Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 425
Filtrar
1.
Adv Ther ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31487006

RESUMO

INTRODUCTION: Effective communication between patients and healthcare professionals (HCPs) is important to enhance outcomes in multiple sclerosis (MS). However, in practice, patients often report a disconnect in communication. Communication tools to aid patient-HCP communication have a long history of use in many chronic conditions. For example, symptom diaries have been shown to enhance outcomes in cancer, headache and sleep disorder management. MS in the 21st Century, a Steering Group of HCP specialists and patients with MS (PwMS), has created two communication tools designed for use by both patients and their HCPs. METHODS: The Steering Group first identified prominent issues in patient-HCP communication through group discussions and survey data. Following this, a series of workshops led to the development of two communication tools as potential solutions to these identified issues in communication. RESULTS: The two most prominent issues identified were HCP time constraints during appointments and the misalignment of patient and HCP priorities-the communication tools developed through the workshops were created to address these. The "myMS priorities" tool [see supplementary materials] is designed to maximize the use of consultation time while the "myMS commitments" tool [see supplementary materials] aims to improve patient-HCP shared decision-making. CONCLUSIONS: The MS in the 21st Century Steering Group adopted a broad, iterative and collaborative approach in the development of these tools to help ensure they would be as useful as possible to both HCPs and PwMS. These tools have been developed through shared patient-HCP expertise and are based on existing tools in other therapy areas as well as a review of the existing literature and data from MS in the 21st Century Steering Group surveys. The next steps will focus on the validation of these tools through testing them in real-world environments and clinical trials. FUNDING: Merck KGaA, Darmstadt, Germany.

3.
Mult Scler Relat Disord ; 35: 19-25, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31279232

RESUMO

There is increasing evidence that agents that target peripheral B cells and in some instances plasma cells can exhibit marked effects on relapsing multiple sclerosis. In addition, B cells, including plasma cells, within the central nervous system compartment are likely to play an important role in disease progression in both relapsing and progressive MS. However, current B cell-targeting antibodies may not inhibit these, because of poor penetration into the central nervous system and often oligoclonal bands of immunoglobulin persist within the cerebrospinal fluid despite immunotherapy. Through targeting B cells and plasma cells in the CNS, it may be possible to obtain additional benefit above simple peripheral depletion of B cells. As such there are a number of inhibitors of B cell function and B cell depleting agents that have been developed for myeloma and B cell leukaemia and lymphoma, which could potentially be used off-label or as an experimental treatment for advanced (progressive) MS.

5.
Lancet Neurol ; 18(9): 845-856, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31285147

RESUMO

BACKGROUND: Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis. METHODS: We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18-58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov, number NCT01864148. FINDINGS: Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0·89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment. INTERPRETATION: Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose. FUNDING: Biogen.

7.
J Neurol ; 266(8): 1897-1906, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31053960

RESUMO

BACKGROUND: Hyposmia can develop with age and in neurodegenerative conditions, including Parkinson's disease (PD). The University of Pennsylvania Smell Identification Test (UPSIT) is a 40-item smell test widely used for assessing hyposmia. However, in a number of situations, such as identifying hyposmic individuals in large populations, shorter tests are preferable. METHODS: We assessed the ability of shorter UPSIT subsets to detect hyposmia in 891 healthy participants from the PREDICT-PD study. Shorter subsets included Versions A and B of the 4-item Pocket Smell Test (PST) and 12-item Brief Smell Identification Test (BSIT). Using a data-driven approach, we evaluated screening performances of 23,231,378 combinations of 1-7 smell items from the full UPSIT to derive "winning" subsets, and validated findings separately in another 191 healthy individuals. We then compared discriminatory UPSIT smells between PREDICT-PD participants and 40 PD patients, and assessed the performance of "winning" subsets containing discriminatory smells in PD patients. RESULTS: PST Versions A and B achieved sensitivity/specificity of 76.8%/64.9% and 86.6%/45.9%, respectively, while BSIT Versions A and B achieved 83.1%/79.5% and 96.5%/51.8%. From the data-driven analysis, 2 "winning" 7-item subsets surpassed the screening performance of 12-item BSITs (validation sensitivity/specificity of 88.2%/85.4% and 100%/53.5%), while a "winning" 4-item subset had higher sensitivity than PST-A, -B, and even BSIT-A (validation sensitivity 91.2%). Interestingly, several discriminatory smells featured within "winning" subsets, and demonstrated high-screening performances for identifying hyposmic PD patients. CONCLUSION: Using abbreviated smell tests could provide a cost-effective means of large-scale hyposmia screening, allowing more targeted UPSIT administration in general and PD-related settings.

