IMPORTANCE: Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions ...and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is detrimental. OBJECTIVE: To determine whether smoking after MS diagnosis is associated with a change in time to SP disease. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients with prevalent MS who smoked at diagnosis (n = 728) taken from the Genes and Environment in Multiple Sclerosis Study, which consists of patients from the Swedish National MS Registry. The study entrance date was at time of first-year smoking. The study was conducted between November 2008 and December 2011, with patient environmental data collected from November 2009 to March 2011 via questionnaire. Study participants were from all counties in Sweden diagnosed as having MS at the time of the Genes and Environment in Multiple Sclerosis Study and registered in the Swedish National MS Registry. Patients with MS with relapsing-remitting disease course or SP were included. These patients’ conditions were diagnosed according to the McDonald criteria and the patients responded to recruitment letters with detailed questionnaires. EXPOSURE: Smoking, considered yearly after diagnosis and combined into a time-invariant covariate before diagnosis. MAIN OUTCOMES AND MEASURES: Time to SPMS, measured using an accelerated failure time model, with smoking as a time-varying covariate. Other covariates included sex, age at diagnosis, snuff use, and smoking before diagnosis. RESULTS: The optimized model illustrated that each additional year of smoking after diagnosis accelerated the time to conversion to SPMS by 4.7% (acceleration factor, 1.047; 95% CI, 1.023-1.072; P < .001). Kaplan-Meier plots demonstrated that those who continued to smoke continuously each year after diagnosis converted to SPMS faster than those who quit smoking, reaching SP disease at 48 and 56 years of age, respectively. CONCLUSIONS AND RELEVANCE: This study provides evidence that continued smoking is associated with an acceleration in time to SPMS and that those who quit fare better. Therefore, we propose that patients with MS should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating MS-related disability.
Compelling evidence indicates that Epstein Barr virus (EBV) infection is a prerequisite for multiple sclerosis (MS). The disease may arise from a complex interplay between latent EBV infection, ...genetic predisposition, and various environmental and lifestyle factors that negatively affect immune control of the infection. Evidence of gene-environment interactions and epigenetic modifications triggered by environmental factors in genetically susceptible individuals supports this view. This review gives a short introduction to EBV and host immunity and discusses evidence indicating EBV as a prerequisite for MS. The role of genetic and environmental risk factors, and their interactions, in MS pathogenesis is reviewed and put in the context of EBV infection. Finally, possible preventive measures are discussed based on the findings presented.
Objectives:
The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment ...decisions influence outcome.
Methods:
We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years). Cox regression models were applied to identify factors correlating with the outcome variable defined as time from treatment start to irreversible score 4 of the Expanded Disability Status Scale (EDSS).
Results:
Patients initiated on treatment later had a greater risk of reaching EDSS 4 (hazard ratio of 1.074 (95% confidence interval (CI), 1.048−1.101)), increased by 7.4% for every year of delay in treatment start after MS onset. Patients who started treatment after 3 years from MS onset reached the outcome sooner with hazard ratio of 2.64 (95% CI, 1.71−4.08) compared with the patients who started treatment within 1 year from MS onset. Baseline EDSS and age at onset were found to be predictive factors of disability progression.
Conclusion:
Early treatment initiation was associated with a better clinical outcome. In addition, we confirmed the well-established prognostic factors of late age at onset and early disability.
Abstract
Study Objectives
The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep ...duration and depression into consideration.
Methods
The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time of 19.2 years. Cox proportional hazards models with attained age as time-scale were used to estimate hazard ratios (HRs) of death by suicide with 95% confidence intervals (CI) for participants categorized by frequency of insomnia symptoms. Causal mediation analysis was performed to assess to what extent the relationship between insomnia and suicide risk is mediated by depression.
