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1.
Cerebellum ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865059

RESUMO

This study aimed to generate evidence to support psychometric validity of the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) among patients with spinocerebellar ataxia (SCA). Psychometric measurement properties and minimal change thresholds of the f-SARA were evaluated using data from a cohort of SCA subjects (recruited at Massachusetts General Hospital [MGH]; n = 33) and data from a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), including a subset of patients with the SCA3 genotype (n = 89). f-SARA item ceiling effects were absent within the MGH cohort, while floor effects were present. Excellent internal consistency reliability was demonstrated (αtotal = 0.90; αitems-removed = 0.86-0.90), and item-to-total correlations were strong (r = 0.82-0.91, per item). High test-retest reliability was demonstrated with intraclass correlation coefficients of 0.91 (total) and 0.73-0.92 (items). Convergent and divergent validity was supported, with strong correlations observed between the f-SARA and similarly constructed scales (FARS-FUNC, BARS, PROM-ADL, and FARS-ADL; all p < 0.001) and weaker correlations observed among measures of differing constructs. Mean item and total scores increased with disease severity (by FARS-FUNC quartile; p < 0.001). A 1-point threshold for meaningful changes was supported as 0.5 × SD = 0.89, SEM = 1.12, and mean changes from baseline for patients classified as "improved," "no change," or "deteriorated" were -0.68, 0.02, and 0.58, respectively. Similar trends were observed in Study 206 all-SCA and SCA3 cohorts. The measurement properties of the f-SARA provide evidence of its psychometric validity, responsiveness, and suitability as a clinical outcome measure in patients with SCA, including those with SCA3.

2.
Cerebellum ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38710966

RESUMO

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

3.
Cerebellum ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217689

RESUMO

SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) regressions were used to identify which early life factors are predictive of SCA6 AAO, severity, and progression. Multiple linear regression models were then used to assess the degree to which these determinants influence SCA6 health outcomes. A total of 105 participants with genetically confirmed SCA6 completed the assessments. SCA6 participants with maternal difficulty during pregnancy, active participation in school sports, and/or longer CAG repeats were determined to have earlier AAO. We found a 13.44-year earlier AAO for those with maternal difficulty in pregnancy than those without (p = 0.008) and a 12.31-year earlier AAO for those active in school sports than those who were not (p < 0.001). Higher education attainment was associated with decreased SCA6 severity and slower progression. Early life biological and social factors can have a strong influence on the SCA6 disease course, indicating that non-genetic factors can contribute significantly to SCA6 health outcomes.

4.
Cerebellum ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713312

RESUMO

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1-2 years, 1-2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.

5.
Cephalalgia ; 44(4): 3331024241232944, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659334

RESUMO

BACKGROUND: The present study evaluated the long-term safety and tolerability of rimegepant, an orally administered small molecule calcitonin gene-related peptide receptor antagonist, in people with migraine. METHODS: This multicenter, long-term, open-label safety study included adults (≥18 years) with ≥1 year history of migraine who were sequentially enrolled into three groups: participants in the first two groups had either 2-8 or 9-14 moderate to severe migraine attacks per month by history and treated as needed (pro re nata [PRN]) with one rimegepant 75 mg oral tablet up to once per calendar day for 52 weeks (PRN 2-8 and PRN 9-14); a third group, included to collect safety data during higher-frequency dosing, had 4-14 moderate to severe migraine attacks per month by history and who took one rimegepant tablet every other day as scheduled dosing plus PRN dosing of one rimegepant tablet for migraine attacks of any severity on nonscheduled dosing days for 12 weeks (every other day (EOD) + PRN). RESULTS: Overall, 1800 participants self-administered rimegepant (PRN 2-8: n = 1033; PRN 9-14: n = 481; EOD + PRN: n = 286). The most common on-treatment adverse events (AEs) were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%) and sinusitis (5.1%). Most AEs were mild or moderate and considered unrelated to rimegepant. Serious AEs considered possibly (n = 1) or unlikely (n = 9) related to rimegepant were reported in ten (0.6%) participants. No signal of drug-induced liver injury because of rimegepant was identified. CONCLUSIONS: Rimegepant 75 mg up to once per day as EOD + PRN for 12 weeks or PRN for up to 52 weeks was safe and well tolerated. No signal of hepatotoxicity, potential drug abuse, or medication-overuse headache was identified.Trial registration: Clinicaltrials.gov: NCT03266588.


