LIVIVO - Search results -

Search results

Result 1 - 10 of total 12

Search options

Article ; Online: Daily low-dose prednisolone to prevent relapse of steroid-sensitive nephrotic syndrome in children with an upper respiratory tract infection: PREDNOS2 RCT.

Health technology assessment (Winchester, England)

2022 Volume 26, Issue 3, Page(s) 1–94

Abstract: Background: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper ... ...

Abstract	Background: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5-7 days during an upper respiratory tract infection reduces the risk of relapse. Objectives: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. Design: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. Setting: A total of 122 UK paediatric departments, of which 91 recruited patients. Participants: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). Interventions: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m Main outcome measures: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. Results: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference -0.024, 95% confidence interval -0.14 to 0.09; Limitations: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. Conclusions: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. Future work: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. Trial registration: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
MeSH term(s)	Child ; Child, Preschool ; Cost-Benefit Analysis ; Humans ; Neoplasm Recurrence, Local ; Nephrotic Syndrome/drug therapy ; Prednisolone/adverse effects ; Prednisolone/therapeutic use ; Quality of Life ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/epidemiology
Chemical Substances	Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2022-01-21
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2006765-3
ISSN	2046-4924 ; 1366-5278
ISSN (online)	2046-4924
ISSN	1366-5278
DOI	10.3310/WTFC5658
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5162: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Economic Evaluation of Using Daily Prednisolone versus Placebo at the Time of an Upper Respiratory Tract Infection for the Management of Children with Steroid-Sensitive Nephrotic Syndrome: A Model-Based Analysis.

PharmacoEconomics - open

2022 Volume 6, Issue 4, Page(s) 605–617

Abstract: Background: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are ... ...

Abstract	Background: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. Objective: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. Methods: A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. Results: The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. Conclusion: A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.
Language	English
Publishing date	2022-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2874287-4
ISSN	2509-4254 ; 2509-4262
ISSN (online)	2509-4254
ISSN	2509-4262
DOI	10.1007/s41669-022-00334-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Mapping the Paediatric Quality of Life Inventory (PedsQL™) Generic Core Scales onto the Child Health Utility Index-9 Dimension (CHU-9D) Score for Economic Evaluation in Children.

Lambe, Tosin / Frew, Emma / Ives, Natalie J / Woolley, Rebecca L / Cummins, Carole / Brettell, Elizabeth A / Barsoum, Emma N / Webb, Nicholas J A

PharmacoEconomics

2017 Volume 36, Issue 4, Page(s) 451–465

Abstract: Background: The Paediatric Quality of Life Inventory (PedsQL™) questionnaire is a widely used, generic instrument designed for measuring health-related quality of life (HRQoL); however, it is not preference-based and therefore not suitable for cost- ... ...

Abstract	Background: The Paediatric Quality of Life Inventory (PedsQL™) questionnaire is a widely used, generic instrument designed for measuring health-related quality of life (HRQoL); however, it is not preference-based and therefore not suitable for cost-utility analysis. The Child Health Utility Index-9 Dimension (CHU-9D), however, is a preference-based instrument that has been primarily developed to support cost-utility analysis. Objective: This paper presents a method for estimating CHU-9D index scores from responses to the PedsQL™ using data from a randomised controlled trial of prednisolone therapy for treatment of childhood corticosteroid-sensitive nephrotic syndrome. Methods: HRQoL data were collected from children at randomisation, week 16, and months 12, 18, 24, 36 and 48. Observations on children aged 5 years and older were pooled across all data collection timepoints and were then randomised into an estimation (n = 279) and validation (n = 284) sample. A number of models were developed using the estimation data before internal validation. The best model was chosen using multi-stage selection criteria. Results: Most of the models developed accurately predicted the CHU-9D mean index score. The best performing model was a generalised linear model (mean absolute error = 0.0408; mean square error = 0.0035). The proportion of index scores deviating from the observed scores by < 0.03 was 53%. Conclusions: The mapping algorithm provides an empirical tool for estimating CHU-9D index scores and for conducting cost-utility analyses within clinical studies that have only collected PedsQL™ data. It is valid for children aged 5 years or older. Caution should be exercised when using this with children younger than 5 years, older adolescents (> 13 years) or patient groups with particularly poor quality of life. Isrctn registry no: 16645249.
MeSH term(s)	Adolescent ; Algorithms ; Child ; Child Health/economics ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Models, Statistical ; Quality of Life ; Randomized Controlled Trials as Topic/statistics & numerical data ; Surveys and Questionnaires/statistics & numerical data
Language	English
Publishing date	2017-12-21
Publishing country	New Zealand
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ZDB-ID	1100273-6
ISSN	1179-2027 ; 1170-7690
ISSN (online)	1179-2027
ISSN	1170-7690
DOI	10.1007/s40273-017-0600-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 3579: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation.

