Nephrologist referrals of older patients with chronic kidney disease in Singapore: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is common in the older population. By 2035, approximately one-quarter of Singapore residents are expected to have CKD. Many of these patients are not referred to nephrologists. AIM: To compare the characteristics of older patients (aged ≥65 years) with CKD stage ≥3B in the referral and non-referral groups. DESIGN & SETTINGS: A cross-sectional study in the primary care organisation National University Polyclinics (NUP), Singapore. METHOD: Retrospective data were extracted from the electronic health records of patients with CKD (aged ≥65 years) with CKD stage ≥3B. RESULTS: From 1 January-31 December 2018, a total of 1536 patients aged ≥65 years were diagnosed with CKD stage ≥3B (non-referral group = 1179 versus referral group = 357). The mean patient age in the non-referral group (78.4 years) was older than that in the referral group (75.9 years) (P<0.001). Indian older patients were referred more compared with their Chinese counterparts (P = 0.008). The non-referral group was prescribed significantly less fibrate, statins, insulin, sulfonylureas, dipeptidyl peptidase-4 (DPP4) inhibitors, and antiplatelet than the referral group (P<0.05), but only the difference in fibrates remained significant on subsequent multivariate analysis. CONCLUSION: This study demonstrates that there is a considerable number of older patients with CKD exclusively managed in the primary care setting (n = 1179) and that referrals primarily depend on demographic factors, namely age and ethnic group, rather than medical determinants of CKD severity or case complexity.

A national Swedish case-control study investigating incidence and factors associated with idiopathic intracranial hypertension.

OBJECTIVE: To study the incidence of idiopathic intracranial hypertension in Sweden and to explore whether previously proposed risk factors are associated with idiopathic intracranial hypertension by investigating the odds of exposure one year prior to diagnosis in patients compared to controls. METHODS: Using Swedish health care registers and validated diagnostic algorithms, idiopathic intracranial hypertension patients diagnosed between 2000-2016 were compared with randomly selected matched controls, five from the general population and five with obesity. RESULTS: We identified 902 idiopathic intracranial hypertension patients and 4510 matched individuals in each control group. Mean incidence among inhabitants ≥18 years of age was 0.71 per 100,000; rising from 0.53 in 2000-2005 to 0.95 in 2012-2016. There were increased odds for idiopathic intracranial hypertension patients compared to general population for exposure to: kidney failure (odds ratio =13.2 (4.1-42.0)), arterial hypertension (odds ratio =17.5 (10.5-29.3)), systemic lupus erythematosus (odds ratio =13.8 (4.3-44.7)), tetracyclines, sulphonamides, lithium, and corticosteroids. In obese controls, odds ratios were also significantly increased for these exposures. Hormonal contraceptive use and exposure to pregnancy did not appear to be associated factors for idiopathic intracranial hypertension development. CONCLUSIONS: The incidence of idiopathic intracranial hypertension in Sweden is lower relative to reports from other countries but is on the rise. This case-control study confirms several previously reported risk factors associated with idiopathic intracranial hypertension.

Effects of technology-enabled blood pressure monitoring in primary care: A quasi-experimental trial.

INTRODUCTION: Technology to enhance hypertension management is increasingly used in primary care; however, it has not been evaluated in an Asian primary care setting. We aimed to understand the clinical impact and cost-effectiveness of a technology-enabled home blood pressure monitor when deployed in primary care, and patients' perspectives about the technology. METHODS: A quasi-experimental cohort study was conducted in a polyclinic in Singapore. In total, 120 patients with hypertension were assigned to the telemonitoring intervention group. Patients received a home blood pressure device connected to the clinical care team's dashboard through a mobile gateway. Tele-consultations and nurse-led tele-support were carried out using established clinical protocols. In total, 120 patients assigned to the control group continued to receive usual care in the polyclinic. Clinical outcomes, cost-effectiveness, and patient satisfaction were measured 6 months after recruitment. RESULTS: In total, 217 patients completed 6 months of follow-up. Telemonitoring intervention patients had significantly increased odds of having controlled blood pressure by a factor of 2.69 (p = 0.01), with the greatest improvement in those whose blood pressure was uncontrolled at baseline (p < 0.05). The incremental cost-effectiveness ratios for all patients was S$23,935.14/quality-adjusted life year (<1 gross domestic product per capita), which was very cost-effective based on World Health Organization cost-effectiveness thresholds. There was greater satisfaction in telemonitoring intervention group relating to the convenience of recording and sharing blood pressure measurements with the health care team, consultation advice received, understanding by the health care team of their condition, and were more motivated to monitor their blood pressure. DISCUSSION: Telemonitoring with tele-consultation improved blood pressure control and was more cost-effective than usual care. Patients receiving telemonitoring intervention were also more motivated and satisfied with their care.

