Development of a new health-related quality of life measure for people with diabetes who experience hypoglycaemia: the Hypo-RESOLVE QoL.

AIMS/HYPOTHESIS: Valid and reliable patient-reported outcome measures are vital for assessing disease impact, responsiveness to healthcare and the cost-effectiveness of interventions. A recent review has questioned the ability of existing measures to assess hypoglycaemia-related impacts on health-related quality of life for people with diabetes. This mixed-methods project was designed to produce a novel health-related quality of life patient-reported outcome measure in hypoglycaemia: the Hypo-RESOLVE QoL. METHODS: Three studies were conducted with people with diabetes who experience hypoglycaemia. In Stage 1, a comprehensive health-related quality of life framework for hypoglycaemia was elicited from semi-structured interviews (N=31). In Stage 2, the content validity and acceptability of draft measure content were tested via three waves of cognitive debriefing interviews (N=70 people with diabetes; N=14 clinicians). In Stage 3, revised measure content was administered alongside existing generic and diabetes-related measures in a large cross-sectional observational survey to assess psychometric performance (N=1246). The final measure was developed using multiple evidence sources, incorporating stakeholder engagement. RESULTS: A novel conceptual model of hypoglycaemia-related health-related quality of life was generated, featuring 19 themes, organised by physical, social and psychological aspects. From a draft version of 76 items, a final 14-item measure was produced with satisfactory structural (χ2=472.27, df=74, p<0.001; comparative fit index =0.943; root mean square error of approximation =0.069) and convergent validity with related constructs (r=0.46-0.59), internal consistency (α=0.91) and test-retest reliability (intraclass correlation coefficient =0.87). CONCLUSIONS/INTERPRETATION: The Hypo-RESOLVE QoL is a rigorously developed patient-reported outcome measure assessing the health-related quality of life impacts of hypoglycaemia. The Hypo-RESOLVE QoL has demonstrable validity and reliability and has value for use in clinical decision-making and as a clinical trial endpoint. DATA AVAILABILITY: All data generated or analysed during this study are included in the published article and its online supplementary files ( https://doi.org/10.15131/shef. DATA: 23295284.v2 ).

Restorabite™: Phase II trial of jaw stretching exercises using a novel device for patients with trismus following head and neck cancer.

Patients treated for oral cancer, may experience restricted mouth opening (trismus). Barriers such as cost have limited the utilization of traditional jaw stretching devices, and consequently, patients experience problems with swallowing, oral care, communication, and cancer surveillance. The safety and efficacy of Restorabite™, a new device designed to overcome these barriers, is evaluated prospectively over 12 months. This phase II investigator-led trial included patients with chronic trismus underwent 10-weeks of trismus therapy using Restorabite™. Safety, adherence, changes in mouth opening, and patient-reported outcomes are presented. 114/120 participants with trismus completed the intervention, and 104 had their progress monitored for 12 months. Thirteen participants withdrew due to tumour recurrence. At the completion of the intervention, mouth opening improved by 10.4 mm (p < .001). This increased to 13.7 mm at 12 months (p < .001). Patient reported outcome all significantly improved and 47 participants were no longer classified as having trismus. There were no serious treatment related adverse events. In patients with trismus following head and neck cancer treatment, a 10-week programme of jaw stretching exercises using Restorbite™ safely improves mouth opening and associated quality of life outcomes with high adherence and the benefits are maintained for 12-months.

The Parent PrU: A measure to assess personal utility of pediatric genomic results.

PURPOSE: We aimed to adapt and validate an existing patient-reported outcome measure, the personal-utility (PrU) scale, for use in the pediatric genomic context. METHODS: We adapted the adult version of the PrU and obtained feedback from 6 parents whose child had undergone sequencing. The resulting measure, the Parent PrU, was administered to parents of children in 4 pediatric cohorts of the Clinical Sequencing Evidence-Generating Research consortium after they received their children's genomic results. We investigated the measure's structural validity and internal consistency. RESULTS: We conducted a principal-axis factor analysis with oblimin rotation on data from 755 participants to determine structural validity. These analyses yielded a 3-factor solution, accounting for 76% of the variance in the 16 items. We used Cronbach's α to assess the internal consistency of each factor: (1) child benefits (α = .95), (2) affective parent benefits (α = .90), and (3) parent control (α = .94). CONCLUSION: Our evidence suggests that the Parent PrU scale has potential as a measure for assessing parent-reported personal utility of their children's genomic results. Additional research is needed to further validate the Parent PrU scale, including by comparing its findings with utility assessments reported by clinicians and children themselves.

