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Summary: Both short (< 6 hr) and long (> 8 hr) sleep are associated with increased mortality. We here investigated whether the association between sleep duration and all‐cause, cardiovascular disease and cancer mortality differs between men and women. A cohort of 34,311 participants (mean age and standard deviation = 50.5 ± 15.5 years, 65% women), with detailed assessment of sleep at baseline and up to 20.5 years of follow‐up (18 years for cause‐specific mortality), was analysed using Cox proportional hazards model to estimate HRs with 95% confidence intervals. After adjustment for covariates, all‐cause, cardiovascular disease and cancer mortalities were increased for both < 5 hr and ≥ 9 hr sleep durations (with 6 hr as reference). For all‐cause mortality, women who slept < 5 hr had a hazard ratio = 1.54 (95% confidence interval = 1.32–1.80), while the corresponding hazard ratio was 1.05 (95% confidence interval = 0.88–1.27) for men, the interaction being significant (p < 0.05). For cardiovascular disease mortality, exclusion of the first 2 years of exposure, as well as competing risk analysis eliminated the originally significant interaction. Cancer mortality did not show any significant interaction. Survival analysis of the difference between the reference duration (6 hr) and the short duration (< 5 hr) during follow‐up showed a gradually steeper reduction of survival time for women than for men for all‐cause mortality. We also observed that the lowest cancer mortality appeared for the 5‐hr sleep duration. In conclusion, the pattern of association between short sleep duration and all‐cause mortality differed between women and men, and the difference between men and women increased with follow‐up time. [ABSTRACT FROM AUTHOR]

Systemic inflammation is thought to mediate the link between sleep and cardiovascular outcomes, but previous studies on sleep habits and inflammation markers have found inconsistent results. This study investigated the relationship between sleep characteristics and C‐reactive protein (CRP), interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα). A representative sample of 319 Swedish women was randomly selected from the general population for in‐home polysomnography, sleep questionnaire and blood samples. As variables were highly correlated, principal component analysis was used to reduce the number of original variables. Linear regression with log‐transformation of the outcomes (lnCRP, lnIL‐6 and lnTNFα) and quantile regression were fitted to estimate cross‐sectional relationships. Multivariable linear regression models suggested a significant association of insomnia symptoms (self‐reported) with higher lnCRP levels (β = 0.11; 95% confidence interval [CI] = 0.02; 0.21), but not with lnIL‐6 and lnTNFα. From quantile regression analysis we found that a high non‐restorative index (subjective) and insomnia symptoms (self‐reported) were associated with higher values of CRP, especially in the highest quantiles of the CRP distribution (90th percentile: β = 0.71; 95% CI = 0.17; 1.24. β = 1.23; 95% CI = 0.44; 2.02, respectively). Additionally, higher amounts of rapid eye movement (REM) sleep were associated with lower CRP values (90th percentile: β = −0.80; 95% CI = −0.14; −1.46). In conclusion, sleep disturbances (self‐reported), specifically difficulties maintaining sleep and early morning awakenings, but not sleep duration (neither subjective nor objective), were associated with higher CRP levels. No association was found with IL‐6 or TNFα. Elevated REM sleep was associated with lower CRP levels. The results suggest that inflammation might be an intermediate mechanism linking sleep and health in women. [ABSTRACT FROM AUTHOR]

Objective: Previous studies investigating the association between nightmares and suicide have yielded different results. We aimed to investigate whether nightmares, directly or indirectly, influence the incidence of suicide.Methods: We used a prospective cohort study, based on 40,902 participants with a mean follow-up duration of 19.0 years. Cox proportional hazards models with attained age as time-scale were fitted to estimate hazard ratios (HR) of suicide with 95% confidence intervals (CI) as a function of the presence or absence of depression and nightmares. Mediation analysis was used to asses to what extent the relationship between nightmares and the incidence rate of suicide could be mediated by depression.Results: No association was observed between nightmares and the incidence of suicide among participants without depression. Compared with non-depressed participants without nightmares, the incidence of suicide among participants with a diagnosis of depression was similar among those with and without nightmares (HR 12.3, 95% CI 5.55-27.2 versus HR 13.2, 95% CI 7.25-24.1). The mediation analysis revealed no significant effects of nightmares on suicide incidence. However, the incidence of depression during follow-up was higher among those who suffered from nightmares than among those who did not (p < 0.001).Conclusions: Our findings indicate that nightmares have no influence on the incidence rate of suicide, but may reflect pre-existing depression. This is supported by a recent discovery of a strong genetic correlation of nightmares with depressive disorders, with no evidence that nightmares would predispose to psychiatric illness or psychological problems. Interventions targeting both depression and nightmares, when these conditions co-occur, may provide additional therapeutic benefit. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an association between body mass index (BMI) and infections, but the literature on type-specific community acquired infections is still limited.Methods: We included 39 163 Swedish adults who completed a questionnaire in September 1997 and were followed through record-linkages until December 2016. Information on BMI was self-reported and infections were identified from the Swedish National Patient Register using International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes. We fitted multivariable Cox proportional hazards models for time-to-first-event analysis, and we used extensions of the standard Cox model when repeated events were included.Results: During a 19-year follow-up 32% of the subjects had at least one infection requiring health care contact, leading to a total of 27 675 events. We found an increased incidence of any infection in obese women [hazard ratio (HR) = 1.22; 95% confidence interval (CI) = 1.12; 1.33] and obese men (HR = 1.25; 95% CI = 1.09; 1.43) compared with normal weight subjects. For specific infections, higher incidences were observed for skin infections in both genders (HR = 1.76; 95% CI = 1.47; 2.12 for obese females and HR = 1.74; 95% CI = 1.33; 2.28 for obese males) and gastrointestinal tract infections (HR = 1.44; 95% CI = 1.19; 1.75), urinary tract infections (HR = 1.30; 95% CI = 1.08; 1.55) and sepsis (HR = 2.09; 95% CI = 1.46; 2.99) in obese females. When accounting for repeated events, estimates similar to the aforementioned ones were found.Conclusions: Obesity was associated with an increased risk of infections in both genders. Results from multiple-failure survival analysis were consistent with those from classic Cox models. [ABSTRACT FROM AUTHOR]

