Clinical Epidemiology最新文献

Background: Socioeconomic differences in health have become an increasing public health concern and priority, leading to a growing number of studies investigating the relationship between socioeconomic position and health outcomes. However, variability in methodological practices hampers the comparability of findings and leads to inefficiencies, as researchers invest substantial resources in selecting appropriate variables and methods. To address these challenges, the SEPLINE initiative was established to develop a methodological guideline aimed at enhancing the comparability, quality, and feasibility of socioeconomic research using Danish registry data.

Methods: The guideline was developed through a consensus-driven approach involving an interdisciplinary group of stakeholders from Danish universities, research institutions, and data warehouses. The guideline addresses socioeconomic position as an exposure based on data from Danish registries, with the cancer continuum applied as a case outcome to illustrate its application. The development process included two collaborative workshops informed by a pre-workshop questionnaire. Workshop I (spring 2024) focused on socioeconomic indicators, data collection, and data management, featuring expert presentations and group discussions. Workshop II (fall 2024) addressed analytical methods, including causal inference challenges and income/wealth assessment methods. Insights from these workshops were integrated into iterative refinements of the guideline.

Conclusions and implications: The guideline provides a structured framework for conducting socioeconomic epidemiological research using Danish registry data, offering specific information on data sources and recommendations about variable selection, measurement timing, and data handling. While tailored to Danish registry-based cancer research, the guideline's methodological principles have broader applicability to other diseases and international contexts. By emphasizing transparency, theoretical grounding, and methodological rigor, SEPLINE aims to advance the study of social determinants of health. Researchers are encouraged to use the guideline as a relevant starting point and adapt it to their specific study populations and research questions, ensuring its relevance across diverse settings.

Objective: Given the lack of data on long-term outcomes among patients with sepsis, this study aimed to examine all-cause 2-year mortality and factors associated with mortality in adults admitted to an emergency department with sepsis.

Study design: Prospective cohort study.

Methods: This study included all emergency department patients admitted with sepsis to Slagelse Hospital, Denmark, between October 1, 2017, and March 31, 2018. Data on patients with infectious diseases was prospectively extracted from electronic health records during the study period. Sepsis was defined as a Sequential Organ Failure Assessment (SOFA) score ≥ 2 from baseline. The outcome was 2-year all-cause mortality. The Kaplan-Meier method was used to estimate the mortality. Cox regression analyses were used to compute adjusted hazard ratios (aHR) with 95% confidence intervals for prognostic factors associated with mortality.

Results: A total of 714 patients (58.4% men) with a median age of 75 years were diagnosed with sepsis. After two years, 354 (49.6%; 45.9-53.3) patients had died. Factors associated with elevated mortality risk included age (< 65 years as reference) 65-85 years (aHR 1.89; 1.35-2.64) or age > 85 years (aHR 2.99; 2.07-4.31); SOFA score > 4 (aHR 2.45; 1.82-3.30) (score of 2 as reference); and history of malignancy (aHR 1.91; 1.44-2.53), ischemic heart disease (aHR 1.38; 1.03-1.84), dementia (aHR 1.84; 1.34-2.53), previous sepsis admission (aHR 1.45; 1.15-1.82), new-onset atrial fibrillation (aHR 1.56; 1.05-2.34), and mildly decreased (6.9-7.9 mmmol/L) hemoglobin values (aHR 1.68; 1.29-2.19) and significantly decreased (<6.9 mmol/L) hemoglobin values (aHR 2.30; 1.74-3.02) with normal range (≥ 8mmol/L) as reference. Skin infection was associated with diminished mortality risk (aHR 0.50; 0.29-0.85) compared to patients with other sources of infection.

Conclusion: Sepsis is associated with a poor prognosis. Our findings underscore the prognostic effects of age, SOFA score, and specific comorbidities on 2-year mortality among patients with sepsis.

