Showing papers by "Carsten Bøcker Pedersen published in 2022"

Mortality Associated With Mental Disorders and Comorbid General Medical Conditions

Abstract: This cohort study examines data from Danish nationwide registries to evaluate how comorbidity between mental disorders and general medical conditions affects life expectancy.

Nitrate in drinking water and risk of birth defects: Findings from a cohort study of over one million births in Denmark

Abstract: A few studies have reported an increased risk of birth defects (BD) with maternal exposure to nitrate in drinking water. We examined this association in a large cohort study with well-characterized exposure.Danish singletons liveborn to Danish-born parents from 1991-2013 were identified using civil and patient registries (n=1,018,914). Exposure to nitrate was estimated using a spatial model based on national data linked with individual addresses. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression.In total, 33,182 cases of BD were identified. Nitrate concentrations were generally well below US and EU standards. We observed an exposure-response relationship (p=0·004) between nitrate during pregnancy and eye BD, and increased risk in the highest exposure group (≥25 mg/L nitrate) (OR: 1·29; 95% CI: 1·00, 1·66). An interaction was observed between maternal age and continuous nitrate exposure for nervous system BD (p<0·001) indicating an increased risk among mothers <25 years-of-age (OR for 10 mg/L (OR10): 1·20; 95% CI: 1·06, 1·35). An interaction (p<0.01) with maternal age and continuous nitrate exposure was also observed for ear, face, and neck BD indicating an increased risk among babies born to mothers <25 years-of-age (OR10: 1·35; 95% CI: 1·11, 1·66). There was evidence of an inverse exposure-response relationship for any, digestive system, female genital, and urinary BD.Our study is the first to report an association between nitrate and eye BD and BD of the ear, face, and neck. It also provides support to prior reports of increased risk of nervous system BD.This study was supported by a grant from the United States National Institute of Environmental Health Sciences (R01 ES027823-01A1).

Temporal changes in sex‐ and age‐specific incidence profiles of mental disorders—A nationwide study from 1970 to 2016

Abstract: Information on mental disorders over time is critical for documenting changes in population burden, and aiding understanding of potential causal and non‐causal factors. The aim of this study was to provide temporal changes in the sex‐ and age‐specific incidence rates (IR) of mental disorders diagnosed in Danish hospitals during five decades and investigate whether such changes may be attributable to changes in administrative reporting practice.

The cost of mental disorders in Denmark: a register-based study

Abstract: Abstract The aim of the study was to undertake a detailed analysis of healthcare cost, public transfer payments, and income loss associated with a broad range of mental disorders in Denmark. Based on all persons living in Denmark, we identified those with a hospital diagnosis of one of 18 types of mental disorders and 10 age- and sex-matched controls per case. For each mental disorder, the outcomes were nationwide totals, cost per case, and cost per capita, investigated by sex, age strata, and the number of years after diagnosis. We found a substantial annual income loss of 5 billion Euros and excess healthcare cost of 1 billion Euros for persons with any mental disorder. Each mental disorder was associated with an income loss, excess healthcare cost, and excess public transfer payments compared to matched controls. An interactive data visualisation site with summary data is available at https://nbepi.com/cost .

Analysis of mortality metrics associated with a comprehensive range of disorders in Denmark, 2000 to 2018: A population-based cohort study

Abstract: Background The provision of different types of mortality metrics (e.g., mortality rate ratios [MRRs] and life expectancy) allows the research community to access a more informative set of health metrics. The aim of this study was to provide a panel of mortality metrics associated with a comprehensive range of disorders and to design a web page to visualize all results. Methods and findings In a population-based cohort of all 7,378,598 persons living in Denmark at some point between 2000 and 2018, we identified individuals diagnosed at hospitals with 1,803 specific categories of disorders through the International Classification of Diseases-10th Revision (ICD-10) in the National Patient Register. Information on date and cause of death was obtained from the Registry of Causes of Death. For each of the disorders, a panel of epidemiological and mortality metrics was estimated, including incidence rates, age-of-onset distributions, MRRs, and differences in life expectancy (estimated as life years lost [LYLs]). Additionally, we examined models that adjusted for measures of air pollution to explore potential associations with MRRs. We focus on 39 general medical conditions to simplify the presentation of results, which cover 10 broad categories: circulatory, endocrine, pulmonary, gastrointestinal, urogenital, musculoskeletal, hematologic, mental, and neurologic conditions and cancer. A total of 3,676,694 males and 3,701,904 females were followed up for 101.7 million person-years. During the 19-year follow-up period, 1,034,273 persons (14.0%) died. For 37 of the 39 selected medical conditions, mortality rates were larger and life expectancy shorter compared to the Danish general population. For these 37 disorders, MRRs ranged from 1.09 (95% confidence interval [CI]: 1.09 to 1.10) for vision problems to 7.85 (7.77 to 7.93) for chronic liver disease, while LYLs ranged from 0.31 (0.14 to 0.47) years (approximately 16 weeks) for allergy to 17.05 (16.95 to 17.15) years for chronic liver disease. Adjustment for air pollution had very little impact on the estimates; however, a limitation of the study is the possibility that the association between the different disorders and mortality could be explained by other underlying factors associated with both the disorder and mortality. Conclusions In this study, we show estimates of incidence, age of onset, age of death, and mortality metrics (both MRRs and LYLs) for a comprehensive range of disorders. The interactive data visualization site (https://nbepi.com/atlas) allows more fine-grained analysis of the link between a range of disorders and key mortality estimates.