Prevalence of adverse pregnancy outcomes after exposure to interferon beta prior to or during pregnancy in women with MS: Stratification by maternal and newborn characteristics in a register-based cohort study in Finland and Sweden.

BACKGROUND: Previous studies reported no increase in the prevalence of adverse pregnancy outcomes after exposure to interferon-beta (IFN-beta). However, no study has investigated if the prevalence of these outcomes after IFN-beta exposure is modified by maternal and newborn characteristics. Our objective was to describe the stratified prevalence of adverse pregnancy outcomes among women with multiple sclerosis (MS) exposed only to IFN-beta or unexposed to any MS disease modifying drugs (MSDMDs). METHODS: This population-based cohort study using Finnish (1996-2014) and Swedish (2005-2014) register data included pregnancies of women with MS exposed only to IFN-beta 6 months before or during pregnancy (n=718) or unexposed to MSDMDs (n=1397). The outcome prevalences were described stratified by maternal and newborn characteristics, with 95% confidence intervals (CIs). Confounder-adjusted analyses were performed if the prevalence results indicated modified effect of IFN-beta in specific strata. RESULTS: The stratified analysis indicated that the prevalence of serious (anomaly or stillbirth) and other adverse pregnancy outcomes was similar among the exposed and unexposed, with no statistically significant difference. Among women treated for MS >5 years, serious adverse pregnancy outcomes occurred in 4.3% (95%CI: 1.9-8.3%) of pregnancies exposed only to IFN-beta 6 months before or during pregnancy and in 2.7% (95%CI: 1.2-5.0%) of unexposed pregnancies. The confounder adjusted analyses did not support the hypothesis that MS treatment duration before pregnancy would modify the risk of adverse pregnancy outcomes after exposure to IFN-beta 6 months before or during pregnancy. CONCLUSION: The prevalence of adverse pregnancy outcomes was not increased after IFN-beta exposure, when pregnancies of women with MS were stratified by maternal and newborn characteristics. The stratified results were similar to the unstratified results in the same population.

The association between family structure and children's BMI over time-the mediating role of income.

PURPOSE: Although both family structure and income have previously been indicated as being associated with body mass index (BMI), the extent to which the effect of family structure on BMI is mediated through income is incompletely understood. Taking the case of the United Kingdom, this study aims to investigate the association between family structure, defined in this study as whether children live in a one- or two-adult household, and childhood BMI, and whether this varies by child sex and with increased age. Second, the study aims to examine whether family equivalised income, as a proxy for socioeconomic status, mediates the association between family structure and childhood BMI. METHODS: This study uses data from the Millennium Cohort Study. Data from 7478 children born between 2000 and 2001 in the UK at the ages of 3, 5, 7, 11, and 14 were used. Mediation analysis was used to consider, at each age, the extent to which the association between living in a one- or two-adult household and BMI was mediated through income overall and stratified by sex. To assess the robustness of the mediation analysis estimates, we used both E-values and multiple confounder adjustment. RESULTS: At ages 3 and 5, there was no direct or indirect effect of family structure mediated by income on BMI. Between the ages of 7 and 11, the overall proportion of the association mediated vastly increased, from 19.70% at age 7 up to 42.70% at the age of 11. The E-values show that substantial unmeasured confounder associations would be needed to fully explain away the conclusions from the mediation analysis. Results remained significant when models were additionally adjusted for geographic region, the main respondent's (usually the mother's) highest educational attainment, and ethnicity. CONCLUSIONS: An increasing proportion of the association between family structure and BMI is mediated by income as children grow older. The study focuses on the mediating role of income between family structure and BMI using the available data as an empirical application of the potential impact of income as mediator in the causal pathway.

Comorbid disease burden among MS patients 1968-2012: A Swedish register-based cohort study.

