Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study.

BACKGROUND: The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation. METHODS: In a cross-sectional study of young healthy individuals (18.0-25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models. RESULTS: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables. CONCLUSIONS: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.

Fecal incontinence and associated pelvic floor dysfunction during and one year after the first pregnancy.

INTRODUCTION: Obstetric anal sphincter injury is an important risk factor for postpartum fecal incontinence but few studies have reported fecal incontinence occurring, even during pregnancy. The first objective of this study was to examine the prevalence of fecal incontinence, obstructed defecation and vaginal bulging early and late in pregnancy and postpartum. The second objective was to assess the association between symptoms in pregnancy, delivery characteristics, and bowel and vaginal bulging symptoms at 1 year postpartum. MATERIAL AND METHODS: This prospective cohort study was conducted between October 2014 and October 2017, including 898 nulliparous women enrolled with the maternity healthcare service in Örebro County, Sweden. The women responded to questionnaires regarding pelvic floor dysfunction in early and late pregnancy and at 8 weeks and 1 year postpartum. The data were analyzed using random effect logistic models estimating odds ratios (ORs) and generalized linear models estimating relative risks, with 95% confidence intervals (CIs). RESULTS: At 1 year postpartum, the prevalence of fecal incontinence, obstructed defecation and vaginal bulging was 6% (40/694), 28% (197/699) and 8% (56/695), respectively. Among women with vaginal delivery, the risk of fecal incontinence and vaginal bulging increased significantly both in late pregnancy, with ORs of 3.4 (95% CI 1.5-7.7) and 3.6 (95% CI 1.6-8.1), respectively, and at 1 year postpartum, with ORs of 5.0 (95% CI 2.1-11.5) and 8.3 (95% CI 3.8-18.1), respectively, compared with early pregnancy. Among all women, factors associated with increased prevalence of fecal incontinence 1 year postpartum were fecal incontinence during pregnancy (adjusted relative risk [aRR] 7.4; 95% CI 4.1-13.3), obstructed defecation during pregnancy (aRR 2.0; 95% CI 1.1-3.9) and concurrent obstructed defecation (aRR 2.4; 95% CI 1.3-4.5). CONCLUSIONS: This prospective study shows an increased risk of fecal incontinence by late pregnancy, suggesting that the pregnancy itself may be involved in the development of postpartum fecal incontinence. Obstructed defecation during pregnancy and postpartum was found to be associated with increased risk of fecal incontinence postpartum, indicating that postpartum fecal incontinence may be a result of incomplete bowel emptying.

Visual Acuity and the Risk of Cycling Injuries: Register-Based Cohort Study From Adolescence to Middle-age.

BACKGROUND: Cycling is increasingly encouraged in many countries as an inexpensive and healthy choice of transportation. Operating any vehicle on the road requires high visual acuity, but few studies to our knowledge have examined the association between vision and cycling injuries. METHODS: We examined whether poorer visual acuity is associated with increased risk of fatal and nonfatal cycling injuries. We used prospectively recorded register data for 691,402 men born between 1970 and 1992 in Sweden. We followed these men from an average age of 18 years, when visual acuity was assessed during the conscription assessment, to age 45 at the latest. We identified fatal and nonfatal cycling and car injuries using Patient and Cause of Death registers. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: Based on visual acuity for the eye with the best vision, moderately impaired acuity 0.9 to 0.6 when wearing refractive correction was associated with increased risk for cycling injuries (hazard ratio = 1.44 [95% confidence interval = 1.16, 1.79]) compared with unimpaired vision (uncorrected visual acuity 1.0) and after adjustment for a wide range of potential confounders. This association remained consistent across various sensitivity analyses. Visual acuity was not associated with car injury risk. CONCLUSIONS: In this cohort study, poorer vision was specifically associated with a higher rate of cycling injuries.

Editor's Choice - Incidence of Lower Limb Amputations in Sweden from 2008 to 2017.

