Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.07.009
Vlado Perkovic , Jonathan C. Craig , Worawon Chailimpamontree , Caroline S. Fox , Guillermo Garcia-Garcia , Mohammed Benghanem Gharbi , Meg J. Jardine , Ikechi G. Okpechi , Neesh Pannu , Benedicte Stengel , Katherine R. Tuttle , Katrin Uhlig , Andrew S. Levey
High-quality clinical trials are the cornerstone of evidence-based prevention and treatment of a disease, but nephrology has a strikingly weak base of such trials. Building the evidence base to improve outcomes for people with a kidney disease, therefore, requires both greater quantity and quality of clinical trials. To address these issues, we propose that we aim to enroll 30% of people with chronic kidney disease in trials by 2030. Goal 1: Strongly encourage and promote the conduct of clinical trials in people with chronic kidney disease to increase the number of clinical trials conducted. Goal 2: Optimize the design of clinical trials in people with chronic kidney disease. Goal 3: Increase the capacity for conducting clinical trials in people with chronic kidney disease.
{"title":"Action plan for optimizing the design of clinical trials in chronic kidney disease","authors":"Vlado Perkovic , Jonathan C. Craig , Worawon Chailimpamontree , Caroline S. Fox , Guillermo Garcia-Garcia , Mohammed Benghanem Gharbi , Meg J. Jardine , Ikechi G. Okpechi , Neesh Pannu , Benedicte Stengel , Katherine R. Tuttle , Katrin Uhlig , Andrew S. Levey","doi":"10.1016/j.kisu.2017.07.009","DOIUrl":"10.1016/j.kisu.2017.07.009","url":null,"abstract":"<div><p>High-quality clinical trials are the cornerstone of evidence-based prevention and treatment of a disease, but nephrology has a strikingly weak base of such trials. Building the evidence base to improve outcomes for people with a kidney disease, therefore, requires both greater quantity and quality of clinical trials. To address these issues, we propose that we aim to enroll 30% of people with chronic kidney disease in trials by 2030. Goal 1: Strongly encourage and promote the conduct of clinical trials in people with chronic kidney disease to increase the number of clinical trials conducted. Goal 2: Optimize the design of clinical trials in people with chronic kidney disease. Goal 3: Increase the capacity for conducting clinical trials in people with chronic kidney disease.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 138-144"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.07.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36935245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.07.002
Josef Coresh , Jiun-Ruey Hu , Aminu K. Bello , Harold I. Feldman , Agnes B. Fogo , Mohammad Reza Ganji , David C. Harris , Andrew S. Levey , Ikechi G. Okpechi , Benedicte Stengel , Bernadette Thomas , Andrzej Wiecek , Ron T. Gansevoort
Chronic kidney disease (CKD) continues to remain high globally, up to 13.4% by one estimate. Although the number, geographic distribution, size, and quality of the studies examining CKD prevalence and incidence have increased over the past decade, the global capacity for CKD surveillance is still far less developed than that for hypertension, diabetes, and cardiovascular disease. Estimating CKD prevalence is constrained by inadequate standardization of serum creatinine and urine albumin assays, heterogeneity in study designs, lack of national registries in many countries, incomplete adoption of disease classification guidelines, and inconsistent use of evidence-based equations for estimating glomerular filtration rate.
Goal 1: Improve monitoring of CKD prevalence. To achieve this, disseminate the rationale for CKD prevalence monitoring, achieve uniform measurement of CKD markers, promote inclusion of CKD measurements in all large chronic disease cohorts and health surveys, harness administrative claims data for CKD surveillance, and incorporate the new CKD classification system in the International Classification of Diseases.
Goal 2: Improve CKD monitoring of populations underrepresented in studies to date. To achieve this, establish registries of chronic dialysis and transplantation in all countries; establish registries for special CKD groups, such as children, patients with rare diseases, and patients with special etiologies of CKD.
Goal 3: Improve identification of individuals with CKD. To achieve this, implement the Kidney Disease: Improving Global Outcomes guidelines for screening and testing, carry out randomized studies on screening strategies, ensure that estimated glomerular filtration rate is reported with all reports of serum creatinine, and leverage new software for identification and follow-up of CKD cases.
