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1.
  • Fall, Tove, et al. (author)
  • Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma
  • 2015
  • In: JAMA pediatrics. - Stockholm : American Medical Association. - 2168-6203 .- 2168-6211. ; 169:11
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE: The association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results.OBJECTIVE: To determine whether exposure to dogs and farm animals confers a risk of asthma.DESIGN, SETTING AND PARTICIPANTS: In a nationwide cohort study, the association between early exposure to dogs and farm animals and the risk of asthma was evaluated and included all children born in Sweden from January 1, 2001, to December 31, 2010 (N = 1 011 051), using registry data on dog and farm registration, asthma medication, diagnosis, and confounders for parents and their children. The association was assessed as the odds ratio (OR) for a current diagnosis of asthma at age 6 years for school-aged children and as the hazard ratio (HR) for incident asthma at ages 1 to 5 years for preschool-aged children. Data were analyzed from January 1, 2007, to September 30, 2012.EXPOSURES: Living with a dog or farm animal.MAIN OUTCOMES AND MEASURES: Childhood asthma diagnosis and medication used.RESULTS: Of the 1 011 051 children born during the study period, 376 638 preschool-aged (53 460 [14.2%] exposed to dogs and 1729 [0.5%] exposed to farm animals) and 276 298 school-aged children (22 629 [8.2%] exposed to dogs and 958 [0.3%] exposed to farm animals) were included in the analyses. Of these, 18 799 children (5.0%) in the preschool-aged children's cohort experienced an asthmatic event before baseline, and 28 511 cases of asthma and 906 071 years at risk were recorded during follow-up (incidence rate, 3.1 cases per 1000 years at risk). In the school-aged children's cohort, 11 585 children (4.2%) experienced an asthmatic event during the seventh year of life. Dog exposure during the first year of life was associated with a decreased risk of asthma in school-aged children (OR, 0.87; 95% CI, 0.81-0.93) and in preschool-aged children 3 years or older (HR, 0.90; 95% CI, 0.83-0.99) but not in children younger than 3 years (HR, 1.03; 95% CI, 1.00-1.07). Results were comparable when analyzing only first-born children. Farm animal exposure was associated with a reduced risk of asthma in both school-aged children and preschool-aged children (OR, 0.48; 95% CI, 0.31-0.76, and HR, 0.69; 95% CI, 0.56-0.84), respectively.CONCLUSIONS AND RELEVANCE: In this study, the data support the hypothesis that exposure to dogs and farm animals during the first year of life reduces the risk of asthma in children at age 6 years. This information might be helpful in decision making for families and physicians on the appropriateness and timing of early animal exposure.
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2.
  • Kennedy, Beatrice, 1982-, et al. (author)
  • App-based COVID-19 syndromic surveillance and prediction of hospital admissions in COVID Symptom Study Sweden
  • 2022
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Here, we include data from 19,161 self-reported PCR tests to create a symptom-based model to estimate the individual probability of symptomatic COVID-19, with an AUC of 0.78 (95% CI 0.74-0.83) in an external dataset. These individual probabilities are employed to estimate daily regional COVID-19 prevalence, which are in turn used together with current hospital data to predict next week COVID-19 hospital admissions. We show that this hospital prediction model demonstrates a lower median absolute percentage error (MdAPE: 25.9%) across the five most populated regions in Sweden during the first pandemic wave than a model based on case notifications (MdAPE: 30.3%). During the second wave, the error rates are similar. When we apply the same model to an English dataset, not including local COVID-19 test data, we observe MdAPEs of 22.3% and 19.0% during the first and second pandemic waves, respectively, highlighting the transferability of the prediction model.
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3.
  • Wernroth, Lisa, et al. (author)
  • Development of gut microbiota during the first 2 years of life
  • 2022
  • In: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
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4.
  • Wernroth, Lisa, et al. (author)
  • Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes : A Nationwide Register-Based Study With Sibling Analysis
  • 2020
  • In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:5, s. 991-999
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The effect of early life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis.RESEARCH DESIGN AND METHODS: = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings.RESULTS: for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00-1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations.CONCLUSIONS: Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10, most prominently in children delivered by cesarean section.
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6.
  • Wernroth, M. -L, et al. (author)
  • Childhood bereavement and risk of type 1 diabetes : a Swedish population-based register study
  • 2021
  • In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:Suppl. 1, s. 140-140
  • Journal article (other academic/artistic)abstract
    • Background and aims: Loss of a first-degree family member in childhood constitutes a major psychological stressor, and is associated both with subsequent psychiatric and somatic morbidity. The potential influence on type 1 diabetes risk has however not yet been fully elucidated. In this study we therefore aimed to investigate the impact of childhood bereavement on type 1 diabetes risk.Materials and methods: We conducted a population-based study in Sweden, encompassing 2,321,318 children born in Sweden January 1 1990 to December 31 2012. The follow up ended December 31 2013, at death of the child, type 1 diabetes diagnosis, emigration or when the child turned 19 years. All children were followed from the age of one, with exposure defined as death of a mother, father, or sibling. Type 1 diabetes diagnoses were extracted from the National Patient Register. We applied Cox proportional hazards models with attained age as time scale and loss of family member as a time varying variable, adjusting for potential confounders including parental type 1 diabetes, parental country of birth, and region of residence. We further categorized child age at bereavement as pre-school (1-6 years), school age (7-12 years) and teenage (13-18 years).Results: During follow-up (median 10.8 years), 50,253 (2.2%) children experienced loss of a family member. Median age at loss was 9.6 years, and 32% of all deaths were categorized as traumatic (accident, suicide, violence, or other sudden unnatural deaths). In total 10,965 children were diagnosed with type 1 diabetes during follow-up and median age at diagnosis was 8.5 years. We observed no overall association between childhood bereavement and type 1 diabetes risk (crude HR 1.00, 95% CI 0.86-1.18, adjusted HR 0.96, 95% CI 0.82 -1.13). The risk was not influenced by sex of the child, cause of death of family member, or familial relationship to the deceased. However, we noted an association when the exposure occurred during the teenage years (adjusted HR 1.67, 95% CI 1.15-2.43).Conclusion: Overall, childhood bereavement was not associated with the risk of type 1 diabetes, but the impact of childhood loss on type 1 diabetes may be modified by age at bereavement.
