BACKGROUND: BK virus (BKV) is a common latent virus that can reactivate in kidney transplant recipients due to immunosuppressive therapy, potentially leading to graft dysfunction or loss. While clinical management of BKV is well studied, little is known about its broader impact on patients’ daily lives and well-being. No conceptual model currently exists to describe the health-related quality of life (HRQoL) impacts of BKV from the patient perspective. METHODS: We conducted a qualitative study using semi-structured concept elicitation interviews with 12 adult kidney transplant recipients who had experienced BKV reactivation. Participants were recruited using purposive sampling to ensure diversity in demographics and clinical experiences. Interviews were transcribed and analyzed using thematic analysis with iterative coding, saturation tracking, and structured impact prioritization to develop a conceptual model of BKV-related HRQoL impacts. RESULTS: Participants described a range of psychosocial and practical challenges associated with BKV, despite the virus often being asymptomatic. Key themes included emotional distress, fear of graft loss, confusion about treatment, disruption to work and daily routines, and increased burden of care coordination. Many participants reported feeling unprepared and unsupported, often needing to advocate for themselves within the healthcare system. These experiences were synthesized into a conceptual model illustrating the multidimensional impact of BKV on HRQoL. CONCLUSIONS: This study presents the first patient-informed conceptual model of BKV-related HRQoL impacts in kidney transplant recipients. Findings highlight the need for improved patient education, communication, and support strategies. The model provides a foundation for future development of patient-reported outcome measures and interventions that address the unique burdens of BKV in transplant care.

BackgroundAttending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.MethodFrom June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease. Based on implementation science guidelines (eg, Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies, Reach, Effectiveness, Adoption, Implementation, Maintenance), we monitored use and captured adaptations in implementation strategies. Clinicians (n=7) and patients (n=30) responded to a 6-month survey that included appropriateness, acceptability, adoption and sustainability.ResultsOut of 1450 eligible patients, 748 (52%) completed at least one PRO invitation (reach). 37% of PRO questionnaire invitations (1421/3882) were completed (fidelity to PRO completion), with higher rates occurring when more implementation strategies were adopted. Among completed postvisit surveys from patients, 57% indicated that the dashboard was discussed at an eligible visit (fidelity to dashboard use). In the 6-month survey, patients endorsed the dashboard’s acceptability and appropriateness: 77% felt it frequently provided clear information and 63% felt it frequently met their needs. Most patients (77%) and clinicians (86%) valued the dashboard for increasing SDM, and 57% of clinicians endorsed the dashboard’s clinical sustainability.DiscussionThis pilot study demonstrated the clinical appropriateness, acceptability and feasibility of implementing an EHR-integrated PRO dashboard for advanced cancer and chronic kidney disease. Results also point to areas for improvement, including strategies to further support patient and clinician engagement, PRO completion and sustainability in real-world implementation.

Patient-reported outcomes (PROs) enable the report of experiences that are only known to the patient, such as how an individual’s symptoms, functioning, and quality of life are impacted by a health condition or treatment. The choice of PRO depends on the intended application and associated research questions, and structuring a rationale for the use of PRO data is key to deciding upon a PRO strategy. Rates of PRO use in paediatric oncology research remain low though the general use of PROs in clinical trials has been gradually increasing. This is likely to have risen due to increased emphasis by regulatory agencies to capture outcomes meaningful to patients. Despite increasing interest in PROs, a range of barriers to their use have been identified by researchers exploring their implementation and a pattern of under-reporting of PRO data has also been observed in general oncology trials. Research with children entails specific challenges, including the need for developmentally-appropriate outcome measures, the complexities of family involvement, and the adaptations required in research procedures and settings to accommodate children's physical, cognitive, and emotional development. With the nascent use of PROs in paediatric oncology, there are opportunities to benefit from learning from trials involving adult participants. The current paper outlines considerations for PRO selection for use in paediatric oncology research, describing five steps to determine the PRO study goals, the study outcomes, the reporter(s), measures, and study implementation. We discuss the breadth of applications of PROs in paediatric oncology research and potential for further learning and harmonisation with the aim of centering children’s experiences.

