Risk of Mortality in Immigrants with Multiple Sclerosis in Ontario, Canada.

INTRODUCTION: Little is known about how mortality in multiple sclerosis (MS) may differ based on sociodemographic factors, such as immigrant status. We compared mortality in immigrants versus long-term residents with MS in Ontario, Canada. METHODS: In this retrospective cohort study, we applied a validated algorithm to linked, population-based immigration and health administrative data to identify incident MS cases in Ontario between 1994 and 2014. We identified date of death, if it occurred. We used a Cox model adjusting for age, sex, income, and comorbidity, to compare survival in immigrants versus long-term residents. RESULTS: There were 23,603 incident MS cases of whom 1,410 (6.0%) were immigrants. After adjusting for covariates, risk of death was higher in immigrants in the first year after diagnosis (hazard ratio [HR] 1.66; 95% CI 1.05-2.63, p = 0.031). However, in years 1-5 (HR 0.63; 95% CI 0.40-0.98, p = 0.041) and 5-10 (HR 0.42; 95% CI 0.24-0.75, p = 0.003) after diagnosis, risk of death was lower in immigrants. Older age at onset and comorbidity were associated with higher mortality; female sex and higher socioeconomic status were associated with lower mortality. CONCLUSIONS: In this large population with universal access to health care, immigrants with MS had higher mortality compared to long-term residents in the first year after onset and lower mortality thereafter. Lower mortality in immigrants to Canada is well described and thought to be due to the healthy immigrant effect. Higher mortality in the first year after MS onset warrants further investigation as some early deaths may be preventable.

Causes that Contribute to the Excess Mortality Risk in Multiple Sclerosis: A Population-Based Study.

BACKGROUND: Lifespan is 6-10 years shorter in multiple sclerosis (MS), but the reasons remain unclear. Using linked clinical- and population-based administrative health databases, we compared cause-specific mortality in an MS cohort to the general population. METHODS: MS patients in British Columbia (BC), Canada, were followed from the later of first MS clinic visit or January 1, 1986, to the earlier of death, emigration, or December 31, 2013. Comprehensive mortality information was obtained by linkage to BC's multiple-cause-of-death mortality data. Causes were grouped using International Classification of Disease codes. Standardized mortality ratios (SMRs) were calculated for underlying cause, and relative mortality ratios (RMRs) for any mention cause, by comparison to mortality rates in the age-, sex-, and calendar year-matched general population. Cause-specific relative mortality was explored by sex and disease course (relapsing onset and primary progressive). RESULTS: Among 6,629 MS patients with 104,236 patient-years of follow-up, 1,416 died. The all-cause mortality risk was increased relative to the general population (SMR 2.71; 95% CI 2.55-2.87). MS was the underlying cause in 50.4%, and a mentioned cause in 77.9%, of deaths. Mortality by underlying cause was higher than expected for genitourinary disorders/infections (SMR 3.55; 95% CI 2.25-5.32), respiratory diseases/infections (SMR 2.69; 95% CI 2.17-3.28), suicide (SMR 2.40; 95% CI 1.61-3.45), cardiovascular disease (SMR 1.57; 95% CI 1.36-1.81), and other infections/septicemia (SMR 1.83; 95% CI 1.15-2.78). Risks of death due to overall cancer, accidents, digestive system disorders, and endocrine/nutritional diseases as underlying causes were similar to the general population. However, mortality with any mention of accidents (RMR 2.71; 95% CI 2.22-3.29) or endocrine/nutritional diseases (RMR 1.75; 95% CI 1.46-2.09) was greater. Bladder cancer mortality was increased in women (SMR 3.87; 95% CI 1.42-8.42) but not men. No notable differences were observed by disease course. CONCLUSIONS: MS itself was the most frequent underlying cause of death. Infections (genitourinary, respiratory, and septicemia), suicides, cardiovascular disease, and accidents contributed significantly to the increased risk of death. Some findings differed by sex, but not disease course. Multiple-cause death data offer advantages over "traditional" use of underlying cause only.

Comorbidity in multiple sclerosis: its temporal relationships with disease onset and dose effect on mortality.

