Search Results (37)

Background/Objectives: The COVID-19 pandemic significantly disrupted healthcare systems worldwide, leading to increased healthcare-associated infection rates, particularly in the intensive care unit (ICU) setting. Little is known about the evolution of this phenomenon in subsequent years. Methods: This retrospective analysis of prospectively collected data (January 2020–December 2024) examined central line-associated bloodstream infections (CLABSI) in the Wroclaw Medical University hospital’s ICU during and after the COVID-19 pandemic. Results: Ninety CLABSI cases were observed in 3149 ICU patients across 39,837 patient-days and 36,038 central-vascular-catheter-days (CVC-D). The mean CLABSI frequency was 2.97 per 100 admissions, with an incidence density of 2.49 per 1000 CVC-D. CLABSI occurred more frequently in males than in females (3.51% vs. 1.69%, p = 0.003) and in patients with concomitant SARS-CoV-2 infection than in individuals without such coinfection (6.06% vs. 1.88%, p = 0.00037). Microbiological analysis revealed Staphylococcus epidermidis as the most frequent etiological factor of CLABSI (33.3%). Alert pathogens constituted 34.26% of all CLABSI etiological factors, with higher prevalence during the pandemic than afterward (51.16% vs. 23.08%, p = 0.005437). Patients with CLABSI had significantly longer ICU stays (53.57 vs. 11.62 days, p = 0.001). After adjusting for immortal time bias using matched cohort analysis, CLABSI was not associated with increased mortality (p = 0.735). The overall compliance level of adherence to CLABSI prevention measures was 86.9%, with no statistically significant difference between the pandemic and post-pandemic periods, p = 0.417. The study did not systematically collect data on catheter types, insertion sites, or clinical circumstances (emergency vs. elective), which are known risk factors that may have influenced the observed CLABSI incidence rates. Conclusions: Despite increased patient volume post-pandemic, CLABSI metrics remained stable, possibly due to the successful adaptation of infection prevention protocols. However, interpretation of incidence data should consider unmeasured confounding factors. These findings address knowledge gaps regarding how the pandemic affected CLABSI epidemiology and antimicrobial resistance patterns, with implications for infection control practices during future healthcare crises. Full article

In observational causal inference studies, unmeasured confounding remains a critical threat to the validity of effect estimates. While proximal causal inference (PCI) has emerged as a powerful framework for mitigating such bias through proxy variables, existing PCI methods cannot directly handle censored data. This article develops a unified proximal causal inference framework that simultaneously addresses unmeasured confounding and right-censoring challenges, extending the proximal causal inference literature. Our key contributions are twofold: (i) We propose novel identification strategies and develop two distinct estimators for the censored-outcome bridge function and treatment confounding bridge function, resolving the fundamental challenge of unobserved outcomes; (ii) To improve robustness against model misspecification, we construct a robust proximal estimator and establish uniform consistency for all proposed estimators under mild regularity conditions. Through comprehensive simulations, we demonstrate the finite-sample performance of our methods, followed by an empirical application evaluating right heart catheterization effectiveness in critically ill ICU patients. Full article

Background: Due to the low certainty of existing evidence, no formal recommendation can be made for or against the use of antipsychotics over usual care in ICU patients with delirium. To advance evidence-based practice, we used observational data from the Medical Information Mart for Intensive Care (MIMIC) to estimate the effect of pre-ICU quetiapine treatment (vs. control) on the length of ICU stay. In a second, head-to-head comparison, we assessed quetiapine vs. haloperidol on the same outcome. Methods: We conducted two propensity score-matched procedures: 518 patients were matched based on receipt of quetiapine versus no antipsychotic (i.e., control), and 336 patients based on quetiapine versus haloperidol prior to ICU admission. After matching, we performed Bayesian generalized additive modeling (GAM) and Bayesian sensitivity analyses within a nonlinear modeling framework. Results: In the quetiapine versus no quetiapine analysis, the original overall covariate distance of 0.48 was reduced to 0.01 post-matching. All covariates achieved an acceptable balance, with absolute standardized mean differences below 0.1. Quetiapine use was associated with a 1.31-day longer ICU stay (posterior mean = 0.36; 95% credible interval: 0.14 to 0.59). Sensitivity analyses indicated that this effect remained robust after accounting for plausible levels of unmeasured confounding. In the quetiapine versus haloperidol analysis, the initial overall distance of 0.40 was reduced to 0.09 after matching, with all covariates similarly balanced. Compared to haloperidol, quetiapine treatment was associated with a 1.46-day longer ICU stay (posterior mean = 0.48; 95% credible interval: 0.09 to 0.88). Bayesian sensitivity analyses again indicated the robustness of the effect estimate. Conclusions: In these emulated clinical trials, pre-ICU treatment with quetiapine was associated with a prolonged ICU stay compared to both untreated and haloperidol conditions. Though more research in this field is needed, these findings do not support the use of quetiapine in ICU patients with delirium. Full article

