An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

Consumer involvement in the development and dissemination of chronic kidney disease guidelines: a summary of a meaningful and sustainable approach developed by Caring for Australians and New ZealandeRs with kidney Impairment guidelines.

OBJECTIVES: The involvement of consumers (people with lived experience of disease) in guidelines is widely advocated to improve their relevance and uptake. However, the approaches to consumer involvement in guidelines vary and are not well documented. We describe the consumer involvement framework of Caring for Australians and New ZealandeRs with kidney Impairment Guidelines. STUDY DESIGN AND SETTING: We used a descriptive document analysis to collate all relevant policies, documents, e-mails, and presentations on consumer involvement in our organizations. We performed a narrative synthesis of collated data to summarize our evolving consumer involvement approach in guidelines. RESULTS: We involve consumers at all levels of Caring for Australians and New ZealandeRs with kidney Impairment guideline development and dissemination according to their capacity, from conducting consumer workshops to inform the scope of guidelines, to including consumers as members of the guideline Working Groups and overseeing operations and governance as members of the Steering Committee and staff. Our approach has resulted in tangible outcomes including high-priority topics on patient education, psychosocial care, and clinical care pathways, and focusing the literature reviews to assess patient-important outcomes. The ongoing partnership with consumers led to the generation of consumer version guidelines to improve guideline dissemination and translation to support shared decision-making. CONCLUSION: Meaningful consumer involvement can be achieved through a comprehensive approach across the entire lifecycle of guidelines. However, it must be individualized by ensuring that the involvement of consumers is timely and flexible. Future work is needed to assess the impact of consumer involvement in guideline development.

Patient-Centered Research and Outcomes in Cancer and Kidney Transplantation.

Cancer has been identified by kidney transplant recipients as a critically important outcome. The co-occurrence of cancer and kidney transplantation represents a complex intersection of diseases, symptoms, and competing priorities for treatments. Research that focuses on biochemical parameters and clinical events may not capture the priorities of patients. Patient-centered research can improve the relevance and efficiency of research and is particularly pertinent in the setting of cancer and kidney transplantation to facilitate shared decision-making in complex clinical situations. In addition, patient-reported outcomes can facilitate the assessment of patients' experiences, symptom burden, treatment side effects, and quality of life. This review discusses patient-centered research in the context of kidney transplantation and cancer, including consumer involvement in research and patient-centered outcomes and their measures and inclusion in core outcome sets.

It matters who you are and where you live: Commonwealth, state and territory policies for access to care for Australians with chronic kidney disease and their caregivers.

OBJECTIVE: To describe how Commonwealth, state and territory policies address access to care for Australians living with chronic kidney disease (CKD) with an emphasis on Aboriginal and Torres Strait Islanders and people residing in rural and remote areas. METHODS: We searched government health department websites for current policies up to March 2022 that addressed access to care for people with CKD. RESULTS: We included 98 policies: 28 were Commonwealth, and 70 were state or territory-based. There was wide variation in the policies for people with CKD in number and type across the jurisdictions. Of CKD specific policies, only three policies were specific for people living with CKD in rural and remote areas and no policies were specific for Aboriginal and Torres Strait Islander people. CONCLUSION: There is a lack of CKD-specific policies addressing access to care for Aboriginal and Torres Strait Islander people and people living in rural and remote communities. IMPLICATIONS FOR PUBLIC HEALTH: Despite the known disparities in the burden of CKD there are few policies addressing CKD disparities for Aboriginal and Torres Strait Islander people and Australians living in rural and remote areas. Policies that specifically address the barriers to accessing care are required to reduce inequities.

Validation of a Core Patient-Reported Outcome Measure for Life Participation in Kidney Transplant Recipients: the SONG Life Participation Instrument.

