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1.
Rev Neurol (Paris) ; 180(3): 125-140, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37567819

RESUMO

A prodrome is an early set of symptoms, which indicates the onset of a disease; these symptoms are often non-specific. Prodromal phases are now recognized in multiple central nervous system diseases. The depth of understanding of the prodromal phase varies across diseases, being more nascent for multiple sclerosis for example, than for Parkinson disease or Alzheimer's disease. Key challenges when identifying the prodromal phase of a disease include the lack of specificity of prodromal symptoms, and consequent need for accessible and informative biomarkers. Further, heterogeneity of the prodromal phase may be influenced by age, sex, genetics and other poorly understood factors. Nonetheless, recognition that an individual is in the prodromal phase of disease offers the opportunity for earlier diagnosis and with it the opportunity for earlier intervention.


Assuntos
Doença de Alzheimer , Esclerose Lateral Amiotrófica , Esclerose Múltipla , Doença de Parkinson , Humanos , Doença de Alzheimer/diagnóstico , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Esclerose Lateral Amiotrófica/diagnóstico , Biomarcadores , Sintomas Prodrômicos
2.
Eur J Neurol ; 27(12): 2625-2629, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32810878

RESUMO

BACKGROUND AND PURPOSE: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. METHODS: We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. RESULTS: A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98-9.96] and 2.20 (95% CI 1.33-3.64), respectively. CONCLUSIONS: This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings.


Assuntos
Pseudotumor Cerebral , Adolescente , Adulto , Anticoncepcionais Orais Combinados , Anticoncepcionais Orais Hormonais/efeitos adversos , Feminino , Humanos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Pseudotumor Cerebral/induzido quimicamente , Pseudotumor Cerebral/epidemiologia , Estudos Retrospectivos , Adulto Jovem
3.
Eur J Neurol ; 26(7): 1032-1036, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30714270

RESUMO

BACKGROUND AND PURPOSE: The multiple sclerosis prodrome remains poorly understood. We aimed to examine the prodrome in people with relapsing remitting multiple sclerosis at onset (RMS) and primary progressive multiple sclerosis (PPMS). METHODS: We conducted a matched cohort study using clinical and linked health administrative data in two Canadian provinces. We identified people with RMS, PPMS and age- sex- and geographically-matched population controls, and compared the number of physician encounters (total number, per International Classification of Diseases chapter, and per physician speciality) in the five years before symptom onset. Negative binomial regression models were sex, age, socioeconomic status and calendar year adjusted. RESULTS: We identified 1887 RMS, 171 PPMS cases, and 9837 matched population controls. No difference existed in the total number of encounters in the five years before index between RMS and PPMS, or between the phenotypes and their respective controls. Compared to RMS cases, PPMS cases had more nervous system-related encounters (adjusted rate ratio, 3.00; 95% confidence interval, 1.06-8.49) and fewer encounters with dermatologists (adjusted rate ratio 0.53; 95% confidence interval, 0.30-0.96). CONCLUSION: Findings suggest that people with RMS and PPMS may both experience a prodrome, although aspects may differ.


Assuntos
Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Sintomas Prodrômicos , Adulto , Canadá , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
4.
Eur J Neurol ; 25(1): 196-199, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29058806

RESUMO

BACKGROUND AND PURPOSE: We set out to revisit and comment on the evidence surrounding a popular figure published in the New England Journal of Medicine (2002), which suggests that the incidence of immune-mediated diseases, including multiple sclerosis (MS), is increased by reduced exposure to infections. METHODS: Commentary. RESULTS: We found that, to date (May 2017), this influential article has been cited >2000 times. However, on close investigation of the figure, we noticed some problems. Specifically, we observed several challenges inherent in using ecological data from disparate studies and countries to make conclusions surrounding the temporal patterns and relationships between diseases. For example, the figure depicts incidence data for MS based solely on a limited group of individuals with MS (n = 637; 455 women and 182 men) living within the region of Sassari on the island of Sardinia, known for its unique genealogy and risk of MS. However, the infectious-related data were based primarily on large population studies from the USA, with one derived from army recruits in France. CONCLUSIONS: We encourage the scientific community to apply rigorous, consistent methods in order to confirm or refute whether a strong, direct relationship does or does not exist between the incidence of MS and infectious diseases. Further, our article highlights a major knowledge gap that would benefit from a thorough review of the temporal trends related to MS incidence. Collation of this wide body of knowledge may provide a balanced understanding of this important topic and would best serve the progress of MS research.