OBJECTIVE: This study examined the recent national and regional incidence of lower limb amputations (LLAs) in Sweden and their annual changes. METHODS: This was an observational study using Swedish national register data. All initial amputations were identified in Sweden from 2008 to 2017 in individuals 18 years or older using the national inpatient register. The amputations were categorised into three levels: high proximal (through or above the knee joint), low proximal (through the tibia to through the ankle joint), and partial foot amputations. To examine the national and regional incidence and annual changes, the age, sex, and region specific population count each year was used as the denominator and Poisson regression or negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) adjusted for age and sex. RESULTS: The national annual incidence of LLAs was 22.1 per 100 000 inhabitants, with a higher incidence in men (24.2) than in women (20.0). The incidence of LLAs (all levels combined) declined during the study period, with an IRR of 0.984 per year (95% CI 0.973 - 0.994). This was mainly due to a decrease in high proximal amputations (0.985, 95% CI 0.974 - 0.995) and low proximal amputations (0.973, 95% CI 0.962 - 0.984). No change in the incidence of partial foot amputations was observed (0.994, 95% CI 0.974 - 1.014). Such declines in LLA incidence (all levels combined) were observed in nine of the 21 regions. Compared with the national average and with adjustment for age, sex, diabetes, and artery disease, the regional IRR varied from 0.85 to 1.36 for all LLAs, from 0.67 to 1.61 for high proximal amputations, from 0.50 to 1.51 for low proximal amputations, and from 0.13 to 3.68 for partial foot amputations. CONCLUSION: The incidence of LLAs has decreased in Sweden. However, regional variations in incidence, time trends, and amputation levels warrant further research.

Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis.

The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections such as the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20 years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970 and 1994 were identified using the Swedish Total Population Register (n = 2 422 969). Multiple sclerosis diagnoses from age 20 years and hospital-diagnosed infections before age 20 years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11-19 years) and earlier childhood (birth-10 years) was estimated using Cox regression, with adjustment for sex, parental socio-economic position, and infection type. None of the infections by age 10 years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21-1.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06-1.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11-3.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13-1.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30-1.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections.

Sexual function in primiparous women: a prospective study.

INTRODUCTION AND HYPOTHESIS: The aim of this prospective study was to examine the impact of sociodemographic, pregnancy and obstetric characteristics on sexual function 12 months postpartum in primiparous women. We hypothesized that sexual function would decrease after childbirth. METHODS: Between 1 October 2014 and 1 October 2017, all nulliparous women in early pregnancy registering for maternity health care in Region Örebro County, Sweden, were invited to participate in this prospective study. A total of 958 women were included. Sexual activity and function were measured at early pregnancy, 8 weeks postpartum and 12 months postpartum using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). The associations between sociodemographic, pregnancy and obstetric characteristics and sexual activity and function from early pregnancy to 12 months postpartum were examined using linear and logistic models based on generalized estimating equations. RESULTS: We found that the prevalence of sexually active women decreased from 98.0% in early pregnancy to 66.7% at 8 weeks postpartum, but increased to 90.0% at 12 months postpartum. Age ≥ 35 years, second-degree perineal tear and current breastfeeding were statistically significant risk factors for sexual inactivity at 12 months postpartum. Poor self-reported health in early pregnancy was statistically significantly associated with decreased sexual function at 12 months postpartum. CONCLUSIONS: A majority of women resumed sexual activity at 8 weeks postpartum and most women at 12 months postpartum; the decrease in sexual function at 12 months postpartum was small and few risk factors were observed.

Parental death in childhood and pathways to increased mortality across the life course in Stockholm, Sweden: A cohort study.

BACKGROUND: Previous studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63. METHODS AND FINDINGS: A cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality. Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study. CONCLUSIONS: Our findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.

Appetite disinhibition rather than hunger explains genetic effects on adult BMI trajectory.

BACKGROUND/OBJECTIVES: The mediating role of eating behaviors in genetic susceptibility to weight gain during mid-adult life is not fully understood. This longitudinal study aims to help us understand contributions of genetic susceptibility and appetite to weight gain. SUBJECTS/METHODS: We followed the body-mass index (BMI) trajectories of 2464 adults from 45 to 65 years of age by measuring weight and height on four occasions at 5-year intervals. Genetic risk of obesity (gene risk score: GRS) was ascertained, comprising 92 BMI-associated single-nucleotide polymorphisms and split at a median (=high and low risk). At the baseline, the Eating Inventory was used to assess appetite-related traits of 'disinhibition', indicative of opportunistic eating or overeating and 'hunger' which is susceptibility to/ability to cope with the sensation of hunger. Roles of the GRS and two appetite-related scores for BMI trajectories were examined using a mixed model adjusted for the cohort effect and sex. RESULTS: Disinhibition was associated with higher BMI (ß = 2.96; 95% CI: 2.66-3.25 kg/m2), and accounted for 34% of the genetically-linked BMI difference at age 45. Hunger was also associated with higher BMI (ß = 1.20; 0.82-1.59 kg/m2) during mid-life and slightly steeper weight gain, but did not attenuate the effect of disinhibition. CONCLUSIONS: Appetite disinhibition is most likely to be a defining characteristic of genetic susceptibility to obesity. High levels of appetite disinhibition, rather than hunger, may underlie genetic vulnerability to obesogenic environments in two-thirds of the population of European ancestry.