PURPOSE Financial toxicity (FT) has been linked to higher symptom burden and poorer clinical outcomes for patients with cancer. Despite the availability of validated tools to measure FT, a simple screen remains an unmet need. We evaluated item 12 (“My illness has been a financial hardship to my family and me”) of the COmprehensive Score for Financial Toxicity (COST) measure as a single-item FT screening measure. METHODS In this secondary analysis, 711 patients with cancer (690 with breast cancer) were recruited via a web-based survey from a philanthropic organization. COST items 1-11 were scored according to Functional Assessment of Chronic Illness Therapy scoring guidelines, with lower scores indicating worse FT. Analyses focused on establishing a correlation, examining item properties, and sensitivity/specificity of item 12 relative to the total COST score. RESULTS Item 12 had a correlation of r = 0.53 with the COST-11 score, and an increase of one point on item 12 is associated with a decrease of approximately three total points on the full scale ( b , 3.35; P < .001; adjusted R 2 , 0.28). Item analysis with the graded-response item in response theory modeling showed very good discrimination ( a , 2.096) for item 12, indicating that it can reliably distinguish between low and high FT in patients. Sensitivity ranged between 75.6% and 95.7% on all item 12 thresholds to screen positive for FT using two COST cutoffs as criteria. Maximizing both sensitivity and specificity was to be found for higher item 12 scores. CONCLUSION To our knowledge, this is the first validation of a single-item screening measure for FT. Overall, these results illustrate that item 12 from the COST measure is a good candidate for a single-item screener. Clinicians can choose among item 12 screening thresholds depending on their tolerance for low specificity.

The American Society of Transplantation commissioned a survey assessing transplant recipients' perceptions of unmet immunosuppressant needs. Topics included medication side effects, treatment burden, health-related quality of life, adherence, self-efficacy, costs, trust, and discrimination; 10 091 responses were included (9543 adults, 548 pediatric respondents) representing 232 transplant centers. Respondents were a mean of 6.6 years posttransplant and were well-represented across age, gender, race, ethnicity, organ, employment, insurance, and immunosuppression. Nearly all (92%) respondents reported at least 1 side effect (median of 3); most side effects occurred "often" or "always." The majority (54%) of side effects were rated as having a "moderate" or "great deal" of impact on daily life. Side effects with the greatest daily burden included skin cancer, pain/neuropathy, skin issues, kidney disease, memory/brain fog, diabetes, cancer, and hypertension. Fatigue, headache, insomnia, tremors, and mood/depression/anxiety were the most selected side effects. Health-related quality of life was rated as "fair" to "good." Trust in providers, self-efficacy, and medication adherence were rated highly, though 25% reported skipping doses due to side effects, and 40% skipped due to costs. The findings demonstrate that side effects are nearly universally experienced and have a major burden on daily life. Immunosuppression induces a heavy toll on transplant recipients; there is an urgent need for new treatments to address these unmet needs.

Background Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial results demonstrate continuous long-term improvement in motor development and cognitive function. We sought to characterize clinically meaningful change in motor function, as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score, and assess correlations with cognition and language domains of the Bayley-III and motor milestone (MM) achievement. Methods Data from N = 30 patients from three single-arm clinical studies of eladocagene exuparvovec were analyzed. Anchor-based estimation of the meaningful score difference (MSD) of Total PDMS-2 score was conducted using mean-difference and receiver operating characteristic curve (ROC) approaches. MM achievement served as the anchor defining meaningful change. Results An MSD of 40 points for Total PDMS-2 score was selected for analysis as it yielded specificity > 0.95 using the ROC approach, and generally aligned with the mean-difference approach. Cumulative incidence analysis reflected that 50% of patients treated with eladocagene exuparvovec may achieve the MSD of 40-point change in Total PDMS-2 score at 6 months, and 86% at 18 months. Correlations between measures were of large magnitude and improved over time (Month 6: r = 0.599 [p = 0.0032]; Month 18: r = 0.796 [p = 0.0002]; Month 60: r = 0.861 [p = 0.0007]). Conclusions The MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function.