Assuntos
Infecções/epidemiologia , Esclerose Múltipla/epidemiologia , Adulto , Epidemias , Métodos Epidemiológicos , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Prevalência
5.
Eur J Neurol ; 23(6): 1093-100, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26992124

RESUMO

BACKGROUND AND PURPOSE: Much clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non-users of the specialty MS clinics in British Columbia, Canada. METHODS: This was a retrospective record-linkage cohort study using prospectively collected data from the British Columbia Multiple Sclerosis database and province-wide health administrative databases. RESULTS: There were 2841 incident MS cases between 1996 and 2004 including 1648 (58%) that had registered at an MS clinic ('clinic cases') and 1193 (42%) that had not ('non-clinic cases'). Gender and socioeconomic status distributions were similar; however, non-clinic cases were older, accessed health services more frequently and had a higher burden of comorbidity than clinic cases. Only 1% of the non-clinic cases had filled a prescription for an MS-specific disease-modifying therapy, compared to 51% of the clinic cases. CONCLUSIONS: Our findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic-based MS cohorts may not always be generalizable to the wider MS population; and access to population-based health administrative data offers the opportunity to gain a broader understanding of MS.


Assuntos
Esclerose Múltipla/epidemiologia , Ambulatório Hospitalar/estatística & dados numéricos , Adulto , Colúmbia Britânica/epidemiologia , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade
6.
Eur J Neurol ; 22(6): 990-1000, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25846809

RESUMO

BACKGROUND AND PURPOSE: Beta-interferons (IFNß) are the most widely prescribed drugs for patients with multiple sclerosis (MS). However, whether or not treatment with IFNß can delay secondary progressive MS (SPMS) onset remains unknown. Our aim was to examine the association between IFNß exposure and SPMS onset in patients with relapsing-remitting MS (RRMS). METHODS: A retrospective cohort study using British Columbia (Canada) population-based clinical and health administrative data (1985-2008) was conducted. RRMS patients treated with IFNß (n = 794) were compared with untreated contemporary (n = 933) and historical (n = 837) controls. Cohort entry was the first clinic visit during which patients became eligible for IFNß treatment (baseline). The outcome was time from baseline to SPMS onset. Cox regression models with IFNß as a time-dependent exposure were adjusted for sex, and baseline age, disease duration, disability, *socioeconomic status and *comorbidities (*available for the contemporary cohorts only). Additional analyses included propensity score adjustment. RESULTS: The median follow-up for the IFNß-treated, untreated contemporary and historical controls were 5.7, 3.7 and 7.3 years, and the proportions of patients reaching SPMS were 9.2%, 11.8% and 32.9%, respectively. After adjustment for confounders, IFNß exposure was not associated with the risk of reaching SPMS when either the contemporary or the historical untreated cohorts were considered (hazard ratio 1.07; 95% confidence interval 0.93-1.48, and hazard ratio 1.04; 95% confidence interval 0.74-1.46, respectively). Further adjustments and the propensity score yielded results consistent with the main analysis. CONCLUSIONS: Amongst patients with RRMS, use of IFNß was not associated with a delayed onset of SPMS.


Assuntos
Interferon beta/farmacologia , Esclerose Múltipla Crônica Progressiva/prevenção & controle , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Colúmbia Britânica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
7.
Mult Scler ; 20(9): 1260-4, 2014 08.
Artigo em Inglês | MEDLINE | ID: mdl-24500603

RESUMO

We linked several population-based clinical and health administrative databases in British Columbia, Canada. We identified and compared birth outcomes of pregnancies fathered by men with multiple sclerosis (MS) (n=202) and men from a frequency-matched general population cohort (n=981) between 1996 and 2010. Using multivariate models, we analyzed the association of paternal MS, disease duration at conception and disability (as measured by the Expanded Disability Status Scale) with birth weight and gestational age. Paternal MS and MS-related clinical factors were not significantly associated with birth outcomes (p>0.05). This study provides assurance to expecting fathers with MS and their families.


