Purpose:Maternal smoking during pregnancy (SDP) is associated with adverse neonatal outcomes, but the specific conditions contributing to morbidity among term infants are poorly characterized. We examined whether maternal SDP increases the risk of neonatal intensive care unit (NICU) admission and antibiotic treatment during the first week of life, and identified NICU diagnoses more common among exposed infants. Methods:This register-based cohort study included all full-term (≥ 37+0 weeks' gestation) singleton births in Finland from 2006 to 2018, using data from the Finnish Medical Birth Register and Hospital Discharge Register (n = 795,836; 95.2% of singleton births). Maternal smoking was categorized as no smoking, quit smoking during the first trimester (early smoking), or continued smoking after the first trimester. Primary outcomes were NICU admission and antibiotic treatment during the first week of life. Secondary outcomes included neonatal diagnoses and perinatal mortality. Stillbirths and early neonatal deaths were excluded from the analyses of treatments and diagnoses. Adjusted odds ratios (aORs) were estimated using logistic regression, adjusting for maternal age, parity, prepregnancy BMI, mode of delivery, and year of delivery. Results:Continued smoking was associated with increased odds of NICU admission (aOR 1.43) and antibiotic treatment (aOR 1.22), while early smoking was associated with more modest increases (aORs 1.17 and 1.19, respectively), compared with no exposure. Both smoking exposures were associated with an increased risk of bacterial sepsis or congenital pneumonia. Neonatal hypoglycemia was increased only with continued smoking. Continued smoking was also associated with an increased the risk stillbirth (aOR, 1.49) whereas early smoking was not associated with perinatal mortality. Conclusion:Maternal smoking during pregnancy was associated with an increased risk of infections and metabolic disturbances requiring intensive care among term infants. Continued smoking also increased the risk of stillbirth. These findings further support the importance of smoking cessation during pregnancy.
Background:Postoperative delirium (POD) is a critical yet underrecognized complication following pulmonary lobectomy, particularly in older adults. While robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) offer advantages over open thoracotomy, their impact on POD is uncertain. This study aimed to determine the incidence and risk factors of POD following RATS or VATS pulmonary lobectomies. Methods:This retrospective study analyzed data from patients aged ≥50 years who underwent RATS or VATS lobectomies for lung cancer using the Nationwide Inpatient Sample (2005-2020). POD was identified using International Classification of Diseases (ICD) codes. Logistic regression was used to assess associations between patient demographics, comorbidities, perioperative complications, and POD risk. Results:Among 35,853 patients (mean age: 68.8 years; 55.9% female), 1.7% developed POD. POD risk was similar between patients receiving RATS and VATS. Key risk factors for POD included advanced age (RATS: adjusted odds ratio [aOR]=1.05, 95% confidence interval [CI]: 1.04-1.07; VATS: aOR=1.08, 95% CI: 1.06-1.09), pneumonia (RATS: aOR=2.23, 95% CI: 1.36-3.66; VATS: aOR=2.77, 95% CI: 1.98-3.86), and infection. Other factors associated with POD were persistent anemia, moderate/severe renal disease, and mechanical ventilation. Conclusion:POD risk was similar between RATS and VATS pulmonary lobectomies and was associated with several patient-related and perioperative factors. These findings may help inform perioperative risk assessment and postoperative monitoring in older adults undergoing minimally invasive pulmonary lobectomy.
Background:Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. China bears the world's largest AMD burden. This study analyzes the evolving AMD burden in China (1990-2023) and the impact of anti-VEGF therapy. Methods:We analyzed data from the Global Burden of Disease (GBD) 2023 study using joinpoint regression, decomposition analysis, and Bayesian modeling. A supplementary meta-analysis of single-arm studies was conducted to assess anti-VEGF efficacy in Chinese patients. Results:From 1990 to 2023, China's age-standardized prevalence rate (ASPR) and disability-adjusted life year rate (ASDR) for AMD decreased by -0.67% and -1.48% annually, respectively. In 2023, China accounted for 35.82% of global cases and 30.25% of global DALYs. A supplementary meta-analysis of 13 single-arm observational studies showed a pooled efficacy rate of 74% for anti-VEGF drugs in China, albeit with substantial heterogeneity (I2 = 93.07%), warranting cautious interpretation. The accelerated decline in ASDR after 2011 coincided temporally with the clinical introduction and subsequent insurance coverage of anti-VEGF therapy. Projections indicate a continued decline in burden through 2038. Conclusion:Despite a declining age-standardized burden, China's absolute AMD burden remains substantial due to rapid population aging and other challenges. The temporal association between anti-VEGF therapy availability and the accelerated burden decline suggests a potential contribution of this treatment, though causality cannot be directly inferred from this ecological analysis. The observed trends likely reflect multiple factors, including improved healthcare access, early diagnosis, socioeconomic development, and anti-VEGF therapy. Comprehensive strategies focusing on prevention and equitable healthcare access are needed.