Postpartum depression: a developed and validated model predicting individual risk in new mothers

Abstract: Postpartum depression (PPD) is a serious condition associated with potentially tragic outcomes, and in an ideal world PPDs should be prevented. Risk prediction models have been developed in psychiatry estimating an individual's probability of developing a specific condition, and recently a few models have also emerged within the field of PPD research, although none are implemented in clinical care. For the present study we aimed to develop and validate a prediction model to assess individualized risk of PPD and provide a tentative template for individualized risk calculation offering opportunities for additional external validation of this tool. Danish population registers served as our data sources and PPD was defined as recorded contact to a psychiatric treatment facility (ICD-10 code DF32-33) or redeemed antidepressant prescriptions (ATC code N06A), resulting in a sample of 6,402 PPD cases (development sample) and 2,379 (validation sample). Candidate predictors covered background information including cohabitating status, age, education, and previous psychiatric episodes in index mother (Core model), additional variables related to pregnancy and childbirth (Extended model), and further health information about the mother and her family (Extended+ model). Results indicated our recalibrated Extended model with 14 variables achieved highest performance with satisfying calibration and discrimination. Previous psychiatric history, maternal age, low education, and hyperemesis gravidarum were the most important predictors. Moving forward, external validation of the model represents the next step, while considering who will benefit from preventive PPD interventions, as well as considering potential consequences from false positive and negative test results, defined through different threshold values.

Prenatal exposure to nitrate from drinking water and the risk of preterm birth

Abstract: Background: Evidence is emerging that preterm birth (PTB, birth before 37 completed weeks of gestation), a risk factor for neonatal mortality and future morbidity, may be induced by maternal nitrate (NO3−) exposure from drinking water. The objective of this study is to assess the association between maternal exposure to nitrate and the risk of PTB in a nationwide study of liveborn singletons. Methods: We estimated maternal nitrate exposure from household tap water for 1,055,584 births in Denmark to Danish-born parents during 1991–2015 by linkage of individual home address(es) with nitrate concentrations from a national monitoring database. Nitrate exposure during pregnancy was modeled using four categories and continuously. Logistic models adjusted for sex, birth year, birth order, urbanicity, and maternal age, smoking, education, income, and employment, with generalized estimating equations were used to account for sibling clusters. Results: A total of 1,009,189 births were included, comprising 51,747 PTB. An increase in the risk of PTB was seen across categories of exposure (P < 0.001) with an odds ratio (OR) in the uppermost category (>25 mg/L nitrate) of 1.05 (95% confidence interval [CI] = 1.00, 1.10). Evidence of an exposure–response relationship was observed in models using continuous nitrate (OR = 1.01 [95% CI = 1.00, 1.03] per 10 mg/L nitrate). In sensitivity analyses, results were robust to the addition of variables for short inter-pregnancy interval (<1 year between births), maternal pre-pregnancy body mass index, paternal socioeconomic status and age, season of birth, and inclusion of post-term births. Results were virtually unchanged when the analysis was restricted to women exposed to less than the current European Union standard of 50 mg/L. Conclusion: We observed an increasing risk of PTB with increases in nitrate in household tap water. These findings add to a growing body of evidence of adverse effects from nitrate in drinking water at levels below current regulatory levels.