Webb, Nicholas J A / Woolley, Rebecca L / Lambe, Tosin / Frew, Emma / Brettell, Elizabeth A / Barsoum, Emma N / Trompeter, Richard S / Cummins, Carole / Deeks, Jonathan J / Wheatley, Keith / Ives, Natalie J

BMJ (Clinical research ed.)

2019 Volume 365, Page(s) l1800

Abstract: Objective: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse.: Design: Double blind, parallel group, phase III ...

Abstract	Objective: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m Main outcome measures: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) Conclusions: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration: ISRCTN16645249; EudraCT 2010-022489-29.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Cost-Benefit Analysis ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Drug Monitoring/methods ; Female ; Glucocorticoids/administration & dosage ; Glucocorticoids/adverse effects ; Glucocorticoids/economics ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Intention to Treat Analysis ; Long-Term Care/economics ; Long-Term Care/methods ; Male ; Nephrotic Syndrome/diagnosis ; Nephrotic Syndrome/drug therapy ; Nephrotic Syndrome/economics ; Nephrotic Syndrome/psychology ; Prednisolone/administration & dosage ; Prednisolone/adverse effects ; Prednisolone/economics ; Quality of Life ; Secondary Prevention/economics ; Secondary Prevention/methods ; Treatment Outcome
Chemical Substances	Glucocorticoids ; Immunosuppressive Agents ; Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2019-05-23
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.l1800
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.10: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Sixteen-week versus standard eight-week prednisolone therapy for childhood nephrotic syndrome: the PREDNOS RCT.

Webb, Nicholas Ja / Woolley, Rebecca L / Lambe, Tosin / Frew, Emma / Brettell, Elizabeth A / Barsoum, Emma N / Trompeter, Richard S / Cummins, Carole / Wheatley, Keith / Ives, Natalie J

Health technology assessment (Winchester, England)

2019 Volume 23, Issue 26, Page(s) 1–108

Abstract: Background: The optimal corticosteroid regimen for treating the presenting episode of steroid-sensitive nephrotic syndrome (SSNS) remains uncertain. Most UK centres use an 8-week regimen, despite previous systematic reviews indicating that longer ... ...

Abstract	Background: The optimal corticosteroid regimen for treating the presenting episode of steroid-sensitive nephrotic syndrome (SSNS) remains uncertain. Most UK centres use an 8-week regimen, despite previous systematic reviews indicating that longer regimens reduce the risk of relapse and frequently relapsing nephrotic syndrome (FRNS). Objectives: The primary objective was to determine whether or not an extended 16-week course of prednisolone increases the time to first relapse. The secondary objectives were to compare the relapse rate, FRNS and steroid-dependent nephrotic syndrome (SDNS) rates, requirement for alternative immunosuppressive agents and corticosteroid-related adverse events (AEs), including adverse behaviour and costs. Design: Randomised double-blind parallel-group placebo-controlled trial, including a cost-effectiveness analysis. Setting: One hundred and twenty-five UK paediatric departments. Participants: Two hundred and thirty-seven children presenting with a first episode of SSNS. Participants aged between 1 and 15 years were randomised (1 : 1) according to a minimisation algorithm to ensure balance of ethnicity (South Asian, white or other) and age (≤ 5 or ≥ 6 years). Interventions: The control group ( Main outcome measures: The primary outcome measure was time to first relapse [Albustix Results: There was no significant difference in time to first relapse between the SC and EC groups (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17; log-rank Limitations: Study drug formulation may have prevented some younger children who were unable to swallow whole or crushed tablets from participating. Conclusions: This trial has not shown any clinical benefit for EC prednisolone therapy in UK children. The cost-effectiveness analysis suggested that EC therapy may be cheaper, with the possibility of a small QALY benefit. Future work: Studies investigating EC versus SC therapy in younger children and further cost-effectiveness analyses are warranted. Trial registration: Current Controlled Trials ISRCTN16645249 and EudraCT 2010-022489-29. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Cost-Benefit Analysis ; Drug Administration Schedule ; Female ; Glucocorticoids/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Male ; Nephrotic Syndrome/drug therapy ; Prednisolone/therapeutic use ; Recurrence ; Standard of Care ; Technology Assessment, Biomedical
Chemical Substances	Glucocorticoids ; Immunosuppressive Agents ; Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2019-06-01
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2006765-3
ISSN	2046-4924 ; 1366-5278
ISSN (online)	2046-4924
ISSN	1366-5278
DOI	10.3310/hta23260
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5162: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Evaluation of Daily Low-Dose Prednisolone During Upper Respiratory Tract Infection to Prevent Relapse in Children With Relapsing Steroid-Sensitive Nephrotic Syndrome: The PREDNOS 2 Randomized Clinical Trial.

