RESUMO
BACKGROUND: Patient-reported outcomes are important for clinical research and care, yet administering and scoring the questionnaires requires considerable effort and time. The Patient Reported Outcomes Measurement Information System (PROMIS) could considerably reduce administrative obstacles and lessen survey burden for participants. OBJECTIVE: Assess the feasibility and validity of PROMIS, compared to commonly-used legacy measures for multiple sclerosis (MS). METHODS: In this cross-sectional survey, 133 participants with confirmed MS completed legacy surveys and PROMIS Computerized Adaptive Tests (CATs) for depression, anxiety, pain, fatigue and physical function. We conducted a multi-trait, multi-method analysis and verified results with confirmatory factor analysis. RESULTS: The correlations between PROMIS and the corresponding legacy measures were large (0.67 to 0.87). The multi-trait, multi-method criteria were generally well met, providing good evidence of the validity of PROMIS measures. PROMIS surveys asked fewer questions and required substantially less time to complete than the legacy scales. CONCLUSIONS: Our results provide evidence of the construct validity of PROMIS for use with MS patients. Several aspects of the PROMIS CATs made them an important resource, including: (a) less time was required to complete them; (b) missing data was reduced; and (c) the automatic scoring referenced the general population. Our findings support the use of PROMIS in MS research and may have broader implications for clinical care, as well.
Assuntos
Esclerose Múltipla/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Estudos Transversais , Depressão/diagnóstico , Depressão/psicologia , Estudos de Viabilidade , Feminino , Pesquisas sobre Atenção à Saúde , Nível de Saúde , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/psicologia , Esclerose Múltipla/terapia , Dor/diagnóstico , Dor/psicologia , Medição da Dor , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo , Fluxo de TrabalhoRESUMO
BACKGROUND: In short-term trials, dalfampridine extended release (ER) improves walking in people with multiple sclerosis (MS). The tolerability and effects of dalfampridine-ER in clinical practice have not been reported. OBJECTIVES: The objective of this paper is to determine the clinical tolerability and effects of dalfampridine on walking and community participation. METHODS: All patients at the Portland VA Medical Center prescribed dalfampridine-ER over one year completed the Timed 25-Foot Walk (T25FW), Multiple Sclerosis Walking Scale-12 (MSWS-12), Two-Minute Timed Walk (2MTW), and Community Integration Questionnaire (CIQ) at baseline and follow-up clinic visits. Ongoing use and measures over one year were analyzed. RESULTS: A total of 39 patients (mean age 56.5 years, mean disease duration 19.5 years, 82% male, 38% relapsing-remitting MS, 62% progressive MS) were prescribed dalfampridine-ER. Twenty-four (62%) continued to take dalfampridine-ER. At initial follow-up, all measures improved significantly from baseline (T25FW: -2.7 s, p = 0.004; 2MTW: 41 feet (ft), p = 0.002; MSWS12: -11, p < 0.001; CIQ: 1.2, p = 0.003). At one year, walking endurance and self-perceived walking were still significantly improved (2MTW: 33 ft, p = 0.03; MSWS-12: 5.9, p = 0.007). CONCLUSIONS: Dalfampridine-ER was associated with short-term improvements in walking speed and community participation, and sustained improvements in walking endurance and self-perceived impact of MS on walking for one year. Our study supports the utility of this medication in late MS.
Assuntos
4-Aminopiridina/uso terapêutico , Participação da Comunidade , Esclerose Múltipla/tratamento farmacológico , Bloqueadores dos Canais de Potássio/uso terapêutico , Caminhada/fisiologia , Adulto , Idoso , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , VeteranosRESUMO
A relationship between vitamin D and several diseases, including multiple sclerosis (MS), has recently received interest in the scientific community. Vitamin D appears to have important actions beyond endocrine function, particularly for the immune system. Risk of development of MS, as well as disease severity, has been associated with vitamin D in a variety of studies. There remains a need for prospective studies to further establish this relationship. Given the current evidence of the potential benefits of vitamin D, it appears to be reasonable and safe to consider vitamin D supplementation at dosing adequate to achieve normal levels in patients with MS and clinically isolated syndrome.