Thongpitak Huabbangyang,1 Gawin Tiyawat,1 Nitiporn Puysopa,1 Thapanee Wattanasaringkarn,1 Jiratchaya Khunjan,1 Warinthorn Inthanon,1 Nattanicha Duangkaew,1 Chanathip Wanphen,2 Adisak Nithimathachoke31Department of Disaster and Emergency Medical Operation, Faculty of Science and Health Technology, Navamindradhiraj University, Bangkok, Thailand; 2Division of Emergency Medical Service and Disaster, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, 10300, Thailand; 3Department of Emergency Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, ThailandCorrespondence: Adisak Nithimathachoke, Email adisak@nmu.ac.thBackground: Early recognition of sepsis in prehospital settings remains challenging because emergency medical services (EMS) clinicians must make rapid triage decisions using limited physiological information before hospital arrival. Several sepsis screening tools have been validated in emergency department settings; however, comparative evidence in prehospital populations remains limited.Purpose: This study evaluated the diagnostic and prognostic performance of five simplified screening tools—mNEWS, qSOFA, mSIRS, mSOS, and MEWS—for identifying sepsis and predicting 30-day mortality in prehospital patients.Methods: This retrospective diagnostic accuracy study included 268 adult patients (≥ 18 years) transported by Vajira Emergency Medical Service, Bangkok, Thailand, to Vajira Hospital between January 2018 and October 2024. Prehospital clinical parameters recorded by paramedics and emergency nurse practitioners were analyzed against the final hospital diagnosis of sepsis and 30-day in-hospital mortality. Predefined thresholds (mSOS ≥ 4, MEWS ≥ 5, mNEWS ≥ 5, qSOFA ≥ 2, and mSIRS ≥ 2) were used for the primary analyses. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AuROC), sensitivity, and specificity.Results: Among 268 patients, MEWS demonstrated the highest discrimination for identifying sepsis (AuROC 0.84; sensitivity 64.9%; specificity 79.1%). mSOS (AuROC 0.83) and mSIRS (AuROC 0.82) demonstrated high sensitivity (> 96%) but lower specificity (~60%), while mNEWS showed the highest sensitivity (99.3%) but poor specificity (47.0%). qSOFA demonstrated the lowest discrimination (AuROC 0.72). For predicting 30-day mortality, MEWS demonstrated the highest performance (AuROC 0.70; sensitivity 72.2%; specificity 64.5%), followed by mNEWS and mSOS (AuROC 0.69 each), whereas qSOFA (AuROC 0.64) and mSIRS (AuROC 0.60) demonstrated lower discrimination.Conclusion: MEWS demonstrated the most balanced diagnostic performance for identifying sepsis and predicting 30-day mortality in prehospital patients. Highly sensitive tools may be useful for early screening, whereas MEWS may better support risk stratification. Further external validation is required before broader implementation.Keywords: sepsis, emergency medical services, prehospital care, diagnostic accuracy, prognosis, mortality
Kalle Korhonen,1 Lotta S Holopainen,2 Mika Gissler,3– 6 Mikael O Ekblad21Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland; 2Department of General Practice, Institute of Clinical Medicine, University of Turku and Turku University Hospital, Turku, Finland; 3THL Finnish Institute for Health and Welfare, Department of Data and Analytics, Helsinki, Finland; 4Research Centre for Child Psychiatry, University of Turku, Turku, Finland; 5Karolinska Institute, Department of Molecular Medicine and Surgery, Stockholm, Sweden; 6Region Stockholm, Academic Primary Health Care Centre, Stockholm, SwedenCorrespondence: Kalle Korhonen, Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Savitehtaankatu 5, Turku, 20520, Finland, Tel +358 2 3130795, Email kalle.korhonen@varha.fiPurpose: Maternal smoking during pregnancy (SDP) is associated with adverse neonatal outcomes, but the specific conditions contributing to morbidity among term infants are poorly characterized. We examined whether maternal SDP increases the risk of neonatal intensive care unit (NICU) admission and antibiotic treatment during the first week of life, and identified NICU diagnoses more common among exposed infants.Methods: This register-based cohort study included all full-term (≥ 37+0 weeks’ gestation) singleton births in Finland from 2006 to 2018, using data from the Finnish Medical Birth Register and Hospital Discharge Register (n = 795,836; 95.2% of singleton births). Maternal smoking was categorized as no smoking, quit smoking during the first trimester (early smoking), or continued smoking after the first trimester. Primary outcomes were NICU admission and antibiotic treatment during the first week of life. Secondary outcomes included neonatal diagnoses and perinatal mortality. Stillbirths and early neonatal deaths were excluded from