Background/Objectives: Sudden sensorineural hearing loss (SSNHL) is an acute condition with unclear etiology, commonly hypothesized to be associated with viral infections. Acute respiratory tract infections (RTIs), particularly those of viral origin, have been implicated in SSNHL through proposed mechanisms such as cochlear invasion and immune-mediated damage. However, robust large-scale epidemiological evidence examining this association remains limited. This study aimed to investigate the potential association between acute RTIs and subsequent risk of developing SSNHL across diverse populations. Methods: We conducted a multinational retrospective cohort study using data from the TriNetX Global Collaborative Network. Adults diagnosed with acute RTIs between 1 January 2012 and 30 June 2023 were compared to matched controls without RTI exposure. Patients with predisposing conditions for SSNHL were excluded. Propensity score matching (1:1) was performed by age and sex. SSNHL diagnoses within 60 days post index were analyzed using Cox proportional hazards models. Subgroup and sensitivity analyses were conducted by race, sex, and age strata. Results: Among 37 million patients analyzed, individuals with acute RTIs had a lower incidence of SSNHL compared to matched controls. Hazard ratios (HRs) for SSNHL were significantly reduced across all racial groups: Whites (HR: 0.572), Blacks (HR: 0.563), and Asians (HR: 0.409). Subgroup analyses revealed stronger inverse associations in males and younger age groups, particularly those aged 18–25 years. Conclusions: Contrary to prior assumptions, acute RTIs were associated with a lower incidence of SSNHL in a large, diverse cohort. While the findings raise the possibility of immunological or physiological factors influencing this association, the results should be interpreted with caution due to unmeasured confounding and the observational nature of the study. Full article

Objectives: Dietary conditions are closely related to maternal health. This study aims to investigate the causal relationship between the first–second-trimester Dietary Inflammatory Index (DII) and developing anemia in the third trimester. Methods: This prospective cohort study comprised 545 pregnant women, with dietary data assessed via a semi-quantitative food frequency questionnaire (FFQ). Hemoglobin levels were obtained by hospital laboratory tests and used to diagnose anemia. Multivariable logistic regression models—adjusted for baseline serum iron, age, pre-pregnancy body mass index (BMI), occupation, education, history of adverse pregnancy outcomes, parity, serum iron, passive smoking exposure, and iron supplementation use during pregnancy—were employed to evaluate the relationships between the first-trimester DII, second-trimester DII, first–second-trimester average DII, and third-trimester anemia. Results: After multivariable adjustment, the first–second-trimester average DII in the pro-inflammatory diet group demonstrated a 3.73-fold elevated risk of third-trimester anemia compared to the anti-inflammatory diet group (Odds Ratio [OR] = 3.73, 95% Confidence Interval [CI]: 1.50–9.25). Conclusions: Pro-inflammatory dietary patterns during pregnancy exhibit a significant correlation with developing third-trimester anemia. This study demonstrates that reducing dietary pro-inflammatory components through prenatal nutrition programs may lower third-trimester anemia risk. Notably, this study carries potential risks of bias, including self-reporting bias in dietary data and incompletely controlled confounding factors (such as unmeasured biomarkers). Full article

Drug–drug interactions (DDIs) can pose significant risks in clinical practice and pharmacovigilance. Although traditional association rule mining techniques, such as the Apriori algorithm, have been applied to drug safety signal detection, their performance in DDI detection has not been systematically evaluated, especially in the Spontaneous Reporting System (SRS), which contains a large number of drugs and AEs with a complex correlation structure and unobserved latent factors. This study fills that gap through comprehensive simulation studies designed to mimic key features of SRS data. We show that latent confounding can substantially distort detection accuracy: for example, when using the reporting ratio (RR) as a secondary indicator, the area under the curve (AUC) for detecting main effects dropped by approximately 30% and for DDIs by about 15%, compared to settings without confounding. A real-world application using 2024 VAERS data further illustrates the consequences of unmeasured bias, including a potentially spurious association between COVID-19 vaccination and infection. These findings highlight the limitations of existing methods and emphasize the need for future tools that account for latent factors to improve the reliability of safety signal detection in pharmacovigilance analyses. Full article