Purpose: Hydrocephalus is a neurological condition characterized by an accumulation of cerebrospinal fluid (CSF) with no cure and limited treatments. There is a significant gap in hydrocephalus research where patients lack opportunities to voice their perspectives on their condition. The Hydrocephalus Association Patient-Powered Interactive Engagement Registry (HAPPIER) database captures the lived experiences of those affected by hydrocephalus and provides a platform for researchers to access these data or distribute their own surveys, ultimately aiming to improve patient-centered care and outcomes. This publication introduces the registry by highlighting the demographics, etiology, treatments, symptom profiles, and diagnosed comorbidities of the participants.

Methods: The Hydrocephalus Association and a 10-member steering committee developed HAPPIER. Other patient registries, existing surveys and assessments, and University of Utah Data Center faculty guided survey development. The Hydrocephalus Association recruited participants using social and traditional media, medical referrals, and advertisements at events.

Results: Of the 691 survey participants with hydrocephalus, 451 (65.3%) responded for themselves. The majority of the registry was female (55.0%), white (86.0%), and from the United States and territories (87.7%). Most were diagnosed between 0-11 months (46.2%), with congenital hydrocephalus as the most reported etiology (43.8%). Participants reported a shunt(s) as the most prevalent treatment (71.2%) and headaches as the most frequent symptom (60.3%), while 69.9% of participants reported being diagnosed with movement impairments and 70.8% with other health conditions.

Conclusion: HAPPIER is a novel database that addresses gaps in data on non-clinical outcomes of hydrocephalus, which are critical to clinical care and understanding hydrocephalus. Patient perspectives and outcomes remain historically underrepresented. By directly engaging individuals living with hydrocephalus and their caregivers, HAPPIER incorporates essential patient perspectives through planned longitudinal data collection and patient surveys. These data are open to investigators interested in analyzing the collected data.

Purpose: Multi-database studies may provide heterogeneous results despite using common protocols, leading to challenges in interpretation, but also providing an opportunity to gain insights on populations or healthcare systems. The objectives of these analyses were to develop a framework for exploring sources of statistical heterogeneity and apply it to the multi-database EXACOS-CV (EXAcerbations of COPD and their OutcomeS on CardioVascular diseases) program.

Methods: A conceptual framework to systematically assess sources of statistical heterogeneity in multi-database studies was developed. This framework distinguishes between methodological diversity and true clinical variation. Methodological diversity includes differences in study design and database selection, while true variation considers population and healthcare differences. Possible sources of methodological diversity were identified via a novel checklist and explored. In turn, hypotheses were generated about true variation. The framework and checklist were applied to EXACOS-CV cohort studies in Germany, Canada, the Netherlands, and Spain which deviated least from the common protocol and so were included. Focus was on adjusted hazard ratios (aHR) for post-exacerbation associations with decompensated heart failure (HF) and all-cause death, for which results were most and least heterogeneous, respectively.

Results: Across EXACOS-CV studies, the adjusted hazard ratios (aHR) for HF in the first 1-7 days post-exacerbation, compared to non-exacerbation periods, ranged from 2.6 (95% CI, 2.3, 2.9) in Germany to 72.3 (64.4, 81.2) in Canada, and the association with death, relative to non-exacerbation periods, ranged from 3.5 (2.4, 5.3) in the Netherlands to 22.1 (19.9, 24.4) in Spain. Completed methodological diversity checklists linked differences in aHRs to possible variation in ability to capture pre-existing cardiovascular comorbidities across studies, as well as differences in confounder measurement. Standardizing adjusted models across studies did not fully explain heterogeneity, suggesting other contributing factors. Heterogeneity may result from genuine variation in prevalence of CV disease. It was hypothesized that patients with pre-existing CV disease have more accurate diagnoses and management of post-exacerbation CV events, possibly leading to lower risks of such events.

Conclusion: Multi-database studies can provide directional insights on the study research question while considering healthcare system and population differences. The developed framework aids assessment of heterogeneity sources.

