Organic solvents and Multiple Sclerosis: the doubled risk dilemma.

BACKGROUND: Compensation for industrial disease in the UK may be obtained in two ways. A State scheme includes a list of accepted associations between occupations and diseases with evidence of a causative association. Epidemiological evidence of a doubled risk in the occupation concerned is usually required. This takes no account of variation of exposures within occupations, excluding many occupations where risk is less than doubled. In such cases, compensation for a perceived industrial illness may be obtained in Civil Courts, where excessive exposures can be considered. AIMS: To show that in the Civil Courts evidence of excessive exposure may lead to compensation for diseases which are not yet compensable as Industrial Injuries in the UK and to draw attention to the association of multiple sclerosis (MS) with solvent exposure. METHODS: We report the case of an industrial spray painter, who claimed his MS had been caused by high-level exposure to organic solvents, and our examination of the epidemiological evidence submitted. RESULTS: The painter received compensation by an out-of-court settlement, despite the overall epidemiological risk in relation to solvent exposure having been shown to be less than doubled. The evidence hinged on individual risk in relation to high exposure, genetic susceptibility and demonstration of a plausible mechanism. CONCLUSIONS: High organic solvent exposure may lead to the development of MS. Those giving evidence in Court need to be able to discuss the epidemiological and toxicological issues in relation to exposure in the individual case.

Widespread non-joint pain in early rheumatoid arthritis.

Objective: The aim of the study was to assess the development of widespread non-joint pain (WNP) in a cohort of patients with early rheumatoid arthritis (RA), the associated health-related quality of life (HRQoL), and clinical and demographic risk factors for WNP.Method: Incident cases with RA, from the Swedish population-based study Epidemiological Investigation of Rheumatoid Arthritis (EIRA), with a follow-up of at least 3 years, constituted the study population. WNP was defined as pain outside the joints in all four body quadrants and was assessed at the 3 year follow-up. Patients who reported WNP were compared to patients without WNP regarding HRQoL, measured by the Short Form-36, at 3 years, and clinical and demographic characteristics at the time of RA diagnosis.Results: A total of 749 patients constituted the study sample, of whom 25 were excluded after reporting already having severe pain before RA diagnosis. At the 3 year follow-up, 8% of the patients reported having WNP as well as statistically significant worse HRQoL. At the time of RA diagnosis, the patients with WNP had worse pain and pain-related features, while no difference was seen in the inflammatory parameters.Conclusion: WNP occurs in a substantial subset of patients with RA, also early in the course of the disease, and the HRQoL for these patients is significantly reduced. Patients who develop WNP at 3 years are already distinguishable at the time of diagnosis by displaying more pronounced pain ratings together with an average level of inflammatory disease activity.

Social stressors and risk of rheumatoid arthritis and their relationship to known modifiable risk factors: results from the Swedish EIRA study.

Objectives: To investigate whether low social support or low decision latitude at work correlate with risk of rheumatoid arthritis (RA), and whether and how those factors are associated with known modifiable risk factors for RA.Method: The Swedish population-based EIRA study included, from 1996 to 2015, 3724 incident RA cases and 5935 controls, matched for age, gender, and residential area. Participants filled in detailed questionnaires at diagnosis. Using logistic regression, we investigated whether low social support and low decision latitude at work were associated with RA risk, and whether and how these exposures are associated with known modifiable risk factors for RA.Results: Low decision latitude at work was associated with RA risk in unadjusted analyses [odd ratio (OR) = 1.52, 95% confidence interval (CI) = 1.20-1.94], but this association was weakened after adjustment for known RA risk factors (adjusted OR = 1.24, 95% CI = 0.93-1.63). Low social support was not associated with RA risk (unadjusted OR = 1.05, 95% CI = 0.95-1.15). Cases reporting low decision latitude were more often smokers (OR = 2.05, 95% CI = 1.33-3.16), without university degrees (OR = 8.23, 95% CI = 5.13-13.22), and more often female (OR = 2.52, 95% CI = 1.66-3.81), with a similar pattern among controls. Cases reporting low social support were more often men (OR = 1.60, 95% CI = 1.40-1.83), smokers (OR = 1.46, 95% CI = 1.26-1.70), obese (OR = 1.29, 95% CI = 1.09-1.54), physically inactive (OR = 2.78, 95% CI = 1.98-3.90), and without university degrees (OR = 2.04, 95% CI = 1.77-2.36), with a similar pattern among controls.Conclusion: Low decision latitude coexisted with several known environmental/social risk factors for RA, together defining groups of individuals at increased risk of RA. These risk factors should be viewed in context when testing actions to diminish RA risk in prospective studies.