Assuntos
Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Transtornos de Enxaqueca , Piperidinas , Piridinas , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/administração & dosagem , Adulto Jovem , Idoso , Adolescente , Resultado do Tratamento
6.
Cephalalgia ; 43(2): 3331024221141686, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36739511

RESUMO

BACKGROUND: This post-hoc analysis from three phase 3 treatment trials of rimegepant 75 mg - an oral small molecule calcitonin gene-related peptide receptor antagonist for acute and preventive treatment of migraine - assessed efficacy in adults with migraine based on triptan treatment experience. METHODS: Participants were assigned to one of four groups based on triptan treatment experience: insufficient response (e.g. lack of efficacy and/or poor tolerability) to 1 triptan, insufficient response to ≥2 triptans, current triptan users, and triptan-naïve participants. The co-primary efficacy endpoints were pain freedom and most bothersome symptom freedom at two hours postdose. RESULTS: In the three trials (N = 3507; rimegepant n = 1749, placebo n = 1758), 1235 (35.2%) participants had a history of insufficient response to 1 triptan (n = 910 [25.9%]) or ≥2 triptans (n = 325 [9.3%]), and 2272 (64.8%) had no history of insufficient response to triptans (current use = 595 [17.0%], naïve = 1677 [47.8%]). Rimegepant was effective on the co-primary endpoints in all subgroups (p ≤ 0.013), except for freedom from the most bothersome symptom in the triptan-naïve group (p = 0.06). No differences on co-primary endpoints were found in pairwise comparisons of rimegepant-treated participants. CONCLUSIONS: Rimegepant was effective for the acute treatment of migraine in adults with a history of insufficient response to 1 or ≥2 triptans and in current triptan users. Efficacy on co-primary endpoints did not differ based on the number of insufficient triptan responses.Trial registration: Clinicaltrials.gov: NCT03235479, NCT03237845, NCT03461757.


Assuntos
Transtornos de Enxaqueca , Triptaminas , Adulto , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Piperidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Triptaminas/uso terapêutico , Ensaios Clínicos Fase III como Assunto
7.
Headache ; 62(4): 473-481, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35343590

RESUMO

OBJECTIVE: The objective of this study was to determine the associations among migraine disability assessment scores, healthcare resource utilization (HCRU; medical visits and pharmacy use) and direct medical costs among people with episodic migraine in a real-world setting. BACKGROUND: Migraine is a public health concern associated with a substantial economic burden in the United States. However, the association between migraine disability and direct medical costs among people with migraine is unknown. METHOD: This retrospective, cohort study used claims and electronic health record data from the Decision Resources Group database. Adults with migraine with or without aura, defined by International Classification of Disease Revision 9 (ICD-9) or ICD Revision 10 (ICD-10) codes, and a completed Migraine Disability Assessment Scale (MIDAS) questionnaire from January 2016 to December 2018 were included (chronic migraine codes not included). The associations of MIDAS score with the cost of HCRU for the 6 months after MIDAS assessment were explored. Results were stratified by treatment setting. RESULTS: Among 7662 included patients, MIDAS scores were distributed as: 3348 (43.7%; I, little/none), 1107 (14.4%; II, mild), 1225 (16.0%; III, moderate), 893 (11.7%; IVa, severe), and 1089 (14.2%; IVb, very severe). Worsening disability was associated with higher medical costs (adjusted from a multivariable model). In the primary care setting, healthcare visit costs were $206 (95% confidence interval: $144-294) for grade I and $631 ($384-1036) for grade IVb patients; corresponding pharmacy costs were $203 (grade I; $136-301) and $719 (grade IVb; $410-1259). For specialty care (e.g., neurologist), healthcare visits cost $509 ($411-629) for grade I and $885 ($634-1236) for grade IVb patients; corresponding pharmacy costs were $494 (grade I; $378-645) and $1020 (grade IVb; $643-1620). CONCLUSION: Higher levels of migraine-related disability (MIDAS assessed) are associated with increased HCRU costs among Americans with episodic migraine. Migraine disability assessment could be useful in the development, testing, and prescription of cost-effective treatments for people with high migraine-related disability.


