European Journal of Epidemiology最新文献

Background

Opioid Agonist Treatment (OAT) is the most effective intervention for opioid use disorder (OUD), but retention has decreased due to increasingly potent drugs like fentanyl. This cohort can be used retrospectively to observe trends in service utilization, healthcare integration, healthcare costs and patient outcomes. It also facilitates the design of observational studies to mimic a prospective design.

Methods

This study used linked administrative data from ICES to create a cohort of 137,035 individuals who received at least one prescription of methadone or buprenorphine/naloxone between 2014 and 2022. Data were linked using de-identified personal health numbers. Variables included age, sex, rurality, income, homelessness, and mental health conditions. Regional differences in OAT use, retention, and mortality were analyzed.

Results

Of the cohort, 56.1% began OAT after 2014. Southern Ontario participants more often started on methadone (53.2%), while Northern Ontario patients favored buprenorphine/naloxone (62.7%). Northern patients were younger, more likely to be female, live in rural areas, and face homelessness. The death rate was higher in Southern Ontario (22.1%) than in Northern Ontario (13.2%). Retention declined over time, with 73.4% of patients remaining in treatment at the study's end.

Conclusions

The findings highlight regional disparities in OAT delivery and emphasize the need for region-specific strategies, particularly in rural areas, to improve retention and reduce mortality.

The Global Burden of Diseases (GBD) network has proposed theoretical minimum risk exposure level (TMREL) for leading risk factors associated with diet that minimize the risk of morbimortality from chronic diseases. TMREL can be applied to develop follow-up or evaluation indicators in individual studies. The validity of these scores can be tested by assessing associations with health outcomes in prospective cohorts. In this study conducted within the NutriNet-Santé cohort, four dietary scores (TMREL-Risk Score, TMREL-Probability of adequacy, TMREL-standardized distance, and TMREL dietary score) using different scoring methods were developed, with higher scores reflecting less healthy diets. Associations of these scores with the risk of type 2 diabetes, cancer, cardiovascular diseases (CVD) and mortality were estimated using multivariable Cox proportional hazards models, adjusted for a wide range of covariates. Counterfactual and marginal structural models were used to infer causality. Analyses were conducted in a sample of up to103,324 participants ((78.3% women, mean age of 43.6 years old (y) (SD = 14.6)), followed for a median of 8.47 (IQR = 14.7) years (2009–2024). The association with dietary scores (for 1SD-increase) varied in magnitude for each health outcome. For mortality, HR varied from 1.12 (95%CI = 1.07–1.18, ) to 1.18 (95%CI = 1.12–1.24) for TMREL-Stdis and TMREL-DI, for overall cancer from 1.07 (95%CI = 1.03–1.12) to 1.09 (1.04–1.13) for TMREL-RS and TMREL-PA, for CVD from 1.07 (95%CI = 1.00-1.16) to 1.12 (95%CI = 1.04–1.20) for TMREL-PA and TMREL-RS, and for type 2 diabetes from 1.33 (95%CI = 1.23–1.43) to 1.47 (95%CI = 1.36–1.59) for TMREL-DI and TMREL-PA. Marginal structural Cox models strengthened all associations compared to classical analyses. Standardized survival curves showed clear associations, especially for the risk of cancer and type 2 diabetes. Dietary scores based on GBD TMREL can serve as key indicators for characterizing diet quality in relation to long-term health, and using different scoring systems helped evaluate the robustness of these associations.

Objectives: The association between leisure-time physical activity (LTPA) and a lower risk of mortality is susceptible to bias from multiple sources. We investigated the potential of biological ageing to mediate the association between long-term LTPA and mortality and whether the methods used to account for reverse causality affect the interpretation of this association. Methods: Study participants were twins from the older Finnish Twin Cohort (n = 22,750; 18–50 years at baseline). LTPA was assessed using questionnaires in 1975, 1981 and 1990. The mortality follow-up lasted until 2020 and biological ageing was assessed using epigenetic clocks in a subsample (n = 1,153) with blood samples taken during the follow-up. Using latent profile analysis, we identified classes with distinct longitudinal LTPA patterns and studied differences in biological ageing between these classes. We employed survival models to examine differences in total, short-term and long-term all-cause mortality, and multilevel models for twin data to control for familial factors. Results: We identified four classes of long-term LTPA: sedentary, moderately active, active and highly active. Although biological ageing was accelerated in sedentary and highly active classes, after adjusting for other lifestyle-related factors, the associations mainly attenuated. Physically active classes had a maximum 7% lower risk of total mortality over the sedentary class, but this association was consistent only in the short term. After accounting for familial factors and excluding participants reporting prevalent cardiovascular diseases, LTPA exhibited less favourable associations with mortality. Conclusion: The association between LTPA and lower all-cause mortality may be largely due to genetic confounding and reverse causality.

