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Hydrologically sensitive areas (HSAs) largely control watershed response to rainfall, along with water and pollutant transport processes. Thus, their identification is critical in watershed management planning. Although watershed processes have been studied enough to provide a good understanding of HSA dynamics, only a few concepts and methods are available for HSA delineation, and they rely on spatial indices that do not consider temporal variation in hydrologic processes. This study introduces alternative concepts and methods to delineate HSAs. Three unique maps showing watershed dynamics were created using the outputs of a long-term hydrologic simulation implemented with a grid-based distributed model. The spatial distributions of HSAs identified using the newly proposed methods were compared with those of topographic indices. Results demonstrated that the new methods highlight transport processes, such as routing (or connection) and travel time, and the roles of soil and land covers, which have not been the focus of other concepts and approaches for HSA identification. In contrast to topographic index-based approaches, the proposed methods provided HSA boundaries with clear physical meanings to improve the interpretability and applicability of HSA maps. The methods are expected to enhance our ability to tackle water issues for improved water resource management by providing unique concepts and alternative ways to explicitly delineate HSAs. [ABSTRACT FROM AUTHOR]

The Ibicuí River basin in Rio Grande do Sul, Brazil, has recurring problems of water deficits, commonly attributed to the indiscriminate use of water to irrigate rice. The objective of this study was a statistical analysis of water flow data in the Ibicuí basin to verify if significant trends in water availability are related to the withdrawal of water for rice crop irrigation. We used data from 11 fluviometric stations for 1970 to 2011, which corresponds to the period of major expansion in rice cultivation in the basin. Daily flows were normalized, and for each month the flow rate was calculated for durations from 50% to 99%. Trends in these series were evaluated using the Mann-Kendall test. Results show that over the 40-year period of study there are trends of increasing water flow for eight of the 11 stations, and at six of those eight stations the increasing trend was statistically significant. In a river with sequential stations, differences between the stations indicated a decreasing trend for durations >80% as reflected by the Mann-Kendall Zs. However, the primary analysis failed to show trends that might reflect increasing irrigation withdrawals. Thus, contrary to expectations, we conclude that, for the Ibicuí basin, analysis of trends in the flow data does not clearly implicate water withdrawals for rice irrigation as the reason for water deficits. [ABSTRACT FROM AUTHOR]

Nonpoint-source (NPS) or diffuse pollution is a major environmental problem in developed countries, and modeling is an important tool used to evaluate the effectiveness of pollution control measures. The use of NPS models in the tropics usually involves the application of models developed for temperate regions with little, if any, adaptation to tropical conditions. In this article, we provide a synthesis of the literature values from studies in the tropics, using the GLEAMS model as a reference for the comparable values used in representing temperate conditions. We found that values for the carbon to nitrogen (C:N) ratio, potentially mineralizable nitrogen to total nitrogen ratio (N0/Ntotal), and base NO3-N and NH4-N concentrations representative of tropical soils were all different from the values considered appropriate for temperate soils. Relationships between phosphorus pools in tropical soils and in phosphorus sorption parameters likewise were different from those used in GLEAMS, with the exception that the GLEAMS ratio between labile and organic phosphorus in highly weathered soils was found to be comparable to data specific for tropical soils. [ABSTRACT FROM AUTHOR]

BSTRACT: A model was developed to evaluate the cost-effectiveness of alternative 'best management practice' (BMP) implementation schemes on two agricultural basins in Florida. The model selectively applies BMPs throughout the basin on a field by field basis, estimates the associated costs, and predicts the relative water quality improvement (reductions in nitrogen and phosphorus). The water quality model links field scale simulation (for detailed BMP evaluation) with basin delivery and attenuation functions to predict the basin-wide effects of any combination of BMPs. Fifteen BMP scenarios were evaluated to aid in prioritizing BMPs for implementation in these basins. Applying the maximum level of BMPs is estimated to cost around $1.2 million (annually), while the four most cost-effective BMPs would cost only one quarter as much, yet are projected to provide approximately 90 percent of the water quality improvement. [ABSTRACT FROM AUTHOR]