Background: Real-world evidence about adherence to proprotein convertase subtilisin/kexin type-9 inhibition (PCSK9i) is needed in Chinese population.

Objective: We aimed to evaluate the adherence patterns using anti-PCSK9 monoclonal antibody in Chinese clinical practice and explored the association between adherence to PCSK9i and low-density lipoprotein cholesterol (LDL-C) reduction ratio and variability.

Methods: A total of 5373 patients initiating PCSK9i in the First Affiliated Hospital of Sun Yat-sen University were included as sub-analysis of the RED-CARPET registry. Adherence to PCSK9i was measured by proportion of days covered (PDC), calculated for treatment covered days divided by 365 days during a one-year period. Reduction ratio (percentage points, range 0-100) was calculated as the ratio of reduction degree (difference between baseline value and the lowest value) to the baseline value. LDL-C variability was measured as standard deviation of three LDL-C measurement 2 weeks after medication initiation. We used linear regression to measure the association between PCSK9i PDC and the reduction ratio and variability of LDL-C. PDC (range 0-1) was scaled by 10 in the model.

Results: At 12 months, the mean PDC was 0.09 ± 0.10. PCSK9i PDC was positively associated with LDL-C reduction ratio after adjustment for traditional risk factors (Adjusted β 4.05, 95% CI [2.61, 5.50]), p<0.001), which means for every 0.1-unit increase in PDC, the LDL-C reduction ratio increases by 4.05 percentage points. PCSK9i PDC was negatively associated with LDL-C standard deviation after fully adjustment (Adjusted β -0.042, 95% CI [-0.066, -0.018]), p=0.001). For every 0.1-unit increase in PDC, the LDL-C standard deviation decreased by 0.042 units, indicating improved lipid stability with higher adherence.

Conclusion: The adherence to PCSK9i presented as a skewed distribution, most people only received one injection, which did not reach the ideal adherence goal. Unsatisfactory adherence to PCSK9i reduce the lipid-lowering effect of PCSK9i.

Background/objectives: Faecal Immunochemical Testing (FIT) is recommended for patients presenting to primary care with symptoms suggestive of colorectal cancer. This study quantified variations in use across England.

Methods: Retrospective cohort of English patients (≥18 years) with a FIT result reported in routinely collected primary care records, 2019-2023. Rates of FIT testing by age, sex, year and region were adjusted using Poisson regression. Multivariate logistic regression compared the effect of factors on the proportion of results exceeding the recommended referral threshold (10µgHb/g).

Results: Between 01/01/2019 and 05/06/2023 there were 531,735 FIT results among 495,121 patients. Rates of testing increased from 0.69 per thousand person-years in 2019 (95% CI 0.68-0.71) to 27.70 in 2023 (95% CI 27.56-27.85). There were large variations in testing between regions, with rates >3-fold higher in the Northeast than the West Midlands: 17.05 (95% CI 16.87-17.23) versus 4.72 (95% CI 4.67-4.76) per thousand person-years. About 20.4% of FIT results were ≥10µgHb/g. Despite increased testing, this did not change over time. The proportion of FIT ≥10µgHb/g was lower in regions with higher rates of testing, from 16.7% (Southwest) to 25.3% (Southeast; rates of testing 14.62 and 8.00 per thousand person-years respectively). This difference in proportion of FIT ≥10µgHb/g persisted after adjusting for year, sex and age (OR 0.57, 95% CI 0.55-0.58).

Conclusion: Rapid increases in FIT testing in primary care show large, persistent variations between English regions, which correlate with the proportion of results meeting the criteria for onward referral. Differences in the population tested and FIT's implementation between regions are likely to explain these variations.

Background: Capmatinib was approved by the US Food and Drug Administration (FDA) in 2020 for the treatment of non-small cell lung cancer with MET exon 14 mutation (METex14). Real-world studies on the safety of Capmatinib are still lacking. The aim of this study was to explore the significant adverse drug reactions (ADRs) associated with Capmatinib through the FDA Adverse Event Reporting System (FAERS) database.

