Prognosis of patients with malignant mesothelioma by expression of programmed cell death 1 ligand 1 and mesothelin in a contemporary cohort in Finland

ObjectivesWe aimed to describe mesothelin (MSLN) and programmed cell death 1 ligand 1 (PD-L1) tumour overexpression amongst patients with malignant mesothelioma (MM), and their associations with survival, amongst a cohort of patients with MM in Finland.MethodsBetween 2004 and 2017, 91 adults with histologically confirmed MM were identified from the Auria Biobank in Finland and followed-up using linked data from electronic health records and national statistics. Biomarker content in tumour cell membranes was determined using automated Immunohistochemistry on histological sections. Stained tumour sections were scored for MSLN and PD-L1 intensity. Adjusted associations between MSLN/PD-L1 co-expression and mortality were evaluated by estimating hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression.ResultsBiomarker overexpression occurred in 52 patients for MSLN and 34 patients for PD-L1 and was associated with tumour histology and certain comorbidities. Fifteen per cent of patients had a tumour that overexpressed both biomarkers; r =-0.244, p-value: 0.02. Compared with MSLN+/PD-L1+ patients, HRs (95% CIs) for death were 4.18 (1.71–10.23) for MSLN-/PD-L1+ patients, 3.03 (1.35–6.77) for MSLN-/PD-L1- patients, and 2.13 (0.97–4.67) for MSLN+/PD-L1- patients.ConclusionsBoth MSLN and PD-L1 markers were independent prognostic indicators in patients with MM. Overexpression of MSLN was associated with longer survival; yet their combined expression gave a better indication of survival. The risk of death was four times higher amongst MSLN-/PD-L1+ patients than in MSLN+/PD-L1+ patients.</p

Risk of Severe Knee and Hip Osteoarthritis in Relation to Level of Physical Exercise: A Prospective Cohort Study of Long-Distance Skiers in Sweden

Background: To complete long-distance ski races, regular physical exercise is required. This includes not only cross-country skiing but also endurance exercise during the snow-free seasons. The aim of this study was to determine whether the level of physical exercise is associated with future risk of severe osteoarthritis independent of previous diseases and injuries. Methodology/Principal Findings: We used a cohort that consisted of 48 574 men and 5 409 women who participated in the 90 km ski race Vasaloppet at least once between 1989 and 1998. Number of performed races and finishing time were used as estimates of exercise level. By matching to the National Patient Register we identified participants with severe osteoarthritis, defined as arthroplasty of knee or hip due to osteoarthritis. With an average follow-up of 10 years, we identified 528 men and 42 women with incident osteoarthritis. The crude rate was 1.1/1000 person-years for men and 0.8/1000 person-years for women. Compared with racing once, participation in &gt;= 5 races was associated with a 70% higher rate of osteoarthritis (multivariable-adjusted hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.33 to 2.22). The association was dose-dependent with an adjusted HR of 1.09, 95% CI 1.05 to 1.13 for each completed race. A faster finishing time, in comparison with a slow finishing time, was also associated with an increased rate (adjusted HR 1.51, 95% CI 1.14 to 2.01). Contrasting those with 5 or more ski races and a fast finish time to those who only participated once with a slow finish time, the adjusted HR of osteoarthritis was 2.73, 95% CI 1.78 to 4.18. Conclusions/Significance: Participants with multiple and fast races have an increased risk of subsequent arthroplasty of knee and hip due to osteoarthritis, suggesting that intensive exercise may increase the risk

Diagnostic and prognostic factors in patients with prostate cancer : a systematic review

Funding PIONEER is funded through the IMI2 Joint Undertaking and is listed under Grant Agreement No. 777492 and is part of the Big Data for Better Outcomes Programme (BD4BO). IMI2 receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views communicated within are those of PIONEER. Neither the IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein.Peer reviewedPublisher PD

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Hip fracture : Risk factors and mortality

The objective of this thesis was to identify factors related to risk of hip fracture and mortality after the hip fracture. We used data from a large population-based case-control study in postmenopausal women aged 50-81 years during 1993-1995 who resided in six counties in Sweden. The analysis was based on 1327 incident post-menopausal cases of hip fracture and 3262 randomly selected controls. Information on possible risk factors was collected by a comprehensive mailed questionnaire. Socioeconomic status and marital status were obtained by record linkage with census data. In addition, all subjects were followed up until December 1998 by the Inpatient and Cause-of Death Registers. Adult weight change and height were the dominant body size risk factors. Current weight had protective effect independent of weight change only among the minority of women who did not gain weight as adults, whereas weight at age 18 appeared not to be a risk factor for hip fracture. High leisure physical activity in the years before interview was inversely associated with risk of hip fracture. This decrease in risk was particularly pronounced in women who had gained weight during adult life. Occupational physical activity was not associated with hip fracture risk. Decreased risk of hip fracture was found among women who were gainfully employed, who had high household income, and among women who were living in a one-family house as opposed to more crowded housing. Divorced, unmarried and widowed women had a higher risk of hip fracture than those who were married or cohabiting. However, occupational grouping and educational level were not associated with risk. A strong association was found between the risk of hip fracture and duration of smoking, but there was no clear relation between the numbers of cigarettes smoked and fracture risk. The impact of smoking appeared to be reversible: 15 years after cessation there was no excess hip fracture risk. Alcohol consumption had a weak inverse association with risk. Hip firacture'patients had a two fold higher mortality rate than control subjects after adjustment for factors associated with risk of hip fracture. The increased mortality did not vary by type of fracture (cervical vs. trochanteric). However, a greater relative risk of death was found among younger women and among those who did not gain weight as adult. The primary causes of death among women who died after hip fracture were cardiovascular disease and cancer