Purpose: The Nordic Nutrition Recommendations (NNR) are developed to prevent diet-related diseases. This study aimed to examine adherence to the NNR and risk of myocardial infarction (MI) and stroke among women and men in Sweden. Methods: We followed 34,898 adults from 1997 to 2016. Dietary intake was assessed once at baseline using a food frequency questionnaire. Adherence scores corresponding to NNR-editions from 2023, 2012, 2004 and 1996 were calculated. Scores were categorized into low (reference category), moderate and high adherence. Cox proportional hazards regression models adjusted for potential confounders were used to estimate hazards ratios (HR) with 95% confidence intervals (CI). Results: We identified 1649 incident cases of MI and 2071 incident cases of stroke during follow-up (mean 17.9 years). For each 1-point increase in the NNR2023-score (range 0–9), the rate of MI decreased by 14% (HR: 0.86; 95% CI 0.78–0.95). High adherence was associated with a lower rate of MI (HR: 0.72; 95% CI 0.59–0.87) (p-trend = 0.01). Moderate adherence was associated with a lower rate of stroke (HR: 0.88; 95% CI 0.78–0.99) (p-trend = 0.31). Among women, a 23% lower rate of MI (HR: 0.77; 95% CI 0.67–0.89) was observed for each 1-point increase, and high adherence was associated with a lower rate of MI (HR: 0.59; 95% CI 0.45–0.78). No associations were found in men. The results were similar, though attenuated, for earlier NNR-editions. Conclusion: Adherence to the NNR was associated with a reduced risk of MI. This association was more pronounced among women than among men and in more recent NNR-editions. The findings for stroke need further investigation. [ABSTRACT FROM AUTHOR]

In epidemiological studies it is often necessary to disentangle the pathways that link an exposure to an outcome. Typically the aim is to identify the total effect of the exposure on the outcome, the effect of the exposure that acts through a given set of mediators of interest (indirect effect) and the effect of the exposure unexplained by those same mediators (direct effect). The traditional approach to mediation analysis is based on adjusting for the mediator in standard regression models to estimate the direct effect. However, several methodological papers have shown that under a number of circumstances this traditional approach may produce flawed conclusions. Through a better understanding of the causal structure of the variables involved in the analysis, with a formal definition of direct and indirect effects in a counterfactual framework, alternative analytical methods have been introduced to improve the validity and interpretation of mediation analysis. In this paper, we review and discuss the impact of the three main sources of potential bias in the traditional approach to mediation analyses: (i) mediator-outcome confounding;(ii) exposure-mediator interaction and (iii) mediator-outcome confounding affected by the exposure. We provide examples and discuss the impact these sources have in terms of bias. [ABSTRACT FROM AUTHOR]

A significant aspect of data modeling with categorical predictors is the definition of a saturated model. In fact, there are different ways of specifying it-the casewise, the contingency table, and the collapsing approaches-and they strictly depend on the unit of analysis considered. The analytical units of reference could be the subjects or, alternatively, groups of subjects that have the same covariate pattern. In the first case, the goal is to predict the probability of success (failure) for each individual; in the second case, the goal is to predict the proportion of successes (failures) in each group. The analytical unit adopted does not affect the estimation process; however, it does affect the definition of a saturated model. Consequently, measures and tests of goodness of fit can lead to different results and interpretations. Thus one must carefully consider which approach to choose. In this article, we focus on the deviance test for logistic regression models. However, the results and the conclusions are easily applicable to other linear models involving categorical regressors. We show how Stata 12.1 performs when implementing goodness of fit. In this situation, it is important to clarify which one of the three approaches is implemented as default. Furthermore, a prominent role is played by the shape of the dataset considered (individual format or events-trials format) in accordance with the analytical unit choice. In fact, the same procedure applied to different data structures leads to different approaches to a saturated model. Thus one must attend to practical and theoretical statistical issues to avoid inappropriate analyses. [ABSTRACT FROM AUTHOR]

A common aim of epidemiological research is to assess the association between a particular exposure and a particular outcome, controlling for a set of additional covariates. This is often done by using a regression model for the outcome, conditional on exposure and covariates. A commonly used class of models is the generalized linear models. The model parameters are typically estimated through maximum likelihood. If the model is correct, then the maximum likelihood estimator is consistent but may otherwise be inconsistent. Recently, a new class of estimators known as doubly robust estimators has been proposed. These estimators use two regression models, one for the outcome and one for the exposure, and are consistent if either model is correct, not necessarily both. Thus doubly robust estimators give the analyst two chances instead of only one to make valid inference. In this article, we describe a new Stata command, drglm, that implements the most common doubly robust estimators for generalized linear models. [ABSTRACT FROM AUTHOR]

A fundamental challenge in meta-analyses of published epidemiological dose-response data is the estimate of the function describing how the risk of disease varies across different levels of a given exposure. Issues in trend estimate include within studies variability, between studies heterogeneity, and nonlinear trend components. We present a method, based on a two-step process, that addresses simultaneously these issues. First, two-term fractional polynomial models are fitted within each study included in the meta-analysis, taking into account the correlation between the reported estimates for different exposure levels. Second, the pooled dose-response relationship is estimated considering the between studies heterogeneity, using a bivariate random-effects model. This method is illustrated by a meta-analysis aimed to estimate the shape of the dose-response curve between alcohol consumption and esophageal squamous cell carcinoma (SCC). Overall, 14 case-control studies and one cohort study, including 3000 cases of esophageal SCC, were included. The meta-analysis provided evidence that ethanol intake was related to esophageal SCC risk in a nonlinear fashion. High levels of alcohol consumption resulted in a substantial risk of esophageal SCC as compared to nondrinkers. However, a statistically significant excess risk for moderate and intermediate doses of alcohol was also observed, with no evidence of a threshold effect. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims To study the association between measured or perceived overweight in adolescence and subsequent uptake of cigarette smoking and of the Swedish smokeless tobacco ‘snus’ (oral moist snuff). Design Population-based prospective cohort study with 7 years' follow-up. Setting Self-administered questionnaires and school nurses' visits. Participants A total of 2922 children of both sexes and mean age 11.6 years at recruitment, resident in the Stockholm region, Sweden. Measurements Tobacco use was self-reported at baseline and on six subsequent surveys. Subjects' height and weight were measured by school nurses during the first 4 years, self-reported thereafter. Overweight perception was self-reported at the age of 15 years. Findings Overweight and perception of overweight were not associated with subsequent uptake of either smoking or snus among males. Among females, overweight at baseline was associated with uptake of smoking [adjusted hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.09–1.63], but not of snus. A similar pattern was found with overweight status during follow-up. Among girls with low-educated parents, overweight at baseline predicted the uptake of both snus and smoking. Among 15-year-old females who never used tobacco perceived overweight was associated with subsequent uptake of smoking (adjusted HR 1.71, 95% CI 1.20–2.46), but not of snus. Conclusions In Sweden, adolescent girls with actual or perceived overweight are at increased risk to start smoking, while indications that this increased risk applies to smokeless tobacco (snus) are limited to girls of low socio-economic status. [ABSTRACT FROM AUTHOR]

