Publications by authors named "Erzsébet Horváth-Puhó"

106 Publications

Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study.

Lancet Child Adolesc Health 2021 Apr 21. Epub 2021 Apr 21.

Maternal, Adolescent, Reproductive & Child Health Centre and Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. Electronic address:

Background: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands.

Methods: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts.

Findings: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts.

Interpretation: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease.

Funding: The Bill & Melinda Gates Foundation.

Translations: For the Dutch and Danish translations of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2352-4642(21)00022-5DOI Listing
April 2021

Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study.

Lancet Child Adolesc Health 2021 Apr 21. Epub 2021 Apr 21.

Maternal, Adolescent, Reproductive & Child Health Centre and Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. Electronic address:

Background: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands.

Methods: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts.

Findings: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts.

Interpretation: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease.

Funding: The Bill & Melinda Gates Foundation.

Translations: For the Dutch and Danish translations of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2352-4642(21)00022-5DOI Listing
April 2021

Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study.

Lancet Child Adolesc Health 2021 Apr 21. Epub 2021 Apr 21.

Maternal, Adolescent, Reproductive & Child Health Centre and Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. Electronic address:

Background: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands.

Methods: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts.

Findings: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts.

Interpretation: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease.

Funding: The Bill & Melinda Gates Foundation.

Translations: For the Dutch and Danish translations of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2352-4642(21)00022-5DOI Listing
April 2021

Long-term risk of epilepsy, cerebral palsy and attention-deficit/hyperactivity disorder in children affected by a threatened abortion in utero.

Int J Epidemiol 2021 Apr 13. Epub 2021 Apr 13.

Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.

Background: The birth of a child affected by a threatened abortion (TAB) in utero is associated with autism spectrum disorder; association with other neurological disorders is unknown.

Methods: This nationwide registry-based cohort study included singletons live-born in Denmark (1979-2010), followed through 2016. The outcomes were epilepsy, cerebral palsy (CP) and attention-deficit/hyperactivity disorder (ADHD). We used Cox regression to compute hazard ratios (HRs), adjusted for birth year, birth order, parental age, morbidity, medication use and maternal socio-economic factors. To remove time-invariant family-shared confounding, we applied sibling analyses.

Results: The study population included 1 864 221 singletons live-born in 1979-2010. Among the TAB-affected children (N = 59 134) vs TAB-unaffected children, at the end of follow-up, the cumulative incidence was 2.2% vs 1.6% for epilepsy, 0.4% vs 0.2% for CP and 5.5% vs 4.2% for ADHD (for children born in 1995-2010). The adjusted HRs were 1.25 [95% confidence interval (CI) 1.16-1.34] for epilepsy, 1.42 (95% CI 1.20-1.68) for CP and 1.21 (95% CI 1.14-1.29) for ADHD. In the sibling design, the adjusted HRs were unity for epilepsy (full siblings: 0.96, 95% CI 0.82-1.12; maternal: 1.04, 95% CI 0.90-1.20; paternal: 1.08, 95% CI 0.93-1.25) and ADHD (full: 1.08, 95% CI 0.92-1.27; maternal: 1.04, 95% CI 0.90-1.20; paternal: 1.08, 95% CI 0.93-1.25). For CP, HRs shifted away from unity among sibling pairs (full: 2.92, 95% CI 1.33-6.39; maternal: 2.03, 95% CI 1.15-3.57; paternal: 3.28, 95% CI 1.36-7.91).

Conclusions: The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD.
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http://dx.doi.org/10.1093/ije/dyab069DOI Listing
April 2021

No benefit of more intense follow-up after surgery for colorectal cancer in the risk group with elevated CEA levels - An analysis within the COLOFOL randomized clinical trial.

Eur J Surg Oncol 2021 Mar 26. Epub 2021 Mar 26.

Department of Surgery, Skåne University Hospital, 205 02, Malmö, Sweden. Electronic address:

Background: Patients with colorectal cancer were examined to determine (1) whether elevated carcinoembryonic antigen (CEA) levels, either before treatment or after surgery, was associated with an increased risk of overall or colorectal cancer-specific mortality or recurrence, and (2) whether high intensity follow-up would benefit those patients.

Materials And Methods: Post-hoc analysis based on 2509 patients that underwent surgery for colorectal cancer, stage II or III, in the COLOFOL randomized trial with 5-year follow-up. Serum CEA levels were ascertained before treatment and one month after surgery. Follow-up examinations included computed tomography of the thorax and abdomen and serum CEA sampling. Patients were randomized to examinations at either 6, 12, 18, 24, and 36 months (high-intensity group) or at 12 and 36 months after surgery (low-intensity group). Levels of CEA >5 μg/l were defined as elevated.

Results: Elevated CEA levels before treatment were associated with increased risk of recurrence (hazard ratio [HR], 1.49; 95% confidence interval [CI]: 1.22-1.83), colorectal cancer-specific mortality (HR, 1.44; 95% CI: 1.08-1.91), and overall mortality (HR, 1.38; 95% CI: 1.07-1.78). Elevated CEA levels after surgery were associated with increased colorectal cancer-specific mortality (HR, 1.68; 95% CI: 1.08-2.61) and overall mortality (HR, 1.79; 95% CI: 1.22-2.63). The intensity of the follow-up regimen had no effect on 5-year outcomes in patients with elevated CEA levels.