Incorporating variability in soil and chemical properties into root zone leaching models should provide a better representation of pollutant distribution in natural field conditions. Our objective was to determine if a more mechanistic rate-based model (Opus) would predict soil water and pesticide mass in the soil profile more accurately thana capacity- based model (GLEAMS) when spatial variability and uncertainty in parameters are considered. Predictions of spatial variationsof soil water content and movement of aldicarb [2-methyl-2(methylthio)-propionaldehyde O-(methylcarbamoyl) oxime] and metolachlor [2-chloro-N-(2-methoxy-1-methylethyl) acetamide] in the root zone were compared using 3 yr of observed data from a 3.9 ha agricultural field in southwest Georgia. Spatial variability of soil physical properties, pesticide properties, and pesticide application were described using probability distributions fined to measured field data, after removing spatial trends that were physically meaningful. There were significant differences in mean soil water content predicted by the two models,although variations around the mean were comparable. Pesticide mass predictions were different on most post-application dates in both mean and spatial variation. The less rigorous GLEAMS predicted mean depth-averaged soil water content and pesticide mass in the 1.2-m profileat least as good as the more mechanistic Opus, although it did not simulate depth distributions of water or pesticide mass as well as Opus. GLEAMS simulated spatial variations of depth-averaged soil water content and pesticide mass in the field with reasonable accuracy whileemploying fewer parameters that exhibit lower spatial variability. [ABSTRACT FROM AUTHOR]

An understanding of stream network topology is necessary for a landscape-level perspective of stream hydrology and ecology. We present a method for quantifying stream network topology that overcomes computational constraints of DEM-based analysis over large geographic extents. This method converts vector stream flow paths to raster flow paths to predict spatially-explicit stream properties from a network-constrained upstream cell count (UCC) to flow origins. UCC data enable calculations of stream network structure at designated grain sizes and spatial extents. UCC values were strongly related to empirical measures of upstream basin area (R2 = 0.94) and stream width (R2 = 0.65) within the mid-Atlantic highlands, USA, suggesting that UCC data provide a reasonable surrogate for empirical measures of stream size within the stream network. By reducing raster grids to the flow path, the UCC method reduced file sizes by 99% compared to digital elevation models. The UCC method can improve our understanding of fluvial landscape hydrology and ecology by enabling spatial analysis of stream networks over large geographic extents. [ABSTRACT FROM AUTHOR]

Background and Aims: The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden., Methods: Two hundred and fifteen participants underwent serial COAs including the CMT-HI, CMT Functional Outcome Measure (CMT-FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES-R). Correlations between the total and subscale scores for the CMT-HI and other COAs were determined. Changes in the CMT-HI scores over 12 months were assessed using paired t-tests. The minimum clinically important difference (MCID) for the CMT-HI and its subscales were calculated by anchoring to a participant global impression of change scale., Results: At baseline, CMT1A participants were 44.5 ± 15 years old (range: 18-75) and 58% were women. The mean CMT-HI was 25.7 ± 18.8 (range: 0-91.9; 100 reflecting maximal disease burden). The CMT-HI correlated with the CMT-FOM (r = .54, p < .0001), CMTNSv2R (r = .48, p < .0001), and CMTES/CMTES-R (r = .52/r = .54, p < .0001). Disease burden was greater in women than in men (CMT-HI 29.1 ± 19.1 vs. 21.2 ± 17.3, p = .001). Over 12 months, there was a nonsignificant mean increase in CMT-HI of 0.40 ± 10.0 (n = 189, p = .89). The MCID for the CMT-HI total score was 3.8 points (95% CI: 1.7-5.9)., Discussion: Patient-reported disease burden in CMT1A as measured by the CMT-HI is associated with measures of neurologic impairment and physical functioning. Women reported a higher disease burden than men. These data will inform the design of clinical trials in CMT1A., (© 2024 Peripheral Nerve Society.)

