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BACKGROUND: The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score. METHODS: Cross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure. RESULTS: Correlations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution. DISCUSSION: Psychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling. REGISTRATION: MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).
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Atividades Cotidianas , Miastenia Gravis , Psicometria , Humanos , Psicometria/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Miastenia Gravis/psicologia , Miastenia Gravis/diagnóstico , Idoso , Estudos Prospectivos , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , Estudos Longitudinais , Adulto , Avaliação de Resultados em Cuidados de SaúdeRESUMO
INTRODUCTION: Glucocorticoids (GCs) are associated with multiple toxicities that have substantial impact on patients. We conducted qualitative interviews with patients to identify the toxicities that are most relevant from their perspective, with the goal of creating a patient-reported companion measure to the Glucocorticoid Toxicity Index (GTI), a clinician-facing instrument. METHODS: Thirty-one patients with recent or current GC use participated in concept elicitation interviews. Participants received GC treatment for myasthenia gravis, chronic inflammatory demyelinating polyradiculoneuropathy, vasculitis, or systemic lupus erythematosus. Transcripts were coded following a thematic analysis approach. RESULTS: Participants reported more than 100 toxicities they believed to be associated with their GC medications. Common toxicities included weight gain (87%), increased appetite (84%), insomnia/sleep problems (77%), cognitive impairment/brain fog (71%), easy bruising (68%), anxiety (65%), irritability/short temper (65%), and osteoporosis (39%). These toxicities often centered on self-esteem, neuropsychiatric effects, skin toxicities, and musculoskeletal function. They can be categorized into domains such emphasizing neuropsychiatric, metabolic/endocrine, musculoskeletal, and dermatological effects, highlighting aspects of GC toxicity that patients are uniquely positioned to appreciate and report. CONCLUSION: Our results confirm that the toxicities associated with GCs are pervasive and diverse, with substantial impact on patients' lives. These data will be used to inform the development of a patient-reported outcome measure assessing GC toxicity. This patient-reported instrument will be designed to complement the clinician-reported GTI, facilitating a more detailed understanding of the nuances of change in GC toxicity.
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Lúpus Eritematoso Sistêmico , Vasculite , Humanos , Glucocorticoides/uso terapêutico , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is a rare neuromuscular disorder where IgG antibodies damage the communication between nerves and muscles, leading to muscle weakness that can be severe and have a significant impact on patients' lives. MG exacerbations include myasthenic crisis with respiratory failure, the most serious manifestation of MG. Recent studies have found MG prevalence increasing, especially in older patients. This study examined trends in hospital admissions and in-hospital mortality for adult patients with MG and readmissions and postdischarge mortality in older (65 years or older) adults with MG. METHODS: Data from the Nationwide Inpatient Sample (NIS), an all-payer national database of hospital discharges, were used to characterize trends in hospitalizations and in-hospital mortality related to MG exacerbations and MG crisis among adult patients aged 18 years or older. The Medicare Limited Data Set, a deidentified, longitudinal research database with demographic, enrollment, and claims data was used to assess hospitalizations, length of stay (LOS), readmissions, and 30-day postdischarge mortality among fee-for-service Medicare beneficiaries aged 65 years or older. The study period was 2010-2019. Multinomial logit models and Poisson regression were used to test for significance of trends. RESULTS: Hospitalization rates for 19,715 unique adult patients and 56,822 admissions increased from 2010 to 2019 at an average annualized rate of 4.9% (MG noncrisis: 4.4%; MG crisis: 6.8%; all p < 0.001). Readmission rates were approximately 20% in each study year for both crisis and noncrisis hospitalizations; the in-hospital mortality rate averaged 1.8%. Among patients aged 65 years or older, annualized increases in hospitalizations were estimated at 5.2%, 4.2%, and 7.7% for all, noncrisis, and crisis hospitalizations, respectively (all p < 0.001). The average LOS was stable over the study period, ranging from 11.3 to 13.1 days, but was consistently longer for MG crisis admissions. Mortality among patients aged 65 years or older was higher compared with that in all patients, averaging 5.0% across each of the study years. DISCUSSION: Increasing hospitalization rates suggest a growing burden associated with MG, especially among older adults. While readmission and mortality rates have remained stable, the increasing hospitalization rates indicate that the raw numbers of readmissions-and deaths-are also increasing. Mortality rates are considerably higher in older patients hospitalized with MG.