Conclusion: Both pre-treatment and post-surgery elevated serum CEA levels were associated with increased overall and cancer-specific mortality. Intensified follow-up showed no benefit over low-intensity follow-up in this high-risk group of patients with elevated CEA levels.
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http://dx.doi.org/10.1016/j.ejso.2021.03.235DOI Listing
March 2021

Mortality Among Parents of Children With Major Congenital Anomalies.

Pediatrics 2021 May 2;147(5). Epub 2021 Apr 2.

Department of Pediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada;

Background: A mother whose child has a chronic condition, such as a major congenital anomaly, often experiences poorer long-term health, including earlier mortality. Little is known about the long-term health of fathers of infants with a major congenital anomaly.

Methods: In this population-based prospective cohort study, we used individual-linked Danish registry data. Included were all mothers and fathers with a singleton infant born January 1, 1986, to December 31, 2015. Cox proportional hazards regression was used to generate hazard ratios for all-cause and cause-specific mortality among mothers and fathers whose infant had an anomaly and fathers of unaffected infants, relative to mothers of unaffected infants (referent), adjusted for child's year of birth, parity, parental age at birth, parental comorbidities, and sociodemographic characteristics.

Results: In total, 20 952 of 965 310 mothers (2.2%) and 20 655 of 951 022 fathers (2.2%) had an infant with a major anomaly. Median (interquartile range) of parental follow-up was 17.9 (9.5 to 25.5) years. Relative to mothers of unaffected infants, mothers of affected infants had adjusted hazard ratios (aHRs) of death of 1.20 (95% confidence interval [CI]: 1.09 to 1.32), fathers of unaffected infants had intermediate aHR (1.62, 95% CI: 1.59 to 1.66), and fathers of affected infants had the highest aHR (1.76, 95% CI: 1.64 to 1.88). Heightened mortality was primarily due to cardiovascular and endocrine/metabolic diseases.

Conclusions: Mothers and fathers of infants with a major congenital anomaly experience an increased risk of mortality, often from preventable causes. These findings support including fathers in interventions to support the health of parental caregivers.
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http://dx.doi.org/10.1542/peds.2020-028571DOI Listing
May 2021

Thromboembolism and the Oxford-AstraZeneca COVID-19 vaccine: side-effect or coincidence?

Lancet 2021 04 30;397(10283):1441-1443. Epub 2021 Mar 30.

Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.1016/S0140-6736(21)00762-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009607PMC
April 2021

Sleep disruption and Alzheimer's disease risk: Inferences from men with benign prostatic hyperplasia.

EClinicalMedicine 2021 Feb 3;32:100740. Epub 2021 Feb 3.

Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Aarhus N, Denmark.

Background: Sleep disturbances may increase risks of Alzheimer's disease (AD) and other dementias. Benign prostatic hyperplasia (BPH) is usually associated with lower urinary tract symptoms, including nocturia, and thereby disturbed sleep. We examined if men with BPH are at increased risk of AD and all-cause dementia.

Methods: In a Danish nationwide cohort (1996-2016), we identified 297,026 men with BPH, defined by inpatient or outpatient hospital diagnosis or by BPH-related surgical or medical treatment, and 1,107,176 men from the general population matched by birth year. We computed rates, cumulative incidences, and adjusted hazard ratios (HRs) of AD and all-cause dementia. Follow-up started 1 year after BPH diagnosis date/index date.

Findings: Median follow-up was 6·9 years (Interquartile range (IQR), 3·6 - 11·6 years] in the BPH cohort and 6·4 years (IQR: 3·4 - 10·8 years) in the comparison cohort. The cumulative 1-10 year risk of AD was 1·15% [95% confidence interval (CI), 1·11-1·20], in the BPH cohort and 1·00% (95% CI, 0·98 - 1·02) in the comparison cohort. The adjusted 1-10-year hazard ratios were 1·16 (95% CI: 1·10-1·21) for AD and 1·21 (95% CI: 1·17-1·25) for all-cause dementia. From >10 years up to 21 years of follow-up, BPH remained associated with 10%- 20% increased risk of AD and all-cause dementia.

Interpretation: During up to 21 years of follow-up, men with BPH had persistently higher risk of AD and all-cause dementia compared with men in the general population. Our results identify BPH as a common, potentially remediable disorder associated with dementia risk.

Funding: Lundbeckfonden, Aarhus University Research Foundation, and the National Institutes of Health.
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http://dx.doi.org/10.1016/j.eclinm.2021.100740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910709PMC
February 2021

Sleep disruption and Alzheimer's disease risk: Inferences from men with benign prostatic hyperplasia.

EClinicalMedicine 2021 Feb 3;32:100740. Epub 2021 Feb 3.

Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, DK-8200 Aarhus N, Denmark.

Background: Sleep disturbances may increase risks of Alzheimer's disease (AD) and other dementias. Benign prostatic hyperplasia (BPH) is usually associated with lower urinary tract symptoms, including nocturia, and thereby disturbed sleep. We examined if men with BPH are at increased risk of AD and all-cause dementia.

Methods: In a Danish nationwide cohort (1996-2016), we identified 297,026 men with BPH, defined by inpatient or outpatient hospital diagnosis or by BPH-related surgical or medical treatment, and 1,107,176 men from the general population matched by birth year. We computed rates, cumulative incidences, and adjusted hazard ratios (HRs) of AD and all-cause dementia. Follow-up started 1 year after BPH diagnosis date/index date.