The contribution of general medical conditions to the non-fatal burden of mental disorders: register-based cohort study in Denmark

Abstract: Background General medical conditions (GMCs) often co-occur with mental and substance use disorders (MSDs). Aims To explore the contribution of GMCs to the burden of disease in people with MSDs, and investigate how this varied by age. Method A population-based cohort of 6 988 507 persons living in Denmark during 2000–2015 followed for up to 16 years. Danish health registers were used to identify people with MSDs and GMCs. For each MSD, years lived with disability and health loss proportion (HeLP) were estimated for comorbid MSDs and GMCs, using a multiplicative model for disability weights. Results Those with any MSD lost the equivalent of 43% of healthy life (HeLP = 0.43, 95% CI 0.40–0.44) after including information on GMCs, which was an increase from 25% before including GMCs (HeLP = 0.25, 95% CI 0.23–0.27). Schizophrenia was associated with the highest burden of disease (HeLP = 0.77, 95% CI 0.68–0.85). However, within each disorder, the relative contribution of MSDs and GMCs varied. For example, in those diagnosed with schizophrenia, MSDs and GMCs accounted for 86% and 14% of the total health loss; in contrast, in those with anxiety disorders, the same proportions were 59% and 41%. In general, HeLP increased with age, and was mainly associated with increasing rates of pulmonary, musculoskeletal and circulatory diseases. Conclusions In those with mental disorders, the relative contribution of comorbid GMCs to the non-fatal burden of disease increases with age. GMCs contribute substantially to the non-fatal burden of disease in those with MSDs.

Observational cohort study of rilpivirine (RPV) utilization in Europe

Abstract: Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce.Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann-Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan-Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL).1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3-5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001).Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).

The health care cost of comorbidity in individuals with mental disorders: A Danish register-based study

Abstract: Aim: The aim of the study was to estimate the annual health care cost by number of comorbid mental and somatic disorders in persons with a mental disorder. Methods: All persons living in Denmark between 2004 and 2017 with a hospital diagnosis of a mental disorder were identified. We investigated the cost of different health care services: psychiatric hospitals, somatic hospitals, primary health care (e.g. general practitioners, psychologists and so on) and subsidised prescriptions. Within those with at least one mental disorder, we examined the costs for people with (a) counts of different types of mental disorders (e.g. exactly 1, exactly 2 and so on up to 8 or more) and (b) counts of different types of somatic disorders (e.g. no somatic disorders, exactly 1, exactly 2 and so on up to 15 or more). The estimates are reported in average cost per case and nationwide annual cost in Euro 2017. Results: In total, 447,209 persons (238,659 females and 208,550 males) were diagnosed with at least one mental disorder in the study period. The average annual health care cost per case and nationwide cost was 4471 Euros and 786 million Euro, respectively, for persons with exactly one mental disorder, and 33,273 Euro and 3.6 million Euro for persons with eight or more mental disorders. The annual health care cost was 4613 Euro per case and 386 million Euro for persons without any somatic disorders, while the cost per case was 16,344 Euro and 0.7 million Euro in nationwide cost for persons with 15 or more disorders. The amount and proportion of the different health care costs varied by type of comorbidity and count of disorders. Conclusions: The annual health care cost per case was higher with increasing number of comorbid mental and somatic disorders, while the nationwide annual health care cost was lower with increasing number of comorbid disorders for persons with a mental disorder in Denmark.

A nationwide study of air pollution on the NCD related morbidity in an unselected population

Abstract: Background and Aim: Very few studies of the effect of air pollution on national mortality exist. Even fewer studies have investigated the effect of air pollution on non-communicable disease (NCD) in the total population. Thus, this study aims to elucidate the burden of air pollution on the morbidity of the total unselected population. Methods: The study cohort consisted of all individuals age 50 years or older who were alive and resided in Denmark on their 50th birthday or 1st January 2004, whichever came later (entry date) (N=2,872,957). All hospital contacts for cancer, type 2 diabetes, asthma, Chronic Obstructive Pulmonary Disease (COPD), Alzheimer’s-, Parkinson’s-, ischemic heart -, and cerebrovascular-disease, between 1st January 2004 and 31st December 2016 were identified. We defined all NCD incident onsets as the date of first contact. For each case and 5 randomly selected controls, we modelled pollution (PM₂.₅, PM10, SIA, NO₂, O₃, BC, PPM₂.₅, Sea salt, and SOA) as personal average concentrations over the 20 years prior to the incident date. We estimated IRRs with 95% CIs for a fixed increase in air pollution assuming a linear exposure response relationship, adjusted for age, gender, calendar time, and individual as well as area-level socio-economic status. Results We found IRR (95% CI) per 5 µg/m³ increase in PM₂.₅ and per 10 µg/m³ increase in NO₂ to be highest for asthma, Alzheimer’s disease, type 2 diabetes, and COPD, table 1. IRR PM₂.₅ IRR NO₂ Type 2 Diabetes 1.47 (1.41 - 1.52)1.27 (1.24 - 1.30) Alzheimer&#x27;s Dis 1.76 (1.67 - 1.87) 1.30 (1.26 - 1.35) Asthma 1.88 (1.76 - 2.01) 1.47 (1.42 - 1.53) COPD 1.34 (1.30 - 1.39) 1.36 (1.33 - 1.39) In conclusion we find key NCDs are associated to PM₂.₅ and NO₂ even in a low exposure environment. Keywords: Air pollution, non-communicable diseases, Nationwide, Cohort.