Background: Target trial emulation involves the application of design principles from randomised controlled trials (RCTs) to observational data, and is particularly useful in situations where an RCT would be unfeasible. Biomarker-guided trials, which incorporate biomarkers within their design to either guide treatment and/or determine eligibility, are often unfeasible in practice due to sample size requirements or ethical concerns. Here, we undertake a systematic review of methodologies used in target trial emulations, comparing treatment effectiveness, critically appraising them, and considering their applicability to the emulation of biomarker-guided trials. Methods: A comprehensive search strategy was developed to identify studies reporting on methods for target trial emulation comparing the effectiveness of treatments using observational data, and applied to the following bibliographic databases: PubMed, Scopus, Web of Science, and Ovid MEDLINE. A narrative description of methods identified in the review was undertaken alongside a critique of their relative strengths and limitations. Results: We identified a total of 59 papers: 47 emulating a target trial (‘application’ studies), and 12 detailing methods to emulate a target trial (‘methods’ studies). A total of 25 papers were identified as emulating a biomarker-guided trial (42%). While all papers reported methods to adjust for baseline confounding, 40% of application papers did not specify methods to adjust for time-varying confounding. Conclusions: This systematic review has identified a range of methods used to control for baseline, time-varying, and residual/unmeasured confounding within target trial emulation and provides a guide for researchers interested in emulation of biomarker-guided trials. Full article

Epidemiologic studies suggest that elevated plasma unconjugated bilirubin confer protection against steatotic liver disease (SLD) in adults. However, evidence supporting this protective role in adolescents remains limited. We aimed to assess the association between serum bilirubin levels and their genetic determinants in protecting against SLD in Chilean adolescents. We conducted a cross-sectional study with 704 adolescents aged 15.4 ± 1 years (52% girls) of the Chilean Growth and Obesity Cohort Study. Ultrasonography echogenicity was used to diagnose SLD. We measured Z-scores of body mass index (z-BMI), total bilirubin (TB), and the genetic determinants of bilirubin (including rs887829 genotypes of UGT1A1 and bilirubin polygenic scores). Multiple logistic regression models evaluated the associations between standardized TB and its genetic determinants with SLD. We found that 1-SD of standardized plasma TB was significantly associated with a 30% reduction in the likelihood of SLD after adjustment by sex, age, z-BMI, and ethnicity (OR = 0.7; 95% CI = 0.50–0.96; p = 0.03). No significant associations were found among the rs887829 genotypes, bilirubin polygenic scores, and SLD in logistic regression models adjusted by covariates. Increased circulating bilirubin levels are unlikely causally associated with protection against SLD, and the cross-sectional association could be due to unmeasured confounding. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms like bradykinesia, tremor, rigidity, and postural instability. Additionally, PD severely impacts physical abilities and independence. Chronic pain, affecting 67.6% of PD patients, varies in form and presentation, and it is often underdiagnosed. Objectives: This study investigated the association between chronic pain and motor symptom severity in PD patients. Methods: This analysis used data from a cross-sectional study on 52 Parkinson’s disease (PD) patients conducted at Jena University Hospital, Germany. The dataset, available on Dryad, included demographics; clinical reports; and assessments of coping strategies, quality of life, and pain. Descriptive statistics, a bivariate analysis, and an ordinal logistic regression model were executed to explore the association between pain and motor symptom severity (MSS). A direct acyclic graph was used to represent the relationship between variables and identify potential confounders, and an outcomes definition sensitivity analysis was used to assess the impact of using pain intensity as an outcome. The E-value was calculated to evaluate the strength of association needed by an unmeasured confounder to nullify the observed association. Results: A total of 50 Parkinson’s disease (PD) patients were included, with 64% being male, with an average age of 76.1 years. The sample included 20 patients without pain and 30 with chronic pain. The bivariate analysis did not identify significant differences in disease duration, cognitive function, and non-motor symptoms between pain and no-pain groups. However, significant differences (p-value < 0.05) emerged in motor symptom severity, coping strategies, and several SF-36 domains (Physical and Social Functioning, Role Functioning, Energy/Fatigue, Pain, General Health, and Health Change). The ordinal logistic regression showed a substantial association between chronic pain and MSS: patients with chronic pain had 3.52 times higher odds (95% CI: 1.40–8.84, effect size d ≈ 0.70, p = 0.02) of low to medium MSS and 5.44 times higher odds (95% CI: 2.03–14.60, effect size d ≈ 0.94, p = 0.01) of medium to severe MSS, indicating a dose–response relationship. Additionally, male patients had increased odds of higher MSS (OR 4.63, 95% CI: 1.15–18.58, effect size d ≈ 0.85, p = 0.03). Conclusions: Chronic pain is strongly associated with MSS in PD patients, with a more pronounced effect as MSS progresses from medium to severe, supporting a dose–response relationship. Effect sizes suggest a robust association, emphasizing the need for pain assessment in managing motor symptoms in PD. Full article