Introduction: Life participation has been established as a critically important core for trials in kidney transplantation. We aimed to validate a patient-reported outcome measure for life participation in kidney transplant recipients. Methods: A psychometric evaluation of the Standardized Outcomes in Nephrology life participation (SONG-LP) measure was conducted in adult kidney transplant recipients. The measure includes 4 items of life participation (leisure, family, work, and social) each with a 5-point Likert scale. Each item is scored from 0 (never) to 4 (always) and the summary measure score the average of each item. Results: A total of 249 adult kidney transplant recipients from 20 countries participated. The SONG-LP instrument demonstrated internal consistency (Cronbach's α = 0.87; 95% confidence intervals [CI]: 0.83-0.90, baseline) and test-retest reliability over 1 week (intraclass correlation coefficient of 0.62; 95% CI: 0.54-0.70). There was moderate to high correlation (0.65; 95% CI: 0.57-0.72) with the PROMIS Ability to Participate in Social Roles and Activities Short Form 8a that assessed a similar construct, and moderate correlation with measures that assessed related concepts (i.e., EQ5D 0.57; 95% CI: 0.49-0.65), PROMIS Cognitive Functional Abilities Subset Short Form 4a (0.40; 95% CI: 0.29-0.50). Conclusion: The SONG-LP instrument is a simple, internally consistent, reliable measure for kidney transplant recipients and correlates with similar measures. Routine incorporation in clinical trials will ensure consistent and appropriate assessment of life participation for informed patient-centered decision-making.

The RETRIEVE Checklist for Studies Reporting the Elicitation of Stated Preferences for Child Health-Related Quality of Life.

BACKGROUND: Recent systematic reviews show varying methods for eliciting, modelling, and reporting preference-based values for child health-related quality-of-life (HRQoL) outcomes, thus producing value sets with different characteristics. Reporting in many of the reviewed studies was found to be incomplete and inconsistent, making them difficult to assess. Checklists can help to improve standards of reporting; however, existing checklists do not address methodological issues for valuing child HRQoL. Existing checklists also focus on reporting methods and processes used in developing HRQoL values, with less focus on reporting of the values' key characteristics and properties. We aimed to develop a checklist for studies generating values for child HRQoL, including for disease-specific states and value sets for generic child HRQoL instruments. DEVELOPMENT: A conceptual model provided a structure for grouping items into five modules. Potential items were sourced from an adult HRQoL checklist review, with additional items specific to children developed using recent reviews. Checklist items were reduced by eliminating duplication and overlap, then refined for relevance and clarity via an iterative process. Long and short checklist versions were produced for different user needs. The resulting long RETRIEVE contains 83 items, with modules for reporting methods (A-D) and characteristics of values (E), for researchers planning and reporting child health valuation studies. The short RETRIEVE contains 14 items for decision makers or researchers choosing value sets. CONCLUSION: Applying the RETRIEVE checklists to relevant studies suggests feasibility. RETRIEVE has the potential to improve completeness in the reporting of preference-based values for child HRQOL outcomes and to improve assessment of preference-based value sets.

Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers, and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in CKD, which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: Online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals, who could read English, Spanish, or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a best-worst scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1 399 participants from 73 countries completed Round 1 of the Delphi survey including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization, and cardiovascular disease (mean difference > 0.3). Consensus was based upon the two groups yielding median scores of ≥ 7 and mean scores > 7, and the proportions of both groups rating the outcome as 'critically important' being greater than 50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers, and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death.

Longitudinal associations between socioeconomic position and overall health of children with chronic kidney disease and their carers.

