Search Results (413)

Background/Objectives: Type 2 diabetes (T2D) and chronic kidney disease (CKD) frequently coexist in older adults. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are recommended for renal and heart protection, yet their use in routine care remains inconsistent. We aimed to investigate differences in SGLT2i prescribing between regional and university hospital settings and assess whether such disparities persist after accounting for patient characteristics. Methods: In this retrospective analysis, patients were stratified by follow-up site (regional vs. university hospital). The primary outcome was SGLT2i use. Logistic regression models were adjusted for strong determinants of prescribing decisions, including age, sex, hypertension, dyslipidemia, heart failure, and estimated glomerular filtration rate. We tested the robustness of the results using additional analyses, including exclusion of frail patients and adjustment with propensity score methods, such as matching and inverse probability weighting (IPTW). Results: The study included 135 patients, of whom 80 were followed at the regional hospital and 55 at the university hospital. SGLT2i use was significantly lower in the regional setting (27.5% vs. 63.6%, p < 0.001). In adjusted models, university follow-up remained strongly associated with SGLT2i prescription [odds ratio 3.60, 95% confidence interval (CI) 1.61–8.03, p = 0.0018]. IPTW demonstrated 4.40-fold higher odds of SGLT2i use in the university hospital setting (95% CI 2.07–9.36, p < 0.001). Conclusions: These findings indicate that the lower use of SGLT2i among older adults with T2D and CKD followed in regional hospitals may reflect patterns consistent with clinical inertia, underscoring the importance of efforts to promote equitable and guideline-aligned prescribing practices across levels of care. Full article

Background/Objectives: Metformin is one of the most frequently used concomitant medications among prostate cancer (PCa) patients. However, the effects of metformin on all-cause and PCa-specific mortality among men diagnosed with advanced/metastatic PCa treated with androgen-deprivation therapy (ADT) remain poorly understood, but they may be specifically explained by emulating a target trial. Methods: We emulated a target trial of metformin therapy and survival using observational data on 7361 patients diagnosed with advanced PCa, who were treated with ADT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2008–2019), with completed follow-up until 2020. We included patients with diabetes, and participants were assigned as either “initiator of metformin within 6 months after advanced PCa diagnosis” or “non-initiator of metformin.” We estimated mortality risks using Cox proportional hazards models with adjustment for risk factors via inverse probability weighting using both intention-to-treat and per-protocol analyses. Results: Over 13 years of follow-up, with a maximum 3 years of follow-up after PCa diagnosis, all-cause mortality occurred in 52 metformin initiators (47.7%) versus 3052 non-initiators (42.1%), while PCa-specific mortality occurred in 36 initiators (33.0%) versus 1919 non-initiators (26.5%). In the intention-to-treat analysis, metformin initiation was not associated with all-cause mortality (Hazard Ratio [HR] = 1.38, 95% CI: 0.98–1.95) or PCa-specific mortality (HR = 0.99, 95% CI: 0.63–1.55). Similarly, in per-protocol analysis, there was no evidence of risk reduction with all-cause (HR = 1.20, 95% CI = 0.80–1.81) or PCa-specific mortality (HR = 1.45, 95% CI = 0.88–2.38) after adjusting for time-varying covariates and allowing a 30-day gap for metformin discontinuation, adjusted for via inverse probability weighting. Conclusions: Our findings align with prior randomized trials showing no survival benefit of metformin in advanced PCa patients receiving ADT. Timing of metformin discontinuation also showed no significant effect. However, the small size of the metformin initiator group precluded subgroup analyses for hormone-sensitive (HSPC) and castrate-resistant prostate cancer (CRPC), limiting our ability to explore potential differential effects. Full article