Introduction. Converging epidemiological evidence based on studies of different designs in a variety of populations and settings show that cancer survival tends to be poorer in low compared to high socioeconomic groups. In an extension of an earlier register-based study, we examined the influence of socioeconomic factors on long-term survival in women with a first diagnosis of invasive breast cancer in 1993 in Sweden, a country with a policy of providing equal access to health care to all at nominal cost within a National Health Care System. Material and methods. The study was based on data set generated by record linkages between the Swedish Cancer Register, Census databases and the Cause of Death Register. Four different categorical variables were used as indicators of socioeconomic standing. Cox proportional hazard regression models were used to estimate the effects of socioeconomic status on risk of death. Results. Of 4 645 eligible women with breast cancer, 1 016 had died from breast cancer at the end of follow-up on December 31, 2003. After adjustment for tumour size and age at diagnosis, risk of death was 19% lower among women belonging to a household of high compared to low socioeconomic status (HR high versus low 0.81; 95% CI: 0.67-0.97). Discussion. These findings indicate that social inequalities in breast cancer survival persist at least up to ten years after an initial diagnosis. While social gradients detected shortly after diagnosis may mainly reflect an influence of socioeconomic differences in overall health status and frailty, differentials persisting beyond five years rather point to a long-term influence of disparities in management of both primary tumours and recurrences. Further studies are needed to explore whether the present findings reflect amendable inequalities in access to state-of- the-art treatment. For all calendar periods, observed survival in the most privileged groups sets the goal for what is achievable for all breast cancer patients. [ABSTRACT FROM AUTHOR]

Information on correlates of total physical activity (PA) levels among middle-aged and elderly women is limited. This article aims to investigate whether total daily PA levels are associated with age, body mass index, smoking, drinking status, and sociodemographic factors. In a cross-sectional study of 38,988 women between the ages of 48 and 83 years residing in central Sweden, information on PA, weight, height, smoking, drinking, and sociodemographic factors was collected through a self-administered questionnaire. Total daily PA levels were measured as metabolic equivalents (MET-h/day). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by ordinal logistic regression models. We observed decreasing level of total PA with increasing age (for 5-year increase: OR = 0.87; 95% CI: 0.85-0.89) and body mass index (for 5-unit, kg/m2, increase: OR = 0.81; 95% CI: 0.79-0.84). Multivariable adjusted correlates of total PA level were smoking (current vs. never: OR = 0.83; 95% CI: 0.79-0.88), drinking (current vs. never: OR = 0.88; 95% CI: 0.82-0.94), educational level (university vs. primary: OR = 0.54; 95% CI: 0.51-0.58), employment status (housewife vs. full-work: OR = 2.59; 95% CI: 2.25-2.98), and childhood environment (city vs. countryside: OR = 0.62; 95% CI: 0.59-0.65). In the present investigation, among middle-aged and elderly women, the likelihood of engaging in higher total daily PA levels decreased with age, body mass index, educational level, smoking, drinking, and growing up in urban places. [ABSTRACT FROM AUTHOR]

Purpose: Few epidemiological studies have been conducted among middle-aged women on long-term total and specific physical activity (PA) trends. We studied in a cross-sectional setting the relationship of self-reported total daily PA with age and calendar time. Methods: In a population-based cohort of 38,988 women aged 49-83 yr in central Sweden, information was collected on physical activity, such as work or occupation, household work, walking or bicycling, exercise, watching TV or reading, and other lifestyle factors through a self-administered questionnaire. Total and specific daily PA levels at ages 15, 30, and 50 yr were recalled retrospectively and measured as metabolic equivalents (MET·h·d-1). Results: Total PA level linearly decreased with calendar time in all three age groups (slope for 5-yr change in calendar time among those 15 yr of age = -0.82; 95% confidence interval (CI), -0.86 to -0.78; among those 30 yr of age = -0.42; 95% CI, -0.45 to -0.38; and among those 50 yr of age = -0.62; 95% CI, -0.66 to -0.58). High-intensity activities such as walking or bicycling decreased by 0.21 MET·h·d-1 (95% CI, -0.22 to -0.20) every 5-calendar-year change among adolescents between the 1930s and 1960s. Total activity level decreased in all age groups by an average of approximately 3 MET·h-1·d-1, corresponding to approximately 45 min of brisk walking. Conclusions: Our results suggest that intervention efforts aimed at engaging in healthful amounts of physical activity are needed throughout the life cycle. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Although glomerular diseases are the third most frequent cause of end‐stage kidney disease worldwide, little is known about their long‐term outcomes.In patients with chronic kidney disease (CKD) stage 3–5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non‐communicable diseases (control‐CKD).We identified 2396 patients with glomerular disease (97% biopsy‐proven, 69% men, 57 years, eGFR 29 mL/min/1.73 m2, uACR 88 mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25 mL/min/1.73 m2, uACR 23 mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow‐up was 6.3 (3.3; 9.9) years. Compared with control‐CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45–0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15–1.37] and 1.34 [1.15–1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline.Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients. [ABSTRACT FROM AUTHOR]

Background: Maternal caffeine intake has repeatedly been linked to babies being born small for gestational age (SGA). SGA babies are known to be at increased risk for adverse neonatal outcomes. The aim of this study was to explore the associations between prenatal caffeine exposure and neonatal health.Methods: The study is based on 67,569 full-term singleton mother-infant pairs from the Norwegian Mother and Child Cohort Study. Caffeine consumption from different sources was self-reported in gestational week 22. Neonatal compound outcomes, namely (1) morbidity/mortality and (2) neonatal intervention, were created based on the Medical Birth Registry of Norway. Adjusted logistic regression was performed.Results: Caffeine exposure was associated to SGA (OR = 1.16, 95%CI: 1.10; 1.23) and being born SGA was significantly associated with neonatal health (OR = 3.09, 95%CI: 2.54; 3.78 for morbidity/mortality; OR = 3.94, 95%CI: 3.50; 4.45 for intervention). However, prenatal caffeine exposure was neither associated with neonatal morbidity/mortality (OR = 1.01, 95%CI: 0.96; 1.07) nor neonatal intervention (OR = 1.02, 95%CI: 1.00; 1.05 for a 100 mg caffeine intake increase). Results did not change after additional adjustment for SGA status.Conclusions: Moderate prenatal caffeine exposure (< 200 mg/day) does not seem to impair neonatal health, although prenatal caffeine exposure is associated with the child being born SGA and SGA with neonatal health. We suggest diversity in neonatal outcomes of SGA infants according to the underlying cause of low birth weight. [ABSTRACT FROM AUTHOR]