{"title":"Action plan for determining and monitoring the prevalence of chronic kidney disease","authors":"Josef Coresh , Jiun-Ruey Hu , Aminu K. Bello , Harold I. Feldman , Agnes B. Fogo , Mohammad Reza Ganji , David C. Harris , Andrew S. Levey , Ikechi G. Okpechi , Benedicte Stengel , Bernadette Thomas , Andrzej Wiecek , Ron T. Gansevoort","doi":"10.1016/j.kisu.2017.07.002","DOIUrl":"10.1016/j.kisu.2017.07.002","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) continues to remain high globally, up to 13.4% by one estimate. Although the number, geographic distribution, size, and quality of the studies examining CKD prevalence and incidence have increased over the past decade, the global capacity for CKD surveillance is still far less developed than that for hypertension, diabetes, and cardiovascular disease. Estimating CKD prevalence is constrained by inadequate standardization of serum creatinine and urine albumin assays, heterogeneity in study designs, lack of national registries in many countries, incomplete adoption of disease classification guidelines, and inconsistent use of evidence-based equations for estimating glomerular filtration rate.</p><p>Goal 1: Improve monitoring of CKD prevalence. To achieve this, disseminate the rationale for CKD prevalence monitoring, achieve uniform measurement of CKD markers, promote inclusion of CKD measurements in all large chronic disease cohorts and health surveys, harness administrative claims data for CKD surveillance, and incorporate the new CKD classification system in the International Classification of Diseases.</p><p>Goal 2: Improve CKD monitoring of populations underrepresented in studies to date. To achieve this, establish registries of chronic dialysis and transplantation in all countries; establish registries for special CKD groups, such as children, patients with rare diseases, and patients with special etiologies of CKD.</p><p>Goal 3: Improve identification of individuals with CKD. To achieve this, implement the Kidney Disease: Improving Global Outcomes guidelines for screening and testing, carry out randomized studies on screening strategies, ensure that estimated glomerular filtration rate is reported with all reports of serum creatinine, and leverage new software for identification and follow-up of CKD cases.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 63-70"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36880364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.07.005
Michelle J. Pena , Peter Stenvinkel , Matthias Kretzler , Dwomoa Adu , Sanjay Kumar Agarwal , Josef Coresh , Harold I. Feldman , Agnes B. Fogo , Ron T. Gansevoort , David C. Harris , Vivekanand Jha , Zhi-Hong Liu , Valerie A. Luyckx , Ziad A. Massy , Ravindra Mehta , Robert G. Nelson , Donal J. O'Donoghue , Gregorio T. Obrador , Charlotte J. Roberts , Laura Sola , Hiddo J.L. Heerspink
Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care. Consensus on how many times and how often albuminuria and estimated glomerular filtration rate are measured should be defined. Meaningful changes in both renal biomarkers should be determined in order to ascertain what is clinically relevant. Increasing social awareness of CKD and partnering with the technological community may be ways to engage patients. Furthermore, improving the prediction of cardiovascular events in patients with CKD can be achieved by including the renal risk markers albuminuria and estimated glomerular filtration rate in cardiovascular risk algorithms and by encouraging uptake of assessing cardiovascular risk by general practitioners and nephrologists. Finally, examining ways to further validate and implement novel biomarkers for CKD will help mitigate the global problem of CKD. The more frequent use of renal biopsy will facilitate further knowledge into the underlying etiologies of CKD and help put new biomarkers into biological context. Real-world assessments of these biomarkers in existing cohorts is important, as well as obtaining regulatory approval to use these biomarkers in clinical practice. Collaborations among academia, physician and patient groups, industry, payer organizations, and regulatory authorities will help improve the global outcomes of people living with CKD.
{"title":"Strategies to improve monitoring disease progression, assessing cardiovascular risk, and defining prognostic biomarkers in chronic kidney disease","authors":"Michelle J. Pena , Peter Stenvinkel , Matthias Kretzler , Dwomoa Adu , Sanjay Kumar Agarwal , Josef Coresh , Harold I. Feldman , Agnes B. Fogo , Ron T. Gansevoort , David C. Harris , Vivekanand Jha , Zhi-Hong Liu , Valerie A. Luyckx , Ziad A. Massy , Ravindra Mehta , Robert G. Nelson , Donal J. O'Donoghue , Gregorio T. Obrador , Charlotte J. Roberts , Laura Sola , Hiddo J.L. Heerspink","doi":"10.1016/j.kisu.2017.07.005","DOIUrl":"10.1016/j.kisu.2017.07.005","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care. Consensus on how many times and how often albuminuria and estimated glomerular filtration rate are measured should be defined. Meaningful changes in both renal biomarkers should be determined in order to ascertain what is clinically relevant. Increasing social awareness of CKD and partnering with the technological community may be ways to engage patients. Furthermore, improving the prediction of cardiovascular events in patients with CKD can be achieved by including the renal risk markers albuminuria and estimated glomerular filtration rate in cardiovascular risk algorithms and by encouraging uptake of assessing cardiovascular risk by general practitioners and nephrologists. Finally, examining ways to further validate and implement novel biomarkers for CKD will help mitigate the global problem of CKD. The more frequent use of renal biopsy will facilitate further knowledge into the underlying etiologies of CKD and help put new biomarkers into biological context. Real-world assessments of these biomarkers in existing cohorts is important, as well as obtaining regulatory approval to use these biomarkers in clinical practice. Collaborations among academia, physician and patient groups, industry, payer organizations, and regulatory authorities will help improve the global outcomes of people living with CKD.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 107-113"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36935241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.08.001