BACKGROUND AND PURPOSE: We aimed to determine the burden of comorbidities at the time of diagnosis of multiple sclerosis (MS), the risk of developing new comorbidities after diagnosis and the effect of comorbidities on mortality in patients with MS. METHODS: This study used data from 2526 patients with incident MS and 9980 age-, sex- and physician-matched controls without MS identified from the UK Clinical Practice Research Datalink. RESULTS: Before the MS diagnosis, the adjusted odds ratio for the association between MS and a Charlson comorbidity index score of 1-2, 3-4 or ≥5 was 131 [95% confidence interval (CI), 1.17-1.47], 1.65 (95% CI, 1.20-2.26) or 3.26 (95% CI, 1.58-6.70), respectively. MS was associated with increased risks of cardiovascular and neurological/mental diseases. After diagnosis, the adjusted hazard ratio for the association between MS and an increased risk of developing comorbidities was 1.13 (95% CI, 1.00-1.29). The risk of developing any comorbidity in terms of neoplasms, musculoskeletal/connective tissue diseases or neurological/mental diseases was higher in MS. Patients with MS had a higher mortality risk compared with controls, with a hazard ratio of 2.29 (95% CI, 1.81-2.73) after adjusting for comorbidities. There was a dose effect of pre-existing comorbidities on mortality. CONCLUSIONS: Patients with MS have an increased risk of developing multiple comorbidities both before and after diagnosis and pre-existing comorbidities have an impact on survival.

Epidemiology of multiple sclerosis in Santiago de Compostela (Spain).

OBJECTIVES: To analyze the frequency and demographic characteristics of multiple sclerosis (MS) in the Council of Santiago de Compostela (SPAIN). MATERIAL AND METHODS: The patients diagnosed with MS according to the McDonald 2010 diagnostic criteria were identified within the population of the District of Santiago de Compostela. Several sources were used (records and databases from Hospital, General Practitioners, Private Clinics, and the MS Patients Association). Demographic and clinical data were obtained from the electronic files. RESULTS: The incidence of MS between 2010 and 2015 was 8/100 000/year (95% CI: 6-10), and the prevalence on December 31, 2015, was 152/100 000 (95% CI: 127-176). The age-standardized prevalence (using the European Standard Population 2013) was 137 (95% CI: 114-159) and the incidence of 7 (95% CI: 2-12). The female:male ratio was 1.84, the mean age at the first symptom was 32.23 years, the diagnosis was delayed 3.12 years, and the mean EDSS was 2.82. 71.17% had relapsing-remitting MS, 16.55% secondary progressive MS, 7.59% primary progressive MS, and 0.69% progressive relapsing MS. A disease-modifying treatment was established in 62.76% of patients in a mean of 1.96 years after the diagnosis. CONCLUSIONS: The northwest of Spain is a high-risk area for MS, with frequencies similar to other Atlantic regions and higher than the rest of the country.

Risk Factors for Suicide in a National Sample of Veterans With Multiple Sclerosis.

OBJECTIVES: To examine risk factors in the year before suicide in a national sample of United States veterans with multiple sclerosis (MS), as well as means of suicide and receipt of mental health services prior to death. DESIGN: Case control study. Individuals in the Veterans Affairs MS National Data Repository were linked to the National Death Index Plus to obtain death records, including specific causes of death. Participants were veterans with MS who died by suicide and randomly selected nonsuicide MS controls (5 per participant) who were alive at the time of the index suicide. Mental health disorders and medical comorbidities were identified in the year before death for suicides and during the identical time period for controls. SETTING: Veterans Health Administration. PARTICIPANTS: Veterans (N=426) who received treatment for MS in the United States Veterans Health Administration between 1999 and 2011. There were 71 deaths by suicide and 355 randomly selected controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Suicide. RESULTS: Results from the adjusted multivariable model suggest that the following factors were associated with an increased risk for suicide: male sex (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.35-9.42), depression (OR, 1.82; 95% CI, 1.03-3.23), and alcohol use disorder (OR, 3.10; 95% CI, 1.38-6.96). Half (50.7%) had a mental health appointment in the year before suicide. The primary means of suicide was by firearm (62.0%). CONCLUSIONS: Routine assessment of suicide risk in individuals with MS is warranted, particularly for those with recent history of depression or alcohol use disorder.

Population size estimation with interval censored counts and external information: Prevalence of multiple sclerosis in Rome.