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Esclerose Múltipla/dietoterapia , Esclerose Múltipla/metabolismo , Vitamina D/fisiologia , Animais , Modelos Animais de Doenças , Humanos , Esclerose Múltipla/imunologia , Caracteres Sexuais , Vitamina D/administração & dosagemRESUMO
Multiple Ag peptides (MAPs) containing eight proteolipid protein (PLP)(139-151) peptides arranged around a dendrimeric branched lysine core were used to influence the expression and development of relapsing experimental allergic encephalomyelitis (EAE) in SJL mice. The PLP(139-151) MAPs were very efficient agents in preventing the development of clinical disease when administered after immunization with the PLP(139-151) monomeric encephalitogenic peptide in CFA. The treatment effect with these MAPs was peptide specific; irrelevant multimeric peptides such as guinea pig myelin basic protein GPBP(72-84) MAP (a dendrimeric octamer composed of the 72-84 peptide) and PLP(178-191) MAP (a dendrimeric octamer composed of the PLP(178-191) peptide) had no treatment effect on PLP(139-151)-induced EAE. PLP(139-151) MAP treatment initiated after clinical signs of paralysis also altered the subsequent course of EAE; it limited developing signs of paralysis and effectively limited the severity and number of disease relapses in MAP-treated mice over a 60-day observation period. PLP(139-151) MAP therapy initiated before disease onset acts to limit the numbers of Th17 and IFN-gamma-producing cells that enter into the CNS. However, Foxp3(+) cells entered the CNS in numbers equivalent for nontreated and PLP(139-151) MAP-treated animals. The net effect of PLP(139-151) MAP treatment dramatically increases the ratio of Foxp3(+) cells to Th17 and IFN-gamma-producing cells in the CNS of PLP(139-151) MAP-treated animals.
Assuntos
Dendrímeros/uso terapêutico , Encefalomielite Autoimune Experimental/prevenção & controle , Peptídeos/uso terapêutico , Animais , Movimento Celular/efeitos dos fármacos , Sistema Nervoso Central/patologia , Progressão da Doença , Encefalomielite Autoimune Experimental/tratamento farmacológico , Feminino , Camundongos , Proteolipídeos , Prevenção Secundária , Linfócitos TRESUMO
OBJECTIVE: To demonstrate the infrastructure and utility of an interactive health system database for multiple sclerosis (MS), we present the MS Surveillance Registry (MSSR) within the US Department of Veterans Affairs (VA). BACKGROUND: Disease specific databases can be helpful in the management of neurologic conditions but few are fully integrated into the electronic health record and linked to health system data. Creating a consistent information technology (IT) architecture and with ongoing support within disease specific registries has been a challenge. METHODS: Building the MSSR was initiated by an iterative process with an IT team and MS health care providers. A common registry platform shared by other VA disease specific registries (eg, traumatic brain injury and cancer) was used to develop the IT infrastructure. MS cases were entered online into the MS Assessment Tool at selected MS Centers of Excellence (MSCoE) clinics in the US. Other large VA databases linked to MSSR are reviewed. Patient demographic and clinical characteristics were compared and contrasted with the broader VA population and other US registry populations. RESULTS: We have enrolled 1,743 patients with MS in the MSSR through fiscal year 2019 from selected MS regional programs in the VA MSCoE network. The mean age of patients was 56.0 years, with a 2.7 male:female ratio. Among those with definite MS, the mean European Database for MS Disability Score was 4.7 and 75% had ever used an MS disease modifying therapy. A summary electronic dashboard was developed for health care providers to easily access demographic and clinical data for individuals and groups of patients. Data on comorbid conditions, pharmacy and prosthetics utilization, outpatient clinic visits, and inpatient admission were documented for each patient. CONCLUSIONS: The MSSR is a unique electronic database that has enhanced clinical management of MS and serves as a national source for clinical outcomes.