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Assistência ao Convalescente , Miastenia Gravis , Estados Unidos/epidemiologia , Humanos , Idoso , Alta do Paciente , Medicare , Hospitalização , Miastenia Gravis/terapia , Imunoglobulina GRESUMO
Objective: Better understanding the impact of social determinants of health (SDOH) barriers from the patient perspective is crucial to improve holistic patient support in generalized myasthenia gravis (gMG), a rare autoimmune disorder with high disease and treatment burden. The objective of this study was to identify economic challenges experienced by individuals living with gMG and SDOH barriers to better address current unmet needs. Methods: Adults (18-75 years) living with gMG and experiencing SDOH barriers in the United States were recruited to a mixed-methods study including qualitative interviews and a web-based quantitative survey. Quotas were implemented to include a balanced spread of baseline demographic categories including insurance type, living environment, and employment status among the study sample. Direct and indirect economic challenges were identified by degree of concern. Results: The survey was completed by 38 individuals living with gMG, the majority of whom were enrolled in public insurance and not employed. The most commonly reported major economic concerns were managing funds for emergency care (66%), loss of income (61%), and non-medical expenses (58%), highlighting the diversity of economic challenges. Individuals who were using public insurance plans, living in non-urban environments, and unemployed experienced pronounced challenges around managing non-medical costs and accessing government assistance. Conclusion: Both direct and indirect costs were emphasized as major concerns among individuals living with gMG and SDOH barriers. Increasing access to relevant, personalized, and holistic resources, including care management, should be prioritized to improve disease management and outcomes for individuals living with gMG.
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The purpose of this study was to investigate the epidemiology, management, and economic burden of myasthenia gravis in settings of real clinical practice. The analysis used administrative databases covering around 12 million subjects across Italy and included all adult patients with hospitalization discharge diagnosis or active exemption code for myasthenia gravis or with ≥1 pyridostigmine prescription from 2011 to 2018. The estimated prevalence of myasthenia gravis during 2018 was in the range 13.5-29.3/100,000 people (depending on the criteria applied), corresponding to 8190-17,728 alive patients, when reproportioning data to the entire Italian population. Overall 4397 patients with myasthenia gravis (mean age 61.7 years, 46.6% males) were included. A large pyridostigmine use was observed (84.0%-46.8% from 1st to 3rd year of follow-up), followed by corticosteroids (54.5%-44.6% from 1st to 3rd year of follow-up) and non-steroidal immunosuppressants (16% over follow-up). Total direct healthcare costs for myasthenia gravis were 4-times higher than those of the general population (3771 and 869, respectively), and up to 9-fold increased when considering patients with exacerbation (7827). These findings showed the epidemiologic burden of myasthenia gravis and the complexity of the therapeutic management for the affected patients, with large use of treatments and elevated healthcare expenditures.
