In 2002,the National Kidney Foundation Kidney Disease Outcomes Quality Initiative(NKF KDOQI)instituted new guidelines that established a novel chronic kidney disease(CKD)staging paradigm.This set of guidelines,since u...In 2002,the National Kidney Foundation Kidney Disease Outcomes Quality Initiative(NKF KDOQI)instituted new guidelines that established a novel chronic kidney disease(CKD)staging paradigm.This set of guidelines,since updated,is now very widely accepted around the world.Nevertheless,the authoritative United States Preventative Task Force had in August 2012acknowledged that we know surprisingly little about whether screening adults with no signs or symptoms of CKD improve health outcomes and that we deserve better information on CKD.More recently,the American Society of Nephrology and the American College of Physicians,two very well respected United States professional physician organizations were strongly at odds coming out with exactly opposite recommendations regarding the need or otherwise for"CKD screening"among the asymptomatic population.In this review,we revisit the various angles and perspectives of these conflicting arguments,raise unanswered questionsregarding the validity and veracity of the NKF KDOQI CKD staging model,and raise even more questions about the soundness of its evidence-base.We show clinical evidence,from a Mayo Clinic Health System Renal Unit in Northwestern Wisconsin,United States,of the pitfalls of the current CKD staging model,show the inexactitude and unpredictable vagaries of current CKD prediction models and call for a more cautious and guarded application of CKD staging paradigms in clinical practice.The impacts of acute kidney injury on CKD initiation and CKD propagation and progression,the effects of such phenomenon as the syndrome of late onset renal failure from angiotensin blockade and the syndrome of rapid onset end stage renal disease on CKD initiation,CKD propagation and CKD progression to end stage renal disease all demand further study and analysis.Yet more research on CKD staging,CKD prognostication and CKD predictions are warranted.Finally and most importantly,cognizant of the very serious limitations and drawbacks of the NKF K/DOQI CKD staging model,the need to individualize CKD care,both in terms of patient care and prognostication,cannot be overemphasized.展开更多
Background: Group B Streptococcus [GBS] is a bacterium which transiently colonises the genital tract and can be transmitted from mother to baby at birth. Babies colonised with GBS can develop early-onset group B strep...Background: Group B Streptococcus [GBS] is a bacterium which transiently colonises the genital tract and can be transmitted from mother to baby at birth. Babies colonised with GBS can develop early-onset group B streptococcus disease [EOGBSD] which can lead to extended hospital stay, disability and death. One of the primary methods for determining which women are most likely to be GBS positive at the time of birth is antenatal universal culture-based screening. Recently Polymerase Chain Reaction [PCR] screening has emerged as a point-of-care method for screening women during the intrapartum period. This study will compare the diagnostic accuracy of this new technology and antenatal culture-based screening at 35 to 37 weeks gestational age, with the reference standard of formal culture-based testing in labour. Methods: This prospective observational study will take place in an Australian hospital. Consecutive women with one or more live fetuses, intending to have a vaginal birth will be asked to participate. Planned screening for GBS colonisation using microbiological culture on a self-collected specimen will occur at 35 to 37 completed weeks gestational age as per our usual hospital policy. A PCR GBS test by Xpert GBS (Cepheid) will be performed on admission to labour ward or at the time of rupture of membranes. The reference standard will be a formal GBS culture on a combined lower vaginal and perianal swab. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios will be estimated for both antenatal screening and the intrapartum Xpert GBS (Cepheid) point-of-care test and compared to the reference standard. Results: It is expected that the study will be completed by mid to late 2020. Conclusion: This study has the potential to improve the accuracy of GBS screening of pregnant women and therefore health outcomes for mothers and babies. There is also the potential for a cost savings to the health system.展开更多
Objective:Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis.This phase 3,multicenter,randomized,double-blind,placebo-c...Objective:Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis.This phase 3,multicenter,randomized,double-blind,placebo-controlled trial(NCT03364309;registered December 6,2017)evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis.Methods:438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks(IXE Q2W,n=176),80 mg ixekizumab every 4 weeks(IXE Q4W,n=174),or placebo(n=88).Efficacy was assessed by evaluating the static Physician’s Global Assessment score of 0 or 1(sPGA[0,1])and Psoriasis Area and Severity Index(PASI)75/90/100 responses,and nonresponder imputation was used for handling missing data.The safety profile was evaluated by assessing treatment emergent adverse events(AEs)and serious AEs.Results:At week 12,the sPGA(0,1)response rates were 3.4%,79.9%,and 86.4%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%,87.4%/75.9%/29.3%,and 93.8%/82.4%/33.0%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.Ixekizumab led to rapid PASI 50 responses,as early as week 1,whereas PASI 75 and sPGA(0,1)responses were observed from week 2.sPGA(0,1)and sPGA(0)responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs.placebo.The safety profile was consistent with previous studies of ixekizumab in psoriasis.Conclusion:Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs,in Chinese patients with moderate-to-severe plaque psoriasis.展开更多
