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Background and ObjectivesTo determine the prevalence and relative importance of symptoms experienced by children and adults with Friedreich ataxia (FA) and to identify factors associated with a higher burden of disease.MethodsWe conducted qualitative interviews with individuals with FA and caregivers of pediatric individuals with FA to identify potential symptoms of importance to those living with FA. We subsequently performed a cross-sectional study to assess which symptoms have the highest prevalence and importance in FA and to determine which factors are associated with a higher burden of disease.ResultsThirty-nine participants provided 2,527 quotes regarding the symptomatic burden of FA. Two hundred two individuals (153 individuals with FA and 49 caregivers) participated in a subsequent cross-sectional study. Individuals with FA and caregivers identified impaired coordination, limitations with mobility and walking, inability to do activities, fatigue, and lower extremity weakness as the most prevalent and life-altering symptomatic themes in FA. Muscle stiffness and functional staging for ataxia were associated with the prevalence of symptomatic themes in FA. In addition, the length of smaller GAA expansion and the mean length of both GAA expansions were strongly associated with the onset of symptoms in FA.DiscussionThere are a wide variety of symptoms that affect the lives of individuals with FA. These symptoms, many underrecognized, have different levels of importance and occur at different rates in the FA population. The most common and life altering of these symptoms represent potential targets for future therapeutic interventions.

Two common approaches to grouping students include an approach where students are grouped based on their aptitude and a cross-sectional approach where equal groups are formed and comprised of students of varied aptitudes. Instructional Grouping Theory is the study of how selection strategies impact the learning of group members. Using a non-biased, mathematically centric analysis, we found that a liked-skilled tiered grouping strategy is preferable to a cross-sectional grouping strategy when the goal is to facilitate the learning of all students. In addition, we found that a higher teacher-to-student ratio provides further benefit when analyzing the potential for facilitated learning.

Background Adrenoleukodystrophy (ALD) is a multifaceted, x-linked, neurodegenerative disorder that affect patients through a variety of physical, emotional, social, and other disease-specific factors that collectively contribute to disease burden. Adrenomyeloneuropathy (AMN) is one of the most frequent clinical manifestations and a subset of ALD. To facilitate clinical care and research, it is important to identify which symptoms are most common and relevant to individuals with ALD and AMN. Methods We conducted semi-structured qualitative interviews and an international cross-sectional study to determine the most prevalent and important symptoms of ALD and AMN. Our studies included adult participants with a diagnosis of ALD and AMN who were recruited from national and international patient registries. Responses were categorized by age, sex, functional status, and other demographic and clinical features. Results Seventeen individuals with ALD and AMN participated in qualitative interviews, providing 1,709 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 ALD and AMN 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 ability, employment disruption, and speech status. Conclusions There are many patient-relevant symptoms and themes that contribute to disease burden in individuals with ALD and AMN. These symptoms, identified by those diagnosed with ALD and AMN, present key targets for further research and therapeutic development.

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. 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. 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. Overall, the Italian FSHD-HI is a valid and well-suited measurement of the multi-dimensional aspects of disease burden in FSHD patients. Facioscapulohumeral muscular dystrophy (FSHD) negatively impacts the quality of life and increases the disease burden.It is important for the clinical community to have a valid instrument that can serially measure a patient’s perception of their multifactorial disease burden in FSHD.The Facioscapulohumeral Muscular Dystrophy – Health Index (FSHD-HI) is a valid instrument that allows patients to provide their perspective regarding their current health state.FSHD-HI-IT provides a valid option for measuring multifactorial disease burden in Italian patients with FSHD during clinical trials. Facioscapulohumeral muscular dystrophy (FSHD) negatively impacts the quality of life and increases the disease burden. It is important for the clinical community to have a valid instrument that can serially measure a patient’s perception of their multifactorial disease burden in FSHD. The Facioscapulohumeral Muscular Dystrophy – Health Index (FSHD-HI) is a valid instrument that allows patients to provide their perspective regarding their current health state. FSHD-HI-IT provides a valid option for measuring multifactorial disease burden in Italian patients with FSHD during clinical trials.

Background:To facilitate advances in spinal muscular atrophy therapeutic research, it is important to determine the impact and prevalence of symptoms experienced by children with spinal muscular atrophy. Methods: We conducted qualitative interviews with caregivers of children with spinal muscular atrophy. From these interviews, we generated a survey inquiring about 260 symptoms of importance grouped into 17 symptomatic themes. Results: Sixteen caregivers of children with spinal muscular atrophy aged from 4 months to 12 years participated in initial interviews, and 77 caregivers completed the survey. Higher symptom prevalence was associated with spinal muscular atrophy type, SMN2 copy number, and functional status. Hip, thigh, or knee weakness had the greatest reported impact on the lives of children with spinal muscular atrophy. Conclusions: This research provides one of the largest data sets regarding disease burden in children with spinal muscular atrophy. The most prevalent symptoms are not identical to those with the greatest impact. This unique insight into the most impactful symptoms will help focus therapeutic development in spinal muscular atrophy.

