Clinical Epidemiology最新文献

Background: Lymphoid-lineage cancers (LC; International Classification of Diseases, 10^th edition [ICD10] C81.x-C90.x, C91.1-C91.9, C95.1, C95.7, C95.9, D47.2, D47.9B, and E85.8A) share many epidemiological and clinical features, which favor meta-learning when developing medical artificial intelligence (mAI). However, access to large, shared datasets is largely missing and limits mAI research.

Aim: Creating a large-scale data repository for patients with LC to develop data-driven hematology.

Methods: We gathered electronic health data and created open-source processing pipelines to create a comprehensive data resource for Danish LC Research (DALY-CARE) approved for epidemiological, molecular, and data-driven research.

Results: We included all Danish adults registered with LC diagnoses since 2002 (n=65,774) and combined 10 nationwide registers, electronic health records (EHR), and laboratory data on a high-powered cloud-computer to develop a secure research environment. Among other, data include treatments (ie 21,750 cytoreductive treatment plans, 21.3M outpatient prescriptions, and 12.7M in-hospital administrations), biochemical analyses (77.3M), comorbidity (14.8M ICD10 codes), pathology codes (4.5M), treatment procedures (8.3M), surgical procedures (1.0M), radiological examinations (3.3M), vital signs (18.3M values), and survival data. We herein describe the data infrastructure and exemplify how DALY-CARE has been used for molecular studies, real-world evidence to evaluate the efficacy of care, and mAI deployed directly into EHR systems.

Conclusion: The DALY-CARE data resource allows for the development of near real-time decision-support tools and extrapolation of clinical trial results to clinical practice, thereby improving care for patients with LC while facilitating streamlining of health data infrastructure across cohorts and medical specialties.

Purpose: This study aims to investigate the potential association between non-selective RET kinase inhibitors and thyroid dysfunction (TD) by conducting a pharmacovigilance analysis using data from the US FDA Adverse Event Reporting System (FAERS).

Methods: Data for non-selective RET MKIs were obtained from the FAERS database, spanning the first quarter of 2015 to the fourth quarter of 2023. Disproportionality analysis was used to quantify the AE signals associated with non-selective RET MKIs and to identify TD AEs. Subgroup analyses and multivariate logistic regressions were used to assess the factors influencing the occurrence of TD AEs. Time-to-onset (TTO) analysis and the Weibull Shape Parameter (WSP) test were also performed.

Results: Descriptive analysis revealed an increasing trend in TD adverse events linked to non-selective RET MKIs, with a notable proportion of serious reactions reported. Disproportionality analysis using ROR, PRR, BCPNN, and EBGM algorithms consistently demonstrated a positive association between Sunitinib, Cabozantinib, and Lenvatinib with TD adverse events. Subgroup analyses highlighted differential susceptibility to TD based on age, gender, and weight, with varying patterns observed for each inhibitor. Logistic regression analyses identified factors independently influencing the occurrence of TD adverse events, emphasizing the importance of age, gender, and weight in patient stratification. Time-to-onset analysis indicated early manifestation of TD adverse events following treatment with non-selective RET MKIs, with a decreasing risk over time.

Conclusion: The results of our study indicate a correlation between the use of non-selective RET MKIs and the occurrence of TD AEs. This may provide support for the clinical monitoring and risk identification of non-selective RET MKIs. Nevertheless, further clinical studies are required to substantiate the findings of this study.

Purpose: The present study aims to evaluate the changes in healthcare utilization following population-based screening for diabetes mellitus (DM) using point-of-care HbA1c measurement in the Viborg Screening Program (VISP) cohort, which invites all 67-year-olds in Viborg, Denmark, for cardiovascular disease (CVD) and DM screening.

Patients and methods: We conducted a cohort study using data from VISP and Danish national health registers. The study included 2386 individuals invited to VISP from August 1, 2014, to May 31, 2017. Exclusion criteria were non-attenders, those with prior DM, and those with missing HbA1c measurements. Pre- and post-screening healthcare utilization was analyzed, stratified by HbA1c levels: <42 mmol/mol (normal), 42-48 mmol/mol (pre-DM), and ≥48 mmol/mol (DM). Statistical analyses were performed using Poisson and logistic regression models to compare ratios of healthcare utilization before and after screening.