We discuss Bayesian log-linear models for incomplete contingency tables with both missing and interval censored cells, with the aim of obtaining reliable population size estimates. We also discuss use of external information on the censoring probability, which may substantially reduce uncertainty. We show in simulation that information on lower bounds and external information can each improve the mean squared error of population size estimates, even when the external information is not completely accurate. We conclude with an original example on estimation of prevalence of multiple sclerosis in the metropolitan area of Rome, where five out of six lists have interval censored counts. External information comes from mortality rates of multiple sclerosis patients.

Epilepsy and associated mortality in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: We aimed to determine the prevalence of epilepsy in patients with multiple sclerosis (MS) at diagnosis, the risk of developing epilepsy after the diagnosis of MS and the relative risk of mortality associated with epilepsy. METHODS: We used the UK Clinical Practice Research Data-link to identify 2526 patients with incident MS and 9980 age-, sex- and index year-matched non-MS controls from 1997 to 2006. Logistic regression was used to estimate odds ratios [95% confidence interval (CI)] for epilepsy and Cox regression was used to estimate hazard ratios (HRs) (95% CI) for epilepsy and mortality. RESULTS: Patients with incident MS were on average 45 years old and 70.9% were female. At diagnosis, the prevalence of epilepsy in patients with MS was 1.30% compared with 0.57% in non-MS controls. At diagnosis, MS was associated with an adjusted odds ratio (95% CI) of 2.11 (1.36-3.27) for pre-existing epilepsy. Among epilepsy-free patients, the cumulative probabilities of developing epilepsy, first recorded within 10 years of the index date, were 2.77% for patients with MS and 0.90% for controls. MS was associated with an adjusted HR (95% CI) of 6.01 (2.94-12.29) for epilepsy. Among patients with MS, epilepsy was associated with an HR (95% CI) of 2.23 (1.02-4.84) for all-cause mortality. CONCLUSIONS: This population-based study found an increased prevalence of epilepsy in patients with MS at diagnosis when compared with non-MS controls and the risk of developing epilepsy was also higher following the MS diagnosis. Patients with MS with epilepsy had a higher risk of mortality compared with those without.

Mortality among autoworkers manufacturing electronics in Huntsville, Alabama.

BACKGROUND: Workers raised concerns over suspected excesses of mortality at automotive electronics manufacturing facilities in Huntsville, Alabama. METHODS: A study of 4396 UAW members ever-employed at Huntsville facilities between 1972 and 1993 was conducted with mortality follow-up through 2016. Standardized Mortality Ratios (SMRs) were estimated using U.S. and Alabama reference rates. RESULTS: Relative to U.S. rates, there was a modest excess of all-cause mortality among White female workers (SMR 1.08, 95%CI: 0.99-1.18) and among all workers hired <1977 at the original plant building (SMR 1.10, 95%CI: 0.99-1.22). There was excess nervous system disorder (SMR 1.24, 95%CI: 0.91-1.65) and brain and nervous system cancer (SMR 1.31, 95%CI: 0.67-2.28) mortality. Estimates for several causes of interest were imprecise. CONCLUSIONS: All-cause mortality estimates were greater than anticipated based on results from other UAW cohorts. The excess of nervous system disease mortality is consistent with other studies of electronics workers exposed to lead-solder and chlorinated solvents.

Randomized controlled trial of a home-based palliative approach for people with severe multiple sclerosis.

BACKGROUND: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. OBJECTIVE: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. METHODS: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). RESULTS: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC ( p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis ( p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. CONCLUSION: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes.

Similar birth-cohort patterns in Crohn's disease and multiple sclerosis.

BACKGROUND: The etiology of Crohn's disease and multiple sclerosis is unknown. Genetic susceptibility and environmental factors are believed to play a role in both diseases. OBJECTIVES: To compare the long-term time trends of the two diseases and thus gain insight about their etiology. METHODS: We analyzed mortality data of Crohn's disease and multiple sclerosis from Canada, England, Italy, the Netherlands, Switzerland, and the United States during the past 60 years. Age-period-cohort (APC) analyses based on logit models served to disentangle the separate influences of age, period, and cohort effects on the overall time trends. RESULTS: The long-term time trends of Crohn's disease and multiple sclerosis have been shaped by strikingly similar birth-cohort patterns. In both diseases alike, mortality increased in all generations born prior to 1910. It peaked among generations born between 1910 and 1930 and then declined in all subsequent generations. Similar birth-cohort patterns of Crohn's disease and multiple sclerosis were found in each country analyzed separately. CONCLUSION: The birth-cohort patterns indicate that the development of Crohn's disease and multiple sclerosis is influenced by exposure to environmental risk factors during an early period of life. These environmental risk factors may be similar or even identical in Crohn's disease and multiple sclerosis.

Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the United States, 1999-2015.

BACKGROUND: Multiple sclerosis (MS) carries high morbidity and shortens life span. While there is recent recognition of other US minority populations such as blacks and Hispanics being affected with MS, examination of MS-specific mortality trends by race/ethnicity has been lacking. OBJECTIVE: To investigate MS mortality rates and trends in the United States by sex, age, and race/ethnicity. METHODS: We used the Compressed Mortality data file for 1999-2015 in the Wide-ranging online Data for Epidemiological Research system developed by the Center for Disease Control and Prevention to calculate the age-adjusted (US 2000 standard population) and age-specific MS mortality rate (per 100,000) by race/ethnicity and sex over time. Five mutually exclusive racial/ethnic groups were included in the analysis: non-Hispanic (NH) white, NH black, NH Asian or Pacific Islander (API), NH American Indian or Alaska Native, and Hispanic. RESULTS: The average annual age-adjusted MS mortality rate was highest among NH whites (0.90 for males and 1.50 for females) immediately followed by NH blacks (0.75 for males and 1.42 for females), and lowest among APIs (0.05 for males and 0.12 for females). Statistically significant, increasing trend in age-adjusted MS mortality was observed during 1999-2015 among NH whites and NH blacks regardless of sex, more substantially in the latter. Age-specific MS mortality patterns showed NH blacks had the highest rate under age 55 and NH whites had the highest rate after that age point. For these 2 groups, MS mortality increased with age in both sexes and peaked at ages 55-64 for NH blacks and 65-74 for NH whites before declining substantially, while for Hispanic and API groups the risk plateaued after age 55. CONCLUSION: MS-specific mortality trends demonstrate distinctive differences by race/ethnicity and age. The observations that whites and females are more likely to die from MS is in line with the overall understanding that these groups are affected more by MS. However, the findings of blacks dying at an earlier age and having more substantially increasing mortality trends than whites suggest that MS burden weighs unequally by race. Further investigation into these trends may provide additional evidence into risk or protective factors within each group.

Excess mortality among patients with multiple sclerosis in Denmark has dropped significantly over the past six decades: a population based study.

BACKGROUND: Lifetime expectancy in multiple sclerosis (MS) is reduced. Few studies have had sufficient follow-up or sufficient number of patients to assess if survival has improved with time. However, a recent meta-analysis found no time-dependent change in MS excess mortality across studies over recent decades. OBJECTIVE: To investigate whether short-term all-cause excess mortality in patients with MS in the total Danish population has changed over the last six decades. PATIENTS AND METHODS: We included all patients with MS recorded in the nationwide Danish MS Registry with definite or probable MS and onset from 1950 through 1999. The Danish Civil Registration System provided date of death for all deceased patients with follow-up in 2015, and Statistics Denmark supplied specific population mortality. We calculated excess number of death per 1000 person-years (EDR) and standardised mortality ratio (SMR). RESULTS: We included 18 847 patients among whom 6102 had died as opposed to 2492 expected deaths. EDR was 10.63 (95% CI 10.19 to 11.09) and a SMR was 2.45 (95% CI 2.39 to 2.51). The 15-year EDR dropped gradually from 11.29 (95% CI 9.95 to 12.73) in the 1950-1959 onset cohort to 2.56 (95% CI 1.98 to 3.18) in the 1990-1999 onset cohort, and SMR dropped from 4.48 (95% CI 4.06 to 4.92) to 1.80 (95% CI 1.62 to 1.99). CONCLUSION: The decline in short-term excess mortality in MS started decades before disease-modifying treatment of MS became available, before use of MRI became widespread, and before the McDonald diagnostic criteria were introduced. A change in the MS cohorts with fewer malignant cases may be a significant contributor.

Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study.