Aminu K. Bello , David W. Johnson , John Feehally , David Harris , Kailash Jindal , Meaghan Lunney , Ikechi G. Okpechi , Babatunde L. Salako , Natasha Wiebe , Feng Ye , Marcello Tonelli , Adeera Levin
There has been considerable effort within individual countries to improve the care of patients with kidney disease. There has been no concerted attempt to summarize these efforts, and therefore little is known about structuring health systems to facilitate acute kidney injury and chronic kidney disease (CKD) care and integration with national and international noncommunicable disease strategies. As part of the “Closing the Gaps Initiative,” the International Society of Nephrology will conduct for the first time a survey of the current state of global kidney care covering both acute kidney injury and CKD and present the results in a Global Kidney Health Atlas. Data will be collected via an online questionnaire and targeted at national nephrology societies, policymakers, and consumer organizations. Individual country information will be provided by at least 3 stakeholders. The Global Kidney Health Atlas will provide concise, relevant, and synthesized information on the delivery of care across different health systems to facilitate understanding of performance variations over time and between countries. First, it will provide an overview of existing CKD care policy and context in the health care system. Second, it will provide an overview of how CKD care is organized in individual countries and a description of relevant CKD epidemiology between countries and regions, focusing on elements that are most germane to service delivery and policy development. Finally, synthesis, comparison, and analysis of individual country/regional data will be provided as a platform for recommendations to policymakers, practitioners, and researchers.
{"title":"Global Kidney Health Atlas (GKHA): design and methods","authors":"Aminu K. Bello , David W. Johnson , John Feehally , David Harris , Kailash Jindal , Meaghan Lunney , Ikechi G. Okpechi , Babatunde L. Salako , Natasha Wiebe , Feng Ye , Marcello Tonelli , Adeera Levin","doi":"10.1016/j.kisu.2017.08.001","DOIUrl":"10.1016/j.kisu.2017.08.001","url":null,"abstract":"<div><p>There has been considerable effort within individual countries to improve the care of patients with kidney disease. There has been no concerted attempt to summarize these efforts, and therefore little is known about structuring health systems to facilitate acute kidney injury and chronic kidney disease (CKD) care and integration with national and international noncommunicable disease strategies. As part of the “Closing the Gaps Initiative,” the International Society of Nephrology will conduct for the first time a survey of the current state of global kidney care covering both acute kidney injury and CKD and present the results in a Global Kidney Health Atlas. Data will be collected via an online questionnaire and targeted at national nephrology societies, policymakers, and consumer organizations. Individual country information will be provided by at least 3 stakeholders. The Global Kidney Health Atlas will provide concise, relevant, and synthesized information on the delivery of care across different health systems to facilitate understanding of performance variations over time and between countries. First, it will provide an overview of existing CKD care policy and context in the health care system. Second, it will provide an overview of how CKD care is organized in individual countries and a description of relevant CKD epidemiology between countries and regions, focusing on elements that are most germane to service delivery and policy development. Finally, synthesis, comparison, and analysis of individual country/regional data will be provided as a platform for recommendations to policymakers, practitioners, and researchers.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 145-153"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36935246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.07.006
Meg J. Jardine , Bertram Kasiske , Dwomoa Adu , Mona Alrukhaimi , Gloria E. Ashuntantang , Shakti Basnet , Worawon Chailimpamontree , Jonathan C. Craig , Donal J. O'Donoghue , Vlado Perkovic , Neil R. Powe , Charlotte J. Roberts , Yusuke Suzuki , Tetsuhiro Tanaka , Katrin Uhlig
There are major gaps between our growing knowledge of effective treatments for chronic kidney disease (CKD), and the delivery of evidence-based therapies to populations around the world. Although there remains a need for new, effective therapies, current evidence suggests that many patients with CKD are yet to fully realize the benefits of blood pressure–lowering drugs (with and without reducing proteinuria with renin-angiotensin system blockade), wider use of statins to reduce atherosclerotic cardiovascular disease events, and better glycemic control in both type 1 and type 2 diabetes. There are many barriers to optimizing evidence-based nephrology care around the world, including access to health care, affordability of treatments, consumer attitudes and circumstances, the dissemination of appropriate knowledge, the availability of expertise and structural impediments in the delivery of health care. Further investment in implementation science that addresses the major barriers to effective care in a cost-effective manner could yield both local and global benefits.