Assuntos
Pai , Esclerose Múltipla/epidemiologia , Resultado da Gravidez , Peso ao Nascer , Colúmbia Britânica/epidemiologia , Bases de Dados Factuais , Avaliação da Deficiência , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Esclerose Múltipla/diagnóstico , Análise Multivariada , Gravidez , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo
8.
Eur J Neurol ; 21(6): 835-44, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24351059

RESUMO

BACKGROUND AND PURPOSE: It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing-remitting multiple sclerosis (RRMS) patients in an observational study from Canada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. METHODS: RRMS patients treated with interferon beta (n = 868) and two cohorts of untreated patients (829 contemporary and 959 historical controls) were included. The main outcome was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained Expanded Disability Status Scale (EDSS) score 6 using a multivariable Cox model, with treatment as a time-varying predictor, testing interaction effects for five pre-specified baseline characteristics: sex, age, disease duration, EDSS and annualized relapse rate (ARR) based on the previous 2 years. RESULTS: Significant heterogeneity was found in the association of interferon beta exposure and disability progression only across ARR, and only when treated patients were compared with historical controls (P = 0.005 at a Bonferroni-adjusted alpha of 0.01). For patients with ARR>1, treatment-exposed time was associated with a hazard ratio of 0.38 (95%CI 0.20-0.75) for disability progression compared with the unexposed time. CONCLUSIONS: RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long-term disability progression.


Assuntos
Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Estudos Retrospectivos
9.
Mult Scler ; 19(9): 1182-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23386429

RESUMO

BACKGROUND: Fatigue and pelvic organ dysfunction are common among women with multiple sclerosis (MS), which may prolong labor and increase the risk of labor induction and/or augmentation. OBJECTIVE: We set out to investigate the association between MS and related clinical factors (disease duration and the Expanded Disability Status Scale, EDSS) with labor induction/augmentation. METHODS: Data from the British Columbia (BC) MS database were linked with the BC Perinatal Database Registry. Multivariable models were used to compare the likelihood of labor induction and augmentation between attempted vaginal deliveries (1998-2009) in women with MS (n=381) and the general population (n=2615). RESULTS: In the MS cohort, 94/381 deliveries (25%) required labor induction and 147/381 deliveries (39%) required labor augmentation. Having MS was not associated with labor induction (adjusted odds ratio (OR)=0.91; 95% confidence interval (CI)=0.68-1.22, p=0.54) or augmentation (adjusted OR=0.91; 95% CI=0.72-1.15, p=0.43), but was associated with multiple methods of labor induction (OR=1.94; 95% CI=1.23-3.06, p=0.004). A higher EDSS score was associated with an increased risk of labor induction (adjusted p=0.04), but not labor augmentation (adjusted p > 0.5). Disease duration was not associated with either outcome (adjusted p > 0.2). CONCLUSIONS: Greater intervention may be required to initiate labor for women with a higher degree of disability due to MS.


Assuntos
Trabalho de Parto Induzido/estatística & dados numéricos , Esclerose Múltipla/complicações , Complicações na Gravidez , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem
10.
J Neurol Neurosurg Psychiatry ; 83(1): 61-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21865212