Although several environmental factors may increase the risk of nervous system anomalies, the association between exposure to particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM_2.5) and nervous system anomalies is not completely understood. This study aimed to examine the association between expoure to PM_2.5 and nervous system anomalies, including specific phenotypes during preconception and early pregnancy and determine the crucial time windows. We conducted a nested case-control study from the Taiwan Maternal and Child Health Database between 2004 and 2017. We applied satellite-based models with a 1 km resolution to estimate the weekly average PM_2.5 from 13 weeks before conception to the first 8 weeks of pregnancy. We used conditional logistic regression with distributed lag nonlinear models (DLNMs) to assess the effects of weekly average PM_2.5 on the risk of nervous system anomalies and exposure-response relationships. We identified 12,383 incident nervous system anomalies cases in 2,571,300 participants. A 10 µg/m³ increase in PM_2.5 concentrations from a reference value of 25 µg/m³ was associated with higher risk of nervous system anomalies (adjusted odds ratio [aOR]: 1.21; 95% confidence incidence [CI]: 1.18, 1.25) and encephalocele (aOR: 1.56; 95% CI: 1.33, 1.84) from 13 weeks before conception to the first 8 weeks of gestation. Anencephaly showed a significant association with PM_2.5 exposure during the 13 weeks before conception (aOR: 1.48; 95% CI: 1.02, 2.51). In DLNMs, the risk of nervous system anomalies was elevated each week from 8 to 11 weeks before conception to 1–8 weeks of gestation. Our findings suggest that exposure to PM_2.5 during preconception and early pregnancy may increase the risk of nervous system anomalies in offspring, particularly neural tube defects such as anencephaly and encephalocele.

Early-stage cutaneous melanoma patients generally have a favorable prognosis, yet a significant proportion of metastatic melanoma cases arise from this group, highlighting the need for improved risk stratification using novel prognostic biomarkers. The Dutch Early-Stage Melanoma (D-ESMEL) study introduces a robust, population-based methodology to develop an absolute risk prediction model for stage I/II melanoma, incorporating clinical, imaging, and multi-omics data to identify patients at increased risk for distant metastases. Utilizing the Netherlands Cancer Registry and Dutch Nationwide Pathology Databank, we collected primary tumor samples from early-stage melanoma patients, with and without distant metastases during follow-up. Our study design includes a discovery set of metastatic cases and matched controls to identify novel prognostic factors, followed by a validation cohort using a nested case–control design to validate these factors and to build a risk prediction model. Tissue sections underwent Hematoxylin & Eosin (H&E) staining, RNA sequencing (RNAseq), DNA sequencing (DNAseq), immunohistochemistry (IHC), and multiplex immunofluorescence (MxIF).The discovery set included 442 primary melanoma samples (221 case–control sets), with 46% stage I and 54% stage II melanomas. The median time to distant metastasis was 3.4 years, while controls had a median follow-up time of 9.8 years. The validation cohort included 154 cases and 154 controls from a random population-based selection of 5,815 patients. Our approach enabled the collection of a large number of early-stage melanoma samples from population-based databases with extensive follow-up and a sufficient number of metastatic events. This methodology in prognostic cancer research holds the potential to impact clinical decision-making through absolute risk prediction.

Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects. Here, we apply an integrated approach combining MR with twin causal models to examine causality between smoking and blood DNAm in the Netherlands Twin Register (N = 2577). Analyses revealed potential causal effects of current smoking on DNAm at > 500 sites in/near genes enriched for functional pathways relevant to known biological effects of smoking (e.g., hemopoiesis, cell- and neuro-development, and immune regulation). Notably, we also found evidence of reverse and bidirectional causation at several DNAm sites, suggesting that variation in DNAm at these sites may influence smoking liability. Seventeen of the loci with putative effects of DNAm on smoking showed highly specific enrichment for gene-regulatory functional elements in the brain, while the top three sites annotated to genes involved in G protein-coupled receptor signalling and innate immune response. These novel findings are partly attributable to the analyses of current smoking in twin models, rather than lifetime smoking typically examined in MR studies, as well as the increased statistical power achieved using multiallelic/polygenic scores as instrumental variables while controlling for potential horizontal pleiotropy. This study highlights the value of twin studies with genotypic and DNAm data for investigating causal relationships of DNAm with health and disease.

