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1دورية أكاديمية
المؤلفون: Jan Dudley, Martin Christian, Alice Andrews, Nicola Andrews, Julie Baker, Sheila Boyle, Mairead Convery, Fiona Gamston, Martin Garcia, Shuman Haq, Shivaram Hegde, Richard Holt, Helen Jones, Shakeeb Khan, Jennifer McCaughan, David Milford, Charlie Pickles, Ben Reynolds, Vijaya Sathyanarayana, Jelena Stojanovic, Yincent Tse, Dean Wallace, Grainne Walsh, Nick Ware, Alun Williams, Pallavi Yadav, Stephen Marks
المصدر: BMC Nephrology, Vol 22, Iss 1, Pp 1-9 (2021)
مصطلحات موضوعية: Diseases of the genitourinary system. Urology, RC870-923
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1471-2369Test
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2دورية أكاديمية
المؤلفون: Martin T Christian, Nicholas JA Webb, Rebecca L Woolley, Nafsika Afentou, Samir Mehta, Emma Frew, Elizabeth A Brettell, Adam R Khan, David V Milford, Detlef Bockenhauer, Moin A Saleem, Angela S Hall, Ania Koziell, Heather Maxwell, Shivaram Hegde, Eric R Finlay, Rodney D Gilbert, Caroline Jones, Karl McKeever, Wendy Cook, Natalie Ives
المصدر: Health Technology Assessment, Vol 26, Iss 3 (2022)
مصطلحات موضوعية: nephrotic syndrome, corticosteroid, prednisolone, relapse, upper respiratory tract infection, urti, health economic, cost-effectiveness, Medical technology, R855-855.5
الوصف: 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/m2) or an equivalent dose of placebo. 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; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. 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 Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information.
وصف الملف: electronic resource
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3دورية أكاديمية
المؤلفون: Katie Wong, David Pitcher, Fiona Braddon, Lewis Downward, Retha Steenkamp, Nicholas Annear, Jonathan Barratt, Coralie Bingham, Constantina Chrysochou, Richard J Coward, David Game, Sian Griffin, Matt Hall, Sally Johnson, Durga Kanigicherla, Fiona Karet Frankl, David Kavanagh, Larissa Kerecuk, Eamonn R Maher, Shabbir Moochhala, Jenny Pinney, John A Sayer, Roslyn Simms, Smeeta Sinha, Shalabh Srivastava, Frederick WK Tam, Andrew Neil Turner, Stephen B Walsh, Aoife Waters, Patricia Wilson, Edwin Wong, Christopher Mark Taylor, Dorothea Nitsch, Moin Saleem, Detlef Bockenhauer, Kate Bramham, Daniel P Gale, Sharirose Abat, Shazia Adalat, Joy Agbonmwandolor, Zubaidah Ahmad, Abdulfattah Alejmi, Rashid Almasarwah, Ellie Asgari, Amanda Ayers, Jyoti Baharani, Gowrie Balasubramaniam, Felix Kpodo, Tarun Bansal, Alison Barratt, Megan Bates, Natalie Bayne, Janet Bendle, Sarah Benyon, Carsten Bergmann, Sunil Bhandari, Preetham Boddana, Sally Bond, Angela Branson, Stephen Brearey, Vicky Brocklebank, Sharanjit Budwal, Conor Byrne, Hugh Cairns, Brian Camilleri, Gary Campbell, Alys Capell, Margaret Carmody, Marion Carson, Tracy Cathcart, Christine Catley, Karine Cesar, Melanie Chan, Houda Chea, James Chess, Chee Kay Cheung, Katy-Jane Chick, Nihil Chitalia, Martin Christian, Tina Chrysochou, Katherine Clark, Christopher Clayton, Rhian Clissold, Helen Cockerill, Joshua Coelho, Elizabeth Colby, Viv Colclough, Eileen Conway, H