Findings: Median follow-up was 6·9 years (Interquartile range (IQR), 3·6 - 11·6 years] in the BPH cohort and 6·4 years (IQR: 3·4 - 10·8 years) in the comparison cohort. The cumulative 1-10 year risk of AD was 1·15% [95% confidence interval (CI), 1·11-1·20], in the BPH cohort and 1·00% (95% CI, 0·98 - 1·02) in the comparison cohort. The adjusted 1-10-year hazard ratios were 1·16 (95% CI: 1·10-1·21) for AD and 1·21 (95% CI: 1·17-1·25) for all-cause dementia. From >10 years up to 21 years of follow-up, BPH remained associated with 10%- 20% increased risk of AD and all-cause dementia.

Interpretation: During up to 21 years of follow-up, men with BPH had persistently higher risk of AD and all-cause dementia compared with men in the general population. Our results identify BPH as a common, potentially remediable disorder associated with dementia risk.

Funding: Lundbeckfonden, Aarhus University Research Foundation, and the National Institutes of Health.
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http://dx.doi.org/10.1016/j.eclinm.2021.100740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910709PMC
February 2021

Latent classes of posttraumatic psychiatric comorbidity in the general population.

J Psychiatr Res 2021 04 13;136:334-342. Epub 2021 Feb 13.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Some narrow patterns of posttraumatic psychiatric comorbidity are well-established (e.g., posttraumatic stress disorder and substance use). However, broad multi-diagnosis profiles of posttraumatic comorbidity are poorly characterized. The goal of the current study was to use latent class analysis (LCA) to identify profiles of posttraumatic psychopathology from 11 International Classification of Diseases (ICD-10) diagnostic categories (e.g., stress, substance, depressive, psychosis, personality). Danish national registries were used to identify 166,539 individuals (median age = 41 years, range = <1 to >100) who experienced a traumatic event between 1994 and 2016 and were diagnosed with one or more mental disorders within 5 years. Two through 14-class LCA solutions were evaluated. A 13-class solution (a) provided the best fit, with the Bayes and Akaike Information Criteria reaching a minimum, (b) was broadly consistent with prior LCA studies, and (c) included several novel classes reflecting differential patterns of posttraumatic psychopathology. Three classes were characterized by high comorbidity: broad high comorbidity (M # diagnoses = 4.3), depression with stress/substance use/personality/neurotic disorders (M# diagnoses = 3.8), and substance use with personality/stress/psychotic disorders (M # diagnoses = 3.1). The other 10 classes were characterized by distinct patterns of mild comorbidity or negligible comorbidity. Compared to the mild and negligible comorbidity classes, individuals in high comorbidity classes were younger, had lower income, and had more pre-event psychiatric disorders. Results suggest that several different comorbidity patterns should be assessed when studying and treating posttraumatic psychopathology.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.013DOI Listing
April 2021

Latent classes of posttraumatic psychiatric comorbidity in the general population.

J Psychiatr Res 2021 04 13;136:334-342. Epub 2021 Feb 13.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Some narrow patterns of posttraumatic psychiatric comorbidity are well-established (e.g., posttraumatic stress disorder and substance use). However, broad multi-diagnosis profiles of posttraumatic comorbidity are poorly characterized. The goal of the current study was to use latent class analysis (LCA) to identify profiles of posttraumatic psychopathology from 11 International Classification of Diseases (ICD-10) diagnostic categories (e.g., stress, substance, depressive, psychosis, personality). Danish national registries were used to identify 166,539 individuals (median age = 41 years, range = <1 to >100) who experienced a traumatic event between 1994 and 2016 and were diagnosed with one or more mental disorders within 5 years. Two through 14-class LCA solutions were evaluated. A 13-class solution (a) provided the best fit, with the Bayes and Akaike Information Criteria reaching a minimum, (b) was broadly consistent with prior LCA studies, and (c) included several novel classes reflecting differential patterns of posttraumatic psychopathology. Three classes were characterized by high comorbidity: broad high comorbidity (M # diagnoses = 4.3), depression with stress/substance use/personality/neurotic disorders (M# diagnoses = 3.8), and substance use with personality/stress/psychotic disorders (M # diagnoses = 3.1). The other 10 classes were characterized by distinct patterns of mild comorbidity or negligible comorbidity. Compared to the mild and negligible comorbidity classes, individuals in high comorbidity classes were younger, had lower income, and had more pre-event psychiatric disorders. Results suggest that several different comorbidity patterns should be assessed when studying and treating posttraumatic psychopathology.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.013DOI Listing
April 2021

Nationwide Trends in Incidence and Mortality of Stroke Among Younger and Older Adults in Denmark.

Neurology 2021 03 10;96(13):e1711-e1723. Epub 2021 Feb 10.

From the Department of Clinical Epidemiology (N.S., K.A., E.H.-P., K.J.R., V.W.H., H.T.S.) and Department of Clinical Biochemistry (K.A.), Thrombosis and Haemostasis Research Unit, Aarhus University Hospital; National Institute of Public Health (N.S., L.C.T.), University of Southern Denmark, Copenhagen; Department of Epidemiology (K.J.R., H.T.S.), Boston University School of Public Health, MA; RTI Health Solutions (K.J.R.), Research Triangle Institute, Research Triangle Park, NC; and Department of Epidemiology and Population Health (V.W.H., H.T.S.) and Department of Neurology and Neurological Sciences, Stanford University, CA.

Objective: To investigate the extent to which the incidence and mortality of a first-time stroke among younger and older adults changed from 2005 to 2018 in Denmark using nationwide registries.