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7.
  • Wernroth, Mona-Lisa, et al. (author)
  • Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood
  • 2017
  • In: JAMA pediatrics. - : AMER MEDICAL ASSOC. - 2168-6203 .- 2168-6211. ; 171:7, s. 663-669
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE The association between early exposure to animals and type 1 diabetes in childhood is not clear. OBJECTIVE To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. DESIGN, SETTING, AND PARTICIPANTS A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. EXPOSURES Having a parent who was registered as a dog owner during the child's first year of life. MAIN OUTCOMES AND MEASURES Childhood-onset type 1 diabetes. RESULTS Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; >= 3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0.43-1.17) for dog exposure. CONCLUSIONS AND RELEVANCE In a nationwide study, no evidence supporting an association of register-derived measures of dog exposure with childhood type 1 diabetes was identified.
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8.
  • Wernroth, Mona-Lisa (author)
  • Type l diabetes in childhood and adolescence, environmental exposures and gut microbiota
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Environmental factors leading to disturbances in the gut microbiota might play an important role as triggers for, and/or contributing factors in, the development of type 1 diabetes (T1D). The overall aim of the research underlying this thesis was to study the influence of environmental factor exposure on the risk of T1D in childhood and adolescence, and gut microbiota composition in early childhood.In this project, national registers provided information about T1D onset and exposure to animals, antibiotics, caesarean section and severe stress, defined as death of a first degree relative. In the first study (1,999 T1D events), no evidence supported an association between early exposure to dog or farm animals and T1D in childhood. In the second study (1,297 T1D events), dispensed prescriptions of antibiotics in the first year of life was found to be associated with T1D during childhood. Sibling analysis did not indicate confounding from familial factors. Furthermore, the effect estimate for the association between antibiotics and T1D was largest in children delivered by caesarean section. In the third study (10,789 T1D events), death of a close relative was associated with an increased risk for T1D within the first years following the loss, and when the loss occurred during the teenage years. The fourth study was a longitudinal study using 16S rRNA sequencing to analyse faecal samples from 83 children to study the gut microbiota development from birth to 2 years of age. Having a furry pet in the household was associated with a lower abundance of a bacterial species belonging to the genus Bifidobacterium. The overall gut microbiota composition was associated with prenatal exposure to antibiotics and caesarean section. Finally, caesarean section was associated with a lower abundance of Bacteroidetes and a higher abundance of Firmicutes.In conclusion, no evidence was found in the present study to support the association of exposure to animals to lowered risk of T1D in the general population. Although exposure to antibiotics was associated with T1D, it is likely to only make a small contribution to the overall risk of T1D. Our findings support the hypothesis that severe stress might accelerate T1D onset during certain time periods. Furthermore, our findings add to the body of research showing that exposure to animals, prenatal antibiotics and caesarean section account for some of the inter-individual variation in early childhood microbiota development.
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9.
  • Akre [Fall], Katja, 1971-, et al. (author)
  • Aspirin and risk for gastric cancer : a population-based case-control study in Sweden
  • 2001
  • In: British Journal of Cancer. - Edinburgh, United Kingdom : Churchill Livingstone. - 0007-0920 .- 1532-1827. ; 84:7, s. 965-8
  • Journal article (peer-reviewed)abstract
    • While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are associated with gastric mucosal damage, they might reduce the risk for gastric cancer. In a population-based case-control study in 5 Swedish counties, we interviewed 567 incident cases of gastric cancer and 1165 controls about their use of pain relievers. The cases were uniformly classified to subsite (cardia/non-cardia) and histological type and information collected on other known risk factors for gastric cancer. Helicobacter pylori serology was tested in a subset of 542 individuals. Users of aspirin had a moderately reduced risk of gastric cancer compared to never users; odds ratio (OR) adjusted for age, gender and socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was apparent for both cardia and non-cardia tumours but was uncertain for the diffuse histologic type. No clear association was observed between gastric cancer risk and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support to the hypothesis that use of aspirin reduces the risk for gastric cancer.
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10.
  • Akre [Fall], Katja, 1971-, et al. (author)
  • Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement
  • 2000
  • In: Cancer Research. - Birmingham, USA : American Asoociation for Cancer Research. - 0008-5472 .- 1538-7445. ; 60, s. 6376-
  • Journal article (peer-reviewed)abstract
    • Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.
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11.
  • Andrén, Ove, 1963-, et al. (author)
  • How well does the Gleason score predict prostate cancer death? : A 20-year followup of a population based cohort in Sweden
  • 2006
  • In: Journal of Urology. - Baltimore : Williams and Wilkins Co.. - 0022-5347 .- 1527-3792. ; 175:4, s. 1337-1340
  • Journal article (peer-reviewed)abstract
    • Purpose Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment. Materials and Methods We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death. Results Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%. Conclusions Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.
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12.
  • Andrén, Ove, et al. (author)
  • Incidence and mortality of incidental prostate cancer : a Swedish register-based study
  • 2009
  • In: British Journal of Cancer. - London : Nature publishing group. - 0007-0920 .- 1532-1827. ; 100:1, s. 170-173
  • Journal article (peer-reviewed)abstract
    • In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.
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13.
  • Andrén, Ove, 1963-, et al. (author)
  • MUC-1 gene is associated with prostate cancer death : a 20-year follow-up of a population-based study in Sweden
  • 2007
  • In: British Journal of Cancer. - London : Harcourt Publishers. - 0007-0920 .- 1532-1827. ; 97:6, s. 730-734
  • Journal article (peer-reviewed)abstract
    • Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.
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15.
  • Arora, Manish, et al. (author)
  • An exploration of shared genetic risk factors between periodontal disease and cancers : a prospective co-twin study
  • 2010
  • In: American Journal of Epidemiology. - Cary, USA : Oxford University Press. - 0002-9262 .- 1476-6256. ; 171:2, s. 253-9
  • Journal article (peer-reviewed)abstract
    • Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers.
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  • Bergh, Cecilia, 1972-, et al. (author)
  • Determinants in adolescence of stroke-related hospital stay duration in men : a national cohort study
  • 2016
  • In: Stroke. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 47:9, s. 2416-2418
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke.Methods: Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first.Results: Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45).Conclusions: Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors.
