Use of Latent Class Analysis to Predict Intensive Care Unit Admission and Mortality in Children with a Major Congenital Anomaly.

OBJECTIVE: To define major congenital anomaly (CA) subgroups and assess outcome variability based on defined subgroups. STUDY DESIGN: This population-based cohort study used registries in Denmark for children born with a major CA between January 1997 and December 2016, with follow-up until December 2018. We performed a latent class analysis (LCA) using child and family clinical and sociodemographic characteristics present at birth, incorporating additional variables occurring until age of 24 months. Cox proportional hazards regression models estimated hazard ratios (HRs) of pediatric mortality and intensive care unit (ICU) admissions for identified LCA classes. RESULTS: The study included 27 192 children born with a major CA. Twelve variables led to a 4-class solution (entropy = 0.74): (1) children born with higher income and fewer comorbidities (55.4%), (2) children born to young mothers with lower income (24.8%), (3) children born prematurely (10.0%), and (4) children with multiorgan involvement and developmental disability (9.8%). Compared with those in Class 1, mortality and ICU admissions were highest in Class 4 (HR = 8.9, 95% CI = 6.4-12.6 and HR = 4.1, 95% CI = 3.6-4.7, respectively). More modest increases were observed among the other classes for mortality and ICU admissions (Class 2: HR = 1.7, 95% CI = 1.1-2.5 and HR = 1.3, 95% CI = 1.1-1.4, respectively; Class 3: HR = 2.5, 95% CI = 1.5-4.2 and HR = 1.5, 95% CI = 1.3-1.9, respectively). CONCLUSIONS: Children with a major CA can be categorized into meaningful subgroups with good discriminative ability. These groupings may be useful for risk-stratification in outcome studies.

Lifetime and 10-year cardiovascular risk prediction in individuals with type 1 diabetes: The LIFE-T1D model.

AIMS: To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. MATERIALS AND METHODS: A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. RESULTS: During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. CONCLUSIONS: The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation.

Sex Differences in Psychopathology Following Potentially Traumatic Experiences.

Importance: Various psychopathology may follow trauma; however, sex differences in these ranging manifestations of posttraumatic psychopathology remain understudied. Objective: To investigate sex-specific incidence of posttraumatic psychopathology. Design, Setting, and Participants: This population-based cohort study of Danish national health registries included a cohort of individuals who experienced a potentially traumatic event (PTE) from 1994 to 2016. Individuals were further categorized by presence of any pretrauma psychopathology. A comparison group of individuals who experienced a nontraumatic stressor (nonsuicide death of a first-degree relative) was examined as a reference cohort. Exposures: At least 1 of 8 PTEs (eg, physical assault, transportation accident) derived through health registry International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, with additional qualifiers to improve classification accuracy. Main Outcomes and Measures: Incidence of 9 categories of ICD-10 psychiatric disorders recorded in registries within 5 years of PTEs. The standardized morbidity ratios (SMRs) for psychopathology outcomes were also calculated to compare individuals experiencing PTEs with those experiencing a nontraumatic stressor. Results: This study included 1 398 026 individuals who had been exposed to trauma (475 280 males [34.0%]; 922 750 females [66.0%]). The group of males who had been exposed to trauma were evenly distributed across age, while most females in the trauma-exposed group were aged 16 to 39 years (592 385 [64.2%]). Males and females were equally distributed across income quartiles and predominantly single. Following PTEs, the most common diagnosis was substance use disorders for males (35 160 [7.4%]) and depressive disorders for females (29 255 [3.2%]); incidence proportions for these and other disorders were higher among males and females with any pretrauma psychopathology. Certain PTEs had elevated onset of various psychiatric disorders and some sex differences emerged. Following physical assault, associations were found with schizophrenia or psychotic disorders for males (SMR, 17.5; 95% CI, 15.9-19.3) and adult personality disorders for females (SMR, 16.3; 95% CI, 14.6-18.3). For noninterpersonal PTEs, males had larger SMRs for substance use, schizophrenia or psychotic disorders, and adult personality disorders (SMR, 43.4; 95% CI, 41.9-45.0), and females had larger SMRs for depressive disorders (SMR, 19.0; 95% CI, 18.6-19.4). Sex differences were also observed, particularly when considering pretrauma psychopathology. For example, among interpersonal PTEs, males were most likely to develop substance use disorders after physical assault, whereas females were more likely to develop various disorders, with stronger associations seen for females without pretrauma psychiatric diagnoses. Among noninterpersonal PTEs, exposure to toxic substance showed robust associations with psychopathology, particularly in those without pretrauma psychopathology, with sex-specific differences across psychiatric categories. Conclusions and Relevance: Mental disorders after trauma were wide-ranging for males and females, and sex differences in patterns of posttraumatic psychopathology were more pronounced when accounting for pretrauma psychopathology. Findings provide new insights for sex-relevant PTEs and their mental health consequences. It also outlines future directions for advancing understanding of a constellation of posttraumatic psychopathology in males and females.

