Search

Objective Antipsychotics may increase serum prolactin, which has particularly been observed with risperidone. Further, hyperprolactinemia has been linked to osteoporosis-related fractures. Therefore, we investigated fracture risk in a nationwide cohort exposed to antipsychotics. Methods Swedish registers were used to identify adults with two consecutive dispensations of risperidone (n = 38 211), other atypical antipsychotics not including paliperidone (n = 60 691), or typical antipsychotics (n = 17 445) within three months between 2006 and 2013. An osteoporosis-related fracture was defined as a non-open hip/femur fracture in primary analyses. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Risperidone users were on average older (mean age of 68, 44, and 63 years for risperidone, other atypical antipsychotics, and typical antipsychotics respectively). Compared with other atypical antipsychotics, there was no association between risperidone and osteoporosis-related fractures in the overall (HR = 1.04, CI: 0.91-1.19) or age-stratified analyses. A significantly increased risk of typical antipsychotics (HR = 1.24, CI: 1.07-1.45) compared with other atypical antipsychotics remained for ages >45 years. Conclusion Risperidone does not appear to be associated with an increased risk of osteoporosis-related fracture compared with other atypical antipsychotic agents as a group. For typical antipsychotics, a moderately elevated risk of hip fractures was noted compared with other atypical antipsychotics, possibly because of residual confounding.

Introduction: A raised risk for several comorbid diseases among MS patients has been identified. Most previous studies examined diseases separately rather than considering the overall burden of comorbidity. Multiple comorbidities may have important implica-tions for clinicians managing MS patients. Aims: To describe the lifetime burden of comorbid diseases among MS patients and the rate of these diseases compared with the general population in Sweden. Methods: MS patients identified using the MS Register and the Patient Register (PR) between 1964-2012 (n=25476) were matched by sex, age and county of residence with up to 10 general population comparators (n=251170). Prevalent and incident diag-noses of diseases other than MS for seven diseases categories were identified using the PR between 1987-2012. The total num-ber of comorbid diseases were compared using chi-square tests and prevalence rate ratios (PRR) were calculated. Hazard ratios (HR) were estimated using Cox regression and flexible non-para-metric survival models with age as the underlying time scale, MS as exposure, an additional comorbid disease as the outcome, adjusted for matching variables, education, number of previous comorbid diseases, and duration since study entry. Results: The proportion of MS patients with 1,2 or 3+ comorbid disease diagnoses was greater than in the comparison cohort across all age groups (p< 0.001). The largest PRR (range 1.22-9.99) were among younger age groups (6-18,19-40,41-60 years) in autoim-mune, cardiovascular, diabetes and seizure disease categories. Additionally, PRR were elevated in depression and respiratory dis-eases, but not for renal diseases. PRR between 61-80 and 81-100 years were reduced compared to younger groups across all comorbid diseases, but remained elevated for respiratory, seizure and renal dis-eases. The adjusted HR for an additional diagnosis in MS patients was 1.7 (95% CI 1.66-1.75). Flexible modelling showed signifi-cantly higher risk for all ag

Introduction: There is an established association between multiple sclerosis (MS) and pain treatment, in particular neuropathic pain. Murine models have confirmed an association between carriage of the DQB1*0302 allele and development of neuropathic pain-like behavior after peripheral nerve injury. Observational studies in patients with spinal disc herniation identified an association between the DQB1*0302 allele and pain, indicating a possible link in humans. This HLA allele has not been previously investigated for its influence on susceptibility to pain in MS patients. Aim: To determine whether the DQB1*0302 genotype is associated with pain in MS patients or member of the general population without MS. Methods: Three Swedish studies (EIMS, GEMS and IMSE) were combined in which enrolled MS patients were matched with 1-2 randomly selected individuals without MS by sex, age and region of residence. Register data was obtained and prescriptions for pain and neuropathic pain were identified as proxy measures for pain. Blood samples were collected and genotyped. Individuals were included if genotype data were available (MS=3877, non-MS=4548). Logistic regression had pain medication use as the outcome, to examine associations with genotype, stratified by MS status. Results: Homo- or heterozygous MS patients with the DQB1*0302 allele had no significantly increased risk of pain (adjusted OR 1.02, 95% CI 0.85-1.23) or neuropathic pain (OR 1.14, 0.97-1.34) compared with MS patients without the allele. Non-MS comparators carrying at least one allele had an increased risk of pain (OR 1.18, 1.03-1.35). Additionally, a zygosity effect appeared present particularly for women in the non-MS cohort, as homozygous individuals had a higher risk of pain compared with heterozygotes. No association was observed for MS patients. Conclusions: The DQB1*0302 allele was associated with increased risk of pain among the non-MS cohort. Zygocity also impacted on pain risk in this cohort, particula

Background and purpose: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients. Methods: A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period. Results: The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53-2.30). In both groups women are at higher risk of attempting suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non-MS cohort (0.68, 0.51-0.91), but not amongst MS patients (1.10, 0.60-2.04). Conclusion: Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients.