Objective: We sought to develop and validate the Crohn's Disease-Health Index (CD-HI), a disease-specific, patient-reported outcome measure that serially measures Crohn's disease (CD) symptomatic burden in adults with CD., Background: As therapeutic interventions are tested among patients with CD, responsive outcome measures are needed to track disease progression and therapeutic gain during clinical trials., Patients and Methods: We conducted a national cross-sectional study of individuals with CD to identify the most prevalent and impactful symptoms of CD. The most relevant symptoms were included in the CD-HI. We used factor analysis, qualitative patient interviews, test-retest reliability evaluation, and known group validity testing to evaluate and optimize the CD-HI., Results: The CD-HI contains 12 subscales that comprehensively measure CD burden using the patient's perspective. Fifteen adults with CD beta tested the CD-HI and found the instrument to be clear, easy to use, and relevant to them. Twenty-three adults with CD participated in an assessment of test-retest reliability, which indicated high reliability of individual questions, subscales, and the full instrument (intraclass correlation coefficient = 0.84 for the full instrument). The CD-HI and its subscales demonstrated a high internal consistency (Cronbach α = 0.98 for the full instrument). The CD-HI distinguished between groups of individuals with CD known to differ in disease severity., Conclusions: This research supports the use of the CD-HI as a valid, sensitive, reliable, and relevant patient-reported outcome to determine the multifactorial disease burden of those with CD, assess the relevance and merit of future CD therapies, and support drug labeling claims., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction/aims: To better understand the disease burden faced by individuals with Duchenne muscular dystrophy (DMD) of all ages and elucidate potential targets for therapeutics, this study determined the prevalence and relative importance of symptoms experienced by individuals with DMD and identified factors associated with a higher disease burden., Methods: We conducted qualitative interviews with individuals with DMD and caregivers of individuals with DMD to identify potential symptoms of importance to those living with DMD. We subsequently performed a cross-sectional study to assess which symptoms have the highest prevalence and importance in DMD and to determine which factors are associated with a higher disease burden., Results: Thirty-nine individuals, aged 11 years and above, provided 3262 quotes regarding the symptomatic burden of DMD. Two hundred participants (87 individuals with DMD and 113 caregivers) participated in a subsequent cross-sectional study. Individuals with DMD identified limitations with mobility or walking (100%), inability to do activities (98.9%), trouble getting around (97.6%), and leg weakness (97.6%) as the most prevalent and life altering symptomatic themes in DMD. The symptomatic themes with the highest prevalence, as reported by caregivers on behalf of those with DMD for whom they care, were limitations with mobility or walking (90.3%), leg weakness (89.2%), and emotional issues (79.6%). Steroid/glucocorticoid use (e.g., prednisone or deflazacort) was associated with a lower level of disease burden in DMD., Discussion: There are many symptomatic themes that contribute to disease burden in individuals with DMD. These symptoms are identified by both individuals with DMD and their caregivers and have a variable level of importance and prevalence in the DMD population., (© 2024 Wiley Periodicals LLC.)