Methods: We used the Danish Stroke Registry and the Danish National Patient Registry to identify patients 18 to 49 years of age (younger adults) and those ≥50 years of age (older adults) with a first-time ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. We computed age-standardized incidence rates and 30-day and 1-year mortality risks separately for younger and older adults and according to smaller age groups, stroke subtype, sex, and severity (Scandinavian Stroke Scale score). Average annual percentage changes (AAPCs) were computed to assess temporal trends.

Results: We identified 8,680 younger adults and 105,240 older adults with an ischemic stroke or intracerebral hemorrhage. The incidence rate per 100,000 person-years of ischemic stroke (20.8 in 2005 and 21.9 in 2018, AAPC -0.6 [95% confidence interval (CI) -1.5 to 0.3]) and intracerebral hemorrhage (2.2 in 2005 and 2.5 in 2018, AAPC 0.6 [95% CI -1.0 to 2.3]) remained steady in younger adults. In older adults, rates of ischemic stroke and intracerebral hemorrhage declined, particularly in those ≥70 years of age. Rates of subarachnoid hemorrhage declined, but more so in younger than older adults. Stroke mortality declined over time in both age groups, attributable largely to declines in the mortality after severe strokes. Most trends were similar for men and women.

Conclusion: The incidence of ischemic stroke and intracerebral hemorrhage was steady in younger adults from 2005 to 2018, while it dropped in adults >70 years of age. Stroke mortality declined during this time.
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http://dx.doi.org/10.1212/WNL.0000000000011636DOI Listing
March 2021

Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia.

J Alzheimers Dis 2021 ;79(4):1601-1612

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia.

Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer's disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes).

Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000-2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200-600 pmol/L). We used multivariable Cox regression to compute 0-15-year hazard ratios for dementia.

Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia.

Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.
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http://dx.doi.org/10.3233/JAD-201096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990402PMC
January 2021

Long-term mortality in young and middle-aged adults hospitalised with chronic disease: a Danish cohort study.

BMJ Open 2020 10 12;10(10):e038131. Epub 2020 Oct 12.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Objectives: To examine the long-term outcomes for patients hospitalised with chronic diseases at age 30, 40 or 50 years.

Design: Nationwide, population-based cohort study.

Setting: All Danish hospitals, 1979-1989, with follow-up through 2014.

Participants: Patients hospitalised during the study period with one, two or three or more chronic diseases and age-matched and sex-matched persons from the general population without chronic disease leading to hospitalisation: age-30 group: 13 857 patients and 69 285 comparators; age-40 group: 24 129 patients and 120 645 comparators; and age-50 group, 37 807 patients and 189 035 comparators.

Main Outcome Measures: Twenty-five-year mortality risks based on Kaplan-Meier estimates, years-of-life-lost (YLLs) and mortality rate ratios based on Cox regression analysis. YLLs were computed for each morbidity level, as well as in strata of income, employment, education and psychiatric conditions.

Results: Twenty-five-year mortality risks and YLLs increased steadily with increasing number of morbidities leading to hospitalisation and age, but the risk difference with general population comparators remained approximately constant across age cohorts. In the age-30 cohort, the risk differences for patients compared with comparators were 35.0% (95% CI 32.5 to 37.5) with two diseases and 62.5% (54.3% to 70.3%) with three or more diseases. In the age-50 cohort, these differences were, respectively, 48.4% (47.4 to 49.3) and 61.7% (60.1% to 63.0%). Increasing morbidity burden augmented YLLs resulting from low income, unemployment, low education level and psychiatric conditions. In the age-30 cohort, YYLs attributable to low income were 2.4 for patients with one disease, 6.2 for patients with two diseases and 11.5 for patients with three or more diseases.

Conclusions: Among patients with multiple chronic diseases, the risk of death increases steadily with the number of chronic diseases and with age. Multimorbidity augments the already increased mortality among patients with low socioeconomic status.
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http://dx.doi.org/10.1136/bmjopen-2020-038131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552875PMC
October 2020

Cancer and risk of Alzheimer's disease: Small association in a nationwide cohort study.

Alzheimers Dement 2020 07 20;16(7):953-964. Epub 2020 May 20.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Introduction: Small observational studies with short-term follow-up suggest that cancer patients are at reduced risk of Alzheimer's disease (AD) compared to the general population.

Methods: A nationwide cohort study using Danish population-based health registries (1980-2013) with cancer patients (n = 949,309) to identify incident diagnoses of AD. We computed absolute reductions in risk attributed to cancer and standardized incidence rate ratios (SIRs) accounting for survival time, comparing the observed to expected number of AD cases.

Results: During up to 34 years of follow-up of cancer survivors, the attributable risk reduction was 1.3 per 10,000 person-years, SIR = 0.94 (95% confidence interval 0.92-0.96). SIRs were similar after stratification by sex, age, and cancer stage, and approached that of the general population for those surviving >10 years.

Discussion: Inverse associations between cancer and AD were small and diminished over time. Incidence rates in cancer survivors approached those of the general population, suggesting limited association between cancer and AD risk.
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http://dx.doi.org/10.1002/alz.12090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351601PMC
July 2020

Comorbidity and risk of venous thromboembolism after hospitalization for first-time myocardial infarction: A population-based cohort study.

J Thromb Haemost 2020 08 14;18(8):1974-1985. Epub 2020 Jun 14.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Myocardial infarction (MI) is a risk factor for venous thromboembolism (VTE). Although comorbidities affect MI prognosis, it is unclear whether they affect VTE risk after MI.

Objectives: We examined the impact of comorbidity on VTE risk after MI.

