| 1. |
- Ahrén, Jonatan, et al.
(författare)
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A hypothesis - generating Swedish extended national cross-sectional family study of multimorbidity severity and venous thromboembolism
- 2023
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Ingår i: BMJ Open. - 2044-6055. ; 13:6, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Venous thromboembolism (VTE) is a common worldwide disease. The burden of multimorbidity, that is, two or more chronic diseases, has increased. Whether multimorbidity is associated with VTE risk remains to be studied. Our aim was to determine any association between multimorbidity and VTE and any possible shared familial susceptibility.DESIGN: A nationwide extended cross-sectional hypothesis - generating family study between 1997 and 2015.SETTING: The Swedish Multigeneration Register, the National Patient Register, the Total Population Register and the Swedish cause of death register were linked.PARTICIPANTS: 2 694 442 unique individuals were analysed for VTE and multimorbidity.MAIN OUTCOMES AND MEASURES: Multimorbidity was determined by a counting method using 45 non-communicable diseases. Multimorbidity was defined by the occurrence of ≥2 diseases. A multimorbidity score was constructed defined by 0, 1, 2, 3, 4 or 5 or more diseases.RESULTS: Sixteen percent (n=440 742) of the study population was multimorbid. Of the multimorbid patients, 58% were females. There was an association between multimorbidity and VTE. The adjusted odds ratio (OR) for VTE in individuals with multimorbidity (2 ≥ diagnoses) was 3.16 (95% CI: 3.06 to 3.27) compared with individuals without multimorbidity. There was an association between number of diseases and VTE. The adjusted OR was 1.94 (95% CI: 1.86 to 2.02) for one disease, 2.93 (95% CI: 2.80 to 3.08) for two diseases, 4.07 (95% CI: 3.85 to 4.31) for three diseases, 5.46 (95% CI: 5.10 to 5.85) for four diseases and 9.08 (95% CI: 8.56 to 9.64) for 5 ≥ diseases. The association between multimorbidity and VTE was stronger in males OR 3.45 (3.29 to 3.62) than in females OR 2.91 (2.77 to 3.04). There were significant but mostly weak familial associations between multimorbidity in relatives and VTE.CONCLUSIONS: Increasing multimorbidity exhibits a strong and increasing association with VTE. Familial associations suggest a weak shared familial susceptibility. The association between multimorbidity and VTE suggests that future cohort studies where multimorbidity is used to predict VTE might be worthwhile.
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| 2. |
- Ali Khan, Uzair, et al.
(författare)
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Personal History of Diabetes as Important as Family History of Colorectal Cancer for Risk of Colorectal Cancer : A Nationwide Cohort Study
- 2020
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Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 115:7, s. 1103-1109
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Diabetes mellitus (DM) and colorectal cancer (CRC) share some risk factors, including lifestyle and metabolic disturbances. We aimed to provide in-depth information on the association of CRC risk, especially early-onset CRC, with DM, family history of CRC, and age at DM diagnosis. METHODS: A nationwide cohort study was conducted using Swedish family cancer data sets, inpatient, and outpatient registers (follow-up: 1964-2015), including all individuals born after 1931 and their parents (12,614,256 individuals; 559,375 diabetic patients; 162,226 CRC patients). RESULTS: DM diagnosis before the age of 50 years was associated with a 1.9-fold increased risk of CRC before the age of 50 years (95% CI for standardized incidence ratio: 1.6-2.3) vs 1.3-fold risk of CRC at/after the age of 50 years (1.2-1.4). DM diagnosis before the age of 50 years in those with a family history of CRC was associated with 6.9-fold risk of CRC before the age of 50 years (4.1-12) and 1.9-fold risk of CRC at/after the age of 50 years (1.4-2.5). Diabetic patients had a similar lifetime risk of CRC before the age of 50 years (0.4%, 95% CI: 0.3%-0.4%) to those with only a family history of CRC (0.5%, 0.5%-0.5%), double that of the population (0.2%, 0.2%-0.2%). DISCUSSION: Our large cohort with valid information on DM and family history of cancer showed that DM is associated with increased risk of CRC in a magnitude close to having family history of CRC. Associations of DM and CRC family history with increased CRC risk were most prominent in young adults. These findings warrant further studies on harms, benefits, and cost-effectiveness of CRC screening in patients with diabetes, especially type 2, at earlier ages than in the general population.