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.

Higher body mass index at ages 16 to 20 years is associated with increased risk of a multiple sclerosis diagnosis in subsequent adulthood among men.

BACKGROUND: Evidence for the association between body mass index (BMI) and multiple sclerosis (MS) among men remains mixed. OBJECTIVE AND METHODS: Swedish military conscription and other registers identified MS after age of 20 years and BMI at ages 16-20 years (N = 744,548). RESULTS: Each unit (kg/m2) BMI increase was associated with greater MS risk (hazard ratio and 95% confidence interval = 1.034, 1.016-1.053), independent of physical fitness (1.021, 1.001-1.042). Categorised, overweight and obesity were associated with statistically significant raised MS risk compared to normal weight, but not after adjustment for physical fitness. CONCLUSION: MS risk rises with increasing BMI, across the entire BMI range.

Stress and urgency urinary incontinence one year after a first birth-prevalence and risk factors. A prospective cohort study.

INTRODUCTION: Few prospective studies have examined the effect of pregnancy and childbirth on stress and urgency urinary incontinence separately. The aim of the present study was to assess the extent to which pregnancy, vaginal delivery, and vaginal delivery characteristics affect the risk of significant stress and urgency incontinence 1 year after delivery. MATERIAL AND METHODS: We conducted a prospective cohort study of 670 nulliparous women from early pregnancy to 1 year partum. The women were recruited at maternity health care service in Region Örebro County, Sweden, between October 1, 2014 and October 1, 2017 and completed questionnaires in early and late pregnancy and at 8 weeks and 1 year postpartum. Primary outcome measures were significant stress and urgency incontinence at 1 year postpartum in women who reported being continent before pregnancy. Generalized linear models were used. RESULTS: Stress and urgency incontinence commencing before pregnancy were reported by 4% and 3% of women, respectively, in the first questionnaire in early pregnancy, and these women were excluded from subsequent analysis. Stress and urgency incontinence were reported by 21% and 8%, respectively, at 1 year postpartum, in women not reporting incontinence before pregnancy. Stress incontinence during pregnancy increased the risk of stress incontinence postpartum (risk ratio [RR] 2.48, 95% CI 1.86-3.3). Urgency incontinence during pregnancy increased the risk of urgency incontinence postpartum (RR 4.07, 95% CI 2.1-7.89). Vaginal delivery increased the risk of stress incontinence postpartum (adjusted RR 2.63, 95% CI 1.39-5.01) but not of urgency incontinence. This effect of vaginal delivery on stress incontinence was similar irrespective of incontinence status during pregnancy. The population-attributable fraction of stress incontinence associated with vaginal delivery was 0.58 (95% CI 0.23-0.77). CONCLUSIONS: This study shows essentially different risk factors for stress and urgency incontinence, supporting stress incontinence as being the subtype mostly associated with pregnancy and childbirth, and urgency incontinence as being more stable over time. At a population level, vaginal delivery was the major risk factor for stress incontinence, followed by reporting stress incontinence during pregnancy.

Risk factors for perineal and vaginal tears in primiparous women - the prospective POPRACT-cohort study.