JAMA pediatrics

2021 Volume 176, Issue 3, Page(s) 236–243

Abstract: Importance: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an ... ...

Abstract	Importance: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. Objective: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. Design, setting, and participants: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. Interventions: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. Main outcomes and measures: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. Results: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). Conclusions and relevance: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. Trial registration: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Child ; Humans ; Male ; Nephrotic Syndrome/complications ; Nephrotic Syndrome/drug therapy ; Prednisolone/therapeutic use ; Quality of Life ; Recurrence ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/prevention & control
Chemical Substances	Adrenal Cortex Hormones ; Prednisolone (9PHQ9Y1OLM)
Language	English
Publishing date	2021-12-19
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2701223-2
ISSN	2168-6211 ; 2168-6203
ISSN (online)	2168-6211
ISSN	2168-6203
DOI	10.1001/jamapediatrics.2021.5189
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Um IV Zs.74: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Plasma exchange and glucocorticoids to delay death or end-stage renal disease in anti-neutrophil cytoplasm antibody-associated vasculitis: PEXIVAS non-inferiority factorial RCT.

Jayne, David / Walsh, Michael / Merkel, Peter A / Peh, Chen Au / Szpirt, Wladimir / Puéchal, Xavier / Fujimoto, Shouichi / Hawley, Carmel / Khalidi, Nader / Jones, Rachel / Flossmann, Oliver / Wald, Ron / Girard, Louis / Levin, Adeera / Gregorini, Gina / Harper, Lorraine / Clark, William / Pagnoux, Christian / Specks, Ulrich /

Smyth, Lucy / Ito-Ihara, Toshiko / de Zoysa, Janak / Brezina, Biljana / Mazzetti, Andrea / McAlear, Carol A / Reidlinger, Donna / Mehta, Samir / Ives, Natalie / Brettell, Elizabeth A / Jarrett, Hugh / Wheatley, Keith / Broadhurst, Elizabeth / Casian, Alina / Pusey, Charles D

Health technology assessment (Winchester, England)

2022 Volume 26, Issue 38, Page(s) 1–60

Abstract: Background: Anti-neutrophil cytoplasm antibody-associated vasculitis is a multisystem, autoimmune disease that causes organ failure and death. Physical removal of pathogenic autoantibodies by plasma exchange is recommended for severe presentations, ... ...