Patients with chronic obstructive pulmonary disease (COPD) are vulnerable to developing severe SARS-CoV-2 infection. This retrospective study evaluated the effectiveness of remdesivir (RDV) initiated with corticosteroids (CCS) versus CCS only in patients with COPD hospitalized for SARS-CoV-2 infection during the Omicron period from December 2021 to February 2024. The analysis used patient-level data from the large, geographically diverse, US hospital administrative billing PINC AI healthcare database. Inverse probability of treatment weighting was used to adjust for potential confounding and enable a scientifically robust comparative assessment of differences in outcomes between treatment groups. Initiation of RDV with CCS upon admission for SARS-CoV-2 infection was associated with a lower mortality risk at 14 and 28 days with an overall adjusted hazard ratio [95% CI] of 0.74 [0.68–0.80] and 0.76 [0.71–0.82], respectively, compared to initiation of CCS only. The combination of RDV and CCS was also associated with a lower mortality risk at 14 and 28 days for patients across baseline oxygen requirements compared to CCS only. These results highlight the benefit of timely RDV treatment in COPD patients hospitalized with SARS-CoV-2 infection and underscore the value of considering established treatment paradigms in the context of the most recent collective evidence. Full article

Control charts are commonly practical as diagnostic tools in statistical applications to recognize probable changes in a process. Control charts find general use as diagnostic tools in statistics in the detection of probable shifts in a process. Among the variety of methods of detection of smaller shifts in processes, the cumulative sum (CUSUM) chart is the most useful in general use. The standard CUSUM chart is often based on the normal distribution, an assumption that does not often align with the quality characters of the majority of real processes. However, many real-world processes exhibit asymmetric and heavy-tailed behavior, which limits the performance of traditional symmetric control chart models. This study presents a new CUSUM control chart based on the inverse Maxwell (IM) distribution and terms it the IMCUSUM chart. The proposed chart’s performance is assessed based on run-length (RL) metrics, which comprise the RL average, the standard deviation of RL, and the median RL. Comparison with the existing IM exponentially weighted moving average (IMEWMA) chart is performed. The results reveal that the proposed IMCUSUM chart performs better compared with the existing IMEWMA chart, especially in the detection of small and moderate shifts in processes. The practical application of the proposed IMCUSUM chart is demonstrated with the application of the proposed and existing control charts in the survival analysis of the lifetimes of brake pads of cars. This real application example highlights the practical application of the proposed IMCUSUM chart in real processes. Full article

Background and Objectives: The best method for reconstructing the stomach after distal gastrectomy surgery in gastric cancer patients continues to be a subject of ongoing discussion. The most beneficial surgical option for patients is Billroth I (BI), yet surgeons may perform Billroth II and Roux-en-Y (BII/RY) procedures because they are easier to execute, although their impact on recovery complications and postoperative function remains unclear. This prospective observational cohort study compares the short- and mid-term surgical outcomes between BI and BII/RY reconstructions. Materials and Methods: We included 150 patients who received curative intent distal gastrectomy at the General Surgical Clinic of Emergency County Hospital in Târgu Mureș, Romania, between October 2021 and December 2024 (72 BI and 78 BII/RY patients), with a mean age of 61.5 ± 10.8 years (60.7% male). The outcomes included recovery parameters, postoperative complications (Clavien–Dindo), and mid-term functional results (PPI use, Los Angeles classification esophagitis, bile reflux gastritis, Sigstad dumping score). Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline covariates. Results: The results indicated that IPTW adjustment did not change the baseline demographics, tumor characteristics, or perioperative factors. The baseline characteristics were comparable between groups (p > 0.05). There were no significant differences in time to flatus (p = 0.12), oral diet (p = 0.70), or hospital stay (p = 0.69). Major morbidity (Clavien–Dindo ≥ III) occurred in 12.7% overall (p = 0.17), and the 90-day mortality was 5.3% (p = 1.00). At 6 months, bile reflux gastritis was more frequent after BII/RY (p = 0.16), whereas dumping syndrome occurred more often after BI (p = 0.16). Conclusions: The short-term surgical results, together with the total postoperative complications, showed no difference between the BI and BII/RY reconstruction methods. The study revealed distinct functional results between the two groups during the mid-term assessment, which demonstrates that surgeons should maintain their practice of choosing reconstruction techniques according to patient-specific requirements. Full article