Adverse perinatal events and maternal interpregnancy weight change: A population-based observational study.

OBJECTIVE: Mothers whose newborn experiences adversity may neglect their own health to care for their affected infant or following a perinatal death. Weight gain after pregnancy is one measure of maternal self-care. We measured interpregnancy weight gain among women whose child had an adverse perinatal event. METHODS: This population-based observational study included 192 154 primigravid women with two consecutive singleton births in Ontario, Canada. Outcomes included net weight gain, and adjusted odds ratios (aOR) of moving to a higher body mass index (BMI) category between pregnancies, comparing women whose child did versus did not experience either a perinatal death, prematurity, severe neonatal morbidity, major congenital anomaly, or severe neurologic impairment. RESULTS: Perinatal death was associated with a +3.5 kg (95% confidence interval [CI]: 2.1-4.9) net higher maternal weight gain in the subsequent pregnancy. Relative to term births, preterm birth <32 weeks (+3.2 kg, 95% CI: 1.9-4.6), 32-33 weeks (+1.8 kg, 95% CI: 0.7-2.8) and 34-36 weeks (+0.9 kg, 95% CI: 0.6-1.3) were associated with higher net weight gain. Having an infant with severe neonatal morbidity was associated with a +1.2 kg (95% CI: 0.3-2.1) weight gain. Likewise, the aOR of moving to a higher BMI category was 1.27 (95% CI, 1.14-1.42) following a perinatal death, 1.21 (95% CI: 1.04-1.41) after a preterm birth <32 weeks, and 1.11 (95% CI: 1.02-1.22) with severe neonatal morbidity. CONCLUSION: Greater interpregnancy weight gain, and movement to a higher BMI category, are each more likely in a woman whose first-born was affected by certain major adverse perinatal events.

Antihypertensive Medications and PTSD Incidence in a Trauma Cohort.

Objective: Antihypertensive medications have been examined as agents for posttraumatic stress disorder (PTSD) prevention in trauma-exposed individuals, given well-documented associations between PTSD and increased risk of cardiovascular disease and purported trauma-relevant mechanisms of action for these medications. Evidence regarding the effectiveness of such drugs for this purpose remains mixed.Methods: We conducted a national population-based cohort study using data from Danish national registries to assess whether 4 classes of antihypertensive drugs (beta-adrenoceptor blockers [beta blockers], angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, and calcium channel blockers) were associated with a decreased incidence of PTSD (diagnosed according to ICD-10) over a 22-year study period. Data for this study originated from a population-based cohort of over 1.4 million persons who experienced a traumatic event between 1994 and 2016 in Denmark. We calculated the incidence rate of PTSD per 100,000 person-years among persons who filled a prescription for each class of drug in the 60 days prior to a traumatic event and for corresponding unexposed comparison groups. We then used Cox proportional hazards regression to compare the rate of PTSD among persons who filled an antihypertensive medication prescription within 60 days before their trauma to the rate among persons who did not.Results: We found evidence that calcium channel blockers were associated with a decreased incidence of PTSD (adjusted hazard ratio = 0.63, 95% confidence interval [CI] = 0.34, 1.2); all other antihypertensive medication classes had null or near null associations.Conclusions: These findings lay a foundation for additional research focusing on antihypertensive medications that appear most effective in reducing PTSD incidence following trauma and for additional replication work aimed at continuing to clarify the disparate findings reported in the literature to date.