Patient-Reported Outcome Measures for Patients With CKD: The Case for Patient-Reported Outcomes Measurement Information System (PROMIS) Tools.

Chronic kidney disease (CKD), kidney failure, and kidney replacement therapies are associated with high symptom burden and impaired health-related quality of life (HRQOL). Symptoms change with disease progression or transition between treatment modalities and frequently go unreported and unmanaged. Tools that reliably monitor symptoms may improve the management of patients with CKD. Patient-reported outcome measures (PROMs) assess symptom severity; physical, psychological, social, and cognitive functioning; treatment-related side effects; and HRQOL. Systematic use of PROMs can improve patient-provider communication, patient satisfaction, clinical outcomes, and HRQOL. Potential barriers to their use include a lack of engagement, response burden, and limited guidance about PROM collection, score interpretation, and workflow integration. Well-defined, acceptable, and effective clinical response pathways are essential for implementing PROMs. PROMs developed by the Patient-Reported Outcomes Measurement Information System (PROMIS) address some challenges and may be suitable for clinical use among patients with CKD. PROMIS tools assess multiple patient-valued, clinically actionable symptoms and functions. They can be administered as fixed-length, customized short forms or computer adaptive tests, offering precise measurement across a range of symptom severities or function levels, tailored questions to individuals, and reduced question burden. Here we provide an overview of the potential use of PROMs in CKD care, with a focus on PROMIS.

Minimal important change and difference in health outcome: An overview of approaches, concepts, and methods.

OBJECTIVE: To provide an overview of approaches, concepts, and methods used to define and assess minimal important change and difference in health outcome. METHOD: A narrative review of the literature, guided by a conceptual framework. RESULTS: We distinguish between (i) interpretation of health outcome in individuals versus groups, (ii) change within individuals or groups versus difference between change within individuals or groups; and (iii) the responder approach (based on the proportion of patients that obtain a defined response) versus the group average approach (based on the average amount of change in a group). We review approaches, concepts, and methods. CONCLUSION: By bringing together and juxtaposing various approaches, concepts, and methods, we set a precursory step in the direction of consensus building in the field concerned with defining and assessing minimal important change and difference in health outcome. We emphasize the need for conceptual clarification and terminological standardization. We argue that assessing minimal importance of change and difference in health outcome is essentially a value judgment involving a range of considerations and perspectives.

Development of a core domain set for ankle osteoarthritis: An international consensus study of patients and health professionals.

OBJECTIVES: To develop an internationally agreed-upon core domain set for ankle osteoarthritis (OA). METHODS: In a three-part Delphi process, a group of multidisciplinary health professionals with expertise in ankle OA and people with ankle OA responded to online questionnaires. The questionnaires proposed a list of 29 candidate domains derived from a systematic review of ankle OA research, and interviews with people with ankle OA and health professionals. Consensus was defined a priori as ≥70% agreement in people with ankle OA and health professionals whether a domain should or should not be included in a core domain set. An online consensus meeting was held to discuss and resolve undecided candidate domains. RESULTS: A total of 100 people (75 health professionals and 25 people with ankle OA) from 18 countries (4 continents) participated in this study. Five domains reached consensus for inclusion in a core domain set for ankle OA - pain severity, health-related quality of life, function, disability and ankle range of motion. Twenty-one candidate domains reached agreement not to be included in the core domain set, and three domains remained undecided (ankle instability, physical capacity, and mental health). CONCLUSION: This international consensus study, which included people with ankle OA and health professionals, has established a core domain set for ankle OA with five domains that should be measured and reported in all ankle OA trials - pain severity, health-related quality of life, function, disability and ankle range of motion. This core domain set will guide the reporting of outcomes in clinical trials on ankle OA. Future research should determine which outcome measurement instruments should be used to measure each of the core domains.