BACKGROUND: Disadvantaged socioeconomic position (SEP) is an important predictor of poor health in children with chronic kidney disease (CKD). The time course over which SEP influences the health of children with CKD and their carers is unknown. METHODS: This prospective longitudinal study included 377 children, aged 6-18 years with CKD (stages I-V, dialysis, and transplant), and their primary carers. Mixed effects ordinal regression was performed to assess the association between SEP and carer-rated child health and carer self-rated health over a 4-year follow-up. RESULTS: Adjusted for CKD stage, higher family household income (adjusted odds ratio (OR) (95% CI) 3.3, 1.8-6.0), employed status of primary carers (1.7, 0.9-3.0), higher carer-perceived financial status (2.6, 1.4-4.8), and carer home ownership (2.2, 1.2-4.0) were associated with better carer-rated child health. Household income also had a differential effect on the carer's self-rated health over time (p = 0.005). The predicted probabilities for carers' overall health being 'very good' among lower income groups at 0, 2, and 4 years were 0.43 (0.28-0.60), 0.34 (0.20-0.51), and 0.25 (0.12-0.44), respectively, and 0.81 (0.69-0.88), 0.84 (0.74-0.91), and 0.88 (0.76-0.94) for carers within the higher income group. CONCLUSIONS: Carers and their children with CKD in higher SEP report better overall child and carer health compared with those in lower SEP. Carers of children with CKD in low-income households had poorer self-rated health compared with carers in higher-income households at baseline, and this worsened over time. These cumulative effects may contribute to health inequities between higher and lower SEP groups over time. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Systematic Review of the Relative Social Value of Child and Adult Health.

OBJECTIVES: We aimed to synthesise knowledge on the relative social value of child and adult health. METHODS: Quantitative and qualitative studies that evaluated the willingness of the public to prioritise treatments for children over adults were included. A search to September 2023 was undertaken. Completeness of reporting was assessed using a checklist derived from Johnston et al. Findings were tabulated by study type (matching/person trade-off, discrete choice experiment, willingness to pay, opinion survey or qualitative). Evidence in favour of children was considered in total, by length or quality of life, methodology and respondent characteristics. RESULTS: Eighty-eight studies were included; willingness to pay (n = 9), matching/person trade-off (n = 12), discrete choice experiments (n = 29), opinion surveys (n = 22) and qualitative (n = 16), with one study simultaneously included as an opinion survey. From 88 studies, 81 results could be ascertained. Across all studies irrespective of method or other characteristics, 42 findings supported prioritising children, while 12 provided evidence favouring adults in preference to children. The remainder supported equal prioritisation or found diverse or unclear views. Of those studies considering prioritisation within the under 18 years of age group, nine findings favoured older children over younger children (including for life saving interventions), six favoured younger children and five found diverse views. CONCLUSIONS: The balance of evidence suggests the general public favours prioritising children over adults, but this view was not found across all studies. There are research gaps in understanding the public's views on the value of health gains to very young children and the motivation behind the public's views on the value of child relative to adult health gains. CLINICAL TRIAL REGISTRATION: The review is registered at PROSPERO number: CRD42021244593. There were two amendments to the protocol: (1) some additional search terms were added to the search strategy prior to screening to ensure coverage and (2) a more formal quality assessment was added to the process at the data extraction stage. This assessment had not been identified at the protocol writing stage.

School attendance and sport participation amongst children with chronic kidney disease: a cross-sectional analysis from the Kids with CKD (KCAD) study.

BACKGROUND: School attendance and life participation, particularly sport, is a high priority for children with chronic kidney disease (CKD). This study is aimed at assessing the association between CKD stage, sports participation, and school absences in children with CKD. METHODS: Using data from the binational Kids with CKD study (ages 6-18 years, n = 377), we performed multivariable regression to evaluate the association between CKD stage, school absences, and sports participation. RESULTS: Overall, 62% of participants played sport with the most frequent sport activities engaged in being swimming (17%) and soccer (17%). Compared to children with CKD 1-2, the incidence rate ratios (IRR) (95% CI) for sports participation amongst children with CKD 3-5, dialysis, or transplant were 0.84 (0.64-1.09), 0.59 (0.39-0.90), and 0.75 (0.58-0.96), respectively. The median (IQR) days of school absences within a four-week period were 1 day (0-1), with children on dialysis reporting the highest number of school absences (9 days (5-15)), followed by transplant recipients (2 days (1-7)), children with CKD 3-5 (1 day (0-3)), and with CKD 1-2 (1 day (0-3)). Duration of CKD modified the association between CKD stage and school absences, with children with a transplant experiencing a higher number of missed school days with increasing duration of CKD, but not in children with CKD 1-5 or on dialysis (p-interaction < 0.01). CONCLUSIONS: Children receiving dialysis and with a kidney transplant had greater school absences and played fewer sports compared to children with CKD stages 1-2. Innovative strategies to improve school attendance and sport participation are needed to improve life participation of children with CKD.