RESUMO

OBJECTIVE: To examine mortality and factors associated with survival in a population based multiple sclerosis (MS) cohort. METHODS: Clinical and demographic data of MS patients registered with the British Columbia MS clinics (1980-2004) were linked to provincial death data, and patients were followed until death, emigration or study end (31 December 2007). Absolute survival and the influence of patient characteristics (sex, disease course (primary progressive (PPMS) vs relapsing onset (R-MS)) and onset age) were estimated by Kaplan-Meier analyses (from birth and disease onset). Mortality relative to the general population was examined using standardised mortality ratios. Excess mortality associated with patient characteristics and time period of cohort entry was assessed by relative survival modelling. RESULTS: Of 6917 patients, 1025 died. Median survival age was 78.6 years (95% CI 77.5 to 79.7) for women and 74.3 years (95% CI 73.1 to 75.4) for men. Survival from onset was longer for R-MS (49.7 years; 95% CI 47.9 to 51.5) than for PPMS (32.5 years; 95% CI 29.5 to 35.7); however, survival age was similar. The overall standardised mortality ratios was 2.89 (95% CI 2.71 to 3.07), and patients survived approximately 6 years less than expected, relative to the general population. PPMS had a higher relative mortality risk compared with R-MS (relative mortality ratio (RMR) 1.52; 95% CI 1.30 to 1.80). Women with PPMS had a relative survival disadvantage compared with men with PPMS (RMR 1.55; 95% CI 1.19 to 2.01). Relative survival within 10 years of cohort entry was similar between time periods. CONCLUSIONS: Some of the longest MS survival times are reported here but the risk of death was still greater than in the age, sex and calendar year matched general population. No evidence of increased survival over time was found when improved survival in the general population was taken into consideration.


Assuntos
Esclerose Múltipla/mortalidade , Adulto , Idade de Início , Idoso , Colúmbia Britânica/epidemiologia , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/mortalidade , Esclerose Múltipla Recidivante-Remitente/mortalidade , Modelos de Riscos Proporcionais , Fatores Sexuais , Análise de Sobrevida , Adulto Jovem
11.
Mult Scler ; 18(4): 460-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21914689

RESUMO

BACKGROUND: The incidence of disease-modifying drug (DMD) exposure during pregnancy in multiple sclerosis (MS) is unknown and limited data exists regarding the potential harm of DMD exposure during pregnancy. OBJECTIVE: To investigate the incidence and effect of in utero DMD exposure on perinatal outcomes. METHODS: We conducted a retrospective analysis by linking two provincial, population-based databases, the British Columbia (BC) MS database with the BC Perinatal Database Registry. Delivery (duration of the second stage of labor, assisted vaginal delivery and Cesarean section) and neonatal (birth weight, gestational age, 5-minute Apgar score and congenital anomalies) outcomes were compared between women exposed and unexposed to a DMD within 1 month prior to conception and/or during pregnancy. Findings were reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In all, 311 women with relapsing-remitting MS delivered 418 singleton babies between April 1998 and March 2009. 21/101 (21%) of births to MS women treated with DMD prior to pregnancy were exposed to a DMD. In all cases, exposure was documented as unintentional and DMD treatment was stopped within 2 months of gestation. The overall incidence of exposure was 21/418 (5%). DMD exposure was associated with a trend towards a greater risk of assisted vaginal delivery compared to the DMD naïve groups (OR = 3.0; 95% CI: 1.0-9.2). All other comparisons of perinatal outcomes were unremarkable. CONCLUSION: The incidence of DMD exposure was relatively low and no cases were intentional. Further studies are needed to ascertain the safety of DMD exposure during pregnancy in MS.


Assuntos
Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Peptídeos/uso terapêutico , Cesárea , Parto Obstétrico , Feminino , Acetato de Glatiramer , Humanos , Interferon beta/efeitos adversos , Peptídeos/efeitos adversos , Gravidez , Complicações na Gravidez/induzido quimicamente , Resultado da Gravidez , Estudos Retrospectivos , Fatores de Risco
12.
Mult Scler ; 17(3): 361-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21148660