Kidney transplantation (KT) is associated with better clinical and health-related quality of life (HRQOL) outcomes than dialysis. However, some KT recipients (KTRs) live with poor kidney function (eGFR ≤ 29 ml/min/1.73 m2). We use the Patient-Reported Outcomes Measurement Information System (PROMIS®) Physical Health (PHS) and Mental Health (MHS) Summary Scores to compare HRQOL between patients on dialysis versus KTRs with either poor (eGFR ≤ 29 ml/min/1.73m2) or preserved (eGFR > 29 ml/min/1.73 m2) kidney function. Secondary analysis of cross-sectional data from a convenience sample of adults treated with dialysis or KT. Exposure: kidney replacement therapy (KRT) type. Outcome: PHS and MHS scores. The PHS and MHS structural validity, test-retest reliability, correlations with legacy measures, and known-group comparisons were evaluated. The independent association between HRQOL and KRT was assessed using multivariable linear regression. Of the 647 participants, 388 (60

Patient-perceived treatment tolerability can affect patient ability and willingness to remain on therapy. We sought to examine completion rates for a single item of overall side effect bother at baseline and at the first on-treatment assessment, the association between this item with other patient-reported outcomes (PROs) and the odds of early discontinuation due to clinician-assessed adverse events or reasons other than disease progression. Data were from three commercial cancer trials in solid tumours, focusing on the safety population. The GP5 item from the Functional Assessment of Cancer Therapy (FACT) was used for side effect bother. Other PROs included items on specific symptoms, functional impacts and global health status, all drawn from validated measures. Descriptive statistics were used for completion rates, and correlation and logistic regression analyses were used to examine associations. GP5 was dichotomised as 0–1 (‘low’) versus 2–4 (‘high’). Completion rates were at or above 90

BACKGROUND:Overall side-effect impact, the aggregated experience of multiple toxicities, can be captured with the single Functional Assessment of Cancer Therapy (FACT) item GP5 ("I am bothered by side effects of treatment"). The objective of this study was to evaluate the ability of item GP5 to indicate treatment tolerability by examining its association with early treatment discontinuation (ETD) due to adverse events (AEs) in four cancer trials. METHODS:The authors analyzed data from four clinical trials coordinated by the ECOG-ACRIN Cancer Research Group, covering breast cancer (E1Z11, all patients received anastrozole; E1Z03, compared anastrozole vs. exemestane), melanoma (E1609, compared ipilimumab vs. high-dose interferon α), and chronic lymphocytic leukemia (E1912, compared ibrutinib-rituximab bs. standard chemoimmunotherapy). In each trial, GP5 responses were categorized as severe bother (i.e., "very much"/"quite a bit") versus moderate/low bother ("somewhat"/"a little bit"/"not at all"). RESULTS:At 3 months, significant associations were observed in each trial, indicating approximately 2.8-6.8 times greater odds of ETD among patients reporting severe bother (E1Z03: adjusted odds ratio [aOR], 2.82; 95% confidence interval [95% CI], 1.10-7.28; E1Z11: aOR, 4.10; 95% CI, 1.69-10.00; E1609: aOR, 6.77; 95% CI, 2.88-15.92; E1912: aOR, 4.15; 95% CI, 1.64-10.49). CONCLUSIONS:These results support prior research demonstrating an association between severe side-effect bother, as reported on responses to the GP5 item, and ETD among patients with newly diagnosed multiple myeloma. The consistent association between GP5 responses and ETD suggests the GP5's ability to capture how well patients tolerate treatment, especially when side-effect bother is observed early in the course of treatment, and signals an opportunity to develop interventions to promote treatment adherence.

Background: End-stage liver disease (ESLD) commonly causes significant impairments in health-related quality of life (HRQOL) that liver transplantation (LT) may correct.However, changes in HRQOL after LT have not been welldescribed using robust patient-reported outcomes measures.The National Institutes of Health Patient-Reported Outcomes Measurement Information System 29-item Profile (PROMIS-29) assesses seven health domains and pain intensity and has been suggested as the "standard HRQOL instrument" for use in this patient population.We hypothesized that LT recipients would report meaningful changes (improvements) in HRQOL as measured by PROMIS-29.Methods: Participants with ESLD were enrolled at the time of LT evaluation.PROMIS-29 profiles were serially administered to participants before and up to four months after LT to assess longitudinal changes in HRQOL.A minimal important change (MIC) threshold was defined as a change in T-score of ≥2.Results: 110 LT candidates were enrolled, of which 24 underwent LT at the time of analysis.The mean age of participants was 54.1 years (SD 12.6), 56.4% were males, and 78.2% were white.The most prevalent etiology of ESLD was Alcohol-related Liver Disease (30.9%).The average Model for End-Stage Liver Disease 3.0 (MELD) score at the time of listing for LT was 16.0.The threshold for MIC was exceeded in all domains after LT (Table), reflecting meaningful improvements in all domains.A change in T-score greater than one standard deviation (>10 T-score points) was observed in the domains of anxiety and sleep disturbance.Pain intensity, measured on 0-10 scale, was significantly lower post LT (mean difference: 3.8, p<0.001).Conclusion: LT Poster Sessionsrecipients reported significant improvements in HRQOL after LT as measured by PROMIS-29.These findings suggest that LT yields significant improvements in HRQOL in specific domains of importance to patients.Greater longitudinal study should be performed to better understand the long-term magnitude and durability of improvements in HRQOL after LT.