OBJECTIVE: Survival and causes of death (COD) in multiple sclerosis (MS) provide ultimate endpoints. We aimed to investigate survival and COD in a 60-year population-based MS cohort compared with the general population. METHODS: All patients with incident multiple sclerosis (MS) (N=1388) with onset during 1953-2012 in Hordaland County, Western Norway, were included. Data were obtained from patient records at Haukeland University Hospital and linked to the Norwegian COD registry. Survival adjusted for sex, age and disease course were estimated by Kaplan-Meier analyses from birth and from disease onset. Mortality and COD in MS relative to the general population were examined by standardised mortality ratio (SMR). RESULTS: Of 1388 patients, 291 had deceased, mainly of MS (56.4%). Median life expectancy was 74.7 years for MS and 81.8 years for the general population (p<0.001); 77.2 years for women with MS and 72.2 years for men with MS (p<0.001). Life expectancy for patients with relapsing remitting MS (RRMS) was 77.8 years and -71.4 years for primary progressive MS (PPMS) (p<0.001). Overall SMR was 2.7 (p>0.0001); 2.9 in women and 2.5 in men (p=0.0009). SMR was 2.4 in RRMS and 3.9 in PPMS (p<0.0001). SMR from disease onset during 1953-1974 was 3.1; 2.6 during 1975-1996 and 0.7 during 1997-2012 (p<0.0083). No difference in cause-specific deaths were found (p=0.0871). CONCLUSION: We found a 7-year shorter life expectancy and almost threefold higher mortality in MS compared with the general population. A rise in survival in MS was observed during the entire observation period.

Temperature dependence of multiple sclerosis mortality rates in the United States.

BACKGROUND: It is well known that multiple sclerosis (MS) patients are very sensitive to heat events. However, how MS patients respond to the significant temperature difference between the high- and low-latitude regions is not understood. OBJECTIVE: The goal is to identify the primary factor responsible for the fact that MS mortality rates of the United States is more than three times higher in the northern states than in the southern states. METHODS: Correlation coefficients between the age-adjusted mortality rate of MS as the underlying cause of death and the state average temperature, altitude, latitude, duration of sunshine hours, and solar radiation in the 48 contiguous states were compared. RESULTS: MS mortality rates correlate significantly and inversely with temperatures in the 48 states (correlation coefficient r = -0.812 and significance p = 0.00). Durations of sunshine hours and solar radiation do not correlate significantly with MS mortality rates ( r = -0.245, -0.14, and p = 0.101, 0.342, respectively). CONCLUSION: High environmental temperature is the primary reason for the low MS mortality rates and likely the low MS prevalence in low-latitude regions. Implication of the study result is that benefits of long-term heat acclimation through gradual and prolonged exposure to environmental heat for MS patients may be greatly underappreciated.

Clinical course of multiple sclerosis: A nationwide cohort study.

BACKGROUND: The course of multiple sclerosis (MS) has been studied in several cohorts; however, results have varied significantly. OBJECTIVE: To describe the clinical course of MS in a nationwide cohort of patients. METHOD: Data from the Swedish MS register (SMSreg) were used to estimate the median time to the sustained Expanded Disability Status Scale (EDSS) scores 3.0, 4.0 and 6.0, onset of secondary progressive multiple sclerosis (SPMS) and death using Kaplan-Meier method. A possible effect of first-line treatments on age at EDSS 6.0 and SPMS was estimated. RESULTS: In all, 12,703 patients were included. Median ages at EDSS scores 3.0, 4.0 and 6.0 were 55.4 (95% confidence interval (CI): 54.8-55.8), 60.7 (95% CI: 60.1-61.2) and 64.3 (95% CI: 63.6-64.7), respectively. Median age at SPMS was 57.4 (95% CI: 56.9-57.9). The median age at the time of death was 80.5 (95% CI: 79.9-81.1). Males and progressive-onset patients showed higher risks of disability worsening. On average, treated patients gained 1.6 years (95% CI: 0.2-3) to EDSS 6.0 as a result of treatment. CONCLUSION: Ages at disability milestones in this population-based cohort were higher than previously described in clinic- and regional-based samples. Nevertheless, MS patients die at younger age and live at an average almost 20 years with moderate and 30 years with severe disability.

An excessive risk of suicide may no longer be a reality for multiple sclerosis patients.