RESUMO

BACKGROUND: Post-marketing studies and case reports have linked beta-interferon (IFNß) treatment with liver enzyme abnormalities and liver injuries in patients with multiple sclerosis (MS). Few predictors of risk exist. OBJECTIVE: We investigated the effect of IFNß and other patient characteristics on levels of the liver enzyme, alanine aminotransferase (ALT). METHOD: Repeated ALT test results were reviewed retrospectively for 1064 MS patients prescribed an IFNß as their first immunomodulatory drug. Liver enzyme abnormality was defined as an ALT elevation twice the upper limit of normal (≥ 2 ULN). The Generalized Estimating Equation (GEE) was used to analyze the effect of age (≤ 35, >35-40, >40-45, >45 years), gender, disease duration, IFNß product, and duration of treatment (≤ 5, >5-15, >15-40, >40 months) on de novo liver enzyme abnormality. RESULTS: Over a mean treatment period of 38.7 months (SD=34.9), 12.4% (95/766) of MS patients developed de novo liver enzyme abnormality. Multivariable GEE results showed a dose frequency response effect of IFNßs on liver enzyme abnormality: OR=3.8(95% CI: 1.6-9.2) for IFNß-1a 44 µg SC, and OR=3.4 (95% CI: 1.5-7.9) for IFNß-1b 250 µg SC compared with the lower frequency IFNß-1a 30 µg IM. Younger age (≤ 40 years), male gender, and ≤ 15 months of IFNß exposure were also independent predictors. CONCLUSION: A dose frequency response effect was observed, with high-frequency IFNßs having the greatest risk. The first 15 months of treatment, men, and younger patients were also associated with elevated risk. Regular ALT monitoring in MS patients appears prudent; long-term consequences of ALT elevations should be further investigated.


Assuntos
Alanina Transaminase/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fatores Imunológicos/efeitos adversos , Interferon beta/efeitos adversos , Testes de Função Hepática , Fígado/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Adulto , Fatores Etários , Análise de Variância , Biomarcadores/sangue , Colúmbia Britânica , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Distribuição de Qui-Quadrado , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Fígado/enzimologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Regulação para Cima
13.
Mult Scler ; 16(6): 694-700, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20378663

RESUMO

The pathophysiology of primary progressive (PP) multiple sclerosis (MS) involves diffuse axonal degeneration which is believed to start early in the disease process, even before the onset of clinical symptoms. Symptomatic onset then occurs when this process reaches a threshold after which the axonal loss can no longer be compensated. A preliminary study showed that patients with familial PPMS had an earlier clinical onset than patients with sporadic disease, suggesting a hereditary component to the disease process of PPMS. In this study, we combined data from two large, population-based, longitudinal MS databases to investigate disease onset in familial and sporadic PPMS. We examined 411 patients with PPMS. There were no differences in gender distribution or onset symptoms between familial and sporadic PPMS. Patients with familial PPMS were significantly younger at disease onset (n = 84, median age: 37.6 years) than patients with sporadic disease (n = 327, median age: 42.7, p = 0.007). This difference was due to a greater proportion of familial cases with a disease onset before the age of 30 and a smaller proportion with disease onset between 40 and 50 years of age (p = 0.002). Gender had no significant effect on the age at disease onset. Further analyses showed that these findings were unlikely to be due to ascertainment bias towards an earlier diagnosis in familial cases. Our findings suggest a hereditary component to the disease process of PPMS. It would be worthwhile to identify patients with familial PPMS for future research on disease modifying genes in MS.


Assuntos
Esclerose Múltipla Crônica Progressiva/epidemiologia , Idade de Início , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Esclerose Múltipla Crônica Progressiva/genética , Fatores de Risco , Fatores Sexuais , Estatísticas não Paramétricas
15.
J Neurol Neurosurg Psychiatry ; 79(12): 1368-74, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18535026

RESUMO

OBJECTIVES: To examine the relative relapse-rate patterns over time in a relapsing multiple sclerosis (MS) cohort and to investigate potential predictors of relapse rates and periods of low-relapse activity. METHODS: This retrospective cohort study followed 2477 relapsing-remitting (RR) MS patients from onset to 1 July 2003. Annualised relapse rates were examined according to sex, age at onset, the patient's current age and disease duration. The relationship between relapse rates and baseline characteristics (sex, onset age and onset symptoms) were examined using Poisson regression. Time to the first 5 years relapse-free was examined using Kaplan-Meier survival analysis. RESULTS: The mean follow-up time (from onset of MS symptoms) was 20.6 years, during which time 11,722 post-onset relapses were recorded. The relapse rate decreased by 17% every 5 years (between years 5 to 30 post-onset), but this decline increased in magnitude with increasing onset age. Women and those with onset sensory symptoms exhibited a higher relapse rate (p< or =0.001). More than three-quarters of patients (1692/2189) experienced a 5-year relapse-free period during the RR phase. CONCLUSION: Relapse rates were age- and time-dependent. Our observations have clinical implications: 1) any drug able to modify relapse rates has the greatest potential for a population impact in patients <40 years old and within the first few demi-decades of disease; 2) continuation of drug beyond these times may be of limited value; 3) long-term follow-up studies must consider that relapse rates probably decline at different rates over time according to the patient's onset age; 4) a relapse-quiescent period in MS is not uncommon.


