Hospital-treated infections and subsequent Parkinson's disease risk: a register-based sibling comparison study.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

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.

Association between dementia risk and ulcerative colitis, with and without colectomy: a Swedish population-based register study.

OBJECTIVE: This study aims to investigate the association of ulcerative colitis (UC) with all-cause dementia and assess differences in those with and without a total colectomy. DESIGN, SETTING AND PARTICIPANTS: This Swedish prospective register-based study comprised 4.8 million individuals aged at least 59 years between 1964 and 2018 with the linkage of several Swedish national registers. PRIMARY AND SECONDARY OUTCOME MEASURES: Individuals with dementia were defined according to International Classification of Diseases diagnostic codes and Anatomical Therapeutic Classification codes for medication prescriptions. Fitting Cox hazards models, the risk of developing all-cause dementia in individuals with and without UC was estimated. Further, we compared the risk of all-cause dementia among those with and without a colectomy. RESULTS: Among 4 821 488 individuals (52.6% females) followed for 84.1 million person-years between 1964 and 2018, the incidence rate of all-cause dementia was 63.90 (63.73-64.07) events per 10 000 person-years in individuals without UC, 94.80 (92.04-97.64) among those with UC, 95.01 (92.25-97.86) in those with UC but without colectomy and 63.42 (40.92-98.31) in those with UC and a colectomy. Adjusted Cox models showed an increased all-cause dementia risk in individuals with UC (HR 1.07, 95% CI 1.04 to 1.10). We found no differences between unexposed individuals and those with UC and a colectomy (HR 0.89, 95% CI 0.57 to 1.38). CONCLUSION: The findings are consistent with previous evidence suggesting a slightly increased dementia risk among individuals with UC. This study provided no evidence of further risk increase of dementia among those who had a colectomy.

Parental death and initiation of antidepressant treatment in surviving children and youth: a national register-based matched cohort study.

Background: Population-based longitudinal studies on bereaved children and youth's mental health care use are scarce and few have assessed the role of surviving parents' mental health status. Methods: Using register data of individuals born in Sweden in 1992-1999, we performed a matched cohort study (n = 117,518) on the association between parental death and subsequent initiation of antidepressant treatment among individuals bereaved at ages 7-24 years. We used flexible parametric survival models to estimate the hazard ratios (HRs) over time after bereavement, adjusting for individual and parental factors. We further examined if the association varied by age at loss, sex, parental sociodemographic factors, cause of death, and the surviving parents' psychiatric care. Findings: The bereaved were more likely to initiate antidepressants treatment than the nonbereaved matched individuals during follow-up (incidence rate per 1000 person years 27.5 [26.5-28.5] vs. 18.2 [17.9-18.6]). The HRs peaked in the first year after bereavement and remained higher than the nonbereaved individuals until the end of the follow-up. The average HR over the 12 years of follow-up was 1.48 (95% confidence interval [1.39-1.58]) for father's death and 1.33 [1.22-1.46] for mother's death. The HRs were particularly high when the surviving parents received psychiatric care before bereavement (2.11 [1.89-2.56] for father's death; 2.14 [1.79-2.56] for mother's death) or treated for anxiety or depression after bereavement (1.80 [1.67-1.94]; 1.82 [1.59-2.07]). Interpretation: The risk of initiating antidepressant treatment was the highest in the first year after parental death and remained elevated over the next decade. The risk was particularly high among individuals with surviving parents affected by psychiatric morbidity. Funding: The Swedish Research Council.

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.

Suicide Around the Anniversary of a Parent's Death in Sweden.