Purpose: Oxidative stress might play an important role in the development of osteoarthritis, but not much is known about the effect of antioxidants on osteoarthritis risk. We, therefore, aimed to investigate the effect of dietary vitamin C, E, beta-carotene, and non-enzymatic antioxidant capacity (NEAC), which measures overall antioxidant activity from the diet, on the risk of osteoarthritis. Methods: For this study 43,865 men and women from the Swedish National March Cohort (SNMC) were followed for up to 19 years. We computed dietary intake of vitamin C, E and beta-carotene using information from a Food Frequency Questionnaire (FFQ). To estimate dietary NEAC we combined the information from the FFQ with food item-specific antioxidant capacity values from an antioxidant food database. Cases of osteoarthritis were identified through the Swedish National Patient Registers. We categorized all exposure variables into sex-specific quartiles and used multivariable-adjusted Cox proportional hazards regression models to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results: In total, we observed 5976 cases of OA during 469,148 person-years of follow-up. After adjusting for potential confounders, we did not find any association between vitamin C, beta-carotene and NEAC (p-values for trend > 0.5), but a positive association was found with higher dietary vitamin E intake (HR Q4 vs Q1: 1.11; 95% CI 1.02–1.21; p for trend = 0.01) and the risk of OA. Conclusion: Our findings do not provide evidence for dietary antioxidants to protect from the development of OA, and a higher dietary vitamin E intake might even increase the risk. [ABSTRACT FROM AUTHOR]

Background: Ideal cardiovascular health (CVH) can be assessed by 7 metrics: smoking, body mass index, physical activity, diet, hypertension, dyslipidemia and diabetes, proposed by the American Heart Association. We examined the association of ideal CVH metrics with risk of all-cause, CVD and non-CVD death in a large cohort. Methods: A total of 29,557 participants in the Swedish National March Cohort were included in this study. We ascertained 3,799 deaths during a median follow-up of 19 years. Cox regression models were used to estimate hazard ratios with 95% confidence intervals (95% CIs) of the association between CVH metrics with risk of death. Laplace regression was used to estimate 25th, 50th and 75th percentiles of age at death. Results: Compared with those having 6–7 ideal CVH metrics, participants with 0–2 ideal metrics had 107% (95% CI = 46-192%) excess risk of all-cause, 224% (95% CI = 72-509%) excess risk of CVD and 108% (31-231%) excess risk of non-CVD death. The median age at death among those with 6–7 vs. 0–2 ideal metrics was extended by 4.2 years for all-causes, 5.8 years for CVD and 2.9 years for non-CVD, respectively. The observed associations were stronger among females than males. Conclusions: The strong inverse association between number of ideal CVH metrics and risk of death supports the application of the proposed seven metrics for individual risk assessment and general health promotion. [ABSTRACT FROM AUTHOR]

Marginal structural Cox models have been used to estimate the causal effect of a time-varying treatment on a survival outcome in the presence of time-dependent confounders. These methods rely on the positivity assumption, which states that the propensity scores are bounded away from zero and one. Practical violations of this assumption are common in longitudinal studies, resulting in extreme weights that may yield erroneous inferences. Truncation, which consists of replacing outlying weights with less extreme ones, is the most common approach to control for extreme weights to date. While truncation reduces the variability in the weights and the consequent sampling variability of the estimator, it can also introduce bias. Instead of truncated weights, we propose using optimal probability weights, defined as those that have a specified variance and the smallest Euclidean distance from the original, untruncated weights. The set of optimal weights is obtained by solving a constrained quadratic optimization problem. The proposed weights are evaluated in a simulation study and applied to the assessment of the effect of treatment on time to death among people in Sweden who live with human immunodeficiency virus and inject drugs. [ABSTRACT FROM AUTHOR]

Presents information on a case-control study which assessed the impact of ultrasound and the risks of childhood lymphatic and myeloid leukemia. Methodology; Results; Discussion on the study findings.

Background Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign. Methods Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started. Results On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7–2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4–0.7)] compared with KTRs. Conclusions The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives. [ABSTRACT FROM AUTHOR]

Objective Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. Methods We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non-insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11–1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00–1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with ≥7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00–1.54, P  = 0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. Conclusion Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden. Methods: This is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007–2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid‐stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out‐migration, or to the end of 2018. Results: We identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9–7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium. Conclusions: In a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels. [ABSTRACT FROM AUTHOR]

Background. In 2012, new clinical guidelines were introduced for use of erythropoiesis-stimulating agents (ESA) in chronic kidney disease (CKD) patients, recommending lower haemoglobin (Hb) target levels and thresholds for ESA initiation. These changes resulted in lower blood levels in these patients. However, there is limited evidence on just when ESA should be initiated and the safety of a low Hb initiation policy. Methods. In this observational inception cohort study, Swedish, nephology-referred, ESA-naı?ve CKD patients (n = 6348) were enrolled when their Hb dropped below 12.0 g/L, and they were followed for mortality and cardiovascular events. Four different ESA treatments were evaluated applying dynamic marginal structural models: (i) begin ESA immediately, (ii) begin ESA when Hb <11.0 g/dL, (iii) begin ESA when Hb <10.0 g/dL and (iv) never begin ESA in comparison with 'current practice' [the observed (factual) survival of the entire study cohort]. The adjusted 3-year survival following ESA begun over a range of Hb (from <9.0 to 12.0 g/dL) was evaluated, after adjustment for covariates at baseline and during follow-up. Results. Overall, 36% were treated with ESA. Mortality during follow-up was 33.4% of the ESA-treated and 27.9% of the non-treated subjects. The adjusted 3-year survival associated with ESA initiation improved for subjects with initial Hb <9.0 to 11 g/dL and then decreased again for those with Hb above 11.5 g/dL. Initiating ESA at Hb <11.0 g/dL and <10.0 g/dL was associated with improved survival compared with 'current practice' [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.79-0.89 and 0.90; 95% CI 0.86-0.94, respectively] and did not increase the risk of a cardiovascular event (HR 0.93; 95% CI 0.87-1.00). Conclusion. In non-dialysis patients with CKD, ESA initiation at Hb < 10.0-11.0 g/dL is associated with improved survival in patients otherwise treated according to guidelines. [ABSTRACT FROM AUTHOR]