Season of birth is associated with multiple sclerosis and disease severity.

BACKGROUND: The latitude gradient in multiple sclerosis incidence indicates that low sun exposure and therefore vitamin D deficiency is associated with multiple sclerosis risk. OBJECTIVE: Investigation of the effect of month of birth, which influences postnatal vitamin D levels, on multiple sclerosis risk and severity in Sweden. METHODS: Patients and population-based controls were included from three nationwide cohorts. Differences in month of birth between cases and controls were analyzed using logistic regression and examined for effect modification by calendar year and geographic region at birth. RESULTS: Males had a reduced risk of multiple sclerosis if born in the winter and increased risk if born in the early fall. Individuals born before 1960 had an increased risk if born in summer or fall. Being born in late summer and early fall was associated with more severe disease. CONCLUSIONS: We identified a birth cohort effect on the association between the month of birth and multiple sclerosis, with a more significant effects for births before 1960. This coincides with a period of lower breastfeeding rates, recommended intake of vitamin D, and sun exposure, resulting in a lower vitamin D exposure during the fall/winter season for infants born in the summer.

Cotinine as a measure of smoking in observational studies of multiple sclerosis.

Studies using cotinine levels to define smokers have generally failed to detect an association between smoking and multiple sclerosis (MS). Using a Swedish population-based case-control study, we show that associations in relation to MS risk and progression differ considerably depending on how smoking is measured. The risk of conversion into secondary progressive disease was increased among smokers when self-reported smoking history, but not presumed cotinine levels, was used to define smokers. Defining smoking by cotinine levels without distinguishing between different sources of nicotine may lead to severely biased estimates of the association between smoking and both MS risk and progression.

Stressful life events are associated with the risk of multiple sclerosis.

BACKGROUND AND PURPOSE: Unexpected stressful life events may alter immune function and affect susceptibility to autoimmune diseases including multiple sclerosis (MS). Current results from epidemiological investigations examining the role of stress in MS remain inconsistent. The aim was to conduct the hitherto largest population-based case-control study on this topic. METHODS: Extensive questionnaire information collected on lifestyle environmental factors available for 2930 incident MS cases and 6170 controls were used to assess the association of 10 major life events that had occurred before disease onset with the risk of MS by unconditional logistic regressions, adjusting for potential confounders. Stratified analyses were also performed by sex and time. RESULTS: Compelling evidence was found for a link between major life events and risk of MS - most events significantly increased disease risk by 17%-30%. It was further observed that women were affected to a greater extent than men under certain stressful scenarios, and that most events that happened recently (≤5 years prior to MS onset) had significant effects on MS, indicating a critical window in disease development. CONCLUSION: Stressful life events may have an adverse effect on the risk of MS. Research into the mechanisms of this observation may give important clues to triggering pathogenetic events in MS.

Breastfeeding is associated with reduced risk of multiple sclerosis in males, predominantly among HLA-DRB1*15:01 carriers.