BACKGROUND: People with multiple sclerosis (pwMS) have increased comorbid disease (CMD) risk. Most previous studies have not considered overall CMD burden. OBJECTIVE: To describe lifetime CMD burden among pwMS. METHODS: PwMS identified using Swedish registers between 1968 and 2012 (n = 25,476) were matched by sex, age, and county of residence with general-population comparators (n = 251,170). Prevalence, prevalence ratios (PRs), survival functions, and hazard ratios by MS status, age, and time period compared seven CMD: autoimmune, cardiovascular, depression, diabetes, respiratory, renal, and seizures. RESULTS: The magnitude of the PRs for each CMD and age group decreased across time, with higher PRs in earlier time periods. Before 1990, younger age groups had higher PRs, and after 1990, older age groups had higher PRs. Male pwMS had higher burden compared with females. Overall, renal, respiratory, and seizures had the highest PRs. Before 2001, 50% of pwMS received a first/additional CMD diagnosis 20 years prior to people without MS, which reduced to 4 years after 2001. PwMS had four times higher rates of first/additional diagnoses in earlier time periods, which reduced to less than two times higher in recent time periods compared to people without MS. CONCLUSION: Swedish pwMS have increased CMD burden compared with the general population, but this has reduced over time.

An evaluation of whether propensity score adjustment can remove the self-selection bias inherent to web panel surveys addressing sensitive health behaviours.

BACKGROUND: In health research, population estimates are generally obtained from probability-based surveys. In market research surveys are frequently conducted from volunteer web panels. Propensity score adjustment (PSA) is often used at analysis to try to remove bias in the web survey, but empirical evidence of its effectiveness is mixed. We assess the ability of PSA to remove bias in the context of sensitive sexual health research and the potential of web panel surveys to replace or supplement probability surveys. METHODS: Four web panel surveys asked a subset of questions from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Five propensity scores were generated for each web survey. The scores were developed from progressively larger sets of variables, beginning with demographic variables only and ending with demographic, sexual identity, lifestyle, attitudinal and sexual behaviour variables together. The surveys were weighted to match Natsal-3 based on propensity score quintiles. The performance of each survey and weighting was assessed by calculating the average 'absolute' odds ratio (inverse of the odds ratio if less than 1) across 22 pre-specified sexual behaviour outcomes of interest comparing the weighted web survey with Natsal-3. The average standard error across odds ratios was examined to assess the impact of weighting upon variance. RESULTS: Propensity weighting reduced bias relative to Natsal-3 as more variables were added for males, but had little effect for females, and variance increased for some surveys. Surveys with more biased estimates before propensity weighting showed greater reduction in bias from adjustment. Inconsistencies in performance were evident across surveys and outcomes. For most surveys and outcomes any reduction in bias was only partial and for some outcomes the bias increased. CONCLUSIONS: Even after propensity weighting using a rich range of information, including some sexual behaviour variables, some bias remained and variance increased for some web surveys. Whilst our findings support the use of PSA for web panel surveys, the reduction in bias is likely to be partial and unpredictable, consistent with the findings from market research. Our results do not support the use of volunteer web panels to generate unbiased population health estimates.

The DQB1*03:02 Genotype and Treatment for Pain in People With and Without Multiple Sclerosis.

Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB1*03:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB1*03:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB1*03:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB1*03:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB1*03:02 allele effect is modified by the presence of MS.

Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden.

BACKGROUND: Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD). METHODS: This cohort study used Finnish (1996-2014) and Swedish (2005-2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity. RESULTS: Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31-0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06-2.78). CONCLUSION: In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

Infectious and inflammatory disorders might increase the risk of developing idiopathic intracranial hypertension - a national case-control study.

OBJECTIVE: To investigate whether conditions causing inflammatory activation are associated with increased risk of idiopathic intracranial hypertension. METHODS: All newly diagnosed idiopathic intracranial hypertension patients (cases) in Sweden between 2000-2016 were identified using pre-determined algorithms (n = 902) and matched with five controls from the general population and five individuals with an obesity diagnosis (n = 4510) for age, sex, region, and vital status. National health registers provided information on infections, inflammatory disorders and dispensed medications. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: Compared to general population controls, the cases had fourfold increased odds of having an infection (odds ratio = 4.3, 95% confidence interval 3.3-5.6), and threefold increased odds of an inflammatory disorder the year prior to idiopathic intracranial hypertension diagnosis (odds ratio = 3.2, 95% confidence interval 2.4-4.3). Organ specific analyses showed that odds were increased for the study diseases in the respiratory organ, kidney organ and gastrointestinal tract, but not for female genital infections. Similar results were found when comparing idiopathic intracranial hypertension with obese controls though the odds ratios were of lower magnitude. Sub-analyses on exposure to anti-infectious and anti-inflammatory drugs confirmed the increased odds ratios for idiopathic intracranial hypertension patients. CONCLUSIONS: These findings suggest that major inflammatory activation may be a risk factor in idiopathic intracranial hypertension development.

