistulas defined as the absence of drainage(in accordance with Present’s criteria),with a PDAI≤4,absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center.We also assessed fistula healing[defined as being in clinical and radiological(magnetic resonance imaging,MRI)remission]and adverse events.RESULTS The study cohort comprised 34 patients who underwent 56 evaluations(patients had between one and four evaluations).Fifteen patients had clinical remissions(44%),four of whom had healed fistulas on MRI.Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not[14(10-16)vs 10(2-15)μg/mL,P=0.01].Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas[11(7-14)vs 10(4-16)μg/mL,P=0.69].The adverse event rate did not differ between different serum ADA concentrations.CONCLUSION We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.
文摘Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.