{"title":"Closing the gap between evidence and practice in chronic kidney disease","authors":"Meg J. Jardine , Bertram Kasiske , Dwomoa Adu , Mona Alrukhaimi , Gloria E. Ashuntantang , Shakti Basnet , Worawon Chailimpamontree , Jonathan C. Craig , Donal J. O'Donoghue , Vlado Perkovic , Neil R. Powe , Charlotte J. Roberts , Yusuke Suzuki , Tetsuhiro Tanaka , Katrin Uhlig","doi":"10.1016/j.kisu.2017.07.006","DOIUrl":"10.1016/j.kisu.2017.07.006","url":null,"abstract":"<div><p>There are major gaps between our growing knowledge of effective treatments for chronic kidney disease (CKD), and the delivery of evidence-based therapies to populations around the world. Although there remains a need for new, effective therapies, current evidence suggests that many patients with CKD are yet to fully realize the benefits of blood pressure–lowering drugs (with and without reducing proteinuria with renin-angiotensin system blockade), wider use of statins to reduce atherosclerotic cardiovascular disease events, and better glycemic control in both type 1 and type 2 diabetes. There are many barriers to optimizing evidence-based nephrology care around the world, including access to health care, affordability of treatments, consumer attitudes and circumstances, the dissemination of appropriate knowledge, the availability of expertise and structural impediments in the delivery of health care. Further investment in implementation science that addresses the major barriers to effective care in a cost-effective manner could yield both local and global benefits.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 114-121"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.07.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36935242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.07.008
Carol Pollock , Anna Zuk , Hans-Joachim Anders , Mohammad Reza Ganji , David W. Johnson , Bertram Kasiske , Robyn G. Langham , Roberto Pecoits-Filho , Giuseppe Remuzzi , Jerome Rossert , Yusuke Suzuki , Tetsuhiro Tanaka , Robert Walker , Chih-Wei Yang , Joseph V. Bonventre
The focus of this article is to define goals and resulting action plans that can be collectively embraced by interested stakeholders to facilitate new therapeutic approaches to mitigate chronic kidney disease progression. The specific goals include identifying druggable targets, increasing the capacity for preclinical and early clinical development, broadening the availability of new therapeutic approaches, and increasing investment in the development of new therapies to limit chronic kidney disease. Key deliverables include the establishment of new regional, national, and global consortia; development of clinical trial networks; and creation of programs to support the temporary mutual movement of scientists between academia and the biotechnology and pharmaceutical sector. Other deliverables include cataloging and maintaining up-to-date records to collate progress in renal research and development, inventorying the capacity of research and clinical networks, and describing methods to ensure novel drug development.
{"title":"The establishment and validation of novel therapeutic targets to retard progression of chronic kidney disease","authors":"Carol Pollock , Anna Zuk , Hans-Joachim Anders , Mohammad Reza Ganji , David W. Johnson , Bertram Kasiske , Robyn G. Langham , Roberto Pecoits-Filho , Giuseppe Remuzzi , Jerome Rossert , Yusuke Suzuki , Tetsuhiro Tanaka , Robert Walker , Chih-Wei Yang , Joseph V. Bonventre","doi":"10.1016/j.kisu.2017.07.008","DOIUrl":"10.1016/j.kisu.2017.07.008","url":null,"abstract":"<div><p>The focus of this article is to define goals and resulting action plans that can be collectively embraced by interested stakeholders to facilitate new therapeutic approaches to mitigate chronic kidney disease progression. The specific goals include identifying druggable targets, increasing the capacity for preclinical and early clinical development, broadening the availability of new therapeutic approaches, and increasing investment in the development of new therapies to limit chronic kidney disease. Key deliverables include the establishment of new regional, national, and global consortia; development of clinical trial networks; and creation of programs to support the temporary mutual movement of scientists between academia and the biotechnology and pharmaceutical sector. Other deliverables include cataloging and maintaining up-to-date records to collate progress in renal research and development, inventorying the capacity of research and clinical networks, and describing methods to ensure novel drug development.</p></div>","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 130-137"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.07.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36935244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-10-01DOI: 10.1016/j.kisu.2017.07.001
Adeera Levin , Kai-Uwe Eckardt , Marcello Tonelli
{"title":"The Global Kidney Health Summit Outputs: details to guide the nephrology community along the road to global kidney health","authors":"Adeera Levin , Kai-Uwe Eckardt , Marcello Tonelli","doi":"10.1016/j.kisu.2017.07.001","DOIUrl":"10.1016/j.kisu.2017.07.001","url":null,"abstract":"","PeriodicalId":48895,"journal":{"name":"Kidney International Supplements","volume":"7 2","pages":"Pages 61-62"},"PeriodicalIF":5.5,"publicationDate":"2017-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.kisu.2017.07.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43294006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}