30 years with the Knee injury and Osteoarthritis Outcome Score (KOOS).

This narrative review describes the development and use of patient-reported outcomes over 30 years, focusing on the Knee injury and Osteoarthritis Outcome Score (KOOS). KOOS is a five-subscale patient-reported instrument intended for use from the time of knee injury to the development of osteoarthritis. Numerous studies have confirmed that the psychometric properties of the KOOS and its short-form KOOS-12 are acceptable. More recent research has focused on the use and interpretation of KOOS scores in clinical trials using thresholds, such as minimal important differences, patient-acceptable symptom states, and treatment failure. As an indication of KOOS's popularity, the total 3854 PubMed results for KOOS have increased exponentially since the first KOOS paper was published 25 years ago and now seem to have plateaued at around 650 annually. The selected articles are not based on a systematic search, but on the author's own publications, reading, and literature search that grew organically from that.

Development of a measuring app for systemic sclerosis-related digital ulceration (SALVE: Scleroderma App for Lesion VErification).

OBJECTIVES: To test the hypothesis that photographs (in addition to self-reported data) can be collected daily by patients with systemic sclerosis (SSc) using a smartphone app designed specifically for digital lesions, and could provide an objective outcome measure for use in clinical trials. METHODS: An app was developed to collect images and patient reported outcome measures (PROMS) including Pain score and the Hand Disability in Systemic Sclerosis-Digital Ulcers (HDISS-DU) questionnaire. Participants photographed their lesion(s) each day for 30 days and uploaded images to a secure repository. Lesions were analysed both manually and automatically, using a machine learning approach. RESULTS: 25 patients with SSc-related digital lesions consented of whom 19 completed the 30-day study, with evaluable data from 27 lesions. Mean (standard deviation [SD]) baseline Pain score was 5.7 (2.4) and HDISS-DU 2.2 (0.9), indicating high lesion and disease-related morbidity. 506 images were used in the analysis (mean number of used images per lesion 18.7, SD 8.3). Mean (SD) manual and automated lesion areas at day 1 were 11.6 (16.0) and 13.9 (16.7) mm2 respectively. Manual area decreased by 0.08mm2 per day (2.4mm2 over 30 days) and automated area by 0.1mm2 (3.0mm2 over 30 days). Average gradients of manual and automated measurements over 30 days correlated strongly (r = 0.81). Manual measurements were on average 40% lower than automated, with wide limits of agreement. CONCLUSION: Even patients with significant hand disability were able to use the app. Automated measurement of finger lesions could be valuable as an outcome measure in clinical trials.

Long-term patient-reported outcomes among patients undergoing revascularization vs medical therapy for intermittent claudication.

OBJECTIVE: Society for Vascular Surgery guidelines recommend revascularization for patients with intermittent claudication (IC) if it can improve patient function and quality of life. However, it is still unclear if patients with IC achieve a significant functional benefit from surgery compared with medical management alone. This study examines the relationship between IC treatment modality (operative vs nonoperative optimal medical management) and patient-reported outcomes for physical function (PROMIS-PF) and satisfaction in social roles and activities (PROMIS-SA). METHODS: We identified patients with IC who presented for index evaluation in a vascular surgery clinic at an academic medical center between 2016 and 2021. Patients were stratified based on whether they underwent a revascularization procedure during follow-up vs continued nonoperative management with medication and recommended exercise therapy. We used linear mixed-effect models to assess the relationship between treatment modality and PROMIS-PF, PROMIS-SA, and ankle-brachial index (ABI) over time, clustering among repeat patient observations. Models were adjusted for age, sex, diabetes, Charlson Comorbidity Index, Clinical Frailty Score, tobacco use, and index ABI. RESULTS: A total of 225 patients with IC were identified, of which 40% (n = 89) underwent revascularization procedures (42% bypass; 58% peripheral vascular intervention) and 60% (n = 136) continued nonoperative management. Patients were followed up to 6.9 years, with an average follow-up of 5.2 ± 1.6 years. Patients who underwent revascularization were more likely to be clinically frail (P = .03), have a lower index ABI (0.55 ± 0.24 vs 0.72 ± 0.28; P < .001), and lower baseline PROMIS-PF score (36.72 ± 8.2 vs 40.40 ± 6.73; P = .01). There were no differences in patient demographics or medications between treatment groups. Examining patient-reported outcome trends over time; there were no significant differences in PROMIS-PF between groups, trends over time, or group differences over time after adjusting for covariates (P = .07, P = .13, and P =.08, respectively). However, all patients with IC significantly increased their PROMIS-SA over time (adjusted P = .019), with patients managed nonoperatively more likely to have an improvement in PROMIS-SA over time than those who underwent revascularization (adjusted P = .045). CONCLUSIONS: Patient-reported outcomes associated with functional status and satisfaction in activities are similar for patients with IC for up to 7 years, irrespective of whether they undergo treatment with revascularization or continue nonoperative management. These findings support conservative long-term management for patients with IC.