It has been suggested that non-live vaccines may increase susceptibility to non-targeted infections and that such deleterious non-specific effects are more pronounced in girls. We investigated whether receipt of non-live vaccine against human papillomavirus (HPV) was associated with increased risk of infectious disease hospitalization. A nationwide cohort study based on detailed individual-level data from national registries was performed in Denmark, Finland, Norway, and Sweden. The cohort consisted of girls aged 11–14 years in Denmark, Finland, and Norway, and 10–14 years in Sweden. Cox regression, with extensive control for potential confounders, was used to assess whether risk of infectious disease hospitalization with at least one overnight stay differed according to time-varying HPV vaccination status. In total, 754 458 girls were included in the analysis. The infectious disease hospitalization rate (per 10 000 person years) was 44.1 in Denmark, 35.7 in Finland, 37.1 in Norway, and 28.5 in Sweden. Comparing HPV-vaccinated with HPV-unvaccinated person time, the adjusted hazard ratio (95% confidence interval) was 0.81 (0.72, 0.90) in Denmark, 0.69 (0.60, 0.80) in Finland, 0.76 (0.66, 0.88) in Norway, and 0.59 (0.49, 0.71) in Sweden. Decreased risk was observed regardless of number of doses, except in Norway, where risk among girls with only one dose did not differ from risk among unvaccinated girls. Receipt of HPV vaccine was consistently associated with decreased risk of infectious disease hospitalization among girls in the Nordic countries. Our study does not support that HPV vaccines have deleterious non-specific effects.

The Stockholm Early Detection of Cancer Study (STEADY-CAN) cohort was established to investigate strategies for early cancer detection in a population-based context within Stockholm County, the capital region of Sweden. Utilising real-world data to explore cancer-related healthcare patterns and outcomes, the cohort links extensive clinical and laboratory data from both inpatient and outpatient care in the region. The dataset includes demographic information, detailed diagnostic codes, laboratory results, prescribed medications, and healthcare utilisation data. Since its inception, STEADY-CAN has collected longitudinal data on 2,732,005 individuals aged ≥ 18 years old living in or having access to health care in Stockholm County during the years 2011–2021. Focusing on cancer, the cohort includes 140,042 (5.1%) individuals with incident cancer and a control group of 2,591,963 (94.9%) cancer-free individuals. The cohort’s diverse adult population enables robust analyses of early symptom detection, incidental findings, and the impact of comorbidities on cancer diagnoses. Utilizing the wide range of available laboratory data and clinical variables allow for advanced statistical analyses and adjustments for important confounding factors. The cohort’s primary focus is to improve understanding of the early diagnostic phase of cancer, offering a crucial resource for studying cancer detection in clinical practice. Its comprehensive data collection provides unique opportunities for research into comorbidities and cancer outcomes, making the cohort a useful resource for ongoing cancer surveillance and public health strategies. The present study gives a detailed description of the rationale for creating the STEADY-CAN cohort, its design, the data collection procedure, and baseline characteristics of collected data.

An association of mental health and in particular depression with cardiovascular disease has been shown in adults and to a lesser extent in the young. Recently improved measurement methods of carotid-intima media thickness (CIMT) and carotid stiffness (CS) allow more differentiated analyses of this link. We examined 4,361 participants of the nationwide KiGGS cohort aged 3–17 years at baseline and 14–28 years at follow-up. Using linear and logistic regressions, we analyzed cross-sectional and longitudinal associations of mental health with systolic blood pressure (SBP), body mass index (BMI) and total cholesterol (TC) as well as CIMT and CS from high-resolution carotid sonography at follow-up. Mental health in children was measured with the Strength and Difficulties Questionnaire (SDQ) and in adults with the Mental Health Inventory (MHI-5) and the Patient Health Questionnaire (PHQ-9). Childhood SDQ scores were associated longitudinally with SBP, BMI and TC (-0.03≤ ß≥ 0.02) but not with CIMT or CS one decade later. Similarly, SDQ at follow-up was associated cross-sectionally with SBP, BMI and TC, but not CIMT or CS. MHI-5 scores were not linked to any outcome. PHQ-9 scores in young adults were associated cross-sectionally with SBP and BMI (-0.26≤ ß≥ 0.01), but not with CIMT or CS. Our study shows that children, adolescents and young adults with impaired mental health also have an increased long-term cardiovascular risk through higher BMI and TC. However, in this sample with predominantly mild mental health impairments carotid remodeling was not evident.

Introduction

Mastocytosis is a group of rare heterogeneous diseases with a prevalence previously found to be 10–23 per 100,000 persons. More awareness and improvements in the diagnostic methods in later years have led to more patients being diagnosed. Here, we set out to present the prevalence and incidence rate of mastocytosis among the adult Danish population. By merging data from the Danish National Patient Register, the Danish Pathology Register and the Danish Cancer Register we included all adult patients (≥ 18 years) diagnosed with mastocytosis in Denmark prior to 2022. A cohort of 1,594 patients with mastocytosis was identified. The prevalence of mastocytosis was 27.43 per 100,000 persons (95% confidence interval [CI]: 25.95–28.96) as of January 1, 2022, and the 25-year average incidence rate between 1997 and 2021 was 1.21 per 100,000 persons (95%CI: 1.02–1.40) with an increasing incidence rate since 2002. We found a higher prevalence of mastocytosis among adults in the Danish population than previously reported, and an increasing incidence rate during the last 20 years. Increased awareness of the disease and better diagnostic methods most likely contributed to this.