Limb girdle muscular dystrophy (LGMD) is a debilitating disease and the fourth most common muscular dystrophy. This study describes the development of the LGMD-Health Index (LGMD-HI). Participants were aged >18 years and recruited from three LGMD registries and GRASP-LGMD consortium. The initial instrument, comprised of 16 thematic subscales and 161 items, underwent expert review resulting in item removal as well as confirmatory factor analysis followed by inter-rater reliability and internal consistency of the subscales. Following expert review, one subscale and 59 items were eliminated. Inter-rater reliability was assessed and five items were removed due to Cohen's kappa <0.5. The final subscales had high internal consistencies with an average Cronbach alpha of 0.92. Test re-test reliability of the final instrument was high (intraclass correlation coefficient=0.97). Known groups validity testing showed a statistically significant difference in LGMD-HI scores amongst subjects based on ambulation status (28.7 vs 50.0, p < 0.0001), but not sex, employment status, or genetic subtype. The final instrument is comprised of 15 subscales and 97 items. The LGMD-HI is a disease-specific, patient-reported outcome measure designed in compliance with published FDA guidelines. This instrument is capable of measuring burden of disease with no significant variation based on LGMD subtype., Competing Interests: Declaration of competing interest Chad Heatwole receives royalties for the use of multiple disease specific instruments. He has provided consultation to Biogen Idec, Ionis Pharmaceuticals, aTyr Pharma, AMO Pharma, Acceleron Pharma, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron Pharmaceuticals, Astellas Pharmaceuticals, AveXis, Recursion Pharmaceuticals, IRIS Medicine, Inc., Takeda Pharmaceutical Company, Scholar Rock, Avidity Biosciences, Novartis Pharmaceuticals Corporation, SwanBio Therapeutics, Neurocrine Biosciences, Sanofi, Lupin Pharmaceuticals, Vertex, and the Marigold Foundation. He receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, Swan Bio Therapeutics, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the Friedreich's Ataxia Research Alliance, Cure Spinal Muscular Atrophy, the Amyotrophic Lateral Sclerosis Association, and the Michael J. Foxx Foundation. He is the director of the University of Rochester's Center for Health and Technology. Nicholas Johnson has received grant funding from NINDS (4K23NS091511; R01NS104010), CDC (DD19-002) and the FDA (7R01FD006071-02). He receives royalties from the CCMDHI and the CMTHI. He receives research funds from Dyne, AveXis, CSL Behring, Vertex Pharmaceuticals, Fulcrum Therapeutics, ML Bio, Sarepta, and Acceleron Pharma. He has provided consultation for AveXis, AMO Pharma, Strongbridge BioPharma, Acceleron Pharma, Fulcrum Therapeutics, Dyne, Avidity, Arthex, and Vertex Pharmaceuticals. He receives licensing fees from the University of Rochester for the CCMDHI and CMTHI. He has received stock options from ML Bio., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to adapt the Facioscapulohumeral Muscular Dystrophy - Health Index (FSHD-HI) to an Italian population affected by FSHD by translating, validating, and testing this instrument in an Italian cohort., Materials and Methods: Italian FSHD patients were interviewed regarding the form and content of the translated instrument. Subsequently, forty FSHD patients were recruited to test the reliability (Intraclass Correlation Coefficient, ICC for test-retest; and Cronbach's Alpha for Internal consistency), known groups (Mann-Whitney U test and Area Under the Curve, AUC) and concurrent validity (Pearson's and Spearman's Rank Correlation Coefficient) of the instrument by serially completing the FSHD-HI and an extensive set of tests measuring the neuromotor, psychological and cognitive functions, and perceived quality of life (QoL) aspects., Results: The Italian translation of the FSHD-HI and its subscales were highly relevant to patients, had a high internal consistency (Cronbach's Alpha = 0.90), optimal test-retest reliability (ICC= 0.95), and was significantly associated with motor function, respiratory function, and QoL assessments., Conclusions: Overall, the Italian FSHD-HI is a valid and well-suited measurement of the multi-dimensional aspects of disease burden in FSHD patients.

Background: Adrenoleukodystrophy (ALD) is a multifaceted, X-linked, neurodegenerative disorder that comprises several clinical phenotypes. ALD affects patients through a variety of physical, emotional, social, and other disease-specific factors that collectively contribute to disease burden. To facilitate clinical care and research, it is important to identify which symptoms are most common and relevant to individuals with any subtype of ALD., Methods: We conducted semi-structured qualitative interviews and an international cross-sectional study to determine the most prevalent and important symptoms of ALD. Our study included adult participants with a diagnosis of ALD who were recruited from national and international patient registries. Responses were categorized by age, sex, disease phenotype, functional status, and other demographic and clinical features., Results: Seventeen individuals with ALD participated in qualitative interviews, providing 1709 direct quotes regarding their symptomatic burden. One hundred and nine individuals participated in the cross-sectional survey study, which inquired about 182 unique symptoms representing 24 distinct symptomatic themes. The symptomatic themes with the highest prevalence in the overall ALD sample cohort were problems with balance (90.9%), limitations with mobility or walking (87.3%), fatigue (86.4%), and leg weakness (86.4%). The symptomatic themes with the highest impact scores (on a 0-4 scale with 4 being the most severe) were trouble getting around (2.35), leg weakness (2.25), and problems with balance (2.21). A higher prevalence of symptomatic themes was associated with functional disability, employment disruption, and speech impairment., Conclusions: There are many patient-relevant symptoms and themes that contribute to disease burden in individuals with ALD. These symptoms, identified by those having ALD, present key targets for further research and therapeutic development., (© 2024. The Author(s).)

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., (© 2024 Wiley Periodicals LLC.)