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  • Bergh, Cecilia, 1972- (author)
  • Life-course influences on occurrence and outcome for stroke and coronary heart disease
  • 2017
  • Doctoral thesis (other academic/artistic)abstract
    • Although typical clinical onset does not occur until adulthood, cardiovascular disease (CVD) may have a long natural history with accumulation of risks beginning in early life and continuing through childhood and into adolescence and adulthood. Therefore, it is important to adopt a life-course approach to explore accumulation of risks, as well as identifying age-defined windows of susceptibility, from early life to disease onset. This thesis examines characteristics in adolescence and adulthood linked with subsequent risk of CVD. One area is concerned with physical and psychological characteristics in adolescence, which reflects inherited and acquired elements from childhood, and their association with occurrence and outcome of subsequent stroke and coronary heart disease many years later. The second area focuses on severe infections and subsequent delayed risk of CVD. Data from several Swedish registers were used to provide information on a general population-based cohort of men. Some 284 198 males, born in Sweden from 1952 to 1956 and included in the Swedish Military Conscription Register, form the basis of the study cohort for this thesis. Our results indicate that characteristics already present in adolescence may have an important role in determining long-term cardiovascular health. Stress resilience in adolescence was associated with an increased risk of stroke and CHD, working in part through other CVD factors, in particular physical fitness. Stress resilience, unhealthy BMI and elevated blood pressure in adolescence were also associated with aspects of stroke severity among survivors of a first stroke. We demonstrated an association for severe infections (hospital admission for sepsis and pneumonia) in adulthood with subsequent delayed risk of CVD, independent of risk factors from adolescence. Persistent systemic inflammatory activity which could follow infection, and that might persist long after infections resolve, represents a possible mechanism. Interventions to protect against CVD should begin by adolescence; and there may be a period of heightened susceptibility in the years following severe infection when additional monitoring and interventions for CVD may be of value.
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  • Bergh, Cecilia, 1972-, et al. (author)
  • Severe infections and subsequent delayed cardiovascular disease
  • 2017
  • In: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 24:18, s. 1958-1966
  • Journal article (peer-reviewed)abstract
    • Background: Severe infections in adulthood are associated with subsequent short-term cardiovascular disease. Whether hospital admission for sepsis or pneumonia is associated with persistent increased risk (over a year after infection) is less well established.Design: The design of this study was as a register-based cohort study.Methods: Some 236,739 men born between 1952-1956 were followed from conscription assessments in adolescence to 2010. All-cause cardiovascular disease ( n = 46,754), including coronary heart disease ( n = 10,279) and stroke ( n = 3438), was identified through national registers 1970-2010 (at ages 18-58 years).Results: Sepsis or pneumonia in adulthood (resulting in hospital admission) are associated with increased risk of cardiovascular disease in the years following infection. The risk is highest during the first year after the infection, with an adjusted hazard ratio (and 95% confidence intervals) of 6.33 (5.65-7.09) and a notably increased risk persisted with hazard ratios of 2.47 (2.04-3.00) for the second and 2.12 (1.71-2.62) for the third year after infection. The risk attenuated with time, but remained raised for at least five years after infection; 1.87 (1.47-2.38). The results are adjusted for characteristics in childhood, cardiovascular risk factors and medical history in adolescence. Similar statistically significant associations were found for coronary heart disease and stroke.Conclusions: Raised risks of cardiovascular disease following hospital admission for sepsis or pneumonia were increased for more than five years after the infection, but with the highest magnitude during the first three years following infection, suggesting a period of vulnerability when health professionals and patients should be aware of the heightened risk for cardiovascular disease.
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21.
  • Bergh, Cecilia, 1972-, et al. (author)
  • Shared unmeasured characteristics among siblings confound the association of Apgar score with stress resilience in adolescence
  • 2019
  • In: Acta Paediatrica. - : Wiley-Blackwell Publishing Inc.. - 0803-5253 .- 1651-2227. ; 108:11, s. 2001-2007
  • Journal article (peer-reviewed)abstract
    • AIM: We investigated the association between low Apgar score, other perinatal characteristics and low stress resilience in adolescence. A within-siblings analysis was used to tackle unmeasured shared familial confounding.METHODS: We used a national cohort of 527,763 males born in Sweden between 1973 and 1992 who undertook military conscription assessments at mean age 18 years (17-20). Conscription examinations included a measure of stress resilience. Information on Apgar score and other perinatal characteristics was obtained through linkage with the Medical Birth Register. Analyses were conducted using ordinary least squares and fixed-effects linear regression models adjusted for potential confounding factors.RESULTS: Infants with a prolonged low Apgar score at five minutes had an increased risk of low stress resilience in adolescence compared to those with highest scores at one minute, with an adjusted coefficient and 95% confidence interval of -0.26 (-0.39, -0.13). The associations were no longer statistically significant when using within-siblings models. However, the associations with stress resilience and birthweight remained statistically significant in all analyses.CONCLUSION: The association with low Apgar score seems to be explained by confounding due to shared childhood circumstances among siblings from the same family, while low birthweight is independently associated with low stress resilience.
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22.
  • Bergh, Cecilia, 1972-, et al. (author)
  • Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age
  • 2015
  • In: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 101:8, s. 623-629
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness.METHODS: In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors.RESULTS: Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001).CONCLUSIONS: Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.
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23.
  • Bergh, Cecilia, 1972-, et al. (author)
  • Stress resilience in male adolescents and subsequent stroke risk : cohort study
  • 2014
  • In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:12, s. 1331-1336
  • Journal article (peer-reviewed)abstract
    • Objective Exposure to psychosocial stress has been identified as a possible stroke risk, but the role of stress resilience which may be relevant to chronic exposure is uncertain. We investigated the association of stress resilience in adolescence with subsequent stroke risk.Methods Register-based cohort study. Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Cox regression estimated the association of stress resilience with stroke, after adjustment for established stroke risk factors.Results Some 3411 diagnoses of first stroke were identified. Lowest stress resilience (21.8%) compared with the highest (23.7%) was associated with increased stroke risk, producing unadjusted HR (with 95% CIs) of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to 1.63) after adjustment for markers of socioeconomic circumstances in childhood; and after further adjustment for markers of development and disease in adolescence (blood pressure, cognitive function and pre-existing cardiovascular disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further adjustment for markers of physical fitness (BMI and physical working capacity) in adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude associations for fatal rather than non-fatal, and for haemorrhagic rather than ischaemic stroke.Conclusions Stress susceptibility and, therefore, psychosocial stress may be implicated in the aetiology of stroke. This association may be explained, in part, by poorer physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress.