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| 3. |
- Ali Khan, Uzair, et al.
(författare)
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Risk of colorectal cancer in patients with diabetes mellitus : A Swedish nationwide cohort study
- 2020
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal cancer (CRC) incidence is increasing among young adults below screening age, despite the effectiveness of screening in older populations. Individuals with diabetes mellitus are at increased risk of early-onset CRC. We aimed to determine how many years earlier than the general population patients with diabetes with/without family history of CRC reach the threshold risk at which CRC screening is recommended to the general population. METHODS AND FINDINGS: A nationwide cohort study (follow-up:1964-2015) involving all Swedish residents born after 1931 and their parents was carried out using record linkage of Swedish Population Register, Cancer Registry, National Patient Register, and Multi-Generation Register. Of 12,614,256 individuals who were followed between 1964 and 2015 (51% men; age range at baseline 0-107 years), 162,226 developed CRC, and 559,375 developed diabetes. Age-specific 10-year cumulative risk curves were used to draw conclusions about how many years earlier patients with diabetes reach the 10-year cumulative risks of CRC in 50-year-old men and women (most common age of first screening), which were 0.44% and 0.41%, respectively. Diabetic patients attained the screening level of CRC risk earlier than the general Swedish population. Men with diabetes reached 0.44% risk at age 45 (5 years earlier than the recommended age of screening). In women with diabetes, the risk advancement was 4 years. Risk was more pronounced for those with additional family history of CRC (12-21 years earlier depending on sex and benchmark starting age of screening). The study limitations include lack of detailed information on diabetes type, lifestyle factors, and colonoscopy data. CONCLUSIONS: Using high-quality registers, this study is, to our knowledge, the first one that provides novel evidence-based information for risk-adapted starting ages of CRC screening for patients with diabetes, who are at higher risk of early-onset CRC than the general population.
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| 4. |
- Amstadter, Ananda B., et al.
(författare)
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Post-traumatic stress disorder and drug use disorder : examination of aetiological models in a Swedish population-based cohort
- 2023
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Ingår i: European Journal of Psychotraumatology. - 2000-8066. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are two primary phenotypic models of comorbidity between post-traumatic stress disorder (PTSD) and drug use disorder (DUD), i.e. self-medication (PTSD precedes and causes DUD) and susceptibility (DUD precedes and causes PTSD). We sought to clarify the longitudinal relationship between PTSD and DUD, while examining sex differences. Method: We used approximately 23 years of longitudinal data from Swedish population registries to conduct two complementary statistical models: Cox proportional hazard models (N ≈ 1.5 million) and a cross-lagged panel model (N ≈ 3.8 million). Results: Cox proportional hazards models, adjusting for cohort and socioeconomic status, found strong evidence for the self-medication hypothesis, as PTSD predicted increased risk for DUD among both women [hazard ratio (HR) = 5.34, 95% confidence interval (CI) 5.18, 5.51] and men (HR = 3.65, 95% CI 3.54, 3.77), and moreover, that the PTSD to DUD association was significantly higher among women (interaction term 0.68, 95% CI 0.65, 0.71). The results of the susceptibility model were significant, but not as strong as the self-medication model. DUD predicted risk for PTSD among both women (HR = 2.43, 95% CI 2.38, 2.50) and men (HR = 2.55, 95% CI 2.50, 2.60), and HR was significantly higher in men (interaction term 1.05, 95% CI 1.02, 1.08). Investigating the pathways simultaneously in the cross-lagged model yielded support for both pathways of risk. The cross-paths instantiating the susceptibility model (0.10–0.22 in females, 0.12–0.19 in males) were mostly larger than those capturing the self-medication model (0.01–0.16 in females, 0.04–0.22 in males). Conclusions: We demonstrate that the relationship between PTSD and DUD is bidirectional, with evidence that future research should prioritize examining specific pathways of risk that may differ between men and women.
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| 5. |
- Amstadter, Ananda B., et al.