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Introduction: Social determinants of health (SDOH) are important contributors to health outcomes, and better understanding their impact on individuals diagnosed with rare, chronic diseases with high burden and unmet need is critical. Characterizing SDOH burden can help improve the design of patient support programs (PSPs), using targeted approaches to remove barriers to access. Methods: This study used a mixed-methods strategy employing a quantitative survey, which was designed based on qualitative interviews, to understand the unmet needs and awareness/utilization of PSPs among individuals living with generalized myasthenia gravis (gMG) and experiencing SDOH barriers. The survey was completed by 38 individuals living with gMG, of which the majority were non-White/Caucasian, unemployed, low income, and enrolled in public insurance. Common SDOH challenges, awareness/utilization of available PSPs, and unmet needs were identified. Results: Financial and mental health concerns were the most common among individuals living with gMG and experiencing SDOH barriers throughout diagnosis, accessing treatment, initiating treatment, and continuing treatment. Awareness and utilization of existing support services were low, especially when accessing treatment. Educational, financial, and personalized support with high "human touch" were commonly perceived as the most valuable resources. Implications: To better serve the needs of individuals with gMG experiencing SDOH barriers, PSPs should use a targeted approach to offer services tailored to harder-to-reach populations. Further, providers, advocacy groups, manufacturers, and public organizations in the gMG ecosystem should strengthen collaborations with PSPs to enable individuals living with gMG to access the services they need to improve their health outcomes.
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Ecossistema , Miastenia Gravis , Humanos , Determinantes Sociais da Saúde , Miastenia Gravis/terapia , Miastenia Gravis/diagnóstico , Fatores Sociais , EscolaridadeRESUMO
INTRODUCTION/AIMS: Myasthenia gravis (MG) is a neuromuscular disease characterized by abnormal skeletal muscle fatiguability. The MG Activities of Daily Living (MG-ADL) scale assesses eight symptoms and is often used as primary endpoint in MG clinical trials where it is completed by neurologists. However, in observational studies, patients frequently complete the MG-ADL scale independently of their neurologist. In this study we aimed to assess the concordance between self- and physician-reported MG-ADL scores. METHODS: An international observational study was conducted among adult patients with MG scheduled for a routine visit or who entered the hospital via emergency services. Consenting patients and physicians completed the MG-ADL. Concordance between assessments was calculated using Gwet's agreement coefficient (Gwet's AC) for the MG-ADL individual items and the intraclass correlation coefficient (ICC) for the MG-ADL total score. RESULTS: Data were collected from 137 patients (63% female; mean age, 57.7 years). Physicians assessed the patient's symptoms as slightly more severe (8.1 vs 7.5 MG-ADL total score, respectively), corresponding to a difference of 0.6 on a range from 0 to 24. The ICC for the MG-ADL total score between the patient and the physician assessment was 0.94 (95% confidence interval, 0.89 to 0.95), showing excellent concordance. Gwet's AC showed substantial to almost perfect agreement for all items, except eyelid droop, for which the agreement was moderate. DISCUSSION: Our results demonstrate that patients and neurologists have a concordant assessment of the patient's MG symptoms when using the MG-ADL scale. This evidence supports patient self-administration of the MG-ADL in clinical practice and research.
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Blefaroptose , Miastenia Gravis , Médicos , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Atividades Cotidianas , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , NeurologistasRESUMO
INTRODUCTION: For patients with generalized myasthenia gravis (gMG), the association between symptom severity, often measured with the Myasthenia Gravis Activities of Daily Living (MG-ADL) instrument, and utility values is unknown. METHODS: Data was analyzed from the phase 3 ADAPT trial, which included adult patients with gMG randomly assigned to treatment with efgartigimod + conventional therapy (EFG + CT) or placebo + CT (PBO + CT). MG-ADL total symptom scores and the EQ-5D-5L, a measure of health-related quality of life (HRQoL), were collected biweekly up to 26 weeks. Utility values were derived from the EQ-5D-5L data with the United Kingdom value set. Descriptive statistics were reported for MG-ADL and EQ-5D-5L at baseline and follow-up. A normal identity-link regression model estimated the association between utility and the eight MG-ADL items. A generalized estimating equations (GEE) model was estimated to predict utility based on the patient's MG-ADL score and treatment received. RESULTS: A total of 167 patients (84 EFG + CT, 83 PBO + CT) contributed 167 baseline and 2867 follow-up measurements of MG-ADL and EQ-5D-5L. EFG + CT-treated patients experienced more improvements than PBO + CT-treated patients in most MG-ADL items and EQ-5D-5L dimensions, with the largest improvements observed in chewing, brushing teeth/combing hair, eyelid droop (MG-ADL); self-care, usual activities, mobility (EQ-5D-5L). The regression model indicated that individual MG-ADL items contributed differently to utility values, with the largest impact from brushing teeth/combing hair, rising from a chair, chewing, and breathing. The GEE model showed that each unit improvement in MG-ADL led to a statistically significant utility increase of 0.0233 (p < 0.001). In addition, a statistically significant improvement of 0.0598 (p = 0.0079) in utility was found for patients in the EFG + CT group compared to the PBO + CT group. CONCLUSION: Among patients with gMG, improvements in MG-ADL were significantly associated with higher utility values. MG-ADL scores alone were not sufficient to capture the utility gained from efgartigimod therapy.