Hemorrhage after ischemic stroke - relation to age and previous hemorrhage in a nationwide cohort of 58 868 patients

Background In randomized controlled trials of secondary prevention after stroke, the risk of hemorrhage varies between 1% and 5% per year in patients with antithrombotic therapy, i.e. anticoagulants and antiplatelets. Aim To explore the rate and the risk of hemorrhage after stroke in a nationwide cohort. Methods We identified 58 868 first ever ischemic stroke patients in the Swedish Stroke Register during 2001 to 2005 (=index stroke) and followed them by record linkage to the National Patient Register. Rates of hemorrhage and hazard ratios, for comparisons of rates between subgroups, were calculated. Results Of the 58 586 ischemic stroke patients identified, 5527 (9.4%) had a history of hemorrhage. During follow-up (mean 2.0 years), 2876 patients endured a hemorrhage, giving an average hemorrhage rate of 2.6 (95% confidence interval 2.5-2.7) per 100 person-years. After index stroke, 11% of the patients were discharged with anticoagulants, and 79% with antiplatelets. Given the differences in baseline characteristics, the hemorrhage rates (per 100 person-years) were 2.5 (95% confidence interval 2.2-2.8), 2.4 (95% confidence interval 2.32.5), and 3.8 (95% confidence interval 3.5-4.2) in patients prescribed anticoagulants, antiplatelets, and no antithrombotics, respectively. There was an increased risk of hemorrhage in patients <75 years compared with those <75 years (hazard ratio?=?1.61, 95% confidence interval 1.49-1.73) and in patients with previous hemorrhages compared with those without (hazard ratio = 1.82, 95% confidence interval 1.64-2.02). Conclusions When antithrombotics were used in large-scale clinical practice, the observed rates of hemorrhage were similar with anticoagulant therapy but increased with antiplatelet therapy compared with rates reported in randomized controlled trials. Old age and previous hemorrhage were associated with an increased risk of hemorrhage after an ischemic stroke

Golf: a game of life and death -reduced mortality in Swedish golf players

The specific health benefits achieved from different forms and patterns of leisure-time physical activity are not established. We analyzed the mortality in a cohort of Swedish golf players. We used the Swedish Golf Federation&apos;s membership registry and the nationwide Mortality Registry. We calculated standardized mortality ratios (SMR) with stratification for age, sex, and socioeconomic status. The cohort included 300 818 golfers, and the total number of deaths was 1053. The overall SMR was 0.60 [95% confidence intervals (CIs): 0.57-0.64]. The mortality reduction was observed in men and women, in all age groups, and in all socioeconomic categories. Golfers with the lowest handicap (the most skilled players) had the lowest mortality; SMR 5 0.53 (95% CI: 0.41-0.67) compared with 0.68 (95% CI: 0.61-0.75) for those with the highest handicap. While we cannot conclude with certainty that all the 40% decreased mortality rates are explained by the physical activity associated with playing golf, we conclude that most likely this is part of the explanation. To put the observed mortality reduction in context, it may be noted that a 40% reduction of mortality rates corresponds to an increase in life expectancy of about 5 years

First-Ever Atrial Fibrillation Documented After Hemorrhagic or Ischemic Stroke: The Role of the CHADS(2) Score at the Time of Stroke.

BACKGROUND: The CHADS(2) score (C, congestive heart failure [CHF]; H, hypertension [HT]; A, age ≥75 y; D, diabetes mellitus; S(2) , prior stroke or transient ischemic attack) is used to assess the risk of ischemic stroke in patients with atrial fibrillation (AF). However, its role in patients without documented AF is not well explored. HYPOTHESIS: The goal of the current study was to explore if the incidence of hospitalization with first-ever AF after stroke increased with increasing CHADS(2) score. METHODS: We identified 57636 patients with nonfatal stroke and no documented AF in the Swedish Stroke Register (Riks-Stroke) during 2001-2004 and followed them for a mean of 2.2 years through record linkage to the Inpatient and Cause of Death registers. Cox regression hazard models were used to estimate the relative risk (RR) of new AF following stroke and its association with different CHADS(2) scores. RESULTS: Overall, 2769 patients were hospitalized with new AF (4.8%, 21.7 per 1000 person-years). The incidence increased from 9.6 per 1000 person-years in CHADS(2) score 0 to 42.7 in CHADS(2) score 6, conferring a RR of 4.2 (95% confidence interval [CI]: 2.5-6.8). For CHADS(2) scores 3-5, the RRs were approximately 3 (vs CHADS(2) score 0). Adjusted RRs were 1.9 (95% CI: 1.7-2.1) for CHF, 1.4 (95% CI: 1.3-1.5) for HT, 2.1 (95% CI: 2.0-2.3) for age ≥75 years, 0.9 (95% CI: 0.8-1.0) for diabetes, and 1.0 (95% CI: 0.91-1.07) for previous stroke. The risk of AF was higher in ischemic than in hemorrhagic stroke. CONCLUSIONS: In this retrospective register study, the incidence of AF following stroke was strongly influenced by higher CHADS(2) scores where age ≥75 years, CHF, and HT were the contributing CHADS(2) components. © 2011 Wiley Periodicals, Inc. Riks-Stroke is funded by the National Board of Health and Welfare and the Swedish Association of Local Authorities and Regions. S. Åsberg has received a research scholarship from the National Association for Stroke Patients in Sweden. All authors have independent affiliations with universities in Sweden. B. Farahmand and K. Henriksson are employees of AstraZeneca R&D, Sweden. A. Terént has received funding from AstraZeneca. N. Edvardsson serves as medical advisor to AstraZeneca R&D, Sweden. The authors have no other funding, financial relationships, or conflicts of interest to disclose