RESUMO
Therapeutic vaccination using T-cell receptor (TCR) peptides from V genes commonly expressed by potentially pathogenic T cells remains an approach of interest for treatment of multiple sclerosis (MS) and other autoimmune diseases. We developed a trivalent TCR vaccine containing complementarity determining region (CDR) 2 peptides from BV5S2, BV6S5 and BV13S1 emulsified in incomplete Freund's adjuvant that reliably induced high frequencies of TCR-specific T cells. To evaluate induction of regulatory T-cell subtypes, immunological and clinical parameters were followed in 23 treatment-naïve subjects with relapsing-remitting or progressive MS who received 12 monthly injections of the trivalent peptide vaccine over 1 year in an open-label study design. Prior to vaccination, subjects had reduced expression of forkhead box (Fox) P3 message and protein, and reduced recognition of the expressed TCR repertoire by TCR-reactive cells compared with healthy control donors. After three or four injections, most vaccinated MS subjects developed high frequencies of circulating interleukin (IL)-10-secreting T cells specific for the injected TCR peptides and significantly enhanced expression of FoxP3 by regulatory T cells present in both 'native' CD4+ CD25+ and 'inducible' CD4+ CD25- peripheral blood mononuclear cells (PBMC). At the end of the trial, PBMC from vaccinated MS subjects retained or further increased FoxP3 expression levels, exhibited significantly enhanced recognition of the TCR V gene repertoire apparently generated by perturbation of the TCR network, and significantly suppressed neuroantigen but not recall antigen responses. These findings demonstrate that therapeutic vaccination using only three commonly expressed BV gene determinants can induce an expanded immunoregulatory network in vivo that may optimally control complex autoreactive responses that characterize the inflammatory phase of MS.
Assuntos
Fatores de Transcrição Forkhead/sangue , Esclerose Múltipla/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Vacinas de Subunidades Antigênicas/uso terapêutico , Adulto , Idoso , Autoantígenos/imunologia , Autoimunidade/imunologia , Regiões Determinantes de Complementaridade/imunologia , Feminino , Genes Codificadores dos Receptores de Linfócitos T/imunologia , Humanos , Tolerância Imunológica/imunologia , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteínas do Tecido Nervoso/imunologia , Linfócitos T Reguladores/imunologia , Vacinação/métodosRESUMO
The US Food and Drug Administration has registered 13 multiple sclerosis (MS) disease-modifying therapies (DMTs). The medications are not interchangeable as they vary in route of administration, efficacy, and safety profile. Selecting the appropriate MS DMT for individual patients requires shared decision-making between patients and neurologists. To reduce costs, insurance companies acting through pharmacy benefit companies restrict access to MS DMTs through tiered coverage and other regulations. We discuss how policies established by insurance companies that limit access to MS DMTs interfere with the process of shared decision-making and harm patients. We present potential actions that neurologists can take to change how insurance companies manage MS DMTs.
RESUMO
OBJECTIVE: To characterize patients misdiagnosed with multiple sclerosis (MS). METHODS: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. RESULTS: Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. CONCLUSIONS: Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.