Wearable, rectifiable aerosol photometers (WRAPs), instruments with combined nephelometer and on-board filter-based sampling capabilities, generally show strong correlations with reference instruments across a range of ambient and household PM_2.5 concentrations. However, limited data exist on their performance when challenged by mixed aerosol exposures, such as those found in dusty occupational environments. Understanding how these instruments perform across a spectrum of environments is critical, as they are increasingly used in human health studies, including those in which concurrent PM_2.5 and coarse dust exposures occur simultaneously. The authors collected co-located, ~24 h. breathing zone gravimetric and nephelometer PM_2.5 measures using the MicroPEM v3.2A (RTI International) and the UPAS v2.1 PLUS (Access Sensor Technologies). Samples were collected from adult brick workers (n = 93) in Nepal during work and non-work activities. Median gravimetric/arithmetic mean (AM) PM_2.5 concentrations for the MicroPEM and UPAS were 207.06 (interquartile range [IQR]: 216.24) and 737.74 (IQR: 1399.98) µg/m³, respectively (p < 0.0001), with a concordance correlation coefficient (CCC) of 0.26. The median stabilized inverse probability-weighted nephelometer PM_2.5 concentrations, after gravimetric correction, for the MicroPEM and UPAS were 169.16 (IQR: 204.98) and 594.08 (IQR: 1001.00) µg/m³, respectively (p-value < 0.0001), with a CCC of 0.31. Digital microscope photos and electron micrographs of filters confirmed large particle breakthrough for both instruments. A possible explanation is that the miniaturized pre-separators were overwhelmed by high dust exposures. This study was unique in that it evaluated personal PM_2.5 monitors in a high dust occupational environment using both gravimetric and nephelometer-based measures. Our findings suggest that WRAPs may substantially overestimate personal PM_2.5 exposures in environments with concurrently high PM_2.5 and coarse dust levels, likely due to large particle breakthrough. This overestimation may obscure associations between exposures and health outcomes. For personal PM_2.5 monitoring in dusty environments, the authors recommend traditional pump and cyclone or impaction-based sampling methods in the interim while miniaturized pre-separators for WRAPs are designed and validated for use in high dust environments. Full article

Backgrounds/Objectives: Trabeculectomy is the gold standard for glaucoma drainage surgery, but it is associated with a risk of sight-threatening complications. The PreserFlo MicroShunt (PF) is a less invasive alternative that aims to reduce complications and simplify post-operative care. This study aimed to compare the effectiveness and safety of PF to trabeculectomy in the management of glaucoma. Methods: This was a retrospective cohort analysis of 95 eyes (48 PF, 47 trabeculectomy) from a single-center private practice in Brisbane, Australia. Data were collected from November 2017 to January 2024. Primary outcomes included intraocular pressure (IOP) and the number of medications. Secondary outcomes included best-corrected visual acuity (BCVA) and complications. Inverse probability of treatment weighting (IPTW) was applied to baseline covariates, and weighted regression and Cox proportional hazards models were then used to estimate treatment effects. Results: The two groups had comparable patient characteristics, although the PF group was older with worse visual field mean deviation. At 12 months, both procedures significantly reduced IOP and medications; however, differences were not statistically significant between groups (2.9 mmHg; 95%CI: −2.0, 7.9; p = 0.303, and 0.4; 95%CI: −0.13, 0.96; p = 0.138, respectively). The estimated probabilities of qualified success were comparable (74.9% PF vs. 72.5% trabeculectomy). Intra-operative stenting in PF eyes eliminated early post-operative hypotony. The incidence of open surgical revision in the PF group vs. the trabeculectomy group was 14.6% vs. 2.1% (p = 0.059, respectively). PF was associated with faster post-operative inflammation resolution (hazard ratio: 6.3; 95%CI: 2.8, 14.5; p < 0.001). Conclusions: Both PF and trabeculectomy are effective for glaucoma management. PF is a less invasive procedure with a lower rate of early hypotony when stented. Trabeculectomy has a tendency for lower IOP reduction and less requirement for open revision, although this did not reach statistical significance. This highlights the need for longer-term studies and improved techniques, such as more effective anti-fibrotic strategies. Full article