BACKGROUND: The aim of this study was to estimate the incidence of second-degree perineal tears, obstetric anal sphincter injuries (OASI), and high vaginal tears in primiparous women, and to examine how sociodemographic and pregnancy characteristics, hereditary factors, obstetric management and the delivery process are associated with the incidence of these tears. METHODS: All nulliparous women registering at the maternity health care in Region Örebro County, Sweden, in early pregnancy between 1 October 2014 and 1 October 2017 were invited to participate in a prospective cohort study. Data on maternal and obstetric characteristics were extracted from questionnaires completed in early and late pregnancy, from a study-specific delivery protocol, and from the obstetric record system. These data were analyzed using unadjusted and adjusted multinomial and logistic regression models. RESULTS: A total of 644 women were included in the study sample. Fetal weight exceeding 4000 g and vacuum extraction were found to be independent risk factors for both second-degree perineal tears (aOR 2.22 (95% CI: 1.17, 4.22) and 2.41 (95% CI: 1.24, 4.68) respectively) and OASI (aOR 6.02 (95% CI: 2.32, 15.6) and 3.91 (95% CI: 1.32, 11.6) respectively). Post-term delivery significantly increased the risk for second-degree perineal tear (aOR 2.44 (95% CI: 1.03, 5.77), whereas, maternal birth positions with reduced sacrum flexibility significantly decreased the risk of second-degree perineal tear (aOR 0.53 (95% CI 0.32, 0.90)). Heredity of pelvic floor dysfunction and/or connective tissue deficiency, induced labor, vacuum extraction and fetal head circumference exceeding 35 cm were independent risk factors for high vaginal tears (aOR 2.32 (95% CI 1.09, 4.97), 3.16 (95% CI 1.31, 7.62), 2.53 (95% CI: 1.07, 5.98) and 3.07 (95% CI 1.5, 6.3) respectively). CONCLUSION: The present study corroborates previous findings of vacuum extraction and fetal weight exceeding 4000 g as risk factors of OASI. We found that vacuum extraction is a risk factor for second-degree tear, and vacuum extraction, fetal head circumference exceeding 35 cm and heredity of pelvic floor dysfunction and/or connective tissue deficiency were associated with increased risk of high vaginal tears. These findings have not been documented previously and should be confirmed by additional studies.

Risk of depression following traumatic limb amputation-a general population-based cohort study.

Background: Individuals with traumatic limb amputation (TLA) may be at risk of depression, but evidence of increased depression after TLA from longitudinal studies has been limited. It is also unknown whether physical function, cognitive function, and employment prior to amputation affects depression risk. We aimed to examine longitudinal associations between TLA and depression in working age men, and to explore the role of pre-amputation occupational and individual characteristics. Methods: A Swedish national register-based cohort of 189,220 men born between 1952 and 1956, and who attended conscription assessments in adolescence, was followed from 1985 to 2009. Physical, cognitive, and psychological characteristics were measured at the conscription examination, and occupational information was obtained from the 1985 census. Main outcome measures were hospital inpatient and outpatient admissions for depression. Results: In total, 401 men underwent TLA; mean age at amputation was 42.5 years (SD 7.4). Cox regression produced an unadjusted hazard ratio (95% confidence interval) of 2.61 (1.62-4.21) for risk of subsequent depression associated with TLA compared with the general population. Adjustment for occupational, physical, cognitive, and psychological characteristics did not change the association much, producing a hazard ratio of 2.53 (1.57-4.08). Conclusions: TLA is associated with an increased risk of depression in men over more than two decades of follow up. Occupational and individual characteristics prior to amputation did not greatly change depression risk following amputation. We speculate that a coordinated combination of social support and medical management may help reduce persistent depression risk in men who experience amputation.

Shared unmeasured characteristics among siblings confound the association of Apgar score with stress resilience in adolescence.

AIM: We investigated the association between low Apgar score, other perinatal characteristics and low stress resilience in adolescence. A within-siblings analysis was used to tackle unmeasured shared familial confounding. METHODS: We used a national cohort of 527 763 males born in Sweden between 1973 and 1992 who undertook military conscription assessments at mean age of 18 years (17-20). Conscription examinations included a measure of stress resilience. Information on Apgar score and other perinatal characteristics was obtained through linkage with the Medical Birth Register. Analyses were conducted using ordinary least squares and fixed-effects linear regression models adjusted for potential confounding factors. RESULTS: Infants with a prolonged low Apgar score at five minutes had an increased risk of low stress resilience in adolescence compared with those with highest scores at one minute, with an adjusted coefficient and 95% confidence interval of -0.26 (-0.39, -0.13). The associations were no longer statistically significant when using within-siblings models. However, the associations with stress resilience and birthweight remained statistically significant in all analyses. CONCLUSION: The association with low Apgar score seems to be explained by confounding due to shared childhood circumstances among siblings from the same family, while low birthweight is independently associated with low stress resilience.

Trajectories of income and social benefits for mothers and fathers of children with cancer: A national cohort study in Sweden.