A Randomized Controlled Trial of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children referred to specialist outpatient clinics by primary care providers often have long waiting times before being seen. We assessed whether an individualized, web-based, evidence-informed management support for children with urinary incontinence while waiting reduced requests for specialist appointments. MATERIALS AND METHODS: A multicenter, waitlisted randomized controlled trial was conducted for children (5-18 years) with urinary incontinence referred to tertiary pediatric continence clinics. Participants were randomized to the web-based eHealth program electronic Advice and Diagnosis Via the Internet following Computerized Evaluation (eADVICE), which used an embodied conversational agent to engage with the child at the time of referral (intervention) or 6 months later (control). The primary outcome was the proportion of participants requesting a clinic appointment at 6 months. Secondary outcomes included persistent incontinence, and the Paediatric incontinence Questionnaire (PinQ) score. RESULTS: From 2018 to 2020, 239 children enrolled, with 120 randomized to eADVICE and 119 to the control arm. At baseline, participants' mean age was 8.8 years (SD 2.2), 62% were males, mean PinQ score was 5.3 (SD 2.2), 36% had daytime incontinence, and 97% had nocturnal enuresis. At 6 months, 78% of eADVICE participants vs 84% of controls requested a clinic visit (relative risk 0.92, 95% CI 0.79, 1.06, P = .3), and 23% eADVICE participants vs 10% controls were completely dry (relative risk 2.23, 95% CI 1.10, 4.50, P = .03). The adjusted mean PinQ score was 3.5 for eADVICE and 3.9 for controls (MD -0.37, 95% CI -0.71, -0.03, P = .03). CONCLUSIONS: The eADVICE eHealth program for children awaiting specialist appointments doubled the proportion who were dry at 6 months and improved quality of life but did not reduce clinic appointment requests.

Multi-center, pragmatic, cluster-randomized, controlled trial of standardized peritoneal dialysis (PD) training versus usual care on PD-related infections (the TEACH-PD trial): trial protocol.

BACKGROUND: Peritoneal dialysis (PD)-related infections, such as peritonitis, exit site, and tunnel infections, substantially impair the sustainability of PD. Accordingly, PD-related infection is the top-priority research outcome for patients and caregivers. While PD nurse trainers teach patients to perform their own PD, PD training curricula are not standardized or informed by an evidentiary base and may offer a potential approach to prevent PD infections. The Targeted Education ApproaCH to improve Peritoneal Dialysis outcomes (TEACH-PD) trial evaluates whether a standardized training curriculum for PD nurse trainers and incident PD patients based on the International Society for Peritoneal Dialysis (ISPD) guidelines reduces PD-related infections compared to usual training practices. METHODS: The TEACH-PD trial is a registry-based, pragmatic, open-label, multi-center, binational, cluster-randomized controlled trial. TEACH-PD will recruit adults aged 18 years or older who have not previously undergone PD training at 42 PD treatment units (clusters) in Australia and New Zealand (ANZ) between July 2019 and June 2023. Clusters will be randomized 1:1 to standardized TEACH-PD training curriculum or usual training practice. The primary trial outcome is the time to the first occurrence of any PD-related infection (exit site infection, tunnel infection, or peritonitis). The secondary trial outcomes are the individual components of the primary outcome, infection-associated catheter removal, transfer to hemodialysis (greater than 30 days and 180 days), quality of life, hospitalization, all-cause death, a composite of transfer to hemodialysis or all-cause death, and cost-effectiveness. Participants are followed for a minimum of 12 months with a targeted average follow-up period of 2 years. Participant and outcome data are collected from the ANZ Dialysis and Transplant Registry (ANZDATA) and the New Zealand Peritoneal Dialysis (NZPD) Registry. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. DISCUSSION: TEACH-PD is a registry-based, cluster-randomized pragmatic trial that aims to provide high-certainty evidence about whether an ISPD guideline-informed standardized PD training curriculum for PD nurse trainers and adult patients prevents PD-related infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816111. Registered on 24 January 2019.