Are current drinking water standards for nitrate sufficient for preventing adverse birth outcomes and childhood cancer– Findings from a cohort of over one million children in Denmark

Abstract: Background and Aims: Current standards for nitrate in drinking water in EU and the US are based on preventing methemoglobinemia a condition that occurs at high levels of exposure. There is growing evidence that exposure to nitrate in water is associated with adverse birth outcomes. Our aim is to summarize the findings from our nationwide studies of the population exposed to levels below the current standards in Denmark. Methods: We studied a cohort of all singletons liveborn to Danish-born parents from 1991–2013 (N=1,018,914). Data on birth weight, head circumference, body length, gestational age, birth defects and childhood cancer were obtained from Danish registers. Nitrate levels were estimated at the individual residential level. The analyses presented here were restricted to women who had pregnancy average exposures during their pregnancy that were lower than the current EU limit (50 mg/L N03). Results: Prenatal exposure to nitrate was found to be significantly associated with a decrease in birth weight (p&#x3c;0.001), body length (p&#x3c;0.01), and increased risk of small-weight-for-gestational age (p=0.002), all markers of fetal growth restriction. However, we did not observe evidence of an effect on head circumference or term low birth weight. Significant evidence of an exposure-response relationship was also observed for preterm births (p&#x3c;0.04), eye cataracts (p=0.004), and for nervous system (p=0.003) and ear, face and neck (p=0.01) birth defects among women &#x3c;25 years of age. A trend was not observed for childhood cancers, but a significant increase in central nervous system cancers was observed for the highest exposure group (&#x3e;25 mg/L) with which was strongest for the preconception period (OR=1.82, 95%CI:1.09 to 3.04). Conclusions: Our findings along with the results from other recent studies suggest that nitrate exposure from drinking water is associated with adverse birth outcomes and childhood CNS cancers at currently allowable levels. Key Words: nitrate, birth outcomes

The complexities of suicide: a multilevel survival analysis examining individual, familial and neighbourhood determinants of suicide risk using Danish register-based data.

Abstract: BACKGROUND Suicide risk is complex and nuanced, and how place impacts suicide risk when considered alongside detailed individual risk factors remains uncertain. We aimed to examine suicide risk in Denmark with both individual and neighbourhood level risk factors. METHODS We used Danish register-based data to identify individuals born in Denmark from 1972, with full parental information and psychiatric diagnosis history. We fitted a two-level survival model to estimate individual and neighbourhood determinants on suicide risk. RESULTS We identified 1723 cases of suicide in Denmark during the follow-up period from 1982 to 2015. Suicide risk was explained mainly by individual determinants. Parental comorbidities, particularly maternal schizophrenia [incidence rate ratio (IRR): 2.29, 95% CI 1.56-3.16] and paternal death (2.29, 95% CI 1.31-3.72) partly explained suicide risk when adjusted for all other determinants. The general contextual effect of suicide risk across neighbourhoods showed a median incidence rate ratio (MRR) of 1.13 (1.01-1.28), which was further reduced with full adjustment. Suicide risk increased in neighbourhoods with a higher proportion of manual workers (IRR: 1.08; 1.03-1.14), and decreased with a higher population density (IRR: 0.89; 0.83-0.96). CONCLUSION Suicide risk varies mainly between individuals, with parental comorbidities having the largest effect on suicide risk. Suicide risk was less impacted by neighbourhood, though, albeit to a lesser extent than individual determinants, some characteristics were associated with suicide risk. Suicide prevention policies might consider targeting interventions towards individuals more vulnerable due to particular parental comorbidities, whilst taking into account that some neighbourhood characteristics might exacerbate this risk further.