3 research outputs found
The trajectory of a range of commonly captured symptoms with standard care in people with kidney failure receiving haemodialysis: consideration for clinical trial design
Background
Despite the recognized high symptom prevalence in haemodialysis population, how these symptoms change over time and its implications for clinical practice and research is poorly understood.
Methods
Prevalent haemodialysis patients in the SHAREHD trial reported 17 POS-S Renal symptoms (none, mild, moderate, severe and overwhelming) at baseline, 6, 12 and 18 months. To assess the prevalence change at population level in people reporting moderate or worse symptoms at baseline, the absolute change in prevalence was estimated using multi-level mixed effects probit regression adjusting for age, sex, time on haemodialysis and Charlson Comorbidity Score. To assess changes at individual level, the proportion of people changing their symptom score every 6 months was estimated.
Results
Five hundred fifty-two participants completed 1725 questionnaires at four timepoints. Across all 17 symptoms with moderate or worse symptom severity at baseline, the majority of the change in symptom prevalence at population level occurred in the ‘severe’ category. The absolute improvement in prevalence of the ‘severe’ category was ≤ 20% over 18 months in eleven of the seventeen symptoms despite a large degree of relatively balanced movement of individuals in and out of severe category every six months. Examples include depression, skin changes and drowsiness, which had larger proportion (75–80%) moving in and out of severe category each 6 months period but  20% were observed in six symptoms, driven by a 9 to 18% difference between movement in and movement out of severe category. All symptoms had > 50% of people in severe group changing severity within 6 months.
Conclusions
Changes in the severity of existing symptoms under standard care were frequent, often occurring within six months. Certain symptoms exhibited clinically meaningful shifts at both the population and individual levels. This highlighted the need to consider improvements in symptom severity when determining sample size and statistical power for trials. By accounting for potential symptom improvements with routine care, researchers can design trials capable of robustly detecting genuine treatment effects, distinguishing them from spontaneous changes associated with standard haemodialysis
Cost effectiveness of difelikefalin compared to standard care for treating chronic kidney disease associated pruritus (CKD-aP) in people with kidney failure receiving haemodialysis
Background: Chronic kidney disease-associated pruritus (CKD-aP) is associated with an increased risk of depression, poor sleep and reduced health-related quality of life. Two phase III studies (KALM-1 and KALM-2) of difelikefalin showed reduced CKD-aP severity and improved itch-related health-related quality of life in patients with moderate and severe CKD-aP receiving haemodialysis for kidney failure. Objective: We aimed to estimate the cost effectiveness of difelikefalin for patients with CKD-aP receiving haemodialysis for kidney failure compared to standard care from a UK National Health Service perspective. Methods: A cohort model was developed with four health states representing levels of pruritus intensity over time, based on the KALM trials augmented with longer term CKD-aP severity data from another haemodialysis trial (SHAREHD) for standard care. Utilities were estimated from a mapping study of 5-D Itch to EQ-5D-5L in 487 patients receiving haemodialysis, costs were estimated based on resource use alongside the SHAREHD and 2018 unit costs, and inflated to 2021 costs. Costs and quality-adjusted life-years were discounted at 3.5% per annum. A de novo economic model was developed in Microsoft Excel with scenario analyses performed using a range of assumptions. Results: In the base-case analysis over a time horizon of 64 weeks, using a placeholder cost of £75 per 28-days for difelikefalin, the incremental cost-effectiveness ratio of difelikefalin compared with standard care was £19,558/quality-adjusted life-year (QALY). Scenario analyses resulted in incremental cost-effectiveness ratios that ranged from £10,154/QALY (severe only) to £16,957/QALY (5-year horizon) for difelikefalin compared to standard care. Probabilistic sensitivity analyses suggested difelikefalin has a 48.6% probability of being cost effective at a threshold of £20,000/QALY and a 57.2% probability of being cost effective at a threshold of £30,000/QALY. Conclusions: The cost effectiveness of difelikefalin in a range of scenarios could make it an important pharmacotherapy to address the high burden of disease and unmet need for treatments associated with CKD-aP in the UK
Symptom burden according to dialysis day of the week in three times a week haemodialysis patients
Background
Haemodialysis patients experience significant symptom burden and effects on healthrelated quality of life. Studies have shown increases in fluid overload, hospitalization and
mortality immediately after the long interdialytic interval in thrice weekly in-centre haemodialysis patients, however the relationship between the dialytic interval and patient reported
outcome measures (PROMs) has not been quantified and the extent to which dialysis day of
PROM completion needs to be standardised is unknown.
Methods
Three times a week haemodialysis patients participating in a stepped wedge trial to increase
patient participation in haemodialysis tasks completed PROMs (POS-S Renal symptom
score and EQ-5D-5L) at recruitment, six, 12 and 18 months. Time from the long interdialytic
interval, HD day of the week, and HD days vs non-HD days were included in mixed effects
Linear Regression, estimating severity (none to overwhelming treated as 0 to 4) of 17 symptoms and EQ-5D-5L, adjusting for age, sex, time on HD, control versus intervention and
Charlson Comorbidity Score.
Results
517 patients completed 1659 YHS questionnaires that could be assigned HD day (510 on
Mon/Tue/Sun, 549 on Wed/Thu/Tue, 308 on Fri/Sat/Thu and 269 on non-HD days). With
the exception of restless legs and skin changes, there was no statistically significant change
in symptom severity or EQ-5D-5L with increasing time from the long interdialytic interval.
Patients who responded on non-HD days had higher severity of poor appetite, constipation,
difficulty sleeping, poor mobility and depression (approximately 0.2 severity level), and
lower EQ-5D-5L (-0.06, CI -0.09 to -0.03) compared to HD days.
PLOS ONE
PLOS ONE | https://doi.org/10.1371/journal.pone.0274599 September 27, 2022 1 / 13
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OPEN ACCESS
Citation: Hnynn Si PE, Gair R, Barnes T, Dunn L,
Lee S, Ariss S, et al. (2022) Symptom burden
according to dialysis day of the week in three times
a week haemodialysis patients. PLoS ONE 17(9):
e0274599. https://doi.org/10.1371/journal.
pone.0274599
Editor: Gianpaolo Reboldi, Universita degli Studi di
Perugia, ITALY
Received: August 8, 2021
Accepted: August 31, 2022
Published: September 27, 2022
Peer Review History: PLOS recognizes the
benefits of transparency in the peer review
process; therefore, we enable the publication of
all of the content of peer review and author
responses alongside final, published articles. The
editorial history of this article is available here:
https://doi.org/10.1371/journal.pone.0274599
Copyright: © 2022 Hnynn Si et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: A minimal dataset
required to reach the conclusions drawn from this
manuscript required the linkage of identifiable
patient information collected during the trial to
Conclusions
Measuring symptom severity and EQ-5D-5L in haemodialysis populations does not need to
account for dialysis schedule, but completion either on HD or non-HD days could introduce
bias that may impact evaluation of interventions. Researchers should ensure completion of
these instruments are standardized on either dialysis or non-dialysis days