Supplement: 11, Meeting Abstract: 93

Background and purpose: Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated. Methods: A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination. Results and conclusions: Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P=0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P=0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS., Funding Agencies:UK Economic and Social Research Council RES-596-28-0001 ES/J019119/1Örebro University

Background and purpose: Multiple sclerosis (MS) patients are at increased infection risk. Here the influences of susceptibility, severity and surveillance bias on infection-related hospital admission are assessed. Methods: Swedish registers identified 20 276 patients with MS, matched with 203 951 people from the general population without MS. Risk of first hospital admission for infection and mortality over 36 years was estimated by Poisson regression. Results: Multiple sclerosis was associated with an increased hospital admission risk for all infections, with an adjusted relative risk (and 95% confidence interval) of 4.26 (4.13-4.40). A proportion of this raised risk was probably due to surveillance and referral bias, although a raised risk remained when MS was compared with other immune-mediated diseases. The 1-month mortality rate following hospital admission for infection was higher in MS patients than in the comparison cohort, with a relative risk of 4.69 (4.21-5.22). There was no clear temporal trend in the results, and risks were higher in males and varied by MS phenotype. Conclusions: Higher hospital admission rates among MS patients for infection are likely to be due to a combination of surveillance bias, cautious medical management and greater susceptibility to severe infections. MS-related functional limitations may increase infection risk and this should be considered in MS management.

Background: Comorbid inflammatory conditions in multiple sclerosis (MS) patients suggest shared risks with MS. Objective: To estimate if the risk of immune-mediated disease in MS patients and their parents is increased. Methods: Swedish register data were analysed using Cox regression to estimate immune-mediated disease risk among 11284 fathers and 12006 mothers of MS patients, compared with 123158 fathers and 129409 mothers of index subjects without MS. Similar analyses were conducted among 20276 index subjects with MS and 203951 without. Results: Parents of patients with MS did not have a significantly altered immune-mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn's disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset. Conclusion: The increased occurrence of other immune-mediated diseases in MS patients may not be due to shared genetic factors and surveillance bias is likely to be the main or possibly the entire explanation. If not entirely explained by surveillance bias, a modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics.

Aim: The aim of this study was to investigate if family stress and parental attachment style are associated with body mass index (BMI) in young children, and identify possible explanations. Methods: A cross-sectional survey with a two-stage design was used. Parents of 873 children participated. They completed a demographic questionnaire, the Swedish Parenthood Stress Questionnaire (SPSQ), the Relationship Questionnaire (RQ) and reported their children's television-viewing habits (as a marker of physical activity). Children's height, weight and BMI were obtained from a general population-based register, BASTA. Associations with over- and underweight in children were assessed using multiple logistic regression analysis. Results: Family stress indicated by SPSQ-score was associated with suboptimal BMI. Maternal, but not paternal, SPSQ-stress score was statistically significantly associated with overweight and underweight, with adjusted odds ratios (and 95% confidence interval) of 4.61 (3.11-6.84; p < 0.001) and 3.08 (1.64-5.81; p < 0.001) respectively. Associations between childhood BMI and parental attachment style were identified, but were not independent of maternal SPSQ-score. Conclusion: Our findings support a role for family stress in development of both overweight and underweight among young children. This is likely to be attributed to behavioural mechanisms but a more direct metabolic influence of stress could also be involved.

Background: Some small studies have reported high risk of suicide after surgical treatment for peptic ulcer. The aim of the present study was to explore the risk of suicide in hospitalised gastric ulcer and duodenal ulcer patients separately among operated and non-operated cohorts. Methods: Retrospective cohorts of 163 579 non-operated patients with gastric ulcer or duodenal ulcer and 28 112 patients with surgical treatment for ulcer, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation, or operation for the surgery cohort, until death, any cancer, emigration, or 31 December 2003. Standardised mortality ratios (SMRs) were calculated, and Poisson regression produced adjusted relative risk estimates among operated and non-operated patients. Results: Non-operated patients hospitalised for peptic ulcer showed a 70% excess risk of suicide (SMR 1.7, 95% CI 1.6 to 1.9) and those who underwent operation had a 60% increased risk (SMR 1.6, 95% CI 1.4 to 1.8). The risk of suicide was very high during the first year after hospitalisation (SMR 4.0, 95% CI 3.4 to 4.7) and more marked among women, patients under 70 and patients hospitalised without complications of ulcer. Both gastric ulcer and duodenal ulcer patients had high risk of suicide completion. Conclusion: Hospitalised patients with gastric ulcer or duodenal ulcer have an increased risk of suicide regardless of surgical treatment. These patients, especially women, are at very high risk during the first year after first hospitalisation/operation. The evaluation and management of suicidal thoughts in patients in medical settings should be further considered.

BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. Results: The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). Conclusions: First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC. © 2008 AGA Institute.

INTRODUCTION: An association between parental smoking and multiple sclerosis (MS) in offspring has been reported. This study examined whether maternal smoking during pregnancy is associated with MS in offspring. METHODS: Swedish general population registers provided prospectively recorded information on maternal smoking during pregnancy. The study identified 143 cases with MS diagnosed by 2006 and 1730 matched controls. Subjects were born since 1982 and individually matched by year of birth, age, sex and region of residence. Conditional logistic regression assessed the association of maternal smoking with MS in offspring with adjustment for socioeconomic index. RESULTS: Maternal smoking during pregnancy was not associated with MS in offspring, with an odds ratio (and 95% confidence interval) of 0.96 (0.65-1.44). When stratified by paediatric or later MS onset there was no association with maternal smoking in either stratum. CONCLUSION: It is unlikely that smoking during pregnancy represents a risk for early-onset MS amongst offspring.