Effects of repeated weight changes on mortality are not well established. In this prospective cohort study, we followed 34,346 individuals from 1997 to 2018 for all-cause mortality, and 2016 for cause-specific mortality. At baseline, participants self-reported amount and frequency of prior weight loss. During 20.6 (median) years of follow-up, we identified 5627 deaths; 1783 due to cancer and 1596 due to cardiovascular disease (CVD). We used Cox Proportional Hazards models to estimate multivariable‐adjusted Hazard Ratios (HRs) and 95% confidence intervals (CI). Participants with a weight loss > 10 kg had higher rates of all-cause (HR 1.22; 95%CI 1.09–1.36) and CVD mortality (HR 1.27; 95%CI 1.01–1.59) compared to individuals with no weight loss. Men who had lost > 10 kg had higher all-cause (HR 1.55; 95%CI 1.31–1.84) and CVD mortality (HR 1.55; 95%CI 1.11–2.15) compared to men with no weight loss. Participants who had lost ≥ 5 kg three times or more prior to baseline had increased rates of all-cause (HR 1.16; 95%CI 1.03–1.30) and CVD mortality (HR 1.49; 95%CI 1.20–1.85) compared to participants with no weight loss. We found no association between weight loss and cancer mortality. We conclude that previous and repeated weight loss may increase all-cause and CVD mortality, especially in men. [ABSTRACT FROM AUTHOR]

Background. The guidelines for anaemia management in chronic kidney disease (CKD) patients have changed substantially during the past 10 years. We here evaluate whether these changes are followed by subsequent modifications in physicians' anaemia management in Sweden. Methods. We included patients incident to the Swedish Renal Registry for CKD non-dialysis (CKD-ND, referred patients with an estimated glomerular filtration rate <45 mL/min/1.73 m2) and haemodialysis (HD) between 2008 and 2013. Time trends in anaemia management were investigated in relation to prescribed medication, laboratory measures and other relevant clinical characteristics. Linear and binominal regression models were used to describe trends across three predefined time periods (2008-09, 2010-11 and 2012-13). Results. Erythropoiesis-stimulating agents (ESAs) use decreased over time among both CKD-ND and HD patients [risk ratio (RR) 2012-13 compared with 2008-09 for CKD-ND 0.88, 95% confidence interval (CI) 0.81-0.96; RR for HD 0.95, 95% CI 0.93-0.97]. Mean ESA dose decreased significantly among HD patients (7% in 2010-11 compared with 2008-09 and another 3% during 2012-13). Over the time periods studied, ESA doses increased slightly in the CKD-ND population. Mean haemoglobin (Hb) levels decreased in CKD-ND patients, among both ESA users and non-users, whereas it decreased to a lesser degree, albeit significantly, among HD ESA users. The risk of having an Hb >120 g/L decreased, especially between 2008-09 and 2010-11. Iron use increased over time, mainly in the HD population, but also among CKD-ND ESA non-users. Conclusions. Changes in guidelines have influenced the clinical anaemia practice of Swedish nephrology care, resulting in lower ESA use and lower Hb levels. [ABSTRACT FROM AUTHOR]

Objective: The knowledge regarding maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We performed a longitudinal investigation of maternal right ventricular (RV) and left atrial (LA) function in a cohort of uncomplicated twin pregnancies compared to singleton pregnancies. Study design: Healthy women with uncomplicated twin pregnancies were prospectively enrolled and assessed by transthoracic echocardiography at 10–15 weeks' (w) gestation (T1), 19-26 w gestation (T2), and 30–38 w gestation (T3). Subjects with uneventful singleton pregnancies were selected as controls at the same gestational ages. Cardiac findings were compared to those of women with uneventful singleton gestations. RV systolic and diastolic functions were assessed by conventional echocardiography (FAC, TAPSE, sPAP, E, A, DT) and tissue Doppler imaging (TDI) (E', A', S', IVA, IVCT, IVRT, ET, MPI), and LA dimensions were calculated. Speckle-tracking imaging was also applied to evaluate RV global longitudinal strain and LA 2D strains (at LV end-systole (LAS) and at atrial contraction (LAA)). Results: Overall, 30 uncomplicated twin and 30 uncomplicated singleton pregnancies were included. Regarding maternal RV function in twins, all the parameters (FAC, TAPSE, sPAP, E, A, E/A, DT, E/E', IVA, IVCT, MPI and 2D longitudinal strain) were almost stable throughout gestation, with the exception of the TDI findings (E' decreased from T1 to T3 (p = 0.03), while E'/A' increased from T1 to T2 and then decreased (p = 0.01); A' and basal S' increased (p = 0.04 and p = 0.03, respectively), while IVRT and ET significantly decreased (p = 0.009 and p = 0.007, respectively)). These findings were similar to those found for singleton pregnancies. LA dimensions significantly increased throughout gestation in both twins and singletons (p < 0.001), without intergroup difference. LA strains did not vary during either twin or singleton pregnancies, except for LAA in T1, which was higher among twins than among singletons. Conclusion: Maternal RV and LA function in uncomplicated twin pregnancies does not seem to undergo more significant changes than in singletons, being characterized by similar findings in RV systolic and diastolic functions, as well as LA dimensions and strains. [ABSTRACT FROM AUTHOR]

Objective: The knowledge of maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We aimed to longitudinally investigate maternal left ventricular (LV) function in uncomplicated twin pregnancies. Methods: 30 healthy and uncomplicated twin pregnant women and 30 controls with normal singleton pregnancies were prospectively enrolled to undergo transthoracic echocardiography at 10–15 week's gestation (w) (T1), 19–26 w (T2) and 30–38 w (T3). LV dimensions and volumes, as well as LV ejection fraction (LVEF), mass (LVM) and diastolic parameters (at transmitral pulsed wave Doppler and mitral annular plane tissue Doppler), were calculated. Speckle-tracking imaging was also applied to evaluate LV global longitudinal (GLS), radial and circumferential 2D strains. Results: During twin pregnancy, maternal LV dimensions, volumes and LVM had an increasing trend from T1 to T3, similar to singletons, while LVEF remained stable. There was LV remodeling/hypertrophy in 50% of women at T2 and T3 in both groups. Diastolic function had a worsening trend from T1 to T3 with no differences between twins and singletons, except for higher LV filling pressure (i.e., E/E′) at T2 in twins. Two-dimensional strains did not vary during gestation in either group, except for a linear trend to increase (i.e., worsen) GLS in singletons. Radial and circumferential 2D strains were impaired in about half of the women at each trimester, while GLS was altered in one-fourth/one-third of them in both groups. Conclusion: Maternal LV geometry, dimensions and function are significantly impaired during twin pregnancies, in particular in the second half of gestation, with no significant differences compared to singletons. [ABSTRACT FROM AUTHOR]