STUDY AIM To bolster Crohn’s disease (CD) clinical trial and research infrastructure through the development and validation of a sensitive, multifactorial, disease-specific, patient-reported outcome measure (PRO) for patient monitoring in therapeutic trials of CD. BACKGROUND As therapeutic advancements are made in the field of CD, it is vital to have a fully validated, sensitive, and reliable, disease-specific PRO to accurately measure changes in disease burden. Importantly, the U.S. Food and Drug Administration has encouraged the use of PROs to measure therapeutic benefit of new treatments on patient populations. This research describes the creation, testing, and validation of a new, multifactorial PRO: The Crohn’s Disease-Health Index (CD-HI). METHODS Questions were selected for the CD-HI based on their importance to patients, potential to respond to therapeutic benefit, reliability, internal consistency, and generalizability (Figure 1). We beta tested the CD-HI to evaluate its clarity, ease of use, and applicability to the CD patient population. We performed test-retest reliability, known groups validity, internal consistency, and area under the curve (AUC) analyses. RESULTS The final version of the CD-HI contains 12 subscales that measure disease burden in the following areas: 1) fatigue, 2) dietary restrictions, 3) gastrointestinal health, 4) sleep and daytime sleepiness, 5) bowel and bladder function, 6) emotional wellbeing, 7) joint health, 8) pain, 9) neck and back health, 10) activity participation, 11) social wellbeing, and 12) skin health. The CD-HI also provides a composite measure of total disease burden. Fifteen participants participated in beta testing and identified the CD-HI as easy to use, clear, relevant, and comprehensive. Twenty-three individuals with CD participated in test-retest reliability testing of the CD-HI, which indicated a high reliability of the individual questions, subscales, and full instrument (intraclass correlation coefficient = 0.84 for the full instrument). The CD-HI and its subscales demonstrated a high internal consistency (Cronbach’s α = 0.98 for the full instrument). The CD-HI total and subscale scores successfully distinguished between patient cohorts with differing disease severity. AUC analysis demonstrated a high sensitivity and specificity of the CD-HI in distinguishing between those with CD on disability vs. not on disability, with an AUC value of 0.9087 (Figure 2). CONCLUSIONS The CD-HI is a fully validated, sensitive, and accurate marker of disease burden in CD. This disease-specific PRO is available for use by researchers, clinicians, patient organizations, and companies to monitor patients and measure disease burden during therapeutic trials

As novel therapeutic interventions are being developed and tested in the amyotrophic lateral sclerosis (ALS) population, there is a need to better understand the symptoms and issues that have the greatest impact on the lives of individuals with ALS. We aimed to determine the frequency and relative importance of symptoms experienced by adults in a national ALS sample and to identify factors that are associated with the greatest disease burden in this population.We conducted 15 qualitative interviews of individuals with varied ALS phenotypes and analyzed 732 quotes regarding the symptomatic disease burden of ALS between August 2018 and March 2019. We subsequently conducted a national, cross-sectional study of 497 participants with ALS and ALS variants through the Centers for Disease Control and Prevention's (CDC) National ALS Registry between July 2019 and December 2019. Participants reported on the prevalence and relative importance of 189 symptomatic questions representing 17 symptomatic themes that were previously identified through qualitative interviews. Analysis was performed to determine how age, sex, education, employment, time since onset of symptoms, location of symptom onset, feeding tube status, breathing status and speech status relate to symptom and symptomatic theme prevalence.Symptomatic themes with the highest prevalence in our sample were an inability to do activities (93.8%), fatigue (92.6%), problems with hands or fingers (87.7%), limitations with mobility or walking (86.7%), and a decreased performance in social situations (85.7%). Participants identified inability to do activities and limitations with mobility or walking as having the greatest overall effect on their lives.Individuals with ALS experience a variety of symptoms that affect their lives. The prevalence and importance of these symptoms differ among the ALS population. The most prevalent and important symptoms offer potential targets for improvements in future therapeutic interventions.Research funding was provided by ALS Association.