the analyses of treatments and diagnoses. Adjusted odds ratios (aORs) were estimated using logistic regression, adjusting for maternal age, parity, prepregnancy BMI, mode of delivery, and year of delivery.Results: Continued smoking was associated with increased odds of NICU admission (aOR 1.43) and antibiotic treatment (aOR 1.22), while early smoking was associated with more modest increases (aORs 1.17 and 1.19, respectively), compared with no exposure. Both smoking exposures were associated with an increased risk of bacterial sepsis or congenital pneumonia. Neonatal hypoglycemia was increased only with continued smoking. Continued smoking was also associated with an increased the risk stillbirth (aOR, 1.49) whereas early smoking was not associated with perinatal mortality.Conclusion: Maternal smoking during pregnancy was associated with an increased risk of infections and metabolic disturbances requiring intensive care among term infants. Continued smoking also increased the risk of stillbirth. These findings further support the importance of smoking cessation during pregnancy.Keywords: smoking, NICU, newborn, infection, hypoglycemia
Zijian Chen,1– 5,* Jiangying Liu,1– 5,* Shizhou Cheng,6 Qihua Xu1– 51School of Optometry, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Orbital Diseases, Ocular Tumors, and Ocular Trauma, The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Jiangxi Provincial Key Laboratory for Ophthalmology, Nanchang, Jiangxi, People’s Republic of China; 4National Clinical Research Center for Ocular Diseases Jiangxi Province Division, Nanchang, Jiangxi, People’s Republic of China; 5Jiangxi Clinical Research Center for Ophthalmic Disease, Nanchang, Jiangxi, People’s Republic of China; 6Department of Ophthalmology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qihua Xu, Email eye281016@163.comBackground: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. China bears the world’s largest AMD burden. This study analyzes the evolving AMD burden in China (1990– 2023) and the impact of anti-VEGF therapy.Methods: We analyzed data from the Global Burden of Disease (GBD) 2023 study using joinpoint regression, decomposition analysis, and Bayesian modeling. A supplementary meta-analysis of single-arm studies was conducted to assess anti-VEGF efficacy in Chinese patients.Results: From 1990 to 2023, China’s age-standardized prevalence rate (ASPR) and disability-adjusted life year rate (ASDR) for AMD decreased by − 0.67% and − 1.48% annually, respectively. In 2023, China accounted for 35.82% of global cases and 30.25% of global DALYs. A supplementary meta-analysis of 13 single-arm observational studies showed a pooled efficacy rate of 74% for anti-VEGF drugs in China, albeit with substantial heterogeneity (I2 = 93.07%), warranting cautious interpretation. The accelerated decline in ASDR after 2011 coincided temporally with the clinical introduction and subsequent insurance coverage of anti-VEGF therapy. Projections indicate a continued decline in burden through 2038.Conclusion: Despite a declining age-standardized burden, China’s absolute AMD burden remains substantial due to rapid population aging and other challenges. The temporal association between anti-VEGF therapy availability and the accelerated burden decline suggests a potential contribution of this treatment, though causality cannot be directly inferred from this ecological analysis. The observed trends likely reflect multiple factors, including improved healthcare access, early diagnosis, socioeconomic development, and anti-VEGF therapy. Comprehensive strategies focusing on prevention and equitable healthcare access are needed.Keywords: age-related macular degeneration, global burden of disease, China, anti-VEGF drugs, meta-analysis
Cheng-Hung How,1,2 Chor-Kuan Lim,3 Jia-Hao Zhang2,4,51Division of Thoracic Surgery, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Nursing, Cardinal Tien College of Healthcare and Management, New Taipei City, Taiwan; 3Department of Respiratory and Internal Medicine, Regency Specialist Hospital, Masai, Johor, Malaysia; 4Department of Critical Care Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 5Department of Chest Medicine, Far Eastern Memorial Hospital, New Taipei City, TaiwanCorrespondence: Jia-Hao Zhang, Department of Chest Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan, Tel +886-2-7728-4525, Email sid5850@gmail.comBackground: Postoperative delirium (POD) is a critical yet underrecognized complication following pulmonary lobectomy, particularly in older adults. While robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) offer advantages over open thoracotomy, their impact on POD is uncertain. This study aimed to determine the incidence and risk