Assuntos
Transtornos de Enxaqueca , Adulto , Estudos de Coortes , Avaliação da Deficiência , Custos de Cuidados de Saúde , Humanos , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/terapia , Estudos Retrospectivos , Estados Unidos
8.
Headache ; 62(9): 1187-1197, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36047857

RESUMO

OBJECTIVE: The objective of this study was to explore patient preference for attributes of calcitonin gene-related peptide (CGRP) inhibitors for the preventive treatment of migraine and to describe differences in treatment preferences between patients. BACKGROUND: CGRP inhibitors are a novel class of migraine drugs specifically developed for the preventive treatment of migraine. Clinicians should understand patient preferences for CGRP inhibitors to inform and support prescribing choices. METHODS: Patients with migraine in the US and Germany were recruited to participate in an online discrete choice experiment (DCE) survey, which presented hypothetical treatment choices using five attributes: mode of administration, side effects, migraine frequency, migraine severity, and consistency of treatment effectiveness. Attribute selection was informed by a literature review and semi-structured patient interviews (n = 35), and evaluated using patient cognitive debriefing interviews (n = 5). RESULTS: Of 680 who consented to participate, 506 participants completed the survey and were included in the study (US = 257; Germany = 249). Overall, participants placed highest importance (preference weight, beta = 1.65, p < 0.001) on the treatment's ability to reduce the severity of migraine (mild vs. unchanged severity), followed by consistent treatment effectiveness (beta = 1.13, p < 0.001), and higher chance of reduced migraine frequency (beta = 1.00, p < 0.001). Participants preferred an oral tablet every other day (beta = 1.00, p < 0.001) over quarterly infusion, quarterly injections (p = 0.019), or monthly injection (p < 0.001). Preference for all treatment attributes were heterogeneous, and the subgroup analyses found that participants naïve to CGRP monoclonal antibody treatments had a stronger preference for oral therapy compared to those with such experience (p = 0.006). CONCLUSION: In this DCE assessing CGRP inhibitors attributes, the main driver of patient choice was treatment effectiveness, specifically reduced migraine severity, and consistent treatment effectiveness. Further, patients exhibited an overall preference for an oral tablet every other day over injectables. Patients' experience with previous treatments informs the value they place on treatment characteristics.


Assuntos
Transtornos de Enxaqueca , Preferência do Paciente , Humanos , Preferência do Paciente/psicologia , Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Transtornos de Enxaqueca/psicologia , Alemanha , Anticorpos Monoclonais
9.
J Headache Pain ; 23(1): 10, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038983

RESUMO

BACKGROUND: The objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks. METHODS: Eligible subjects were adults with ≥1 year history of migraine and ≥ 6 MMD at baseline, who used rimegepant 75 mg up to once daily PRN (at their discretion) for up to 52-weeks in an open-label safety study (BHV3000-201; NCT03266588). Mean MMD were calculated at each 4-week period, along with mean monthly tablets taken. Migraine-specific quality of life (MSQv2) data were mapped to EQ-5D utilities and used to characterize HRQoL over time. A published network meta-analysis was used to characterize pain hours as well as time periods spent migraine free. RESULTS: One thousand forty four subjects were included in this post-hoc analysis. Overall mean MMD were 10.9 at baseline and decreased to 8.9 by week 52. Tablet use remained stable over the follow-up period. A total of 0.08 incremental QALYs were associated with rimegepant use. CONCLUSION: For subjects with 6 or more MMD, acute treatment of migraine attacks with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD frequency without an increase in monthly tablet utilization, and improved HRQoL. There was no evidence of medication-related increases in MMDs when rimegepant 75 mg was used as needed for the acute treatment of migraine over 52-weeks. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03266588 .