Terence Cook, Wendy Cook, Theresa Cooper, Sarah Crosbie, Gabor Cserep, Anjali Date, Katherine Davidson, Amanda Davies, Neeraj Dhaun, Ajay Dhaygude, Lynn Diskin, Abhijit Dixit, Eunice Doctolero, Suzannah Dorey, Lewis Downard, Mark Drayson, Gavin Dreyer, Tina Dutt, Kufreabasi Etuk, Dawn Evans, Jenny Finch, Frances Flinter, James Fotheringham, Lucy Francis, Hugh Gallagher, Eva Garcia, Madita Gavrila, Susie Gear, Colin Geddes, Mark Gilchrist, Matt Gittus, Paraskevi Goggolidou, Christopher Goldsmith, Patricia Gooden, Andrea Goodlife, Priyanka Goodwin, Tassos Grammatikopoulos, Barry Gray, Megan Griffith, Steph Gumus, Sanjana Gupta, Patrick Hamilton, Lorraine Harper, Tess Harris, Louise Haskell, Samantha Hayward, Shivaram Hegde, Bruce Hendry, Sue Hewins, Nicola Hewitson, Kate Hillman, Mrityunjay Hiremath, Alexandra Howson, Zay Htet, Sharon Huish, Richard Hull, Alister Humphries, David PJ Hunt, Karl Hunter, Samantha Hunter, Marilyn Ijeomah-Orji, Nick Inston, David Jayne, Gbemisola Jenfa, Alison Jenkins, Caroline A Jones, Colin Jones, Amanda Jones, Rachel Jones, Lavanya Kamesh, Mahzuz Karim, Amrit Kaur, Kelly Kearley, Arif Khwaja, Garry King, Grant King, Ewa Kislowska, Edyta Klata, Maria Kokocinska, Mark Lambie, Laura Lawless, Thomas Ledson, Rachel Lennon, Adam P Levine, Ling Wai Maggie Lai, Graham Lipkin, Graham Lovitt, Paul Lyons, Holly Mabillard, Katherine Mackintosh, Khalid Mahdi, Eamonn Maher, Kevin J Marchbank, Patrick B Mark, Sherry Masoud, Bridgett Masunda, Zainab Mavani, Jake Mayfair, Stephen McAdoo, Joanna Mckinnell, Nabil Melhem, Simon Meyrick, Putnam Morgan, Ann Morgan, Fawad Muhammad, Shona Murray, Kristina Novobritskaya, Albert CM Ong, Louise Oni, Kate Osmaston, Neal Padmanabhan, Sharon Parkes, Jean Patrick, James Pattison, Riny Paul, Rachel Percival, Stephen J Perkins, Alexandre Persu, William G Petchey, Matthew C Pickering, Jennifer Pinney, Lucy Plumb, Zoe Plummer, Joyce Popoola, Frank Post, Albert Power, Guy Pratt, Charles Pusey, Ria Rabara, May Rabuya, Tina Raju, Chadd Javier, Ian SD Roberts, Candice Roufosse, Adam Rumjon, Alan Salama, Richard Sandford, Kanwaljit S Sandu, Nadia Sarween, Neil Sebire, Haresh Selvaskandan, Asheesh Sharma, Edward J Sharples, Neil Sheerin, Harish Shetty, Rukshana Shroff, Manish Sinha, Kerry Smith, Lara Smith, Ian Stott, Katerina Stroud, Pauline Swift, Justyna Szklarzewicz, Fred Tam, Kay Tan, Robert Taylor, Marc Tischkowitz, Kay Thomas, Yincent Tse, Alison Turnbull, A Neil Turner, Kay Tyerman, Miranda Usher, Gopalakrishnan Venkat-Raman, Alycon Walker, Angela Watt, Phil Webster, Ashutosh Wechalekar, Gavin I Welsh, Nicol West, David Wheeler, Kate Wiles, Lisa Willcocks, Angharad Williams, Emma Williams, Karen Williams, Deborah H Wilson, Patricia D Wilson, Paul Winyard, Grahame Wood, Emma Woodward, Len Woodward, Adrian Woolf, David Wright
مصطلحات موضوعية: Uncategorized, RaDaR consortium
الوصف: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure.People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m 2 or more to first eGFR of less than 30 mL/min per 1·73 m 2 (the therapeutic trial window).Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases.Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are ...