Hospital diagnosed pneumonia before age 20 years and multiple sclerosis risk.

INTRODUCTION: Respiratory inflammation has been proposed as a risk factor for MS. This study aims to determine if hospital-diagnosed pneumonia in adolescence (before age 20 years) is associated with subsequent multiple sclerosis (MS). METHODS: This case-control study included incident MS cases after age 20 years identified using the Swedish national registers. Cases were matched with 10 general population controls by age, sex and region. Pneumonia diagnoses were identified between 0-5, 6-10, 11-15 and 16-20 years of age. Conditional logistic regression models adjusted for infectious mononucleosis (IM) and education calculated ORs with 95% CIs. Urinary tract infections (UTIs), a common complication of MS, before age 20 years were included as a control diagnosis for reverse causation. RESULTS: There were 6109 cases and 49 479 controls included. Pneumonia diagnosed between age 11-15 years was associated with subsequent MS (adj OR 2.00, 95% CI 1.22 to 3.27). Although not statistically significant, sensitivity analyses showed similar magnitude associations of pneumonia between age 11-15 years and MS. No statistically significant associations with MS for pneumonia at other age groups were observed. Adjustment for IM had no notable effect on associations, but was statistically significantly associated with MS. UTIs were not associated with MS. CONCLUSION: Pneumonia at 11-15 years of age was associated with MS, suggesting a possible role for inflammation of the respiratory system in the aetiology of MS during a period of susceptibility in adolescence. Further research on respiratory infections prior to MS onset should be conducted to replicate this finding and determine explanatory causal mechanisms.

The association between exposure to interferon-beta during pregnancy and birth measurements in offspring of women with multiple sclerosis.

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.

The association between multiple sclerosis and pain medications.

The patients with multiple sclerosis (MS) are at greater risk of pain than people without the disease; however, the occurrence and characteristics of pain among these patients are incompletely described. We aimed to assess characteristics of pain amongst MS patients using MS patients who were recruited to participate in 3 studies in Sweden (n = 3877) and were matched with individuals without MS (n = 4548) by sex, year of birth, and region of residence. The Prescribed Drugs Register identified prescribed pain medication, overall and restricted to those given 4 or more prescriptions in 1 year to assess chronic pain. Anatomical therapeutic chemical codes classified whether pain was neuropathic, musculoskeletal, or migraine. Cox-proportional hazard models were used to estimate associations. Our findings showed the patients with MS were at increased risk of pain treatment, with a hazard ratio (HR) of 2.52 (95% confidence interval 2.38-2.66). The largest magnitude HR was for neuropathic pain (5.73, 5.07-6.47) for which 34.2% (n = 1326) of the MS and 7.15% (n = 325) of the non-MS cohort were prescribed a treatment. The HR for chronic pain treatment was 3.55 (3.27-3.84), indicating an increased effect size relative to any pain treatment. Chronic neuropathic pain showed the largest HR at 7.43 (6.21-8.89). Neuropathic pain was shown to be the primary mechanism leading to increased risk of pain in patients with MS.

The national incidence of PML in Sweden, 1988-2013.

OBJECTIVE: To investigate the incidence of progressive multifocal leukoencephalopathy (PML) and patient characteristics in Sweden between 1988 and 2013. METHODS: All PML diagnoses in Sweden between 1988 and 2013 were identified in the National Patient Register. Information to validate the diagnosis and patient characteristics was obtained from medical records. RESULTS: Medical record review classified 108 out of 250 patients (43%) as definite (n = 84), probable (n = 4), or possible (n = 20) PML according to diagnostic criteria. Accurate diagnoses were more common in records obtained from neurology departments (82% of patients seen in neurology departments) compared with other departments (31%) (p < 0.001). The incidence of PML increased from a largely stable level at 0.026 (95% confidence interval [CI] 0.021-0.031) per 100,000 individuals per year during 1988-2010 to 0.11 (95% CI 083-0.137) during 2011-2013, during which time there was a notable increase (p < 0.001). Hematologic malignancies (n = 34), HIV/AIDS (n = 33), and autoimmune disease (n = 23) were the most common underlying diseases. Treatment with a monoclonal antibody prior to PML diagnosis was identified in 26 patients. CONCLUSION: An increased incidence of PML in Sweden was observed and coincided with the prior use of monoclonal antibody treatment. The high level of misdiagnosis emphasizes the importance of immediate contact with a neurology center upon suspicion of PML.