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Miastenia Gravis , Qualidade de Vida , Adulto , Humanos , Atividades Cotidianas , Nível de Saúde , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Inquéritos e Questionários , Reino UnidoRESUMO
There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG.
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Miastenia Gravis , Qualidade de Vida , Recém-Nascido , Humanos , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Receptores Colinérgicos , Resultado do Tratamento , AutoanticorposRESUMO
OBJECTIVE: To evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation. METHODS: Patients with gMG who initiated IVIg treatment were identified from a United States claims database (Symphony Health's Integrated Dataverse [IDV]®, January 1, 2014 - December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the year post-IVIg initiation were analyzed. Usage patterns of IVIg and concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared. RESULTS: Among 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received ≥6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs. intermittent IVIg users ($161,478 vs. $64,888, p < 0.001). The proportion of patients using corticosteroids and nonsteroidal immunosuppressive treatments (NSISTs) was not reduced over the 3-year follow-up period following IVIg initiation, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation. CONCLUSIONS: Nearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, the proportion of patients using corticosteroids and NSISTs did not decrease over 3 years despite IVIg initiation.
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Imunoglobulinas Intravenosas , Miastenia Gravis , Adulto , Humanos , Estados Unidos , Imunoglobulinas Intravenosas/uso terapêutico , Miastenia Gravis/tratamento farmacológico , ImunossupressoresRESUMO
BACKGROUND/OBJECTIVES: While the clinical manifestations of myasthenia gravis (MG) are well understood, its humanistic impact is not. The objective of this systematic literature review (SLR) was to provide a comprehensive understanding of the humanistic burden of MG with regards to psychological symptoms and health-related quality of life (HRQoL) according to patients and caregivers. METHODS: A systematic search was conducted on December 27, 2019, in MEDLINE and Embase to identify English-language studies that were published from January 1, 2009-December 27, 2019 and presented relevant information on the humanistic burden among adults with MG and their caregivers. Title/abstract and full-text screening was performed by two investigators, with any discrepancies resolved by a third investigator. RESULTS: Sixty-seven publications were included in the SLR. Compared with the general population, patients with MG experienced worse HRQoL. Studies reporting on psychological symptoms of MG, including depression, anxiety, fatigue, and sleep, were heterogeneous in terms of the scales and instruments used to assess patients, as well as the patient populations themselves. However, in general those with more severe symptoms and hospitalization days had worse depression and anxiety, and fatigue and sleep improved with disease remission and/or improvement. Scores were worse for females compared with males and where evaluated, HRQoL scores generally improved following treatment. CONCLUSION: While the literature demonstrates that symptoms associated with MG get better with disease improvement and remission, additional options in efficacious therapy that adequately address the disease-related symptoms and also improve HRQoL may contribute to beneficial outcomes in a greater number of patients with MG.