10.
Brain ; 142(5): 1166-1167, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31032846
11.
Neurology ; 92(15): 713-719, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30894447

RESUMO

OBJECTIVE: To establish the gender distribution of multiple sclerosis (MS) researchers across high-impact neurologic publications, MS-specific journals, and the European Committee for Treatment and Research in MS (ECTRIMS). METHODS: Journal editorial boards and contents were retrieved online to assess first-named and senior authors. Published tables of contents for each journal from 2017 were reviewed. Congrex, the ECTRIMS organizers, were contacted and speaker names were obtained from online abstracts to assess visible opinion leaders. RESULTS: A total of 2,080 articles were analyzed across 4 general neurology journals, and 452 across 2 MS journals. Overall, 36% of general neurology articles had a female first name author and 25% had a female senior author. In MS-specific journals, 44% of first authors and 35% of senior authors were female, with similar proportions of unique authors. There is limited female representation on the ECTRIMS executive board, but reasonable balance on Council. Almost 50% of attendees in 2017 were female, but only 35% of invited speakers. CONCLUSIONS: There is substantial female drop-off between junior and senior research level across multiple areas. Strategies to support gender balance are urgently required, including developing mentorship schemes, ensuring gender balance in conferences, and thorough examination of the barriers facing female academics with direct challenges to address unconscious bias.

12.
Mult Scler Relat Disord ; 29: 157-167, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30885374

RESUMO

BACKGROUND: Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously. OBJECTIVE: Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets. METHODS: Data for patients treated with cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg) as monotherapy (n = 923) or placebo (n = 641) in Phase III clinical trials (CLARITY, CLARITY Extension and ORACLE-MS) and followed up in the PREMIERE registry were aggregated (Monotherapy Oral cohort). To better characterize rare events, additional data from earlier studies which involved the use of parenteral cladribine in patients with MS, and the ONWARD study, in which patients were given cladribine tablets in addition to interferon (IFN)-ß or placebo plus IFN-ß were included in an All Exposed cohort (cladribine, n = 1926; placebo, n = 802). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100 PY) were calculated for the integrated analyses. RESULTS: The incidence rate of treatment-emergent adverse events (TEAEs) in the Monotherapy Oral cohort was 103.29 vs. 94.26 Adj-AEs per 100 PY for placebo. TEAEs that occurred more frequently with cladribine tablets were mainly driven by the TEAEs of lymphopenia (Adj-AE per 100 PY 7.94 vs. 1.06 for placebo) and lymphocyte count decreased (Adj-AE per 100 PY 0.78 vs. 0.10 for placebo) as anticipated due to the mode of action of cladribine. An increase in TEAE incidence rate was also observed in the cladribine tablets 3.5 mg/kg group vs. placebo for herpes zoster (Adj-AE per 100 PY 0.83 vs. 0.20, respectively). There were no cases of systemic, serious disseminated herpes zoster attributed to treatment with cladribine tablets. In general there was no increase in the risk of infections including opportunistic infections with cladribine tablets versus placebo, except for herpes zoster. Periods of severe lymphopenia (< 0.5 × 109 cells/L) were associated with an increased frequency of infections, but the nature of these was not different to that observed in the overall patient group treated with cladribine tablets 3.5 mg/kg. Within the constraints of a limited sample size, malignancy rates in the overall clinical program for cladribine in MS did not show evidence of an increase compared to placebo-treated patients and there was no increase in the incidence of malignancies over time in cladribine-treated patients. CONCLUSION: The AE profile for cladribine tablets 3.5 mg/kg as a monotherapy has been well-characterized in a pooled population of patients from early to more advanced relapsing MS. There was no increased risk for infections in general except for a higher incidence of herpes zoster. Lymphopenia was amongst the most frequently observed TEAEs that occurred at a higher incidence with cladribine relative to placebo. There was also no increase in malignancy rates for cladribine relative to placebo.