Importance: Bereavement following parental death experienced in adulthood may be associated with suicide over many years, but this risk has received scant attention. Objective: To investigate whether the risk of suicide increases among adult children around the anniversary of a parent's death. Design, Setting, and Participants: This case-crossover study used Swedish register-based longitudinal data from 1990 to 2016, based on the entire national population. Participants included all adults aged 18 to 65 years who experienced parental death and subsequently died by suicide. Conditional logistic regression was used to quantify the association between the anniversary (or preanniversary and postanniversary periods) and suicide, controlling for time-invariant confounding. All analyses were stratified by sex of the offspring. The analyses were also stratified by the sex of the deceased parent, time since parental death, age, and marital status. Data analyses were performed in June 2022. Exposures: Anniversary of a parent's death (or preanniversary and postanniversary periods). Main Outcomes and Measures: Suicide. Results: Of 7694 individuals who died by suicide (76% intentional self-harm), 2255 (29%) were women, and the median (IQR) age at suicide was 55 (47-62) years. There was evidence of an anniversary reaction among women, with a 67% increase in the odds of suicide when exposed to the period from the anniversary to 2 days after the anniversary, compared with when not being exposed (odds ratio [OR], 1.67; 95% CI, 1.07-2.62). The risk was particularly pronounced among maternally bereaved women (OR, 2.29; 95% CI, 1.20-4.40) and women who were never married (OR, 2.08; 95% CI, 0.99-4.37), although the latter was not statistically significant. An increased risk of suicide from the day before up to the anniversary was observed among women bereaved between the ages of 18 and 34 years (OR, 3.46; 95% CI, 1.14-10.56) and between the ages of 50 and 65 years (OR, 2.53; 95% CI, 1.04-6.15). Men had an attenuated suicide risk for the period from the day before up to the anniversary (OR, 0.57; 95% CI, 0.36-0.92). Conclusions and Relevance: These findings suggest that the anniversary of a parent's death is associated with an increased suicide risk among women. Women bereaved at younger or older ages, those who were maternally bereaved, and those who never married appeared to be particularly vulnerable. Families and social and health care professionals need to consider anniversary reactions in suicide prevention.

Myopia in late adolescence and subsequent multiple sclerosis among men.

BACKGROUND: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS. METHODS: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010. RESULTS: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]). CONCLUSION: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.

Caregiving and changes in health-related behaviour.

Potential health risks for informal caregivers have been hypothesised to be partly related to adverse changes in health-related behaviour, but evidence is limited. We examined whether smoking, drinking, eating, physical activity or leisure pursuits change in relation to co-resident or out-of-home caregiving (for someone outside the household), and if associations differ by sex, educational attainment, and welfare state typology. We conducted a longitudinal study using six waves of the Survey of Health, Ageing and Retirement in Europe, collecting data repeatedly from 2004 to 2017 for adults aged 50 years and older living in 17 European countries (57,962 individuals). To control for measured and unmeasured within-individual time-invariant confounders, we used fixed effects logistic models to analyse the repeated measures of caregiving, behaviour and covariates and estimated odds ratios (OR) with 95% confidence intervals (95%CI). Among male participants, unhealthy eating increased while smoking decreased [ORs 1.26 (95%CI 1.01-1.58) and 0.53 (0.36-0.78), respectively] in survey waves in which they provided co-resident care, compared with the waves that they did not. Among female participants, there was little change in behaviour between waves with and without co-resident caregiving. When providing out-of-home care, lacks of physical activity and leisure pursuits declined. But in the same time, drinking increased both men and women, and especially among individuals with lower educational attainment and residing in non-Nordic countries. To conclude, overall, increased drinking when providing out-of-home care was most consistent, especially among individuals with lower educational attainment and residing in non-Nordic countries. Otherwise, the associations varied by the type of care, behaviour and population subgroups. These findings indicated that not all caregivers are susceptible to behavioural changes, and that not all behaviour may be involved similarly in linking caregiving to health risks. This opens possibilities to target specific behaviour and groups to prevent adverse changes in health behaviour in caregivers.

Trends in health and health inequality during the Japanese economic stagnation: Implications for a healthy planet.