The Development of a New Patient-Reported Outcome Measure in Recessive Ataxias: The Person-Reported Ataxia Impact Scale.

Autosomal recessive cerebellar ataxias (ARCAs) are inherited neurological disorders that can affect both the central and peripheral nervous systems. To assess the effects of interventions according to the perception of people affected, patient-reported outcome measures (PROMs) must be available. This paper presents the development process of the Person-Reported Ataxia Impact Scale (PRAIS), a new PROM in recessive ataxias, and the documentation of its content validity, interpretability, and construct validity (structural and discriminant). The development followed the PROMIS framework and the Food and Drug Administration guidelines. A mixed-method study design was used to develop the PROM. A systematic review of the literature, semistructured interviews, and discussion groups was conducted to constitute an item pool. Experts' consultation helped formulate items, and the questionnaire was sent online to be completed by people affected. Statistical analyses were performed to assess the structural and discriminant validity. A total of 125 people affected by recessive ataxia completed the questionnaire. The factor analysis confirmed the three components: physical functions and activities, mental functions, and social functions. The statistical analysis showed that it can discriminate between stages of mobility and level of autonomy. It showed very good levels of internal consistency (0.79 to 0.89). The Person-Reported Ataxia Impact Scale (PRAIS) is a 38-item questionnaire that assesses the manifestations and impacts of the disease according to the perception of people affected by recessive ataxia. It can be used in clinical and research settings.

A longitudinal study of disease progression in facioscapulohumeral muscular dystrophy (FSHD).

INTRODUCTION/AIMS: In preparation for clinical trials, it is important to better understand how disease burden changes over time in facioscapulohumeral muscular dystrophy (FSHD) and to assess the capability of select metrics to detect these changes. This study aims to evaluate FSHD disease progression over 1 year and to examine the sensitivity of several outcome measures in detecting changes during this interval. METHODS: We conducted a 12-month prospective observational study of 41 participants with FSHD. Participants were evaluated at baseline, 6 months, and 12 months with serial strength testing (manual muscle testing or MMT and maximum voluntary isometric contraction testing or MVICT), functional testing (FSHD-Composite Outcome Measure or FSHD-COM, FSHD Clinical Severity Score or CSS, and FSHD Evaluation Score or FES), sleep and fatigue assessments, lean body mass measurements, respiratory testing, and the FSHD-Health Index patient-reported outcome. Changes in these outcome measures were assessed over the 12-month period. Associations between changes in outcome measures and both age and sex were also examined. RESULTS: In a 12-month period, FSHD participant function remained largely stable with a mild worsening of strength, measured by MMT and standardized MVICT scores, and a mild loss in lean body mass. DISCUSSION: The abilities and disease burden of adults with FSHD are largely static over a 12-month period with participants demonstrating a mild average reduction in some measures of strength. Selection of patients, outcome measures, and trial duration should be carefully considered during the design and implementation of future clinical studies involving FSHD patients.

Emotion constructs and outcome measures following false positive breast screening test results: A systematic review of reporting clarity and selection rationale.