factors of POD following RATS or VATS pulmonary lobectomies.Methods: This retrospective study analyzed data from patients aged ≥ 50 years who underwent RATS or VATS lobectomies for lung cancer using the Nationwide Inpatient Sample (2005– 2020). POD was identified using International Classification of Diseases (ICD) codes. Logistic regression was used to assess associations between patient demographics, comorbidities, perioperative complications, and POD risk.Results: Among 35,853 patients (mean age: 68.8 years; 55.9% female), 1.7% developed POD. POD risk was similar between patients receiving RATS and VATS. Key risk factors for POD included advanced age (RATS: adjusted odds ratio [aOR]=1.05, 95% confidence interval [CI]: 1.04– 1.07; VATS: aOR=1.08, 95% CI: 1.06– 1.09), pneumonia (RATS: aOR=2.23, 95% CI: 1.36– 3.66; VATS: aOR=2.77, 95% CI: 1.98– 3.86), and infection. Other factors associated with POD were persistent anemia, moderate/severe renal disease, and mechanical ventilation.Conclusion: POD risk was similar between RATS and VATS pulmonary lobectomies and was associated with several patient-related and perioperative factors. These findings may help inform perioperative risk assessment and postoperative monitoring in older adults undergoing minimally invasive pulmonary lobectomy.Keywords: postoperative delirium, nationwide inpatient sample, pulmonary lobectomy, robotic-assisted thoracoscopy, video-assisted thoracoscopy
Hannah Christina Puhr,1 Martin Korpan,1 Vincent Sunder-Plassmann,1 Gerd Jomrich,2 Dagmar Kollmann,2 Sebastian F Schoppmann,2 Julia M Berger,1 Gerald W Prager,1 Elisabeth S Bergen,1 Eva K Masel,3 Matthias Preusser,1 Aysegül Ilhan-Mutlu,1 Feroniki Adamidis31Department of Medicine I - Division of Oncology, Medical University of Vienna, Vienna, Austria; 2Department of General Surgery - Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria; 3Department of Medicine I - Division of Palliative Medicine, Medical University of Vienna, Vienna, AustriaCorrespondence: Feroniki Adamidis, Department of Medicine I - Division of Palliative Medicine, Medical University of Vienna, Vienna, Austria, Email feroniki.adamidis@meduniwien.ac.atBackground: Despite therapeutic advances, gastroesophageal cancers remain associated with high mortality. While most deaths are cancer-related, improvements in therapy and supportive care may alter mortality patterns over time. This study aimed to characterize causes of death and associated clinical factors in a large real-world European cohort.Methods: We retrospectively included 2518 patients with histologically confirmed esophageal, gastric, or gastroesophageal junction carcinomas treated at the Medical University of Vienna between 1994 and 2024. Causes of death were obtained from Austria’s national death registry and categorized using International Classification of Diseases (ICD) codes. Fine–Gray competing risk models were applied to identify factors associated with cancer- and non-cancer-related deaths.Results: At data cutoff, 1863 patients (74%) had died. Of these, 85% of deaths were cancer-related, 12% non-cancer-related, 2% unknown, and < 1% suicide. Tumor stage was the strongest predictor of cancer-related mortality, with subdistribution hazard ratios (sHR) increasing from 2.34 (95% CI 1.91– 2.86) in stage 2 to 7.42 (95% CI 6.15– 8.96) in stage 4 disease compared with stage 1 (all p
Caroline Hartwell Garred,1 Clara Friis,1 Mariam Elmegaard,1 Daniel Mølager Christensen,1 Emil Wolsk,1 Lars Køber,1,2 Morten Schou1,21Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark; 2Department of Clinical Medicine, Faculty of Health and Science, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Caroline Hartwell Garred, Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark, Tel +45 23 60 16 06, Email caroline.amalie.hartwell.garred.01@regionh.dkBackground: The Danish administrative registers are a powerful tool for heart failure (HF) research. However, the coding system has historically does not distinguished between HF phenotypes. We aimed to identify the distribution of HF with reduced ejection fraction (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) within the Danish National Patient Register overall and across age groups.Methods: We manually reviewed electronic health records of all patients with an incident primary diagnosis of HF (ICD-10: I50) at two large university hospitals in the Capital Region of Denmark between June 2021 and May 2024. HFrEF was defined as left ventricular ejection fraction (LVEF) ≤ 40%, HFmrEF as 41– 49%, and HFpEF as ≥ 50%. Patients without available echocardiographic measurements were classified together with the HFpEF group. The phenotypic distribution was stratified by age groups (< 65, 65– 79, and ≥ 80 years) and six clinical subgroups (female sex, obesity, chronic kidney disease, atrial fibrillation/flutter, diabetes, and ischemic heart disease).Results: Following manual review of 1888 patients with a primary diagnosis of HF (median age 74, 67% male), 1687 (89%) had HFrEF, 72 (4%) HFmrEF, and 129 (7%) HFpEF. HFrEF was dominant across all ages but was lower with advancing age: 95% in patients aged < 65 years, 90% in those aged 65– 79, and 83% among those aged ≥ 80. In all clinical subgroups, the proportion of HFrEF remained high, ranging from 83 to 90%.Conclusion: Patients with an incident hospital diagnosis of HF at two Danish university hospitals predominantly presented with HFrEF. This phenotype distribution may reflect that of patients diagnosed with HF in the Danish National Patient Register. Even among those aged ≥ 80 years, fewer than one in five patients presented with HFmrEF or HFpEF. These findings provide a necessary reference for interpreting Danish registry-based HF data and inform the design of future registry-based clinical trials.Keywords: heart failure, phenotype, register data, epidemiology
The Danish National Patient Register (DNPR) is an important data source for register-based health-related research, providing detailed information on all hospital contacts in Denmark. With the transition from the second version of the DNPR (DNPR2) to the third version (DNPR3) in early 2019, the variable distinguishing inpatient and outpatient contacts was discontinued, introducing substantial methodological challenges for epidemiological research. This perspective provides a narrative synthesis of current approaches to classifying hospital stays in DNPR3 and highlights key epidemiological considerations. Two main methodological approaches were identified: consensus-based frameworks, which emphasize interpretability and clinical reasoning and data-driven algorithms, which leverage patterns in register data to improve classification performance. Existing methods generally provide reasonable classification for inpatient and elective outpatient contacts. However, classification of acute outpatient visits remains a persistent and unresolved challenge, reflecting heterogeneous registration practices and the absence of a gold-standard reference in DNPR3. Further, current methodological approaches are fragmented and context-dependent, limiting comparability across studies and over time. We therefore call for coordinated efforts to develop transparent, validated, and consensus-driven classification frameworks. Such efforts are essential to ensure valid, reproducible, and interpretable epidemiological research using DNPR data.
Background:Real-world selection of lipid-lowering therapies (LLT) is often affected by patient prognosis, leading to residual bias in comparing treatment effects. We used negative control outcomes (NCOs) to assess the comparability in a traditional active comparator design (evolocumab vs other LLT initiators) and in a study design between patients treated and non-treated after evolocumab initiation. Methods:Using Tianjin Regional Healthcare Database, an electronic health records (EHR) database in China, we identified patients who initiated evolocumab and patients who initiated other LLT from 2018 to 2023. Within the evolocumab cohort, we further defined patients who filled the second prescription of evolocumab as "treated" and patients who did not as "non-treated" after evolocumab initiation. We evaluated residual confounding by calculating hazard ratios (HR) to compare the one-year risk of NCOs in the domains of frailty and health-seeking behavior in the two designs after applying inverse probability of treatment weighting (IPTW). Results:14,978 evolocumab initiators (5708 patients treated and 9270 patients non-treated), and 658,255 other LLT initiators were identified. Compared to other LLT initiators, evolocumab initiators showed a lower risk of fracture in domain of frailty (HR 0.75, 95% CI 0.56-1.00), and a higher risk of visual test in domain of health-seeking behavior (HR 2.41, 95% CI 1.31-4.47). Between patients treated and non-treated after evolocumab initiation, no association was identified in domain of frailty: fracture (HR 1.02, 95% CI 0.81-1.54) and incident cancers excluding nonmelanoma skin cancers (HR 1.01, 95% CI 0.81-1.28), whereas event numbers were insufficient for evaluating NCOs in the health-seeking behavior domain. Conclusion:Comparing evolocumab to other LLTs may result in biased estimates, while the treated and non-treated evolocumab initiators are more comparable in the measured confounding and the NCO domain of frailty. This study provides important insights for consideration when designing a comparative study in China.