Background/Objectives: Liver transplantation (LT) remains the standard treatment for end-stage liver disease. While donation after brain death (DBD) is the predominant source of grafts, non-standard donors are increasingly used. Optimizing procurement techniques may improve graft function and reduce early allograft dysfunction (EAD). Methods: This retrospective monocenter study analyzed 231 first LT performed between 2013 and 2024. Patients were divided into two eras: Era 1 (n = 143, 2013–2019, standard aortic perfusion) and Era 2 (n = 88, 2019–2024, refined procurement strategies including combined aortic-portal perfusion, adjusted perfusion volumes, and additional caval venting). Exclusion criteria were retransplantation, DCD, split grafts, combined transplants, and early thrombosis. The primary endpoint was EAD. Secondary endpoints included graft loss and mortality. Stabilized inverse probability of treatment weighting (IPTW) was applied to balance groups. Results: After IPTW, EAD incidence was significantly reduced in Era 2 (42.3% vs. 24.6%, p < 0.0001). Similarly, graft loss (12.6% vs. 32.2%, p < 0.0001) and mortality (11.6% vs. 30.8%, p < 0.0001) decreased. Kaplan–Meier analysis showed improved graft survival in Era 2 (HR = 0.52, 95%CI: 0.28–0.99, p = 0.046). Sub-analysis of expanded criteria donors confirmed significant reductions in EAD, graft loss, and mortality. Conclusions: Refined procurement strategies in DBD grafts significantly reduced EAD, graft loss, and mortality. These simple, cost-effective refinements represent a valuable approach to optimize outcomes, particularly with marginal donors, and warrant validation in multicenter prospective studies. Full article

Renin–angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), have been associated with improved outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the differential impact of ACEIs versus ARBs on survival and cardiovascular outcomes in individuals with MASLD. Using data from the UK Biobank, we identified 52,143 participants with exclusive use of either an ACEI or ARB. Individuals with viral, autoimmune, cholestatic, or alcohol-related liver disease were excluded. MASLD was defined as fatty liver index ≥ 60 with ≥1 cardiometabolic risk factor. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders. Outcomes included all-cause mortality, cardiovascular events, hepatic decompensation, and hepatocellular carcinoma (HCC), analyzed using Cox proportional hazards models. Among MASLD participants, ARB use was associated with significantly lower all-cause mortality compared to ACEI use (HR, 0.94; 95% CI, 0.90–1.00; p = 0.031) after IPTW adjustment. Cardiovascular risk was also lower with ARBs (HR, 0.92; 95% CI, 0.89–0.96; p < 0.001), particularly in subgroups with BMI ≥ 25 kg/m², no diabetes, and advanced fibrosis. No differences in hepatic decompensation or HCC incidence were observed. Benefits of ARBs were not significant in participants without steatotic liver disease. ARB use was associated with improved survival and reduced cardiovascular events in individuals with MASLD, whereas ACEIs expressed no comparable benefit. These findings suggest that ARBs might be a more effective RAS inhibitor subclass in MASLD and support their preferential use in patients with steatotic liver disease requiring antihypertensive therapy. Full article