Study Aim: The goal of this research is to develop and validate a novel, disease-specific patient-reported outcome measure (PRO) for use in clinical monitoring and therapeutic trials in Lung Cancer (LC). Methods: LC currently accounts for the greatest number of cancer deaths worldwide, driving an increased need for novel therapeutic development in LC. To bolster clinical trial infrastructure, it is critical to have a comprehensive, sensitive and reliable PRO that accurately tracks LC multifactorial disease burden. This research describes the development and validation of the Lung Cancer-Health Index (LC-HI) as an efficient mechanism for assessing how patients with LC feel and function in response to therapeutic treatment. We conducted semi-structured, qualitative interviews with 15 individuals diagnosed with LC and collected 653 direct participant quotes to determine the most frequent and important symptoms in LC. Based upon participant responses, we designed a survey that inquired about 162 symptoms from 14 symptomatic themes. This survey was implemented in a cross-sectional study with 139 participants with LC. The collected data was used to generate the first version of the LC-HI, which contained symptom questions showing the highest impact to the population and the potential to respond to therapeutic intervention. Symptom questions were grouped into distinct subscales using factor analysis. We beta-tested the LC-HI with 15 patients with LC to evaluate its usability, clarity, and applicability. Based on patient feedback, we modified the instrument and evaluated its test-retest reliability with 22 individuals with LC. Known groups testing was performed with the final instrument. Results: The final version of the LC-HI contains 45 symptom questions grouped into 10 subscales that measure the following areas of LC health: 1) fatigue, 2) physical function, 3) emotional health, 4) sleep and daytime sleepiness, 5) activity participation, 6) breathing function, 7) gastrointestinal function, 8) cognitive function, 9) social performance, and 10) pain. Total LC disease burden is measured using a weighted composite of these subscale scores. During beta interviews, individuals with LC deemed the instrument to be easy to use, clear, relevant, and comprehensive. Statistical and psychometric analyses confirmed that the LC-HI is reliable, valid, sensitive, specific, of high internal consistency, and able to differentiate between groups with known varying levels of disease burden (based on disability status and smoking history). Conclusions: Our research demonstrates the validity of the LC-HI as a marker of the multifaceted disease burden in LC. This disease-specific PRO provides researchers and clinicians with a reliable tool to use in patient monitoring, clinical trials, and to support FDA drug labeling claims. Citation Format: Anika Varma, Spencer Rosero, Jamison Seabury, Jennifer Weinstein, Charlotte Engebrecht, Christine Zizzi, Nuran Dilek, John Heatwole, Megan Baumgart, Deborah Mulford, Ronald Maggiore, Lainie Conrow, Jennifer King, Jacinta Wiens, Chad Heatwole. Development and validation of the Lung Cancer-Health Index (LC-HI), a clinically-relevant, disease-specific patient-reported outcome measure. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4383.

Patients with Crohn's disease (CD) experience a variety of symptoms that significantly affect their lives. In this study, we (i) ascertain the most prevalent and impactful symptoms in CD and (ii) identify modifying factors that are associated with a higher disease burden in CD.We conducted semistructured interviews with adult participants with CD to determine what issues have the greatest impact on their lives. Next, we conducted a large cross-sectional study of individuals with CD to determine the prevalence and relative importance of those symptoms and themes and to identify the demographic features that are associated with a higher disease burden.Sixteen individuals with CD provided 792 direct quotes regarding their symptomatic burden. Four hundred three people with CD participated in our cross-sectional study. The symptomatic themes with the highest prevalence in CD were gastrointestinal issues (93.0%), fatigue (86.4%), dietary restrictions (77.9%), and impaired sleep or daytime sleepiness (75.6%). The symptomatic themes that had the greatest impact on patients' lives (0-4 scale) related to fatigue (1.82), impaired sleep or daytime sleepiness (1.71), gastrointestinal issues (1.66), and dietary restrictions (1.61). Symptomatic theme prevalence was strongly associated with a higher number of soft stools per day, greater number of bowel movements per day, missed work, employment and disability status, and having perianal disease.Patients with CD experience numerous symptoms that affect their daily life. These symptoms, some underrecognized, vary based on disease and demographic characteristics and represent potential targets for future therapeutic interventions.

ObjectiveTo assess mexiletine's long-term safety and effect on 6-minute walk distance in a well-defined cohort of patients with myotonic dystrophy type 1 (DM1).MethodsWe performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory patients with DM1. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and ECG results at 3 and 6 months.ResultsForty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine- and placebo-treated participants.ConclusionsThere was no benefit of mexiletine on 6-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction measures were seen over the 6-month follow-up period.Classification of EvidenceThis study provides Class I evidence that for ambulatory patients with DM1, mexiletine does not significantly change 6-minute walk distance at 6 months.