BACKGROUND: The contribution of different income sources from work and social benefits to trajectories of income for the parents of children with cancer has not been empirically investigated. METHODS: Using Swedish registers, parents of children with an incidence cancer diagnosis between 2004 and 2009 were identified and matched with parents of children without cancer (reference parents). A total of 20,091 families were followed from the year before the diagnosis to a maximum of 8 years. Generalized linear models estimated the ratios of mean incomes from work and social benefits and of its total. RESULTS: Around the time of the child's cancer diagnosis, the total income was on average up to 6% higher among the mothers of children with cancer compared with reference mothers, but no differences were noted among fathers. Income from work dropped to the lowest level around the time of a cancer diagnosis, with swift recovery noted for fathers but not for mothers. Sickness and childcare-related benefits were up to 6 times larger for the parents of children with cancer than reference parents. As social benefits diminished after approximately 3 years, the total income of mothers of children with cancer became lower than that of reference mothers, and the gap widened over time. CONCLUSIONS: Social benefits appeared to ease the financial burden during the years around a cancer diagnosis. However, mothers experienced persistently lower income after benefits diminished. Experiences differed by single-parent versus dual-parent households, the survival of the child with cancer, and other relevant characteristics. Further investigation is needed for potential long-term consequences for mothers, including their career and future pension in retirement. Cancer 2018;124:1492-500. © 2018 American Cancer Society.

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.

Resilience to stress and risk of gastrointestinal infections.

Background: Exposure to psychological stress can elicit a physiological response that may influence characteristics of the gastrointestinal mucosa, including increased intestinal permeability, in turn possibly increasing susceptibility to gastrointestinal infections. We investigated whether low stress resilience in adolescence is associated with an 'increased' risk of gastrointestinal infections in subsequent adulthood. Methods: Data were provided by Swedish registers for a cohort of 237 577 men who underwent military conscription assessment in late adolescence (1969-76). As part of the assessment procedure, certified psychologists evaluated stress resilience through semi-structured interviews. The cohort was followed from conscription assessment until 31 December 2009 (up to age 57 years). Cox regression assessed the association of stress resilience with gastrointestinal infections (n = 5532), with adjustment for family background measures in childhood and characteristics in adolescence. Peptic ulcer disease (PUD) in adulthood was modelled as a time-dependent covariate. Results: Compared with high stress resilience, lower stress resilience was associated with a 'reduced' risk of gastrointestinal infections after adjustment for family background in childhood, characteristics in adolescence and PUD in adulthood, with hazard ratios (and 95% confidence intervals) of 0.88 (0.81-0.97) and 0.83 (0.77-0.88) for low and moderate stress resilience, respectively. Conclusion: Lower stress resilience in adolescence is associated with reduced risk of gastrointestinal infections in adulthood, rather than the hypothesized increased risk.

Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: The findings of prospective cohort studies are inconsistent regarding the association between dietary magnesium intake and serum magnesium concentration and the risk of hypertension. We aimed to review the evidence from prospective cohort studies and perform a dose-response meta-analysis to investigate the relationship between dietary magnesium intake and serum magnesium concentrations and the risk of hypertension. METHODS: We searched systematically PubMed, EMBASE and the Cochrane Library databases from October 1951 through June 2016. Prospective cohort studies reporting effect estimates with 95% confidence intervals (CIs) for hypertension in more than two categories of dietary magnesium intake and/or serum magnesium concentrations were included. Random-effects models were used to combine the estimated effects. RESULTS: Nine articles (six on dietary magnesium intake, two on serum magnesium concentration and one on both) of ten cohort studies, including 20,119 cases of hypertension and 180,566 participates, were eligible for inclusion in the meta-analysis. We found an inverse association between dietary magnesium intake and the risk of hypertension [relative risk (RR) = 0.92; 95% CI: 0.86, 0.98] comparing the highest intake group with the lowest. A 100 mg/day increment in magnesium intake was associated with a 5% reduction in the risk of hypertension (RR = 0.95; 95% CI: 0.90, 1.00). The association of serum magnesium concentration with the risk of hypertension was marginally significant (RR = 0.91; 95% CI: 0.80, 1.02). CONCLUSIONS: Current evidence supports the inverse dose-response relationship between dietary magnesium intake and the risk of hypertension. However, the evidence about the relationship between serum magnesium concentration and hypertension is limited.