BACKGROUND: Breastfeeding as an infant appears protective against later development of some autoimmune diseases, but research into its influence on multiple sclerosis (MS) risk has yielded inconclusive results. OBJECTIVE: We investigated the possible impact of breastfeeding on MS risk. METHODS: We used two population-based case-control studies comprising 3670 cases and 6737 matched controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between MS and exposure to prolonged breastfeeding (4 months or longer) versus reduced breastfeeding (less than 4 months). A meta-analysis of case-control studies that assessed the impact of breastfeeding on MS risk among women and men was conducted. RESULTS: Prolonged breastfeeding was associated with reduced MS risk among men (OR 0.7, 95% CI 0.5-0.9) but not among women (OR 0.9, 95% CI 0.8-1.1). Among men, a synergistic effect was observed between HLA-DRB1*15:01 carrier status and reduced breastfeeding. CONCLUSIONS: Findings from the current study add to accumulating evidence that breastfeeding may be a modifiable protective factor for reducing the risk of MS in offspring. When possible, mothers should be supported to breastfeed their infants; however, the mechanism of a sex-specific biologic effect of breastfeeding on MS risk is unclear.

The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis.

The current review uses rheumatoid arthritis (RA) as a prominent example for how studies on the interplay between environmental and genetic factors in defined subsets of a disease can be used to formulate aetiological hypotheses that subsequently can be tested for causality using molecular and functional studies. Major discussed findings are that exposures to airways from many different noxious agents including cigarette smoke, silica dust and more interact with major susceptibility genes, mainly HLA-DR genetic variants in triggering antigen-specific immune reactions specific for RA. We also discuss how several other environmental and lifestyle factors, including microbial, neural and metabolic factors, can influence risk for RA in ways that are different in different subsets of RA.The description of these processes in RA provides the best example so far in any immune-mediated disease of how triggering of immunity at one anatomical site in the context of known environmental and genetic factors subsequently can lead to symptoms that precede the classical inflammatory disease symptoms and later contribute also to the classical RA joint inflammation. The findings referred to in the review have led to a change of paradigms for very early therapy and prevention of RA and to efforts towards what we have named 'personalized prevention'. We believe that the progress described here for RA will be of relevance for research and practice also in other immune-mediated diseases.

Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study.

AIM: Coffee consumption is inversely related to risk of type 2 diabetes (T2D). In contrast, an increased risk of latent autoimmune diabetes in adults (LADA) has been reported in heavy coffee consumers, primarily in a subgroup with stronger autoimmune characteristics. Our study aimed to investigate whether coffee consumption interacts with HLA genotypes in relation to risk of LADA. METHODS: This population-based study comprised incident cases of LADA (n=484) and T2D (n=1609), and also 885 healthy controls. Information on coffee consumption was collected by food frequency questionnaire. Odds ratios (ORs) with 95% CIs of diabetes were calculated and adjusted for age, gender, BMI, education level, smoking and alcohol intake. Potential interactions between coffee consumption and high-risk HLA genotypes were calculated by attributable proportion (AP) due to interaction. RESULTS: Coffee intake was positively associated with LADA in carriers of high-risk HLA genotypes (OR: 1.14 per cup/day, 95% CI: 1.02-1.28), whereas no association was observed in non-carriers (OR: 1.04, 95% CI: 0.93-1.17). Subjects with both heavy coffee consumption (≥4 cups/day) and high-risk HLA genotypes had an OR of 5.74 (95% CI: 3.34-9.88) with an estimated AP of 0.36 (95% CI: 0.01-0.71; P=0.04370). CONCLUSION: Our findings suggest that coffee consumption interacts with HLA to promote LADA.

Increased cardiovascular mortality in people with schizophrenia: a 24-year national register study.