Background: Atrial fibrillation (AF) is a common tachyarrhythmia associated with increased morbidity. AF frequently occurs alongside mitral regurgitation (MR). Although the impact of MR severity on AF is well proven, its effect on AF recurrence post-ablation is unclear and was the focus of our study. Methods: Retrospective single-center cohort of patients who underwent AF catheter ablation from 2014 to 2024. Pre-procedural transthoracic echocardiograms evaluated pre-ablation baseline MR severity. Patients with ‘significant’ MR (defined as moderate–severe or severe MR) were compared to those with ‘non-significant’ MR. Univariate Kaplan–Meier (KM) survival analysis, multivariable Cox proportional hazards models, and inverse probability treatment weighting (IPTW) method were applied to assess the association between baseline MR and AF recurrence post-ablation. Results: Among 444 patients undergoing AF ablation, 28 (6.3%) had ‘significant’ baseline MR. Over median follow-up of 19 months, 104 (23.4%) patients experienced AF recurrence. Univariate and KM survival analyses showed a non-significant trend for increased AF recurrence among patients with ‘significant’ MR. Applying KM analysis on balanced IPTW pseudo-population revealed robust association between ‘significant’ MR and AF recurrence post-ablation (HR = 2.41, 95% CI 1.80–3.22, p < 0.001). Multivariate analysis, performed on IPTW-adjusted pseudo-population, including age, gender, LA diameter, LVEF, and AF type, showed ‘significant’ MR to be independently associated with AF recurrence post-ablation (HR = 2.11, 95% CI 1.43–5.73, p = 0.003). Conclusions: Use of IPTW pseudo-population suggests a significant association between baseline MR severity, regardless of its etiology, and AF recurrence post-ablation. This association should be confirmed by future larger studies. Full article

Background/Objectives: This study aimed at evaluating the association between maternal pre-pregnancy glycemic status and growth delay in offspring using nationwide health screening data. Methods: A retrospective cohort of 258,367 mother–child dyads born between 2014 and 2021 was analyzed. Maternal glycemic status was categorized as normal (<100 mg/dL), impaired fasting glucose (IFG, 100–125 mg/dL), or diabetes mellitus (DM, ≥126 mg/dL). Growth delay was defined as measurements below the 10th percentile of height, weight, and head circumference at 18–24 and 30–36 months. Visual and auditory development were assessed using caregiver questionnaires. Inverse probability of treatment weighting was applied, and weighted relative risks (RRs) were estimated. Results: The prevalence of growth delay was 3.5% for height, 3.8% for weight, and 4.3% for head circumference; visual and auditory problems were reported in 1.2% and 8.2% of children, respectively. Both the DM (1.2%) and IFG (9.3%) groups showed increased risks of growth delay across both age periods. Maternal hyperglycemia was also associated with offspring’s visual and auditory development, with age- and period-specific differences observed. Conclusions: Maternal pre-pregnancy glycemic status was significantly associated with delayed growth in Korean children aged 18–36 months. These findings highlight the importance of optimizing maternal glycemic control prior to pregnancy for favorable child developmental outcomes. Full article

The growing use of nonprobability samples in survey statistics has motivated research on methodological adjustments that address the selection bias inherent in such samples. Most studies, however, have concentrated on the estimation of the population mean. In this paper, we extend our focus to the finite population distribution function and quantiles, which are fundamental to distributional analysis and inequality measurement. Within a data integration framework that combines probability and nonprobability samples, we propose two estimators, a regression estimator and a doubly robust estimator, and discuss their asymptotic properties. Furthermore, we derive quantile estimators and construct Woodruff confidence intervals using a bootstrap method. Simulation results based on both a synthetic population and the 2023 Korean Survey of Household Finances and Living Conditions demonstrate that the proposed estimators perform stably across scenarios, supporting their applicability to the production of policy-relevant indicators. Full article

Background: Surgical delay in abdominal trauma with hemorrhage is a leading cause of preventable death, yet the precise time threshold for adverse outcomes remains uncertain. This study examined the association between emergency department (ED)-to-operating room (OR) time and hemorrhagic mortality and evaluated the impact of preoperative computed tomography (CT). Methods: We retrospectively analyzed patients ≥15 years old who underwent emergency laparotomy for abdominal trauma at two Level I trauma centers in South Korea (2016–2023). The primary outcome was hemorrhagic death, adjudicated by a multidisciplinary review panel. Multivariable and segmented logistic regression was used to assess the association between ED-to-OR time and mortality. The effect of preoperative CT was evaluated using inverse probability of treatment weighting (IPTW). Results: Among 414 patients, 71 (17.1%) died from hemorrhage. Each 1-min increase in ED-to-OR time was associated with 1.8% higher odds of hemorrhagic death (adjusted OR = 1.018; 95% CI, 1.007–1.030). Segmented regression identified a changepoint at 91 min (bootstrap 95% CI, 62.0–97.6), beyond which mortality risk rose sharply. Preoperative CT was performed in 27.5% of patients and was associated with a mean surgical delay of over 30 min. After IPTW adjustment, CT use was not significantly associated with hemorrhagic death (14.3% vs. 10.3%, p = 0.542). Conclusions: Longer ED-to-OR intervals were associated with increased hemorrhagic mortality, particularly beyond approximately 90 min. Although preoperative CT contributed to procedural delay, it was not independently associated with worse outcomes when selectively used in stable patients. These findings represent observational associations in current practice rather than causal effects, underscoring the importance of minimizing surgical delay while cautiously considering CT in appropriate patients. Full article