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24.
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25.
  • Blattner, Mirjam, et al. (author)
  • SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts
  • 2014
  • In: Neoplasia. - New York : Elsevier. - 1522-8002 .- 1476-5586. ; 16:1, s. 14-U34
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.
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26.
  • Bond, Emily, et al. (author)
  • Sexually transmitted infections after bereavement - a population-based cohort study
  • 2016
  • In: BMC Infectious Diseases. - London, England : BioMed Central. - 1471-2334. ; 16
  • Journal article (peer-reviewed)abstract
    • Background: Loss of a loved one has consistently been associated with various health risks. Little is however known about its relation to sexually transmitted infections (STIs).Methods: We conducted a population-based cohort study during 1987-2012 using the Swedish Multi-Generation Register, including 3,002,209 women aged 10-44 years. Bereavement was defined as death of a child, parent, sibling or spouse (N = 979,579, 33 %). STIs were defined as hospital visits with an STI as main or secondary diagnosis. Poisson regression and negative binomial regression were used to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) of STIs, comparing incidence rates of women who had experienced loss to those who had not.Results: Bereaved women were at significantly higher risk of nearly all STIs studied. The relative risk of any STI was highest during the first year after loss (IRR: 1.45, 95 % CI: 1.27-1.65) and predominantly among women with subsequent onset of psychiatric disorders after bereavement (IRR: 2.61, 95 % CI: 2.00-3.34). Notably, a consistent excess risk, persisting for over five years, was observed for acute salpingitis (IRR: 1.28, 95 % CI: 1.13-1.44), a severe complication of bacterial STIs.Conclusion: These data suggest that women who have experienced bereavement are at increased risk of STIs.
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27.
  • Carlsson, Sigrid, 1982, et al. (author)
  • Risk of suicide in men with low-risk prostate cancer
  • 2013
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 49:7, s. 1588-1599
  • Journal article (peer-reviewed)abstract
    • Purpose:Risk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing.Patients and Methods:Relative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997-2009 to 528,658 matched prostate cancer-free men.Results:During the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0-10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1-21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3-12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68-1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1-2.9).Conclusion:Although the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness.
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28.
  • Chen, Ruoqing, et al. (author)
  • Childhood injury after a parental cancer diagnosis
  • 2015
  • In: eLIFE. - Stockholm : eLife Sciences Publications Ltd. - 2050-084X. ; 4
  • Journal article (peer-reviewed)abstract
    • A parental cancer diagnosis is psychologically straining for the whole family. We investigated whether a parental cancer diagnosis is associated with a higher-than-expected risk of injury among children by using a Swedish nationwide register-based cohort study. Compared to children without parental cancer, children with parental cancer had a higher rate of hospital contact for injury during the first year after parental cancer diagnosis (hazard ratio [HR]=1.27, 95% confidence interval [CI]=1.22-1.33), especially when the parent had a comorbid psychiatric disorder after cancer diagnosis (HR=1.41, 95% CI=1.08-1.85). The rate increment declined during the second and third year after parental cancer diagnosis (HR=1.10, 95% CI=1.07-1.14) and became null afterwards (HR=1.01, 95% CI=0.99-1.03). Children with parental cancer also had a higher rate of repeated injuries than the other children (HR=1.13, 95% CI= 1.12-1.15). Given the high rate of injury among children in the general population, our findings may have important public health implications.
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29.
  • Chen, Ruoqing, et al. (author)
  • Impact of parental cancer on IQ, stress resilience, and physical fitness in young men
  • 2018
  • In: Clinical Epidemiology. - : DOVE Medical Press Ltd.. - 1179-1349. ; 10, s. 593-602
  • Journal article (peer-reviewed)abstract
    • Background: A parental cancer diagnosis is a stressful life event, potentially leading to increased risks of mental and physical problems among children. This study aimed to investigate the associations of parental cancer with IQ, stress resilience, and physical fitness of the affected men during early adulthood.Materials and methods: In this Swedish population-based study, we included 465,249 men born during 1973-1983 who underwent the military conscription examination around the age of 18 years. We identified cancer diagnoses among the parents of these men from the Cancer Register. IQ, stress resilience, and physical fitness of the men were assessed at the time of conscription and categorized into three levels: low, moderate, and high (reference category). We used multinomial logistic regression to assess the studied associations. Results: Overall, parental cancer was associated with higher risks of low stress resilience (relative risk ratio [RRR]: 1.09 [95% confidence interval (CI) 1.04-1.15]) and low physical fitness (RRR: 1.12 [95% CI 1.05-1.19]). Stronger associations were observed for parental cancer with a poor expected prognosis (low stress resilience: RRR: 1.59 [95% CI 1.31-1.94]; low physical fitness: RRR: 1.45 [95% CI 1.14-1.85]) and for parental death after cancer diagnosis (low stress resilience: RRR: 1.29 [95% CI 1.16-1.43]; low physical fitness: RRR: 1.40 [95% CI 1.23-1.59]). Although there was no overall association between parental cancer and IQ, parental death after cancer diagnosis was associated with a higher risk of low IQ (RRR: 1.11 [95% CI 1.01-1.24]).Conclusion: Parental cancer, particularly severe and fatal type, is associated with higher risks of low stress resilience and low physical fitness among men during early adulthood. Men who experienced parental death after cancer diagnosis also have a higher risk of low IQ.
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30.