AimsPeople who have schizophrenia die earlier from somatic diseases than do people in the general population, but information about cardiovascular deaths in people who have schizophrenia is limited. We analysed mortality in all age groups of people with schizophrenia by specific cardiovascular diseases (CVDs), focusing on five CVD diagnoses: coronary heart disease, acute myocardial infarction, cerebrovascular disease, heart failure and cardiac arrhythmias. We also compared hospital admissions for CVDs in people who had schizophrenia with hospital admissions for CVDs in the general population. METHODS: This national register study of 10 631 817 people in Sweden included 46 911 people who were admitted to the hospital for schizophrenia between 1 January 1987 and 31 December 2010. Information from national registers was used to identify people who had schizophrenia and obtain data about mortality, causes of death, medical diagnoses and hospitalisations. RESULTS: CVDs were the leading cause of death in people who had schizophrenia (5245 deaths), and CVDs caused more excess deaths than suicide. The mean age of CVD death was 10 years lower for people who had schizophrenia (70.5 years) than the general population (80.7 years). The mortality rate ratio (MRR) for CVDs in all people who had schizophrenia was 2.80 (95% confidence interval (CI) 2.73-2.88). In people aged 15-59 years who had schizophrenia, the MRR for CVDs was 6.16 (95% CI 5.79-6.54). In all people who had schizophrenia, the MRR for coronary heart disease was 2.83 (95% CI 2.73-2.94); acute myocardial infarction, 2.62 (95% CI 2.49-2.75); cerebrovascular disease, 2.4 (95% CI 2.25-2.55); heart failure, 3.25 (95% CI 2.94-3.6); and cardiac arrhythmias, 2.06 (95% CI 1.75-2.43). Hospital admissions for coronary heart disease were less frequent in people who had schizophrenia than in the general population (admission rate ratio, 0.88 (95% CI 0.83-0.94). In all age groups, survival after hospital admission for CVD was lower in people who had schizophrenia than in the general population. CONCLUSIONS: People who had schizophrenia died 10 years earlier from CVDs than did people in the general population. For all five CVD diagnoses, mortality risk was higher for those with schizophrenia than those in the general population. Survival after hospitalisation for CVDs in people who had schizophrenia was comparable with that of people in the general population who were several decades older.

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA).

BACKGROUND: A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. METHODS: Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n=378] and T2D (GADA-negative, n=1199), and their matched controls (n=1484). First-degree relatives with disease onset at age<40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. RESULTS: Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-T1D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P=0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P=0.0576). CONCLUSION: The risk of LADA is substantially increased with FHD-T1D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-T1D had more T1D-like features, emphasizing the heterogeneity of LADA.

Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data.

BACKGROUND: Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. METHOD: We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. RESULTS: We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). CONCLUSIONS: Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

VAV1 regulates experimental autoimmune arthritis and is associated with anti-CCP negative rheumatoid arthritis.

Rheumatoid arthritis (RA) patients can be stratified into two subgroups defined by the presence or absence of antibodies against citrullinated circular peptides (anti-CCP) with most of the genetic association found in anti-CCP positive RA. Here we addressed the role of VAV1, previously associated to multiple sclerosis (MS), in the pathogenesis of RA in experimental models and in a genetic association study. Experimental arthritis triggered by pristane or collagen type II was induced in DA rats and in the DA.BN-R25 congenic line that carries a polymorphism in Vav1. Difference in arthritis severity was observed only after immunization with pristane. In a case-control study, 34 SNPs from VAV1 locus were analyzed by Immunochip genotyping in 11475 RA patients (7573 anti-CCP positive and 3902 negative) and 15,870 controls in six cohorts of European Caucasians. A combination of the previous MS-associated haplotype and two additional SNPs was associated with anti-CCP negative RA (alleles G-G-A-A of rs682626-rs2546133-rs2617822-rs12979659, OR=1.13, P=1.27 × 10-5). The same markers also contributed to activity of RA at baseline with the strongest association in the anti-CCP negative group for the rs682626-rs12979659 G-A haplotype (ß=-0.283, P=0.0048). Our study suggests a role for VAV1 and T-cell signaling in the pathology of anti-CCP-negative RA.

Expectations of recovery: A prognostic factor in patients with neck pain undergoing manual therapy treatment.