This study determined the frequency and impact of symptoms on quality of life (QoL) in patients diagnosed with limb girdle muscular dystrophy (LGMD). Participants with a diagnosis of LGMD in registries based at the Coalition to Cure Calpain-3, the Jain foundation, and the Global FKRP Registry competed a survey to report the frequency and relative impact of themes and symptoms of LGMD. Frequency, mean impact, and population impact scores were calculated, and responses were categorized by age, symptom duration, gender, employment status, use of assistive devices, and LGMD subtypes. 134 participants completed the survey. The most prevalent themes included an inability to do activities (100%), limitation with mobility (99.3%), and lower extremity weakness (97.0%). Themes with the greatest impact were: limitations with mobility, lower extremity weakness, and an inability to do activities. Symptom duration and the use of assistive devices were associated with the presence of multiple themes. Employment was associated with the impact of several themes with no differences in frequency. The prevalence and impact of these themes vary in the LMGD population. The most prevalent and impactful themes were related to weakness, but additional concerns related to emotional challenges should also be considered in clinical and research settings.

ObjectiveTo determine the frequency and relative importance of the most meaningful symptoms in facioscapulohumeral muscular dystrophy (FSHD) and to identify the demographic and clinical features that are associated with the greatest disease burden in this population.MethodsWe performed a cross-sectional study involving 328 participants with FSHD. Collectively, participants reported the prevalence and relative importance of 274 symptoms and 15 symptomatic themes. We assessed the association between symptomatic theme prevalence and participants' age, sex, disease duration, pain level, employment status, and education.ResultsParticipants answered >48,000 questions regarding their disease burden. The symptomatic themes with the highest prevalence in our sample were problems with shoulders or arms (96.9%), limitations with activities (94.7%), core weakness (93.8%), fatigue (93.8%), limitations with mobility and walking (93.6%), changed body image due to the disease (91.6%), and pain (87.7%). Problems with shoulders and arms and limitations with mobility and walking had the greatest effect on participants' lives. Employment status and the report of pain had the most extensive association with the prevalence of symptoms, with employment being associated with 8 of 15 of the symptomatic themes and pain being associated with 7 of 15 of the symptomatic themes. Men and women with FSHD experienced a similar prevalence of all symptomatic themes.ConclusionsAdults with FSHD experience a variety of symptoms that play an important role in their disease burden. These symptoms have a variable prevalence and importance in the FSHD population and are associated with disease duration, employment status, and pain level.

Introduction The prevalence and impact of symptoms affecting individuals with pediatric forms of myotonic dystrophy type-1 (DM1) are not well understood. Methods Patients from the United States, Canada, and Sweden completed a survey that investigated 20 themes associated with pediatric-onset DM1. Participants reported the prevalence and importance of each theme affecting their lives. Surveys from participants were matched with surveys from their caregivers for additional analysis. Results The most prevalent symptomatic themes included problems with hands or fingers (79%) and gastrointestinal issues (75%). Problems with urinary/bowel control and gastrointestinal issues were reported to have the greatest impact on patients' lives. Responses from participants and their caregivers had varying levels of agreement among symptomatic themes. Discussion Many symptoms have meaningful impact on disease burden. The highest levels of agreement between caregivers and individuals with pediatric forms of myotonic dystrophy were found for physical activity themes.

Introduction Limb-girdle muscular dystrophy (LGMD) consists of over 30 genetic conditions with varying clinical phenotypes primarily affecting pelvic girdle, shoulder girdle, and other proximal limb muscles. Studies focusing on the physical, mental, and social effects of this disease from the patient's perspective are limited. Methods Adults with LGMD were interviewed and asked to identify issues that have the greatest impact on their quality of life. Each interview was recorded, transcribed, coded, and analyzed. Results Participants provided 1385 direct quotes. One hundred sixty-five potential symptoms of importance were identified and grouped into 15 larger themes. The most frequently reported themes included limitations with mobility, difficulty performing activities, social role limitations, and emotional distress. Discussion There are multiple symptoms that alter the lives of adults with LGMD. These affect their physical, emotional, and social health, and may be amenable to medical intervention.

Purpose of reviewMyotonic dystrophy type 2 (DM2) is a rare, progressive multisystem disease particularly affecting the skeletal muscle. A causal therapy is not yet available; however, prompt, appropriate symptomatic treatments are essential to limit disease-related complications. Evidence-based guidelines to assist medical practitioners in the care of DM2 patients do not exist.Recent findingsThe Myotonic Dystrophy Foundation (MDF) previously worked with an international group of 66 clinicians to develop consensus-based care recommendations for myotonic dystrophy type 1. Following a similar approach, the MDF recruited 15 international clinicians with long-standing experience in the care of DM2 patients to develop consensus-based care recommendations. The single text procedure was adopted. This process generated a 4-page Quick Reference Guide and a comprehensive 55-page document that provides care recommendations for DM2 patients.SummaryThe resulting recommendations will help standardize and improve care for DM2 patients and facilitate appropriate management in centers without neuromuscular specialists.