Recommendations for culturally safe clinical kidney care for First Nations Australians: a guideline summary.

INTRODUCTION: First Nations Australians display remarkable strength and resilience despite the intergenerational impacts of ongoing colonisation. The continuing disadvantage is evident in the higher incidence, prevalence, morbidity and mortality of chronic kidney disease (CKD) among First Nations Australians. Nationwide community consultation (Kidney Health Australia, Yarning Kidneys, and Lowitja Institute, Catching Some Air) identified priority issues for guideline development. These guidelines uniquely prioritised the knowledge of the community, alongside relevant evidence using an adapted GRADE Evidence to Decision framework to develop specific recommendations for the management of CKD among First Nations Australians. MAIN RECOMMENDATIONS: These guidelines explicitly state that health systems have to measure, monitor and evaluate institutional racism and link it to cultural safety training, as well as increase community and family involvement in clinical care and equitable transport and accommodation. The guidelines recommend earlier CKD screening criteria (age ≥ 18 years) and referral to specialists services with earlier criteria of kidney function (eg, estimated glomerular filtration rate [eGFR], ≤ 45 mL/min/1.73 m2 , and a sustained decrease in eGFR, > 10 mL/min/1.73 m2 per year) compared with the general population. CHANGES IN MANAGEMENT AS RESULT OF THE GUIDELINES: Our recommendations prioritise health care service delivery changes to address institutional racism and ensure meaningful cultural safety training. Earlier detection of CKD and referral to nephrologists for First Nations Australians has been recommended to ensure timely implementation to preserve kidney function given the excess burden of disease. Finally, the importance of community with the recognition of involvement in all aspects and stages of treatment together with increased access to care on Country, particularly in rural and remote locations, including dialysis services.

Psychometric Evaluation of the PedsQL GCS and CHU9D in Australian Children and Adolescents with Common Chronic Health Conditions.

BACKGROUND: Generic instruments such as the Pediatric Quality of Life Inventory™ v4.0 Generic Core Scales (PedsQL GCS) and Child Health Utility 9D (CHU9D) are widely used to assess health-related quality of life (HRQOL) of the general childhood population, but there is a paucity of information about their psychometric properties in children with specific health conditions. This study assessed psychometric properties, including acceptability, reliability, validity, and responsiveness, of the PedsQL GCS and the CHU9D in children and adolescents with a range of common chronic health problems. METHODS: We used data from the Longitudinal Study of Australian Children (LSAC), for children aged 10-17 years with at least one of the following six parent-reported health conditions: asthma, anxiety/depression, attention deficit hyperactivity disorder (ADHD), autism/Asperger's, epilepsy, and type 1 diabetes mellitus. The LSAC used parent proxy-reported PedsQL GCS and child self-reported CHU9D assessments. The performance of each instrument (PedsQL GCS and CHU9D) for each psychometric property (acceptability, reliability, validity, and responsiveness) was assessed against established criteria. RESULTS: The study sample included 7201 children and adolescents (mean age = 14 years; range 10.1-17.9 years; 49% female) with 15,568 longitudinal observations available for analyses. Across the six health conditions, acceptability of the PedsQL GCS was high, while acceptability for the CHU9D was mixed. Both the PedsQL GCS and CHU9D showed strong internal consistency (Cronbach's alpha range: PedsQL GCS = 0.70-0.95, CHU9D = 0.76-0.84; item-total correlations range: PedsQL GCS = 0.35-0.84, CHU9D = 0.32-0.70). However, convergent validity for both the PedsQL GCS and CHU9D was generally weak (Spearman's correlations ≤ 0.3). Known group validity was strong for the PedsQL GCS (HRQOL differences were detected for children with and without asthma, anxiety/depression, ADHD, autism/Asperger's, and epilepsy). CHU9D was only able to discriminate between children with and without anxiety/depression, ADHD, and autism/Asperger's. The responsiveness of both the PedsQL GCS and CHU9D was variable across the six conditions, and most of the estimated effect sizes were relatively small (< 0.5). CONCLUSION: This study expands the evidence base of psychometric performance of the PedsQL GCS and CHU9D and can aid in appropriate HRQOL instrument selection for the required context by researchers and clinicians.