文摘In 2002,the National Kidney Foundation Kidney Disease Outcomes Quality Initiative(NKF KDOQI)instituted new guidelines that established a novel chronic kidney disease(CKD)staging paradigm.This set of guidelines,since updated,is now very widely accepted around the world.Nevertheless,the authoritative United States Preventative Task Force had in August 2012acknowledged that we know surprisingly little about whether screening adults with no signs or symptoms of CKD improve health outcomes and that we deserve better information on CKD.More recently,the American Society of Nephrology and the American College of Physicians,two very well respected United States professional physician organizations were strongly at odds coming out with exactly opposite recommendations regarding the need or otherwise for"CKD screening"among the asymptomatic population.In this review,we revisit the various angles and perspectives of these conflicting arguments,raise unanswered questionsregarding the validity and veracity of the NKF KDOQI CKD staging model,and raise even more questions about the soundness of its evidence-base.We show clinical evidence,from a Mayo Clinic Health System Renal Unit in Northwestern Wisconsin,United States,of the pitfalls of the current CKD staging model,show the inexactitude and unpredictable vagaries of current CKD prediction models and call for a more cautious and guarded application of CKD staging paradigms in clinical practice.The impacts of acute kidney injury on CKD initiation and CKD propagation and progression,the effects of such phenomenon as the syndrome of late onset renal failure from angiotensin blockade and the syndrome of rapid onset end stage renal disease on CKD initiation,CKD propagation and CKD progression to end stage renal disease all demand further study and analysis.Yet more research on CKD staging,CKD prognostication and CKD predictions are warranted.Finally and most importantly,cognizant of the very serious limitations and drawbacks of the NKF K/DOQI CKD staging model,the need to individualize CKD care,both in terms of patient care and prognostication,cannot be overemphasized.
文摘Background: Group B Streptococcus [GBS] is a bacterium which transiently colonises the genital tract and can be transmitted from mother to baby at birth. Babies colonised with GBS can develop early-onset group B streptococcus disease [EOGBSD] which can lead to extended hospital stay, disability and death. One of the primary methods for determining which women are most likely to be GBS positive at the time of birth is antenatal universal culture-based screening. Recently Polymerase Chain Reaction [PCR] screening has emerged as a point-of-care method for screening women during the intrapartum period. This study will compare the diagnostic accuracy of this new technology and antenatal culture-based screening at 35 to 37 weeks gestational age, with the reference standard of formal culture-based testing in labour. Methods: This prospective observational study will take place in an Australian hospital. Consecutive women with one or more live fetuses, intending to have a vaginal birth will be asked to participate. Planned screening for GBS colonisation using microbiological culture on a self-collected specimen will occur at 35 to 37 completed weeks gestational age as per our usual hospital policy. A PCR GBS test by Xpert GBS (Cepheid) will be performed on admission to labour ward or at the time of rupture of membranes. The reference standard will be a formal GBS culture on a combined lower vaginal and perianal swab. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios will be estimated for both antenatal screening and the intrapartum Xpert GBS (Cepheid) point-of-care test and compared to the reference standard. Results: It is expected that the study will be completed by mid to late 2020. Conclusion: This study has the potential to improve the accuracy of GBS screening of pregnant women and therefore health outcomes for mothers and babies. There is also the potential for a cost savings to the health system.
基金This study was sponsored by Eli Lilly, the manufacturer/licensee of ixekizumab.
文摘Objective:Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis.This phase 3,multicenter,randomized,double-blind,placebo-controlled trial(NCT03364309;registered December 6,2017)evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis.Methods:438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks(IXE Q2W,n=176),80 mg ixekizumab every 4 weeks(IXE Q4W,n=174),or placebo(n=88).Efficacy was assessed by evaluating the static Physician’s Global Assessment score of 0 or 1(sPGA[0,1])and Psoriasis Area and Severity Index(PASI)75/90/100 responses,and nonresponder imputation was used for handling missing data.The safety profile was evaluated by assessing treatment emergent adverse events(AEs)and serious AEs.Results:At week 12,the sPGA(0,1)response rates were 3.4%,79.9%,and 86.4%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%,87.4%/75.9%/29.3%,and 93.8%/82.4%/33.0%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.Ixekizumab led to rapid PASI 50 responses,as early as week 1,whereas PASI 75 and sPGA(0,1)responses were observed from week 2.sPGA(0,1)and sPGA(0)responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs.placebo.The safety profile was consistent with previous studies of ixekizumab in psoriasis.Conclusion:Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs,in Chinese patients with moderate-to-severe plaque psoriasis.