Purpose:Patients represented in biobank cohorts may differ from the broader registry-defined cancer population. This study aimed to describe demographic, clinical, and survival differences between biobank-linked and non-biobank-linked patients with liver cancer in a nationwide cancer registry. Patients and Methods:This retrospective, registry-based exploratory study linked patients from the Taiwan Liver Cancer Network (TLCN), a multicenter liver cancer biobank, to the Taiwan Cancer Registry (TCR) database and identified patients diagnosed with liver cancer (ICD-O-3: C22) from 2007 to 2020. Comorbidities and survival follow-up were obtained from the National Health Insurance Research Database and the Death Registry. Patients were classified as TLCN-linked or non-TLCN-linked according to linkage status with the TLCN. Group differences were described using absolute standardized mean differences (ASMDs), and overall survival was summarized using Kaplan-Meier estimates and compared using Log rank tests. Results:We compared 4790 TLCN-linked patients with 126547 non-TLCN-linked patients identified in the cancer registry. Using an ASMD threshold of 0.20, several meaningful between-group differences were observed. Compared with non-TLCN-linked patients, TLCN-linked patients were younger and had higher proportions of men (79.0% vs 69.9%), early stage (stages I-II: 78.6% vs 57.2%), and surgery as first-course treatment (94.8% vs 50.75%), as well as a lower proportion of recorded metastasis (1.5% vs 12.6%). Differences in most comorbidities were small by ASMD. Among patients who received surgery, median overall survival was longer in TLCN-linked patients than in non-TLCN-linked patients across stages; for example, among stage I patients, median survival was 10.89 versus 7.27 years, respectively. Conclusion:Although TLCN biospecimens and associated data provide an important resource for translational research, TLCN-linked patients differed from non-TLCN-linked patients in the nationwide registry. These findings highlight the importance of considering the composition of the TLCN cohort when interpreting the applicability of future studies using TLCN biospecimens and associated data.
Purpose:This study aimed to develop and validate a clinical prediction model for target lesion revascularization (TLR) at one-year follow-up in patients undergoing percutaneous coronary intervention (PCI) with implantation of a drug-eluting stent (DES). Patients and Methods:Using real-world data from the Netherlands Heart Registration, we included patients treated with at least one DES between 2019 and October 2022. The study cohort comprised 96,758 patients from 29 centers, while a sub-cohort of 11,789 patients from 11 centers had additional procedural data. Multivariable logistic regression with backward stepwise selection was used for model development. Final coefficients were pooled across 20 imputed datasets, and separate models were built for both cohorts. Results:The study cohort model included age, sex, interaction between age and sex, diabetes mellitus, renal insufficiency, multivessel disease, out-of-hospital cardiac arrest (OHCA), cardiogenic shock, previous myocardial infarction, previous coronary intervention, access site, number of treated vessels, PCI in the left main, and PCI in arterial or venous grafts. The optimism-corrected area under the curve (AUC) was 0.645 (95% confidence interval (CI): 0.633-0.657). The sub-cohort model incorporated total stent length in the left anterior descending artery, arterial or venous grafts, and left main, along with renal insufficiency, previous coronary intervention, and OHCA, yielding an AUC of 0.662 (95% CI: 0.631-0.693). Conclusion:The developed models provide a basis for predicting one-year TLR using routinely collected data. Despite strong calibration, their modest discrimination suggests a need for more detailed variables and advanced modelling approaches to improve performance.
