Managing the symptom burden associated with maintenance dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Abstract

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference—Symptom-Based Complications in Dialysis—to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources. Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference—Symptom-Based Complications in Dialysis—to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources. Recognition is growing of the frequency and burden of symptoms experienced by individuals undergoing either hemodialysis or peritoneal dialysis. A multitude of symptoms are reported (Figures 1 and 2), such as fatigue, pain, poor mood, dry skin, poor sleep, and muscle cramps, with fatigue being the most common, and pain the most severe.1Fletcher B.R. Damery S. Aiyegbusi O.L. et al.Symptom burden and health-related quality of life in chronic kidney disease: a global systematic review and meta-analysis.PLoS Med. 2022; 19e1003954Crossref PubMed Scopus (31) Google Scholar, 2Manera K.E. Johnson D.W. Craig J.C. et al.Establishing a core outcome set for peritoneal dialysis: report of the SONG-PD (Standardized Outcomes in Nephrology-Peritoneal Dialysis) Consensus Workshop.Am J Kidney Dis. 2020; 75: 404-412Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 3Evangelidis N. Tong A. Manns B. et al.Developing a set of core outcomes for trials in hemodialysis: an international Delphi survey.Am J Kidney Dis. 2017; 70: 464-475Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar, 4Flythe J.E. Hilliard T. Castillo G. et al.Symptom prioritization among adults receiving in-center hemodialysis: a mixed methods study.Clin J Am Soc Nephrol. 2018; 13: 735-745Crossref PubMed Scopus (80) Google Scholar, 5Gregg L.P. Bossola M. Ostrosky-Frid M. et al.Fatigue in CKD: epidemiology, pathophysiology, and treatment.Clin J Am Soc Nephrol. 2021; 16: 1445-1455Crossref PubMed Scopus (32) Google Scholar, 6Abdel-Kader K. Unruh M.L. Weisbord S.D. Symptom burden, depression, and quality of life in chronic and end-stage kidney disease.Clin J Am Soc Nephrol. 2009; 4: 1057-1064Crossref PubMed Scopus (336) Google Scholar The exact incidence and prevalence of individual symptoms vary depending on patient population studied (age, comorbidities, sex and gender, frailty, psychosocial concerns, etc.) or development of dialysis-related complications (e.g., vascular access related "steal" syndrome, dialysis-associated amyloid, or encapsulating peritoneal sclerosis). In addition to physical symptoms, approximately 40% of people receiving dialysis have symptoms of anxiety.7Huang C.W. Wee P.H. Low L.L. et al.Prevalence and risk factors for elevated anxiety symptoms and anxiety disorders in chronic kidney disease: a systematic review and meta-analysis.Gen Hosp Psychiatry. 2021; 69: 27-40Crossref PubMed Scopus (34) Google Scholar Rates of depression vary by method of assessment,8Lopes A.A. Albert J.M. Young E.W. et al.Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS.Kidney Int. 2004; 66: 2047-2053Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 9Tian N. Chen N. Li P.K. Depression in dialysis.Curr Opin Nephrol Hypertens. 2021; PubMed Scopus Google Scholar, S. M. Craig J.C. et al.Prevalence of depression in chronic kidney disease: systematic review and of Int. Full Text Full Text PDF PubMed Scopus Google Scholar when symptoms are with to and health-related quality of et of life and depression in Med. 2018; PubMed Scopus Google and and a S.D. et of symptoms and pain with dialysis and in patients receiving chronic J Am Soc Nephrol. PubMed Scopus Google The of in end-stage disease: associations with psychosocial and clinical PubMed Scopus Google Scholar Symptom burden for people undergoing dialysis can in and and life of symptom among people undergoing as by a patient of Symptom and management in maintenance dialysis individuals and of Routine symptom assessment is not universal or standardized and is by J.M. A. et a outcome for hemodialysis patients in clinical of patients and on J Am Soc Nephrol. 2020; PubMed Scopus Google Scholar A that is is the responsibility for managing symptoms with or care symptoms of or and chronic and dialysis The of most symptoms is not and the and of symptoms can vary to Even when symptoms are identified, treatment is initiated Weisbord S.D. et of symptoms in patients on maintenance Symptom Full Text Full Text PDF PubMed Scopus Google S.D. et of symptom management for pain, and depression in patients receiving chronic hemodialysis: a J Am Soc Nephrol. PubMed Scopus Google Scholar options be limited, the evidence base is M. et review of management for symptoms in 2021; Full Text Full Text PDF PubMed Scopus Google J.E. Hilliard T. et in symptom management among hemodialysis patients: for muscle cramps, and J Am Soc Nephrol. PubMed Scopus Google Scholar and and complexities are related to medication and behavioral in the dialysis an high burden and the of to symptom burden, people are to take M. et burden, and quality of life in maintenance dialysis J Am Soc Nephrol. 