(författare)
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Testing Phenotypic Models of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity Using Longitudinal Registry Data
- 2023
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Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 84:3, s. 378-388
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Two predominant phenotypic models of causality exist to explain the high co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD): the self-medication and susceptibility models. Population-based longitudinal studies that simultaneously examine both models are needed. Thus, the goal of the pres-ent study is to test these models using the Swedish National Registries. Method: Registries were used to conduct longitudinal Cox proportional hazard models (n ≈ 1.5 million) and cross-lagged panel models (N ≈ 3.8 million) with follow-up periods of ~23 years. Results: Covarying for cohort and socioeconomic status, Cox proportional hazards model results found strong support for the self-medication model. Results showed that PTSD predicted increased risk for AUD among both men (HR = 4.58 [4.42, 4.74]) and women (HR = 4.14 [3.99, 4.30]), significantly more so for men (interaction HR = 1.11 [1.05, 1.16]). Support was also found for the susceptibility model, although the effects were lower in magnitude than those for the self-medication model. AUD increased risk for PTSD among men (HR = 2.53 [2.47, 2.60]) and women (HR = 2.06 [2.01, 2.12]), and significantly more so for men (interaction term HR = 1.23 [1.18, 1.28]). Cross-lagged model results of simultaneously testing both models found support for bidirectionality. The PTSD-to-AUD paths and the AUD-to-PTSD paths were of modest effect for men and women. Conclusions: The results from both complementary statistical approaches demonstrate that the models of comorbidity are not mutually exclusive. Although the Cox model results evidenced more support for the self-medication pathway, the cross-lagged model results suggest that the prospective relationships between these disorders are nuanced across development. (J. Stud. Alcohol Drugs, 84, 378–388, 2023).
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| 6. |
- Blunk, Inga, et al.
(författare)
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Genomic imprinting analyses identify maternal effects as a cause of phenotypic variability in type 1 diabetes and rheumatoid arthritis
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Imprinted genes, giving rise to parent-of-origin effects (POEs), have been hypothesised to affect type 1 diabetes (T1D) and rheumatoid arthritis (RA). However, maternal effects may also play a role. By using a mixed model that is able to simultaneously consider all kinds of POEs, the importance of POEs for the development of T1D and RA was investigated in a variance components analysis. The analysis was based on Swedish population-scale pedigree data. With P = 0.18 (T1D) and P = 0.26 (RA) imprinting variances were not significant. Explaining up to 19.00% (± 2.00%) and 15.00% (± 6.00%) of the phenotypic variance, the maternal environmental variance was significant for T1D (P = 1.60 × 10−24) and for RA (P = 0.02). For the first time, the existence of maternal genetic effects on RA was indicated, contributing up to 16.00% (± 3.00%) of the total variance. Environmental factors such as the social economic index, the number of offspring, birth year as well as their interactions with sex showed large effects.
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| 7. |
- Calling, Susanna, et al.
(författare)
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Coronary heart disease in mothers and fathers of adult children with alcohol use disorders
- 2021
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Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 116:12, s. 3390-3397
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Having a family member with an alcohol use disorder (AUD) may negatively affect a person's health. Our aim was to study the long-term risk of coronary heart disease (CHD) in parents who have an offspring with AUD. Design: Cohort study with Cox regression models and co-sibling analyses. Setting: Sweden. Participants: From population registers, we selected all parent-offspring pairs in which the parent was born in Sweden between 1945 and 1965. Measurements: Baseline was set when the offspring was 15 years old and AUD was assessed from medical and criminal registers. The parents were followed for CHD during a mean follow-up of 18 years. Hazard ratios (HRs) in mothers and fathers were calculated and adjusted for potential confounders (year of birth, age at childbirth, sex of the child, parent' AUD, educational level, and marital status). Findings: In mothers, the adjusted HR for CHD was 1.24 (95% CI = 1.19–1.28) in relation to having a child with AUD. In fathers, the HR for CHD was lower than in mothers but still increased; the adjusted HR was 1.08 (95% CI = 1.05–1.12). In the co-sibling analyses, the HRs for mothers were similar to the HRs estimated from the population-based sample, but in fathers the association did not remain significant (HR = 0.98 [0.90–1.06]). Conclusions: In Sweden, there appears to be an association between having an offspring with alcohol use disorder and increased risk of developing coronary heart disease. For fathers, the association did not remain in co-sibling analyses.
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| 8. |
- Calling, Susanna, et al.
