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BACKGROUND: The cause of amyotrophic lateral sclerosis (ALS) is unknown, but occupations have been explored as a potential proxy measure of risk. There is a substantial body of literature connecting military service to ALS. We aimed to summarize and assess the quality of this evidence. METHODS: Systematic review of the literature, including observational studies which explored one of the following exposures: general military service (army, air force, marines, or navy); or specific exposures associated with military service measured among military personnel. The outcome of interest was ALS incidence, which could include onset, diagnosis, or death from ALS. RESULTS: A total of 2642 articles were screened. Following exclusion, 19 articles remained for inclusion in the systematic review, including 1 meta‐analysis and 18 original observational studies. Most studies were of moderate quality. In general, the relationship between military service was suggestive of an increased risk, particularly among Gulf War and WWII veterans. Exposure to pesticides (including Agent Orange) certain chemicals (exhaust, burning agents), heavy metals, and head trauma appeared to increase the risk of ALS among military personnel. CONCLUSIONS: There is a possible association between military service and the subsequent development of ALS; however, the evidence was limited. Studies were generally hindered by small sample sizes and inadequate follow‐up time. Future studies should endeavor to objectively measure specific exposures, or combinations thereof, associated with military service, as this will be of vital importance in implementing preventative strategies into military organizations.

ABSTRACTObjectivesMuch clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non-users of the specialty MS clinics in British Columbia, Canada.
ApproachThis was a retrospective record linkage cohort study using prospectively collected data from the BCMS database and province-wide health administrative databases. Incident MS cases were identified in the general population using a validated algorithm of hospital and physician diagnostic codes.
Results There were 2,841 incident MS cases between 1996 and 2004 including 1,648 (58%) that had registered at an MS clinic ('clinic cases') and 1,193 (42%) that had not ('non-clinic cases'). Sex and socioeconomic status distributions were similar; however, non-clinic cases were older, accessed health services more frequently, and had a higher burden of comorbidity than clinic cases. Only 1% of the non-clinic cases had filled a prescription for an MS-specific disease-modifying therapy, compared to 51% of the clinic cases.
ConclusionOur findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic-based MS cohorts may not always be generalizable to the wider MS population; and access to population-based health administrative data offers the opportunity to gain a broader understanding of MS.

ObjectiveMaternal exposure to cardiovascular disease (CVD) is associated with adverse maternal and neonatal health outcomes. However, its association with offspring's long-term neurodevelopmental disorders (NDDs) is not yet known. We aimed to investigate the association between maternal pre-existing CVDs and children's NDDs.
ApproachThis nationwide cohort study included 2.7 million live singleton births recorded in the Swedish Medical Birth Register between 1990 and 2019. Information on maternal pre-pregnancy CVDs was extracted from the National Patient Register, including diagnosis of cerebrovascular disease, heart failure, arrhythmia, valvular and congenital heart diseases. Registered diagnoses of offspring NDDs included Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and intellectual disability. Cox proportional hazards models were fitted to estimate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the associations. All estimates were adjusted for offspring's age at diagnosis, sex, calendar period, and maternal characteristics including age at birth, parity, education, country of birth, cohabitation status, smoking, psychiatric illness, pre-gestational diabetes, and hypertension.
ResultsThe overall prevalence of maternal CVDs was 0.8% between 1990 and 2019. A total of 141 651 individuals (5.2%) received a diagnosis of ADHD, 64 691 (2.4%) of ASD, and 22 913 (0.9%) received a diagnosis of intellectual disability. The adjusted analyses showed that offspring of mothers with CVD had 16% higher rate of ADHD (HR 1.16; 95% CI: 1.09-1.24) and 12% higher rate of ASD (HR 1.12; 95% CI: 1.02-1.23), compared with offspring of mothers without CVD. Specifically, maternal heart failure was associated with 1.93-fold increased HR of ASD (95% CI: 1.21-3.08), maternal arrhythmia with 14% increased rate of ADHD (95% CI: 1.04-1.24), and maternal cerebrovascular disease was associated with 30% elevated rate of ASD (95% CI: 1.07-1.59) and 17% elevated rate of ADHD (95% CI: 1.02-1.36). No association was found between maternal CVDs and intellectual disability.
ConclusionMaternal CVD before pregnancy may be a risk factor for offspring's ADHD and ASD, with varied risks by CVD subtypes. The mechanisms behind the associations warrant further investigations.