Introduction: Human health and wellbeing may depend on economic growth, the implication being that policymakers need to choose between population health and the health of ecosystems. Over two decades of low economic growth, Japan's life expectancy grew. Here we assess the temporal changes of subjective health and health inequality during the long-term low economic growth period. Methods: Eight triennial cross-sectional nationally representative surveys in Japan over the period of economic stagnation from 1992 to 2013 were used (n = 625,262). Health is defined positively as wellbeing, and negatively as poor health, based on self-rated health. We used Slope and Relative Indices of Inequality to model inequalities in self-rated health based on household income. Temporal changes in health and health inequalities over time were examined separately for children/adolescents, working-age adults, young-old and old-old. Results: At the end of the period of economic stagnation (2013), compared to the beginning (1992), the overall prevalence of wellbeing declined slightly in all age groups. However, poor health was stable or declined in the young-old and old-old, respectively, and increased only in working-age adults (Prevalence ratio: 1.14, 95% CI 1.08, 1.20, <0.001). Over time, inequality in wellbeing and poor self-rated health were observed in adults but less consistently for children, but the inequalities did not widen in any age group between the start and end of the stagnation period. Conclusions: Although this study was a case study of one country, Japan, and inference to other countries cannot be made with certainty, the findings provide evidence that low economic growth over two decades did not inevitably translate to unfavourable population health. Japanese health inequalities according to income were stable during the study period. Therefore, this study highlighted the possibility that for high-income countries, low economic growth may be compatible with good population health.

Systemic inflammation measured by erythrocyte sedimentation rate and cognitive function among young men in Sweden: A within-sibling analysis.

This study assesses the extent to which the association between erythrocyte sedimentation rate, a marker of inflammation, and cognitive function is explained by shared familial factors using within-sibling analyses. Men who were born in Sweden between 1950 and 1965 and recorded in the Swedish Military Conscription Register between 1969 and 1983 were included (N = 632,396). Erythrocyte sedimentation rate and cognitive function were measured at the conscription assessment (median age = 18.3 years, with a range from 15.5 to 28.5 years). Conventional linear regression and multilevel linear regression with a hybrid modeling approach were used, with the latter to obtain within-effect estimation in which unmeasured familial confounding shared by siblings was controlled for. We found that the association between erythrocyte sedimentation rate and cognitive function at conscription assessment was partly accounted for by, but remained independent of, shared familial factors.

Ageing accounts for much of the association between decreasing grip strength and subsequent loneliness: the English Longitudinal Study of Ageing.

BACKGROUND: Loneliness at older ages has been associated with higher morbidity and mortality. One of the risk factors for loneliness may be age-related decline in skeletal muscle strength, which may limit the possibilities for engagement in usual social activities and maintaining relationships. We aimed to identify if decrease in grip strength is an independent determinant of subsequent change in loneliness. METHODS: Prospective cohort study of participants aged 50 years or older living in private households and provided data in the English Longitudinal Study of Ageing waves 2 (2004/2005), 4 (2008/2009) and 6 (2012/2013) (n=6118). We used fixed effects linear models to estimate ß coefficients and 95% confidence intervals. RESULTS: The adjusted estimates for a 5-kilogramme decrease in grip strength and loneliness score (ranging from 3 to 9) are ß 0.04 and 95% CI -0.003 to 0.08 among men and ß 0.03 and 95% CI -0.02 to 0.09 among women. In age-stratified analysis, a statistically significant association was observed among men below the age of 80 years (0.04, 0.0001 to 0.08) but not among older men (0.04, -0.28 to 0.35), and among women below the age of 80 years (0.03, -0.002 to 0.09) or above (-0.02, -0.32 to 0.28). CONCLUSION: Muscle strength declines with age and may help explain the greater social isolation that occurs at older ages. Decline in strength was only independently associated with modestly increased loneliness among men younger than 80 years of age, indicating its limitation as a potential marker of loneliness risk.

Job Quality in the Late Career in Sweden, Japan and the United States.

Increasing numbers of older workers continue to work after being eligible to claim a state pension, yet little is known about the quality of these jobs. We examine how psychosocial and physical job quality as well as job satisfaction vary over the late career in three contrasting national settings: Sweden, Japan and the United States. Analyses using random effects modelling drew on data from the Swedish Longitudinal Occupational Survey of Health (n = 13,936-15,520), Japanese Study of Ageing and Retirement (n = 3704) and the Health and Retirement Study (n = 6239 and 8002). Age was modelled with spline functions in which two knots were placed at ages indicating eligibility for pensions claiming or mandatory retirement. In each country, post-pensionable-age jobs were generally less stressful, freer and more satisfying than jobs held by younger workers, results that held irrespective of gender or education level.