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Miastenia Gravis , Qualidade de Vida , Adulto , Ansiedade , Cuidadores/psicologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Miastenia Gravis/terapiaRESUMO
The Myasthenia Gravis Activities of Living (MG-ADL) scale is an 8-item patient-reported scale that measures myasthenia gravis (MG) symptoms and functional status. The objective of the current review is to summarize the psychometric properties of the MG-ADL and published evidence of MG-ADL use. A targeted literature review for published studies of the MG-ADL was conducted using a database and gray literature search. A total of 48 publications and 35 clinical trials were included. Studies indicated that the MG-ADL is a reliable and valid measure that has been used as an outcome in clinical trials and observational studies to measure MG symptoms and response to treatment. While most often used as a secondary endpoint in clinical trials, its use as a primary endpoint has increased in recent years. The most common MG-ADL endpoint is change in MG-ADL score from baseline, although there has been an increase in the analysis of a responder threshold using the MG-ADL. A new concept of minimal symptom expression (MSE) has emerged more recently. Duration of treatment effect is another important construct that is being increasingly evaluated using the MG-ADL. The use of the MG-ADL as a primary endpoint in clinical trials and in responder threshold analyses to indicate treatment improvement has increased in recent years. MSE using the MG-ADL shows promise in helping to determine success of treatment and may be the aspirational goal of MG treatment for the future once validated, particularly given the evolving treatment landscape in MG.
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Atividades Cotidianas , Miastenia Gravis , Humanos , PsicometriaRESUMO
INTRODUCTION: Limited evidence exists for healthcare resource utilization (HCRU) and costs associated with generalized myasthenia gravis (gMG), a rare autoimmune disorder, for adults in the United States. METHODS: Adults with ≥1 diagnostic claim for MG between 2014 and 2019 were identified using Symphony Health's Integrated Dataverse®. Using a novel algorithm, HCRU and costs over 12 months following index dates were evaluated for patients with gMG including those with exacerbation events. For patients who experienced crisis events, HCRU and costs were analyzed during the 36 months preceding, during, and 12 months following the events. RESULTS: Mean HCRU and costs were higher for newly diagnosed patients compared with previously diagnosed patients (hospitalizations: 0.46 vs. 0.34; all-cause costs: $26,419.20 vs. $24,941.47; direct costs for gMG treatments: $9,890.37 vs. $9,186.47) and further increased for patients with exacerbation events (hospitalizations: 0.72; all-cause costs: $43,734.15; direct costs for gMG treatments: $21,550.02). For patients who experienced crisis events, HCRU and costs markedly increased during the 12 months immediately before the crisis event (hospitalizations: 1.35; all-cause costs: $49,236.68) compared with the 2 preceding years and increased further during the 12 months following the crisis index date (hospitalizations: 2.78; all-cause costs: $173,956.99). Cost increases were, in large part, attributed to treatments received. DISCUSSION: New diagnosis, exacerbation, and crisis events were drivers of HCRU and cost for patients with gMG. Particularly, high costs of gMG-specific medications associated with intervention for exacerbation and crisis events contributed to increased all-cause costs.
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INTRODUCTION: The Neuro-QoL is a standardized approach to assessing health-related quality of life in people with neurological conditions, including multiple sclerosis (MS). Item banks were developed with item response theory (IRT) methodology so items are calibrated along a continuum of each construct. The purpose of this study was to develop a preference-based scoring algorithm for the Neuro-QoL to derive utilities that could be used in economic modeling. METHODS: With input from neurologists, 6 Neuro-QoL domains were selected based on relevance to MS and used to define health states for a utility elicitation study in the United Kingdom. General population participants and individuals with MS valued the health states and completed questionnaires (including Neuro-QoL short forms). The Neuro-QoL Utility Scoring System (NQU) was derived based on multi-attribute utility theory using data from the general population sample. Single-attribute disutility functions for 6 Neuro-QoL domains were estimated using isotonic regression with linear interpolation and then combined with a multiplicative model. NQU validity was assessed using MS participant data. RESULTS: Interviews were completed with 203 general population participants (50.2% female; mean age = 45.0 years) and 62 participants with MS (62.9% female; mean age = 46.1 years). Mean (SD) NQU scores were 0.94 (0.06) and 0.82 (0.13) for the general population and MS samples, respectively. The NQU demonstrated known-groups validity by differentiating among subgroups categorized based on level of disability. The NQU demonstrated convergent validity via correlations with generic measures (0.66 and 0.63 with EQ-5D-5L and Health Utilities Index Mark 3, respectively; both P < 0.001). DISCUSSION: With the NQU, utilities can be derived from any MS treatment group, subgroup, or patient sample who completes items from 6 Neuro-QoL domains. Because the Neuro-QoL is frequently used with MS patients, the NQU greatly expands the options for quantifying outcomes in cost-utility analyses conducted to inform allocation of resources for MS treatment.