Assuntos
Transtornos de Enxaqueca , Qualidade de Vida , Adulto , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Método Duplo-Cego , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Piperidinas , Piridinas , Resultado do Tratamento
10.
J Headache Pain ; 23(1): 65, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676636

RESUMO

BACKGROUND: The debilitating nature of migraine attacks is widely established; however, less is known about how the interictal burden (i.e., how patients are affected in-between migraine episodes) of migraine impacts on patients' health-related quality of life (HRQL). Acute and preventive treatments may lift the burden of the disease, but they often have unwanted side effects and limited effectiveness. The objective of this study was to understand the interictal burden of migraines, from the patient perspective, and to explore patient experience with migraine treatments. METHODS: Participants (n=35) with a self-reported diagnosis of migraine were recruited in the US, UK and Canada, including a subgroup of patients who had taken calcitonin gene-related peptide monoclonal antibody (CGRP mAb) treatment for at least three months. Participants completed a background questionnaire, followed by a semi-structured interview via telephone or video call. The interviews explored patients' migraine symptoms, perception of interictal burden and treatment experience. The interview transcripts were analysed using thematic analysis. RESULTS: The most reported migraine symptom was migraine pain, followed by aura, sensory sensitivity and nausea. Most participants reported interictal impact on HRQL, lifestyle changes they made to avoid triggers or in anticipation of an attack, impacts on work, career, daily activities and relationships. Emotional impacts were reported by all participants, including anger, depression, anxiety and hopelessness. Many participants who took preventive treatments reported improvements in HRQL and functioning but still experienced breakthrough attacks. Among patients who took CGRP mAbs, participants noted varying consistency of treatment effectiveness between treatment administrations. CONCLUSION: This study detailed the additional HRQL impact of migraine in-between migraine attacks and described the unmet need for effective treatment options to prevent and mitigate migraine attacks.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Anticorpos Monoclonais/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Pesquisa Qualitativa , Qualidade de Vida , Inquéritos e Questionários
11.
J Headache Pain ; 23(1): 97, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941572

RESUMO

BACKGROUND: Previous research has extensively documented the impact of migraine episodes ('ictal') on patients' health-related quality of life. Few studies have looked at the impact of migraine on migraine-free days ('interictal'). This study was designed to describe interictal burden of migraine in a mixed group of people affected by migraine and to explore patient characteristics associated with interictal burden. METHODS: People with migraine in the United States (US) and Germany were recruited for a cross-sectional online survey, including a subgroup treated with calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb). The survey included the Migraine Interictal Burden Scale (MIBS-4), Headache Impact Test (HIT-6), and items measuring patient demographics, clinical and treatment background. Data were analyzed using descriptive statistics and linear regression. RESULTS: Five hundred six people with migraine completed the survey (US: n = 257; Germany: n = 249), of whom 195 had taken a CGRP mAb for three or more months. Participants had a mean of 8.5 (SD = 6.4) Monthly Migraine Days (MMD) and 10.4 (SD = 7.1) Monthly Headache Days (MHD). The mean MIBS-4 score was 6.3 (SD = 3.4), with 67% reporting severe interictal burden (MIBS-4: ≥5). The mean HIT-6 score was 65.3 (SD = 6.0), with 86% reporting severe migraine impact (HIT-6: ≥60). MIBS-4 was correlated with the HIT-6 (r = 0.37), MMD and MHD (both r = 0.27). The HIT-6, MMD, MHD, CGRP mAb treatment, and depression all had an independent positive association with the MIBS-4. CONCLUSION: Two-thirds of the study sample reported substantial interictal burden. Whilst interictal burden was associated with migraine frequency and impact of migraine attacks, study results also show it represented a distinct aspect of the overall disease burden. Study findings further indicate unique associations between interictal burden and depression. A unique positive association between interictal burden and CGRP mAb treatment suggests a remaining unmet need among people affected by migraine treated with CGRP mAb.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Anticorpos Monoclonais/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Estudos Transversais , Cefaleia/tratamento farmacológico , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Qualidade de Vida , Estados Unidos
12.
Mov Disord ; 36(10): 2367-2377, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34115419