BACKGROUND: Expectations have been investigated in populations seeking care for neck pain, however not considering potential confounding factors. The aim of this study was to investigate if pretreatment expectations of recovery is a prognostic factor for recovery from neck pain at 7 weeks follow-up in patients seeking manual therapy treatment. METHOD: The study was based on the Stockholm Manual Intervention Trial, a randomized controlled trial investigating efficiency of three combinations of manual therapy. The patients with neck pain were included in this study (n = 716). Expectations of recovery was measured at baseline; 'How likely is it, according to your judgment, that you are completely recovered from your neck/back problems in 7 weeks'. Patients answered on a 11-point scale, further categorized into low, moderate and high expectations. The outcome was measured at 7 weeks follow-up by a modified version of the Global Perceived Recovery Question. Potential effect measure modifiers and confounders were measured at baseline. Multivariable log binomial regression models were used to analyse the association between expectations and recovery, presented as relative risks and 95% confidence intervals (CI). RESULTS: High expectations of recovery yielded a 47% increased probability of being recovered at 7 weeks follow-up. High expectations of recovery yielded improved recovery in both men and women separately, but moderate expectations yielded improved recovery only among men. CONCLUSION: Our results suggest that expectations of recovery is a prognostic factor for recovery in patients with neck pain seeking manual therapy treatment. WHAT DOES THIS STUDY ADD?: We found that high expectations of recovery yielded a higher probability of recovery compared to having low expectations, also when considering potential confounding factors. Expectations seemed to have a more distinct influence on recovery among men.

High consumption of coffee is associated with decreased multiple sclerosis risk; results from two independent studies.

OBJECTIVE: Previous studies on consumption of caffeine and risk of multiple sclerosis (MS) have yielded inconclusive results. We aimed to investigate whether consumption of coffee is associated with risk of MS. METHODS: Using two population-representative case-control studies (a Swedish study comprising 1620 cases and 2788 controls, and a US study comprising 1159 cases and 1172 controls), participants with different habits of coffee consumption based on retrospective data collection were compared regarding risk of MS, by calculating ORs with 95% CIs. Logistic regression models were adjusted for a broad range of potential confounding factors. RESULTS: Compared with those who reported no coffee consumption, the risk of MS was substantially reduced among those who reported a high consumption of coffee exceeding 900 mL daily (OR 0.70 (95% CI 0.49 to 0.99) in the Swedish study, and OR 0.69 (95% CI 0.50 to 0.96) in the US study). Lower odds of MS with increasing consumption of coffee were observed, regardless of whether coffee consumption at disease onset or 5 or 10 years prior to disease onset was considered. CONCLUSIONS: In accordance with studies in animal models of MS, high consumption of coffee may decrease the risk of developing MS. Caffeine, one component of coffee, has neuroprotective properties, and has been shown to suppress the production of proinflammatory cytokines, which may be mechanisms underlying the observed association. However, further investigations are needed to determine whether exposure to caffeine underlies the observed association and, if so, to evaluate its mechanisms of action.

Smoking is a major preventable risk factor for multiple sclerosis.

BACKGROUND: Both smoking and exposure to passive smoking have repeatedly been associated with increased multiple sclerosis (MS) risk, but have never before been studied together. We assessed the public health impact of these factors. METHODS: In a Swedish population-based case-control study (2455 cases, 5336 controls), we calculated odds ratios of developing MS associated with different categories of tobacco smoke exposure, together with 95% confidence intervals, by using logistic regression. The excess proportion of cases attributable to smoking and passive smoking was calculated as a percentage. RESULTS: Both smoking and exposure to passive smoking contribute to MS risk in a dose-dependent manner. At the population level, 20.4% of all cases were attributable to smoke exposure. Among subjects carrying the genetic risk factor HLA-DRB1*15 but lacking HLA-A*02, 41% of the MS cases were attributable to smoking. CONCLUSIONS: From a public health perspective, the impact of smoking and passive smoking on MS risk is considerable. Preventive measures in order to reduce tobacco smoke exposure are, therefore, essential. In particular, individuals with a history of MS in the family should be informed regarding the impact of smoking on the risk of MS, and the importance of preventing their children from being exposed to passive smoke.