Background/Objectives: The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. Methods: This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. Results: Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91–2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57–0.70]), and females had a negative effect modification on the association between MPH and PP. Conclusions: Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP. Full article

Background: Living donor kidney transplantation (LDKT) is a crucial treatment for end-stage renal disease, with pre-emptive LDKT (transplantation before dialysis initiation) offering significant benefits in graft function and patient survival. The selection of a vasopressor during LDKT, particularly between norepinephrine and dopamine, and its impact on renal arterial hemodynamics measured using the renal arterial resistive index (RARI) is poorly understood. Methods: This retrospective observational cohort study enrolled 347 eligible pre-emptive LDKT recipients from the Seoul St. Mary’s Hospital between January 2019 and June 2023. Utilizing propensity score matching (PSM), the patients were categorized into dopamine and norepinephrine groups to compare the effects of these vasopressors on the intraoperative RARI, postoperative estimated glomerular filtration rate (eGFR), and hourly urine output. The RARI was measured via the Doppler ultrasonography of the renal hilum and parenchyma post-graft vascular and ureteral anastomoses. Results: The preoperative differences in the recipients’ and donors’ characteristics were mitigated following PSM. The dopamine group exhibited higher intraoperative RARI values at the renal hilum (0.77 ± 0.11 vs. 0.66 ± 0.13, p < 0.001) and parenchyma (0.71 ± 0.1 vs. 0.6 ± 0.1, p < 0.001) compared to those of the norepinephrine group. However, these differences were not statistically significant on postoperative day 7. The norepinephrine infusion adjusted for the propensity scores was associated with significantly lower odds of an RARI > 0.8 (hilum: OR = 0.214, 95% CI = 0.12–0.382, p < 0.001; parenchyma: OR = 0.1, 95% CI = 0.029–0.348, p < 0.001). The early postoperative outcomes showed a higher eGFR (day 1: 30.0 ± 13.3 vs. 25.1 ± 17.4 mL/min/1.73 m², p = 0.004) and hourly urine output (day 1: 41.8 ± 16.9 vs. 36.5 ± 14.4 mL/kg/h, p = 0.002) in the norepinephrine group. Furthermore, the long-term outcomes were comparable between the groups. Conclusions: Norepinephrine infusion during pre-emptive LDKT is associated with more favorable intraoperative renal arterial hemodynamics, as evidenced by a lower RARI and improved early postoperative renal function compared to those of dopamine. These findings suggest a potential preferential role for norepinephrine in optimizing perioperative management and early graft functions in LDKT recipients. Given the retrospective nature of this study, further prospective studies are needed to confirm these observations. Additionally, the study limitations include the potential for unmeasured confounding factors and the inability to determine causality due to its observational design. Full article

Purpose: Racial disparities in infant mortality in the United States persist after adjustment for known confounders of race and mortality association, as well as heterogeneity assessment. Epidemiologic and clinical data continue to show the survival disadvantages of Black/AA children: when Black/AAs are compared to whites, they are three times as likely to die from all-cause mortality. The persistent inability to remove the variance in race–mortality association is partly due to unobserved, unmeasured, and residual confounding, as well as implicit biases in public health and clinical medicine in health equity transformation. This current epidemiologic-perspective explanatory model study aimed to examine the possible explanation of racial differences in U.S. infant mortality using medical misadventures as errors and mistakes, and infants’ involvement in motor vehicular traffic accidents. Materials and Method: Using CDC WONDER ecologic data from 1968 to 2015, we assessed the infant mortality-rate ratio and percent change associated with medical misadventures as well as motor vehicular accidents or trauma. The rate ratio and percent change were estimated using stratification analysis and trend homogeneity, respectively. Results: There was a Black–white racial difference in medical misadventures during the study period. Relative to the years 1968–1978 (rate ratio [RR], 1.43), there was a steady increase in the mortality-rate ratio in 1979–1998 (52%, RR = 1.52), and mortality was more than two times as likely in 1999–2015 (RR = 2.37). However, with respect to motor vehicular accident/trauma mortality, the mortality ratio, although lower among Blacks in 1968–1978 (RR, 0.92), increased in 1979–1998 by 27% (RR = 1.27) but decreased in 1999–2015 (RR, 1.17), though there was still an excess of 17% mortality among Black/AAs. The percent change for medical misadventures indicated an increasing trend from 9.3% in 1998 to 52% in 2015. However, motor vehicular-related mortality indicated a positive trend in 1998 (38.5%) but a negative trend in 2015 (−8.4%). Conclusions: There were substantial race differentials or variances in infant mortality associated with medical misadventures compared to traffic accidents, and Black/AA children relative to whites experienced a survival disadvantage. These comparative findings are suggestive of medical misadventures and motor vehicular trauma as potential explanations for some of the persistent Black–white disparities in overall infant mortality in the U.S. From these findings, we recommend a national effort to address these issues, thus narrowing the observed disparities in the U.S. infant mortality burden among Black/AAs. Full article