Purpose:The Danish Lymphoid Cancer Research (DALY-CARE) Genetic Cohort was established to support research into how genetic factors influence clinical outcomes in lymphoid cancers (LCs), including disease progression, treatment response, toxicity, and survival. Individual-level genetic data were combined with detailed clinical information from national health registers, hospital-based electronic health records (EHR), laboratory data, and pathology reports. The cohort enables large-scale studies of genetic susceptibility, disease course, and therapy-related outcomes in LCs and provides a platform for genetic epidemiology and future multi-omics research within a unified data infrastructure. Participants:The genetic cohort includes 8675 genotyped individuals drawn from the broader DALY-CARE population (n=74,251, as of April 2025), including individuals diagnosed with LCs such as diffuse large B-cell lymphoma (DLBCL, n=1349), chronic lymphocytic leukemia (CLL, n=1245), multiple myeloma (MM, n=1209), follicular lymphoma (FL, n=704), Hodgkin lymphoma (HL, n=407), Waldenström macroglobulinemia and lymphoplasmacytic lymphoma (WM/LPL, n=368), marginal zone lymphoma (MZL, n=287), and precursor states such as monoclonal gammopathy of undetermined significance (MGUS, n=1299). Descriptive Findings:Hematologic malignancy was the most frequent cause of death (30%), followed by infections (27%) and other cancers (15%). Polypharmacy, as a more sensitive proxy for comorbidity than hospital diagnosis codes, was substantial (median 7-8 drugs pre-diagnosis). Frequently observed comorbidities were hypertension (47%), cardiovascular disease (16%), cerebrovascular disease (11%) and type 2 diabetes (10%). Kinship analysis identified limited relatedness (41 parent-offspring, 51 siblings), while ancestry inference confirmed predominantly Northwestern European descent (97%). Future Opportunities:The DALY-CARE Genetic Cohort provides a foundation for studying genetic and clinical determinants of LC outcomes. Integration of genotype data with EHR and national health registers enables exploration of germline risk and protective variants. Future expansions will integrate additional omics data types, such as whole-genome sequencing, transcriptomics, proteomics, and immunophenotyping, positioning the cohort as a national platform for multi-omics research in LC.
Purpose: Stress disorders are associated with immunosuppression, potentially reducing the ability to clear human papillomavirus (HPV) infections, leading to an increased risk of HPV-related cancers. We investigated the association between stress disorders and HPV-related cancers in Denmark. Patients and Methods: Using population-based medical registries, we identified patients with an incident hospital-diagnosed stress disorder between 1 January 1995 and 31 December 2021 (acute stress reaction, posttraumatic stress disorder, adjustment disorder, and other/unspecified reactions to severe stress), matched them by age and sex to individuals without any stress disorder diagnoses in the general population (1:5 ratio), and identified subsequent HPV-related cancer diagnoses (cervical, anal, vulvar, vaginal, penile, base of tongue, tonsillar, oropharyngeal) through 2022. Follow-up began after a 1-year lag period and was censored at first HPV-related cancer, other cancer diagnosis, emigration, death, or end of study. Covariates were measured prior to stress disorder diagnosis or matching date. We used Cox proportional hazards regression to estimate the sex-stratified adjusted hazard ratio (aHR) and 95% confidence interval (CI) of any HPV-related cancer and specific HPV-related cancers, adjusting for potential confounders. Results: During a median follow-up of approximately 10 years, there were 755 cases of HPV-related cancer in the stress disorder cohort (n=242,828) and 2,820 cases in the comparison cohort. Women with diagnosed stress disorders were more likely to develop any HPV-related cancer (aHR=1.3, 95% CI: 1.1-1.4), while men with stress disorders had an elevated rate of anal cancer specifically (aHR=1.7, 95% CI: 1.0-2.9) than their counterparts without stress disorders. The association between stress disorders and HPV-related cancer increased with younger age at stress disorder diagnosis and with longer follow-up time. Conclusion: Our results suggest an association between stress disorders and slightly elevated rates of HPV-related cancer, which strengthens with longer follow-up, underscoring the need to understand biological and behavioral pathways linking stress disorders to increased risk of HPV-related cancer.
The growth in evidence-based medicine clearly benefits patient care but it is important that evidence is accessible and usable. Translating research results into usable, meaningful information can be challenging and impede the implementation of robust evidence. There are many aspects to making the statistical parts of a research study actionable for practicing clinicians and policy makers. These include ensuring that the right questions are asked, the study is designed appropriately, and results are transparent and applicable to the clinical setting. In this perspectives-style article we offer guidance on these considerations by highlighting several approaches that we have found effective for improving the interpretability and practical application of statistical findings. Our over-arching aim is to stimulate interdisciplinary dialogue throughout the research process. Specifically, we discuss the interpretation of p-values, effect estimates, differences between means, scaling regression coefficients, unadjusted/adjusted estimates, Minimal Clinically Important Difference, absolute and relative risk, and suggest how clinical meaning can be enhanced by presenting the same information in different but complementary ways. We conclude with a recommendation that study teams prioritize interdisciplinary discussions around clinical meaningfulness throughout our research studies to maximize their clinical impact.