Patient Preferences for the Management of Gastrointestinal Symptoms in Kidney Transplantation: a Discrete Choice Experiment.

Introduction: Gastrointestinal (GI) symptoms in kidney transplant are common and debilitating. We aimed to ascertain patients' preferences for GI symptom management options to help future interventions align with treatment priorities. Methods: A discrete choice experiment was conducted with kidney transplant recipients in 3 Australian nephrology units. A multinomial logit model was used to quantify the preferences and trade-offs between 5 characteristics: cost, formulation, symptom burden, dietary changes, and medication quantities. Results: Seventy patients participated (mean age ± SD: 47 ± 15 years, 56% female), 57% had GI symptoms. Patients preferred interventions that will achieve complete resolution of GI symptoms compared to no improvement (odds ratio [95% confidence interval]: 15.3 [1.80, 129.50]), were delivered as a tablet rather than a sachet (1.6 [1.27, 2.08]), retained their current diet compared to eliminating food groups (6.0 [2.19, 16.27]), reduced medication burden (1.4 [1.06, 1.79]), and had lower costs (0.98 [0.96, 1.00]). Participants would be willing to pay AUD$142.20 [$83.90, $200.40] monthly to achieve complete resolution of GI symptoms or AUD$100.90 [$9.60, $192.10] to have moderate improvement in symptoms. Conclusions: Interventions that are highly effective in relieving all GI symptoms without the need for substantive dietary changes, and in tablet form, are most preferred by kidney transplant recipients.