Assuntos
Cladribina/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Sistema de Registros , Adolescente , Adulto , Idoso , Cladribina/administração & dosagem , Estudos de Coortes , Feminino , Herpes Zoster/induzido quimicamente , Humanos , Imunossupressores/administração & dosagem , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Mult Scler Relat Disord ; 29: 168-174, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30885375

RESUMO

BACKGROUND: Immune reconstitution therapies (IRT) for patients with multiple sclerosis are used for short, intermittent treatment periods to induce immune resetting and allow subsequent treatment-free periods. Cladribine tablets are postulated to be an IRT that causes selective and transient reductions in CD19+ B cells and T cells, followed by reconstitution of adaptive immune function. OBJECTIVE: To characterize long-term lymphocyte count changes in pooled data from the 2-year CLARITY and subsequent 2-year CLARITY Extension studies, and the PREMIERE registry (Long-term CLARITY cohort). METHODS: Data from patients randomized to placebo (n = 435) or cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg; n = 685) in CLARITY or CLARITY Extension, including time spent in the PREMIERE registry were pooled to provide long-term follow-up data. The study investigated absolute lymphocyte counts (ALC) up to 312 weeks and B and T cell subsets up to 240 weeks after the first dose, in patients receiving placebo or cladribine tablets 3.5 mg/kg administered as two short (4 or 5 days) weekly treatments at the start of months 1 and 2 in each treatment year, followed by no further active treatment. RESULTS: Treatment with cladribine tablets 3.5 mg/kg resulted in selective reductions in B and T lymphocytes. Lymphocyte recovery began soon after treatment in each of years 1 and 2. Median ALC recovered to the normal range and CD19+ B cells recovered to threshold values by week 84, approximately 30 weeks after the last dose of cladribine tablets in year 2. Median CD4+ T cell counts recovered to threshold values by week 96 (approximately 43 weeks after the last dose of cladribine tablets in year 2). Median CD8+ cell counts never dropped below the threshold value. CONCLUSION: These results show the dynamics of lymphocyte count changes following treatment with cladribine tablets 3.5 mg/kg. The immune cell repopulation results provide further evidence that cladribine tablets may represent a form of IRT.


Assuntos
Cladribina/farmacologia , Imunossupressores/farmacologia , Linfócitos/efeitos dos fármacos , Linfopenia/induzido quimicamente , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos , Sistema de Registros , Adolescente , Adulto , Idoso , Cladribina/administração & dosagem , Cladribina/efeitos adversos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Estudos de Coortes , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Contagem de Linfócitos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Comprimidos , Adulto Jovem
17.
Acta Neurol Scand ; 139(5): 422-427, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30657162