Introduction The Myotonic Dystrophy Health Index (MDHI) is a disease-specific, patient-reported outcome measure. The objective of this study was to translate, evaluate, and validate a Japanese version of the MDHI (MDHI-J). Methods We utilized forward and backward translations and qualitative interviews with 11 myotonic dystrophy type 1 (DM1) participants. We subsequently tested the internal consistency, test-retest reliability, concurrent validity against muscle strength, and 3 quality-of-life measures, and the known-groups validity of the MDHI-J with 60 adult patients. Results The MDHI-J was found to be culturally appropriate, comprehensive, and clinically relevant. The MDHI-J and its subscales had high internal consistency (mean Cronbach's α = 0.91), test-retest reliability (intraclass coefficient 0.678-0.915), and concurrent validity (Spearman's ρ - 0.869 to 0.904). MDHI-J scores were strongly associated with employment, duration of symptoms, and modified Rankin Scale. Discussion The MDHI-J is suitable and valid to measure patient-reported disease burden in adult Japanese patients with DM1. Muscle Nerve 59:577-577, 2019.

Introduction: Myotonic dystrophy (DM) is a chronic, multisystemic, neurological condition. Patients and caregivers are uniquely suited to identify what symptoms are most important and highlight the unmet needs that are most relevant to DM. Methods: We conducted a North American, cross‐sectional study of people with DM type‐1, congenital DM, and DM type‐2 and their family members. We sent patients and caregivers separate surveys to identify and quantitate the issues of greatest importance, examine the differences between groups, and identify the most important challenges experienced by this population. Results: 1,180 people with DM and 402 family members/caregivers responded to the surveys. They reported considerable physical and cognitive symptoms, extensive diagnostic delays, and varying clinical phenotypes on the basis of DM type. Discussion: Marked disease burden and numerous unmet needs exist in DM. These needs vary based on DM type and highlight the complex clinical phenotypes of these neurological disorders. Muscle Nerve 59:457–464, 2019

INTRODUCTION The Spinal Muscular Atrophy Health Index (SMA-HI) is a multifaceted, disease-specific, patient-reported outcome to measure an SMA patient's perception of their disease burden. In preparation for upcoming therapeutic trials, we examine the validity, reliability, and usability of the SMA-HI in adults, teenagers, and children with SMA. METHODS Using data from a cross-sectional study of 359 international adult patients with SMA, we identified the most relevant symptoms to include in the SMA-HI. We utilized factor analysis, patient interviews with adults and minors (age 8-15 years), known-group validity testing, and test-retest reliability assessments to evaluate and refine the SMA-HI. RESULTS The SMA-HI measures overall disease burden and 15 areas of SMA health. Fifteen adult patients and five patients, age 8 to 15 years, participated in semistructured qualitative interviews and found the SMA-HI to be comprehensive, easily completed, and to have clear meaning. The final SMA-HI and its subscales demonstrated good internal consistency (Cronbach α = 0.77-0.96), high test-retest reliability (intraclass correlation coefficient = 0.60-0.96), and an ability to differentiate between SMA groups with different disease severities affecting areas such as employment and ambulation (P

This study aims to investigate intra-rater reliability and construct validity of the Facioscapulohumeral Dystrophy Composite Outcome Measure (FSHD-COM), in childhood FSHD. Participants included eighteen children with FSHD, and matched healthy controls. Reliability data were collected from 15 participants with FSHD over two testing sessions. Validity data were collected from all participants. Participants with FSHD completed; the FSHD-COM (and modified pediatric version), Motor Function Measure-32 (MFM-32), FSHD Severity Scales, Performance of the Upper Limb 2.0, Pediatric Quality of Life™ Neuromuscular Module and pediatric FSHD Health-Index Questionnaire. Both versions of the FSHD-COM showed excellent intra-rater reliability (ICC1,2 > 0.99, lower 95%CI > 0.98) with a Minimal Detectable Change (MDC95%) of ≤14.5%. The FSHD-COM had robust and widespread correlations with other related outcome measures. The FSHD-COM versions and 6 min walk test effectively discriminated between children with and without FSHD; the MFM-32 and 10 m walk/run test did not. Ceiling effects were not observed on either version of the FSHD-COM. Reliability and validity findings in this childhood FSHD study concord with estimates in adults. Both versions of the FSHD-COM were effective in discriminating disease in children with mild FSHD symptoms. The FSHD-COM has the potential to be a useful measure of function across the life span.