Methods: We used nationwide population-based registries to identify first-time hospitalizations for MI and subsequent occurrence of VTE in Denmark (1995-2013). We included a comparison cohort from the general population matched 5:1 with MI patients by sex, age, and comorbidities. We computed 30-day and 1- to 12-month cumulative risks, rates, and hazard ratios of VTE. We also assessed the interaction between MI and comorbidity, defined as excess VTE risk in patients with both MI and comorbidity, by computing interaction contrasts and attributable fractions relating to the interaction.

Results: Thirty-day and 1- to 12-month VTE risks were 0.6% and 0.5% in the MI cohort (n = 160 338) and 0.03% and 0.3% in the comparison cohort (n = 792 384). The 30-day hazard ratio for VTE in the MI cohort was 23 (95% confidence interval, 20-27), which decreased during 1-year follow-up. Thirty days after MI, interactions between MI and comorbidity accounted for 16% and 39% of VTE rates in MI patients with low-to-moderate and high comorbidity, respectively. The interactions were driven primarily by hemiplegia and cancer.

Conclusions: Thirty-day VTE risk was substantially increased after MI compared with the general population. Although the absolute VTE risk was low, comorbidity substantially increased this risk, especially hemiplegia and cancer. VTE prophylaxis might be indicated in such high-risk patients but warrants further investigation.
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http://dx.doi.org/10.1111/jth.14865DOI Listing
August 2020

The interaction effect of cardiac and non-cardiac comorbidity on myocardial infarction mortality: A nationwide cohort study.

Int J Cardiol 2020 06 29;308:1-8. Epub 2020 Jan 29.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Whether the prognostic impact of comorbidity on myocardial infarction (MI) mortality is due to comorbidity alone or/and its interaction effect is unknown.

Methods: We used Danish medical registries to conduct a nationwide cohort study of all first-time MIs during 1995-2016 (n = 179,515) and a comparison cohort matched on age, sex, and individual comorbidities (n = 880,347). We calculated age-standardized 5-year all-cause mortality rates. Interaction was examined on an additive scale by calculating interaction contrasts (difference in rate differences).

Results: Among individuals without comorbidity, the 30-day mortality rate per 1000 person-years was 1851 (95% CI: 1818-1884) for MI patients and 22 (21-24) for comparison cohort members (rate difference = 1829). For individuals with low comorbidity, corresponding baseline mortality rates were 2498 (2436-2560) in the MI and 54 (50-57) in the comparison cohort (rate difference = 2444). The interaction contrast (616) indicated that the interaction accounted for 25% (616/2498) of the total 30-day mortality rate in MI patients with low comorbidity. This percentage increased further for moderate (35%) and severe (45%) comorbidity levels. Absolute and relative interaction effects were largest within the first 30 days and younger individuals. Dose-response patterns were also observed during 31-365 days and 1-5 years of follow-up (p-values for trends<0.002). The interaction differed substantially between individual types of cardiac and non-cardiac comorbidities.

Conclusion: Cardiac and non-cardiac comorbidities interact with MI to increase short- and long-term mortality beyond that explained by their additive effects. The interaction had a dose-response relation with comorbidity burden and a magnitude of clinical importance.
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http://dx.doi.org/10.1016/j.ijcard.2020.01.059DOI Listing
June 2020

Initiation of statins and risk of venous thromboembolism: Population-based matched cohort study.

Thromb Res 2019 Dec 6;184:99-104. Epub 2019 Nov 6.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.

Background: The effects of statins in prevention of venous thromboembolism (VTE) is not well established.

Objectives: To examine the risks of first-time VTE in a cohort of patients initiating statin treatment and in a matched general population comparison cohort.

Methods: We conducted a nationwide, population-based, matched cohort study based on data from Danish health registries. The study period was 1 January 2005-31 December 2015. We identified statin initiators (without VTE, myocardial infarction, or ischemic stroke) and sex-, age-, and calendar year-matched (1,3) individuals from the general population (without statin use, VTE, myocardial infarction, or ischemic stroke). We computed cumulative risks and comorbidity-adjusted hazard ratios (HRs) of VTE, myocardial infarction, and ischemic stroke.

Results: Among 601,011 statin initiators and 1,803,033 matched population cohort members during 2005-2015, the cumulative risk after 11 years was 2.8% for VTE (both cohorts), 4.7% vs. 2.9% for myocardial infarction, and 7.1% vs. 5.2 for ischemic stroke. After adjustment, statin use was associated with a slightly decreased risk of VTE (adjusted HR: 0.95 [95% CI: 0.92-0.97]), driven by a reduced risk of unprovoked VTE (adjusted HR: 0.92 [95% CI: 0.89-0.95]). The reduced risks of VTE were more pronounced among patients who had an imaging examination performed. The adjusted HRs were elevated for myocardial infarction and ischemic stroke.

Conclusion: Statin initiation was associated with a reduced risk of VTE, with no indication of a healthy-user effect. Based on available evidence, statins have weak thromboprophylactic effects.
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http://dx.doi.org/10.1016/j.thromres.2019.11.003DOI Listing
December 2019

Alzheimer's and Parkinson's Diseases and the Risk of Cancer: A Cohort Study.