RESUMO

BACKGROUND: Assessment of cerebellar ataxia has been confined to rating scales, gait laboratories, and wearable sensors agnostic to patient input. OBJECTIVES: The objective of this study was to develop a Patient-Reported Outcome Measure of Ataxia. METHODS: (1) The conceptual framework, item pool development, and domain selection were developed using online surveys completed by 147 ataxia patients. Responses generated the 70-item Patient-Reported Outcome Measure of Ataxia, scored on a 0-4 Likert scale. (2) Cognitive debrief in 17 patients grouped by ataxia severity assessed content validity, readability, and comprehension. (3) Psychometric validation by 78 anonymized ataxia patients included test-retest reliability, responsiveness to ataxia severity, internal consistency (Cronbach's alpha), and item-total score correlations. (4) Validation was tested against measures of ataxia and quality of life in 20 patients. (5) Items were rank-ordered to develop the Patient-Reported Outcome Measure of Ataxia Short Form. RESULTS: Three thousand eight hundred fifty-five symptoms were grouped into 3 domains (physical, activities of daily living, mental health) and 14 subdomains. The Patient-Reported Outcome Measure of Ataxia was comprehensible, important, and relevant. Internal consistency, reliability, and test-retest reliability were high. Scores were responsive to ataxia severity stages 1, 2, and 3: mean ± standard deviation 81.0 ± 37.0, 129.6 ± 32.0, and 151.1 ± 41.3, respectively (r = 0.58, P < 0.0001). The Patient-Reported Outcome Measure of Ataxia was validated against measures of motor ataxia, quality of life, and mental health. It had an R2 of 0.82 (P < 0.0001) with the preliminary Patient-Reported Outcome Measure of Ataxia Short Form. CONCLUSIONS: The Patient-Reported Outcome Measure of Ataxia is valid and reliable in cerebellar ataxia patients. It has the potential to improve patient care and natural history studies and quantify the efficacy of novel therapeutics in clinical trials. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Ataxia Cerebelar , Qualidade de Vida , Atividades Cotidianas , Ataxia/diagnóstico , Ataxia Cerebelar/diagnóstico , Humanos , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes
13.
BMC Neurol ; 21(1): 425, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727873

RESUMO

BACKGROUND: A synthesis of real-world discontinuation and switching patterns among triptan users and rates of acute medication use among patients with medication overuse headache (MOH) is needed to better understand the burden among patients with migraine. The study objectives were to: (1) synthesize rates of switching and discontinuation from triptans; (2) characterize acute medication use among patients with MOH; and (3) describe the associated burden. METHODS: A systematic literature review was conducted, under the Preferred Reporting Items for Systematic Review guidelines, using MEDLINE/EMBASE from database inception to July 2019. The search strategy targeted studies of adults with migraine, and included terms related to migraine and its treatment. Continuous variables were summarized using means, standard deviations, and ranges. Dichotomous and categorical variables were summarized using the number and proportion of individuals. RESULTS: Twenty studies were included; seven describing patterns of switching and discontinuation among triptan users, and 13 characterizing triptan overuse among patients with MOH. High rates of switching to non-specific acute medications and low two-year retention rates were reported; among US samples switching to opioids at the first refill (18.2%) or after 1-year (15.5%) was frequent. Compared to persistent use of triptans, switchers experienced greater headache related impact and either no improvement or increased headache-related disability. Rates of medication overuse by agent among patients with MOH varied greatly across the included studies, and only one study described factors associated with the risk of MOH (e.g. duration of medication overuse). Medication agent, increased headache frequency (p = .008), and increased disability (p = .045) were associated with unsuccessful withdrawal; patients overusing triptans were more successful at withdrawal than those overusing opioids or combination analgesics (P < .0001). CONCLUSIONS: The evidence summarized here highlights that rates of WCS are low and many patients turn to other acute medication at their first refill. Patients may experience no improvement in disability when switching from one triptan agent to another, or experience increasing disability and/or increasing migraine frequency when turning to traditional acute treatment for migraine. Variability in health care settings, patient severity, and study design contributed to heterogeneity across the synthesis.