  • Chen, Ruoqing, et al. (author)
  • Marital status, telomere length and cardiovascular disease risk in a Swedish prospective cohort
  • 2020
  • In: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 106:4, s. 267-272
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association.DESIGN: Population-based prospective cohort study SETTINGS: Swedish Twin Registry.PARTICIPANTS: Based on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique.MAIN OUTCOME MEASURES: Incident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (βs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index.RESULTS: A total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (β:-0.014, 95% CI: -0.035, 0.007), widowed (β:-0.035, 95% CI: -0.061, -0.010), or living alone (β:-0.033, 95% CI: -0.052, -0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34).CONCLUSIONS: Living singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.
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31.
  • Chen, Ruoqing, et al. (author)
  • Parental cancer diagnosis and child mortality : a population-based cohort study in Sweden
  • 2015
  • In: Cancer Epidemiology. - Stockholm : American Diabetes Association. - 1877-7821 .- 1877-783X. ; 39:1, s. 79-85
  • Journal article (peer-reviewed)abstract
    • Objective: Cancer diagnosis is known to induce severe psychological stress for the diagnosed patients; however, how it affects the next-of-kin is less well documented. This study aimed to assess the impact of parental cancer on the risk of childhood death.Methods: A population-based cohort study was conducted using the Swedish national registries, including 2,871,242 children followed during the period of 1991-2009. Parental cancer diagnosis was defined as a time-varying exposure. We used Cox proportional hazards regression to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) as an estimate of the association between parental cancer and childhood mortality. We adjusted for attained age, sex, gestational age, mode of delivery and birth weight of the child, maternal age at child's birth, as well as educational level and socioeconomic classification of the parents in the analyses.Results: Among 113,555 children with parental cancer, 127 deaths occurred during 561,198 person-years of follow-up. A parental cancer diagnosis was associated with an increased rate of death among children at the age of 1-18 (HR for all-cause death: 1.39; 95% CI: 1.16-1.66). For young children (aged 112), an increased rate was only noted for death due to cancer (HR: 2.06; 95% CI: 1.13-3.75) after parental cancer diagnosis. Among adolescents (aged 13-18), an increased rate was noted for all-cause death (HR: 1.52; 95% CI: 1.25-1.86), and for both non-cancer-related (HR: 1.43; 95% CI: 1.14-1.79) and cancer-related (HR: 2.07; 95% CI: 1.33-3.24) death in the exposed children.Conclusion: Children have an increased rate of death if they have a parent diagnosed with cancer as compared to children without such experience; this association appears to be slightly stronger among adolescents. (C) 2014 Elsevier Ltd. All rights reserved.
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32.
  • Chen, Ruoqing, et al. (author)
  • Psychiatric disorders among children of parents with cancer : a Swedish register-based matched cohort study
  • 2018
  • In: Psycho-Oncology. - : John Wiley & Sons. - 1057-9249 .- 1099-1611. ; 27:7, s. 1854-1860
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate the risk of psychiatric disorders among children of parents with cancer in a nationwide population-based setting.METHODS: Based on Swedish national registers, the study included 101,339 children with parental cancer diagnosed either during pregnancy (N=1,047) or after birth (N=100,292) that were born during 1983-2000. For each exposed child, we randomly selected 10 unexposed children from the general population after individual matching by year of birth and sex. The matched cohort was followed during 2001-2010. Clinical diagnoses of psychiatric disorders and use of prescribed psychiatric medications were identified for all children. Cox regression and logistic regression were used to evaluate the associations of parental cancer with psychiatric disorder diagnosis and psychiatric medication use respectively.RESULTS: Parental cancer during pregnancy was not associated with the risk of psychiatric disorders overall, although paternal cancer during pregnancy was associated with a higher risk of psychiatric medication use among females. Parental cancer after birth was associated with higher risks of psychiatric disorder diagnoses, particularly stress reaction and adjustment disorders (males:hazard ratio[HR]:1.24, 95% confidence interval[CI]:1.08-1.43; females:HR:1.27, 95%CI:1.14-1.41), and use of psychiatric medication (males:odds ratio[OR]:1.09, 95%CI:1.04-1.13;females:OR:1.14, 95%CI:1.10-1.18). The positive associations were stronger for parental cancer with poor expected survival and for parental death after cancer diagnosis.CONCLUSIONS: Parental cancer, primarily the life-threatening cancer, might confer a higher risk of psychiatric disorders among children. These findings have potential implications for healthcare professionals in providing targeted support to children living with a parent with cancer.
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33.
  • Daníelsdóttir, Hilda Björk, et al. (author)
  • Adverse Childhood Experiences and Adult Mental Health Outcomes
  • 2024
  • In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 81:6, s. 586-594
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders.OBJECTIVE: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding.DESIGN, SETTING, AND PARTICIPANTS: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023.EXPOSURES: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey.MAIN OUTCOMES AND MEASURES: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register.RESULTS: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11).CONCLUSIONS AND RELEVANCE: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.
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34.
  • Daníelsdóttir, Hilda Björk, et al. (author)
  • Adverse childhood experiences and resilience among adult women : A population-based study
  • 2022
  • In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
  • Journal article (peer-reviewed)abstract
    • Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear.Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18-69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders.Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability (β = -0.14; 95% CI-0.15,-0.13) and lower psychiatric resilience (β = -0.28; 95% CI-0.29,-0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood.Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood.
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35.
  • Davidsson, Sabina, 1972-, et al. (author)
  • Androgen deprivation therapy in men with prostate cancer is not associated with COVID-2019 infection
  • 2023
  • In: The Prostate. - : Alan R. Liss Inc.. - 0270-4137 .- 1097-0045. ; 83:6, s. 555-562
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Androgens may play a role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and host responses as the virus is dependent on the androgen-regulated protein transmembrane serine protease 2 for cell entry. Studies have indicated that prostate cancer patients receiving androgen deprivation therapy (ADT) are at reduced risk of SARS-CoV-2 infection and serious complications compared with patients without ADT, but data are inconsistent.METHODS: A total of 655 prostate cancer patients who were under surveillance at two urology departments in Sweden on April 1, 2020 were included in the study as well as 240 patients with benign prostatic hyperplasia (BPH). At follow-up early in 2021, the participants completed a questionnaire containing information about symptoms compatible with coronavirus disease 2019 (COVID-19). Blood samples were also collected for the assessment of SARS-CoV-2 IgG antibodies (SARS-CoV-2 Total; Siemens). We used multivariable logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ADT and the risk of SARS-CoV-2 infection.RESULTS: The cumulative incidence of SARS-CoV-2 seropositivity was 13.4% among patients receiving ADT and 10.4% among patients without ADT. After adjusting for potential confounders, we observed no differences in symptoms or risk of SARS-CoV-2 infection between patients with and without ADT (OR: 0.98; 95% CI: 0.52-1.85). Higher body mass index, Type 1 diabetes, and prostate cancer severity, defined by high Gleason score (8-10; OR: 2.06; 95% CI: 1.04-4.09) or elevated levels of prostate-specific antigen (>20 µg/l; OR: 2.15; 95% CI: 1.13-4.07) were associated with increased risk of SARS-CoV-2 infection. Overall, the risk of SARS-CoV-2 infection was not higher among men with prostate cancer than among men with BPH.CONCLUSIONS: Our results do not support the hypothesis that ADT use in prostate cancer patients reduces the risk or symptom severity of SARS-CoV-2 infection or that prostate cancer patients are at increased risk of COVID-19 compared with men without prostate cancer.
