The association of short and long sleep with mortality in men and women.

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.

Nordic Nutrition Recommendations and risk of myocardial infarction and stroke: a prospective cohort study.

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.

Ideal cardiovascular health and risk of death in a large Swedish cohort.

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.

Cardiorenal Outcomes Among Patients With Atrial Fibrillation Treated With Oral Anticoagulants.

RATIONALE & OBJECTIVE: Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). DOACs cause fewer bleeding complications, but their other advantages, particularly related to kidney outcomes, remain inconclusive. We studied the risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) after DOAC and VKA administration for nonvalvular AF. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Cohort study of Swedish patients enrolled in the Stockholm Creatinine Measurements (SCREAM) project with a diagnosis of nonvalvular AF during 2011-2018. EXPOSURE: Initiation of DOAC or VKA treatment. OUTCOME: Primary outcomes were CKD progression (composite of >30% estimated glomerular filtration rate [eGFR] decline and kidney failure) and AKI (by diagnosis or KDIGO-defined transient creatinine elevations). Secondary outcomes were death, major bleeding, and the composite of stroke and systemic embolism. ANALYTICAL APPROACH: Propensity score weighted Cox regression was used to balance 50 baseline confounders. Sensitivity analyses included falsification end points, subgroups, and estimation of per-protocol effects. RESULTS: We included 32,699 patients (56% initiated DOAC) who were observed for a median of 3.8 years. Their median age was 75 years, 45% were women, and 27% had an eGFR <60mL/min/1.73m2. The adjusted HRs for DOAC versus VKA were 0.87 (95% CI, 0.78-0.98) for the risk of CKD progression and 0.88 (95% CI, 0.80-0.97) for AKI. HRs were 0.77 (95% CI, 0.67-0.89) for major bleeding, 0.93 (95% CI, 0.78-1.11) for the composite of stroke and systemic embolism, and 1.04 (95% CI, 0.95-1.14) for death. The results were similar across subgroups of age, sex, and baseline eGFR when restricting to patients at high risk for thromboembolic events and when censoring follow up at treatment discontinuation or change in type of anticoagulation. LIMITATIONS: Missing information on time in therapeutic range and treatment dosages. CONCLUSIONS: Among patients with nonvalvular AF treated in routine clinical practice compared with VKA use, DOAC use was associated with a lower risk of CKD progression, AKI, and major bleeding but a similar risk of the composite of stroke, systemic embolism, or death.

Quality of laboratory biomarker monitoring during treatment with lithium in patients with bipolar disorder.

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.

Results of the first nationwide cohort study of outcomes in dialysis and kidney transplant patients before and after vaccination for COVID-19.

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.

Interactive association between insomnia symptoms and sleep duration for the risk of dementia-a prospective study in the Swedish National March Cohort.

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.

International Registry of Coronavirus Exposure in Pregnancy (IRCEP): Cohort Description and Methodological Considerations.

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.

Sleep duration and mortality, influence of age, retirement, and occupational group.

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.

Dietary fat intake and risk of Parkinson disease: results from the Swedish National March Cohort.

BACKGROUND: Following progressive aging of the population worldwide, the prevalence of Parkinson disease is expected to increase in the next decades. Primary prevention of the disease is hampered by limited knowledge of preventable causes. Recent evidence regarding diet and Parkinson disease is inconsistent and suggests that dietary habits such as fat intake may have a role in the etiology. OBJECTIVE: To investigate the association between intake of total and specific types of fat with the incidence of Parkinson disease. METHODS: Participants from the Swedish National March Cohort were prospectively followed-up from 1997 to 2016. Dietary intake was assessed at baseline using a validated food frequency questionnaire. Food items intake was used to estimate fat intake, i.e. the exposure variable, using the Swedish Food Composition Database. Total, saturated, monounsaturated and polyunsaturated fat intake were categorized into quartiles. Parkinson disease incidence was ascertained through linkages to Swedish population-based registers. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of the association between fat intake from total or specific types of fats and the incidence of Parkinson disease. The lowest intake category was used as reference. Isocaloric substitution models were also fitted to investigate substitution effects by replacing energy from fat intake with other macronutrients or specific types of fat. RESULTS: 41,597 participants were followed up for an average of 17.6 years. Among them, 465 developed Parkinson disease. After adjusting for potential confounders, the highest quartile of saturated fat intake was associated with a 41% increased risk of Parkinson disease compared to the lowest quartile (HR Q4 vs. Q1: 1.41; 95% CI: 1.04-1.90; p for trend: 0.03). Total, monounsaturated or polyunsaturated fat intake were not significantly associated with Parkinson disease. The isocaloric substitution models did not show any effect. CONCLUSIONS: We found that a higher consumption of large amounts of saturated fat might be associated with an increased risk of Parkinson disease. A diet low in saturated fat might be beneficial for disease prevention.