Same-Sex Marriage and Common Mental Health Diagnoses: A Sibling Comparison and Adoption Approach.

We aimed to test whether the association between same-sex marriage and common mental health diagnoses was explained by shared genetic and environmental familial influences using sibling comparison and adoption analyses. For the sibling comparison analysis, participants (1,177,712 men and 1,266,917 women) were individuals born in Sweden between 1932 and 1994 and had ever been recorded as married (in opposite-sex or same-sex marriages). For the adoption analysis, participants were 147,164 and 1,298 female-female full sibling and adoptive sibling pairs, respectively. Based on medical records, prescribed medication, and death certificates, depression, substance abuse, and suicide (completed and attempted) from age 18 years were identified. For both sexes, being in a same-sex marriage was associated with greater risk of depression, substance abuse, and suicide, compared with being in an opposite-sex marriage. Controlling for shared familial confounding reduced this difference by less than 20% in magnitude, but overall mental health disparities for individuals in same-sex marriages remained statistically significant. Among women, only the genetic correlation between same-sex marriage and depression was statistically significant (r = .33). Same-sex marriage, as a proxy for sexual orientation, was associated with increased risk of certain mental health diagnoses and shared familial confounding explained a small component of this association, depending on the diagnosis. The findings indicate that sexual orientation disparities in mental health outcomes may involve unmeasured factors, and a relatively small proportion should be considered that may be due to shared familial confounding relevant to both sexual orientation and psychopathology.

Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide.

Importance: In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia. Objective: To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide. Design, Setting, and Participants: This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022. Main Outcomes and Measures: A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide. Exposures: A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use. Results: Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54]). Conclusions and Relevance: This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.

Acute appendicitis and ulcerative colitis: a population-based sibling comparison study.

OBJECTIVE: To assess the inverse relationship between acute appendicitis and ulcerative colitis (UC) using a sibling comparison design to adjust for unmeasured familial genetic and environmental factors. DESIGN: The cohort comprised 3.1 million individuals resident in Sweden between 1984 and 2018 with the linkage of several Swedish national registers. Fitting Cox hazards models, we calculated the risk for developing UC in individuals with and without acute appendicitis by the age 20 years adjusting for several potential confounding factors. Further, we performed sibling-stratified analyses to adjust for shared unmeasured familial confounding factors. RESULTS: During 57.7 million person-years of follow-up, 20 848/3 125 232 developed UC among those without appendicitis (3.63 (3.59-3.68) per 10 000 person-years), whereas only 59/35 848 people developed UC among those with appendicitis before age 20 years (1.66 (1.28-2.14) per 10 000 person-years). We found a decreased risk for developing UC in those with acute appendicitis by the age 20 years compared with individuals who did not have appendicitis by this age (HR=0.37 (95% CI 0.29 to 0.48)). When adjusting for shared familial confounders, we observed only a slight attenuation in this association (HR=0.46 (95% CI 0.32 to 0.66)). CONCLUSION: Individuals who had acute appendicitis by late adolescence showed a decreased risk for developing UC compared with those who did not. Genetic and shared familial environmental factors seem to potentially play only a small role in this relationship. Our results suggest an independent association of acute appendicitis, or its underlying causes, with UC risk.

The Relationships between Caregivers' Concern about Child Weight and Their Non-Responsive Feeding Practices: A Systematic Review and Meta-Analysis.