J Alzheimers Dis 2019 ;72(4):1269-1277

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Observational studies have shown inverse associations between neurological diseases, particularly dementia, and subsequent cancer risk, but is unknown whether this association is valid or arises from bias. We conducted a Danish nationwide cohort study using population-based health registries (1980-2012). The study included patients with dementia (n = 173,434) and with Parkinson's disease (n = 28,835). We followed patients for 10 years to assess subsequent cancer diagnoses. We computed absolute reduction in cancer risk attributable to dementia or Parkinson's disease (expected minus the observed number of cancer cases divided by the person time) and standardized incidence rate ratios (SIRs) as the observed to expected number of cancers, based on sex-, age-, and calendar year-standardized national incidence rates. During 10 years, the reduction in cancer cases were 79.9 per 10,000 person-years for Alzheimer's disease [SIR = 0.68 (95% CI: 0.66, 0.70)], 74.4 per 10,000 person-years for vascular dementia [SIR = 0.71 (95% CI: 0.67, 0.74)], 55.8 per 10,000 person-years [SIR = 0.77 (95% CI: 0.75, 0.78)] for all-cause dementia, and 4.0 per 10,000 person-years [SIR = 0.98 (95% CI: 0.95, 1.02) for Parkinson's disease. Associations were nearly similar for solid tumors diagnosed at localized, regional, or distant stages. We found an inverse association between dementia and cancer risk, with similar associations when considering only cancers diagnosed at distant stage. The cancer risk varied by type of dementia, with a gradient toward a stronger protective effect associated with Alzheimer's disease and vascular dementia, which may favor a biological explanation. Overall results do not show an inverse association between Parkinson's disease and cancer.
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http://dx.doi.org/10.3233/JAD-190867DOI Listing
December 2020

Alzheimer's and Parkinson's Diseases and the Risk of Cancer: A Cohort Study.

J Alzheimers Dis 2019 ;72(4):1269-1277

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Observational studies have shown inverse associations between neurological diseases, particularly dementia, and subsequent cancer risk, but is unknown whether this association is valid or arises from bias. We conducted a Danish nationwide cohort study using population-based health registries (1980-2012). The study included patients with dementia (n = 173,434) and with Parkinson's disease (n = 28,835). We followed patients for 10 years to assess subsequent cancer diagnoses. We computed absolute reduction in cancer risk attributable to dementia or Parkinson's disease (expected minus the observed number of cancer cases divided by the person time) and standardized incidence rate ratios (SIRs) as the observed to expected number of cancers, based on sex-, age-, and calendar year-standardized national incidence rates. During 10 years, the reduction in cancer cases were 79.9 per 10,000 person-years for Alzheimer's disease [SIR = 0.68 (95% CI: 0.66, 0.70)], 74.4 per 10,000 person-years for vascular dementia [SIR = 0.71 (95% CI: 0.67, 0.74)], 55.8 per 10,000 person-years [SIR = 0.77 (95% CI: 0.75, 0.78)] for all-cause dementia, and 4.0 per 10,000 person-years [SIR = 0.98 (95% CI: 0.95, 1.02) for Parkinson's disease. Associations were nearly similar for solid tumors diagnosed at localized, regional, or distant stages. We found an inverse association between dementia and cancer risk, with similar associations when considering only cancers diagnosed at distant stage. The cancer risk varied by type of dementia, with a gradient toward a stronger protective effect associated with Alzheimer's disease and vascular dementia, which may favor a biological explanation. Overall results do not show an inverse association between Parkinson's disease and cancer.
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http://dx.doi.org/10.3233/JAD-190867DOI Listing
December 2020

Lack of seasonality in occurrence of pericarditis, myocarditis, and endocarditis.

Ann Epidemiol 2019 09 10;37:77-80. Epub 2019 Jul 10.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.

Purpose: The etiology of pericarditis, myocarditis, and endocarditis is predominantly infectious, and infections often show seasonal variation. Little is known, however, about seasonal patterns in these cardiopathies.

Methods: Using Danish health care registries, we identified all patients with a first-time hospital-based diagnosis of pericarditis, myocarditis, or endocarditis between 1994 and 2016. We estimated peak-to-trough ratios from fitted sine curves to measure the intensity of seasonal variation in occurrence during the study period. Because randomness will lead to small apparent seasonal patterns, we also conducted a plasmode simulation to assess the degree of seasonality that randomness would produce.

Results: Crude peak-to-trough ratios of monthly frequencies summarized over a year were small. We estimated a peak-to-trough ratio of 1.10 (95% confidence interval [CI], 1.05-1.14) for pericarditis, 1.11 (95% CI, 1.02-1.21) for myocarditis, and 1.01 (95% CI, 1.00-1.07) for endocarditis. The simulated mean peak-to-trough ratios found after randomly reassigning the monthly frequencies within each year were 1.04 (95% CI, 1.00-1.09) for pericarditis, 1.04 (95% CI, 1.00-1.13) for myocarditis, and 1.04 (95% CI, 1.00-1.10), for endocarditis.

Conclusion: The data indicate no important seasonal variation in the occurrence of pericarditis, myocarditis, and endocarditis in Denmark between 1994 and 2016.
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http://dx.doi.org/10.1016/j.annepidem.2019.07.005DOI Listing
September 2019

Usefulness of CHADS-VASc Score to Predict Stroke Risk Independent of Atrial Fibrillation.

Am J Cardiol 2019 10 15;124(7):1059-1063. Epub 2019 Jul 15.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Cardiology, Regional Hospital West Jutland, Herning, Denmark.