BACKGROUND: Few recent studies have shown that there is no longer an increased risk of suicide in patients affected with multiple sclerosis (MS). OBJECTIVES: To describe suicide cases within a large French MS cohort and assess whether MS patients are at a higher risk of suicide compared with the general population. METHODS: Data derives from a study on long-term mortality of 27,603 prevalent cases from 15 MS specialist centres. Of 1,569 deceased MS patients (5.7%) on 1 January 2010, 47 were suicides. RESULTS: The mean time between MS clinical onset and death was 13.5 years (standard deviation (SD): 9.3 years; none within the first 3 years) and was significantly shorter than for MS patients who had died from other causes (mean = 21.4 (SD = 11.6), p < 0.0001). Age at death was also lower (46.3 vs 56.7). The standardized mortality rates were around 1 in several sensitivity analyses, reflecting no excess mortality in MS compared with general population. CONCLUSION: Our findings indicate that an excess suicide risk may no longer be true for MS patients and highlight the changing profile of cases, occurring later in the disease course. Further studies in population-based registries are needed to confirm and explain these potential changes (e.g. treatments' impact?).

Multiple sclerosis and suicide.

Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.

Increased frequency of multiple sclerosis among patients with bullous pemphigoid: a population-based cohort study on comorbidities anchored around the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a disease of the elderly and may be associated with neurological and cardiovascular diseases and diabetes. Mortality rates strongly exceed those of the background population. OBJECTIVES: To investigate the frequency of comorbidities and their temporal relation to BP. METHODS: A register-based matched-cohort study on all Danish patients with a hospital-based diagnosis of BP (n = 3281). The main outcomes were multiple sclerosis (MS), Parkinson disease (PD), Alzheimer disease (AD), stroke, diabetes types 1 and 2, malignancies, ischaemic heart disease (IHD), hypertension and eventually death. RESULTS: At baseline, patients with BP had increased prevalences of MS [odds ratio (OR) 9·7, 95% confidence interval (CI) 6·0-15·6], PD (OR 4·2, 95% CI 3·1-5·8), AD (OR 2·6, 95% CI 1·8-3·5) and stroke (OR 2·7, 95% CI 2·4-2·9). Furthermore, malignancies, cardiovascular disease and diabetes were over-represented among patients with BP: type 1 diabetes (OR 3·1, 95% CI 2·5-3·8), type 2 diabetes (OR 2·3, 95% CI 2·0-2·6), malignancies (OR 1·3, 95% CI 1·1-1·4), IHD (OR 1·7, 95% CI 1·5-1·9) and hypertension (OR 2·0, 95% CI 1·8-2·2). During follow-up, the risk of MS was significantly higher among patients with BP [hazard ratio (HR) 9·4, 95% CI 4·9-18·0], even if events during the first year after diagnosis of BP were excluded (HR 5·1, 95% CI 2·3-11·3). Patients with BP had an average increased mortality rate of 2·04 (95% CI 1·96-2·13). CONCLUSIONS: We discovered a significantly increased frequency of MS among patients with BP. At the time of diagnosis, patients with BP had an excessive number of comorbidities and an increased mortality rate over the following years.

The change in the sex ratio in multiple sclerosis is driven by birth cohort effects.

BACKGROUND AND PURPOSE: Birth cohort effects have greatly shaped long-term trends in multiple sclerosis (MS). This study examined whether birth cohort effects have also determined trends in the sex ratio. METHODS: Age-period-cohort analyses were applied to Swiss mortality data, 1901-2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C. RESULTS: Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex-specific birth cohort estimates were not congruent. CONCLUSION: The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex-specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors.

Causes of death in critically ill multiple sclerosis patients.

BACKGROUND: Patients with multiple sclerosis (MS) experience higher mortality rates as compared to the general population. While the risk of intensive care unit (ICU) admission is also reported to be higher, little is known about causes of death CoD in critically ill MS patients. AIM: To study the causes of death (CoD) in the series of critically ill patients with MS verified by autopsy. METHODS: We reviewed hospital electronic charts of MS patients treated at the neurological ICU of a tertiary care hospital between 2000 and 2015. We compared clinical and pathological CoD for those who were autopsied. RESULTS: Overall, 10 patients were identified (seven female; median age at death 65 years, range 27-80), and six of them were autopsied. The median MS duration prior to ICU admission was 27.5 years (range 1-50), and the median EDSS score at the time of ICU admission was 9 (range 5-9.5). The median length of ICU stay was 3 days (range 2-213). All the individuals in our series had experienced respiratory insufficiency during their ICU stay. The autopsy examination of brain tissue did not reveal evidences of MS lesions in one patient. In another patient, Lewy bodies were found on brain immunohistochemistry. CONCLUSION: Mortality in critically ill MS patients is largely driven by respiratory complications. Sporadic disparities between clinical and pathological findings can be expected.