Results
Insomnia was only associated with suicide risk among short sleepers, whereas no significant association was observed among those who slept 7 h/night or more. The total effect of insomnia in the context of short sleep on suicide risk, expressed on the HR scale, was 2.85 (95% CI 1.42–5.74). The direct effect was 2.25 (95% CI 1.12–4.54) and the indirect effect, mediated by depression, was 1.27 (95% CI 1.05–1.53). Of the total effect, 32% was mediated by depression. The association between insomnia and suicide risk became more pronounced with decreasing depressive symptoms (p value for trend <0.05).
Conclusions
Insomnia in the context of short sleep increases suicide risk, both directly and indirectly by affecting the risk of depression. Abnormalities of sleep duration and insomnia symptoms should be evaluated when assessing suicide risk.
Abstract
Background
Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated ...protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.
Methods
Anti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets.
Results
Autoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined “seronegative” RA, associated with worse clinical outcome.
Conclusions
“Seronegative” RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2−/IgM RF− patients with a high need for active treatment.
Objective
Multiple studies have found a relationship between alcohol consumption and disease activity in rheumatoid arthritis (RA), although reverse causation has been suggested to explain the ...association. We aimed to study the relationship between alcohol consumption and disease activity, disease progression, and health‐related quality of life in patients with RA.
Methods
We followed up 1,228 patients with newly diagnosed RA from a population‐based case–control study, Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Drinkers and non‐drinkers were compared to evaluate risk of unfavorable outcomes regarding disease activity and health‐related quality of life. Odds ratios with 95% confidence intervals were calculated using logistic regression models.
Results
Non‐drinkers at baseline had higher disease activity and estimated their pain as more severe compared to drinkers. At 1 year of follow‐up, non‐drinkers reported higher swollen and tender joint counts and experienced more pain and fatigue, lower global health scores, and lower health‐related quality of life. The inverse relationship between alcohol consumption and RA‐specific outcomes was also observed when comparing drinkers and non‐drinkers who had not changed their alcohol consumption habits at or after the year of disease onset. Those who stopped drinking postbaseline experienced higher disease activity, more pain, and lower health‐related quality of life at 1 year of follow‐up, compared to drinkers, although there was no difference in disease activity at baseline between drinkers who continued versus discontinued drinking. Our findings argue against bias due to reverse causation.
Conclusion
Alcohol consumption was associated with lower disease activity and higher health‐related quality of life in RA patients in a dose‐dependent manner.
Previous studies have observed an inverse association between alcohol consumption and multiple sclerosis (MS) risk. We aimed to investigate possible interactions between alcohol consumption, ...MS-associated human leukocyte antigen (HLA) genes and smoking regarding MS risk. We used a Swedish population-based case-control study (2059 incident cases, 2887 controls) matched by age, sex, and residential area. Subjects with different genotypes and alcohol consumption habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals using logistic regression models. Interaction on the additive scale between non-drinking and both genotype and smoking were assessed by calculating the attributable proportion due to interaction (AP). There was a dose-dependent inverse association between alcohol consumption and MS risk (p for trend < 0.0001). A potentiating effect was observed between non-drinking and presence of DRB1*15:01 (AP 0.3, 95% CI 0.2-0.5) which was of similar magnitude irrespective of smoking habits. Non-drinking also interacted with smoking to increase MS risk (AP 0.2, 95% CI 0.06-0.4). Non-drinking interacts with DRB1*15:01 and smoking to increase the risk of MS. Better understanding of the mechanisms behind our findings may help to define ways to achieve protection against MS by other means than alcohol consumption.
Objective
Smoking is associated with an increased risk of rheumatoid arthritis (RA) in subsets of patients defined according to the presence or absence of anti–citrullinated protein antibodies ...(ACPAs) and rheumatoid factors (RFs). Moreover, an interaction between smoking and the HLA–DRB1 shared epitope (SE) has been demonstrated to be a risk factor for seropositive RA. The aim of this study was to investigate the interplay between smoking and the HLA–DRB1 SE with regard to risk of RA in different patient subsets based on ACPA and RF status.