Assuntos
Transtornos da Cefaleia Secundários , Transtornos de Enxaqueca , Adulto , Analgésicos/efeitos adversos , Analgésicos Opioides , Cefaleia , Transtornos da Cefaleia Secundários/induzido quimicamente , Transtornos da Cefaleia Secundários/epidemiologia , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Triptaminas/efeitos adversos
14.
Headache ; 61(6): 906-915, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34021585

RESUMO

OBJECTIVE: Rimegepant is an orally administered small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, with demonstrated efficacy in the acute treatment of migraine. Recent estimates from a single-arm trial (BHV3000-201) have also shown evidence of long-term preventive effects in monthly migraine days (MMDs) and health-related quality of life (HRQoL). This study aimed to compare MMDs and HRQoL data for oral rimegepant to those obtained in placebo-controlled trials for injectable anti-CGRP monoclonal antibodies (mAbs) galcanezumab and erenumab. METHODS: Matching-adjusted indirect comparisons (MAICs) were conducted using rimegepant subject-level data and published aggregate-level results from mAb trials. Rimegepant baseline characteristics were matched to the pooled subject characteristics from EVOLVE-I/II (galcanezumab vs. placebo; n = 1773) and STRIVE (ereumab vs. placebo; n = 955) by reweighting the rimegepant subjects to more closely match the distributions observed in these trials. To align with inclusion criteria of the mAb trials, only the subset of rimegepant subjects with a history of 4-14 MMDs were included (n = 257). Weighted mean differences were used to calculate adjusted change in MMDs, Migraine Disability Assessment Test (MIDAS) score, and Migraine-Specific Quality of Life Questionnaire version 2 (MSQv2) scores from baseline to week 12. RESULTS: When matched to the EVOLVE trials, rimegepant was superior to placebo with a mean difference in MMD change from baseline [95% confidence interval] of -1.16 [-1.80, -0.52] and was not statistically significantly different from galcanezumab 0.59 [-0.13, 1.32]. When matched to the STRIVE trial, rimegepant was superior to placebo -1.59 [-2.15, -1.03] and was not statistically significantly different from erenumab -0.06 [-0.61, 0.50]. Rimegepant showed superior MIDAS and MSQv2 results compared with placebo in both EVOLVE trials and in the STRIVE trial, no statistically significant differences from galcanezumab and erenumab regarding MIDAS, and favorable results compared with erenumab across all MSQv2 domains, while being generally similar to galcanezumab across all MSQv2 domains. CONCLUSIONS: When adjustments were made to reflect baseline characteristics in published literature, supporting data from BHV3000-201 suggest that rimegepant every other day is an effective therapy in reducing disability and MMDs and enhancing migraine-specific HRQoL. These data support the preventive benefit observed in randomized trials of rimegepant and further validate its efficacy for both acute and preventive treatment of migraine.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Piperidinas/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Adulto , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Placebos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento
15.
Hepatology ; 66(3): 784-793, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28370058