Several observational studies have compared apixaban with rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), but these analyses may be confounded by unmeasured characteristics. This study used provider prescribing preference (PPP) as an instrumental variable (IV) to assess the association between prescriber choice of rivaroxaban vs. apixaban and the study outcomes of stroke/systemic embolism (SE), major bleeding, and death in a retrospective cohort of NVAF patients in the US. Initiators of either medication were linked to their prescribers and followed until the first of the study outcome, the end of rivaroxaban/apixaban use, or 365 days after initiation. PPP for each patient was the percent of rivaroxaban initiations issued by the provider for the prior 10 NVAF patients. Cox regression models tested associations between quintiles of PPP and each outcome. A total of 61,155 patients and 1726 providers were included. The IV was a strong predictor of rivaroxaban prescription (OR = 17.9; 95% CI: 16.6, 19.3). There were statistically significant associations between increasing preference for rivaroxaban and rates of major bleeding (ptrend = 0.041) and death (ptrend = 0.031), but not stroke/SE (ptrend = 0.398). This analysis provides evidence of the relative safety of apixaban over rivaroxaban for the risk of major bleeding and death. Full article

Unhealthy dietary behaviors and body dissatisfaction are becoming increasingly common among college students. Understanding the association between body image flexibility and intermittent fasting is particularly meaningful, especially for medical college students. This study aimed to investigate the association between body image flexibility and intermittent fasting among medical students. We conducted a cross-sectional study with 5138 medical college students at Jitang College of North China University of Science and Technology. Univariate and multivariate logistic regression were used to evaluate the association between body image flexibility and intermittent fasting. Subgroup analysis and interaction tests were further used to examine the possible interaction between body image flexibility and intermittent fasting. In this study, 1329 (25.87%) students had intermittent fasting behavior. After adjustment for confounding factors, there was a negative association between body image flexibility and intermittent fasting (OR = 0.94, 95%CI = 0.93 to 0.95, p < 0.001). A significant interaction between body image flexibility and intermittent fasting was found in gender, academic year, major, and monthly living expenses (p for interaction < 0.05). E-value analysis suggested there was unlikely to be an unmeasured confounding. This association could contribute to the establishment of personalized health intervention strategies and provide recommendations for promoting the physical and mental health of medical students. Full article

Background: Whether the positive associations of gastric cancer (GC) with autoimmune diseases are causal has always been controversial. This study aims to estimate the causal relationship between GC and 12 autoimmune diseases by means of Mendelian randomization (MR) analysis. Methods: After rigorous evaluation, potential candidate single nucleotide polymorphisms (SNPs) for GC and 12 autoimmune diseases were extracted from genome-wide association study (GWAS) datasets. We performed the MR analyses using the inverse variance weighted (IVW) method as the primary approach to the analysis. Three sensitivity analysis methods were added to assess the robustness of the results. In addition, heterogeneity was measured using Cochran’s Q-value, and horizontal pleiotropy was assessed using MR-Egger regression and leave-one-out analysis. Results: The IVW result, which is the main method of analysis, shows no evidence of a causal association between GC and any autoimmune disease. The results of IVW analysis show the relationship between rheumatoid arthritis (p = 0.1389), systemic lupus erythematosus (p = 0.1122), Crohn‘s disease (p = 0.1509), multiple sclerosis (p = 0.3944), primary sclerosing cholangitis (p = 0.9022), primary biliary cirrhosis (p = 0.7776), type 1 diabetes (p = 0.9595), ulcerative colitis (p = 0.5470), eczema (p = 0.3378), asthma (p = 0.7436), celiac disease (p = 0.4032), and psoriasis (p = 0.7622) and GC susceptibility. The same result was obtained with the weighted median and the MR-egger (p > 0.05). Conclusion: Our study did not find a genetic causal relationship between susceptibility to these autoimmune diseases and GC, which suggests that unmeasured confounders (e.g., inflammatory processes) or shared genetic architecture may be responsible for the reported epidemiologic associations. Further studies of ancestral diversity are warranted to validate such causal associations. Full article