Bulbar and jaw muscles are impaired in patients with Spinal Muscular Atrophy (SMA) but the assessment of their severity and progression are limited by the lack of age-appropriate and disease-specific measures. We investigated mastication and swallowing in children and adults with SMA, sitters and walkers. In a 2-year multicentre cross-sectional prospective study, lip and tongue strength (Iowa Oral Performance Instrument), chewing and swallowing (Test of Masticating and Swallowing Solids), active mouth opening (aMMO) were compared to age-appropriate normative data. The perceived burden of oro-bulbar involvement (SMA-Health Index) was recorded. 78 patients were included, 45 children (median age 7.4 years),22 adults (median age 26.8 years) on nusinersen and 11 untreated (median age 32.7 years). Forty-three percent children had reduced mouth opening, 50% had prolonged total time to eat. These issues were more prominent in sitters than in walkers (p = 0.019, p = 0.014). Sixty-six percent needed increased swallows for bolus clearance. Nusinersen treated adults had median aMMO, tongue strength and total time at TOMASS values within normal range (z score: -1.40, -1.22, -1.32, respectively) whereas untreated adults had reduced aMMO (z score: -2.68) and tongue strength (z score: -2.20). Only a minority of children (2/17) and treated adults (5/21) reported burden in swallowing or mastication compared to all untreated adults (5/5). After 16 months, mastication and swallowing were stable in treated children and adults, whether sitters or walkers. The reported multimodal approach to assess oro-bulbar functions demonstrate that swallowing and mastication are impaired in SMA despite patients' perception. These results suggest a trend towards stabilization of oro-bulbar function in patients on long-term treatment with nusinersen., (© 2023. The Author(s).)

Background and Objectives: To develop a valid, disease-specific, patient-reported outcome (PRO) measure for adolescents and adults with Friedreich ataxia (FA) for use in therapeutic trials., Methods: We conducted semistructured qualitative interviews and a national cross-sectional study of individuals with FA to determine the most prevalent and burdensome symptoms and symptomatic themes to this population. These symptoms and symptomatic themes were included as questions in the first version of the Friedreich's Ataxia-Health Index (FA-HI). We subsequently used factor analysis, beta interviews with 17 individuals with FA, and test-retest reliability assessments with 20 individuals with FA to evaluate, refine, and optimize the FA-HI. Finally, we determined the capability of the FA-HI to differentiate between subgroups of FA participants with varying levels of disease severity., Results: Participants with FA identified 18 symptomatic themes of importance to be included as subscales in the FA-HI. The FA-HI demonstrates high internal consistency and test-retest reliability, and it was identified by participants as highly relevant, comprehensive, and easy to complete. FA-HI total and subscale scores statistically differentiated between subgroups of participants with varying levels of disease burden., Discussion: Initial evaluation of the FA-HI supports its validity and reliability as a PRO for assessing how individuals with FA feel and function., Competing Interests: J. Seabury reports no disclosures relevant to the manuscript; D. Alexandrou reports no disclosures relevant to the manuscript; C. Engebrecht reports no disclosures relevant to the manuscript; N. Dilek reports no disclosures relevant to the manuscript; B. Greco reports no disclosures relevant to the manuscript; J. Heatwole reports no disclosures relevant to the manuscript; J. Larkindale is a paid employee of PepGen Inc.; D.R. Lynch receives grant support from the NIH, FDA, Friedreichs Ataxia Research Alliance, Reata Pharmaceuticals, Retrotope, PTC Therapeutics, Design Pharmaceuticals; C. Park reports no disclosures relevant to the manuscript; S. Rosero reports no disclosures relevant to the manuscript; S. Subramony receives research support from the NIH, FDA, Wyck, Friedreichs Ataxia Research Alliance, Muscular Dystrophy Association, Facioscapulohumeral Muscular Dystrophy Society, National Ataxia Foundation, Reata, PTC, Retrotope, Biohaven, Takeda, Acceleron, Pharnext, Avidity, and Reneo. He has provided consultation or served on advisory boards for Dyne, Avidity, Reata, and Avexis; A. Varma reports no disclosures relevant to the manuscript; E. Wagner reports no disclosures relevant to the manuscript; S. Walther reports no disclosures relevant to the manuscript; J. Weinstein reports no disclosures relevant to the manuscript; M. Wells reports no disclosures relevant to the manuscript; C. Zizzi has provided consultation to Recursion Pharmaceuticals; C. Heatwole receives royalties for the use of multiple disease-specific instruments. He has provided consultation to Biogen Idec, Ionis Pharmaceuticals, aTyr Pharma, AMO Pharma, Acceleron Pharma, Cytokinetics, Expansion Therapeutics, Harmony Biosciences, Regeneron Pharmaceuticals, Astellas Pharmaceuticals, AveXis, Recursion Pharmaceuticals, IRIS Medicine, Inc., Takeda Pharmaceutical Company, Scholar Rock, Avidity Biosciences, Novartis Pharmaceuticals Corporation, SwanBio Therapeutics, and the Marigold Foundation. He receives grant support from the Department of Defense, Duchenne UK, Parent Project Muscular Dystrophy, Recursion Pharmaceuticals, SwanBio Therapeutics, the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the Friedreichs Ataxia Research Alliance, Cure Spinal Muscular Atrophy, and the Amyotrophic Lateral Sclerosis Association. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2023 American Academy of Neurology.)