Methods
Incident cases of RA (3,645 cases, 5,883 matched controls) were divided into 4 subgroups based on the presence or absence of RF and anti–cyclic citrullinated peptide 2 (anti‐CCP2) antibodies. The influence of smoking on the risk of disease was determined in each RA subgroup, using logistic regression models with calculation of odds ratios and 95% confidence intervals (95% CIs). The potential interaction between smoking and HLA–DRB1 SE genes was evaluated by calculating the attributable proportion due to interaction (AP).
Results
In the RF+/anti‐CCP2+ subset of RA patients, both smoking and the presence of the HLA–DRB1 SE conferred independent disease risks, and there was a strong interaction between the 2 risk factors (AP 0.4, 95% CI 0.3, 0.5). In the RF−/anti‐CCP2+ patient subset, the HLA–DRB1 SE conferred an increased risk of RA, whereas the independent influence of smoking was limited. However, there was a significant interaction between the HLA–DRB1 SE and smoking (AP 0.2, 95% CI 0.02, 0.5). In the RF+/anti‐CCP2− patient subset, there was an increased risk of disease among smokers, which was only marginally affected by the presence of the HLA–DRB1 SE, and no interaction between the 2 factors was observed (AP 0.002, 95% CI −0.3, 0.3). In the RF−/anti‐CCP2− patient subset, neither smoking nor the presence of the HLA–DRB1 SE conferred an increased risk of RA.
Conclusion
These findings demonstrate different effects of smoking and HLA–DRB1 in the 4 serologically defined RA subsets.
Background and purpose
The association between socioeconomic status (SES) and the risk of multiple sclerosis (MS) is unclear. The aim was to study whether a potential association between indicators ...of SES and MS risk in Sweden is explained by lifestyle/environmental factors.
Methods
Using the Swedish MS registry and the Swedish patient registries, a register study was performed comprising all cases diagnosed with MS in Sweden between 1990 and 2018 (N = 24,729) and five randomly selected controls per case, matched by year and age at disease onset, sex and residential area at disease onset. Data from two matched case–control studies combined comprising data on environment/lifestyle factors (7193 cases, 9609 controls, inclusion period 2005–2018) were also utilized. For all participants, information regarding ancestry, formal education (available 1990–2018) and family income (available 1998–2018) was retrieved from the National Board of Health and Welfare.
Results
The registry study revealed no association between education and MS risk, whereas an income exceeding the upper quartile was associated with lower MS risk compared to having an income in the lowest quartile (odds ratio 0.86, 95% confidence interval 0.82–0.90). These findings were replicated in the crude analyses of the case–control study. However, after adjustment for confounding, no association was observed between income and risk of MS.
Conclusions
Education and income were not associated with occurrence of MS after adjustment for a few lifestyle‐related factors (smoking, alcohol consumption, body mass index and sun exposure habits), indicating that SES has no influence on MS risk besides its association with these lifestyle factors in the Swedish context.
Background:
Surgical outcomes in patients with multiple sclerosis (MS) following metabolic surgery appear to be similar compared to those of the general bariatric population.
Objective:
To study the ...impact of metabolic surgery on the clinical course of MS.
Methods:
Using data from the Scandinavian Obesity Surgery Registry and the Swedish Multiple Sclerosis register, we compared disease outcomes in 122 cases of MS who had undergone metabolic surgery with those of 122 cases of MS without surgery, matched by a two-staged Propensity score match, including age at disease onset, sex, MS phenotype, body mass index, and preoperative severity of MS as measured by the Expanded Disability Status Scale.
Results:
The time to 6-month confirmed disability progression during the first five years postbaseline was shorter among the surgical patients (hazard ratio (HR) = 2.31, 95% confidence interval (CI) = 1.09–4.90; p = 0.03). No differences were observed regarding postoperative annual relapse rate (p = 0.24) or time to first postoperative relapse (p = 0.52).
Conclusion:
Although metabolic surgery appears to be a safe and efficient treatment of obesity in patients with MS, the clinical course of the disease might be negatively affected. Long-term nutritional follow-up after surgery and supplementation maintenance are crucial, particularly among those with preoperative deficits.
PDF
