Early mortality in children with cancer in Denmark and Sweden: The role of social background in a setting with universal healthcare.

Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (ORadj_Low_vs_High 1.65 [95% CI 1.22-2.23]) and income (ORadj_Q1(lowest)_vs_Q4(highest) 1.77 [1.25-2.49]). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis.

Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

BACKGROUND: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation. METHODS: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay. CONCLUSIONS: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.

Disease incidence and not case fatality drives the rural disadvantage in myocardial-infarction-related mortality in Germany.

OBJECTIVE: Demographic and infrastructural developments might compromise medical care provision in rural regions, particularly for acute health conditions. Studying the case of myocardial infarction (MI), we investigated how MI-related mortality at ages 65+ varies between rural and urban regions in Germany and to what extent differences are driven by varying case fatality and disease incidence. METHODS: The study relies on data containing all hospitalizations, cause-specific deaths and population counts for the total German population between years 2012-2018 and ages 65+. MI-related mortality, MI incidence and case fatality are compared between urban and rural regions in a population-wide analysis. The impacts of changing incidence and case fatality on rural-urban MI-related mortality differences are assessed using a counterfactual approach. RESULTS: Rural regions in Germany show systematically higher MI-related death rates and MI incidence at ages 65+ compared to urban regions. Higher mortality is primarily the result of higher MI incidence in rural regions, while case fatality is largely similar. The rural excess in MI-related death rates would be nullified and 1 out of 6 MI-related deaths in rural regions could be prevented if rural regions in Germany would have at least the median MI incidence of urban regions. CONCLUSIONS: MI incidence and not case fatality drives the rural disadvantage in MI-related mortality in Germany. Higher MI incidence points towards potential regional variation in the effectiveness of disease prevention. The findings highlight that improving disease prevention at the patient level carries larger opportunities for reducing regional MI-related mortality inequalities in Germany.

Frailty Among Breast Cancer Survivors: Evidence From Swedish Population Data.

Incidence and survival of breast cancer, the most common cancer among women, have been increasing, leaving survivors at risk of aging-related health conditions. In this matched cohort study, we examined frailty risk with the Hospital Frailty Risk Score among breast cancer survivors (n = 34,900) and age-matched comparison subjects (n = 290,063). Women born in 1935-1975, registered in the Swedish Total Population Register (1991-2015), were eligible for inclusion. Survivors had a first breast cancer diagnosis in 1991-2005 and survived ≥5 years after initial diagnosis. Death date was determined by linkage to the National Cause of Death Registry (through 2015). Cancer survivorship was weakly associated with frailty (subdistribution hazard ratio (SHR) = 1.04, 95% confidence interval (CI): 1.00, 1.07). In age-stratified models, those diagnosed at younger ages (<50 years) had higher risk of frailty (SHR = 1.12, 95% CI: 1.00, 1.24) than those diagnosed at ages 50-65 (SHR = 1.03, 95% CI: 0.98, 1.07) or >65 (SHR = 1.09, 95% CI: 1.02, 1.17) years. Additionally, there was increased risk of frailty for diagnoses in 2000 or later (SHR = 1.15, 95% CI: 1.09, 1.21) compared with before 2000 (SHR = 0.97, 95% CI: 0.93, 1.17). This supports work from smaller samples showing that breast cancer survivors have increased frailty risk, particularly when diagnosed at younger ages.

Childhood cancer risk in offspring of parents occupationally exposed to dusts: A register-based nested case-control study from Sweden of 5 decades.

BACKGROUND: Some largely inconsistent associations between parental occupational dust exposure and childhood cancer have been reported, with maternal exposures inadequately studied. The authors examined whether maternal or paternal occupational exposure to animal, wood, textile, or paper dust around a child's birth was associated with an increased risk of childhood cancer, both overall and by type (leukemias, lymphomas, central nervous system tumors, and other cancers). METHODS: In this nationwide, register-based, case-control study, children who were diagnosed with cancer from 1960 to 2015 were compared with up to 25 matched controls regarding maternal and paternal occupational dust exposure (9653 cases in maternal analyses and 12,521 cases in paternal analyses). Exposures were assessed using a job-exposure matrix and occupational information from census and register data. By using conditional logistic regression models, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Neither maternal nor paternal occupational exposure to animal, wood, textile, or paper dust was associated with childhood cancer overall, leukemias, or central nervous system tumors. Maternal, but not paternal, wood dust exposure was associated with an increased risk of lymphoma (OR, 1.42; 95% CI, 1.10-1.84), particularly non-Hodgkin lymphoma (OR, 2.03; 95% CI, 1.21-3.40). CONCLUSIONS: The current study did not confirm the associations reported previously but is the first to suggest a link between maternal occupational exposure to wood dust around pregnancy and lymphoma in the offspring.

Maternal smoking during pregnancy and type 1 diabetes in the offspring: a nationwide register-based study with family-based designs.

BACKGROUND: Maternal smoking during pregnancy was reported to be associated with a reduced risk of type 1 diabetes in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. METHODS: We included 2,995,321 children born in Sweden between 1983 and 2014 and followed them for a diagnosis of type 1 diabetes until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Apart from conducting a traditional cohort study, we performed a nested case-control study (quasi-experiment) comparing children with type 1 diabetes to their age-matched siblings (or cousins). Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Multivariable adjusted Cox proportional hazards regression and conditional logistic regression were used. RESULTS: A total of 18,617 children developed type 1 diabetes, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort (hazard ratio 0.78, 95% confidence interval [CI] 0.75-0.82). The corresponding odds ratio was 0.78 (95% CI 0.69-0.88) in the sibling and 0.72 (95% CI 0.66-0.79) in the cousin comparison analysis. CONCLUSIONS: This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring type 1 diabetes. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Late mortality among survivors of childhood acute lymphoblastic leukemia diagnosed during 1971-2008 in Denmark, Finland, and Sweden: A population-based cohort study.

OBJECTIVE: Investigate all-cause and cause-specific late mortality after childhood acute lymphoblastic leukemia (ALL) in a population-based Nordic cohort. METHODS: From the cancer registries of Denmark, Finland, and Sweden, we identified 3765 five-year survivors of ALL, diagnosed before age 20 during 1971-2008. For each survivor, up to five matched comparison subjects were randomly selected from the general population (n = 18,323). Causes of death were classified as relapse related, health related, and external. Late mortality was evaluated by cumulative incidences of death from 5-year survival date. Mortality hazard ratios (HR) were evaluated with Cox proportional models. RESULTS: Among the survivors, 315 deaths occurred during a median follow-up of 16 years from 5-year survival date (range 0-42). The majority were attributable to relapse (n = 224), followed by second neoplasm (n = 45). Cumulative incidence of all-cause late mortality at 15 years from diagnosis decreased gradually over treatment decades, from 14.4% (95% confidence interval [CI]: 11.6-17.2) for survivors diagnosed during 1971-1981, to 2.5% (95% CI: 1.3-3.7) for those diagnosed during 2002-2008. This was mainly attributable to a reduction in relapse-related deaths decreasing from 13.4% (95% CI: 10.7-16.1) for survivors diagnosed during 1971-1981 to 1.9% (95% CI: 0.9-2.8) for those diagnosed during 2002-2008. Health-related late mortality was low and did not change substantially across treatment decades. Compared to comparison subjects, all-cause mortality HR was 40 (95% CI: 26-61) 5-9 years from diagnosis, and 4.4 (95% CI: 3.4-5.6) ≥10 years from diagnosis. CONCLUSIONS: Survivors of ALL have higher late mortality than population comparison subjects. Among the survivors, there was a temporal reduction in risk of death from relapse, without increments in health-related death.

Occupational exposure to pesticides in mothers and fathers and risk of cancer in the offspring: A register-based case-control study from Sweden (1960-2015).

Maternal and paternal occupational exposure to pesticides was linked to leukemia in the offspring in some previous studies. Risks for other cancers, particularly from maternal exposure, are largely unknown. We examined the association between maternal and paternal exposure to pesticides and childhood cancer in a Swedish register-based case-control study (1960-2015). Cancer cases <20 years old were identified from the Cancer Register (n = 17313) and matched to controls (1:25) on birth year and sex. Employment history of each biological parent around the child's birth was retrieved from six censuses and a nationwide register, and exposure to any of herbicides, insecticides, and fungicides was evaluated using the Swedish job-exposure matrix (SWEJEM) in 9653/172194 mothers and 12521/274434 fathers of cases/controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models for any cancer, leukemia, lymphoma, central nervous system [CNS], and other solid tumors. We found an OR of 1.42 (95% CI 0.78, 2.57; 12 exposed cases) for lymphoma and 1.30 (95% CI 0.88, 1.93; 27 exposed cases) for other solid tumors associated with maternal occupational exposure to pesticides. No associations were observed between maternal exposure and leukemia or CNS tumors, or paternal exposure and any of the cancers examined, except for a potential association between pesticides exposure and myeloid leukemia (OR 1.15 [95% CI 0.73, 1.79; 22 exposed cases]). Although these findings merit further investigation, they indicate that parental exposure to pesticides may lead to higher risks of childhood cancer even in settings of low exposure.

Number of siblings and survival from childhood leukaemia: a national register-based cohort study from Sweden.

BACKGROUND: Previous studies suggest worse leukaemia survival for children with siblings, but the evidence is sparse, inconsistent and does not consider clinical factors. We explored the associations between number of siblings in the household, birth order and survival from childhood acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML). METHODS: In this nationwide register-based study we included all children aged 1-14, diagnosed with ALL and AML between 1991-mid-2015 in Sweden (n = 1692). Using Cox regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) according to number of siblings and birth order, adjusting for known prognostic and sociodemographic factors. RESULTS: A tendency towards better ALL survival among children with one, or ≥2, siblings was observed, adjHRs (95% CI): 0.73 (0.49-1.10) and 0.63 (0.40-1.00), respectively. However, this was mainly limited to children with low risk profiles. An indication of better AML survival among children with siblings was seen, adjHRs (95% CI) 0.68 (0.36-1.29) and 0.71 (0.34-1.48) but diminished after adjusting for birth order. CONCLUSION: Our results do not support previous findings that a larger number of siblings is associated with poorer survival. Inconsistencies might be explained by underlying mechanisms that differ between settings, but chance cannot be ruled out.

Ability of Noninvasive Scoring Systems to Identify Individuals in the Population at Risk for Severe Liver Disease.

BACKGROUND & AIMS: Noninvasive scoring systems are used to identify persons with advanced liver fibrosis. We investigated the ability of scoring systems to identify individuals in the general population at risk for future liver-related events. METHODS: We collected data from the Swedish Apolipoprotein Mortality Risk cohort on persons 35 to 79 years old who had blood samples collected from 1985 through 1996. We collected APRI (n = 127,302), BARD (n = 75,303), FIB-4 (n = 126,941), Forns (n = 122,419), and the nonalcoholic fatty liver disease (NAFLD) fibrosis scores (NFS, n = 13,160). We ascertained incident cases of cirrhosis or complications by linking Swedish health data registers. Cox regression was used to estimate hazard ratios (HRs) for severe liver disease at 5, 10, and a maximum follow-up time of 27 years. The predictive ability of the scores was evaluated using area under the receiver operating characteristic (AUROC) curve and C-statistics analyses. Our specific aims were to investigate the predictive capabilities of scoring systems for fatal and nonfatal liver disease, determine which scoring system has the highest level of accuracy, and investigate the predictive abilities of the scoring systems in persons with a higher probability of NAFLD at baseline. RESULTS: A similar proportion of individuals evaluated by each scoring system developed cirrhosis or complications thereof (1.0%-1.4%). The incidence of any outcome was increased in intermediate- and high-risk groups compared with low-risk groups, with HRs at 10 years in the high-risk group ranging from 1.67 for the BARD score to 45.9 for the APRI score. The predictive abilities of all scoring systems decreased with time and were higher in men. All scoring systems were more accurate in persons with risk factors for NAFLD at baseline, with AUROCs reaching 0.83. CONCLUSIONS: Higher scores from noninvasive scoring systems to evaluate fibrosis are associated with an increased risk of cirrhosis in a general population, but their predictive ability is modest. Performance was better when patients were followed for shorter time periods and in persons with a higher risk of NAFLD, with AUROC values reaching 0.83. New scoring systems are needed to evaluate risk of fibrosis in the general population and in primary care.

Mortality rates and cardiovascular disease burden in type 2 diabetes by occupation, results from all Swedish employees in 2002-2015.

OBJECTIVE: To identify occupations where employees with type 2 diabetes have a high risk of cardiovascular disease (CVD) and mortality, and their prevalence of CVD risk factors. This study can contribute in the creation of targeted interventions at the workplace. RESEARCH DESIGN AND METHODS: This nationwide registry-based study included all employees with type 2 diabetes born in Sweden in 1937-1979 (n = 180,620) and followed up in 2002-2015. We calculated age-standardized incidence (per 100,000 person-years) of all-cause and CVD mortality, ischemic heart disease (IHD) and stroke across the 30 most common occupations. Information on prognostic factors was retrieved from the National Diabetes Register. RESULTS: In males with type 2 diabetes, mortality rates were highest in manufacturing workers (1782) and machine operators (1329), and lowest in specialist managers (633). The risk of death at age 61-70 years was 21.8% in manufacturing workers and 8.5% in managers. In females with type 2 diabetes, mortality rates were highest in manufacturing workers (1150) and cleaners (876), and lowest in writers and artists (458); the risk of death at age 61-70 years was 12.4% in manufacturing workers and 4.3% in writers and artists. The same occupations also had relatively high incidences of CVD mortality, IHD and stroke. Occupational groups with poor prognosis had high prevalence of CVD risk factors including poor glycemic control, smoking and obesity. CONCLUSIONS: Manufacturing workers, machine operators and cleaners with type 2 diabetes have two to three times higher mortality rates than managers, writers and artists with type 2 diabetes. Major health gains would be made if targeted workplace interventions could reduce CVD risk factors in these occupations.

Impaired fasting glucose: a risk factor for atrial fibrillation and heart failure.

BACKGROUND: Dysglycaemia is associated with overall cardiovascular disease even at prediabetes levels. The aim of this study was to explore the association between glucose levels and future risk of developing atrial fibrillation and heart failure, respectively. METHODS: In this prospective cohort study subjects from the Swedish AMORIS-cohort with fasting glucose from health examinations 1985-1996 without previous cardiovascular disease (N = 294,057) were followed to 31 December 2011 for incident atrial fibrillation or heart failure. Cox proportional hazard models with attained age as timescale and adjustments for sex, cholesterol, triglycerides, and socioeconomic status were used to estimate hazard ratios by glucose categorized groups (normal glucose 3.9-6.0 mmol/L, impaired fasting glucose; 6.1-6.9 mmol/L, undiagnosed diabetes ≥ 7.0 mmol/L, and diagnosed diabetes). RESULTS: During a mean follow-up time of 19.1 years 28,233 individuals developed atrial fibrillation and 25,604 developed heart failure. The HR for atrial fibrillation was 1.19 (95% confidence interval 1.13-1.26) for impaired fasting glucose, 1.23 (1.15-1.32) for undiagnosed diabetes and 1.30 (1.21-1.41) for diagnosed diabetes. Corresponding figures for heart failure were; 1.40 (1.33-1.48), 2.11 (1.99-2.23), 2.22 (2.08-2.36) respectively. In a subset with BMI data (19%), these associations were attenuated and for atrial fibrillation only remained statistically significant among subjects with diagnosed diabetes (HR 1.25; 1.02-1.53). CONCLUSIONS: Fasting glucose at prediabetes levels is associated with development of atrial fibrillation and heart failure. To some extent increased BMI may drive this association.

Elevated Apolipoprotein B/A-1 Ratio is Associated With an Increased Risk of Aortic Stenosis: Experience From the AMORIS Cohort.

BACKGROUND: Lipoproteins are associated with acquired aortic valve stenosis (AS). This study investigated whether an elevated apolipoprotein (apo)B/apoA-1 ratio was associated with an increased risk of AS and if this association was influenced by a history of a major adverse cardiovascular event (MACE) defined as stroke, myocardial infarction or revascularisation. METHODS: A study was undertaken of 131,816 individuals, aged ≥30 years, from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort, with measurements of apolipoproteins B and A-1 at health examinations during 1985-1996. RESULTS: There were fewer women and the average age was 4 years older in the highest apoB/apoA-1 quintile compared with the lowest. Being overweight, having reduced renal function and diabetes mellitus were more frequent. Low-density lipoprotein cholesterol, triglyceride and apolipoprotein B levels were higher in the top apoB/apoA-1 quintile. During follow-up through 2011, non-rheumatic aortic valve disease was diagnosed in 2,999 individuals (2.3%). Using ICD-10 codes from 1997, AS was identified in 1,887 patients. An elevated apoB/apoA-1 ratio was associated with an increased incidence of aortic valve disease after multivariable adjustment [hazard ratio (HR) (95% CI) for the fifth vs first quintile of 1.28 (1.09-1.50)]. Restricting the analyses to incident AS during 1997-2011 yielded an HR of 1.41 (1.15-1.72). This increased incidence was primarily seen in women and individuals aged ≥65 years. History of MACE did not influence these associations. CONCLUSIONS: An elevated apoB/apoA-1 ratio was associated with an increased incidence of AS, particularly in women and individuals aged ≥65 years, regardless of previous MACE.

Incidence and prevalence of type 2 diabetes by occupation: results from all Swedish employees.

AIMS/HYPOTHESIS: The workplace is a potentially important arena for prevention of type 2 diabetes and the first step is to identify occupations where the disease is common and/or risk is high. Therefore, our aim was to analyse incidence and prevalence of type 2 diabetes across all occupational groups in Sweden. METHODS: This nationwide study included all Swedish citizens born between 1937 and 1979 and gainfully employed between 2001 and 2013 (N = 4,550,892), and followed for a diagnosis of diabetes from 2006 to 2015 (n = 201,717) through national registers. Prevalence in 2013 (mean age 51 years; range 35-67) and age-standardised incidence (per 1000 person-years) were analysed across the 30 most common occupations among men and women. Information on BMI, physical fitness and smoking was obtained through the National Conscription (mean age 18) and Medical Birth Registers (mean age 29). RESULTS: Prevalence of type 2 diabetes was 5.2% in men and 3.2% in women; in men it was highest among motor vehicle drivers (8.8%) and in women it was highest among manufacturing workers (6.4%). Incidence varied dramatically across occupational groups. In men, it was highest among manufacturing workers (9.41) and professional drivers (9.32) and lowest among university teachers (3.44). In women, incidence was highest in manufacturing workers (7.20) and cleaners (6.18) and lowest in physiotherapists (2.20). We found major differences in the prevalence of being overweight and smoking and in the level of physical fitness across these occupational groups even at young ages. CONCLUSIONS/INTERPRETATION: Professional drivers, manufacturing workers and cleaners have a threefold increased risk of type 2 diabetes compared with university teachers and physiotherapists. These differences most likely reflect dramatic differences in the prevalence of lifestyle risk factors. If workplace interventions could reduce weight and increase physical activity among employees in these occupations, major health gains may be made.

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study.

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980-2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28-1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92-1.39) and 1.55 (95% CI 1.04-2.31) 10-14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83-1.52; HR 1.08, 95% CI 0.79-1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.

Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease.

BACKGROUND & AIMS: It is unclear whether the identification of individuals at risk of cirrhosis using non-invasive tests can be improved by repeated measurements. Herein, we tested whether repeated measurements of fibrosis-4 index (FIB-4) could improve the identification of individuals at risk of severe liver disease. METHODS: Data were derived from the population-based Swedish AMORIS cohort with baseline examinations from 1985-1996. FIB-4 was calculated at 2 time points within 5 years. Thereafter, we associated changes in FIB-4 with outcomes. Incident severe liver disease data was ascertained through linkage to Swedish national registers until 2011. Hazard ratios (HRs) and CIs for outcomes were calculated using Cox regression. RESULTS: Of 126,942 individuals with available FIB-4 data, 40,729 (32.1%) underwent a second test within 5 years (mean interval 2.4 years). During 613,376 person-years of follow-up, 581 severe liver disease events were documented (0.95/1,000 person-years). An increase of 1 unit in FIB-4 was associated with an elevated risk of severe liver disease (adjusted hazard ratio [aHR] 1.81; 95% CI 1.67-1.96). Transitioning from a low- or intermediate- to a high-risk group was associated with an increased risk of severe liver disease compared with those consistently in the low-risk group (aHR 7.99 and 8.64, respectively). A particularly increased risk of severe liver disease was found in individuals defined as high risk at both tests (aHR 17.04; 95% CI 11.67-24.88). However, almost half of all events occurred in those consistently in the low-risk group. CONCLUSIONS: Repeated testing of FIB-4 within 5 years improves the identification of individuals at an increased risk of severe liver disease in the general population. However, the sensitivity is comparatively low and improved tests are needed for screening in a general population or primary care setting. LAY SUMMARY: The fibrosis-4 scoring system is often used to estimate the risk of advanced fibrosis in liver diseases. Herein, we found that changes in this score over time are associated with the risk of future severe liver disease in a population-based cohort. However, even if the prediction is improved by repeated testing, the overall ability of the score to predict future events is relatively low.

Burden and prevalence of prognostic factors for severe COVID-19 in Sweden.

The World Health Organization and European Centre for Disease Prevention and Control suggest that individuals over the age of 70 years or with underlying cardiovascular disease, cancer, chronic obstructive pulmonary disease, asthma, or diabetes are at increased risk of severe COVID-19. However, the prevalence of these prognostic factors is unknown in many countries. We aimed to describe the burden and prevalence of prognostic factors of severe COVID-19 at national and county level in Sweden. We calculated the burden and prevalence of prognostic factors for severe COVID-19 based on records from the Swedish national health care and population registers for 3 years before 1st January 2016. 9,624,428 individuals were included in the study population. 22.1% had at least one prognostic factor for severe COVID-19 (2,131,319 individuals), and 1.6% had at least three factors (154,746 individuals). The prevalence of underlying medical conditions ranged from 0.8% with chronic obstructive pulmonary disease (78,516 individuals) to 7.4% with cardiovascular disease (708,090 individuals), and the county specific prevalence of at least one prognostic factor ranged from 19.2% in Stockholm (416,988 individuals) to 25.9% in Kalmar (60,005 individuals). We show that one in five individuals in Sweden is at increased risk of severe COVID-19. When compared with the critical care capacity at a local and national level, these results can aid authorities in optimally planning healthcare resources during the current pandemic. Findings can also be applied to underlying assumptions of disease burden in modelling efforts to support COVID-19 planning.

No association between waiting time to surgery and mortality for healthier patients with hip fracture: a nationwide Swedish cohort of 59,675 patients.

Background and purpose - Waiting time to surgery for patients with hip fractures and its potential association with mortality has been frequently studied with the hypothesis that longer waiting time is associated with adverse outcomes. However, despite numerous studies, there is no consensus regarding which time frames are appropriate, and whether some patients are more vulnerable to waiting than others. We explored the association between waiting time to surgery and short-term mortality and whether sex, age, surgical method, and comorbidity (ASA) modified this association.Patients and methods - This is a nationwide cohort study of 59,675 patients undergoing hip fracture surgery between January 1, 2013 and December 31, 2017 with a 4-month follow-up of mortality. Data were extracted from the Swedish Registry for Hip Fracture Patients and Treatment (RIKSHÖFT) and mortality was obtained from Statistics Sweden.Results - Unadjusted analyses revealed an association between waiting more than 24 hours for surgery and increased mortality, primarily for women. However, when stratifying for ASA grade, an association persisted only among patients with ASA 3 and 4. Furthermore, the absolute differences in mortality risk between those waiting less or longer than 24 hours were small. Age, fracture type, and surgical method did not modify the association between waiting time and mortality.Interpretation - This study suggests that there may be a need for new guidelines, which take into account the heterogeneity of the patient population.

Suicides and deaths linked to risky health behavior in childhood cancer patients: A Nordic population-based register study.

BACKGROUND: Childhood cancer survivors have been reported to be vulnerable to psychiatric morbidities and risky health behavior. Suicides, substance abuse, accidents, and violence as causes of death can be regarded as an extreme manifestation of risky health behavior. In the current study, the authors studied the risk of suicide and other risky health behavior-related deaths among childhood cancer patients in Denmark, Finland, and Sweden. METHODS: Using linkage between national cancer, population, and cause-of-death registries, the authors investigated the causes of death in 29,285 patients diagnosed with cancer before age 20 years between 1971 and 2009 compared with a cohort of 146,282 age-matched, sex-matched, and country-matched population comparisons. Rate ratios (RRs) with 95% CIs were estimated using Poisson regression models, adjusting for demographic factors. RESULTS: The overall risk of dying of a risky health behavior was found to be increased among childhood cancer patients (RR, 1.25; 95% CI, 1.06-1.47) when compared with population comparisons. The elevated risk was statistically significant among patients with central nervous system tumors (RR, 1.49; 95% CI, 1.08-2.05) and patients diagnosed at ages 5 to 9 years and 15 to 19 years (RR, 1.50 [95% CI, 1.01-2.24] and RR, 1.31 [95% CI, 1.03-1.67], respectively). The overall risk of suicide was found to be increased (RR, 1.37; 95% CI, 1.02-1.83), and statistically significantly so when patients were diagnosed between ages 15 and 19 years (RR, 1.61; 95% CI, 1.09-2.39). CONCLUSIONS: Childhood cancer patients appear to have an increased risk of risky health behavior-related causes of death compared with the general population. The results of the current study suggest the importance of integrating psychosocial support into the follow-up care of these individuals.

Temporal trends in incidence, recurrence and prevalence of stroke in an era of ageing populations, a longitudinal study of the total Swedish population.

BACKGROUND: Stroke incidence has declined during the past decades. Yet, there is a concern that an ageing population together with improved survival after stroke will result in a raised proportion of the population who have experienced a stroke, as well as increasing incidence rate of recurrent strokes, and, absolute numbers of strokes. The objectives of this study were to investigate how the age specific incidence rates of recurrent strokes have developed in relation to the incidence rates of first strokes and how the postponement in age look like, and to see how the prevalence proportion of stroke as well as the absolute number of incident strokes has changed over time. METHODS: This study includes the total Swedish population born 1890-1954 living in Sweden from 1987. Stroke was identified through hospital admissions and deaths in national health registers (mandatory for all hospitals in Sweden). Age specific incidence rates were calculated for first, second, all recurrent, and all strokes for each calendar year between 1994 and 2014 for each age between 60 and 104 years. The proportion in the population with a history of stroke up to 7 years back in time was also calculated for different age groups and for different calendar years. RESULTS: Not only the incidence rate of first stroke but also of recurrent strokes have declined. The declines are evident in all ages up to 90 years of age, but not in ages above 90 years. Despite improved survival in stroke, the prevalence proportion has declined over the period and was around 3% in 2014 (somewhat higher for men than women). Even incident cases of stroke in absolute number has declined. CONCLUSIONS: Decreasing incidence rates of stroke have offset an increase in both absolute and relative numbers of stroke that otherwise would have taken place due to improved survival and an ageing population. The decline in stroke recurrence has been as strong as the decline in first strokes.