OBJECTIVE: (i) To systematically identify constructs and outcome measures used to assess the emotional and mood impact of false positive breast screening test results; (ii) to appraise the reporting clarity and rationale for selecting constructs and outcome measures. METHODS: Databases (MEDLINE, CINAHL, PsycINFO) were systematically searched from 1970. Studies using standardised and non-standardised outcome measures to evaluate the emotion or mood impact of false positive breast screening test results were eligible. A 15-item coding scheme was devised to appraise articles on clarity and rationale for selected constructs and measures. RESULTS: Forty-seven articles were identified. The most investigated constructs were general anxiety and depression and disease-specific anxiety and worry. Twenty-two standardised general outcome questionnaire measures and three standardised disease-specific outcome questionnaire measures were identified. Twenty articles used non-standardised scales/items. Reporting of constructs and outcome measures was generally clear, but rationales for their selection were lacking. Anxiety was typically justified, but justification for depression was almost always absent. Practical and psychometric justification for selecting outcome measures was lacking, and theoretical rationale was absent. CONCLUSIONS: Heterogeneity in constructs and measures, coupled with unclear rationale for these, impedes a thorough understanding of why there are emotional effects of false positive screening test results. This may explain the repeated practice of investigating less relevant outcomes such as depression. There is need to develop a consensual conceptual model of and standardised approach to measuring emotional impact from cancer screening test results, to address heterogeneity and other known issues of interpreting an inconsistent evidence base.

Further psychometric evaluation of the WOUND-Q: A responsiveness study.

The WOUND-Q is a modular patient-reported outcome measure (PROM) with 13 scales measuring constructs across 4 domains (i.e., wound characteristics, health related quality of life, experience of care and wound treatment). The psychometrics of the WOUND-Q were previously assessed and the 13 scales evidenced good validity and reliability. However, the responsiveness (i.e., ability to detect clinical change) of the WOUND-Q has yet to be assessed. The objective of this study was to evaluate responsiveness for 9 WOUND-Q scales that assess outcomes, in a sample of people 18 years of age or older with chronic wounds that were present for at least 3 months. This study conducted a 4 month follow-up of 421 participants who completed the WOUND-Q as part of a previous psychometric study. Participants completed an online survey answering questions about their current wound state (e.g., number, type, size, smell, drainage), anchor questions about change, as well as the WOUND-Q scales that they had completed in their initial assessment. Pre-defined hypotheses were tested with a 75% acceptance threshold indicating sufficient evidence of responsiveness. Minimally important differences (MIDs) were also calculated using both anchor-based and distribution-based methods. Of 390 invited participants, 320 provided responses, ranging in age from 19 to 84 years. Acceptance of hypotheses ranged from 60% to 100%, with only the Symptom scale not meeting the 75% threshold. The findings of this study provide evidence that the WOUND-Q can validly measure clinical change in patients with chronic wounds.

Generating Utilities for the Château-Santé Base: A Novel, Generic, and Patient-Centered Health-Outcome Measure.

OBJECTIVES: We have developed a new patient-centered, preference-based generic health-outcome measure, Château-Santé Base (CS-Base), which is based on a novel multiattribute preference response (MAPR) measurement framework. This study aimed to generate a first utility set for the CS-Base, making it suitable for use in health-economic evaluations. METHODS: CS-Base comprises 12 health attributes: mobility, vision, hearing, cognition, mood, anxiety, pain, fatigue, social functioning, daily activities, self-esteem, and independence, each with 4 levels. Our methodology to generate utilities for the CS-Base was 2-fold. First, we derived coefficients from patient MAPR data to calculate CS-Base values. Subsequently, these were normalized to a 0.0 to 1.0 utility scale, in which 0.0 signifies dead. The dead position was estimated using general population data from a discrete choice experiment (discrete choice experiment + dead), using a division-value strategy, which localize the position of states better or worse than dead. RESULTS: We analyzed MAPR data from 3222 patients and discrete choice experiment + dead data from 1995 respondents. All MAPR coefficients were negative, logically ordered, and significantly different from the reference level. The dead position was denoted by a division value of -148.385. Utility values spanned from -0.071 to 1.0, and only 53 of 16 777 216 states were deemed worse than dead. CONCLUSIONS: This study introduced the first CS-Base utility set, underlining a 2-step utility derivation method. This method, blending societal and patient views, surpasses traditional preference-based approaches, yielding firmer results. However, improvement of the normalization procedure is expected. Estimating CS-Base utilities is an ongoing process that gains precision over time.