Risk of psychopathology following traumatic events among immigrants and native-born persons in Denmark.

PURPOSE: Immigrants may have increased risk of mental disorders compared with native-born persons. We aimed to expand the limited research on immigrants' posttraumatic psychopathology related to traumatic experiences in their country of resettlement. METHODS: We obtained data from a cohort of Danish residents with ≥ 1 traumatic event recorded in health and administrative national registries during 1994-2016. We calculated risks of posttraumatic stress disorder (PTSD), depression, and substance use disorders (SUD) within 5 years post-trauma among native-born Danes and immigrants who had been in Denmark for ≥ 10 years at the time of their index trauma (including immigrants overall and immigrants from specific regions). Risks were compared via age- and sex-standardized risk ratios (SRR) with 95% confidence intervals (CI). We restricted to persons with no record of the disorder under investigation in the 10 years pre-trauma, and stratified by non-interpersonal (e.g., transport accidents) versus interpersonal trauma (e.g., assaults). RESULTS: Following non-interpersonal trauma, immigrants were more likely than native-born Danes to be diagnosed with PTSD (SRR = 5.2, 95% CI 4.6, 5.9), about as likely to be diagnosed with depression (SRR = 0.98, 95% CI 0.92, 1.1), and less likely to be diagnosed with SUD (SRR = 0.89, 95% CI 0.82, 0.95). Results were similar following interpersonal trauma, except the SRR for PTSD was reduced in magnitude (SRR = 3.0, 95% CI 1.7, 5.4). There were differences by region of birth. CONCLUSION: Immigrants to Denmark have higher risk of PTSD following traumatic experiences than do native-born Danes, possibly due to the combined influence of adverse pre-, peri-, and/or post-migration experiences.

Risk factors for suicide one year after discharge from hospitalization for physical illness in Denmark.

While suicide risk following psychiatric hospitalization has been studied extensively, risk following hospitalization for physical illness is less well understood. We used random forests to examine risk factors for suicide in the year following physical illness hospitalization in Denmark. In this case-cohort study, suicide cases were all individuals who died by suicide within one year of a hospitalization for a physical illness (n = 4563) and the comparison subcohort was a 5% random sample of individuals living in Denmark on January 1, 1995 who had a hospitalization for a physical illness between January 1, 1995 and December 31, 2015 (n = 177,664). We used random forests to examine identify the most important predictors of suicide stratified by sex. For women, the top 10 most important variables for random forest prediction were all related to psychiatric diagnoses. For men, many physical health conditions also appeared important to suicide prediction. Among the top 10 variables in the variable importance plot for men were influenza, injuries to the head, nervous system surgeries, and cerebrovascular diseases. Suicide prediction after a physical illness hospitalization requires comprehensive consideration of different and multiple factors for each sex.

Risk of Major Cardiovascular and Cerebrovascular Events in Users of Lisdexamfetamine and Other Medications for Attention-Deficit/Hyperactivity Disorder in Denmark and Sweden: A Population-Based Cohort Study.

INTRODUCTION: This study aimed to estimate risks of cardiovascular and cerebrovascular events in patients treated with lisdexamfetamine dimesylate (LDX) compared with patients previously treated with other attention-deficit/hyperactivity disorder (ADHD) medications (amphetamine, dexamphetamine, methylphenidate or atomoxetine). METHODS: This population-based cohort study used data from Danish and Swedish medical and administrative national registers. The LDX cohort included adult patients initiating LDX with at least 12 months' data preceding first LDX dispensing (index date). A random sample of patients treated with at least one non-LDX ADHD medication in the 6-24 months (but not less than 6 months) before index date (previous-users cohort) were matched to LDX users on age, sex, region and calendar year. The primary outcome, a composite of major adverse cardiovascular and cerebrovascular events (MACE), included first hospitalisation for acute myocardial infarction or stroke and out-of-hospital coronary heart disease or cerebrovascular disease death. Incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) of MACE were estimated using Poisson regression. RESULTS: From Denmark/Sweden, 5516/40,163 LDX users and 27,494/200,389 previous users were included. In Denmark, IRs of MACE/1000 person-years (95% CI) were similar for LDX (1.63 [0.85-3.14]) and previous users (1.61 [1.28-2.01]). In Sweden, IRs (95% CI) were 1.40 (1.09-1.79) in LDX users and 1.17 (1.00-1.38) in previous users. Adjusted MACE IRRs (95% CI) for LDX versus previous use were 1.01 (0.48-2.13) in Denmark, 1.13 (0.75-1.71) in Sweden, and 1.10 (0.77-1.58) in the pooled analysis. CONCLUSION: Our findings suggest little to no increased risk of cardiovascular and cerebrovascular events in patients treated with LDX compared with patients previously treated with other ADHD medications.