The CHADS-VASc score is used to predict stroke risk among patients with atrial fibrillation (AF). We examined whether a CHADS-VASc score predicts stroke risk among individuals without hospital-diagnosed AF and quantified the magnitude of the association in comparison to AF patients. We used data from population-based medical registries (1995 to 2005) covering all Danish hospitals to identify patients diagnosed with AF (n = 122,980). We matched ≤5 non-AF individuals (n = 612,723) to each AF patient on the individual risk factors included in the CHADS-VASc score. We calculated 10-year absolute risk of ischemic and all-cause stroke in AF and non-AF individuals and compared the stroke risk between cohorts within strata of CHADS-VASc scores using Cox regression. The 10-year risk of ischemic/all-cause stroke was 4.4%/8.8% among non-AF individuals and 6.2%/12% in AF patients, corresponding to a risk difference of 1.8% for ischemic stroke and 3.3% for all-cause stroke. In both cohorts, the stroke risk correlated with increasing CHADS-VASc scores. However, in individuals with CHADS-VASc scores ≥5 who were <75 years or male, the absolute risk of ischemic stroke in individuals without AF exceeded the risk in AF patients. In the same subgroups, the hazard ratio approached unity. Similar results were observed for all-cause stroke. The CHADS-VASc score was associated with 10-year stroke risk also among individuals without hospital-diagnosed AF. In conclusion, primary prophylactic anticoagulation therapy may be relevant in male and younger non-AF individuals with CHADS-VASc scores ≥5. These findings should be confirmed in clinical trials.
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http://dx.doi.org/10.1016/j.amjcard.2019.06.028DOI Listing
October 2019

Risk of amyotrophic lateral sclerosis and other motor neuron disease among men with benign prostatic hyperplasia: a population-based cohort study.

BMJ Open 2019 07 4;9(7):e030015. Epub 2019 Jul 4.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Objectives: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder. Sleep disturbance may interfere with clearance of abnormal proteins that aggregate in neurodegenerative diseases. The objective of this study was to examine the association between benign prostatic hyperplasia (BPH), a common disorder causing nocturia and sleep disturbance, and risk of ALS and other motor neuron disease (MND). We hypothesised that men with BPH, in comparison to men in the general population, would be at increased risk.

Design: This is a nationwide, population-based cohort study.

Setting: This study was conducted among the population of Denmark.

Participants: We used linked Danish medical databases to identify all men with a first-time diagnosis of BPH between 1 January 1980 and 30 November 2013 and no prior diagnosis of MND (BPH cohort, n=223 131) and an age-matched general population comparison cohort of men without BPH or MND (n=1 115 642).

Primary Outcome Measure: The primary outcome is diagnosis of MND after the BPH diagnosis (index) date, with follow-up until MND diagnosis, emigration, death or 30 November 2013.

Results: We used Cox regression to compute adjusted HR, comparing men with and without BPH. After 34 years of follow-up, there were 227 cases of MND in the BPH cohort (incidence rate 0.13/1000 person-years) and 1094 MND cases in the comparison cohort (0.12/1000 person-years; HR 1.05, 95% CI 0.90 to 1.22). Risk did not vary by follow-up time.

Conclusions: BPH is not associated with an increased risk of ALS and other MND. Future studies should examine the relation between other disorders that disrupt sleep and MND risk in men and women.
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http://dx.doi.org/10.1136/bmjopen-2019-030015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615877PMC
July 2019

Venous Thromboembolism in Denmark: Seasonality in Occurrence and Mortality.

TH Open 2019 Apr 18;3(2):e171-e179. Epub 2019 Jun 18.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

 Many cardiovascular conditions exhibit seasonality in occurrence and mortality, but little is known about the seasonality of venous thromboembolism.  Using Danish registries, we identified all patients with deep vein thrombosis, pulmonary embolism, splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis during 1977-2016. We tallied monthly deaths occurring within 90 days of the venous thromboembolism diagnosis. We estimated peak-to-trough ratios and timing of the peak of both diagnoses and deaths summed over all years of the study period. The departure from 1.0 of the peak-to-trough ratio measures the intensity of any seasonal pattern.  We estimated a peak-to-trough ratio of 1.09 (95% confidence interval: 1.07-1.11) for deep vein thrombosis and 1.22 (1.19-1.24) for pulmonary embolism occurrence. The peak-to-trough ratios for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence were 1.10 (1.01-1.20), 1.19 (1.00-1.40), and 1.12 (1.07-1.17), respectively. The occurrence of all conditions peaked during winter or fall. In time trend analyses, the peak-to-trough ratio increased considerably for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis occurrence. In associated mortality, the peak-to-trough ratio for deep vein thrombosis was larger (1.15, 1.07-1.23) than that for pulmonary embolism (1.04, 1.01-1.08).  Excess winter risks were modest, but more marked for pulmonary embolism occurrence than for deep vein thrombosis occurrence. The seasonal pattern intensified throughout the study period for splanchnic vein thrombosis, cerebral vein thrombosis, and retinal vein thrombosis. The winter peak in mortality following pulmonary embolism was smaller than that for deep vein thrombosis.
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http://dx.doi.org/10.1055/s-0039-1692399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598086PMC
April 2019

Vaginal bleeding in early pregnancy and risk of occult cancer.

Int J Gynaecol Obstet 2019 09 13;146(3):387-389. Epub 2019 Jun 13.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Vaginal bleeding in early pregnancy is not associated with a higher cancer risk compared with pregnancies in women from the general population of similar age.
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http://dx.doi.org/10.1002/ijgo.12867DOI Listing
September 2019

Risk of thromboembolic and bleeding outcomes following hematological cancers: A Danish population-based cohort study.

J Thromb Haemost 2019 08 5;17(8):1305-1318. Epub 2019 Jun 5.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Background: Therapeutic advances have improved survival after hematological cancers. In turn, patients may be at increased risk of thromboembolic and bleeding events.