Abstract	Background: Anti-neutrophil cytoplasm antibody-associated vasculitis is a multisystem, autoimmune disease that causes organ failure and death. Physical removal of pathogenic autoantibodies by plasma exchange is recommended for severe presentations, along with high-dose glucocorticoids, but glucocorticoid toxicity contributes to morbidity and mortality. The lack of a robust evidence base to guide the use of plasma exchange and glucocorticoid dosing contributes to variation in practice and suboptimal outcomes. Objectives: We aimed to determine the clinical efficacy of plasma exchange in addition to immunosuppressive therapy and glucocorticoids with respect to death and end-stage renal disease in patients with severe anti-neutrophil cytoplasm antibody-associated vasculitis. We also aimed to determine whether or not a reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen with respect to death and end-stage renal disease. Design: This was an international, multicentre, open-label, randomised controlled trial. Patients were randomised in a two-by-two factorial design to receive either adjunctive plasma exchange or no plasma exchange, and either a reduced or a standard glucocorticoid dosing regimen. All patients received immunosuppressive induction therapy with cyclophosphamide or rituximab. Setting: Ninety-five hospitals in Europe, North America, Australia/New Zealand and Japan participated. Participants: Participants were aged ≥ 16 years with a diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, and either proteinase 3 anti-neutrophil cytoplasm antibody or myeloperoxidase anti-neutrophil cytoplasm antibody positivity, and a glomerular filtration rate of < 50 ml/minute/1.73 m Interventions: Participants received seven sessions of plasma exchange within 14 days or no plasma exchange. Oral glucocorticoids commenced with prednisolone 1 mg/kg/day and were reduced over different lengths of time to 5 mg/kg/day, such that cumulative oral glucocorticoid exposure in the first 6 months was 50% lower in patients allocated to the reduced-dose regimen than in those allocated to the standard-dose regimen. All patients received the same glucocorticoid dosing from 6 to 12 months. Subsequent dosing was at the discretion of the treating physician. Primary outcome: The primary outcome was a composite of all-cause mortality and end-stage renal disease at a common close-out when the last patient had completed 10 months in the trial. Results: The study recruited 704 patients from June 2010 to September 2016. Ninety-nine patients died and 138 developed end-stage renal disease, with the primary end point occurring in 209 out of 704 (29.7%) patients: 100 out of 352 (28%) in the plasma exchange group and 109 out of 352 (31%) in the no plasma exchange group (adjusted hazard ratio 0.86, 95% confidence interval 0.65 to 1.13; Conclusions: Plasma exchange did not prolong the time to death and/or end-stage renal disease in patients with anti-neutrophil cytoplasm antibody-associated vasculitis with severe renal or pulmonary involvement. A reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen and was associated with fewer serious infections. Future work: A meta-analysis examining the effects of plasma exchange on kidney outcomes in anti-neutrophil cytoplasm antibody-associated vasculitis is planned. A health-economic analysis of data collected in this study to examine the impact of both plasma exchange and reduced glucocorticoid dosing is planned to address the utility of plasma exchange for reducing early end-stage renal disease rates. Blood and tissue samples collected in the study will be examined to identify predictors of response to plasma exchange in anti-neutrophil cytoplasm in antibody-associated vasculitis. The benefits associated with reduced glucocorticoid dosing will inform future studies of newer therapies to permit further reduction in glucocorticoid exposure. Data from this study will contribute to updated management recommendations for anti-neutrophil cytoplasm antibody-associated vasculitis. Limitations: This study had an open-label design which may have permitted observer bias; however, the nature of the end points, end-stage renal disease and death, would have minimised this risk. Despite being, to our knowledge, the largest ever trial in anti-neutrophil cytoplasm antibody-associated vasculitis, there was an insufficient sample size to assess clinically useful benefits on the separate components of the primary end-point: end-stage renal disease and death. Use of a fixed-dose plasma exchange regimen determined by consensus rather than data-driven dose ranging meant that some patients may have been underdosed, thus reducing the therapeutic impact. In particular, no biomarkers have been identified to help determine dosing in a particular patient, although this is one of the goals of the biomarker plan of this study. Trial registration: This trial is registered as ISRCTN07757494, EudraCT 2009-013220-24 and Clinicaltrials.gov NCT00987389. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in
MeSH term(s)	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Autoantibodies/therapeutic use ; Cost-Benefit Analysis ; Cyclophosphamide/therapeutic use ; Cytoplasm ; Glucocorticoids/therapeutic use ; Humans ; Kidney Failure, Chronic/therapy ; Myeloblastin ; Peroxidase/therapeutic use ; Prednisolone/therapeutic use ; Rituximab/therapeutic use
Chemical Substances	Autoantibodies ; Glucocorticoids ; Rituximab (4F4X42SYQ6) ; Cyclophosphamide (8N3DW7272P) ; Prednisolone (9PHQ9Y1OLM) ; Peroxidase (EC 1.11.1.7) ; Myeloblastin (EC 3.4.21.76)
Language	English
Publishing date	2022-10-05
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2006765-3
ISSN	2046-4924 ; 1366-5278
ISSN (online)	2046-4924
ISSN	1366-5278
DOI	10.3310/PNXB5040
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5162: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The authors reply.