Evaluation of Neurologic and Psychiatric Outcomes After Hospital Discharge Among Adult Survivors of Cardiac Arrest.

Importance: Long-term risks of neurologic and psychiatric disease after cardiac arrest are largely unknown. Objective: To examine the short-term and long-term risks of common neurologic outcomes (stroke, epilepsy, Parkinson disease, and dementia) and psychiatric outcomes (depression and anxiety) in patients after hospitalization for cardiac arrest. Design, Setting, and Participants: This nationwide population-based cohort study with 21 years of follow-up included data on 250 838 adults from all Danish hospitals between January 1, 1996, and December 31, 2016. Danish medical registries were used to identify all patients with a first-time diagnosis of cardiac arrest and 2 matched comparison cohorts. The first comparison cohort included patients with a first-time diagnosis of myocardial infarction; the second comprised people from the general population. Data analysis was performed from November 1, 2020, to June 30, 2021. Exposures: In-hospital or out-of-hospital cardiac arrest. Main Outcomes and Measures: Neurologic and psychiatric outcomes after hospital discharge were ascertained using medical registries. Twenty-one-year hazard ratios (HRs) and 95% CIs were computed based on Cox regression analysis, controlled for matching factors, and adjusted for comorbidity and socioeconomic status. Results: Among the 250 838 individuals included in this study (median age, 67 years [IQR, 57-76 years]; 173 946 [69.3%] male), 3 groups were identified: 12 046 patients with cardiac arrest, 118 332 patients with myocardial infarction, and 120 460 people from the general population. Compared with patients with myocardial infarction, patients with cardiac arrest had an increased rate of ischemic stroke (10 per 1000 persons; HR, 1.30; 95% CI, 1.02-1.64) and hemorrhagic stroke (2 per 1000 persons; HR, 2.03; 95% CI, 1.12-3.67) in the first year after discharge. During the full follow-up period, rates were as follows: for epilepsy, 28 per 1000 persons (HR, 2.01; 95% CI, 1.66-2.44); for dementia, 73 per 1000 persons (HR, 1.23; 95% CI, 1.09-1.38); for mood disorders including depression, 270 per 1000 persons (HR, 1.78; 95% CI, 1.68-1.89); and for anxiety, 187 per 1000 persons (HR, 1.98; 95% CI, 1.85-2.12). The rate of Parkinson disease was similar in the 2 cohorts (8 per 1000 persons; HR, 0.96; 95% CI, 0.65-1.42). The rates of the aforementioned outcomes were highest during the first year after cardiac arrest and then declined over time. Comparisons between the cohort of patients with cardiac arrest and the general population cohort showed higher rates of epilepsy, dementia, depression, and anxiety in the cardiac arrest group. Conclusions and Relevance: In this cohort study, patients discharged after cardiac arrest had an increased rate of subsequent stroke, epilepsy, dementia, depression, and anxiety compared with patients with myocardial infarction and people from the general population, with declining rates over time. These findings suggest the need for preventive strategies and close follow-up of cardiac arrest survivors.

Interpregnancy Weight Change Among Mothers of a Child with a Major Congenital Anomaly: A Danish Nationwide Cohort Study.