Objectives: To examine the risks of myocardial infarction (MI), ischemic stroke, venous thromboembolism (VTE), and bleeding requiring hospital contact in patients with hematological cancers.

Methods: We conducted a Danish population-based cohort study (2000-2013). We identified all adult hematological cancer patients and sampled a general population comparison cohort in a 1:5 ratio matched by age, sex, previous thromboembolic events, bleeding, and solid cancer. Ten-year absolute risks of thromboembolism and bleeding were calculated and hazard ratios (HRs) were computed, controlling for matching factors.

Results: Among 32 141 hematological cancer patients, the 10-year absolute risk of any thromboembolic or bleeding complication following hematological cancer was 19%: 3.3% for MI, 3.5% for ischemic stroke, 5.2% for VTE, and 8.5% for bleeding. Except among patients with myeloid leukemia, acute lymphoid leukemia, or myelodysplastic syndrome, the risk of thromboembolic events surpassed that of bleeding. The hematological cancer cohort overall was at increased risk for MI [HR = 1.36, 95% confidence interval (CI): 1.25-1.49], ischemic stroke (HR = 1.22, 95% CI: 1.12-1.33), VTE (HR = 3.37, 95% CI: 3.13-3.64), and bleeding (HR = 2.39, 95% CI: 2.26-2.53) compared with the general population.

Conclusions: Approximately 2 of 10 hematological cancer patients experienced MI, ischemic stroke, VTE, or bleeding requiring hospital contact within 10 years. The hematological cancer cohort had higher hazards of MI, ischemic stroke, VTE, and bleeding requiring hospital contact than a general population comparison cohort.
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http://dx.doi.org/10.1111/jth.14475DOI Listing
August 2019

Cardiovascular Disease Among Women Who Gave Birth to an Infant With a Major Congenital Anomaly.

JAMA Netw Open 2018 09 7;1(5):e182320. Epub 2018 Sep 7.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Importance: Having a child with a major birth defect can be a life-changing and stressful event that may be associated with higher cardiovascular disease (CVD) risk, yet the long-term burden of CVD for the child's mother is unknown.

Objective: To assess whether mothers of an infant born with a major congenital anomaly are at higher risk of CVD compared with a comparison cohort.

Design, Setting, And Participants: A population-based cohort study using individual-level linked registry data in Denmark included 42 943 women who gave birth to an infant with a major congenital anomaly between January 1, 1979, and December 31, 2013; and follow-up was conducted until 2015. A comparison group, comprising 428 401 randomly selected women, was 10:1 matched to each affected mother by maternal age, parity, and her infant's year of birth. Data analyses were performed between November 1, 2017, and February 28, 2018.

Exposures: Live birth of an infant with a major congenital anomaly.

Main Outcomes And Measures: The primary outcome was a CVD composite outcome of acute myocardial infarction, coronary revascularization, or stroke. Secondary outcomes included individual components of the CVD composite and other cardiovascular outcomes, including unstable angina, congestive heart failure, atrial fibrillation, peripheral artery disease, ischemic heart disease, and aortic aneurysm. Cox proportional hazards regression analyses generated hazard ratios (HRs), adjusted for maternal demographic, socioeconomic, and chronic health indicators.

Results: Median maternal age at baseline was 28.8 years (interquartile range, 25.3-32.5 years). After a median follow-up of 19.5 years (interquartile range, 9.9-27.6 years), 914 women whose infant had a major congenital anomaly experienced a CVD event (1.21 per 1000 person-years; 95% CI, 1.13-1.28 per 1000 person-years) vs 7516 women in the comparison group (0.99 per 1000 person-years; 95% CI, 0.97-1.01 per 1000 person-years), corresponding to an unadjusted HR of 1.23 (95% CI, 1.15-1.32), and an adjusted HR (aHR) of 1.15 (95% CI, 1.07-1.23). Women who gave birth to an infant with multiorgan anomalies had an even higher aHR (1.37; 95% CI, 1.08-1.72). Mothers of infants with a major anomaly also had an increased aHR of the individual components of the composite outcome and the other cardiovascular outcomes.

Conclusions And Relevance: Women whose child had a major congenital anomaly experienced a 15% to 37% higher risk of premature cardiovascular disease. These women may benefit from targeted interventions aimed at improving their cardiovascular health.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.2320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324496PMC
September 2018

Stress Disorders and Dementia in the Danish Population.

Am J Epidemiol 2019 03;188(3):493-499

Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark.

There is an association between stress and dementia. However, less is known about dementia among persons with varied stress responses and sex differences in these associations. We used this population-based cohort study to examine dementia among persons with a range of clinician-diagnosed stress disorders, as well as the interaction between stress disorders and sex in predicting dementia, in Denmark from 1995 to 2011. This study included Danes aged 40 years or older with a stress disorder diagnosis (n = 47,047) and a matched comparison cohort (n = 232,141) without a stress disorder diagnosis with data from 1995 through 2011. Diagnoses were culled from national registries. We used Cox proportional hazards regression to estimate associations between stress disorders and dementia. Risk of dementia was higher for persons with stress disorders than for persons without such diagnosis; adjusted hazard ratios ranged from 1.6 to 2.8. There was evidence of an interaction between sex and stress disorders in predicting dementia, with a higher rate of dementia among men with stress disorders except posttraumatic stress disorder, for which women had a higher rate. Results support existing evidence of an association between stress and dementia. This study contributes novel information regarding dementia risk across a range of stress responses, and interactions between stress disorders and sex.
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http://dx.doi.org/10.1093/aje/kwy269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395166PMC
March 2019