Physical exercise has been suggested to be neuroprotective in the nigrostriatal system. Yang et al. prospectively investigate the association between physical activity and Parkinson’s disease risk in 43 368 Swedish subjects. They show that increased levels of physical activity are associated with a lower risk of Parkinson’s disease.See Tanner and Comella (doi:10.1093/brain/awu351) for a scientific commentary on this article.Physical exercise has been associated with neuroprotective effects in the nigrostriatal dopaminergic system. To examine the impact of physical activity on Parkinson’s disease risk prospectively, we followed 43 368 individuals who provided extensive information on physical activity at baseline. We estimated hazard ratios with 95% confidence intervals using Cox proportional hazards regression. During an average of 12.6 years of follow-up, 286 incident Parkinson’s disease cases were identified. In males, there was an inverse association with Parkinson’s disease for total physical activity (hazard ratio 0.55, 95% confidence interval 0.35–0.87 for medium versus low level), for sum of household, commuting and leisure time exercise (hazard ratio 0.53, 95% confidence interval 0.33–0.85 for high versus low level), and for household and commuting physical activity specifically (hazard ratio 0.50, 95% confidence interval 0.31–0.81 for >6 versus <2 h per week). No association was observed for leisure time exercise or occupational physical activity with Parkinson’s disease, among either males or females. Meta-analysis of the present study and five previous prospective studies showed a pooled hazard ratio of 0.66 (95% confidence interval 0.57–0.78) for highest versus lowest physical activity level. Our results indicate that a medium level of physical activity lowers Parkinson’s disease risk. [ABSTRACT FROM AUTHOR]

Limited data are available about the potential health effects of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pregnant women and their developing offspring. We established the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) to provide data on the risk of major adverse obstetric and neonatal outcomes among women with varying degrees of severity and timing of coronavirus disease 2019 (COVID-19) during pregnancy. We describe here the cohort and share the lessons learned. The IRCEP enrolls women tested for SARS-CoV-2 or with a clinical diagnosis of COVID-19 during pregnancy and obtains information using an online data collection system. By March 2021, 17,532 participants from 77 countries had enrolled; 54% enrolled during pregnancy and 46% afterward. Among women with symptomatic COVID-19 with a positive SARS-CoV-2 test (n  = 4,934), symptoms were mild in 41%, moderate in 52%, and severe in 7%; 7.7% were hospitalized for COVID-19 and 1.7% were admitted to an intensive care unit. The biggest challenges were retention of participants enrolled during pregnancy and the potential bias introduced when participants enroll after pregnancy outcomes are known. Multiple biases need to be considered and addressed when estimating and interpreting the effects of COVID-19 in pregnancy in these types of cohorts. [ABSTRACT FROM AUTHOR]

Summary: Previous work has shown that both long and short sleep duration is associated with increased mortality, with lowest risk around 7 hr. This has had widespread impact on views on the optimal sleep duration. However, age, being employed/retired, and blue‐/white‐collar status, may influence the time available for sleep and thus, confound the association. We investigated the role of these factors on the association between sleep duration and mortality. We used employed and retired participants (N = 25,430) from the Swedish National March Cohort and Cox proportional hazards regression to model the shape of the association. We found a significant U‐shaped association in a multivariable model with a hazard ratio (HR) of 1.24 (95% confidence interval [CI] 1.10, 1.39) for <5‐hr sleep duration, and a HR of 1.30 (95% CI 1.12, 1.51) for ≥9‐hr sleep duration, with the lowest HR for 7 hr, but with a span of low HRs from 5 to 8 hr. Unadjusted values showed a pronounced U‐shape. Adjusting for age accounted for most of the attenuation in the multivariable model. Stratification into five age groups showed a significant U‐shape only in those aged >60.3 years at baseline. The shape of the association did not differ between blue‐/white‐collar workers, nor between employed and retired groups. We conclude that the U‐shaped association between sleep duration and mortality is present only in older individuals. [ABSTRACT FROM AUTHOR]

Background: Partial implementation may explain modest effectiveness of many school-based preventive programmes against substance use. We studied whether specific characteristics of the class could predict the level of implementation of a curriculum delivered by class teachers in schools from some European countries. Methods: Secondary analysis of data from an evaluation trial. In seven European countries, 78 schools (173 classes) were randomly assigned to a 12-unit, interactive, standardized programme based on the comprehensive social influence model. Curriculum completeness, application fidelity, average unit duration and use of role-play were monitored using structured report forms. Predictors of implementation were measured by aggregating at class level information from the baseline student survey. Class size, gender composition, mean age, factors related to substance use and to affection to school were analysed, with associations estimated by multilevel regression models. Results: Implementation was not significantly predicted by mean age, proportion of students with positive academic expectation or liking school. Proportion of boys was associated with a shorter time devoted to each unit [β = −0.19, 95% confidence intervals (CI) −0.32 to −0.06]. Class size was inversely related to application fidelity [Odds ratio (OR) 0.92, 95% CI 0.85 to 0.99]. Prevalence of substance use was associated with a decreased odds of implementing all the curriculum units (OR 0.81, 95% CI 0.65 to 0.99). Students’ connectedness to their class was associated with increased odds of teachers using role-play (OR 1.52, 95% CI 1.03 to 2.29). Conclusions: Teachers’ implementation of preventive programmes may be affected by structural and social characteristics of classes and therefore benefit from organizational strategies and teachers’ training in class management techniques. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity is a known risk factor for cardiovascular disease, but it is unclear if total and leisure time activity have different impact on the risk of myocardial infarction and stroke. In this cohort, we aimed to investigate the associations between both total and leisure time physical activity in detail, and the risks of myocardial infarction and stroke, both overall and for men and women separately.Methods: We assessed the association between total and leisure time physical activity on the risk of myocardial infarction and stroke in a cohort of 31,580 men and women through record linkages from 1997-2016. We used Cox proportional hazards regression models to estimate hazard ratios (HR) with 95% confidence intervals (CI) based on detailed self-reported physical activity. In the adjusted analyses, we included age, sex, body mass index, level of education, cigarette smoking, alcohol consumption, diabetes, lipid disturbance and hypertension as potential confounders.Results: We identified 1,621 incident cases of myocardial infarction and 1,879 of stroke. Among men, there was an inverse association between leisure time activity and myocardial infarction in the third tertile compared to the first (HR: 0.78; 95% CI: 0.62-0.98; p for trend = 0.03). We also found an inverse association between leisure time activity and stroke in the third tertile compared to the first (HR: 0.78; 95% CI: 0.61-0.99; p for trend = 0.04), while the corresponding HR for stroke among women was 0.91; 95% CI: 0.74-1.13. We found no significant association between total physical activity and MI (HR: 1.12; 95% CI: 0.93-1.34) or stroke (HR: 1.14 95% CI: 0.94-1.39) comparing the highest to the lowest tertile in men. Women in the highest tertile of total physical activity had a 22% lower risk of myocardial infarction compared to the lowest tertile (HR: 0.78; 95% CI: 0.63-0.97; p for trend = 0.02) and an 8% (95% CI: 0.87-0.98) reduced risk of myocardial infarction with each 1 METh/day increase of leisure time physical activity.Conclusion: Total physical activity was inversely associated with the risk of myocardial infarction in women, while leisure time physical activity was inversely associated with the risk of myocardial infarction and stroke in men. [ABSTRACT FROM AUTHOR]