Systematic Review of Outcomes for Assessment of Medication Adherence Enhancing Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: The lack of universal guidance on outcome measures for evaluating medication adherence enhancing interventions (MAEIs) poses a challenge for assessing their effectiveness. This literature review aimed to provide a systematic overview of outcome measures currently used for the value assessment of MAEIs. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched MEDLINE, PsycINFO, Scopus, CINAHL, and Academic Search Complete for randomized and nonrandomized clinical trials, prospective cohort studies, model-based economic evaluations, and value frameworks published in English between January 2010 and September 2020. Two independent reviewers screened all titles and abstracts, followed by a full-text review. Due to the large number of relevant studies, data extraction was limited to articles published between January 2018 and September 2020. We collected data on the general characteristics of the study, the type of intervention, and the outcomes measured. RESULTS: We screened 14 685 records and identified 308 articles for data extraction. Behavioral interventions were the most common (n = 143), followed by educational interventions (n = 110) and mixed-method interventions (n = 73). Outcomes were clustered into 7 categories with medication adherence (n = 286) being the most frequently measured, followed by clinical outcomes (n = 155), health-related quality of life (n = 57), resource use (n = 43), patient satisfaction (n = 31), economic outcomes (n = 18), and other outcomes (n = 76). CONCLUSIONS: Various outcomes measures have been used to evaluate MAEIs, with only a small number of studies exploring economic and patient-reported outcomes. Future research is warranted to develop a consensus-based set of criteria for assessing MAEIs to facilitate the comparison of interventions and enable informed decision making.

Psychometric Evaluation of the Diary for Irritable Bowel Syndrome Symptoms-Constipation in a Prospective Observational Study.

OBJECTIVES: To evaluate the psychometric properties of the Diary for Irritable Bowel Syndrome Symptoms-Constipation (DIBSS-C), which was developed to support primary and secondary endpoints in irritable bowel syndrome (IBS) with predominant constipation (IBS-C) clinical trials. METHODS: Observational data were collected from 108 adults with IBS-C using a smartphone-type device for 17 days. DIBSS-C data regarding bowel movements (BMs) were collected for each event (along with the Bristol Stool Form Scale); abdominal symptoms were rated each evening. Global status items and the Gastrointestinal Symptom Rating Scale-IBS were completed on day 10 and day 17 and the IBS-Symptom Severity Scale on day 17. Item-level performance, internal consistency reliability, test-retest reliability, and construct validity were evaluated. RESULTS: The Abdominal Symptoms Domain score demonstrated high internal consistency reliability (Cronbach's alpha week 1 = 0.98; week 2 = 0.96) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.93). Test-retest reliability was stronger for abdominal symptoms (ICC = 0.91-0.94) than for the frequency-based BM-related outcomes (ICC = 0.54-0.66). Key construct validity hypotheses were supported by moderate to strong correlations with the corresponding Gastrointestinal Symptom Rating Scale-IBS, IBS-Symptom Severity Scale, and Bristol Stool Form Scale items. All known-groups comparisons were statistically significant for the abdominal symptom items and domain score; evidence for known-groups validity of BM-related outcomes was supportive when based on constipation severity. CONCLUSIONS: The results of this study provided key psychometric evidence for the DIBSS-C, ultimately contributing to its qualification by the US Food and Drug Administration for use in IBS-C clinical trials.

Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures.

While the use of electronic methods to collect patient-reported outcome data in clinical trials continues to increase, it remains the case that many patient-reported outcome measures (PROMs) have originally been developed and validated on paper. Careful consideration during the move from paper PROMs to electronic format is required to preserve the integrity of the measure and ensure a "faithful migration." Relevant literature has long called out the importance of following migration best practices during this process; nevertheless, such best practices are distributed across multiple documents. This article consolidates and builds upon existing electronic PROM implementation best practice recommendations to provide a comprehensive, up-to-date, single point of reference. It reflects the current consensus based on the significant advances in technology capabilities and knowledge gleaned from the growing evidence base on electronic migration and implementation, to balance the need for maintaining the integrity of the measure while optimizing respondent usability. It also specifies whether the practice is rooted in evidence or expert consensus, to enable those using these best practices to make informed and considered decisions when conducting migration.