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36.
  • Davidsson, Sabina, et al. (author)
  • CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer
  • 2013
  • In: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 26:3, s. 448-455
  • Journal article (peer-reviewed)abstract
    • Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T(regs)), a subpopulation of T cells that have a role in promoting tumor growth. T(regs) counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n=261) and controls are men who survived >10 years after their diagnosis (n=474). Infiltration of both T(helper) and T(cytotoxic) cells was frequently observed and the majority of the T(regs) were CD4(+). T(helper) or T(cytotoxic) cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4(+) T(reg) cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4(+) T(regs) in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4(+) T(regs) in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.Modern Pathology advance online publication, 5 October 2012; doi:10.1038/modpathol.2012.164.
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37.
  • Davidsson, Sabina, et al. (author)
  • Inflammation, Focal Atrophic Lesions, and Prostatic Intraepithelial Neoplasia with Respect to Risk of Lethal Prostate Cancer
  • 2011
  • In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:10, s. 2280-2287
  • Journal article (peer-reviewed)abstract
    • Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. less thanbrgreater than less thanbrgreater thanMethods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. less thanbrgreater than less thanbrgreater thanResults: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). less thanbrgreater than less thanbrgreater thanConclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. less thanbrgreater than less thanbrgreater thanImpact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease.
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38.
  • Dickerman, Barbra A., et al. (author)
  • Midlife metabolic factors and prostate cancer risk in later life
  • 2018
  • In: International Journal of Cancer. - Hoboken, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:6, s. 1166-1173
  • Journal article (peer-reviewed)abstract
    • Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967-1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high-grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0-4) combining the risk factors: BMI ≥30 kg/m2 ; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self-reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high-grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3-4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.
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39.
  • Downer, Mary K., et al. (author)
  • Dairy intake in relation to prostate cancer survival
  • 2017
  • In: International Journal of Cancer. - Hoboken : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 140:9, s. 2060-2069
  • Journal article (peer-reviewed)abstract
    • Dairy intake has been associated with increased risk of advanced prostate cancer. Two US cohort studies reported increased prostate cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with prostate cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed prostate cancer (diagnosed 1989-1994). We identified and confirmed deaths through February 2011 (n = 222 prostate cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and prostate cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with prostate cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized prostate cancer, compared to men who consumed <1 servings/day of high-fat milk, those who drank >= 3 servings/day had an increased hazard of prostate cancer mortality (HR = 6.10; 95% CI: 2.14, 17.37; p-trend = 0.004; multivariate-adjusted model). Low-fat milk intake was associated with a borderline reduction in prostate cancer death among patients with localized prostate cancer. These associations were not observed among patients diagnosed with advanced stage prostate cancer. Our data suggest a positive association between high-fat milk intake and prostate cancer progression among patients diagnosed with localized prostate cancer. Further studies are warranted to investigate this association and elucidate the mechanisms by which high-fat milk intake may promote prostate cancer progression.
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40.
  • Elenis, Evangelia, 1983-, et al. (author)
  • Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality : a multiregister nationwide matched cohort study in Sweden
  • 2024
  • In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 22:1
  • Journal article (peer-reviewed)abstract
    • BackgroundIt has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT).MethodsThis is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated.ResultsUse of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes.ConclusionsSystemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations.
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41.
  • Emilsson, Louise, et al. (author)
  • Colorectal cancer death after adenoma removal in Scandinavia
  • 2017
  • In: Scandinavian Journal of Gastroenterology. - Oxfordshire, United Kingdom : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 52:12, s. 1377-1384
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Improved understanding of the subsequent risk death from colorectal cancer (CRC) among individuals who had adenomas removed is needed. We aimed to quantify this risk using prospectively collected data from population-based cohorts.MATERIALS AND METHODS: Using Norwegian and Swedish registries, a cohort of 90,864 individuals with colorectal adenomas removed between 1980 and 2013 was identified. Surveillance was only recommended for high-risk adenomas. The validity of the registry data did not allow classification into low- and high-risk adenomas. Virtually complete follow-up was achieved through linkage to nationwide registers. We calculated incidence-based standardised mortality ratios (SMRs) with 95% confidence intervals (CI).RESULTS: The median follow-up was 7.2 years; 48,058 individuals were followed for more than 10 years. We observed 819 deaths (0.9%) from CRC and expected 731 CRC deaths (0.8%), corresponding to an absolute excess risk of 88 cases (0.1%) and a relative risk of 12% (SMR 1.12; 95%CI 1.05-1.20). The relative risk of CRC death following adenoma removal was slightly higher in Sweden (SMR 1.22; 95%CI 1.11-1.34) than in Norway (SMR 1.03; 95%CI 0.93-1.14), and higher in women (SMR 1.24; 95%CI 1.12-1.36) than in men (SMR 1.02; 95%CI 0.93-1.13). Among individuals with more than 10 years of follow-up, the estimates were similar to the overall cohort, absolute excess risk 0.1% (SMR 1.15; 95%CI 1.06-1.24).CONCLUSION: The excess risk of CRC death following adenoma removal is small. Optimal surveillance recommendations should be tested in randomised trials.
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42.