Assuntos
Erros de Diagnóstico , Esclerose Múltipla/diagnóstico , Centros Médicos Acadêmicos , Biomarcadores/líquido cefalorraquidiano , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunomodulação , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Estados UnidosRESUMO
OBJECTIVE: To examine the pricing trajectories in the United States of disease-modifying therapies (DMT) for multiple sclerosis (MS) over the last 20 years and assess the influences on rising prices. METHODS: We estimated the trend in annual drug costs for 9 DMTs using published drug pricing data from 1993 to 2013. We compared changes in DMT costs to general and prescription drug inflation during the same period. We also compared the cost trajectories for first-generation MS DMTs interferon (IFN)-ß-1b, IFN-ß-1a IM, and glatiramer acetate with contemporaneously approved biologic tumor necrosis factor (TNF) inhibitors. RESULTS: First-generation DMTs, originally costing $8,000 to $11,000, now cost about $60,000 per year. Costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%-60% higher than existing DMTs. Significant increases in the cost trajectory of the first-generation DMTs occurred following the Food and Drug Administration approvals of IFN-ß-1a SC (2002) and natalizumab (reintroduced 2006) and remained high following introduction of fingolimod (2010). Similar changes did not occur with TNF inhibitor biologics during these time intervals. DMT costs in the United States currently are 2 to 3 times higher than in other comparable countries. CONCLUSIONS: MS DMT costs have accelerated at rates well beyond inflation and substantially above rates observed for drugs in a similar biologic class. There is an urgent need for clinicians, payers, and manufacturers in the United States to confront the soaring costs of DMTs.
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Custos e Análise de Custo , Indústria Farmacêutica/economia , Fatores Imunológicos/economia , Imunossupressores/economia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/economia , Humanos , Estados UnidosRESUMO
We have used a peptide derived from Acanthamoeba castellanii (ACA) to treat the relapsing phase of EAE that develops in SJL mice following immunization with the PLP 139-151 peptide. The native sequence of the ACA 81-95 peptide that shares key residues with the PLP 139-151 peptide is weakly encephalitogenic in SJL mice but is not recognized by antiserum from SJL mice immunized with PLP 139-151. A single amino acid change to the ACA 81-95 peptide sequence significantly enhanced its encephalitogenicity. When administered to SJL mice as a nonlinear peptide octamer, the modified ACA peptide prevented relapsing episodes of EAE in SJL mice previously immunized with the PLP 139-151 encephalitogenic peptide.
Assuntos
Anafilaxia/imunologia , Anafilaxia/prevenção & controle , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Proteína Proteolipídica de Mielina/imunologia , Proteína Proteolipídica de Mielina/farmacologia , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/farmacologia , Acanthamoeba castellanii/genética , Acanthamoeba castellanii/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos/imunologia , Modelos Animais de Doenças , Feminino , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Mimetismo Molecular/imunologia , Dados de Sequência Molecular , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteína Proteolipídica de Mielina/genética , Fragmentos de Peptídeos/genética , Linfócitos T/imunologiaRESUMO
BACKGROUND: Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS. OBJECTIVES: To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren's Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren's Syndrome. METHODS: Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center. RESULTS: Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren's Syndrome. CONCLUSIONS: Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease.
Assuntos
Autoanticorpos , Esclerose Múltipla/imunologia , Síndrome de Sjogren/diagnóstico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos Transversais , Feminino , Humanos , Oregon , Síndrome de Sjogren/imunologiaRESUMO
BACKGROUND: Health care providers recommend an annual visit to a multiple sclerosis specialty care provider. OBJECTIVE: To examine potential barriers to the implementation of this recommendation in the Veterans Health Administration. DESIGN: Observational cohort study. SETTING: Veterans Health Administration. PARTICIPANTS: Participants were drawn from the Veterans Affairs Multiple Sclerosis National Data Repository and were included if they had an outpatient visit in 2007 and were alive in 2008 (N = 14,723). MAIN OUTCOME MEASUREMENTS: Specialty care visit, receipt of medical services. RESULTS: A total of 9643 (65.5%) participants had a specialty care visit in 2007. Veterans who were service connected, had greater medical comorbidity, and who lived in urban settings were more likely to have received a specialty care visit. Veterans who were older and had to travel greater distances to a center were less likely to have a specialty care visit. CONCLUSIONS: Access to care in rural areas and areas at a greater distance from a major medical center represent notable barriers to rehabilitation and other multiple sclerosis-related care.