Development of a functional outcome measure for riboflavin transporter deficiency.

BACKGROUND AND AIMS: Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease-modifying therapies including genetic therapies. The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) is a well-validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD. However, the CMTPedS requires modifications to account for phenotypic differences between children with CMT and RTD. The aim of this study was to develop a functional outcome measure based on the CMTPedS for specific use in individuals with RTD. METHODS: The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children's Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS. RESULTS: CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. 'Shoulder internal rotation' and the '30-s sit to stand test' were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single 'Feet apart on a line eyes open' balance item. 'Pinprick sensation' was removed due to a floor effect. INTERPRETATION: This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies.

Mental health and neurodevelopmental patient-reported outcome measures (PROMs) for children and young people with epilepsy: A systematic review.

Children and young people with epilepsy are at higher risk of mental health disorders and atypical neurodevelopmental outcomes compared to the general population. It is essential to detect such comorbidities early in children with epilepsy and provide appropriate interventions, to improve clinical outcomes. We aimed to identify and evaluate the measurement properties of Patient-Reported Outcome Measures (PROMs) that have been validated specifically to measure mental health and neurodevelopmental outcomes in children and/or young people with epilepsy. We searched Embase, Medline, and PsycINFO in May 2023 for relevant studies. Mental health was defined as psychological symptoms (e.g., anxiety, depression, psychosis) and/or behavioural difficulties (e.g., conduct disorders). Neurodevelopmental outcomes included neurodevelopmental disorder traits such as attention-deficit hyperactivity disorder (ADHD) and autistic spectrum disorders. We assessed methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidance. Twelve papers were identified that psychometrically evaluated 13 relevant PROMs (two epilepsy-specific, eleven generic). The appraisal of the PROMs was limited by the availability of only one or two published articles for each, and incomplete psychometric evaluations in some cases. The tool demonstrating the strongest evidence was The Neurological Disorders Depression Inventory-Epilepsy for Youth. The ADHD Rating Scale-IV and The Paediatric Symptom Checklist -17 demonstrated good evidence in favour of at least two measurement properties. This review identified only a small number of mental health and neurodevelopmental PROMs evaluated specifically in paediatric epilepsy. There is a need for further validation of mental health and neurodevelopmental PROMs in children with epilepsy.

Determining the minimally clinically important difference for the pediatric liver transplant quality of life questionnaire.

PURPOSE: The Pediatric Liver Transplant Quality of Life (PeLTQL) questionnaire is a disease-specific patient reported outcome measure for pediatric liver transplant (LT) recipients. To-date, threshold values above which a change in PeLTQL score is considered meaningful to patients are unavailable. This study proposes the first values for the minimally clinically important difference (MCID) for the PeLTQL. METHODS: In this retrospective cohort study, anchor and distribution-based methods were used to estimate the MCID for the PeLTQL. Questionnaires completed between March 2013, and July 2022 were included if data from two sequential visits were available. An internal anchor question was used for anchor-based determination of the MCID. A final MCID estimate was ascertained from triangulation of all methods. RESULTS: PeLTQL data from 65 LT recipients (26 [40%] male, 17 [42%] biliary atresia, median age at LT 3.08 years [interquartile range 0.99-7.30]), and their caregivers were included for analysis. Median patient age at time of baseline PeLTQL completion was 13.84 (10.90-15.86) years. The MCID for self-PeLTQL total scores ranged from 4.53 to 8.46, and from 4.47 to 8.85 for proxy responses. By triangulation, the MCID of the PeLTQL total score was 6.45 and 6.78 for self and proxy responses respectively. CONCLUSION: A change in PeLTQL score of 6.5 or more points suggests a change in health status that is meaningful to the patient, providing the clinical team an opportunity to engage the patient's voice in reassessing current health status and management strategies.