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المؤلفون: Nafsika, Afentou, Emma, Frew, Samir, Mehta, Natalie J, Ives, Rebecca L, Woolley, Elizabeth A, Brettell, Adam R, Khan, David V, Milford, Detlef, Bockenhauer, Moin A, Saleem, Angela S, Hall, Ania, Koziell, Heather, Maxwell, Shivaram, Hegde, Eric, Finlay, Rodney D, Gilbert, Caroline, Jones, Karl, McKeever, Wendy, Cook, Nicholas J A, Webb, Martin T, Christian, Annette, Bolger Team
المصدر: PharmacoEconomics - Open. 6:605-617
مصطلحات موضوعية: Pharmacology, Health Policy, Pharmacology (medical)
الوصف: 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.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.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.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.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.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78d2e5a8e5befca745d1fb5b4812455dTest
https://doi.org/10.1007/s41669-022-00334-6Test -
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المؤلفون: Lucy Plumb, Winnie Magadi, Anna Casula, Ben C Reynolds, Mairead Convery, Shuman Haq, Shivaram Hegde, Andrew Lunn, Michal Malina, Henry Morgan, Mordi Muorah, Kay Tyerman, Manish D Sinha, Dean Wallace, Carol Inward, Stephen Marks, Dorothea Nitsch, James Medcalf
المصدر: Plumb, L, Magadi, W, Casula, A, Reynolds, B, Convery, M, Haq, S, Hegde, S, Lunn, A, Malina, M, Morgan, H, Wallace, D, Inward, C D, Marks, S D, Nitsch, D & Medcalf, J 2022, ' Advanced chronic kidney disease among UK children ', Archives of Disease in Childhood, vol. 107, no. 11, pp. 1043-1045 . https://doi.org/10.1136/archdischild-2021-323686Test
مصطلحات موضوعية: Pediatrics, Perinatology and Child Health
الوصف: The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT.MethodsIn March 2020, all UK Paediatric Nephrology centres submitted data on children aged 2.ResultsIn total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population.ConclusionsThe prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffed2a9a455c0031cb8a17ce7fcde275Test
https://research-information.bris.ac.uk/en/publications/678a9272-18d2-4992-9064-c55d3b006178Test -
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المؤلفون: Agnieszka Bierzynska, Katherine Bull, Sara Miellet, Philip Dean, Chris Neal, Elizabeth Colby, Hugh J. McCarthy, Shivaram Hegde, Manish D. Sinha, Carmen Bugarin Diz, Kathleen Stirrups, Karyn Megy, Rutendo Mapeta, Chris Penkett, Sarah Marsh, Natalie Forrester, Maryam Afzal, Hannah Stark, NIHR BioResource, Maggie Williams, Gavin I. Welsh, Ania B. Koziell, Paul S. Hartley, Moin A. Saleem
المساهمون: Saleem, Moin A [0000-0002-9808-4518], Apollo - University of Cambridge Repository
المصدر: Bierzynska, A, Bull, K, Miellet, S, Dean, P, Neal, C, Colby, E, McCarthy, H J, Hegde, S, Sinha, M D, Bugarin Diz, C, Stirrups, K, Megy, K, Mapeta, R, Penkett, C, Marsh, S, Forrester, N, Afzal, M, Stark, H, BioResource, N, Williams, M, Welsh, G I, Koziell, A B, Hartley, P S & Saleem, M A 2022, ' Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model ', Pediatric Nephrology, vol. 37, no. 11, pp. 2643-2656 . https://doi.org/10.1007/s00467-022-05440-5Test
Pediatric Nephrologyمصطلحات موضوعية: Adult, Nephrotic Syndrome, Podocytes, Nephrocyte, Drug Resistance, Podocyte, High-Throughput Nucleotide Sequencing, Nuclear Pore Complex Proteins, FSGS, Disease Models, Animal, Drosophila melanogaster, Nephrology, SRNS, Pediatrics, Perinatology and Child Health, Mutation, Animals, Humans, NUP93, Child, Glucocorticoids
الوصف: Background Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model. Methods Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers. Results Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood. Conclusion We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information
وصف الملف: application/zip; text/xml; application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b20ca2e7b3023d1c2067023bde5c63f0Test
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المؤلفون: Martin T. Christian, Nicholas J. A. Webb, Samir Mehta, Rebecca L. Woolley, Nafsika Afentou, Emma Frew, Elizabeth A. Brettell, Adam R. Khan, David V. Milford, Detlef Bockenhauer, Moin A. Saleem, Angela S. Hall, Ania Koziell, Heather Maxwell, Shivaram Hegde, Hitesh Prajapati, Rodney D. Gilbert, Caroline Jones, Karl McKeever, Wendy Cook, Natalie Ives
المصدر: Christian, M T, Webb, N J A, Mehta, S, Woolley, R L, Afentou, N, Frew, E, Brettell, E A, Khan, A R, Milford, D V, Bockenhauer, D, Saleem, M A, Hall, A S, Koziell, A, Maxwell, H, Hegde, S, Prajapati, H, Gilbert, R D, Jones, C, McKeever, K, Cook, W & Ives, N 2021, ' 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 . https://doi.org/10.1001/jamapediatrics.2021.5189Test
JAMA Pediatricsمصطلحات موضوعية: Male, Evidence-Based Medicine, Nephrotic Syndrome, Research, Prednisolone, Featured, Treatment Outcome, Adrenal Cortex Hormones, Recurrence, Pediatrics, Perinatology and Child Health, Quality of Life, Online First, Humans, Child, Glucocorticoids, Respiratory Tract Infections, Comments, Original Investigation
الوصف: Key Points Question In children with relapsing corticosteroid-sensitive nephrotic syndrome, does daily low-dose corticosteroid given at the time of upper respiratory tract infection prevent upper respiratory tract infection–related relapse? Findings In this randomized clinical trial of 365 children, daily low-dose corticosteroid therapy resulted in no difference in the frequency of upper respiratory tract infection–related relapses compared with placebo. Meaning Results of this study suggest that low-dose corticosteroid treatment is not beneficial as a strategy to prevent upper respiratory tract infection–related relapses.