Assuntos
Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/terapia , Adulto , Fatores Etários , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
17.
Mult Scler Relat Disord ; 4(5): 470-476, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26346797

RESUMO

BACKGROUND: Comorbidities are common in multiple sclerosis (MS). The high prevalence of pain in MS is well-established but the influence of comorbidities on pain, specifically, pain-related interference in activity is not. OBJECTIVE: To examine the relationship between comorbidity and pain in MS. METHODS: We recruited 949 consecutive patients with definite MS from four Canadian centres. Participants completed the Health Utilities Index (HUI-Mark III) and a validated comorbidity questionnaire at 3 visits over 2 years. The HUI's pain scale was dichotomized into two groups: those with/without pain that disrupts normal activities. We used logistic regression to assess the association of pain with each comorbidity individually at baseline and over time. RESULTS: The incidence of disruptive pain over two years was 31.1 per 100 persons. Fibromyalgia, rheumatoid arthritis, irritable bowel syndrome, migraine, chronic lung disease, depression, anxiety, hypertension, and hypercholesterolemia were associated with disruptive pain (p<0.006). Individual-level effects on the presence of worsening pain were seen for chronic obstructive pulmonary disease (odds ratio [OR]: 1.50 95% CI: 1.08-2.09), anxiety (OR: 1.49 95% CI: 1.07-2.08), and autoimmune thyroid disease (OR: 1.40 95% CI: 1.00-1.97). CONCLUSION: Comorbidity is associated with pain in persons with MS. Closer examination of these associations may provide guidance for better management of this disabling symptom in MS.


Assuntos
Atividade Motora , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/fisiopatologia , Dor/epidemiologia , Canadá/epidemiologia , Comorbidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Esclerose Múltipla/complicações , Dor/complicações , Dor/fisiopatologia , Medição da Dor , Prevalência , Autorrelato , Índice de Gravidade de Doença , Inquéritos e Questionários
18.
QJM ; 95(11): 753-6, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12391388

RESUMO

BACKGROUND: Th1/Th2 imbalance is hypothesized to up-regulate some diseases and down-regulate others. Compared to controls, multiple sclerosis (MS) (Th1-mediated) has been linked to a reduced risk of allergy and asthma (Th2-mediated), based on patient questionnaire studies and a review of asthma medication. AIM: To investigate whether MS is associated with a reduced risk of Th2-associated diseases and an increased risk of Th1-associated diseases. DESIGN: Retrospective matched case-control study. METHODS: Three hundred and twenty MS patients and controls matched for age, gender, location and smoking were selected from the Welsh General Practice Morbidity Database from 1995-99. Case and control records were assessed for Th1-mediated and Th2-mediated diseases. RESULTS: Overall, 346 MS patients were identified, giving a prevalence of 127 per 100 000. There was an inverse relationship between multiple sclerosis (MS) and asthma (OR 0.33; 95%CI 0.15-0.77). No statistically significant relationships emerged between other Th2-associated (eczema, dermatitis) or any Th1-associated (rheumatoid arthritis, thyroid disorders, inflammatory bowel disease [IBD], type 1 diabetes) diseases and MS, although no patient in either group had treated type 1 diabetes. A trend existed for IBD, with 5/320 of cases affected and no controls; OR infinity; 95%CI 1.30-infinity; p=0.063. DISCUSSION: This inverse association between MS and asthma is compatible with a Th1/Th2 imbalance. Although the Th1/Th2 theory is probably an over-simplification in MS, a shift from Th1 cytokine dominance towards Th2 may provide drug-targeting routes for MS.