(författare)
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Total cholesterol/HDL-C ratio versus non-HDL-C as predictors for ischemic heart disease : a 17-year follow-up study of women in southern Sweden
- 2021
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A distorted blood lipid profile is an important risk factor for ischemic heart disease (IHD) but the predictive ability of the different lipid measures has rarely been studied. Our aim was to examine and compare, in a large sample of women, the predictive ability of total cholesterol/HDL cholesterol ratio (TC/HDL-C) and non-HDL-C in relation to IHD, adjusted for age, exercise, smoking, waist-hip ratio, blood pressure, and diabetes mellitus. Methods: Between 1995 and 2000, a total of 6537 women aged 50–59 years from the Women’s Health in Lund area (WHILA) study in southern Sweden were included and underwent a baseline examination. The women were followed through national registers for incidence of IHD during a mean follow-up of 17 years. The prediction accuracy was estimated through Harrell’s C and Akaike Information Criterion (AIC). Results: Increasing TC/HDL-C as well as non-HDL-C showed strong associations with IHD, with the highest risk in the 5th quintile, where the HR was 2.30 (95% CI: 1.70–3.11) for TC/HDL-C and 1.67 (95% CI: 1.25–2.24) for non-HDL-C, after adjustments. Comparisons using Harrell’s C and AIC indicated that TC/HDL-C has a slightly higher predictive ability than that of non-HDL-C (Harrell’s C 0.62 and 0.59 respectively, p = 0.003 for difference, age-adjusted model; AIC for TC/HDL-C < AIC for non-HDL-C). Conclusions: TC/HDL-C ratio and non-HDL-C are both clinical predictors for IHD in middle-aged women. The results indicate that the predictive ability of TC/HDL-C was higher than that of non-HDL-C; however, non-HDL-C was linearly related to IHD (p = 0.58) and may be easier to calculate and interpret in clinical practice, for early identification of future IHD in women.
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| 9. |
- Calling, Susanna, et al.
(författare)
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Trajectories of body mass index and risk for coronary heart disease : A 38-year follow-up study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:10 October 2021
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Tidskriftsartikel (refereegranskat)abstract
- Objective Obesity is a well-known risk factor for coronary heart disease (CHD), but there is little evidence on the effect of long-term trajectories of body mass index (BMI) over the life course. By using repeated assessments, the aim was to study the risk of CHD in adults during 38 years in different trajectories of BMI. Methods A sample of 2129 men and women, aged 20-59 years at baseline, took part in four repeated interviews between 1980 and 2005. Data on BMI, medical history, lifestyle and socioeconomy were collected. Based on the World Health Organization categories of BMI, life course trajectories of stable normal weight, stable overweight, stable obesity, increasing BMI and fluctuating BMI were created. The individuals were followed through national registers for first hospitalization of CHD (389 events) until the end of 2017, and Hazard Ratios (HRs) were calculated, adjusted for age, sex, socioeconomic factors, lifestyle factors and metabolic comorbidities. Results Stable normal weight in all assessments was the reference group. Those who had an increase in BMI from normal weight in the first assessment to overweight or obesity in later assessments had no increased risk of CHD, HR 1.04 (95% CI: 0.70-1.53). The HR for individuals with fluctuating BMI was 1.25 (0.97-1.61), for stable overweight 1.43 (1.03-1.98), for stable obesity 1.50 (0.92-2.55), and for stable overweight or obesity 1.45 (1.07-1.97), after full adjustments. Conclusion Having a stable overweight or obesity throughout adult life was associated with increased CHD risk but changing from normal weight at baseline to overweight or obesity was not associated with increased CHD risk. Prevention of obesity early in life may be particularly important to reduce CHD risk.
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| 10. |
- Cardoso, Rafael, et al.
(författare)
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Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study
- 2021
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Ingår i: The Lancet Oncology. - 1474-5488. ; 22:7, s. 1002-1013
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. Methods: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. Findings: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from −2·5% (95% CI −2·8 to −2·2) to −1·6% (−2·0 to −1·2) in men and from −2·4% (−2·7 to −2·1) to −1·3% (−1·7 to −0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from −0·2% (95% CI −1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from −0·5% (−1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. Interpretation: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. Funding: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research. © 2021 Elsevier Ltd
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