Patient report outcome measures in Spinal Muscular Atrophy (SMA) represent a potential complement to observer rated scales which can be used to better understand treatment response. We developed, translated and validated an Italian version of the the Spinal Muscular Atrophy Health Index (SMAHI), a disease-specific, patient reported outcome measure questionnaire, designed to estimate the patients’ perception of disease burden. Test-retest reliability was assessed in 37 patients (16 children aged 12-17 and 21 adults) and was excellent in both cohorts. Internal consistency in an additional 98 patients (24 children, 74 adults) was also excellent (Cronbach's alpha = 0.93 and 0.91 respectively). In children the highest level of disease burden was generated from lower limb dysfunction and fatigue as well as their perception of decreased performance in social situations. Most patients in the adult cohort were sitters and complained of problems with upper limb functions as well as of fatigue. The SMAHI-IT was also able to differentiate between SMA types according to diseases severity. The results of our study demonstrate that the SMAHI can be considered a marker of disease-specific burden in patients with SMA with a high test-retest reliability and internal validity in Italian patients aged 12 and older.

The Charcot-Marie-Tooth Health Index (CMT-HI) is a disease-specific patient-reported outcome measure measuring overall disease burden in Charcot-Marie-Tooth (CMT) patients, designed for natural history studies and clinical trials in English-speaking affected individuals. We developed and validated its Italian Charcot-Marie-Tooth Health Index (I-CMT-HI) version. The questionnaire was translated and culturally adapted from source into Italian by two neurologists experienced in CMT and neuromuscular disorders (NMDs). The two translations were reviewed by a panel of seven experts in CMT and NMD. The provisional version was back-translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the panel and a patient representative from ACMT-Rete. A series of clinically and genetically characterized CMT patients completed the final questionnaire; 11 participated in a test-retest reliability assessment of the instrument. The I-CMT-HI was administered to 30 CMT patients (13 CMT1A, eight CMTX1, two CMT1B, two CMT1E, two CMT2I, one CMT2A, one CMT2N, one distal Hereditary Motor Neuropathy), with test-rest in 11:14 females and 16 males, aged (mean ± SD) 48.0 ± 16.4 years (range 18-81), with CMT Examination Score (CMTES) = 10.0 ± 4.4 (range 2-18). The I-CMT-HI mean total score was 29.4 ± 21.2 (range 0.1-60.3). The I-CMT-HI showed a high test-retest reliability: intraclass correlation coefficient = 0.95 (95% confidence interval, 0.84-0.99). No patient had difficulty in completing the questionnaire and none reported any problem with the questions' formulation. The total CMT-HI score was positively correlated with age and CMTES, with higher disease burden with increasing age and disease severity according to the CMTES. The I-CMT-HI is now ready for use in clinical studies in the Italian population.

Objective: Amyotrophic lateral sclerosis (ALS) has profound effects on people with ALS (PALS) and caregivers. There is a paucity of research detailing and comparing PALS and caregiver day-to-day perspectives of ALS. Methods: A survey developed collaboratively by The ALS Association and a panel of experts in ALS care was designed to broadly sample the experience of PALS and caregivers with respect to physical and emotional symptoms, the efficacy of treatment approaches, and goals for future treatments. Specific physical symptoms assessed consisted of fatigue, pain, weakness, shortness of breath, difficulty sleeping, speech problems, depression and other mood changes, and cognitive changes. PALS, caregivers of living patients with ALS (C-LPALS), and caregivers of deceased patients with ALS (C-DPALS) were contacted by email to participate in a 30-minute online survey. Results: 887 PALS, 444 C-LPALS, and 193 C-DPALS responded to the survey. In comparison to PALS, C-LPALS perceived that PALS had significantly higher rates of all surveyed symptoms except for pain and weakness. Caregivers self-reported higher stress levels than PALS (p p Conclusions: PALS and caregivers report a number of symptoms beyond weakness that affect daily life which may be targets of future interventions. There are opportunities to improve services and care for caregivers to reduce the burden of illness.

STUDY AIM The goal of this research is to develop and validate a novel, disease-specific patient-reported outcome measure (PROM) for use in clinical monitoring and therapeutic trials of Crohn’s Disease (CD). BACKGROUND With approximately 780,000 cases of CD in the U.S., it is important to have a comprehensive, sensitive, and reliable disease-specific PROM that accurately indicates patient function, perceived health, and quality of life. Moreover, as clinical trials are planned for individuals with CD, a valid PROM is vital to determine the overall effect of potential treatments on patient disease burden. This research describes the construction and testing of the Crohn’s Disease-Health Index (CD-HI) as an efficient mechanism to quantify how patients with CD feel and function, and to measure key changes in a patient’s multifactorial health. METHODS We conducted semi-structured, qualitative interviews with 16 CD patients to determine the most frequent and important symptoms in CD. Based on patient responses, we designed a survey which inquired about 148 symptoms from 17 symptomatic themes. This survey was used in a cross-sectional study with 403 patients with CD recruited through the Crohn’s and Colitis Foundation and IBD Partners. The collected data was used to generate the first version of the CD-HI, which contained symptom questions that had the highest impact to the population and the potential to respond to therapeutic intervention. Symptom questions were grouped into distinct symptomatic themes using factor analysis. We beta-tested the CD-HI with 15 patients with CD to evaluate its usability, clarity, and applicability. Based on patient feedback, we modified the instrument and evaluated its longitudinal reliability with 23 patients with CD. Known groups testing was performed with the final instrument. The final version of the health index is now available for use in clinical trials. RESULTS The final version of the CD-HI contains subscales that measure the following areas of CD health: 1) fatigue, 2) dietary restrictions, 3) gastrointestinal health, 4) sleep and daytime sleepiness, 5) bowel and bladder function, 6) emotional wellbeing, 7) joint health, 8) pain, 9) neck and back health, 10) activity participation, 11) social wellbeing, and 12) skin health. Total CD disease burden is measured using a weighted composite of these subscale scores. During beta interviews, patients with CD deemed the instrument to be easy to use, clear, relevant, and comprehensive. Statistical analyses confirmed the reliability, validity, sensitivity, specificity, and internal consistency of the instrument. CONCLUSIONS Our research demonstrates the validity of the CD-HI as a marker of disease burden in CD. This disease-specific PROM provides researchers and clinicians with a reliable tool to use in patient monitoring and clinical trials.