Background To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3–5 in routine care. Methods We studied cohorts of adults with confirmed CKD G3–5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N  = 57 880) and Geisinger, PA, USA (N  = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression. Results During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80–0.90] in SCREAM and OR 0.80 [95% CI 0.72–0.89] in Geisinger}. Conclusions One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury. [ABSTRACT FROM AUTHOR]

Dialysis has been used in the treatment of patients with end-stage renal disease since the 1960s. Recently, several large observational studies have been conducted to assess whether early initiation of dialysis prolongs survival, as compared with late initiation. However, these studies have used analytic approaches which are likely to suffer from either lead-time bias or immortal-time bias. In this paper, the authors demonstrate that recently developed methods in the causal inference literature can be used to avoid both types of bias and accurately estimate the ideal time for dialysis initiation from observational data. This is illustrated using data from a nationwide population-based cohort of patients with chronic kidney disease in Sweden (1996–2003). [ABSTRACT FROM PUBLISHER]

Background: Although social environments may influence alcohol-related behaviours in youth, the relationship between neighbourhood socioeconomic context and effectiveness of school-based prevention against underage drinking has been insufficiently investigated. We study whether the social environment affects the impact of a new school-based prevention programme on alcohol use among European students. Methods: During the school year 2004-2005, 7079 students 12-14 years of age from 143 schools in nine European centres participated in this cluster randomised controlled trial. Schools were randomly assigned to either control or a 12-session standardised curriculum based on the comprehensive social influence model. Randomisation was blocked within socioeconomic levels of the school environment. Alcohol use and alcohol-related problem behaviours were investigated through a self-completed anonymous questionnaire at baseline and 18 months thereafter. Data were analysed using multilevel models, separately by socioeconomic level. Results: At baseline, adolescents in schools of low socioeconomic level were more likely to report problem drinking than other students. Participation in the programme was associated in this group with a decreased odds of reporting episodes of drunkenness (OR = 0.60, 95% CI = 0.44-0.83), intention to get drunk (OR = 0.60, 95% CI = 0.45-0.79), and marginally alcohol-related problem behaviours (OR = 0.70, 95% CI = 0.46-1.06). No significant programme's effects emerged for students in schools of medium or high socioeconomic level. Effects on frequency of alcohol consumption were also stronger among students in disadvantaged schools, although the estimates did not attain statistical significance in any subgroup. Conclusions: It is plausible that comprehensive social influence programmes have a more favourable effect on problematic drinking among students in underprivileged social environments. [ABSTRACT FROM AUTHOR]

To assess the role of rural-urban migration in the risks of under-five death; to identify possible mechanisms through which migration may influence mortality; and to determine individual- and community-level relationships between migration status and under-five death. Multilevel Cox regression analysis was used on a nationally representative sample of 6029 children from 2735 mothers aged 15-49 years and nested within 365 communities from the 2003 Nigeria Demographic and Health Survey. Hazard ratios with 95% confidence intervals were used to express the measures of association between the characteristics, and intra-class coefficients were used to express the measures of variation. Children of rural non-migrant mothers had significantly lower risks of under-five death than children of rural-urban migrant mothers. The disruption of family and community ties, low socio-economic position and vulnerability, and the difficulties migrants face in adapting into the new urban environment, may predispose the children of rural-urban migrants to higher mortality. Our results stress the need for community-level and socio-economic interventions targeted at migrant groups within urban areas to improve their access to health care services, maternal education, as well as the general socio-economic situation of women. [ABSTRACT FROM AUTHOR]

Aims: Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer. Methods: A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. Results: During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI: 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (⩽ 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI: 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI: 0.57, 1.32). Conclusions: Swedish snus use does not appear to be implicated in the development of oral cancer in men. [ABSTRACT FROM AUTHOR]

The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain, despite considerable research efforts. With the aim to examine these associations with an improved precision, we used data from a large population-based prospective cohort study in central Sweden. We estimated nutrient intake from a self-administered food-frequency questionnaire filled in by 60,689 women, aged 40–74 years at baseline during 1987–1990. During follow-up, we observed 3986 women with a fracture at any site and 1535 with a hip fracture. Rate ratio of fractures (RR) and 95% CI were estimated using Cox proportional hazards models. We found no dose–response association between dietary calcium intake and fracture risk. The age-adjusted RR of hip fracture was 1.01 (95% CI 0.96–1.06) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 (95% CI 0.96–1.03). Furthermore, women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes: RR 1.07 (95% CI 0.92–1.24) and RR 1.00 (95% CI 0.79–1.27), respectively. Vitamin D intake was not associated with fracture risk. Furthermore, women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures (95% CI 0.88–1.17). Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women. [Copyright &y& Elsevier]

Background: Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI).Objectives: This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease.Methods: All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil.Results: This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1.Conclusions: In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design. [ABSTRACT FROM AUTHOR]

Background: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project.Methods: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use.Results: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount.Conclusions: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality. [ABSTRACT FROM AUTHOR]

Objective: There is scant information about maternal cardiovascular hemodynamic change during twin pregnancies. Aim of the study is to investigate longitudinal changes in maternal arterial stiffness, elastic aortic properties and ventricular-arterial coupling (VAC) in uncomplicated twin pregnancies compared to singleton ones. Approach: In this prospective longitudinal study, we performed applanation tonometry and transthoracic echocardiography in the first (T1; 10–15 weeks' gestation (w)), second (T2; 19–26 w) and third trimesters (T3; 30–38 w) in women with uncomplicated twin pregnancies, both monochorionic and dichorionic. Heart-rate-corrected augmentation index (AIx@75) was studied as indicator of arterial stiffness. Aortic diameters and elastic properties were calculated. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular end-systolic elastance (Ees). Finally, stroke volume (SV), cardiac output (CO) and total vascular resistance (TVR) were evaluated. The findings were compared to those of women with uncomplicated singleton pregnancies. Main results: Thirty women with twin gestations (11 monochorionic) and 30 singleton controls were obtained for analysis. Blood pressure and TVR significantly decreased from T1 to T2 and then rose in T3, with higher values in twins than in singletons. AIx@75 showed the same trend in both groups with lower values at T2 in twins. SV and CO linearly increased throughout gestation with no significant intergroup difference. Aortic diameters and elastic properties remained stable throughout gestation, with no significant intergroup differences. Both Ea and Ees were greater (i.e. worse) in twins than in singletons at T1 and T3, showing a significant linear trend towards reduction in the two groups, meaning lower vascular and ventricular loads. Using longitudinal analysis blood pressure, TVR, Ea and Ees depended from both multiple gestation and gestational age. Significance: In twins, maternal hemodynamics does not seem to undergo more significant changes than in singletons being characterized by higher blood pressures and TVR with no differences in CO, SV, aortic dimensions and elastic properties. Despite VAC is maintained within its normal range, total vascular load (i.e., Ea) resulted higher in twin than singleton pregnancies throughout gestation. It is conceivable that these findings may represent one of the underlying cause for the increased risk of adverse obstetric outcomes described in multiple gestations. [ABSTRACT FROM AUTHOR]