Introduction/aims: As promising therapeutic interventions are tested among patients with facioscapulohumeral muscular dystrophy (FSHD), there is a clear need for valid and reliable outcome tools to track disease progression and therapeutic gain in clinical trials and for clinical monitoring. Our aim was to develop and validate the Facioscapulohumeral Muscular Dystrophy-Health Index (FSHD-HI) as a multifaceted patient-reported outcome measure (PRO) designed to measure disease burden in adults with FSHD., Methods: Through initial interviews with 20 individuals and a national cross-sectional study with 328 individuals with FSHD, we identified the most prevalent and impactful symptoms in FSHD. The most relevant symptoms were included in the FSHD-HI. We used patient interviews, test-retest reliability evaluation, known groups validity testing, and factor analysis to evaluate and optimize the FSHD-HI., Results: The FSHD-HI contains 14 subscales that measure FSHD disease burden from the patient's perspective. Fourteen adults with FSHD participated in semistructured beta interviews and found the FSHD-HI to be clear, usable, and relevant to them. Thirty-two adults with FSHD participated in test-retest reliability assessments, which demonstrated the high reliability of the FSHD-HI total score (intraclass correlation coefficient = 0.924). The final FSHD-HI and its subscales also demonstrated a high internal consistency (Cronbach α = 0.988)., Discussion: The FSHD-HI provides researchers and clinicians with a reliable and valid mechanism to measure multifaceted disease burden in patients with FSHD. The FSHD-HI may facilitate quantification of therapeutic effectiveness, as demonstrated by its use as a secondary and exploratory measure in several clinical trials., (© 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Objective : The identification of effective therapeutics for ALS necessitates valid and responsive outcome measures to track disease progression and therapeutic gain in clinical trial settings. The Amyotrophic Lateral Sclerosis-Health Index (ALS-HI) is a multifaceted, disease-specific patient-reported outcome measure (PRO) designed to measure ALS symptomatic disease burden in adults with ALS. Methods: Through a national cross-sectional study of individuals with ALS, we identified the most important symptoms in ALS. These symptoms were incorporated into the ALS-HI, a measure that quantifies the multifaceted disease burden in ALS. We performed factor analysis, qualitative patient interviews, test-retest reliability assessment, and known groups analysis to evaluate and validate the ALS-HI. Results: The cross-sectional study included 497 participants with ALS who identified the most important symptoms to include in the ALS-HI. Fifteen participants beta tested the ALS-HI and found it to be clear, easy to use, and relevant. Twenty-one participants engaged in a test-retest reliability study, which indicated the reliability of the instrument (intraclass correlation coefficient = 0.952 for full instrument). The final ALS-HI and its subscales demonstrated a high internal consistency (Cronbach's α = 0.981 for full instrument) and an ability to differentiate between groups with dissimilar disease severity. Conclusions: This research supports use of the ALS-HI as a valid, sensitive, reliable, and relevant PRO to assess the multifactorial disease burden faced by adults with ALS. The ALS-HI has potential as a mechanism to track disease progression and treatment efficacy during therapeutic trials.