  • Enblad, Anna Pia, et al. (author)
  • PSA testing patterns in a large Swedish cohort before the implementation of organized PSA testing
  • 2020
  • In: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 54:5, s. 376-381
  • Journal article (peer-reviewed)abstract
    • Background: Organized PSA testing for asymptomatic men aged 50-74 years will be implemented in Sweden to reduce opportunistic testing in groups who will not benefit. The aim of this study was to describe the opportunistic PSA testing patterns in a Swedish region before the implementation of organized PSA testing programs.Method: We included all men in the Uppsala-orebro health care region of Sweden who were PSA tested between 1 July 2012 and 30 June 2014. Information regarding previous PSA testing, prostate cancer diagnosis, socioeconomic situation, surgical procedures and prescribed medications were collected from population-wide registries to create the Uppsala-orebro PSA cohort (UPSAC). The cohort was divided into repeat and single PSA testers. The background population used for comparison consisted of men 40 years or older, living in the Uppsala-orebro region during this time period.Results: Of the adult male population in the region, 18.1% had undergone PSA testing. Among men over 85 years old 21% where PSA tested. In our cohort, 62.1% were repeat PSA testers. Of men with a PSA level <= 1 mu g/l 53.8% had undergone repeat testing. Prostate cancer was found in 2.7% and 4.8% of the repeat and single testers, respectively.Conclusion: Every fifth man in the male background population was PSA tested. Repeated PSA testing was common despite low PSA values. As repeated PSA testing was common, especially among older men who will not be included in organized testing, special measures to change the testing patterns in this group may be required.
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43.
  • Epstein, Mara M, et al. (author)
  • Dietary fatty acid intake and prostate cancer survival in Örebro county, Sweden
  • 2012
  • In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 176:3, s. 240-252
  • Journal article (peer-reviewed)abstract
    • Although dietary fat has been associated with prostate cancer risk, the association between specific fatty acids and prostate cancer survival remains unclear. Dietary intake of 14 fatty acids was analyzed in a population-based cohort of 525 Swedish men with prostate cancer in Örebro County (1989-1994). Multivariable hazard ratios and 95% confidence intervals for time to prostate cancer death by quartile and per standard deviation increase in intake were estimated by Cox proportional hazards regression. Additional models examined the association by stage at diagnosis (localized: T0-T2/M0; advanced: T0-T4/M1, T3-T4/M0). Among all men, those with the highest omega-3 docosahexaenoic acid and total marine fatty acid intakes were 40% less likely to die from prostate cancer (P(trend) = 0.05 and 0.04, respectively). Among men with localized prostate cancer, hazard ratios of 2.07 (95% confidence interval: 0.93, 4.59; P(trend) = 0.03) for elevated total fat, 2.39 (95% confidence interval: 1.06, 5.38) for saturated myristic acid, and 2.88 (95% confidence interval: 1.24, 6.67) for shorter chain (C4-C10) fatty acid intakes demonstrated increased risk for disease-specific mortality for the highest quartile compared with the lowest quartile. This study suggests that high intake of total fat and certain saturated fatty acids may worsen prostate cancer survival, particularly among men with localized disease. In contrast, high marine omega-3 fatty acid intake may improve disease-specific survival for all men.
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44.
  • Epstein, Mara M., et al. (author)
  • Dietary zinc and prostate cancer survival in a Swedish cohort
  • 2011
  • In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:3, s. 586-593
  • Journal article (peer-reviewed)abstract
    • Background: Zinc is involved in many essential cellular functions, including DNA repair and immune system maintenance. Although experimental evidence supports a role for zinc in prostate carcinogenesis, epidemiologic data are inconsistent; no data on cancer-specific survival have been reported. Objective: Our objective was to determine whether dietary zinc assessed near the time of prostate cancer diagnosis is associated with improved disease-specific survival. Design: This population-based cohort consists of 525 men aged < 80 y from Orebro County, Sweden, with a diagnosis of prostate cancer made between 1989 and 1994. Study participants completed self-administered food-frequency questionnaires, and zinc intake was derived from nutrient databases. Cox proportional hazards regression was used to estimate multivariate hazard ratios (HRs) and 95% CIs for time to death from prostate cancer as well as death from all causes through February 2009 by quartile (Q) of dietary zinc intake. Models were also stratified by disease stage at diagnosis (localized or advanced). Results: With a median follow-up of 6.4 y, 218 (42%) men died of prostate cancer and 257 (49%) died of other causes. High dietary zinc intake was associated with a reduced risk of prostate cancer-specific mortality (HRQ4 vs Q1: 0.64; 95% CI: 0.44, 0.94; P for trend = 0.05) in the study population. The association was stronger in men with localized tumors (HR: 0.24; 95% CI: 0.09, 0.66; P for trend = 0.005). Zinc intake was not associated with mortality from other causes. Conclusion: These results suggest that high dietary intake of zinc is associated with lower prostate cancer-specific mortality after diagnosis, particularly in men with localized disease.
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45.
  • Epstein, Mara M, et al. (author)
  • Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue
  • 2012
  • In: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 23:8, s. 1359-1366
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Recent studies suggest variation in genes along the vitamin D pathway, as well as vitamin D receptor (VDR) protein levels, may be associated with prostate cancer. As serum vitamin D levels vary by season, we sought to determine whether the expression of genes on the vitamin D pathway, assessed in prostate tumor tissue, do the same.METHODS: Our study incorporates mRNA expression data from 362 men in the Swedish Watchful Waiting cohort, diagnosed between 1977 and 1999, and 106 men enrolled in the US Physicians' Health Study (PHS) diagnosed between 1983 and 2004. We also assayed for VDR protein expression among 832 men in the PHS and Health Professionals Follow-up Study cohorts. Season was characterized by date of initial tissue specimen collection categorically and by average monthly ultraviolet radiation levels. One-way analysis of variance was used to examine variation in the expression levels of six genes on the vitamin D pathway-VDR, GC, CYP27A1, CYP27B1, RXRα, CYP24A1-and VDR protein by season, adjusted for age at diagnosis and Gleason grade. Variation was also examined separately among lethal and nonlethal cases.RESULTS: Tumor expression levels of the six genes did not vary significantly by season of tissue collection. No consistent patterns emerged from subgroup analyses by lethal versus nonlethal cases.CONCLUSIONS: Unlike circulating levels of 25(OH) vitamin D, expression levels of genes on the vitamin D pathway and VDR protein did not vary overall by season of tissue collection. Epidemiological analyses of vitamin D gene expression may not be biased by seasonality.