Objective The development of a disease-specific patient-reported outcome for Charcot-Marie-Tooth disease is an important step in the preparation for therapeutic trials. This study describes the development of the Charcot-Marie-Tooth Health Index (CMTHI). Methods Inherited Neuropathy Consortium Contact Registry participants were queried on the symptoms that most impacted their lives. The CMTHI was developed based on these responses. Factor analysis, assessment of test-retest reliability, known group validity, and patient interviews were utilized to refine the instrument. Results The final CMTHI contains 18 themes that capture Charcot-Marie-Tooth disease (CMT) burden. The CMTHI has a high internal consistency and test-retest reliability. The CMTHI was able to discriminate between patient groups expected to have different disease burden. The CMTHI was able to discriminate levels of disability as measured by the CMT examination score and the mobility-Disability Severity Index. Interpretation The CMTHI represents a valid and reliable outcome to assess patient-reported disease burden in CMT. Ann Neurol 2018;84:225-233.

Congenital muscular dystrophies (CMD) cause progressive muscle weakness resulting in severe motor disabilities. Previous studies focused on the effects of motor disability. Here, we explore other factors affecting health related quality-of-life (HRQOL) in CMD. Qualitative interviews were conducted with participant-parent dyads to identify symptoms having the greatest impact on HRQOL. Symptoms were classified into themes and domains representing physical, mental, social health, and disease specific issues. Social role limitations and specific activity impairment were frequently mentioned. A greater understanding of symptoms impacting HRQOL will provide a framework for improved clinical care and patient centered outcomes as new therapies are developed.

Item does not contain fulltext INTRODUCTION: Electrical impedance myography (EIM) is a noninvasive technique for measuring muscle composition and a potential physiological biomarker for facioscapulohumeral muscular dystrophy (FSHD). METHODS: Thirty-two participants with genetically confirmed and clinically affected FSHD underwent EIM in 7 muscles bilaterally. Correlations between EIM and baseline clinical measures were used to select EIM variables of interest in FSHD, and EIM and clinical measures were followed for 1 year. RESULTS: There were no significant changes in the EIM variables. Although 50-kHZ reactance correlated the strongest with clinical measures at baseline, the 50-211-kHZ phase ratio demonstrated lower within-subject 12-month variability, potentially offering sample size savings for FSHD clinical trial planning. DISCUSSION: EIM did not identify significant disease progression over 12 months. It is currently unclear whether this is because of limitations of the technology or the slow rate of disease progression in this cohort of FSHD patients over this period of time. Muscle Nerve 58: 213-218, 2018.

Introduction We developed an evaluator-administered functional facioscapulohumeral muscular dystrophy composite outcome measure (FSHD-COM) comprising patient-identified areas of functional burden for future clinical trials. Methods We performed a prospective observational study of 41 patients with FSHD at 2 sites. The FSHD-COM includes functional assessment of the legs, shoulders and arms, trunk, hands, and balance/mobility. We determined the test-retest reliability and convergent validity compared to established FSHD disease metrics. Results The FSHD-COM demonstrated excellent test-retest reliability (intraclass correlation coefficient [ICC] 0.96; subscale ICC range, 0.90-0.94). Cross-sectional associations between the FSHD-COM and disease duration, clinical severity, and strength were moderate to strong (Pearson correlation coefficient range |0.51-0.92|). Discussion The FSHD-COM is a disease-relevant, functional composite outcome measure suitable for future FSHD clinical trials that shows excellent test-retest reliability and cross-sectional associations to disease measures. Future directions include determining multisite reliability, sensitivity to change, and the minimal clinically important change in the FSHD-COM. Muscle Nerve, 2018.