Methods: We employed the reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM) as primary algorithms for the disproportionality analysis. Adverse events (AEs) were classified as adverse drug reactions (ADRs) solely upon fulfillment of criteria across all four algorithms.

Results: In our study, there were 1767 cases explicitly attributed to Capmatinib. A total of 38 ADRs in preferred terms (PTs) level in 14 system-organ categories (SOCs) were identified after filtering. Notably, unexpected SOC "Ear and labyrinth disorders" and PTs "hypoacusis" and "deafness" were identified, without being specified in the drug label.

Conclusion: Our study identified unexpected ADRs associated with Capmatinib, with a focus on ototoxicity-related events, underscoring the need for enhanced clinical monitoring and further investigation into the underlying mechanisms.

Background: Previous studies have suggested a potential association between plasma aldosterone concentration (PAC) and calcium regulation. However, it remains unclear whether elevated PAC levels increase the risk of urinary stones. Therefore, this study aimed to investigate the relationship between PAC levels and urinary stones, including their subtypes, in patients with hypertension.

Methods: This large-scale study included a total of 35161 hypertensive patients. Multivariable logistic regression was used to analyze the association between PAC levels and urinary stones, as well as their subtypes. Additionally, a dose-response relationship was explored using restricted cubic spline (RCS) analysis, and a two-stage comparative analysis was conducted based on the RCS turning point. The importance of PAC was further confirmed through variable importance analysis. Finally, extensive subgroup analyses and sensitivity analyses were performed to assess the robustness of the findings.

Results: Multivariable logistic regression revealed a significant association between elevated PAC levels and the occurrence of urinary stones and their subtypes. Specifically, for every 5 ng/dL increase in PAC, the risk of urinary stones increased by 26% (odds ratios [OR] 1.26, 95% confidence interval [CI], 1.22-1.30, P<0.001). Furthermore, RCS threshold analysis demonstrated a marked increase in urinary stone risk when PAC levels exceeded 14.2 ng/dL (OR 1.50, 95% CI, 1.38-1.63, P<0.001). These findings were consistent across subtypes, including kidney stones and ureteral stones. Subgroup analyses showed that the results were unaffected by stratification factors, and sensitivity analyses further confirmed the stability of the findings.

Conclusion: This study demonstrated that elevated PAC levels are significantly associated with the occurrence of urinary stones and their subtypes in hypertensive patients. These findings suggest that controlling PAC levels in hypertensive patients may help reduce the risk of urinary stone formation.

Introduction: Venous thromboembolism (VTE) is a common disease with a serious prognosis. Nonetheless, many aspects of this multicausal disease are poorly understood. The aim of establishing The Danish Venous Thromboembolism Cohort was to study VTE risk and prognosis within a life-course context.

Methods: The Danish Venous Thromboembolism Cohort was based on respondents to the questionnaire-based Danish National Health Survey (DNHS) conducted in 2010, 2013, and 2017 and was linked to Danish national health and administrative registries.

Results: A total of 474,022 unique respondents to the DNHS were included in this cohort, 8,460 of whom were diagnosed with VTE before the survey response date. The survey's response rate varied between 54% and 60%. The median age at the survey response date was 54 years (interquartile range: 40-66 years), and 46.1% of respondents were men. The cohort contains detailed information on lifestyle factors (smoking habits, alcohol consumption, physical activity level, and dietary habits), health status indicators (healthcare-seeking behavior, body mass index, self-rated health, and mental distress), and self-reported morbidities. In addition, the survey data were linked to records in Danish medical and administrative registries to obtain information on clinical data and outcomes, including hospitalizations, medication use, laboratory test results, labor market participation, vital status, and causes of death.

Discussion: The Danish Venous Thromboembolism Cohort is a valuable data resource for use in future studies on VTE research, with a focus on risk factors, complications, interactions, and prognosis.