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
This randomized clinical trial investigates whether a low daily dose of prednisolone in children with relapsing steroid-sensitive nephrotic syndrome prevents upper respiratory tract infection–related relapse.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::624ff0a56a1e917664485ed8159ee9c3Test
https://pubmed.ncbi.nlm.nih.gov/35410970Test -
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المؤلفون: Stephen D. Marks, Vijaya Sathyanarayana, Shakeeb Khan, Martin Christian, Alun Williams, Helen Jones, Ben C Reynolds, Richard C. L. Holt, Mairead Convery, Jennifer McCaughan, Shuman Haq, Shivaram Hegde, Jelena Stojanovic, Jan Dudley, Julie Baker, Pallavi Yadav, Grainne Walsh, Alice Andrews, Yincent Tse, Charlie Pickles, Nicola Andrews, Sheila Boyle, David V. Milford, Martin E. Garcia, Fiona Gamston, Nick Ware, Dean Wallace
المصدر: BMC Nephrology
BMC Nephrology, Vol 22, Iss 1, Pp 1-9 (2021)مصطلحات موضوعية: Nephrology, Drug, medicine.medical_specialty, Adolescent, media_common.quotation_subject, Guidelines, Drug Administration Schedule, Anti-Infective Agents, Internal medicine, Humans, Medicine, Anti infectives, Child, media_common, business.industry, Kidney Transplantation, Diseases of the genitourinary system. Urology, United Kingdom, Transplantation, Clinical Practice, Steroids, RC870-923, Patient Participation, business, Immunosuppressive Agents
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::45a102b251c6d99b7308cdb387a0b643Test
https://doi.org/10.1186/s12882-021-02460-5Test -
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المؤلفون: Wendy Cook, Moin A. Saleem, Caroline Jones, Samir Mehta, Detlef Bockenhauer, Karl McKeever, Angela S Hall, Elizabeth Brettell, Martin Christian, Afentou Nafsika, Emma Frew, Shivaram Hegde, Nicholas J. A. Webb, Ania Koziell, Adam Khan, Natalie Ives, Hitesh Prajapati, Heather Maxwell, Rodney D. Gilbert, Rebecca Woolley, David V. Milford
المصدر: Nephrology Dialysis Transplantation. 36
مصطلحات موضوعية: Transplantation, medicine.medical_specialty, Randomization, Intention-to-treat analysis, Cost effectiveness, business.industry, Urea reduction ratio, medicine.disease, Upper respiratory tract infection, Quality of life, Nephrology, Internal medicine, Epidemiology, medicine, Prednisolone, business, medicine.drug
الوصف: Background and Aims At least 80% of children with steroid sensitive nephrotic syndrome (SSNS) have relapses and many are triggered by upper respiratory tract infections (URTIs). Previous small studies (4 studies, 232 patients in total), mostly in children already taking maintenance corticosteroid in countries where URTI epidemiology is different to Europe, showed that giving daily low-dose prednisolone for 5-7 days during an URTI reduces the risk of relapse. The objective of the PREDNOS 2 trial was to determine if these findings were replicated in a large UK population of children with relapsing SSNS on different background medication or none. Method A randomised, double-blind, placebo-controlled trial, including a model-based economic evaluation was carried out in 122 UK paediatric departments. Between February 2013 and January 2019, 365 children with relapsing SSNS (mean age: 7.6 ± 3.5 y) were recruited from 91 sites and randomised (1:1) according to a minimisation algorithm based on background treatment (no background treatment; low-dose prednisolone only; low-dose prednisolone and other immunosuppression; other immunosuppression only). At the start of an URTI, children received 6 days of prednisolone 15 mg/m2 or matching preparation of placebo. Those already taking alternate day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 or their alternate-day dose, whichever was the greater. The primary outcome was the incidence of first URTI-related relapse (URR) following any URTI over 12 months. 