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Esclerose Múltipla/complicações , Qualidade de Vida/psicologia , Projetos de Pesquisa/tendências , Design Centrado no Usuário , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Psicometria/instrumentação , Psicometria/métodos , Projetos de Pesquisa/estatística & dados numéricos , Inquéritos e Questionários , Reino UnidoRESUMO
Aims: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with no currently approved therapies. Treatments are in development, and cost-utility analyses will be needed to examine their value. These models will require health state utilities representing FCS. Therefore, the purpose of this study was to estimate utilities for FCS and an associated episode of acute pancreatitis (AP).Methods: Because it is not feasible to gather a large enough sample of patients with this extremely rare condition to complete standardized preference-based measures, vignette-based methods were used to estimate utilities. In time trade-off interviews, general population participants in the UK and Canada valued health state vignettes drafted based on literature review, clinician input, and interviews with patients. Four health states described variations of FCS. A fifth health state, describing AP, was added to one of the other health states to evaluate its impact on utility.Results: A total of 308 participants provided utility data (208 UK; 100 Canada). Mean utilities for FCS health states ranged from 0.46 to 0.83, with higher triglycerides, more severe symptoms, and a history of AP associated with lower utility values. The disutility (i.e. utility decrease) of AP ranged from -0.17 to -0.25, with variations depending on the health state to which it was added. Utility means were similar in the UK and Canada.Conclusions: The vignette-based approach is useful for estimating utilities of a rare disease. The health state utilities derived in this study would be useful in models examining cost-effectiveness of treatments for FCS.
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Hiperlipoproteinemia Tipo I/complicações , Hiperlipoproteinemia Tipo I/fisiopatologia , Pancreatite/etiologia , Preferência do Paciente , Absenteísmo , Canadá , Análise Custo-Benefício , Feminino , Nível de Saúde , Humanos , Hiperlipoproteinemia Tipo I/psicologia , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Doenças Raras , Triglicerídeos/sangue , Reino UnidoRESUMO
Background: FCS significantly affects health-related quality of life (HRQOL). Legacy patient-reported outcome measures are often not sensitive to FCS's impact. NIH PROMIS and Neuro-QoL measures may accurately capture HRQOL in FCS patients. This study assessed a broad range of PROMIS and Neuro-QoL measures covering physical, mental, and social HRQOL to determine their suitability for the FCS population.Methods: Adult FCS patients in the United States (N = 25) were recruited to an online survey study and completed several PROMIS short forms and Neuro-QoL computer adaptive tests.Results: Scores were more than 0.5 standard deviations (SD) worse than the normative mean on 10 of 16 normed measures, and more than 0.75 SDs worse than the normative mean on two measures. Responses at the floor and ceiling were occasionally observed, marginal reliabilities were strong, and significant differences across performance status (ps < 0.05) provided preliminary support for construct validity. The measures correlated with each other strongly and as expected.Conclusion: Results support the ability of PROMIS and Neuro-QoL measures to detect HRQOL impairment among patients with FCS. PROMIS and Neuro-QoL measures captured the functional impact and symptom burden associated with FCS, and the broad range of symptom severity experienced by patients with FCS.