Assuntos
Asma/epidemiologia , Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Asma/complicações , Asma/imunologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/epidemiologia , Eczema/epidemiologia , Medicina de Família e Comunidade , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/imunologia , Estudos Retrospectivos , Fatores de Risco , País de Gales/epidemiologia
19.
Chronic Dis Inj Can ; 34(2-3): 145-53, 2014 Jul.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-24991777

RESUMO

INTRODUCTION: As the population ages and the prevalence of comorbid conditions increases, the need for feasible, validated methods of comorbidity surveillance in chronic diseases such as multiple sclerosis (MS) increases. METHODS: Using kappa (k) statistics, we evaluated the performance of administrative case definitions for comorbidities commonly observed in MS by comparing agreement between Manitoba (MB) administrative data and self-report (n = 606) and Nova Scotia (NS) administrative data and self-report (n = 1923). RESULTS: Agreement between the administrative definitions and self-report was substantial for hypertension (k = 0.69 [NS], 0.76 [MB]) and diabetes (k = 0.70 [NS], 0.66 [MB]); moderate for hyperlipidemia (k = 0.53 [NS], 0.51 [MB]) and heart disease (k = 0.42 [NS], 0.51 [MB]) and fair for anxiety (k = 0.27 [NS], 0.26 [MB]). In NS, agreement was substantial for inflammatory bowel disease (k = 0.71) and moderate for epilepsy (k = 0.48). CONCLUSION: Administrative definitions for commonly observed comorbidities in MS performed well in 2 distinct jurisdictions. This suggests that they could be used more broadly across Canada and in national studies.


TITRE: Performance des définitions administratives de cas pour les affections concomitantes de la sclérose en plaques au Manitoba et en Nouvelle-Écosse. INTRODUCTION: Au fur et à mesure du vieillissement de la population et de l'augmentation de la prévalence d'affections concomitantes, le recours à des méthodes fiables et efficaces de surveillance des affections concomitantes de maladies chroniques telles que la sclérose en plaques (SP) s'avère de plus en plus nécessaire. MÉTHODOLOGIE: Nous avons évalué, au moyen de la statistique kappa (k), la performance des définitions administratives de cas pour les affections concomitantes fréquemment observées en lien avec la SP en comparant les concordances entre les données administratives et les données provenant d'autodéclarations au Manitoba (MB) (n = 606) et en Nouvelle-Écosse (NS) (n = 1 923). RÉSULTATS: Les concordances entre les définitions administratives et les autodéclarations étaient bonnes pour l'hypertension (k = 0,69 [NS] et 0,76 [MB]) et le diabète (k = 0,70 [NS] et 0,66 [MB]), modérées pour l'hyperlipidémie (k = 0,53 [NS] et 0,51 [MB]) et la cardiopathie (k = 0,42 [NS] et 0,51 [MB]) et médiocres pour l'anxiété (k = 0,27 [NS] et 0,26 [MB]). La concordance était bonne en Nouvelle-Écosse pour la maladie inflammatoire chronique de l'intestin (k = 0,71) et modérée pour l'épilepsie (k = 0,48). CONCLUSION: Les définitions administratives étaient performantes dans les deux provinces pour plusieurs affections concomitantes fréquemment observées en lien avec la SP. À la lumière de ces résultats, il semble que ces définitions puissent être utilisées plus largement au Canada et dans les études nationales.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Epilepsia/epidemiologia , Cardiopatias/epidemiologia , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Esclerose Múltipla/epidemiologia , Adulto , Ansiedade/diagnóstico , Comorbidade , Bases de Dados Factuais , Depressão/diagnóstico , Diabetes Mellitus/diagnóstico , Epilepsia/diagnóstico , Feminino , Cardiopatias/diagnóstico , Humanos , Hiperlipidemias/diagnóstico , Hipertensão/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Classificação Internacional de Doenças , Masculino , Manitoba/epidemiologia , Pessoa de Meia-Idade , Nova Escócia/epidemiologia , Autorrelato
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