Background: The mother of an infant with a major congenital anomaly is at a higher risk of premature cardiometabolic disease, possibly from chronic caregiver stress and distraction from self-care, including maintaining a healthy lifestyle and body weight. Objective: To compare the interpregnancy weight gain in women whose first infant had a major congenital anomaly vs those without an affected child. Methods: Multivariable linear regression compared women whose infant had an anomaly vs those whose infant did not, adjusting for interpregnancy time interval, demographics, smoking and health status at the first pregnancy. Results: Of the 199,536 women who had two consecutive singleton births, 4035 (2.0%) had a child with an anomaly at the first birth. The mean (SD) maternal BMI at the start of the first pregnancy was 24.1 (4.7) and 23.7 (4.4) kg/m2 in women with, and without, an anomaly-affected newborn. By the start of the second pregnancy, 3 years later, they had gained a mean (SD) of 2.2 (5.5) and 1.8 (5.2) kg, respectively - an adjusted absolute higher gain of 0.26 kg (95% CI 0.10 to 0.42) in women with an anomaly-affected first-born infant compared to those with an unaffected pregnancy. The adjusted interpregnancy weight gain difference was greatest in women whose first-born infant had a multi-organ anomaly at 0.59 kg (95% CI 0.02 to 1.16). The adjusted odds ratio of moving from a normal BMI category of 18.5-24.9 kg/m2 in the first pregnancy, to an overweight or obese BMI category of 25+ kg/m2 in the second, was 1.18 (95% CI 1.06 to 1.32) comparing mothers with vs without an anomaly-affected child in the first pregnancy. Conclusion: Mothers of an infant with a major congenital anomaly have a modestly higher interpregnancy weight gain and tend to climb to a higher BMI category. The long-term implications of this greater weight trajectory require further study.

Pre-trauma predictors of severe psychiatric comorbidity 5 years following traumatic experiences.

BACKGROUND: A minority of persons who have traumatic experiences go on to develop post-traumatic stress disorder (PTSD), leading to interest in who is at risk for psychopathology after these experiences. Complicating this effort is the observation that post-traumatic psychopathology is heterogeneous. The goal of this nested case-control study was to identify pre-trauma predictors of severe post-traumatic psychiatric comorbidity, using data from Danish registries. METHODS: The source population for this study was the population of Denmark from 1994 through 2016. Cases had received three or more psychiatric diagnoses (across all ICD-10 categories) within 5 years of a traumatic experience (n = 20 361); controls were sampled from the parent cohort using risk-set sampling (n = 81 444). Analyses were repeated in samples stratified by pre-trauma psychiatric diagnoses. We used machine learning methods (classification and regression trees and random forest) to determine the important predictors of severe post-trauma psychiatric comorbidity from among hundreds of pre-trauma predictor variables spanning demographic and social variables, psychiatric and somatic diagnoses and filled medication prescriptions. RESULTS: In the full sample, pre-trauma psychiatric diagnoses (e.g. stress disorders, alcohol-related disorders, personality disorders) were the most important predictors of severe post-trauma psychiatric comorbidity. Among persons with no pre-trauma psychiatric diagnoses, demographic and social variables (e.g. marital status), type of trauma, medications used primarily to treat psychiatric symptomatology, anti-inflammatory medications and gastrointestinal distress were important to prediction. Results among persons with pre-trauma psychiatric diagnoses were consistent with the overall sample. CONCLUSIONS: This study builds on the understanding of pre-trauma factors that predict psychopathology following traumatic experiences, by examining a broad range of predictors of post-trauma psychopathology and comorbidity beyond PTSD.

Risk of Parkinson Disease and Secondary Parkinsonism in Myocardial Infarction Survivors.