Results: Of the participants, 16.5% had pre-DM, and 3.4% had DM. Screening resulted in increased general physician contacts across all HbA1c groups, the highest increase was seen in the DM group with a pre- vs post-screening odds ratio [OR] of 3.25 (95% CI: 1.06-9.95) and a relative odds ratio [ROR] of 2.70 (0.87-8.39). Also, in this group, the OR for having ≥1 HbA1c measurement one year pre- vs post-screening was 5.56 (2.77 -11.14) and 26.8% (17.6-37.9) started glucose-lowering treatment within two years post-screening. Despite expectations, healthcare utilization did not decrease among those with normal HbA1c levels.

Conclusion: Population-based screening for DM and CVD among 67-year-olds resulted in increased healthcare utilization, particularly among those with screen-detected DM and pre-DM. The anticipated reduction in healthcare utilization among individuals with normal HbA1c levels was not observed. These findings highlight the potential for screening to enhance disease management and underscore the need for strategies to optimize healthcare resource use following screening, especially for individuals without DM.

Trial registration: NCT03395509.

Purpose: In recent decades, numerous non-invasive tests (NITs) for diagnosing nonalcoholic fatty liver disease (NAFLD) have been developed, however, a comprehensive comparison of their relative diagnostic accuracies is lacking. We aimed to assess and compare the diagnostic accuracy of various NITs for NAFLD using network meta-analysis (NMA).

Materials and methods: We conducted a systematic search in seven databases up to April 2024 to identify studies evaluating the diagnostic values of NITs, with liver biopsy as the gold standard. The participants included patients with suspected or confirmed NAFLD, irrespective of age, sex, ethnicity. Statistical analysis was conducted using R 4.0.3 for Bayesian NMA and STATA 17.0 for pairwise meta-analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUC), and superiority index were calculated. Bayesian calculations were performed using the Rstan package, specifying parameters like MCMC chain count, iteration count, and operational cycles. The methodological quality of included studies was assessed using the QUADAS-2 tool.

Results: Out of 15,877 studies, 180 were included in the quantitative synthesis, and 102 were used in head-to-head meta-analyses. For diagnosing steatosis stage 1, Hydrogen Magnetic Resonance Spectroscopy (H-MRS, DOR 15,745,657.6, 95% CI 17.2-1,014,063.59) proved to be the most accurate. For significant fibrosis, HRI leading (DOR 80.94, 95% CI 6.46-391.41), For advanced fibrosis, CK-18 showed the highest performance (DOR 102654.16, 95% CI 1.6-134,059.8). For high-risk NASH, Real-Time Elastography showing the highest performance (DOR 18.1, 95% CI 0.7-96.33). Meta-regression analyses suggested that variability in the diagnostic accuracy of NITs for NAFLD may result from differences in study design, thresholds, populations, and performance indicators.

Conclusion: We conducted a network meta-analysis to rank the accuracy of these tests. While some results are promising, not all NITs demonstrate substantial accuracy, highlighting the need for validation with larger datasets. Future research should concentrate on studying the thresholds of NITs and enhancing the clarity of methodological reporting.

Objective: Patients who undergo major lower extremity amputation (MLEA) have the highest postoperative mortality among orthopedic patient groups. The comorbidity profile for MLEA patients is often extensive and associated with elevated postoperative mortality. This study primarily aimed to investigate the increased short- and long-term mortality following first and subsequent major lower extremity amputation. Secondarily, to examine the mediation role of post-amputation complications.

Study design and setting: With data from the Danish National Patient Registry, 11,695 first-time MLEAs in patients aged ≥50 years were identified between January 1, 2010, and December 31, 2021, along with 58,466 unamputated persons matched 1:5 by year of birth, sex, and region of residence. Mediators were identified through diagnosis codes (ICD-10) present in 6 months following MLEA.

Results: The increased mortality following MLEA was highest in the month following MLEA, hazard ratio (HR) 38.7 (95% confidence interval (CI) 30.5-48.9) in women and HR 55.7 (CI 44.3-70.2) in men compared to a matched unamputated cohort. Subsequent amputation resulted in an increased mortality the month after a subsequent amputation (overall HR 3.2 (CI 2.8-3.7) in women and HR 3.2 (CI 2.8-3.6) in men) and almost normalized after the first year. The proportion of the mortality risk that potentially could be reduced by preventing sepsis was 16% (CI 11.7-20.3) for women and 17% (CI 13.4-20.4) for men. For pneumonia, it was 10.5% (CI 7.1-13.9) in women and 14.9% (11.6-18.2) in men.