BACKGROUND: It is unclear whether caregivers' concern about child weight impacts their non-responsive feeding practices. This systematic review aimed to examine their relationships. METHODS: A systematic search of PubMed, Embase, PsycINFO, Web of Science core collection, CINAHL and grey literature was conducted from inception to March 2022, following PRISMA guidelines. Data synthesis was performed using a semi-quantitative approach and a meta-analysis. RESULTS: A total of 35 studies with 22,933 respondents were included in the review for semi-quantitative analyses. Thirty-four studies examined 52 associations between concern about child weight and restriction with 40 statistically significant associations being observed. A total of 34 relationships between concern about child weight and pressure to eat were investigated, with 12 being statistically significant. The pooled regression coefficients (ß) demonstrated that caregivers' concern about child overweight was positively associated with restriction (ß = 0.22; 95%CI: 0.12, 0.31), negatively associated with use of food as a reward (ß = -0.06; 95%CI: -0.11, -0.01), and not statistically associated with pressure to eat (ß = -0.05; 95%CI: -0.13, 0.04). The pooled odds ratios (ORs) indicated that caregivers who were concerned about child overweight were found to use restrictive feeding more often (OR = 2.34; 95%CI: 1.69, 3.23), while less frequently adopting pressure to eat (OR = 0.76; 95%CI: 0.59, 0.98) compared with those without concerns. The results also showed that caregivers who were concerned about child underweight were more likely to force their children to eat (OR = 1.83; 95%CI: 1.44, 2.33) than those without concerns. CONCLUSION: Caregivers' concern about child weight may be an important risk factor for non-responsive feeding practices. Thus, interventions are needed to focus on managing and relieving caregivers' excessive concern about child weight, especially overweight, which may optimize feeding practices and subsequently contribute to child health.

Substance use disorder and suicide-related behaviour around dates of parental death and its anniversaries: a register-based cohort study.

BACKGROUND: Parental death and its anniversaries, including anticipation of these dates, might cause distress and increase the risk of substance use disorder and suicide-related behaviour in bereaved adolescents and young adults. We examined whether the risk of substance use disorder and suicide-related behaviour increases around the date of parental death and subsequent anniversaries. METHODS: Using Swedish national registers, we conducted a cohort study of individuals aged 12-24 years. We included individuals aged 12-24 years between Jan 1, 2001, and Dec 31, 2014, whose parents were alive at entry (n=1 858 327) and followed up with them until the end of age 24 years. We excluded individuals with a half-sibling, a history of emigration, a previous record of the outcome events, a parental death before study entry, two parental deaths on the same day during the follow-up, or missing data for relevant variables. Follow-up ended on the day of an outcome event or on Dec 31, 2014; at age 25 years, emigration, or death; or a year before the second parental death. We studied substance use disorder and suicide-related behaviour outcomes separately and included non-fatal and fatal events in both outcomes. We used Cox regression to estimate hazard ratios (HRs), controlling for baseline psychiatric, demographic, and socioeconomic characteristics. Parental death was modelled as a time-varying exposure over 72 monthly periods, starting from 1 year before the parental death to the fifth year and later after the death. Unmeasured confounding was also addressed in within-individual comparisons using a case-crossover design. FINDINGS: During follow-up (median 7·5 [IQR 4·3-10·6] years), there were 42 854 substance use disorder events, with a crude rate of 3·1 per 1000 person-years. For suicide-related behaviour, there were 19 827 events, with a crude rate of 1·4 per 1000 person-years. Most of the events studied were non-fatal. In the month of parental death, the HR for substance use disorder risk was 1·89 (95% CI 1·07-3·33) among male participants, and, for suicide-related behaviour, was 3·76 (1·79-7·89) among male participants and 2·90 (1·61-5·24) among female participants. In male participants, there was an increased risk around the first anniversary (substance use disorder: HR 2·64 [95% CI 1·56-4·46] during the anniversary month; 2·21 [1·25-3·89] for the subsequent month; and for suicide-related behaviour: 3·18 [1·32-7·66] for the subsequent month). Among female participants, an increased risk of substance use disorder recurred around every year consistently in the month before the anniversary of the death and there was an increased risk for suicide-related behaviour in the months of the first and second anniversaries. INTERPRETATION: Although effect sizes were large in this cohort study, the number of individuals who had the outcomes was small. Nevertheless, adolescents and young adults, especially women and girls, who had the death of a parent showed increased risk of substance use disorder and suicide-related behaviour around the first few death anniversaries. Adolescents and young adults, especially women and girls, who had the death of a parent could benefit from preventive measures to reduce distress around the first few years of death anniversaries. FUNDING: Swedish Research Council.

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.