2009; 4: PubMed Scopus Google Scholar on the and the the be for for such as behavioral for depression, and such be to an high of treatment and the to undergoing dialysis. The of symptoms experienced by people on dialysis and or by nephrology care is S.D. et of symptoms in patients on maintenance J Am Soc Nephrol. PubMed Scopus Google Scholar 1 has that of hemodialysis patients with pain and a with Weisbord S.D. et of symptoms in patients on maintenance Symptom Full Text Full Text PDF PubMed Scopus Google Scholar is not recently, nephrology care has on numerical targets for laboratory measures, and outcomes such as such as on dialysis that symptoms and to dialysis is of limited or In Disease: Improving Global initiated a of Controversies on dialysis. The of and et and a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Int. Full Text Full Text PDF PubMed Scopus Google and in J.E. et and management in dialysis: a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Int. 2020; Full Text Full Text PDF PubMed Scopus Google and et dialysis: a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Int. Full Text Full Text PDF PubMed Scopus Google the of patient and life in kidney A on symptom-based complications in in May of to identify the optimal means for and symptom-based complications in people undergoing dialysis. of and can be Participants the of the dialysis behavioral therapists, nurses, pharmacists, and clinical and included people on dialysis. The core outcomes included and and undergoing dialysis of related to identifying and addressing clinicians not people on dialysis symptoms, or to that symptom on functioning can be important to patients symptom frequency or or symptoms be symptoms that in that and outlined foundational principles and consensus points related to identifying and addressing dialysis symptom-based complications J.M. A. et a outcome for hemodialysis patients in clinical of patients and on J Am Soc Nephrol. 2020; PubMed Scopus Google S. Manns B. et outcome in the care of hemodialysis 2021; PubMed Scopus Google Scholar, O.L. et and on outcome in the management of CKD: a J Kidney Dis. Full Text Full Text PDF PubMed Scopus (32) Google Scholar, N. et of a the of an outcome in the management of patients with chronic kidney 2022; Scopus Google Scholar, et symptom burden and health-related quality of life in dialysis patients: the of outcome Kidney 2020; PubMed Scopus Google Scholar, C.W. of patient reported outcomes is and patient in chronic kidney Int. 2017; PubMed Scopus Google and described gaps in the knowledge base and priorities for points symptom-based complications in should and focus on symptoms most important to individual in symptom management should be based on patient of symptoms are most to the life they to teams should take the lead in symptom management, with care as the symptom is the responsibility of the kidney care should in this they to be to in symptoms will the of to symptom should of dialysis global symptom should be clinical should an that patient priorities for symptom management standardized and burden are for to be be or should be to symptom an important in identifying symptoms should not be in are not for dialysis of are as they on the or patient they not necessarily identify all and are frequently and they be to for clinical care should to patients with kidney with evidence for and limited for for and patients, such as are or have and to being to for in the dialysis and will based on frequency of symptom should be frequency of symptom assessment to patient outcomes and burden is not of a to J.M. A. et a outcome for hemodialysis patients in clinical of patients and on J Am Soc Nephrol. 2020; PubMed Scopus Google S. Manns B. et outcome in the care of hemodialysis 2021; PubMed Scopus Google Scholar, O.L. et and on outcome in the management of CKD: a J Kidney Dis. Full Text Full Text PDF PubMed Scopus (32) Google Scholar, N. et of a the of an outcome in the management of patients with chronic kidney 2022; Scopus Google Scholar, et symptom burden and health-related quality of life in dialysis patients: the of outcome Kidney 2020; PubMed Scopus Google Scholar, C.W. of patient reported outcomes is and patient in chronic kidney Int. 2017; PubMed Scopus Google Scholar and by patients and the risk of should be patient to clinical assessment they should be to the and nephrology and the to symptom the patient and most the care and will based on of to patients should such as be with patient can be and for symptom assessment and management are outcome in a related to symptom-based complications in of symptom assessment in outcomes and patient of symptoms related to chronic kidney are patient symptoms, symptoms such as and and the symptom burden and or factors (e.g., depression and anxiety can in does the treatment of symptoms health-related