Association between total and leisure time physical activity and risk of myocardial infarction and stroke - a Swedish cohort study.

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.

Metadata Correction: Clinical Outcomes Among Working Adults Using the Health Integrator Smartphone App: Analyses of Prespecified Secondary Outcomes in a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/24725.].

Clinical Outcomes Among Working Adults Using the Health Integrator Smartphone App: Analyses of Prespecified Secondary Outcomes in a Randomized Controlled Trial.

BACKGROUND: There is a need to find new methods that can enhance the individuals' engagement in self-care and increase compliance to a healthy lifestyle for the prevention of noncommunicable diseases and improved quality of life. Mobile health (mHealth) apps could provide large-scale, cost-efficient digital solutions to implement lifestyle change, which as a corollary may enhance quality of life. OBJECTIVE: Here we evaluate if the use of a smartphone-based self-management system, the Health Integrator app, with or without telephone counseling by a health coach, had an effect on clinical variables (secondary outcomes) of importance for noncommunicable diseases. METHODS: The study was a 3-armed parallel randomized controlled trial. Participants were randomized to a control group or to 1 of 2 intervention groups using the Health Integrator app with or without additional telephone counseling for 3 months. Clinical variables were assessed before the start of the intervention (baseline) and after 3 months. Due to the nature of the intervention, targeting lifestyle changes, participants were not blinded to their allocation. Robust linear regression with complete case analysis was performed to study the intervention effect among the intervention groups, both in the entire sample and stratifying by type of work (office worker vs bus driver) and sex. RESULTS: Complete data at baseline and follow-up were obtained from 205 and 191 participants, respectively. The mean age of participants was 48.3 (SD 10) years; 61.5% (126/205) were men and 52.2% (107/205) were bus drivers. Improvements were observed at follow-up among participants in the intervention arms. There was a small statistically significant effect on waist circumference (ß=-0.97, 95% CI -1.84 to -0.10) in the group receiving the app and additional coach support compared to the control group, but no other statistically significant differences were seen. However, participants receiving only the app had statistically significantly lower BMI (ß=-0.35, 95% CI -0.61 to -0.09), body weight (ß=-1.08, 95% CI -1.92 to -0.26), waist circumference (ß=-1.35, 95% CI -2.24 to -0.45), and body fat percentage (ß=-0.83, 95% CI -1.65 to -0.02) at follow-up compared to the controls. There was a statistically significant difference in systolic blood pressure between the two intervention groups at follow-up (ß=-3.74, 95% CI -7.32 to -0.16); no other statistically significant differences in outcome variables were seen. CONCLUSIONS: Participants randomized to use the Health Integrator smartphone app showed small but statistically significant differences in body weight, BMI, waist circumference, and body fat percentage compared to controls after a 3-month intervention. The effect of additional coaching together with use of the app is unclear. TRIAL REGISTRATION: ClinicalTrials.gov NCT03579342; https://clinicaltrials.gov/ct2/show/NCT03579342. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-6595-6.

Relationship between sleep characteristics and markers of inflammation in Swedish women from the general population.

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 (ß = 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: ß = 0.71; 95% CI = 0.17; 1.24. ß = 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: ß = -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.

Dietary antioxidants, non-enzymatic antioxidant capacity and the risk of osteoarthritis in the Swedish National March Cohort.

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.

No association between moist oral snuff (snus) use and oral cancer: pooled analysis of nine prospective observational studies.

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.

Cross-sectional and prospective relationships of passive and mentally active sedentary behaviours and physical activity with depression.

BACKGROUND: Sedentary behaviour can be associated with poor mental health, but it remains unclear whether all types of sedentary behaviour have equivalent detrimental effects. AIMS: To model the potential impact on depression of replacing passive with mentally active sedentary behaviours and with light and moderate-to-vigorous physical activity. An additional aim was to explore these relationships by self-report data and clinician diagnoses of depression. METHOD: In 1997, 43 863 Swedish adults were initially surveyed and their responses linked to patient registers until 2010. The isotemporal substitution method was used to model the potential impact on depression of replacing 30 min of passive sedentary behaviour with equivalent durations of mentally active sedentary behaviour, light physical activity or moderate-to-vigorous physical activity. Outcomes were self-reported depression symptoms (cross-sectional analyses) and clinician-diagnosed incident major depressive disorder (MDD) (prospective analyses). RESULTS: Of 24 060 participants with complete data (mean age 49.2 years, s.d. 15.8, 66% female), 1526 (6.3%) reported depression symptoms at baseline. There were 416 (1.7%) incident cases of MDD during the 13-year follow-up. Modelled cross-sectionally, replacing 30 min/day of passive sedentary behaviour with 30 min/day of mentally active sedentary behaviour, light physical activity and moderate-to-vigorous activity reduced the odds of depression symptoms by 5% (odds ratio 0.95, 95% CI 0.94-0.97), 13% (odds ratio 0.87, 95% CI 0.76-1.00) and 19% (odds ratio 0.81, 95% CI 0.93-0.90), respectively. Modelled prospectively, substituting 30 min/day of passive with 30 min/day of mentally active sedentary behaviour reduced MDD risk by 5% (hazard ratio 0.95, 95% CI 0.91-0.99); no other prospective associations were statistically significant. CONCLUSIONS: Substituting passive with mentally active sedentary behaviours, light activity or moderate-to-vigorous activity may reduce depression risk in adults.

Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study.

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.

Prospective study of job stress and risk of infections in Swedish adults.

OBJECTIVES: Psychological stress may influence both susceptibility and severity of infections. Although work-related stress is a widespread concern among many employees, few studies have been conducted with the focus on work stressors and infections. We therefore aimed to investigate this association in a prospective cohort study. METHODS: Our study included 25 029 employed individuals who filled-out a questionnaire in September 1997 and were followed through record linkages until retirement or December 2016. Work stress was assessed at baseline using a Swedish version of the Demand-Control Questionnaire, whereas hospital contacts related to infections were identified from the National Patient Register. We fitted extensions of the standard Cox model to account for recurrent infections. RESULTS: In total, we observed 8257 infections. Individuals in the third tertile of job demand had a 13% higher hazard of infections (HR=1.13; 95% CI=1.03 to 1.24) compared with individuals in the first tertile, specifically an increased incidence of upper respiratory tract infections (HR=1.15; 95% CI=1.00 to 1.33) and urinary tract infections (HR=1.31; 95% CI=1.09 to 1.57) was found. Employees with the highest job control (third tertile) had no lower risk of infections than individuals in the lowest tertile (HR=1.02; 95% CI=0.92 to 1.13). When combining the demand and control dimensions into job strain scale, no association between high job strain and infections was observed (HR=1.08; 95% CI=0.97 to 1.21). CONCLUSION: High job demand, but not low job control, is associated with an increased occurrence of infections. No difference was observed in workers with high strain jobs compared with those with low strain jobs.

Sleep duration and mortality - Does weekend sleep matter?

Previous studies have found a U-shaped relationship between mortality and (weekday) sleep duration. We here address the association of both weekday and weekend sleep duration with overall mortality. A cohort of 43,880 subjects was followed for 13 years through record-linkages. Cox proportional hazards regression models with attained age as time-scale were fitted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals for mortality; stratified analyses on age (<65 years, ≥65 years) were conducted. Among individuals <65 years old, short sleep (≤5 hr) during weekends at baseline was associated with a 52% higher mortality rate (hazard ratios 1.52; 95% confidence intervals 1.15-2.02) compared with the reference group (7 hr), while no association was observed for long (≥9 hr) weekend sleep. When, instead, different combinations of weekday and weekend sleep durations were analysed, we observed a detrimental association with consistently sleeping ≤5 hr (hazard ratios 1.65; 95% confidence intervals 1.22-2.23) or ≥8 hr (hazard ratios 1.25; 95% confidence intervals 1.05-1.50), compared with consistently sleeping 6-7 hr per day (reference). The mortality rate among participants with short sleep during weekdays, but long sleep during weekends, did not differ from the rate of the reference group. Among individuals ≥65 years old, no association between weekend sleep or weekday/weekend sleep durations and mortality was observed. In conclusion, short, but not long, weekend sleep was associated with an increased mortality in subjects <65 years. In the same age group, short sleep (or long sleep) on both weekdays and weekend showed increased mortality. Possibly, long weekend sleep may compensate for short weekday sleep.