Purpose: Heart disease complicating pregnancy is a major contributor to maternal morbidity and mortality worldwide, yet its true burden remains underexplored. Electronic medical records may help address this gap. However, the accuracy of the data that can be obtained needs to be established before undertaking estimations. This study evaluates the sensitivity of administrative coding in identifying pregnancies complicated by heart disease during childbirth admissions in a tertiary Australian setting. Patients and Methods: Using a prospectively maintained clinical database of 155 women who received specialized cardio-obstetric care, we compared ICD-10-AM codes recorded in hospital administrative data related to their delivery admission against a cardiologist-adjudicated reference standard. Case and individual code-level comparisons were undertaken. Results: The sensitivity of administrative coding for detecting any cardiac disease was 66.5%. Only 25.2% of cases were completely matched to the clinical diagnosis, and 41.3% mismatched (partial or incorrect). Notably, 33.5% of cases were not coded with any cardiac-related code. At the individual code level, sensitivity varied widely across disease categories: the lowest sensitivity (19%) was shown for arrhythmias. Congenital heart disease, the most common etiology in this cohort, was frequently not coded, particularly when surgically corrected. Conclusion: In addition to incorrect coding, findings reflect the structure of ICD-10-AM, which captures only diagnoses requiring active management during the hospital encounter. As most cardio-obstetric care is delivered antenatally, mainly to prevent peripartum complications, well-managed conditions with uncomplicated delivery may not be coded, leading to underestimation that is independent of the severity of the cardiac condition and associated risk. While exact estimates of coding sensitivity may vary by context, most of the identified issues would be common across Australia and the world. Epidemiological studies and service planning based on ICD-10-AM data should consider enhanced case-ascertainment strategies, including patient-level data linkage and diagnostic look-back periods, to improve accuracy.
Purpose:Cancer outcome studies frequently utilize registry data, which provide large-scale population-level information. However, these registries often lack detailed clinical information regarding comorbidities, lifestyle factors, and in-hospital treatments. The Central Denmark Cancer Cohort (CDCC) was established to address these limitations by linking medical and administrative registry data with clinical electronic medical records (EMR), to facilitate research to better understand the clinical course of cancer and its complications. Patients and Methods:The CDCC includes all patients with incident cancer, except non-melanoma skin cancer, diagnosed in the Central Denmark Region between 2012 and 2021, with complete follow-up through December 31, 2021. The CDCC was identified from the Danish Cancer Registry and linked via the Civil Personal Registration number to the Central Denmark Region Clinical Information System (CDRCIS) and to national registries, including the Danish National Patient Registry, National Prescription Registry, and Register of Laboratory Results for Research. We extracted data on demographics, lifestyle factors, comorbidities, treatments, and survival outcomes and assessed the availability of these data. Results:The CDCC included 68,028 patients with a median age of 68 years (interquartile range: 59-76 years); 47.2% were female. The most common cancers were prostate cancer (10,024 patients), breast cancer (9,100 patients), and non-small cell lung carcinoma (7,264 patients). At diagnosis, 98.0% of patients had laboratory test results available, 87.5% received at least one in-hospital medication, and 86.9% had at least one characteristic documented in CDRCIS. During median follow-up of 2.6 years, 37.8% of patients died and five-year survival was 59.0% (95% confidence interval: 58.6-59.4%). Data completeness varied by cancer type. Conclusion:The CDCC integrates clinical, lifestyle, and laboratory data with cancer registry information. By capturing factors typically unavailable in registry-based research, this platform offers a unique foundation for longitudinal studies on the clinical course of cancer.
Background and objective: Prediction stability is increasingly recognised as important for reliable clinical prediction model development, but the effect of continuous predictor modelling choices is unclear. This study examined how approaches to modelling continuous predictors influence prediction stability. Methods: We used a real clinical dataset of 19,418 emergency department patients to create five sample size scenarios ranging from 437 to 8,739 patients. Six methods were compared: dichotomisation at the median (DIC), tertile categorisation (TER), linear terms (LIN), quadratic terms (QUA), multivariable fractional polynomials (MFP), and extreme gradient boosting (XGB). Prediction stability was evaluated using a bootstrap-based framework. Optimism-corrected AUC and calibration were estimated through internal validation. A method was considered stable when at least 90