Body mass index during adolescence, rather than childhood, is critical in determining MS risk.

OBJECTIVE: Obesity in childhood and during adolescence has repeatedly been associated with increased risk of developing multiple sclerosis (MS). We aimed to investigate whether the most critical period occurs during childhood or later, during adolescence. METHODS: Using a population-based case-control study (1586 cases and 2800 controls), individuals with different body sizes at age 10 and different body mass indices at age 20 were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals. Potential interactions between HLA-DRB1*15 and absence of HLA-A*02, respectively, and both childhood and adolescent obesity were evaluated by calculating the attributable proportion due to interaction. RESULTS: Regardless of body size at age 10, individuals with adolescent obesity had a 90% increased risk of MS. Among participants who were not obese at age 20, no association was observed between body size at age 10 and subsequent MS risk. An interaction was observed between the HLA MS risk genes and adolescent, but not childhood, obesity. CONCLUSIONS: Our results suggest that BMI during adolescence, rather than childhood, is critical in determining MS risk.

Comparative analysis of first-year fingolimod and natalizumab drug discontinuation among Swedish patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) and fingolimod (FGL) are mainly used second line in relapsing-remitting multiple sclerosis (MS), although pivotal trials included mainly treatment-naïve patients. OBJECTIVE: This study aims to provide real-world data on safety and discontinuation rates. METHODS: Using IMSE, a drug monitoring registry for all newer MS drugs in Sweden, we analysed differences in baseline characteristics and 1-year drug survival for patients registered 2011-2013, initiating treatment with NTZ (n=640) or FGL (n=876). Among FGL initiators, n=383 (44%) had previously used NTZ (FGL(afterNTZ)). RESULTS: Compared with NTZ, the FGL cohort was older and more often male (36/38 years, 24%/33% males). Baseline Expanded Disability Status Scale was similar across groups, but MS Severity Score was higher in NTZ patients, and Symbol Digit Modalities Test and MS Impact Scale (MSIS-29) was higher in FGL(afterNTZ) versus FGL(NTZ-naïve) patients. Proportion on drug after 1 year was high, NTZ=87%, FGL(NTZ-naïve)=83% and FGL(afterNTZ)=76%. Adverse events was the most frequent reason for discontinuing FGL (FGL(NTZ-naïve)=9%, FGL(afterNTZ)=12%), and was significantly higher than on NTZ (3%). In contrast, the proportion of patients stopping treatment due to lack of effect was more similar: NTZ=4%, FGL(NTZ-naïve)=3%, FGL(afterNTZ)=8%. CONCLUSION: FGL and NTZ were both well tolerated, but FGL less so than NTZ, especially in patients switching to FGL from NTZ. Group differences were not explained by differences in recorded baseline characteristics.

Shift work influences multiple sclerosis risk.

BACKGROUND: An association between working shift at a young age and subsequent risk for multiple sclerosis (MS) has been observed. OBJECTIVE: To investigate whether this finding could be replicated, and to further explore the influence of age at first exposure to shift work. METHODS: Using a Swedish population-based, case-control study (2337 cases and 4904 controls), the incidence of MS among subjects whom had worked shifts was compared with that of those whom had not, by calculating odds ratios (ORs) with 95% confidence intervals (CIs) by means of logistic regression. RESULTS: The OR of developing MS was 1.5 (95% CI 1.2-1.8) among those whom started working shifts before age 20, whereas a less pronounced association was observed among those whom started working shifts at age 20 or later (OR 1.2; 95% CI 1.1-1.4). The effect of shift work was more pronounced among subjects whom had been exposed at a young age, regardless of the duration between the start of shift work and disease onset. CONCLUSION: Some aspects of adolescence seem to be of great importance, regarding the impact of shift work on MS risk. Circadian disruption and sleep deprivation may contribute towards explaining the association; however, the exact mechanisms behind our observations remain to be elucidated.