quality of or does and the and of be and for or for of symptom assessment and management in dialysis is to care as care in or should be symptom burden, health-related quality of the and of symptoms of patients undergoing of symptom assessment and management is most a patient in care in patient this the to to be for identifying and symptoms such as depression, pain, fatigue, and (e.g., with dialysis systems to and standardized assessment the existing implementation to and symptom assessment dialysis systems are the optimal methods for in symptom assessment and management of symptom-based complications in dialysis core in is the optimal to the of quality of life in is the to for initiation of dialysis is to for is the of treatment in treatment in is the of anxiety in patients receiving is the of and for management of with depression, should anxiety be for as an is the of among patients and are the and of universal for in a to symptom-based complications in the of symptoms and symptom to the development of fatigue and have a and are by and as a on in people undergoing maintenance as have been and are by trials to and for depression in patients on to the of management for physical symptoms in (e.g., and for a to identify with a of evidence for individualized on and when the is by and to identify clinical or that symptoms or symptom be a for an outcome for symptom that be in the development a in and in clinical for that patient for treatment the research. be by of or or by trials with a a population outcome and treatment patient and in a outcome core of symptom management is of with of patient of of treatment the care by the should focus on and managing symptoms that are most important to for symptom assessment and management should take the and factors the as as the in the existing delivery and education systems have a in addressing symptom assessment and management for people undergoing maintenance to existing clinical symptom should be clinical A. et of the Controversies on in Kidney Disease: a to quality Int. Full Text Full Text PDF PubMed Scopus Google Scholar the of is to identify and symptoms, when treatment options are limited, and symptoms is important because and to people with and can be S. et and in the quality among patients with and care Symptom 2018; Full Text Full Text PDF PubMed Scopus Google Scholar Symptom a the patient and the with a focus on symptoms that are most important or to the Recognition of symptoms and the that dialysis not provide to all symptoms of and of symptoms can be by of the and be by or when patients in-center dialysis. A recognized is that individual and vary and are by and In the of a to symptoms, to and clinicians can such as the are with life is patients with a of symptoms that are to or reported by undergoing dialysis can to of symptoms and the that as for is to be A that symptoms such as pain, symptoms, and symptoms, is in and on dialysis can a of The Symptom has S.D. et of a symptom assessment for chronic hemodialysis patients: the Symptom Symptom 2004; Full Text Full Text PDF PubMed Scopus Google Scholar and this individuals on hemodialysis report a of S.D. et and of physical and symptoms in chronic hemodialysis Am Soc Nephrol. 16: PubMed Scopus Google Scholar of people undergoing S.D. et and of physical and symptoms in chronic hemodialysis Am Soc Nephrol. 16: PubMed Scopus Google The prevalence of symptoms in end-stage disease: a systematic Kidney Dis. Full Text Full Text PDF PubMed Scopus Google Scholar The symptom burden the patient to and of symptoms that to has for clinical care. clinicians to symptoms to symptom symptom management, on or 1 symptom and as a that symptoms are not and can have can lead to in and and can lead to pain and and anxiety S. et depression, and dialysis symptom J Am Soc Nephrol. 2022; PubMed Scopus Google Scholar of in the clinical does have as this patient of symptoms and lead to of symptoms that not The of the not of methods for depression, evidence of is that for symptoms and in Depression and or et and in maintenance hemodialysis J Kidney Dis. Full Text Full Text PDF PubMed Scopus Google et and in peritoneal dialysis: a J Kidney Dis. Full Text Full Text PDF PubMed Scopus Google Scholar patient and and are to be the of depression, of and an to for depression is for all dialysis patients, a with a to depression in this such as K. The of a depression Med. 16: PubMed Scopus Google Scholar, S. T. et of depression in dialysis J Kidney Dis. Full Text Full Text PDF PubMed Scopus (242) Google Scholar, K. et for patients with kidney a systematic J Am Soc Nephrol. 2020; PubMed Scopus Google Scholar should be with clinical and is not this a clinical of is most not have consensus universal for should be as that the such an are assessment are et of for in patients receiving maintenance Am Soc Nephrol. 