RESUMO

The association between hepatitis C virus (HCV) infection and end-stage renal disease (ESRD) remains controversial without considering the role of HCV viral load and genotype. This study aimed to determine whether HCV RNA level and genotype affect the risk of developing ESRD. Between 1991 and 1992, 19,984 participants aged 30-65 years were enrolled in a community-based prospective cohort study in Taiwan. Chronic HCV infection was defined by detectable HCV viral load. ESRD was determined as the need for chronic dialysis or renal transplantation. Conventional Cox proportional hazard and competing risk models were used to determine the hazard ratio (HR) for ESRD. After a median follow-up of 16.8 years, 204 cases were detected during 319,474 person-years. The incidence rates of ESRD for nonchronically HCV-infected and chronically HCV-infected patients were 60.2 and 194.3 per 100,000 person-years, respectively. The multivariable HR was 2.33 (95% confidence interval [CI] 1.40-3.89) when comparing patients with and without chronic HCV infection. Patients with low and high HCV RNA levels were at higher risk of ESRD than those who were nonchronically HCV-infected (HR, 2.11, 95% CI 1.16-3.86, and HR, 3.06, 95% CI 1.23-7.58; Ptrend < 0.001). This association remained robust after taking pre-ESRD death as a competing event for ESRD. Patients with HCV genotype 1 tended to have a higher risk of developing ESRD (HR, 3.60 95% CI 1.83-7.07) compared with nonchronically HCV-infected subjects. CONCLUSIONS: This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784-793).


Assuntos
Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Seguimentos , Genótipo , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , RNA Viral/análise , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Análise de Sobrevida , Taiwan/epidemiologia , Fatores de Tempo , Carga Viral
16.
Kidney Int ; 92(3): 703-709, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28532708

RESUMO

Associations between chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD) remain controversial. Here we aimed to clarify the association between HCV viral load, genotype, and CKD in 13,805 participants aged 30-65 years enrolled in the REVEAL-HCV Study, a community-based prospective study conducted in 1991-1992. CKD was defined by consecutive proteinuria or an estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2. Chronic HCV infection was defined by detectable HCV viral load. Logistic regression models were used to estimate prevalence odds ratio of CKD for chronic HCV infection after adjusting for other risk factors. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio (95% confidence interval) for CKD was significantly increased to 1.91 (1.27-2.88) for chronically HCV-infected participants. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio of CKD was 1.21 (0.54-2.70), 1.40 (0.66-3.00) and 3.44 (1.92-6.14) for chronically HCV-infected participants with low to high tertiles of serum HCV RNA, respectively. The adjusted prevalence odds ratios of CKD were 0.54 (0.17-1.75) for participants with low HCV RNA and genotype 1, 1.80 (0.84-3.87) for those with low HCV RNA and genotype 2, 2.62 (1.11-6.17) for those with high HCV RNA and genotype 1 and 4.99 (2.25-11.06) for those with high HCV RNA and genotype 2, compared with non-chronically HCV-infected participants. Thus, chronic HCV infection is associated with an increased risk of CKD. High HCV viral load and HCV genotype 2 are strong CKD predictors.


Assuntos
Hepacivirus/fisiologia , Hepatite C Crônica/epidemiologia , RNA Viral/sangue , Insuficiência Renal Crônica/epidemiologia , Carga Viral , Adulto , Feminino , Genótipo , Taxa de Filtração Glomerular , Hepatite C Crônica/sangue , Hepatite C Crônica/urina , Hepatite C Crônica/virologia , Humanos , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Proteinúria/urina , RNA Viral/isolamento & purificação , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Insuficiência Renal Crônica/virologia , Fatores de Risco , Taiwan/epidemiologia
18.
Int J Cancer ; 135(5): 1119-26, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24482200

RESUMO

The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case-control and cohort studies. In the case-control study, 397 HCC cases from medical centers were compared with 410 community-based non-HCC controls. All of them were anti-HCV-seropositive, HBsAg-seronegative with serum HCV RNA levels ≥1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti-HCV-seropositive individuals were followed from 1991 to 2008 to assess the long-term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow-up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64 vs. 55%, p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 × 10(6) IU/mL) than those infected with HCV non-1b (1.2 × 10(6) IU/mL, p < 0.001). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.43 (1.02-2.02). After the long-term follow-up, the cumulative lifetime (30-80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non-1b and 1b, respectively (p < 0.001). The multivariate-adjusted hazard ratio (95% CI) was 1.85 (1.06-3.22) for HCV 1b compared to non-1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.