Background In addition to primary neurodegenerative processes, vascular disorders, such as stroke, can lead to parkinsonism. However, some cardiovascular risk factors, such as smoking and elevated cholesterol levels, are associated with reduced risk of Parkinson disease. We examined the risk of Parkinson disease and secondary parkinsonism in 1-year survivors of myocardial infarction (MI). Methods and Results We conducted a nationwide population-based matched cohort study using Danish medical registries from 1995 to 2016. We identified all patients with a first-time MI diagnosis and sampled a sex-, age-, and calendar year-matched general population comparison cohort without MI. Cox regression analysis was used to compute adjusted hazard ratios (aHRs) for Parkinson disease and secondary parkinsonism, controlled for matching factors and adjusted for relevant comorbidities and socioeconomic factors. We identified 181 994 patients with MI and 909 970 matched comparison cohort members (median age, 71 years; 62% men). After 21 years of follow-up, the cumulative incidence was 0.9% for Parkinson disease and 0.1% for secondary parkinsonism in the MI cohort. Compared with the general population cohort, MI was associated with a decreased risk of Parkinson disease (aHR, 0.80; 95% CI, 0.73-0.87) and secondary parkinsonism (aHR, 0.72; 95% CI, 0.54-0.94). Conclusions MI was associated with a 20% decreased risk of Parkinson disease and 28% decreased risk of secondary parkinsonism. Reduced risk may reflect an inverse relationship between cardiovascular risk factors and Parkinson disease.

Using Danish national registry data to understand psychopathology following potentially traumatic experiences.

Research on posttraumatic psychopathology has focused primarily on posttraumatic stress disorder (PTSD); other posttraumatic psychiatric diagnoses are less well documented. The present study aimed to (a) develop a methodology to derive a cohort of individuals who experienced potentially traumatic events (PTEs) from registry-based data and (b) examine the risk of psychopathology within 5 years of experiencing a PTE. Using data from Danish national registries, we created a cohort of individuals with no age restrictions (range: 0-108 years) who experienced at least one of eight possible PTEs between 1994 and 2016 (N = 1,406,637). We calculated the 5-year incidence of nine categories of ICD-10 psychiatric disorders among this cohort and examined standardized morbidity ratios (SMRs) comparing the incidence of psychopathology in this group to the incidence in a nontraumatic stressor cohort (i.e., nonsuicide death of a relative; n = 423,270). Stress disorders (2.5%), substance use disorders (4.1%), and depressive disorders (3.0%) were the most common diagnoses following PTEs. Overall, the SMRs for the associations between any PTE and psychopathology varied from 1.9, 95% CI [1.9, 2.0], for stress disorders to 5.2, 95% CI [5.1. 5.3], for personality disorders. All PTEs except pregnancy-related trauma were associated with all forms of psychopathology. Associations were consistent regardless of whether a stress disorder was present. Traumatic experiences have a broad impact on psychiatric health. The present findings demonstrate one approach to capturing trauma exposure in medical record registry data. Increased traumatic experience characterization across studies will help improve the field's understanding of posttraumatic psychopathology.

Long-term Risk of Parkinson Disease Following Influenza and Other Infections.

Importance: Influenza has been associated with the risk of developing Parkinson disease, but the association is controversial. Objective: To examine whether prior influenza and other infections are associated with Parkinson disease more than 10 years after infection. Design, Setting, and Participants: This case-control study used data from 1977 to 2016 from the Danish National Patient Registry. All individuals with Parkinson disease, excluding those with drug-induced parkinsonism, were included and matched to 5 population controls on sex, age, and date of Parkinson diagnosis. Data were analyzed from December 2019 to September 2021. Exposures: Infections were ascertained between 1977 and 2016 and categorized by time from infection to Parkinson disease diagnosis. To increase specificity of influenza diagnoses, influenza exposure was restricted to months of peak influenza activity. Main Outcomes and Measures: Parkinson disease diagnoses were identified between January 1, 2000, and December 31, 2016. Crude and adjusted odds ratios (ORs) and 95% CIs were calculated by conditional logistic regression overall and stratified by time between infection and Parkinson disease (5 years or less, more than 5 to 10 years, more than 10 years). Results: Of 61 626 included individuals, 23 826 (38.7%) were female, and 53 202 (86.3%) were older than 60 years. A total of 10 271 individuals with Parkinson disease and 51 355 controls were identified. Influenza diagnosed at any time during a calendar year was associated with Parkinson disease more than 10 years later (OR, 1.73; 95% CI, 1.11-2.71). When influenza exposure was restricted to months of highest influenza activity, an elevated OR with a wider confidence interval was found (OR, 1.52; 95% CI, 0.80-2.89). There was no evidence of an association with any type of infection more than 10 years prior to Parkinson disease (OR, 1.04; 95% CI, 0.98-1.10). Several specific infections yielded increased odds of Parkinson disease within 5 years of infection, but results were null when exposure occurred more than 10 years prior. Conclusions and Relevance: In this case-control study, influenza was associated with diagnoses of Parkinson disease more than 10 years after infection. These observational data suggest a link between influenza and Parkinson disease but do not demonstrate causality. While other infections were associated with Parkinson disease diagnoses soon after infection, null associations after more than 10 years suggest these shorter-term associations are not causal.