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46.
  • Etzioni, Ruth, et al. (author)
  • Increasing use of radical prostatectomy for nonlethal prostate cancer in Sweden
  • 2012
  • In: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 18:24, s. 6742-6747
  • Journal article (peer-reviewed)abstract
    • PURPOSE: The number of patients in Sweden treated with radical prostatectomy for localized prostate cancer has increased exponentially. The extent to which this increase reflects treatment of nonlethal disease detected through prostate-specific antigen (PSA) screening is unknown.EXPERIMENTAL DESIGN: We undertook a nationwide study of all 18,837 patients with prostate cancer treated with radical prostatectomy in Sweden from 1988 to 2008 with complete follow-up through 2009. We compared cumulative incidence curves, fit Cox regression and cure models, and conducted a simulation study to determine changes in treatment of nonlethal cancer, in cancer-specific survival over time, and effect of lead-time due to PSA screening.RESULTS: The annual number of radical prostatectomies increased 25-fold during the study period. The 5-year cancer-specific mortality rate decreased from 3.9% [95% confidence interval (CI), 2.5-5.3] among patients diagnosed between 1988 and 1992 to 0.7% (95% CI, 0.4-1.1) among those diagnosed between 1998 and 2002 (P(trend) < 0.001). According to the cure model, the risk of not being cured declined by 13% (95% CI, 12%-14%) with each calendar year. The simulation study indicated that only about half of the improvement in disease-specific survival could be accounted for by lead-time.CONCLUSION: Patients overdiagnosed with nonlethal prostate cancer appear to account for a substantial and growing part of the dramatic increase in radical prostatectomies in Sweden, but increasing survival rates are likely also due to true reductions in the risk of disease-specific death over time. Because the magnitude of harm and costs due to overtreatment can be considerable, identification of men who likely benefit from radical prostatectomy is urgently needed.
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47.
  • Fadl, Shalan, et al. (author)
  • The highest mortality rates in childhood dilated cardiomyopathy occur during the first year after diagnosis
  • 2018
  • In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 107:4, s. 672-677
  • Journal article (peer-reviewed)abstract
    • AIM: The aim of the study was to assess the incidence, mortality and morbidity of dilated cardiomyopathy (DCM) and non-compaction of the left ventricle (LVNC) in Swedish children.METHODS: We reviewed hospital records of all children with dilated cardiomyopathy (DCM) or left ventricular non-compaction cardiomyopathy (LVNC) up to the age of 18 in the healthcare region of western Sweden from 1991 to 2015.RESULTS: In total, 69 cases (61% males) were identified. The combined incidence of DCM and LVNC was 0.77 (95% CI 0.59-0.96) per 100,000 person years. Children were divided into six groups and their outcomes were analysed depending on their aetiology. Idiopathic DCM was reported in 43% and familial dilated and left ventricular non-compaction aetiology was present in 32%. DCM due to various diseases occurred in 8%. DCM associated with neuromuscular diseases was present in 16%. The overall risk of death or receiving transplants in children with idiopathic and familial DCM was 30% over the study period and 21% died in the first year after diagnosis.CONCLUSION: The combined incidence of DCM and LVNC was similar to previous reports. Most children with idiopathic DCM presented during infancy and mortality was highest during the first year after diagnosis.
  •  
48.
  • Fall, Katja, 1971-, et al. (author)
  • Antibiotic treatment and risk of gastric cancer
  • 2006
  • In: Gut. - London, United Kingdom : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 55:6, s. 793-6
  • Journal article (peer-reviewed)abstract
    • Background/aims: Helicobacter pylori infection is undoubtedly an important risk factor for gastric cancer. It remains unclear however whether antibiotic treatment may prevent gastric cancer development. Our aim was to assess long term gastric cancer risks in historic cohorts of patients presumed to have been heavily exposed to antibiotics.Subjects: Using the Swedish Inpatient Register, we identified 501 757 individuals discharged with any one of 10 selected infectious disease diagnoses between 1970 and 2003.Methods: We counted person time and non-cardia gastric cancer occurrences through linkage to virtually complete population and health care registers. Standardised incidence ratios (SIRs) were calculated for comparisons with cancer incidence rates of the general population in Sweden.Results: No reduction in gastric cancer risk was observed in the infectious disease cohort in total (SIR 1.08 (95% confidence intervals 1.00-1.17) or for any of the presumed antibiotic regimens. There were no clear trends towards decreasing risk with time of follow up, but the risk tended to fall with increasing age at first hospitalisation for the infection (p<0.04).Conclusions: Our results do not confirm earlier observational findings of a reduced risk of gastric cancer following exposure to heavy antibiotic treatment among hip replacement patients. Suboptimal drug regimens, inadequate timing of H pylori eradication, or insufficient follow up time may possibly explain the lack of association in this setting. Although our findings do not rule out the cancer preventive potential of H pylori eradication, they emphasise that detection of such an effect, if any, may require considerable efforts.
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49.
  • Fall, Katja, et al. (author)
  • Bra prognosstudier kan ge bättre kliniska beslut
  • 2013
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 110:6, s. 279-283
  • Journal article (peer-reviewed)abstract
    • Syftet med prognosstudier är primärt att skatta risken för ett utfall bland patienter på grupp- eller individnivå. För att kunna göra individuella riskbedömningar krävs prognosmodeller som baseras på risk- eller pro­gnosfaktorer.Modellens användbarhet är beroende av dess validitet och förmåga att korrekt skilja ut personer som i framtiden kommer att få ett ogynnsamt utfall från personer som inte kommer att få det.En kliniskt relevant risk- eller prognosfaktor (eller riskekvation som kombinerar flera sådana faktorer) kan kännas igen på att den när den används förändrar predicerad risk i hög grad och åt rätt håll, hos personer med en relevant absolut risk, vilket gör att den påverkar kliniskt beslutsfattande.
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50.
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