Assuntos
Carcinoma Hepatocelular/virologia , Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Neoplasias Hepáticas/virologia , Adulto , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genótipo , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , RNA Viral/sangue , Risco , Fatores de Risco , Taiwan/epidemiologia
19.
Hepatology ; 58(1): 54-64, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23389841

RESUMO

UNLABELLED: Recent United States guidelines recommend one-time birth cohort testing for hepatitis C infection in persons born between 1945 and 1965; this represents a major public health policy undertaking. The purpose of this study was to assess the role of treatment timing and prioritization on predicted cost-effectiveness. The MONARCH hepatitis C lifetime simulation model was used in conjunction with a testing and treatment decision tree to estimate the cost-effectiveness of birth cohort versus risk-based testing incorporating information on age, fibrosis stage and treatment timing. The study used a 1945-1965 birth cohort and included disease progression, testing and treatment-related parameters. Scenario analysis was used to evaluate the impact of hepatitis C virus (HCV) prevalence, treatment eligibility, age, fibrosis stage and timing of treatment initiation on total costs, quality-adjusted life years (QALYs), HCV-related complications and cost-effectiveness. The cost-effectiveness of birth cohort versus risk-based testing was $28,602. Assuming 91% of the population is tested, at least 278,000 people need to be treated for birth cohort testing to maintain cost-effectiveness. Prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of $7.5 billion and 59,035 fewer HCV-related complications. Total QALYs and complications avoided are maximized when treatment initiation occurs as soon as possible after testing. CONCLUSION: This study confirms that birth cohort testing is, on average, cost-effective. However, this remains true only when enough tested and HCV-positive subjects are treated to generate sufficient cost offsets and QALY gains. Given the practical and financial challenges associated with implementing birth cohort testing, the greatest return on investment is obtained when eligible patients are treated immediately and those with more advanced disease are prioritized.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/patogenicidade , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Adulto , Antivirais/economia , Estudos de Coortes , Análise Custo-Benefício , Hepatite C Crônica/economia , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/patologia , Humanos , Cadeias de Markov , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Vigilância da População/métodos , Anos de Vida Ajustados por Qualidade de Vida , Risco , Estados Unidos/epidemiologia
20.
Value Health ; 17(2): 254-60, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24636384

RESUMO

OBJECTIVE: In spite of increases in short-term kidney transplant survival rates and reductions in acute rejection rates, increasing long-term graft survival rates remains a major challenge. The objective here was to project long-term graft- and survival-related outcomes occurring among renal transplant recipients based on short-term outcomes including acute rejection and estimated glomerular filtration rates observed in randomized trials. METHODS: We developed a two-phase decision model including a trial phase and a Markov state transition phase to project long-term outcomes over the lifetimes of hypothetical renal graft recipients who survived the trial period with a functioning graft. Health states included functioning graft stratified by level of renal function, failed graft, functioning regraft, and death. Transitions between health states were predicted using statistical models that accounted for renal function, acute rejection, and new-onset diabetes after transplant and for donor and recipient predictors of long-term graft and patient survival. Models were estimated using data from 38,015 renal transplant recipients from the United States Renal Data System. The model was populated with data from a 3-year, randomized phase III trial comparing belatacept to cyclosporine. RESULTS: The decision model was well calibrated with data from the United States Renal Data System. Long-term extrapolation of Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial was projected to yield a 1.9-year increase in time alive with a functioning graft and a 1.2 life-year increase over a 20-year time horizon. CONCLUSIONS: This is the first long-term follow-up model of renal transplant patients to be based on renal function, acute rejection, and new-onset diabetes. It is a useful tool for undertaking comparative effectiveness and cost-effectiveness studies of immunosuppressive medications.


Assuntos
Técnicas de Apoio para a Decisão , Sobrevivência de Enxerto , Transplante de Rim/métodos , Modelos Estatísticos , Avaliação de Resultados em Cuidados de Saúde , Abatacepte , Adulto , Ensaios Clínicos Fase III como Assunto , Ciclosporina/uso terapêutico , Diabetes Mellitus/epidemiologia , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Humanos , Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Cadeias de Markov , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
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