Association of Timing of Sexual Partnerships and Perceptions of Partners' Concurrency With Reporting of Sexually Transmitted Infection Diagnosis.

Importance: The timing of sexual partnerships is important for sexually transmitted infection (STI) transmission potential. Studies often measure timing as whether partnerships overlap in time (concurrency), but this measure does not account for how STI risk from previous partners can be carried forward into future partnerships even when there is a time gap between them (serial monogamy) if the infectious period is greater than this time gap. Objective: To examine the association of the timing of partnerships, measured as the time gap or time overlap between partners, and perceptions of partners' concurrency with STI transmission. Design, Setting, and Participants: This survey study that was conducted in 2017 included 8867 participants in Britain aged 16 to 44 years who reported 1 or more sexual partners in the 5 years before the interview. Data were collected from 2010 to 2012 from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a large probability survey (response rate, 57.7%) designed to be broadly representative of the general population. Exposures: Gaps between participants' 3 or fewer most recent partners in the past 5 years were calculated from dates of the last sexual encounter with former partners and the first sexual encounter with subsequent partners. Negative gaps denote overlapping partnerships (concurrency); positive gaps denote serial monogamy. Participant perception of most recent partner concurrency was proxied by asking participants whether they knew or thought that their partners had had sex with other partners since their first sexual encounter together. Main Outcomes and Measures: Reported STI diagnosis in the past 5 years. Results: Of 8867 participants eligible for this analysis, 3509 (39.6%) were male and 5158 (58.2%) were female, with a mean age of 28 years. Overall, 48.1% of males and 39.5% of females reported 2 or more partners and 1 or more time gaps. The median time gap was 2 months (interquartile range, -3 months to 8 months). Although 67.0% of the time gaps were 1 month or more, many were sufficiently short time gaps for STI transmission. The time gap was independently associated with STI diagnosis, without a significant decrease in likelihood until the time gap was 4 months or more for females (adjusted odds ratio [OR]: 0.39, 95% CI, 0.19-0.81) and 6 months or more for males (adjusted OR: 0.42, 95% CI, 0.20-0.85) compared with time overlaps of 2 years or more. Participant perception of partners' concurrency (reported by half of the participants) was independently associated with STI diagnosis among females (reporting no partner concurrency vs reporting partner concurrency: adjusted OR, 0.32; 95% CI, 0.22-0.49). Conclusions and Relevance: The findings suggest that the gap between partners is often sufficiently small to permit STI transmission and that many people, although themselves monogamous, have partners who are not, which itself is associated with an increase in the risk of STI acquisition. Public health practitioners should communicate these epidemiological facts, and researchers should develop measures that better capture the risk of STI transmission from partners.

Concussion in adolescence and risk of multiple sclerosis.

OBJECTIVE: To assess whether concussion in childhood or adolescence is associated with subsequent multiple sclerosis (MS) risk. Previous research suggests an association, but methodological limitations included retrospective data collection and small study populations. METHODS: The national Swedish Patient Register (hospital diagnoses) and MS Register were used to identify all MS diagnoses up to 2012 among people born since 1964, when the Patient Register was established. The 7,292 patients with MS were matched individually with 10 people without MS by sex, year of birth, age/vital status at MS diagnosis, and region of residence (county), resulting in a study population of 80,212. Diagnoses of concussion and control diagnoses of broken limb bones were identified using the Patient Register from birth to age 10 years or from age 11 to 20 years. Conditional logistic regression was used to examine associations with MS. RESULTS: Concussion in adolescence was associated with a raised risk of MS, producing adjusted odds ratios (95% confidence intervals) of 1.22 (1.05-1.42, p = 0.008) and 2.33 (1.35-4.04, p = 0.002) for 1 diagnosis of concussion and >1 diagnosis of concussion, respectively, compared with none. No notable association with MS was observed for concussion in childhood, or broken limb bones in childhood and adolescence. INTERPRETATION: Head trauma in adolescence, particularly if repeated, is associated with a raised risk of future MS, possibly due to initiation of an autoimmune process in the central nervous system. This further emphasizes the importance of protecting young people from head injuries. Ann Neurol 2017;82:554-561.

Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012.

OBJECTIVE: To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden. METHODS: Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS. RESULTS: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86-2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators. CONCLUSIONS: There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.