2020; PubMed Scopus Google Scholar universal for the for an and and a of The optimal frequency of symptom assessment among patients on dialysis to clinical outcomes the patients is not of J.M. A. et a outcome for hemodialysis patients in clinical of patients and on J Am Soc Nephrol. 2020; PubMed Scopus Google S. Manns B. et outcome in the care of hemodialysis 2021; PubMed Scopus Google Scholar, O.L. et and on outcome in the management of CKD: a J Kidney Dis. Full Text Full Text PDF PubMed Scopus (32) Google Scholar, N. et of a the of an outcome in the management of patients with chronic kidney 2022; Scopus Google Scholar, et symptom burden and health-related quality of life in dialysis patients: the of outcome Kidney 2020; PubMed Scopus Google Scholar, C.W. of patient reported outcomes is and patient in chronic kidney Int. 2017; PubMed Scopus Google Scholar The frequency of symptom a treatment or and of patient and the assessment being in symptoms are assessment the the clinical and the assessment to the and and the outcome have been in clinical research. such as for depression or assessment of health-related quality of are in of the and they the and patients and of J Med. 2017; PubMed Scopus Google Scholar evidence in the for A systematic review of the of of patient reported outcome on patients, and in an 13: PubMed Scopus Google Scholar, B. K. et of a for symptoms among adults with receiving 2022; Scopus Google Scholar, et al.Symptom with outcomes a PubMed Scopus Google Scholar are for symptom on the and they not necessarily identify all In in the of that symptoms with to improvements in and with the of be to is that trials are to this the of in clinical gaps and evidence be and the of the clinicians and patients, be N. T. et to outcomes assessment in clinical Scholar, The of with outcome to the quality of a systematic review of PubMed Scopus Google Scholar, B. outcome in care clinical a systematic review of and Med. PubMed Scopus Google Scholar, N. et systems for chronic patients on hemodialysis: of a 2017; 4: PubMed Scopus Google Scholar, A. M. et of in patients with and J 2018; PubMed Scopus Google Scholar, M. S. M. et physical and in hemodialysis patients a PubMed Scopus Google Scholar, A. G. M. et a for in J PubMed Scopus Google Scholar, a for outcomes for 2021; Scopus Google have in be by evidence of to kidney failure A. et of the Controversies on in Kidney Disease: a to quality Int. Full Text Full Text PDF PubMed Scopus Google S.D. et of a symptom assessment for chronic hemodialysis patients: the Symptom Symptom 2004; Full Text Full Text PDF PubMed Scopus Google Johnson of a symptom assessment in dialysis patients: a assessment of symptom Int. 69: Full Text Full Text PDF PubMed Scopus Google Scholar, et al.Developing a health-related for end-stage disease: The J Kidney Dis. Full Text Full Text PDF PubMed Google Scholar, J.E. A. et and of a hemodialysis symptom outcome PubMed Scopus Google Scholar, and assessment of the physical symptom Symptom 16: Full Text Full Text PDF PubMed Scopus Google Scholar, A. and of the Symptom for chronic kidney disease and Nephrol. 16: PubMed Scopus Google Scholar, et al.Symptom burden in patients with chronic kidney disease not Kidney 2017; PubMed Scopus Google be and with limited burden, and be for patients as with limited frailty, or a they are being to treatment, should be and to in should 1 response or to of symptoms not included on the in this is to the delivery of as a part of clinical assessment and not as a will patient in symptoms and the clinical of The of a to the patient is to the and for are should be by the for of clinical of N. T. et to outcomes assessment in clinical or of a for to focus on and for and of and patients to teams and patients the clinical The of with outcome to the quality of a systematic review of PubMed Scopus Google patient and of as part of B. outcome in care clinical a systematic review of and Med. PubMed Scopus Google delivery of as part of the clinical assessment and not as a of the and be to people undergoing and to for patients such as are with and to can be in of and or of symptoms to symptoms not and care of patient of to clinical and to be to all of the care points of and is of of a and of among with to responsibility and of implementation such as and to for to such as population can be to although this can be (e.g., can be to and needs of or in the of systems and patient of for to care N. et systems for chronic patients on hemodialysis: of a 2017; 4: PubMed Scopus Google be to as evidence of A. M. et of in patients with and J 2018; PubMed Scopus Google be to on in hemodialysis M. S. M. et physical and in hemodialysis patients a PubMed Scopus Google systems can and and can be in A. G. M. et a for in J PubMed Scopus Google a for outcomes for 2021; Scopus Google Scholar be for the with and to to with clinical to symptoms by management, treatment in all aspects of to the of treatment is not or be when symptoms be health-related quality of peritoneal outcome in a with evidence of for symptom assessment in chronic kidney kidney