Conclusion: We observed an increased mortality in the month following MLEA, which remained elevated for years compared to the matched unamputated cohort. A subsequent amputation results in increased mortality in the following year, but declined and normalized after the first year. Sepsis and pneumonia arising after the amputation appeared to be important factors that contributed to the increased postoperative mortality.

Purpose: The thyroid gland is an organ at risk in breast cancer survivors who receive radiation therapy to the supraclavicular lymph nodes. We investigated the effect of radiation dose to the thyroid gland on the incidence of hypothyroidism in early-stage breast cancer patients treated with CT-guided radiation therapy.

Patients and methods: We recruited women aged ≤75 years diagnosed with breast cancer from March 2016 through August 2017 at Odense University Hospital, Denmark. Thyroid function was measured in blood samples drawn at baseline, 6, 12, and 18 months. We delineated the thyroid gland using CT scans to estimate thyroid volume and radiation dose to the thyroid. Subclinical hypothyroidism was defined as a thyroid-stimulating hormone (TSH) level of >4 milli-international units per liter (mIU/l) in the presence of normal free thyroxine. We also conducted a subanalysis with a threshold resulting in approximately 20% events within the cohort. We used mixed logistic regression to estimate associations between radiation dose to the thyroid and subclinical hypothyroidism.

Results: Among 102 patients, four developed subclinical hypothyroidism. There was no association between increasing radiation dose to the thyroid and incidence of subclinical hypothyroidism. However, a trend was observed suggesting that higher mean radiation dose to the thyroid was associated with elevated risk of subclinical hypothyroidism at a TSH threshold of >2.5mIU/l.

Conclusion: Using current reference levels, increasing radiation dose to the thyroid was not associated with subclinical hypothyroidism, but at lower TSH thresholds, radiation therapy may predispose to hypothyroidism.

Purpose: This nationwide Danish cohort study compared overall survival (OS) between non-Western immigrant patients and Danish-born patients with lymphoma in Denmark. Furthermore, differences in clinical and socioeconomic variables were compared, and mediators of OS differences were explored to explain possible outcome differences.

Patients and methods: The study included a total of 540 non-Western patients and 16,294 Danish-born patients diagnosed with lymphoma in the period 2000-2020. Inverse probability weighting and mediation analysis using a natural effects Cox model were used to investigate the causal relationship between immigration status and OS.

Results: Indirect effects mediated through differences in performance status and income indicated a trend towards inferior OS for non-Western immigrant patients with HRs of 1.06 (0.99-1.14) and 1.06 (0.99-1.14). However, no total causal effect of immigration status on OS was observed overall (HR: 0.94 [0.79-1.12]) and within subtype-specific analyses, except for classical Hodgkin lymphoma.

Conclusion: No significant differences in OS between non-Western immigrant patients and Danish-born patients were discovered.

Purpose: The COVID-19 pandemic had a severe influence on the entire health sector. Until today, the effect of a SARS-CoV-2 infection on older patients with a proximal humeral fracture (PHF) is unknown. This study examined the following questions: Did the incidence of PHF of older people in Germany vary during the pandemic? Did the treatment change between the lockdown and non-lockdown periods? Was a SARS-CoV-2 infection associated with a worse outcome?

Methods: Retrospective claims data of the BARMER health insurance were analysed. All in- and outpatient cases of insurance holders ≥65 years from 01/2010 to 09/2022, with coded diagnosis of PHF were analysed. Primary endpoints were the 1-month incidence of PHF per 100,000 insurance holders, number of operative therapies, in-hospital death and in-hospital major adverse events (MAEs).

Results: 174,898 inpatient PHF cases were included. During the lockdown periods, the total incidence fell, while the outpatient incidence partially increased during the pandemic-period. Regarding the therapy allocation, there were no relevant persisting changes. In a detailed analysis of 23,979 PHF cases from 01/2020 to 09/2022, 4.1% patients suffered from a SARS-CoV-2 infection and showed a notably higher in-hospital mortality (8.1% vs 2.5%; risk adjusted OR 2.79, 95% CI 2.11-3.70, p < 0.001) and more MAEs (17.0% vs 7.8%; risk adjusted OR 1.43, 95% CI 1.15-1.77, p < 0.001).

Conclusion: During the COVID-19 pandemic, the overall incidence of PHF in older patients was reduced. The treatment allocation did not change between the pre- and intra-pandemic period. An infection with SARS-CoV-2 was associated with higher mortality and more MAEs.