Introduction When preparing for clinical trials in myotonic dystrophy type-1 (DM1), it is important that researchers develop and identify patient-reported outcome measures with good measurement properties. Methods Fifty-two DM1 patients enrolled in 2 clinical studies completed the Myotonic Dystrophy Health Index (MDHI), 36-Item Short Form Health Survey (version 2; SF-36v2), Individualized Neuromuscular Quality of Life questionnaire (INQoL), and a questionnaire comparing the relevance, usability, overall preference, and perceived responsiveness of each measure. The associations between instrument scores and physical function, genetic test results, and employment status were examined. Results The MDHI was preferred over the INQoL in 13 of 13 areas and was preferred over the SF-36v2 in 9 of 13 areas. The MDHI was the only score that was associated with participant employment status, CTG repeat length, and the 3 measurements of clinical function. Discussion The MDHI correlates well with physical function and is viewed favorably by participants in DM1 clinical studies. Muscle Nerve, 2018.

The Myotonic Dystrophy Health Index (MDHI) is a disease-specific, self-reported outcome measure that assesses total disease burden and 17 areas of Myotonic Dystrophy type 1 (DM1) specific health. This study translated the MDHI into Italian and validated the instrument using a cohort of Italian DM1 patients. Italian DM1 patients were interviewed regarding the form and content of the instrument. Thirty-eight DM1 patients were subsequently recruited to test the reliability and concurrent validity of the instrument by serially completing the MDHI and a battery of clinical tests. Lastly, we determined the internal consistency of the Italian MDHI and each of its subscales. The internal consistency was excellent in the total Italian MDHI score and acceptable in all of its subscales; the test-retest reliability was high (intraclass correlation coefficient = 0.95); Italian MDHI total scores and subscales were associated with neuromuscular function, cognitive and social health, respiratory function, and quality of life. Overall, the Italian MDHI is valid and well suited to measure the multi-dimensional aspects of disease burden in Myotonic Dystrophy clinical trials.

Introduction: The effects of spinal bulbar muscular atrophy (SBMA) on quality of life (QoL) are not well understood. This study describes symptoms from the patient's perspective, and the impact these symptoms have on QoL. Methods: We conducted open-ended interviews with 21 adult males with genetically confirmed SBMA. Using a qualitative framework technique, interviews were coded and analyzed to identify symptoms and resulting themes. Results: From these interviews, 729 quotations were extracted. We identified 200 SBMA-specific symptoms and 20 symptomatic themes. Weakness was mentioned by all interviewees. Symptoms within the domain of mental health and the specific themes of emotional issues and psychological impact were also frequently mentioned. Discussion: Numerous symptoms affect QoL for SBMA subjects. We identified previously unrecognized symptoms that are important to address in enhancing clinical care for patients with SBMA, and in developing tools to evaluate efficacy in future clinical trials. This article is protected by copyright. All rights reserved.

Myotonic dystrophy (DM) is an autosomal dominant, repeat expansion, progressive disorder with no drug therapies. Consequently, to better define a regulatory pathway in anticipation of new treatment strategies under investigation, the Myotonic Dystrophy Foundation convened a workshop entitled "Patient-Centered Therapy Development for Myotonic Dystrophy" in September 2015. Participants included representatives from academia, industry, the patient community, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). Presenters described the symptom burden of the disease, and existing data on DM biomarkers, endpoints, natural history, and benefit-risk considerations. FDA participants helped clarify the regulatory requirements for new drug treatment approvals and DM-specific issues such as variability, slow progression, and low prevalence. Workshop attendees gained a better understanding of DM and the current status of existing data and tools to support therapeutic drug research and development.

Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 (DM1).To analyze changes of Individualized Neuromuscular Quality of Life questionnaire (INQoL) scores in clinic patients with DM1 over a 6-year period.Patients completed the INQoL at baseline and after a 6-year period through their attendance in a neurology outpatient clinic. Severity of muscular involvement in DM1 was analyzed using the Muscular Impairment Rating Scale (MIRS).Ninety-nine DM1 patients completed a baseline visit. Sixty-seven of these patients were retested at an interval time. The overall INQoL score improved in our sample of patients (P.05) as did the following subscales: myotonia (P.05), pain (P.05), activities (P.01), social relationships (P.01), and body image (P.05). No changes were observed for the independence and emotions scales. There were no differences in mean change of INQoL scores between patients with worsened MIRS and those with no change in MIRS scale after follow-up (P.05).Individualized Neuromuscular Quality of Life questionnaire scores improved in our cohort of DM1 patients during a 6-year period. INQoL score did not correlate with progression of muscle weakness. This must be better understood before the selection of the instrument for use in trials to measure therapeutic benefit in DM1 patients.