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Hiperlipoproteinemia Tipo I/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.
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OBJECTIVE: We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery. METHODS: Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form-36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness. RESULTS: The performance measures had excellent test-retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening. CONCLUSION: These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures.
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Esclerose Múltipla/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto JovemRESUMO
OBJECTIVE: No available assessment tool offers a brief and psychometrically sound way for clinicians to quantify assessment of MS in a typical office visit. The objective of this study was to develop a brief clinician-reported outcome measure of MS signs and symptoms to standardize and quantify assessments that occur during a typical neurology office visit. METHODS: A questionnaire, called the Clinician Rating of Multiple Sclerosis (CRoMS), was developed in the following steps: literature review; concept elicitation interviews (to generate questionnaire themes and content) with patients with MS (nâ¯=â¯14); concept elicitation interviews with neurologists (nâ¯=â¯9); online qualitative survey with neurologists in the US, UK, Germany, and Sweden (nâ¯=â¯72); online survey with neurologists to evaluate the first draft of the clinician-reported outcome measure (ClinRO) (nâ¯=â¯26); an in-person meeting with neurologists to discuss and revise the draft ClinRO (nâ¯=â¯9); and interviews with neurologists and MS nurses to further refine and finalize the ClinRO (nâ¯=â¯16). RESULTS: Across all steps of this research, several signs and symptoms consistently emerged as important for assessment in a typical office visit: walking, balance, upper limb function, coordination, weakness, fatigue, pain, sensory symptoms, bladder function, visual function, cognition, spasticity, spasms, and mood. The importance of these signs and symptoms was supported by neurologists during the online surveys and the in-person meeting. Neurologists were generally able to complete the draft ClinRO measure without difficulty, although minor revisions were suggested to refine the ClinRO for future use. CONCLUSION: The CRoMS may be a useful tool for efficiently assessing the severity of MS symptoms. This brief clinician-reported measure could help standardize and quantify assessments in clinical studies and clinical settings.
Assuntos
Fadiga/fisiopatologia , Esclerose Múltipla/diagnóstico , Equilíbrio Postural/fisiologia , Caminhada/fisiologia , Adulto , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Psicometria , Índice de Gravidade de Doença , Inquéritos e Questionários , Suécia , Avaliação de Sintomas , Reino Unido , Estados UnidosRESUMO
INTRODUCTION: In the clinic, the assessment of patients with multiple sclerosis (MS) is typically qualitative and non-standardized. OBJECTIVES: To describe the MS Performance Test (MSPT), an iPad Air® 2 (Apple, Cupertino, CA, USA)-based neurological assessment platform allowing patients to input relevant information without the aid of a medical technician, creating a longitudinal, clinically meaningful, digital medical record. To report results from human factor (HF) and usability studies, and the initial large-scale implementation in a practice setting. METHODS: The HF study examined use-error patterns in small groups of MS patients and healthy controls (n = 14), the usability study assessed the effectiveness of patient interaction with the tool by patients with a range of MS disability (n = 60) in a clinical setting, and the implementation study deployed the MSPT across a diverse population of patients (n = 1000) in a large MS center for routine clinical care. RESULTS: MSPT assessments were completed by all users in the HF study; minor changes to design were recommended. In the usability study, 73% of patients with MS completed the MSPT, with an average administration time of 32 min; 85% described their experience with the tool as satisfactory. In the initial implementation for routine care, 84% of patients with MS completed the MSPT, with an average administration time of 28 min. CONCLUSION: Patients with MS with varying disability levels completed the MSPT with minimal or no supervision, resulting in comprehensive, efficient, standardized, quantitative, clinically meaningful data collection as part of routine medical care, thus allowing for large-scale, real-world evidence generation. FUNDING: Biogen. TRIAL REGISTRATION: NCT02664324.