Background Despite long-standing clinical use of sodium polystyrene sulphonate (SPS) for hyperkalaemia management in chronic kidney disease (CKD), its safety profile remains poorly investigated. Methods We undertook an observational analysis of nephrology-referred adults with incident CKD Stage 4+ in Sweden during 2006–16 and with no previous SPS use. We studied patterns of use and adverse events associated to SPS initiation during follow-up. Patterns of SPS use were defined by chronicity of treatment and by prescribed dose. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with SPS initiation (time-varying exposure) for the risk of severe (intestinal ischaemia, thrombosis or ulceration/perforation) and minor (de novo dispensation of laxatives or anti-diarrheal drugs) gastrointestinal (GI) events. Results Of 19 530 SPS-naïve patients with CKD, 3690 initiated SPS during follow-up. A total of 59% took SPS chronically, with an average of three dispensations/year. The majority (85%) were prescribed lower dosages than specified on the product label. During follow-up, 202 severe and 1149 minor GI events were recorded. SPS initiation was associated with a higher incidence of severe adverse events [adjusted HR 1.25 95% CI 1.05–1.49)], particularly in those receiving per label doses [1.54 (1.09–2.17)] and mainly attributed to ulcers and perforations. SPS initiation was also associated with higher incidence of minor GI events [adjusted HR 1.11 (95% CI 1.03–1.19)], regardless of dose, and mainly accounted for by de novo dispensation of laxatives. Conclusions Initiation of SPS in patients with advanced CKD is associated with a higher risk of severe GI complications as well as the initiation of GI-related medications, particularly when prescribed at per label doses. [ABSTRACT FROM AUTHOR]

Background: As distinct from mentally-active sedentary behaviors (e.g. reading), passive sedentary behaviors (e.g. TV-viewing) have been linked to a higher risk of depression, but the underlying mechanisms are unclear. We examined the potential mediating role of sleep problems in prospective relationships of passive sedentary behaviors with major depressive disorder (MDD).Method: In 1997, 43 863 adults were surveyed and responses linked to clinician diagnoses of MDD until 2010. The questionnaire included items on sedentary behavior and sleep problems (Karolinska Sleep Questionnaire). Cox proportional hazard models and the 'counterfactual approach' were used to identify potential mediating effects of sleep problems in the association of passive sedentary behavior and MDD.Results: Of the total sample, 3,065 (7.6%) were excluded for having indications of depression at baseline. Of 33,116 participants with complete data (mean age = 51.3 years, SD = 15.7, 64% female); 472 (1.4%) incident cases of MDD were identified during the 13-year follow-up. In Cox regression analyses, higher durations of passive sedentary behavior (≥3 h/day versus <3 h/day) were associated with greater hazards of developing MDD (HR = 1.27; 95% CI = 1.01, 1.58). This relationship remained after adjusting for confounders (HR = 1.29; 95% CI = 1.03, 1.63). Adding sleep problems into the analysis significantly attenuated these relationships (HR = 1.25; 95% CI = 0.99, 1.57). The excess MDD relative risk of passive sedentary behaviors due to sleep problems was statistically significant.Limitations: Measures of sedentary behavior, physical activity and sleep were self-reported.Conclusion: Sleep problems appear to mediate detrimental associations of passive sedentary behavior with depression. Findings require further confirmation using objective measures. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.Methods: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.Results: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.Conclusions: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and aortic stenosis (AS) share many risk factors.Objectives: This study sought to evaluate whether kidney dysfunction is associated with the development of AS in the community.Methods: The study included 1,121,875 Stockholm citizens without a prior diagnosis of AS from the SCREAM (Stockholm CREAtinine Measurements) project. Estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated from serum creatinine. AS incidence during follow-up was ascertained by clinical diagnostic codes. The association between eGFR and AS incidence was estimated with multivariable Cox proportional hazards models. Sensitivity analyses included analysis of possible reverse causation bias by excluding the first 6 months to 2 years after enrollment and excluding individuals with comorbid heart failure.Results: The median age was 50 years (interquartile range [IQR]: 36 to 64 years), and 54% of participants were women. Median eGFR was 96 ml/min/1.73 m2 (IQR: 82 to 109 ml/min/1.73 m2), and 66,949 (6.0%) participants had CKD (eGFR <60 ml/min/1.73 m2). During a median follow-up of 5.1 years (IQR: 3.3 to 6.1 years), 5,858 (0.5%) individuals developed AS (incidence rate [IR] 1.13/1,000 person-years). Compared with eGFR >90 (IR 0.34/1,000 person-years), lower eGFR strata were associated with higher hazards of AS: eGFR 60 to 90 ml/min/1.73 m2; IR: 1.88; hazard ratio (HR): 1.14; 95% confidence interval (CI): 1.05 to 1.25; eGFR 45 to 59 ml/min/1.73 m2; IR: 4.61; HR: 1.17; 95% CI: 1.05 to 1.30; eGFR 30 to 44 ml/min/1.73 m2; IR: 6.62; HR: 1.22; 95% CI: 1.07 to 1.39; and eGFR 30 ml/min/1.73 m2; IR: 8.27; HR: 1.56; 95% CI: 1.29 to 1.87. Sensitivity analysis attenuated only slightly the magnitude of the association; individuals with eGFR ≤44 ml/min/1.73 m2 remained at an approximate 20% risk of AS both when excluding events within the 2 years after baseline (HR: 1.22; 95% CI: 1.06 to 1.42) and when excluding participants with heart failure (HR: 1.20; 95% CI: 1.03 to 1.39).Conclusions: CKD, even in moderate to severe stages, is associated with an increased risk of AS. [ABSTRACT FROM AUTHOR]