Synbiotics, prebiotics and probiotics for people with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability). OBJECTIVES: This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) measuring and reporting the effects of synbiotics, prebiotics, or probiotics in any combination and any formulation given to people with CKD (CKD stages 1 to 5, including dialysis and kidney transplant). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors using a standard data extraction form. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Forty-five studies (2266 randomised participants) were included in this review. Study participants were adults (two studies in children) with CKD ranging from stages 1 to 5, with patients receiving and not receiving dialysis, of whom half also had diabetes and hypertension. No studies investigated the same synbiotic, prebiotic or probiotic of similar strains, doses, or frequencies. Most studies were judged to be low risk for selection bias, performance bias and reporting bias, unclear risk for detection bias and for control of confounding factors, and high risk for attrition and other biases. Compared to prebiotics, it is uncertain whether synbiotics improve estimated glomerular filtration rate (eGFR) at four weeks (1 study, 34 participants: MD -3.80 mL/min/1.73 m², 95% CI -17.98 to 10.38), indoxyl sulfate at four weeks (1 study, 42 participants: MD 128.30 ng/mL, 95% CI -242.77 to 499.37), change in gastrointestinal (GI) upset (borborymgi) at four weeks (1 study, 34 participants: RR 15.26, 95% CI 0.99 to 236.23), or change in GI upset (Gastrointestinal Symptom Rating Scale) at 12 months (1 study, 56 participants: MD 0.00, 95% CI -0.27 to 0.27), because the certainty of the evidence was very low. Compared to certain strains of prebiotics, it is uncertain whether a different strain of prebiotics improves eGFR at 12 weeks (1 study, 50 participants: MD 0.00 mL/min, 95% CI -1.73 to 1.73), indoxyl sulfate at six weeks (2 studies, 64 participants: MD -0.20 µg/mL, 95% CI -1.01 to 0.61; I² = 0%) or change in any GI upset, intolerance or microbiota composition, because the certainty of the evidence was very low. Compared to certain strains of probiotics, it is uncertain whether a different strain of probiotic improves eGFR at eight weeks (1 study, 30 participants: MD -0.64 mL/min, 95% CI -9.51 to 8.23; very low certainty evidence). Compared to placebo or no treatment, it is uncertain whether synbiotics improve eGFR at six or 12 weeks (2 studies, 98 participants: MD 1.42 mL/min, 95% CI 0.65 to 2.2) or change in any GI upset or intolerance at 12 weeks because the certainty of the evidence was very low. Compared to placebo or no treatment, it is uncertain whether prebiotics improves indoxyl sulfate at eight weeks (2 studies, 75 participants: SMD -0.14 mg/L, 95% CI -0.60 to 0.31; very low certainty evidence) or microbiota composition because the certainty of the evidence is very low. Compared to placebo or no treatment, it is uncertain whether probiotics improve eGFR at eight, 12 or 15 weeks (3 studies, 128 participants: MD 2.73 mL/min, 95% CI -2.28 to 7.75; I² = 78%), proteinuria at 12 or 24 weeks (1 study, 60 participants: MD -15.60 mg/dL, 95% CI -34.30 to 3.10), indoxyl sulfate at 12 or 24 weeks (2 studies, 83 participants: MD -4.42 mg/dL, 95% CI -9.83 to 1.35; I² = 0%), or any change in GI upset or intolerance because the certainty of the evidence was very low. Probiotics may have little or no effect on albuminuria at 12 or 24 weeks compared to placebo or no treatment (4 studies, 193 participants: MD 0.02 g/dL, 95% CI -0.08 to 0.13; I² = 0%; low certainty evidence). For all comparisons, adverse events were poorly reported and were minimal (flatulence, nausea, diarrhoea, abdominal pain) and non-serious, and withdrawals were not related to the study treatment. AUTHORS' CONCLUSIONS: We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.

Participant Perceptions in a Long-term Clinical Trial of Autosomal Dominant Polycystic Kidney Disease.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated. Study Design: Qualitative study. Setting & Participants: All participants (N=187) were invited to complete a 16-item questionnaire at the final study visit of the primary trial. Participants were recruited to complete a semistructured interview using purposeful sampling according to age, self-reported gender, and randomization group. Analytical Approach: Descriptive statistics were used for demographic data and questionnaires. The interview transcripts underwent inductive thematic coding. Results: One hundred and forty-six of the 187 randomized participants (79%) completed the post-trial questionnaire, and 31 of the 187 participants (21%) completed the interview. Most participants (94%) rated their global satisfaction with the trial as high (a score of 8 or more out of 10). Altruism, knowledge gain, and access to new treatments were the main motivators for recruitment. The main reasons for considering leaving the study were concerns about the risk of intervention and family or work issues. Strategies that favored retention included flexibility in attending different study sites, schedule flexibility, staff interactions, and practical support with parking and reminders. The main burden was time away from work with lost wages, and burden associated with magnetic resonance imaging scans and 24-hour urine output collections. Limitations: The study population was restricted to participants in a single nondrug clinical trial, and the results could be influenced by selection and possible social desirability bias. Conclusions: Participants reported high levels of satisfaction that occurred as a function of the trial meeting participants' expectations. Furthermore, retention was a balance between the perceived benefits and burden of participation. Consideration of these perspectives in the design of future clinical trials will improve their efficiency and conduct. Plain-Language Summary: Advances in the clinical practice of autosomal dominant polycystic kidney disease (ADPKD) require affected individuals to voluntarily participate in long-term multicenter randomized controlled trials (RCTs). In this qualitative post hoc study of a 3-year RCT of increased water intake in ADPKD, altruism, knowledge gain, and access to a nondrug treatment positively influenced the decision to volunteer. Ongoing participation was enabled by building flexibility into the study protocol and staff prioritizing a participant's needs during study visits. Although participants completed the required tests, most were considered burdensome. This study highlights the importance of incorporating protocol flexibility into trial design; the preference for interventions with a low risk of adverse effects; and the urgent requirement for robust surrogate noninvasive biomarkers to enable shorter RCTs in ADPKD.