A. et of the Controversies on in Kidney Disease: a to quality Int. Full Text Full Text PDF PubMed Scopus Google Symptom Johnson of a symptom assessment in dialysis patients: a assessment of symptom Int. 69: Full Text Full Text PDF PubMed Scopus Google with a numerical for in of on the patient the to and for Symptom S.D. et of a symptom assessment for chronic hemodialysis patients: the Symptom Symptom 2004; Full Text Full Text PDF PubMed Scopus Google 1 all to for Outcomes in for et al.Developing a health-related for end-stage disease: The J Kidney Dis. Full Text Full Text PDF PubMed Google health-related to the to the symptom assessment as 1 of on and and health-related quality of on J.E. A. et and of a hemodialysis symptom outcome PubMed Scopus Google for in chronic hemodialysis patients. a treatment and a to symptom chronic kidney Symptom and assessment of the physical symptom Symptom 16: Full Text Full Text PDF PubMed Scopus Google to in to Symptom A. and of the Symptom for chronic kidney disease and Nephrol. 16: PubMed Scopus Google symptoms of the Symptom S.D. et of a symptom assessment for chronic hemodialysis patients: the Symptom Symptom 2004; Full Text Full Text PDF PubMed Scopus Google and frequency of as on a numerical by Symptom et al.Symptom burden in patients with chronic kidney disease not Kidney 2017; PubMed Scopus Google frequency and health-related of the symptoms and burden of of kidney the health-related chronic kidney Kidney of outcome or in a health-related quality of peritoneal outcome chronic kidney Kidney of outcome or for symptom-based complications in dialysis care are to and to dialysis-related and a and access to dialysis does not necessarily to access to related to or by that symptom management dialysis dialysis treatment access to kidney or of care is patient and and Recognition of factors such as and sex or should an of the patient as an to patients can be to (age, of of and a care gaps in can be with in dialysis or a of a A. et of the Controversies on in Kidney Disease: a to quality Int. Full Text Full Text PDF PubMed Scopus Google Scholar or should be to of that have of management should be based on and should be individualized to existing patient and and symptoms symptoms depression pain, and the be symptom the for medication to The risk of should be as of in the and and of as The nephrology will not necessarily have ownership of all and should be the of all care people for the of undergoing dialysis and although to dialysis is not based on existing B. et patient on functioning and in PubMed Scopus Google Scholar, G. et and in patients with chronic kidney PubMed Scopus Google Scholar, M. M. K. et care the not and Int. PubMed Scopus Google Scholar, et and to dialysis in chronic kidney J Kidney Dis. Full Text Full Text PDF PubMed Scopus Google Scholar, G. K. K. does education to a with and Nephrol. 2017; PubMed Scopus Google Scholar the dialysis to with individual patient is although have a is in physical symptoms with hemodialysis in a patient et of hemodialysis: the Int. Full Text Full Text PDF PubMed Scopus Google et hemodialysis J Med. PubMed Scopus Google Scholar knowledge gaps as to of dialysis delivery or peritoneal has clinical on physical or symptom A.A. A. T. et quality of life in dialysis patients to in-center hemodialysis patients: a systematic review and Med. 2020; Full Text Full Text PDF PubMed Scopus Google Scholar, B. A. et of outcome of quality of life by dialysis in the treatment of kidney a systematic J Kidney Dis. 2020; PubMed Scopus Google Scholar, et quality of life of peritoneal dialysis to hemodialysis a dialysis Scholar, et al.Symptom of anxiety and depression in patients receiving peritoneal dialysis to Int. 2022; PubMed Scopus Google Scholar, K. et options for dialysis in the in quality of life on peritoneal dialysis to for PubMed Scopus Google Scholar clinical of hemodialysis on the of quality of et of hemodialysis and quality of Am Soc Nephrol. 2017; PubMed Scopus Google B. et of dialysis with quality of J Am Soc Nephrol. PubMed Scopus Google Scholar behavioral or of or addressing of such as and and have the of and of for interactions with in delivery and and a burden of of are by evidence in the et on the of with in peritoneal dialysis patients and on Med. 2021; K. J.M. et of in outcomes in individuals on dialysis: a PubMed Scopus Google Scholar evidence for and for most in dialysis patients is evidence that such as behavioral have in et is an treatment for depression in hemodialysis Int. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar, N. et depression, quality of and in Am Soc Nephrol. PubMed Scopus Google Scholar, M. et for and depression in dialysis Google Scholar, Unruh M. et of for treatment of depression for patients undergoing maintenance hemodialysis: a clinical Med. PubMed Google Scholar and are recognized to access to behavioral that and the prevalence of et of in people undergoing

Topics & Concepts