Assuntos
Acessibilidade aos Serviços de Saúde , Esclerose Múltipla/terapia , Neurologia , Medicina Física e Reabilitação , Saúde dos Veteranos , Adulto , Idoso , Assistência Ambulatorial , Estudos de Coortes , Feminino , Hospitalização , Hospitais de Veteranos , Humanos , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
Upon recovery from the initial episode of experimental autoimmune encephalomyelitis (EAE), virtually all SJL mice develop relapsing/remitting episodes of disease. These relapses may occur due to the reactivation of memory T cells initially stimulated as part of the disease-inducing protocol or naïve T-cell populations stimulated by distinct encephalitogens derived from the inflammatory disease process (epitope spread). We have used encephalitogen-specific non-linear peptide octamers to modify the course of relapsing EAE (rEAE) in SJL mice immunized with an oliogodendrocyte-specific protein peptide (OSP 55-71). Our studies show that the peptide-octamers, which target the T cells stimulated by the priming encephalitogen, but not other candidate encephalitogens, prevent rEAE.
Assuntos
Claudinas/imunologia , Encefalomielite Autoimune Experimental , Epitopos de Linfócito T/imunologia , Imunoterapia/métodos , Fragmentos de Peptídeos/farmacologia , Linfócitos T/imunologia , Doença Aguda , Animais , Movimento Celular/imunologia , Claudinas/farmacologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Imunização , Memória Imunológica/imunologia , Camundongos , Camundongos Endogâmicos , Fragmentos de Peptídeos/imunologia , Prevenção Secundária , Linfócitos T/patologiaAssuntos
Custos e Análise de Custo , Indústria Farmacêutica/economia , Fatores Imunológicos/economia , Imunossupressores/economia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/economia , HumanosAssuntos
Esclerose Múltipla , Autoria , Custos e Análise de Custo , Indústria Farmacêutica , Humanos , EditoraçãoAssuntos
Custos e Análise de Custo , Indústria Farmacêutica/economia , Fatores Imunológicos/economia , Imunossupressores/economia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/economia , HumanosRESUMO
The study's objective was to develop a real-time measurement for fatigue and to evaluate whether it is an effective clinical trial outcome measure compared with the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Forty-nine subjects with MS and an FSS >4 recorded Real-Time Digital Fatigue Scores (RDFSs) on a wrist-worn device four times a day over 3 weeks. Scores were scaled 0-10, with 10 representing the worst possible fatigue. FSS and MFIS were evaluated and compared with RDFSs. Mean RDFSs significantly correlated with FSS (r = 0.55, p < 0.001) and MFIS (r = 0.55, p < 0.001). RDFS captured circadian variations in fatigue, with scores increasing from mean 3.4 at 9 a.m., to 4.0 at 1 p.m., 4.5 at 5 p.m., and 5.0 at 9 p.m. When all scores over all days were included in a mixed-model analysis of circadian variation, the differences in RDFS between times were more significant than in an analysis that included only single scores of data isolated from the first day of monitoring. RDFS is a promising measure. RDFS significantly correlated with FSS and MFIS, captured real-time daily and circadian variations in fatigue, and provided multiple measurements of fatigue that provided statistical advantages over FSS and MFIS.
Assuntos
Fadiga/diagnóstico , Fadiga/etiologia , Esclerose Múltipla/complicações , Índice de Gravidade de Doença , Adulto , Idoso , Ritmo Circadiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/instrumentação , Reprodutibilidade dos TestesRESUMO
Nephrogenic systemic fibrosis is primarily a skin disorder associated with renal insufficiency and exposure to gadolinium-containing (GAD+) contrast. We present the case of a 64-year-old man who was exposed to gadolinium while in acute renal failure, and months later developed limb stiffness, proximal weakness, and woody muscle texture. Muscle biopsy demonstrated chronic non-inflammatory fibrosing myopathy. CD34+ fibroblasts have previously been reported to be specific for nephrogenic systemic fibrosis dermopathy, and we found these in fibrotic areas of muscle and fascia. Nephrogenic systemic fibrosis is an emerging disorder, and our case highlights that it may present as a progressive myopathy with minimal skin findings.