Can language enhance physical therapists' willingness to follow Choosing Wisely recommendations? A best-worst scaling study.

BACKGROUND: Choosing Wisely recommendations could reduce physical therapists' use of low-value care. OBJECTIVE: To investigate whether language influences physical therapists' willingness to follow the Australian Physiotherapy Association's (APA) Choosing Wisely recommendations. DESIGN: Best-worst Scaling survey METHODS: The six original APA Choosing Wisely recommendations were modified based on four language characteristics (level of detail, strength- qualified/unqualified, framing, and alternatives to low-value care) to create 60 recommendations. Physical therapists were randomised to a block of seven choice tasks, which included four recommendations. Participants indicated which recommendation they were most and least willing to follow. A multinomial logistic regression model was used to create normalised (0=least preferred; 10=most preferred) and marginal preference scores. RESULTS: 215 physical therapists (48.5% of 443 who started the survey) completed the survey. Participants' mean age (SD) was 38.7 (10.6) and 47.9% were female. Physical therapists were more willing to follow recommendations with more detail (marginal preference score of 1.1) or that provided alternatives to low-value care (1.3) and less willing to follow recommendations with negative framing (-1.3). The use of qualified ('don't routinely') language (vs. unqualified - 'don't') did not affect willingness. Physical therapists were more willing to follow recommendations to avoid imaging for non-specific low back pain (3.9) and electrotherapy for low back pain (3.8) vs. recommendation to avoid incentive spirometry after upper abdominal and cardiac surgery. CONCLUSION: Physical therapists were more willing to follow recommendations that provided more detail, alternatives to low-value care, and were positively framed. These findings can inform the development of future Choosing Wisely recommendations and could help reduce low-value physical therapy.

Long-term Trends in Infection-Related Mortality in Adults Treated With Maintenance Dialysis.

RATIONALE & OBJECTIVE: Infection is 1 of the top 3 causes of death in patients receiving maintenance dialysis. We evaluated the trends over time and risk factors for infection-related deaths among people receiving dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We included all adults who began dialysis between 1980 and 2018 in Australia and New Zealand. EXPOSURE: Age, sex, dialysis modality, and dialysis era. OUTCOME: Infection-related death. ANALYTICAL APPROACH: Incidence was described and standardized mortality ratios (SMR) calculated for infection-related death. Fine-Gray subdistribution hazards models were fitted, with non-infection-related death and kidney transplantation treated as competing events. RESULTS: The study comprised 46,074 patients who received hemodialysis and 20,653 who were treated with peritoneal dialysis who were followed for 164,536 and 69,846 person-years, respectively. There were 38,463 deaths during the follow-up period, 12% of which were ascribed to infection. The overall rate of mortality from infection (per 10,000 person-years) was 185 and 232 for patients treated with hemodialysis and peritoneal dialysis, respectively. The rates were 184 and 219 for males and females, respectively; and 99, 181, 255, and 292 for patients aged 18-44, 45-64, 65-74, 75 years and over, respectively. The rates were 224 and 163 for those commencing dialysis in years 1980-2005 and 2006-2018, respectively. The overall SMR declined over time, from 37.1 (95% CI, 35.5-38.8) in years 1980-2005 to 19.3 (95% CI, 18.4-20.3) in years 2006-2018, consistent with the declining 5-year SMR trend (P<0.001). Infection-related mortality was associated with being female, older age, and Aboriginal and/or a Torres Strait Islander or Maori. LIMITATIONS: Mediation analyses defining the causal relationships between infection type and infection-related death could not be undertaken as disaggregating the data was not feasible. CONCLUSIONS: The excess risk of infection-related death in patients on dialysis has improved substantially over time but remains more than 20 times higher than in the general population.