Latent classes of posttraumatic psychiatric comorbidity in the general population.

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.

Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study.

OBJECTIVES: To assess the risks of myocardial infarction, stroke, peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter and heart failure in patients with constipation compared with a general population cohort. DESIGN: Population-based matched cohort study. SETTING: All Danish hospitals and hospital outpatient clinics from 2004 to 2013. PARTICIPANTS: Patients with a constipation diagnosis matched on age, sex and calendar year to 10 individuals without constipation from the general population. MAIN OUTCOMES MEASURES: Comorbidity-adjusted and medication-adjusted hazard ratios (aHRs) for cardiovascular outcomes based on Cox regression analysis. RESULTS: 83 239 patients with constipation were matched to 832 384 individuals without constipation. The median age at constipation diagnosis was 46.5% and 41% were men. Constipation was strongly associated with venous thromboembolism (aHR 2.04, 95% CI 1.89 to 2.20), especially splanchnic venous thrombosis (4.23, 95% CI 2.45 to 7.31). Constipation was also associated with arterial events, including myocardial infarction (1.24, 95% CI 1.14 to 1.35), ischaemic stroke (1.50, 95% CI 1.41 to 1.60), haemorrhagic stroke (1.46, 95% CI 1.26 to 1.69), peripheral artery disease (1.34, 95% CI 1.20 to 1.50), atrial fibrillation or atrial flutter (1.27, 95% CI 1.20 to 1.34) and heart failure (1.52, 95% CI 1.42 to 1.62). The associations were strongest during the first year after the constipation diagnosis and strengthened with an increased number of laxative prescriptions. CONCLUSIONS: Constipation was associated with an increased risk of several cardiovascular diseases, in particular venous thromboembolism.

Cohort profile: the Funen Diabetes Database-a population-based cohort of patients with diabetes in Denmark.

PURPOSE: Detailed population-based data are essential to understanding the epidemiology of diabetes and its clinical course. This article describes the Funen Diabetes Database (FDDB). The purpose of the FDDB was to serve as a shared electronic medical record system for healthcare professionals treating patients with diabetes. The cohort can also be used for research. PARTICIPANTS: The FDDB covers a geographical area of almost 500 000 Danish inhabitants. It currently includes 3691 patients with type 1 diabetes, 19 085 patients with type 2 diabetes, 292 patients with other types of diabetes and 5992 patients with an unknown type of diabetes. Patients have been continuously enrolled from general practitioners and endocrinology departments in the Funen area in Denmark since 2003. Patients undergo a clinical work-up at their first diabetes contact and during follow-up visits. The information collected includes type of diabetes contact, blood pressure, height, weight, lifestyle factors (smoking, exercise), laboratory records (eg, haemoglobin A1c and cholesterol levels), results from foot examinations (eg, pulse, cutaneous sensitivity and ankle brachial index), results from eye examinations (eg, degree of retinopathy assessed by retinal photo and eye examination), glucose-lowering drugs and diabetic complications. FINDINGS TO DATE: The FDDB cohort was followed for a total of 212 234 person-years up to 2016. A cross-sectional study described the prevalence of diabetic retinopathy and its associated risk factors. The clinical outcomes of patients with type 1 diabetes, type 2 diabetes and latent autoimmune diabetes in adults have been assessed. Linkage to population-based medical registries with complete follow-up has enabled the collection of extensive continuous data on general practice contacts, diagnoses and procedures from hospital contacts, medication use and mortality. FUTURE PLANS: The FDDB serves as a strong data resource that will be used in future studies of diabetes epidemiology with focus on occurrence, risk factors, treatment, complications and prognosis.