Post-traumatic osteoarthritis (PTOA) is a distinct form of knee osteoarthritis characterized by accelerated joint degeneration following injury. It poses unique challenges in post-menopausal women due to hormonal changes and altered bone metabolism that create complex pathophysiological environments. This retrospective cohort study compared the effectiveness of different anti-osteoporotic medications in preventing total knee replacement (TKR) in 6155 postmenopausal women with PTOA treated between 2011 and 2021. We compared raloxifene and denosumab, with alendronate serving as the reference group. The primary outcome was TKR occurrence. Cox proportional hazards regression and inverse probability of treatment weighting (IPTW) were performed to estimate hazard ratios, with Kaplan–Meier survival analysis for time-to-event assessment. Participants’ mean (SD) age was 69.4 (10.0) years. Given the retrospective nature and typical delayed presentation of PTOA symptoms, cohort entry was defined as the concurrent diagnosis of PTOA and osteoporosis requiring anti-resorptive therapy. Over a mean follow-up of 5.47 years, 26 patients (0.42%) underwent TKR. Raloxifene was associated with a significantly reduced TKR risk compared to alendronate (IPTW-HR 0.81, 95% CI 0.67–0.99, p = 0.040), representing a 19% relative risk reduction. Kaplan–Meier analysis demonstrated raloxifene maintained the lowest cumulative TKR incidence compared to alendronate and denosumab over time, particularly beyond 5 years. These findings suggest that raloxifene may offer superior joint protection compared with alendronate and denosumab in postmenopausal women with PTOA, supporting its potential as a disease-modifying therapeutic option for this vulnerable population. Full article

Background: Post-transplant cyclophosphamide (PTCy) is a standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT). While effective, concerns remain about cyclophosphamide-related cardiotoxicity, especially in patients with pre-existing cardiac morbidity, a population often underrepresented in clinical trials. Objectives: To assess the incidence and outcomes of early (ECE, ≤100 days) and late (LCE, >100 days) cardiac events in acute myeloid leukemia (AML) patients with and without baseline cardiac morbidity undergoing allo-HCT with PTCy. Study Design: Retrospective multicenter study by the Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) including 461 AML patients (62 with cardiac morbidity) transplanted between 2012 and 2022. Cardiac morbidity was defined by documented cardiac disease or left ventricular ejection fraction < 45%. Cumulative incidence, overall survival (OS), and non-relapse mortality (NRM) were analyzed using competing risks models and adjusted with propensity score matching (PSM) and inverse probability weighting (IPW). Results: Cardiac events occurred in 13.2% of patients: 11% vs. 7% ECE (p = 0.93) and 8% vs. 5.3% LCE (p = 0.85) in those with vs. without cardiac morbidity. Most ECEs were arrhythmias or heart failure. Adjusted analyses confirmed no significant differences in CE incidence, OS, or NRM between groups. Two-year OS was 69% vs. 70% (p = 0.50); NRM was 18% vs. 17% (p = 0.20). ECE was associated with higher mortality in both groups. Conclusions: PTCy is feasible in AML patients with pre-existing cardiac morbidity when combined with comprehensive cardiovascular evaluation and cardio-oncology follow-up, supporting its safe use in broader patient populations with appropriate cardiologic support. Full article