RATIONALE & OBJECTIVE:Valid measures of side effects are important to inform clinical use of calcineurin inhibitors (CNIs). This study developed and established the content validity of a patient-reported outcome (PRO) measure to capture side effects among kidney transplant recipients taking CNIs. STUDY DESIGN:Qualitative interviews for concept elicitation and cognitive debriefing. SETTING & PARTICIPANTS:Participants enrolled in the qualitative study were adults who had received a kidney transplant≤5 years earlier and were currently taking a CNI for immunosuppression. ANALYTICAL APPROACH:Concept elicitation interview data were analyzed by developing a codebook from a list of symptoms described by participants that they attributed to CNIs or their immunosuppression regimen and by applying the constant comparative approach separately by 2 coders. The most bothersome and important side effects reported by participants were used to select existing PRO items. Cognitive debriefing examined item comprehensibility, comprehensiveness, and relevance. RESULTS:Among 24 participating patients, 12 underwent concept elicitation interviews. Most participants (n=10) reported neurological or cognitive CNI side effects, and a majority of those (n=6) reported the neurological and cognitive side effects were the most bothersome adverse consequences of therapy. Based on these findings, 16 items were either selected from the Functional Assessment for Chronic Illness Therapy (FACIT) PRO item library or were newly written. These items were refined and reduced to 13 for cognitive debriefing, which was completed by 18 participants. These items were organized into 2 scales: Tremors and Cognitive Side Effects. LIMITATIONS:Though a diverse set of patients participated, they were not representative of all recipients of kidney transplants. The PRO measure's reliability, convergent and known-groups validity, and responsiveness to change were not evaluated. Symptoms could not be definitively attributed to CNIs. CONCLUSIONS:A newly developed PRO measure, the Functional Assessment of Chronic Illness Therapy-Calcineurin Inhibitor-Neurotoxicity (FACIT-CNI-Ntx), captures important side effects among patients receiving CNIs. PLAIN-LANGUAGE SUMMARY:People undergoing kidney transplantation require a lifelong regimen of immunosuppressing medications, including calcineurin inhibitors. Calcineurin inhibitors have side effects that may negatively impact transplant recipients' lives, sometimes interfering with important daily activities. We created a new survey for kidney transplant recipients to report on their experiences with calcineurin inhibitor side effects that we named the Functional Assessment of Chronic Illness Therapy-Calcineurin Inhibitor-Neurotoxicity (FACIT-CNI-Ntx) and that captures important side effects among patients receiving CNIs.

This study aims to establish meaningful within-person change (MWPC) thresholds for the Total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®), its Physical Function (PF) subscale, and the Visual Analog Scale (VAS) for Pain, in patients with knee osteoarthritis (OA). A secondary objective is to evaluate the effectiveness of a single injection of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (ADMSCs) using these thresholds. The study included 252 patients with knee OA enrolled in a clinical trial. An anchor-based predictive modeling approach, using KOOS-12, SF-36, and IKDC scores with literature-based cut-offs, was applied to determine MWPC thresholds for WOMAC and VAS Pain. MWPC thresholds were derived from both the ADMSCs injection and Control (autoserum) groups at 3- and 6-month follow-ups. Treatment effectiveness was assessed by comparing MWPC range with between-group differences and within-person changes. MWPC thresholds were identified as follows: 5–17 points for WOMAC Total, 4–12 points for WOMAC PF, and 8–14 points for VAS Pain (all on 0–100 scales). The adjusted differences between the ADMSCs injection and Control (autoserum) groups of all three measures (3 months: WOMAC Total 5.9, WOMAC Function 4.2, VAS Pain 8.6; 6 months: WOMAC Total 9.3, WOMAC Function 6.5, VAS Pain 11.7) were within each corresponding MWPC threshold range. The proposed MWPC thresholds could be beneficial for healthcare professionals as a tool to identify meaningful change in physical function and pain in response to treatment and evaluate the meaningfulness of treatment benefits.