Lamb, Edmund J / Sitch, Alice J / Barratt, Jonathan / Brettell, Elizabeth A / Cockwell, Paul / Dalton, R Neil / Deeks, Jon J / Eaglestone, Gillian / Pellatt-Higgins, Tracy / Kalra, Philip A / Khunti, Kamlesh / Loud, Fiona C / Morris, Frances S / Ottridge, Ryan S / Stevens, Paul E / Sharpe, Claire C / Sutton, Andrew J / Taal, Maarten W / Rowe, Ceri

Kidney international

2020 Volume 97, Issue 1, Page(s) 214–215

MeSH term(s)	Glomerular Filtration Rate ; Humans ; Renal Insufficiency, Chronic
Language	English
Publishing date	2020-01-04
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2019.10.014
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 797: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Biological variation of measured and estimated glomerular filtration rate in patients with chronic kidney disease.

Rowe, Ceri / Sitch, Alice J / Barratt, Jonathan / Brettell, Elizabeth A / Cockwell, Paul / Dalton, R Neil / Deeks, Jon J / Eaglestone, Gillian / Pellatt-Higgins, Tracy / Kalra, Philip A / Khunti, Kamlesh / Loud, Fiona C / Morris, Frances S / Ottridge, Ryan S / Stevens, Paul E / Sharpe, Claire C / Sutton, Andrew J / Taal, Maarten W / Lamb, Edmund J

Kidney international

2019 Volume 96, Issue 2, Page(s) 429–435

Abstract: When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical ... ...

Abstract	When assessing changes in glomerular filtration rate (GFR) it is important to differentiate pathological change from intrinsic biological and analytical variation. GFR is measured using complex reference methods (e.g., iohexol clearance). In clinical practice measurement of creatinine and cystatin C are used in the Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equations to provide estimated GFR. Here we studied the biological variability of measured and estimated GFR in twenty nephrology outpatients (10 male, 10 female; median age 71, range 50-80 years) with moderate CKD (GFR 30-59 ml/min per 1.73 m
MeSH term(s)	Aged ; Aged, 80 and over ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Reference Standards ; Renal Insufficiency, Chronic/physiopathology
Language	English
Publishing date	2019-03-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2019.02.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 797: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial.

Bhandari, Sunil / Ives, Natalie / Brettell, Elizabeth A / Valente, Marie / Cockwell, Paul / Topham, Peter S / Cleland, John G / Khwaja, Arif / El Nahas, Meguid

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

2015 Volume 31, Issue 2, Page(s) 255–261

Abstract: Background: Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin-angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild ...

Abstract	Background: Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin-angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in patients with advanced progressive CKD. Methods: The STOP-ACEi trial (trial registration: current controlled trials, ISRCTN62869767) is an investigator-led multicentre open-label, randomized controlled clinical trial of 410 participants with advanced (Stage 4 or 5) progressive CKD receiving ACEi, ARBs or both. Patients will be randomized in a 1:1 ratio to either discontinue ACEi, ARB or combination of both (experimental arm) or continue ACEi, ARB or combination of both (control arm). Patients will be followed up at 3 monthly intervals for 3 years. The primary outcome measure is eGFR at 3 years. Secondary outcome measures include the number of renal events, participant quality of life and physical functioning, hospitalization rates, BP and laboratory measures, including serum cystatin-C. Safety will be assessed to ensure that withdrawal of these treatments does not cause excess harm or increase mortality or cardiovascular events such as heart failure, myocardial infarction or stroke. Results: The rationale and trial design are presented here. The results of this trial will show whether discontinuation of ACEi/ARBs can improve or stabilize renal function in patients with advanced progressive CKD. It will show whether this simple intervention can improve laboratory and clinical outcomes, including progression to end-stage renal disease, without causing an increase in cardiovascular events.
MeSH term(s)	Aged ; Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Blood Pressure/drug effects ; Disease Progression ; Female ; Follow-Up Studies ; Glomerular Filtration Rate/drug effects ; Humans ; Male ; Middle Aged ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/physiopathology ; Withholding Treatment
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors
Language	English
Publishing date	2015-09-30
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfv346
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2198: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 329: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito