Trends in Hip Fracture Incidence, Recurrence, and Survival by Education and Comorbidity: A Swedish Register-based Study.

BACKGROUND: Hip fractures are common and severe conditions among older individuals, associated with high mortality, and the Nordic countries have the highest incidence rates globally. With this study, we aim to present a comprehensive picture of trends in hip fracture incidence and survival in the older Swedish population stratified by education, birth country, and comorbidity level. METHODS: This study is based on a linkage of several population registers and included the entire population over the age of 60 living in Sweden. We calculated age-standardized incidence rates for first and recurrent hip fractures as well as age-standardized proportions of patients surviving 30 and 365 days through the time period 1998 to 2017. We calculated all outcomes for men and women in the total population and in each population stratum. RESULTS: Altogether, we observed 289,603 first hip fractures during the study period. Age-standardized incidence rates of first and recurrent fractures declined among men and women in the total population and in each educational-, birth country-, and comorbidity group. Declines in incidence were more pronounced for recurrent than for first fractures. Approximately 20% of women and 30% of men died within 1 year of their first hip fracture. Overall, survival proportions remained constant throughout the study period but improved when taking into account comorbidity level. CONCLUSIONS: Hip fracture incidence has declined across the Swedish population, but mortality after hip fracture remained high, especially among men. Hip fracture patients constitute a vulnerable population group with increasing comorbidity burden and high mortality risk.

The rate by which mortality increase with age is the same for those who experienced chronic disease as for the general population.

BACKGROUND: Mortality doubles approximately every 6-7 years during adulthood. This exponential increase in death risk with chronological age is the population-level manifestation of ageing, and often referred to as the rate-of-ageing. OBJECTIVE: We explore whether the onset of severe chronic disease alters the rate-of-ageing. METHODS: Using Swedish register data covering the entire population of the birth cohorts 1927-30, we analyse whether being diagnosed with myocardial infarction, diabetes or cancer results in a deviation of the rate-of-ageing from those of the total population. We also quantify the long-term mortality effects of these diseases, using ages with equivalent mortality levels for those with disease and the total population. RESULTS: None of the diseases revealed a sustained effect on the rate-of-ageing. After an initial switch upwards in the level of mortality, the rate-of-ageing returned to the same pace as for the total population. The time it takes for the rate to return depends on the disease. The long-term effects of diabetes and myocardial infarction amount to mortality levels that are equivalent to those aged 5-7 years older in the total population. For cancer, the level of mortality returns to that of the total population. CONCLUSION: Our results suggest an underlying process of ageing that causes mortality to increase at a set pace, with every year older we become. This process is not affected by disease history. The persistence of the rate-of-ageing motivates a critical discussion of what role disease prevention can play in altering the progression of ageing.

Disability pensions related to heavy physical workload: a cohort study of middle-aged and older workers in Sweden.

OBJECTIVES: The aim of the study was to examine the associations between heavy physical workload among middle-aged and older workers and disability pension due to any diagnosis, as well as musculoskeletal, psychiatric, cardiovascular or respiratory diagnoses. The population-based design made it possible to examine dose-response and potential gender differences in the associations. METHODS: About 1.8 million men and women aged 44-63 years and registered as living in Sweden in 2005 were followed regarding disability pension during 2006-2016, until ages 55-65 years. Mean values of physical workload and job control, estimated through gender-specific job-exposure matrices (JEMs), were assigned to individuals through their occupational titles in 2005. Exposure values were ranked separately for women and men and divided into quintiles. Associations were analyzed with Cox proportional-hazards regression. RESULTS: The analyses showed robust, dose-response associations between physical workload and disability pension with a musculoskeletal diagnosis in both genders: the adjusted hazard ratio and 95% confidence interval for those with the heaviest exposure was 2.58 (2.37-2.81) in women and 3.34 (2.83-3.94) in men. Dose-response associations were also seen in relation to disability pension with a cardiovascular or a respiratory diagnosis, though the hazard ratios were smaller. Physical workload was not associated with disability pension with a psychiatric diagnosis after adjustment for job control. CONCLUSION: This study of the entire Swedish population of middle-aged and older workers suggests that higher degrees of physical workload may increase the risk of disability pension overall, and specifically with musculoskeletal, cardiovascular or respiratory diagnosis, in both women and men.

Impact of winter holiday and government responses on mortality in Europe during the first wave of the COVID-19 pandemic.

BACKGROUND: This aggregated population study investigated the impact of the seemingly quasi-randomly assigned school winter holiday in weeks 6-10 (February to early March) on excess mortality in 219 European regions (11 countries) during the COVID-19 pandemic in the spring 2020. A secondary aim was to evaluate the impact of government responses to the early inflow of infected cases. METHODS: Data on government responses weeks 8-14 were obtained from the Oxford COVID-19 Government Response Tracker. Regional data on total all-cause mortality during weeks 14-23 in 2020 were retrieved from Eurostat and national statistical agencies and compared with the average mortality during same period 2015-2019. Variance-weighted least square regression was used with mortality difference as dependent variable with adjustment for country, population density and age distribution. RESULTS: Being a region with winter holiday exclusively in week 9 was in the adjusted analysis associated with 16 weekly excess deaths [95% confidence interval (CI) 13-20] per million inhabitants during weeks 14-23, which corresponds to 38% of the excess mortality in these regions. A more stringent response implemented in week 11, corresponding to 10 additional units on the 0-100 ordinal scale, was associated with 20 fewer weekly deaths (95% CI 18-22) per million inhabitants. CONCLUSIONS: Winter holiday in week 9 was an amplifying event that contributed importantly to the excess mortality observed in the study regions during the spring 2020. Timely government responses to the resulting early inflow of cases reduced the excess in mortality.

Excess mortality from COVID-19: weekly excess death rates by age and sex for Sweden and its most affected region.

BACKGROUND: Sweden has one of the highest numbers of COVID-19 deaths per inhabitant globally. However, absolute death counts can be misleading. Estimating age- and sex-specific mortality rates is necessary in order to account for the underlying population structure. Furthermore, given the difficulty of assigning causes of death, excess all-cause mortality should be estimated to assess the overall burden of the pandemic. METHODS: By estimating weekly age- and sex-specific death rates during 2020 and during the preceding 5 years, our aim is to get more accurate estimates of the excess mortality attributed to COVID-19 in Sweden, and in the most affected region Stockholm. RESULTS: Eight weeks after Sweden's first confirmed case, the death rates at all ages above 60 were higher than for previous years. Persons above age 80 were disproportionally more affected, and men suffered greater excess mortality than women in ages up to 75 years. At older ages, the excess mortality was similar for men and women, with up to 1.5 times higher death rates for Sweden and up to 3 times higher for Stockholm. Life expectancy at age 50 declined by <1 year for Sweden and 1.5 years for Stockholm compared to 2019. CONCLUSIONS: The excess mortality has been high in older ages during the pandemic, but it remains to be answered if this is because of age itself being a prognostic factor or a proxy for comorbidity. Only monitoring deaths at a national level may hide the effect of the pandemic on the regional level.

Trends in life expectancy: did the gap between the healthy and the ill widen or close?

BACKGROUND: During the past decades, life expectancy has continued to increase in most high-income countries. Previous research suggests that improvements in life expectancy have primarily been driven by advances at the upper end of the health distribution, while parts of the population have lagged behind. Using data from the entire Swedish population, this study aims to examine the life expectancy development among subgroups of individuals with a history of common diseases relative to that of the general population. METHODS: The remaining life expectancy at age 65 was estimated for each year in 1998-2017 among individuals with a history of disease, and for the total Swedish population. We defined population subgroups as individuals with a history of myocardial infarction, ischemic or hemorrhagic stroke, hip fracture, or colon, breast, or lung cancer. We further distinguished between different educational levels and Charlson comorbidity index scores. RESULTS: Life expectancy gains have been larger for men and women with a history of myocardial infarction, ischemic or hemorrhagic stroke, and colon or breast cancer than for the general population. The life expectancy gap between individuals with a history of hip fracture or lung cancer and the general population has, however, been growing. Education and comorbidity have affected mortality levels, but have not altered the rate of increase in life expectancy among individuals with disease history. The female advantage in life expectancy was less pronounced among individuals with disease history than among the general population. CONCLUSIONS: Life expectancy has increased faster in many subpopulations with a history of disease than in the general population, while still remaining at lower levels. Improvements in life expectancy have been observed regardless of comorbidity or educational level. These findings suggest that the rise in overall life expectancy reflects more than just improved survival among the healthy or the delayed onset of disease.

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.

Commonly used estimates of the genetic contribution to disease are subject to the same fallacies as bad luck estimates.

The scientific debate following the initial formulation of the "bad luck" hypothesis in cancer development highlighted how measures based on analysis of variance are inappropriately used for risk communication. The notion of "explained" variance is not only used to quantify randomness, but also to quantify genetic and environmental contribution to disease in heritability coefficients. In this paper, we demonstrate why such quantifications are generally as problematic as bad luck estimates. We stress the differences in calculation and interpretation between the heritability coefficient and the population attributable fraction, the estimated fraction of all disease events that would not occur if an intervention could successfully prevent the excess genetic risk. We recommend using the population attributable fraction when communicating results regarding the genetic contribution to disease, as this measure is both more relevant from a public health perspective and easier to understand.

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.

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis.

BACKGROUND: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines. METHODS: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies. RESULTS: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92-1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders. CONCLUSIONS: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated.

Estimating incidence and prevalence from population registers: example from myocardial infarction.

AIM: To illustrate how the fundamental epidemiological measures, incidence rate and prevalence proportion, can be estimated based on Swedish population registers using acute myocardial infarction (MI) as an example, together with a discussion about the analytical decisions. METHODS: All individuals in Sweden aged 60-89 (born 1904-1954) during the study period 1994-2014 were identified through the Total Population Register. Cases of MI were defined and identified from information on hospital admissions and causes of death. Incidence rates of all, first, and recurrent MI were calculated together with prevalence proportions. RESULTS: The incidence rate of all, first, and recurrent MI declined over the study period. While the incidence rates of first MI are lower for women than men, the incidence rates of recurrent MI are considerably higher but similar for men and women. The prevalence calculated with duration of disease set at 28 days also declined. This was despite improved survival from MI and increased life expectancy over the same period meaning that the decline in incidence was large enough to compensate for increased survival. CONCLUSIONS: Calculating incidence and prevalence of diseases using population registers requires detailed and well-reasoned definitions. The definitions will affect both the study population and the number of disease events and it is essential that the cases and the study population are defined in a coherent way. Different measures of disease occurrence contribute with different aspects of the disease panorama and a joint interpretation contributes to a thorough understanding of the disease development in a population.

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Association between prediagnostic glucose, triglycerides, cholesterol and meningioma, and reverse causality.

BACKGROUND: Although meningioma is a benign tumour, it may cause significant morbidity. Obesity and diabetes are positively associated with meningioma. To evaluate the potential effects of obesity-related prediagnostic glucose, triglycerides and cholesterol on meningioma and of prediagnostic meningioma on these biomarkers, we conducted a cohort study. METHODS: We identified 41 355 individuals in the Apolipoprotein MOrtality RISk cohort with values for these biomarkers within 15 years before meningioma diagnosis, death, migration or the end of follow-up. We then estimated hazard ratios (HRs) and their interactions with time and age using Cox regression. RESULTS: Meningioma was diagnosed in 181 women and 115 men whose median follow-up time was 7 years. Fasting serum glucose level was inversely related to meningioma among women (Ptrend=0.0006) but not men (Ptrend=0.24). Prediagnostic diabetes was inversely related to meningioma in both sexes combined (HR=0.45, 95% confidence interval (CI) 0.29-0.71), as was serum cholesterol within the year before diagnosis (HR=0.50, 95% CI 0.34-0.72). CONCLUSIONS: Paradoxically, hyperglycaemia is inversely associated with meningioma in women. This finding does not necessarily negate the positive role of obesity or diabetes in meningioma development; rather, it may indicate that their effects depend on the stage of development. Furthermore, the prediagnostic tumour may reduce serum cholesterol levels.

Amyotrophic lateral sclerosis among cross-country skiers in Sweden.

A highly increased risk of amyotrophic lateral sclerosis (ALS) has been suggested among professional athletes. We aimed to examine whether long distance cross-country skiers have also a higher risk of ALS and whether the increased risk was modified by skiing performance. We followed 212,246 cross-country skiers in the Swedish Vasaloppet cohort and a random selection of 508,176 general Swedes not participating in the Vasaloppet during 1989-2010. The associations between cross-country skiing as well as skiing performance (i.e., type of race, finishing time and number of races) and the consequent risk of ALS were estimated through hazard ratios (HRs) derived from Cox model. During the study, 39 cases of ALS were ascertained among the skiers. The fastest skiers (100-150% of winner time) had more than fourfold risk of ALS (HR 4.31, 95% confidence interval [CI] 1.78-10.4), as compared to skiers that finished at >180% of winner time. Skiers who participated >4 races during this period had also a higher risk (HR 3.13, 95% CI 1.37-7.17) than those participated only one race. When compared to the non-skiers, the fastest skiers still had a higher risk (HR 2.08, 95% CI 1.12-3.84), as skiers who had >4 races (HR 1.88, 95% CI 1.05-3.35), but those finishing at >180% of winner time had a lower risk (HR 0.46, 95% CI 0.24-0.87). In conclusion, long distance cross-country skiing is associated with a higher risk of ALS, but only among the best skiers; recreational skiers appear to have a largely reduced risk.

Stable or improved health status in the population 65 years and older in Stockholm, Sweden - an 8-year follow-up of self-reported health items.

BACKGROUND: Previous studies have reached different conclusions about whether health is improving in the ageing population. More studies with narrow age groups analyzed separately for men and women will contribute to the literature. AIM: To describe trends in self-reported indicators of health and health-related quality of life between 2002 and 2010, focusing on differences between gender and age groups. A population-based survey of individuals 65+ in the Stockholm County was used. RESULTS: Prevalence of health problems increased with age both among men and women. Men generally reported having no health problems to a larger extent than women, but the proportions reporting severe problems were similar. The larger picture is one of stability in health-related quality of life, even if several items developed for the better, especially among women. While the proportions reporting no health/functional problems increased for many items, the proportions reporting severe problems remained unchanged among men and improved only for two items among women. CONCLUSIONS OVERALL, IMPROVEMENTS WERE SEEN IN MANY OF THE HEALTH-RELATED QUALITY OF LIFE ITEMS AS WELL AS FOR SELF-RATED HEALTH AMONG WOMEN THE PROPORTIONS REPORTING LONG-TERM ILLNESS OR PERSISTENT HEALTH PROBLEMS INCREASED, BUT FEWER SEEM TO BE LIMITED IN THEIR DAILY ACTIVITIES BY THESE PROBLEMS THE STABLE PROPORTIONS OF POOR SELF-RATED HEALTH INDICATES THAT WHILE HEALTH AND FUNCTIONING SEEM TO BE IMPROVING FOR THE MAJORITY OF THE OLDER POPULATION, SOME GROUPS MAY BE LAGGING BEHIND FUTURE STUDIES SHOULD PAY ATTENTION TO CHANGES BOTH IN THE UPPER AND LOWER ENDS OF THE HEALTH SPECTRUM.

Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data.

We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 × 10(-11) ), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with ∼3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma.

Unprovoked seizures after traumatic brain injury: A population-based case-control study.

OBJECTIVE: To quantify the risk of unprovoked seizures after traumatic brain injury (TBI) METHODS: We used the Stockholm Incidence Registry on Epilepsy to carry out a population-based case-control study, including 1,885 cases with incident unprovoked seizures from September 1, 2000 through August 31, 2008, together with 15,080 matched controls. Information of prior hospitalizations for TBI was obtained through record linkage with the Swedish National Inpatient Registry for the period 1980-2008. Relative risks (RRs) for unprovoked seizures were estimated after various TBI diagnoses, and influences of TBI severity and time since trauma were studied in detail. RESULTS: After hospitalization for mild TBI, the RR was 2.0 (95% confidence interval [CI] 1.5-2.7). The RR was higher after brain contusion (5.9, 95% CI 2.4-15.0) or intracranial hemorrhage (ICH) (4.5, 95% CI 2.2-9.0), whereas a combination of both diagnoses led to a further sevenfold increase in RR (42.6, 95% CI 12.2-148.5). The risk was greatest during the first 6 months after severe TBI (RR 48.9, 95% CI 10.9-218.9) or mild TBI (RR 8.1, 95% CI 3.1-21.7), but was still elevated >10 years after any TBI. SIGNIFICANCE: Herein we present a large population-based case-control study on TBI as a risk factor for unprovoked epileptic seizures, including cases of all ages with individually validated seizure diagnoses. The risk for epileptic seizures was substantially increased after TBI, especially during the first 6 months after the injury and in patients with a combination of ICH and brain contusion.