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. The economic evaluation used trial data and a decision-analytic model to estimate Quality-Adjusted-Life-Years (QALYs) and costs at 1-year, which were then extrapolated over 16 years. Results 80 children completed 12 m follow-up without an URTI. Consent was withdrawn for 32 children, 14 prior to an URTI, leaving a modified intention to treat analysis population of 271 children (134 and 137 in prednisolone and placebo arms respectively). There were 384 URTIs and 82 URRs in the prednisolone arm, and 407 URTIs and 82 URRs in the placebo arm. The number of patients experiencing a URR was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms respectively (adjusted risk difference: -0.024, 95% CI: -0.14 to 0.095; P=0.7). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. A post-hoc subgroup analysis assessing primary outcome in 58 children of South Asian ethnicity (RR 0.66, 95% CI: 0.396 to 1.105) versus 213 of other ethnicity (RR 1.11, 95% CI: 0.806 to 1.535) showed possible efficacy of intervention in those of South Asian ethnicity (test for interaction P=0.09). Giving daily prednisolone at the time of an URTI was found to increase QALYs and decrease overall costs, when compared to standard care, a finding that was robust to sensitivity analysis. Conclusion In a large and methodologically-robust study, PREDNOS 2 has shown that giving 6 days of daily low-dose prednisolone at the time of an URTI does not reduce the risk of relapse of nephrotic syndrome in UK children, but could offer a cost-effective use of health care resources. Further work is needed to investigate inter-ethnic differences in treatment response, and the pathogenesis of individual viral infections and their effect on nephrotic syndrome.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b7d948cd561925791c691ae0dbd5f915Test
https://doi.org/10.1093/ndt/gfab134.003Test -
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المؤلفون: Sharon D. Whatley, David J. Griffiths, Johann te Water Naude, Andrew E. Fry, Zachary D. du Toit, Shivaram Hegde, Sara Martins, Martin A. McClatchey, David Hywel Thomas, Angus John Clarke, Rhys Vaughan
مصطلحات موضوعية: Male, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Nerve Tissue Proteins, Peritoneal dialysis, Frameshift mutation, Epilepsy, Focal segmental glomerulosclerosis, Intellectual Disability, Intellectual disability, Genetics, medicine, Humans, Child, Genetics (clinical), Proteinuria, medicine.diagnostic_test, business.industry, Glomerulosclerosis, Focal Segmental, General Medicine, Syndrome, medicine.disease, Mutation, Renal biopsy, medicine.symptom, business, Carrier Proteins, Nephrotic syndrome
الوصف: Mutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein. A previous patient with TRIM8-related epileptic encephalopathy was reported to have nephrotic syndrome. Here we describe the clinical, radiological and histological features of an 8-year-old male patient with a TRIM8 mutation who, in contrast to previous patients, had only mild intellectual disability and well-controlled epilepsy. The patient was found to have proteinuria at 2 years of age. Renal biopsy findings were suggestive of focal segmental glomerulosclerosis. His kidney function declined and peritoneal dialysis was started at 5 years of age. He underwent renal transplant at 7 years of age. Trio-based whole genome sequencing identified a novel de novo heterozygous frameshift mutation in TRIM8 (NM_030912.2) c.1198_1220del, p.(Tyr400ArgfsTer2). This patient is further evidence that TRIM8 mutations cause a syndrome with both neurological and renal features. Our findings suggest the spectrum of TRIM8-related disease may be wider than previously thought with the possibility of milder neurodevelopmental problems and/or a more severe, progressive renal phenotype. We highlight the need for proteinuria screening in patients with TRIM8 mutations.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe4b040a36958d761ad4201aa7f3246eTest
https://orca.cardiff.ac.uk/id/eprint/133666/1/TRIM8_manuscript_EJMG_FINAL.pdfTest
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