RESUMO

BACKGROUND: Little is known about what leads to recovery between relapses in multiple sclerosis (MS), particularly following treatment. In the past, it has been demonstrated that soluble neural cell adhesion molecule (sNCAM), a putative biomarker of neuroplasticity, increased following steroid treatment in the Cerebrospinal fluid (CSF) of MS subjects undergoing acute relapses. Taking this a step further, we have evaluated the effect of disease-modifying treatment (DMTs) on CSF sNCAM levels in various subtypes of MS. METHODS: We measured CSF sNCAM levels at baseline and after 12-24 months of DMT in 69 patients, 49 relapsing-remitting MS (RRMS), 20 progressive MS(PMS), and 24 healthy controls (HC) using an in-house ELISA. Of this, 31 patients had received natalizumab, 17 mitoxantrone, and 21 fingolimod. Changes in disability were measured using EDSS and disease severity by MSSS. In conjunction, CSF NfL levels were also measured. RESULTS: At baseline, the mean sNCAM level was 268.7 ng/mL (SD: 109 ng/mL) in MS patients compared with 340.6 ng/ml (SD: 139 ng/mL) in HC, and PMS had significantly lower sNCAM (239.2 ng/mL, SD: 123.0, P = 0.019) compared to RRMS (269.4, SD: 127.4, P = 0.043). After natalizumab and mitoxantrone treatments, we observed an increase in mean sNCAM. However, in the fingolimod-treated group, mean sNCAM decreased. There was no correlation found with EDSS or MSSS, or NfL levels as a whole. CONCLUSIONS: Cerebrospinal fluid sNCAM levels were found to be lower in MS than in HC and the lowest sNCAM levels were found in PMS. Following natalizumab and mitoxantrone treatments, we observed an elevation in sNCAM levels, an effect that was not observed following fingolimod treatment. These changes, however, did not appear to correlate with disability in the short-term or NfL levels.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Antígeno CD56/líquido cefalorraquidiano , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/dietoterapia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Cloridrato de Fingolimode/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Esclerose Múltipla/líquido cefalorraquidiano , Natalizumab/uso terapêutico
18.
Pract Neurol ; 19(2): 106-114, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612100

RESUMO

Multiple sclerosis (MS) is more common in women than men and is most commonly diagnosed in early adulthood; thus, many patients will not have completed their families at the time of diagnosis. There is increasing awareness of the importance of early treatment in preventing long-term disability in MS. Delaying treatment until women with MS have completed their families can lead to the development of irreversible disability in at least some cases. It is therefore important to discuss family planning and pregnancy proactively. However, to date there is limited evidence to inform such discussions. We set out to develop consensus guidelines for the treatment of MS in pregnancy to encourage and facilitate discussions in this important area. The guidelines draw on available evidence from drug-specific pregnancy registers and published literature and have been scored by a panel of experts from a variety of disciplines using modified Delphi criteria. They cover prepregnancy counselling, management during pregnancy, delivery and anaesthetic options, postpartum advice and specific advice regarding currently licensed disease-modifying drugs. As the complexity and range of available disease-modifying drugs increase, further data gathering via a UK-wide MS pregnancy register is recommended.


Assuntos
Esclerose Múltipla/terapia , Neurologistas/legislação & jurisprudência , Guias de Prática Clínica como Assunto , Gravidez , Feminino , Humanos , Esclerose Múltipla/complicações , Período Pós-Parto/fisiologia , Fatores Sexuais , Reino Unido
19.
Brain Behav ; 9(1): e01169, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30536750

RESUMO

Social capital (SC) is a broad term that encompasses the many resources derived from social connections. The contemporary study of SC in public health has deep roots in the related fields of sociology, economics, and politics. Its multidisciplinary nature and the varying potential ways it could affect individuals have resulted in different but overlapping models to approach SC in the health field. There are currently no standardized measures of SC, and even more challenging its impact on health outcomes seems to vary according to the level of analysis. Despite the accumulating evidence that supports a protective effect of SC on mental and physical health, and mortality, not enough attention has been paid to the potential drawbacks of SC. The role of SC in neurological disease is just beginning to be explored. Concerted efforts are needed to ensure that empirical evidence on SC could be properly translated into interventions for health-promoting purposes. In this paper, we review the current state of scientific knowledge on the subject of SC, with a focus on its application in the field of neurology.


Assuntos
Neurologia/organização & administração , Saúde Pública/economia , Capital Social , Humanos , Rede Social , Fatores Socioeconômicos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA