This study aimed to measure the changes in rural hospital bypass for 11 common elective surgeries following the implementation of the Pennsylvania Rural Health Model (PARHM), a global budget payment model.

We leveraged a natural experiment arising from the phase-in of PHARM in Pennsylvania. We conducted a comparative interrupted time series analysis to assess changes in rural hospital bypass, comparing trends in rural hospital bypass among patients in hospital service areas (HSAs) with PARHM-participating hospitals to patients in control HSAs with hospitals eligible for but not participating in PARHM. Analyses accounted for staggered entry into PARHM and examined outcomes up to 4 years post-entry.

We used Pennsylvania all-payer visit-level inpatient discharge data (2016-2022) to measure rural hospital bypass, encompassing 175,138 surgeries.

The average bypass rate for elective surgeries was 59.9%, with an increasing trend observed during the study period. Overall, differential changes in bypass rates between PARHM-participating and control HSAs were not statistically significant, from a low of 0.53 percentage points (-8.17-9.22) among Cohort 2 HSAs and a high of 5.96 percentage points (-4.63-16.55) among Cohort 1 HSAs. However, among critical access hospitals, PARHM participation was associated with a significant relative increase in levels and trends in bypass rates compared to controls, from a low of 9.12 percentage points (2.45-15.79) among Cohort 1 HSAs and a high of 29.70 percentage points (12.54-46.86) among Cohort 2 HSAs. These relative increases were largely due to a stable rate in PARHM-participating HSAs and a marked decrease in control HSAs.

This study fills a gap in the relationship between global budgets and hospital bypass. Although PARHM did not broadly alter rural bypass rates overall, the differential increase in bypass among HSAs with CAHs participating in PARHM suggests meaningful effect heterogeneity, warranting further research and analysis of impacts on patient outcomes.

Our objective was to quantify the cumulative total and out-of-pocket (OOP) costs for 3 non-metastatic prostate cancer treatment modalities: radiation, surgery, and conservative management at intervals of 1-, 3-, and 5-years post-diagnosis. We predicted these cumulative costs for a typical patient to improve cost transparency, facilitate conversations about potential costs, and to help advance non-metastatic prostate cancer cost evaluation.

We used Merative™ MarketScan® Commercial Database data from 2007-2020. The cumulative total costs evaluated from the healthcare sector perspective were patient, clinician, and system/facility costs. We used descriptive statistics to summarize the sociodemographic characteristics of the cohort and a multivariable regression model to estimate the association between each treatment option (radiation, surgery, conservative management) and costs with inverse probability of treatment weighting (IPTW) to account for potential selection bias. We then predicted total and OOP costs defined by sample mode characteristics.

This cohort included 74,324 patients. Cumulative total and OOP costs were significantly higher for radiation (p < 0.0001) and for surgery (p < 0.0001) at Years 1, 3, and 5 compared to conservative management. For a typical patient, total cumulative cost estimates for conservative management at Years 1/3/5 were: $15,896/$33,436/$48,110 and the cumulative patient OOP costs were: $2,003/$4,540/$6,621. The cumulative total costs for surgery at Years 1/3/5 were: $38,348/$49,424/$60,885 and the cumulative OOP costs were: $2,980/$5,255/$7,221. The cumulative total costs for radiation at Years 1/3/5 were: $65,397/$77,859/$91,497 and the cumulative OOP costs were: $3,151/$5,481/$7,504.

For all years, the cumulative costs of radiation were highest, followed by surgery and conservative management, respectively. Radiation as the first treatment modality had higher costs compared to surgery and conservative management at the 3 time points.

These cost estimates support non-metastatic prostate cancer treatment related cost transparency. These estimates can help researchers evaluate costs and facilitate patient-clinician cost conversations.

Evaluating recurrent events within a time-to-event analysis framework effectively utilizes all relevant information to address the clinical question of interest fully and has certain advantages in randomized controlled trials (RCTs). However, the Prentice, Williams, and Peterson (PWP) model disrupts the randomness of the risk set for subsequent recurrent events other than the first and consequently introduces bias in estimating effects. This study aimed to propose a weighted PWP model, evaluate its statistical performance, and assess the potential consequences of using common practices when each recurrence has different baseline hazard functions.

We proposed adjusting the estimate of treatment effect through a weighting strategy that constructed a virtual population balanced between groups in each risk set. A simulation study was carried out. The characteristic of the simulation data was the baseline hazard changed with the number of events. The proposed weighted PWP model was compared with current methods, including Cox for time-to-first-event, Poisson, negative binomial (NB), Andersen-Gill (AG), Lin-Wei-Yang-Ying (LWYY), and PWP models. Model performance was evaluated by bias, type I error rates, and statistical power. All models were applied to a real case from a randomization trial of Chemoprophylaxis treatment for Recurrent Stage I Bladder Tumors.

The results showed that the proposed weighted PWP model performed best with the lowest bias and highest statistical power. However, other models, including the Cox for time-to-first-event, Poisson, NB, AG, LWYY, and PWP models, all showed different degrees of bias and inflated type I error rates or low statistical power in the case of the baseline hazard changed with the number of events. Covariate adjustment via outcome regression can lead to inflated type I error rates. When the number of recurrent events was restricted, all weighting strategies yielded stable and nearly consistent results.

Recurrent event data should be analyzed with caution. The proposed methods may be generalized to model recurrent events. Our findings serve as an important clarification of how to deal with collider bias in the PWP model in RCTs.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease found primarily in older people, with the use of systemic steroids linked to poor outcomes. However, the role of inhaled corticosteroids (ICSs) in IPF remains unclear. This study investigated the association between ICS use and IPF risk using national insurance data, particularly in individuals with chronic airway diseases.

Using the National Health Insurance Service-National Sample Cohort database, our study included patients diagnosed with chronic obstructive pulmonary disease or asthma. ICS exposure was assessed via treatment claims, and IPF cases were identified using broad and narrow criteria. We used inverse probability of treatment weighting (IPTW) with propensity scores for balanced covariate analysis.

Of 57 456 patients (mean age: 55.9 years, 42.3% men), 16.5% used ICS and 83.5% did not. ICS users showed higher rates of broad (0.98 vs 0.41 per 1000) and narrow IPF (0.61 vs 0.21 per 1000) than non-users. Pre-IPTW, ICS use was associated with increased IPF risk; however, this was not significant post-IPTW. Post-IPTW, both ICS dose as a continuous variable (broad adjusted HR per 100 µg/day: 1.03, 95% CI: 1.02 to 1.04; narrow adjusted HR per 100 µg/day: 1.03, 95% CI: 1.01 to 1.04 post-IPTW) and high-dose ICS (≥1000 µg/day) (broad adjusted HR: 3.89, 95% CI: 1.61 to 9.41; narrow adjusted HR: 3.99, 95% CI: 1.19 to 13.41) use correlated with an elevated IPF risk.

While no overall significant association between ICS use and IPF risk was observed post-IPTW, there may be an increased risk in patients using high-dose ICS.

Over the past decade, there has been a considerable shift in the use of pharmacologic agents for venous thromboembolism (VTE), with direct oral anticoagulants replacing warfarin as the drugs of choice for VTE recurrence prevention; however, evidence from head-to-head comparison studies remains limited.

To compare the effectiveness and safety of 3 common oral anticoagulants (apixaban, rivaroxaban, and warfarin) in patients with VTE.

This population-based cohort study used Medicare and 2 commercial insurance databases from 2016 up to 2024 to identify patients 18 years and older who initiated an oral anticoagulant following VTE and had at least 1 year of continuous insurance enrollment before the index date.

Initiation of apixaban, rivaroxaban, or warfarin within 30 days after VTE discharge.

The primary effectiveness outcome was hospitalization for recurrent VTE. The primary safety outcome was major bleeding. Patients were followed up from treatment initiation until outcome occurrence, treatment discontinuation/switch, disenrollment, death, or end of available data. Propensity score-matching weights were used to adjust for confounding. Weighted Cox proportional hazard models estimated weighted hazard ratios (HRs) and 95% CIs.

Among 163 593 eligible individuals (mean [SD] age, 71.4 [13.5] years; 56.7% female), 58.5% initiated apixaban, 25.7% initiated rivaroxaban, and 15.8% initiated warfarin. Overall, 3270 hospitalizations for recurrent VTE and 4229 hospitalizations for bleeding events occurred. Compared with warfarin, patients taking apixaban (HR, 0.67; 95% CI, 0.61-0.75) and rivaroxaban (HR, 0.77; 95% CI, 0.69-0.87) had a lower risk of recurrent VTE. Apixaban showed a further decrease in risk compared with rivaroxaban (HR, 0.87; 95% CI, 0.78-0.96). Patients taking apixaban also had a lower risk of major bleeding compared with warfarin (HR, 0.70; 95% CI, 0.64-0.76) and rivaroxaban (HR, 0.69; 95% CI, 0.63-0.75). No difference in bleeding risk was observed between rivaroxaban and warfarin (HR, 1.02; 95% CI, 0.92-1.12). These findings were consistent across subgroups defined by age, sex, cancer, chronic kidney disease, bleeding history, and frailty.

In this cohort study of patients with VTE who initiated an oral anticoagulant, apixaban was associated with a lower risk of VTE recurrence and major bleeding compared with rivaroxaban and warfarin. These results provide evidence to guide the selection of appropriate initial oral anticoagulant regimens for adult patients with VTE.

The role of radiation therapy in combination with systemic treatment for stage IVb esophageal squamous cell carcinoma (ESCC) is unclear. We aimed to investigate the effectiveness of primary chemoradiotherapy for these patients and compare it to that chemotherapy alone.

In this retrospective cohort study, we adopted a target trial emulation framework to identify eligible patients in the Taiwan Cancer Registry diagnosed between 2011 and 2021. In the primary analysis, overall survival (OS) was the primary endpoint, whereas the incidence of esophageal cancer mortality was the secondary endpoint. Extensive supplementary analyses were also conducted.

We included 5294 patients in the primary analysis and found that OS was significantly better for those treated with chemoradiotherapy (n = 5065) than for those treated with chemotherapy only (n = 229). The propensity score weighting adjusted hazard ratio of death was 0.46 (95% confidence interval 0.41-0.52, p < 0.0001). The secondary endpoint and supplementary analyses also favored the chemoradiotherapy group.

The OS of stage IVb ESCC patients treated with chemoradiotherapy was significantly better than that of patients treated with chemotherapy alone. The results of relevant ongoing clinical trials are eagerly awaited.

Target trial emulation (TTE) aims to estimate treatment effects by simulating randomized controlled trials using real-world observational data. Applying TTE across distributed datasets shows great promise in improving generalizability and power but is always infeasible due to privacy and data-sharing constraints. Here we propose a Federated Learning-based TTE framework, FL-TTE, that enables TTE across multiple sites without sharing patient-level data. FL-TTE incorporates federated protocol design, federated inverse probability of treatment weighting, and a federated Cox proportional hazards model to estimate time-to-event outcomes across heterogeneous data. We validated FL-TTE by emulating Sepsis trials using eICU and MIMIC-IV data from 192 hospitals, and Alzheimer's trials using INSIGHT Network across five New York City health systems. FL-TTE produced less biased estimates than traditional meta-analysis methods when compared to pooled results and is theoretically supported. Our FL-TTE enables federated treatment effect estimation across distributed and heterogeneous data in a privacy-preserved way.

The aim of this study was to compare the efficacy and safety of endoscopic endonasal approaches (EEA) with craniofacial resection (CFR) for sinonasal cancers invading the skull base, using an unanchored matching-adjusted indirect comparison (MAIC).

A MAIC approach was used to analyse data from two large cohorts: the MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers (MUSES) cohort, comprising sinonasal cancer patients treated endoscopically, and a historical CFR cohort reported by Ganly et al. Individual patient data were available only for the first cohort. Patients with olfactory neuroblastomas were excluded. Key prognostic factors were used to match and adjust the two cohorts, minimising selection bias. The primary endpoint was overall survival (OS), with secondary endpoints including recurrence-free survival (RFS), perioperative mortality, complication rates, and resection margins.

A total of 724 EEA-treated and 334 CFR-treated patients were included. EEA showed significantly improved OS before (HR= 2.33, 95 % CI= 1.88-2.87) and after MAIC adjustment (HR= 1.93, 95 % CI= 1.60-2.34). Observed RFS was higher in the EEA group (HR= 1.39, 95 % CI = 1.14-1.69) but no longer differed after adjustment (HR= 1.06, 95 % CI= 0.91-1.23). EEA was associated with significantly better Disease Specific Survival (HR= 1.71, 95 % CI = 1.39-2.13), lower perioperative mortality (OR= 8.12, 95 % CI= 3.45-36.7) and fewer complications than CFR (OR= 3.68, 95 % CI= 2.47-5.42).

In this MAIC study based on the 2 largest cohorts of sinonasal cancer with skull base invasion, EEA offered comparable oncologic outcomes to CFR with reduced morbidity, supporting it as a valid alternative when performed in expert centres.

Residential greenness may influence COPD mortality, but the causal links, risk trajectories, and mediation pathways between them remain poorly understood.

We aim to comprehensively identify the potential causal links, characterize the dynamic progression of hospitalization or posthospital risk, and quantify mediation effects between greenness and COPD.

This study was conducted using a community-based cohort enrolling individuals aged ≥ 18 years in southern China from January 1, 2009 to December 31, 2015. Greenness was characterized by normalized difference vegetation index (NDVI) around participants' residential addresses. We applied doubly robust Cox proportional hazards model, multi-state model, and multiple mediation method, to investigate the potential causal links, risk trajectories among baseline, COPD hospitalization, first readmission due to COPD or COPD-related complications, and all-cause death, as well as the multiple mediation pathways (particulate matter [PM], temperature, body mass index [BMI] and physical activity) connecting greenness exposure to COPD mortality.

Our final analysis included 581,785 participants (52.52% female; average age: 48.36 [Standard Deviation (SD): 17.56]). Each interquartile range (IQR: 0.06) increase in NDVI was associated with a reduced COPD mortality risk, yielding a hazard ratio (HR) of 0.88 (95 % CI: 0.81, 0.96). Furthermore, we observed per IQR (0.04) increase in NDVI was inversely associated with the risk of multiple transitions (baseline - COPD hospitalization, baseline - death, and readmission - death risks), especially a declined risk of all-cause death after readmission (HR = 0.66 [95 %CI: 0.44, 0.99]). Within the observed association between greenness and COPD mortality, three mediators were identified, namely PM, temperature, and BMI (HR for the total indirect effect: 0.773 [95 % CI: 0.703, 0.851]), with PM showing the highest mediating effect.

Our findings revealed greenness may be a beneficial factor for COPD morbidity, prognosis, and mortality. This protective effect is primarily attributed to the reduction in PM concentration.

Prevention of dementia represents a public health priority. Hypertension is a risk factor for mild cognitive impairment (MCI), a precursor to progressive dementia. A great effort is underway to develop accurate and sensitive tools to detect the MCI condition in hypertensive patients. To investigate the potential association of subclinical left ventricular dysfunction expressed by the global longitudinal strain (GLS) with the MCI, defined by the Italian version of the quick mild cognitive impairment (Qmci-I). This multi-centric study included 180 consecutive hypertensive patients without medical diseases and/or drugs with known significant effects on cognition but with a not negligible comorbidity burden to avoid a possible "hyper-normality bias". The study cohort was classified into two main groups concerning the median value of the GLS. A weighted logistic regression model was employed after an inverse probability of treatment weighting (IPTW) analysis to characterize a potential association between GLS and MCI. Almost 41,1% of the whole study population was female. The mean age was 65,6 ± 7,2. 39 patients (21,7%) showed MCI. After IPTW, the GLS was significantly associated with the study endpoint (OR, 1,22; 95% CI: 1,07-1,39, P = 0.003). Our results highlight that the GLS is a potential predictor of MCI and, therefore, a valuable tool for establishing preventive strategies to arrest the progression toward a cognitive decline in hypertensive patients.

Timely antibiotic initiation is critical to sepsis management, but there are limited data on the impact of giving β-lactams first versus vancomycin first among patients prescribed both agents.

We retrospectively analyzed all adults admitted to 5 US hospitals from 2015-2022 with suspected sepsis (blood culture collected, antibiotics administered, and organ dysfunction) treated with vancomycin and a broad-spectrum β-lactam within 24 hours of arrival. We estimated associations between β-lactam- versus vancomycin-first strategies and in-hospital mortality using inverse probability weighting (IPW) to adjust for potential confounders.

Among 25 391 patients with suspected sepsis, 21 449 (84.4%) received β-lactams first and 3942 (15.6%) received vancomycin first. Compared with the β-lactam-first group, patients administered vancomycin first tended to be less severely ill, had more skin/musculoskeletal infections (20.0% vs 7.8%), and received β-lactams a median of 3.5 hours later relative to emergency department arrival. On IPW analysis, the β-lactam-first strategy was associated with lower mortality (adjusted odds ratio [aOR]: .89; 95% CI: .80-.99). Point estimates were directionally similar but nonsignificant in a sensitivity analysis using propensity score matching rather than IPW (aOR: .94; 95% CI: .82-1.07) and in subgroups of patients with positive blood cultures, methicillin-resistant Staphylococcus aureus cultures, and those administered antipseudomonal β-lactams.

Among patients with suspected sepsis prescribed vancomycin and β-lactam therapy, β-lactam administration before vancomycin was associated with a modest reduction in in-hospital mortality. These findings support prioritizing β-lactam therapy in most patients with sepsis but merit confirmation in randomized trials given the risk of residual confounding in observational analyses.

Hyperkalemia is a common complication of taking a renin-angiotensin-aldosterone system inhibitor (RAASi). Post hoc analyses of large randomized clinical trials suggested that the addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may attenuate this risk. It is unknown if this observation extends to daily clinical practice.

To evaluate the association between SGLT2i initiation and hyperkalemia in individuals receiving RAASi with a background of diabetes, heart failure, or chronic kidney disease.

This population-based retrospective cohort study was conducted in Ontario, Canada, from July 1, 2015, to June 30, 2021. The cohort comprised adults 66 years and older who were prescribed a RAASi and had a history of diabetes or heart failure, an estimated glomerular filtration rate of less than 45 mL/min/1.73 m2, and/or a urine albumin to creatinine ratio of greater than 30 mg/mmol. The data were analyzed between March 28, 2023, and March 22, 2024.

The study exposure was a new prescription of an SGLT2i compared to noninitiation of an SGLT2i. Inverse probability of treatment weighting by a propensity score for the receipt of SGLT2i was used to achieve balance of baseline covariates in both exposure groups.

The primary study outcome was hyperkalemia, defined as a serum potassium of greater than 5.5 mEq/L or an administrative code for an inpatient or outpatient encounter with hyperkalemia within 1 year of the index date.

A total of 20 063 individuals who initiated an SGLT2i (mean [SD] age, 76.9 [6.6] years; 12 020 [59.9%] male) were compared to a pseudopopulation of 19 781 nonusers (mean [SD] age, 76.8 [7.0] years; 11 731 [59.3%] male). In the overall cohort, 95% had diabetes, 17% had heart failure, and 32% had stage 3 to 5 chronic kidney disease. SGLT2i initiation was associated with a lower risk of hyperkalemia (hazard ratio, 0.89 [95% CI, 0.82-0.96]). SGLT2i users had a significantly lower rate of RAASi discontinuation compared to nonusers (36% vs 45%; P < .001).

This cohort study demonstrated that, among individuals with diabetes, heart failure, or chronic kidney disease who were receiving a RAASi, SGLT2i initiation was associated with a lower risk of hyperkalemia and RAASi discontinuation.

To investigate the risk of cancer recurrence in patients with rheumatoid arthritis (RA) and a prior solid cancer in remission treated with biological disease-modifying antirheumatic drugs (bDMARDs) compared with those who received only conventional synthetic DMARDs (csDMARDs).

Nationwide registry-based cohort study of Danish patients with RA and one of the six algorithm-specific solid cancers in remission (breast, colorectal, melanoma, bladder, endometrial and lung) who initiated treatment with a bDMARD or a csDMARD. Three bDMARD exposure groups were defined according to the type(s) of bDMARD initiated: (1) any bDMARD, (2) tumour necrosis factor inhibitors (TNFi) and (3) rituximab. Patients were identified in Danish Rheumatology Quality Register and followed for cancer recurrence from 2002 to 2021 using validated cancer-specific recurrence algorithms. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate HRs for cancer recurrence in each bDMARD exposure group compared with a csDMARD-treated group.

Among 720 unique patients with RA and an algorithm-specific solid cancer in remission, 170 any bDMARD, 81 TNFi, 99 rituximab and 651 csDMARD initiators were identified. No statistically significant increased HRs for cancer recurrence were found with any type of bDMARD 0.92 (95% CI 0.38 to 1.73), TNFi 1.10 (95% CI 0.21 to 3.16) or rituximab 0.94 (95% CI 0.32 to 2.11). Also, no increased HRs were shown for breast cancer recurrence specifically.

No indications of increased cancer recurrence risk were found for bDMARDs as used in clinical practice in patients with RA and a solid cancer in remission when compared with csDMARD treatment.

Despite evidence that sleep-disorders alter sleep-stage dynamics, only a limited amount of these parameters are included and interpreted in clinical practice, mainly due to unintuitive methodologies or lacking normative values. Leveraging the matrix of sleep-stage transition proportions, we propose (i) a general framework to quantify sleep-dynamics, (ii) several novel markers of their alterations, and (iii) demonstrate our approach using obstructive sleep apnea (OSA), one of the most prevalent sleep-disorder and a significant risk factor. Using causal inference techniques, we address confounding in an observational clinical database and estimate markers personalized by age, gender, and OSA-severity. Importantly, our approach adjusts for five categories of sleep-wake-related comorbidities, a factor overlooked in existing research but present in 48.6% of OSA-subjects in our high-quality dataset. Key markers, such as NREM-REM-oscillations and sleep-stage-specific fragmentations, were increased across all OSA-severities and demographic groups. Additionally, we identified distinct gender-phenotypes, suggesting that females may be more vulnerable to awakenings and REM-sleep-disruptions. External validation of the transition markers on the SHHS database confirmed their robustness in detecting sleep-disordered-breathing (average AUROC = 66.4%). With advancements in automated sleep-scoring and wearable devices, our approach holds promise for developing low-cost screening tools for sleep-, neurodegenerative-, and psychiatric-disorders exhibiting altered sleep patterns.

Use of intracytoplasmic sperm injection (ICSI) continues to increase as the most common mode of oocyte insemination during in vitro fertilisation (IVF), sometimes in the absence of clear indications (i.e. male factor infertility). Several studies suggest an increased risk of congenital abnormalities after ICSI. The association between the ICSI technique and long-term childhood development remains unclear.

Our population-based study included singleton infants conceived via IVF and born between 2005 and 2013. The cohort included state-wide linked maternal and childhood administrative data from Victoria, Australia. The primary exposure was conception via ICSI (without severe male factor infertility), with those born following standard IVF as controls. Childhood development was examined using the Australian Early Development Census (AEDC), a broad assessment of childhood development across five domains of health and neurodevelopment performed in Australian schools every triennium at school entry (age 4-6 years). Our primary outcome used a validated global measure-developmental vulnerability-defined as scoring less than the 10th percentile in two or more of the five developmental domains (DV2). Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The adjustment variable set was determined a priori via a modified Delphi procedure. Given the use of observational data, there were missing data and inherent differences in the covariate profile between exposure cohorts. Multiple imputation, bootstrapping and doubly robust inverse probability weighted regression adjustment modelling was utilised to allow a causal interpretation of results.

Our cohort (N = 3656) included 1489 IVF and 2167 ICSI-conceived children. We found no causal effect of ICSI on the risk of AEDC-defined developmental vulnerability at school-entry age compared with children conceived via standard IVF; adjusted risk difference - 1.11% (95% CI - 4.23 to 2.01%) and adjusted risk ratio 0.90 (95% CI 0.68 to 1.21).

Our findings suggest that the use of ICSI in IVF cycles without severe male factor infertility does not increase the risk of early childhood developmental vulnerability among children in their first year of school. These findings provide important reassurance for current and prospective parents and clinicians alike.

We set out to investigate the potential impact of unemployment on HIV viral load in individuals living with HIV at the biggest HIV-related healthcare centre in Chile. We analysed a cross-sectional dataset of 803 adults living with HIV on antiretroviral therapy. The main exposure was employment status. The outcome, detectable HIV viral load, was operationalised using a cut-off of HIV viral load at 20 copies/mL. We applied a propensity score method, the inverse probability of treatment weighting to control for measured confounders. We found that 219 (27.3%) of participants were unemployed. Being unemployed was associated with increased odds of being detectable (OR = 1.78, 95%CI = 1.18-2.71) compared to being employed. Additionally, we found that those unemployed and non-adherents have higher odds of being detectable (OR = 2.53, 95%CI = 1.18-5.41). Unemployment status may influence HIV viral load. However, further research is needed to determine and understand the social structure behind those relationships in the Chilean people living with HIV.

Pneumococcal meningitis is a leading cause of bacterial meningitis and the most deadly pneumococcal disease in children worldwide. There is a paucity of evidence concerning the benefit of dexamethasone to prevent death in paediatric pneumococcal meningitis. We aimed to compare the effect of early adjunctive therapy with dexamethasone versus no dexamethasone on death in children with pneumococcal meningitis.

We did a non-randomised, comparative, multicentre, retrospective, quasi-experimental, propensity score-based study using data from a French national surveillance system of pneumococcal meningitis in children that collates data for 238 French paediatric wards working with 168 microbiology laboratories. We compared outcomes of adjunctive therapy with dexamethasone treatment (0·15 mg/kg every 6 h, for 4 days, per national guidelines) given within 12 h of antibiotic treatment versus no dexamethasone among all children aged 0-17 years with confirmed pneumococcal meningitis who had been hospitalised in one of the participating centres between Jan 1, 2005, and Nov 1, 2022. The primary outcome was 30-day all-cause death after hospital admission. The main propensity score analysis was based on inverse probability treatment weighting (IPTW), allowing adjustment for initial severity and baseline characteristics. Sensitivity analyses, such as propensity score matching, were done to assess the robustness of the results.

Between Jan 1, 2005, and Nov 1, 2022, 1765 cases of pneumococcal meningitis were reported to the National Surveillance System of Paediatric Bacterial Meningitis. 534 were excluded from the analysis and 1231 were included, with a median age of 1·1 years (IQR 0·5-5·0, range 0-17·9). 495 (40%) of 1231 patients were female, 716 (58%) were male, and 20 (1%) were missing data for sex. 650 (53%) of 1231 children received dexamethasone and 581 (47%) children did not receive dexamethasone. 108 (9%) of 1231 patients died. Within 30 days of hospitalisation, 105 (9%) patients died, 36 (6%) of 650 in the dexamethasone group and 69 (12%) of 581 in the no dexamethasone group. After IPTW, the adjusted 30-day death rate was 6% in the dexamethasone group and 12% in the no dexamethasone group (marginal odds ratio 0·39, 95% CI 0·23-0·65). All sensitivity analyses gave similar results.

Adjunctive dexamethasone within 12 h of starting antibiotic treatment was associated with a reduced 30-day risk of death in children hospitalised with pneumococcal meningitis. Our findings support the use of dexamethasone to reduce the risk of death in paediatric pneumococcal meningitis.

Pfizer, ACTIV, and National Institute of Health and Medical Research (Inserm) Centre.

Limited evidence exists on the prognostic role of continuing medical therapy in patients with heart failure (HF) and an ejection fraction (EF) that has improved over time. This study assessed rates of, patient profiles, and associations with morbidity/mortality of renin-angiotensin inhibitors (RASi), angiotensin receptor-neprilysin inhibitors (ARNi), beta-blockers (BBL), and mineralocorticoid receptor antagonists (MRA) withdrawal in patients with HF with improved EF.

Patients with a first recorded EF <40% and a later EF ≥40% from the Swedish HF registry between June 11, 2000, and December 31, 2023, were included in this retrospective observational study. Withdrawal was defined as a patient on treatment at the first (reduced) but not at the second (improved) registration. The association between withdrawal and time to first cardiovascular mortality/hospitalization for HF with censoring at 1 year was assessed by Cox regression model using overlap weighting.

Of 8728 patients with HF with improved EF (median age, 70 years [25th to 75th percentile, 61-78], 2611 [29.9%] women), 96%, 94%, and 46% received RASi/ARNi, BBL, and MRA, respectively, when EF was <40%. The withdrawal rates at the time of the improved EF registration were 4.4% for RASi/ARNi, 3.3% for BBL, and 17.2% for MRA. Predictors of withdrawal included lower use of other HF medications, higher EF at the later EF registration, and a longer time between the 2 EF assessments. After weighting, withdrawal was independently associated with a higher risk of cardiovascular mortality/hospitalization for HF by 38% for RASi/ARNi and 36% for MRA, but not for BBL. Withdrawal of BBL was associated with a higher risk of the primary outcome in the subgroup of patients with an improved EF of 40% to 49% versus ≥50% (P-interaction 0.03).

In patients with HF with improved EF, HF therapy withdrawal was rare. Withdrawing RASi/ARNi and MRA was associated with higher mortality/morbidity at 1 year. No association was found for BBL withdrawal, albeit with a significant heterogeneity for EF at improvement, suggesting better outcomes with continuing BBL only until EF improves up to 50%. These results are hypothesis-generating and highlight the need for randomized controlled trials testing BBL withdrawal in patients with HF with improved EF.

The choice of bioprosthetic or mechanical surgical aortic valve replacement (AVR) should balance individual valve durability with the potential liabilities of oral anticoagulation.

To inform clinical practice, this study sought to evaluate contemporary, real-world, long-term AVR outcomes from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD).

All patients undergoing primary isolated bioprosthetic or mechanical AVR were identified. Patients aged <40 and >75 years with endocarditis, emergency/salvage status, shock, ejection fraction ≤25%, and any prior cardiac surgery were excluded. Validated methodology was applied for linkage to the National Death Index to define longitudinal all-cause mortality (2008-2019). Robust risk adjustment was performed by using age-specific inverse probability weighting and restricted cubic splines to model nonlinear age relationships. Sensitivity analyses excluded pure aortic insufficiency, intermediate/high risk (STS predicted risk of operative mortality >4%), and discontinued valve types.

A total of 109,842 patients underwent bioprosthetic (n = 94,125) or mechanical (n = 15,717) AVR during the study period. After risk adjustment, freedom from all-cause mortality favored mechanical valves in patients aged 60 years and younger. Age group-specific analyses showed that mechanical valves were associated with lower all-cause mortality in all age groups ≤60 years. These results remained consistent across all sensitivity analyses.

In patients aged ≤60 years, mechanical AVR was associated with an independent risk-adjusted survival benefit compared with bioprosthetic AVR. These contemporary 12-year survival data further inform patient and provider shared clinical decision-making regarding prosthetic aortic valves.

Despite many atrial fibrillation (AF) patients being at risk of bleeding, very limited data are available on bleeding rates of different direct oral anticoagulants based on the spectrum of bleeding risk.

We aimed to compare the risk of major bleeding and thromboembolic events with apixaban vs rivaroxaban for AF patients stratified by bleeding risk.

We conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada, who were treated with apixaban or rivaroxaban between April 1, 2011, and March 31, 2020. Bleeding risk was estimated by the HAS-BLED score, with high bleeding risk defined as a score of ≥3. The primary safety outcome was major bleeding, and the primary efficacy outcome was thromboembolic events. Comparisons were adjusted for baseline comorbidities by inverse probability of treatment weighting.

This study included 18,156 AF patients with high bleeding risk and 55,186 AF patients with low bleeding risk. Apixaban use was more common in patients with high bleeding risk; 63% of high-risk patients used apixaban compared with 56% of low-risk patients. Apixaban users had lower rates of major bleeding in high-risk patients (2.9% vs 4.2% per year; hazard ratio [HR], 0.69; 95% CI, 0.58-0.81) and in low-risk patients (1.8% vs 2.9% per year; HR, 0.63; 95% CI, 0.56-0.70) compared with rivaroxaban. There were no differences in rates of thromboembolic events, 3.1% vs 3.0% per year (HR, 1.02; 95% CI, 0.86-1.22) in high-risk patients and 1.9% vs 1.9% per year (HR, 1.00; 95% CI, 0.89-1.14) in low-risk patients.

In older AF patients with high or low bleeding risk, treatment with apixaban was associated with lower rates of major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.

Given the uncertain generalizability of recent clinical trial data, a comparative effectiveness analysis evaluating the long-term survival of "real world" patients may clarify the role of lobectomy and sublobar resection (segmentectomy or wedge resection) in the treatment of early stage NSCLC.

Adult patients undergoing lung resection for clinical stage IA NSCLC (≤2 cm) between 2012 and 2022 were identified from the Society of Thoracic Surgeons General Thoracic Surgery Database. Long-term vital status was determined by linkage to the National Death Index and Centers for Medicare & Medicaid Services inpatient data. The primary end point was overall survival (OS); secondary end points included lung cancer-specific survival (LCSS). Stabilized inverse probability weighted Cox regression was used to account for selection bias and derive hazard ratios (HRs) with 95% confidence intervals comparing the lobectomy, segmentectomy, and wedge resection cohorts.

Overall, 32,340 patients with stage IA NSCLC (19,778 lobectomies [OS = 71.9% (5 y), 44.8% (10 y)], 4279 segmentectomies [OS = 69.6%, 44.2%], and 8283 wedge resections [OS = 66.3%, 41.4%]) were evaluated. After risk adjustment, lobectomy was associated with improved OS and LCSS compared with sublobar resection (HR [OS] = 0.87 [0.83-0.92]; HR [LCSS] = 0.84 [0.73-0.97]). Both lobectomy (HR [OS] = 0.84 [0.80-0.88]; HR [LCSS] = 0.72 [0.56-0.93]) and segmentectomy (HR [OS] = 0.88 [0.81-0.95]; HR [LCSS] = 0.77 [0.66-0.89]) were associated with improved survival compared with wedge resection. No differences in OS or LCSS were observed between lobectomy and segmentectomy.

In routine clinical practice, lobectomy and segmentectomy are associated with improved OS and LCSS compared with wedge resection for stage IA NSCLC (≤2 cm). These findings highlight the potential gap between trial efficacy and real-world effectiveness.

SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) contribute to many hospitalizations and deaths each year. Understanding relative disease severity can help to inform vaccination guidance.

To compare disease severity of COVID-19, influenza, and RSV among US veterans.

This retrospective cohort study analyzed national US Veterans Health Administration electronic health record data of nonhospitalized veterans who underwent same-day testing for SARS-CoV-2, influenza, and RSV, and were diagnosed with a single infection between August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024.

Infection with SARS-CoV-2, influenza, or RSV.

Following inverse probability weighting, the cumulative incidence and risk differences (RDs) were calculated for the primary outcomes of 30-day hospitalization, intensive care unit admission, and death, as well as the secondary outcome of long-term death extending through 180 days.

Among 68 581 patients included in the 2022 to 2023 cohort (6239 [9.1%] with RSV, 16 947 [24.7%] with influenza, and 45 395 [66.2%] with COVID-19) and 72 939 in the 2023 to 2024 cohort (9748 [13.4%] with RSV, 19 242 [26.4%] with influenza, and 43 949 [60.3%] with COVID-19), the median (IQR) age was 66 (53-75) years, and 123 090 (87.0%) were male. During the 2023 to 2024 season, the 30-day risk of hospitalization was similar for COVID-19 (16.2%) and influenza (16.3%) but lower for RSV at 14.3% (RD for COVID-19 vs RSV, 1.9% [95% CI, 0.9%-2.9%]; RD for influenza vs RSV, 2.0% [95% CI, 0.8%-3.3%]). The 30-day risk of death during the 2022 to 2023 season was slightly higher for COVID-19 (1.0%) compared with influenza (0.7%) (RD, 0.4% [95% CI, 0.1%-0.6%]) or RSV (0.7%) (RD, 0.4% [95% CI, 0.1%-0.6%]) but similar during the 2023 to 2024 season. Mortality risk at 180 days was higher for COVID-19 during both seasons (2023-2024 RD for COVID-19 vs influenza, 0.8% [95% CI, 0.3%-1.2%]; RD for COVID-19 vs RSV, 0.6% [95% CI, 0.1%-1.1%]). Higher mortality in both seasons was observed for veterans without COVID-19 vaccination in the previous year compared to veterans without seasonal influenza vaccination. In contrast, among groups vaccinated against their respective infections, there were no mortality differences at any time point between COVID-19 and influenza.

This cohort study showed that, during the 2022 to 2023 season, infection with SARS-CoV-2 was associated with more severe disease outcomes than influenza or RSV, whereas differences were less pronounced during the 2023 to 2024 season. During both seasons, RSV remained a milder illness, whereas COVID-19 was associated with higher long-term mortality. Vaccination attenuated differences in disease severity and long-term mortality.

No large randomized clinical trial has directly compared empagliflozin with dapagliflozin, leaving their comparative effectiveness regarding kidney outcomes unknown.

To compare kidney outcomes between initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who were receiving antihyperglycemic treatment.

This target trial emulation used nationwide, population-based routinely collected Danish health care data to compare initiation of empagliflozin vs dapagliflozin in adults with type 2 diabetes who received antihyperglycemic treatment between June 1, 2014, and October 31, 2020. Data were analyzed from October 2023 to August 2024. Persons were followed up until an outcome, emigration, death, 6 years, or December 31, 2021, whichever occurred first.

Initiation of empagliflozin vs dapagliflozin.

Outcomes included acute kidney injury, incident chronic kidney disease (stages G3 to G5 or stage A2 or A3), and progression of chronic kidney disease (≥40% decrease in estimated glomerular filtration rate from baseline). Risks of kidney outcomes were estimated in intention-to-treat and per-protocol analyses using an Aalen-Johansen estimator that adjusted for 56 potential confounders and considered death as a competing event.

A total of 32 819 individuals who initiated treatment with empagliflozin and 17 464 with dapagliflozin were included (median [IQR] age, 63 [54-71] years; 18 872 female individuals [37.5%]; median [IQR] estimated glomerular filtration rate, 88 [73-104] mL/min/1.73 m2). After weighting, all measured covariates were well balanced between the groups. In intention-to-treat analyses, people who initiated treatment with empagliflozin and dapagliflozin exhibited comparable 6-year risks of acute kidney injury (18.2% vs 18.5%; risk ratio, 0.98; 95% CI, 0.91-1.06), chronic kidney disease stages G3 to G5 (11.8% vs 12.1%; risk ratio, 0.97; 95% CI, 0.89-1.05), chronic kidney disease stage A2 or A3 (14.8% vs 14.3%; risk ratio, 1.04; 95% CI, 0.93-1.15), and progression of chronic kidney disease (5.3% vs 5.7%; risk ratio, 0.94; 95% CI, 0.56-1.58). The primary analyses were supported by corresponding per-protocol analyses.

The results of this cohort study suggest that people with type 2 diabetes who initiated treatment with empagliflozin and dapagliflozin had comparable long-term kidney outcomes.

Rationale: Whether extubation immediately after a successful spontaneous breathing trial is associated with clinical benefits in adult patients with acute brain injury is unknown. Objectives: We sought to estimate the association between a prompt extubation attempt and ventilator-free days among adult patients with acute brain injury. Methods: We performed an emulation of a previously designed randomized controlled trial using data from the Toronto Intensive Care Observational Registry in eight ICUs in Toronto, Ontario, Canada. We included mechanically ventilated adult patients with acute brain injury who had a first successful spontaneous breathing trial. Our main exposure was prompt extubation (i.e., on the same calendar day after the first successful spontaneous breathing trial). The primary outcome was ventilator-free days up to 28 days. We used inverse probability of treatment weighting to adjust for confounding and reported treatment effects using incidence rate ratios and 95% confidence intervals. Measurements and Main Results: A total of 1,406 patients from April 2014 through March 2023 met inclusion criteria. The main reasons for admission were traumatic brain injury (40%), stroke (ischemic or hemorrhagic; 20%), seizures (11%), and subarachnoid hemorrhage (9%). Over half (57%) of patients underwent prompt extubation after their first successful spontaneous breathing trial. Prompt extubation was associated with more ventilator-free days (incidence rate ratio, 1.24; 95% confidence interval, 1.19-1.29) when compared with no prompt extubation. Conclusions: Prompt extubation after a first successful spontaneous breathing trial was associated with more ventilator-free days (up to 28 d) among adults with acute brain injury receiving invasive mechanical ventilation. The original trial protocol was registered with www.clinicaltrials.gov (NCT04291235).

To investigate cancer risk in RA patients treated with tocilizumab/sarilumab, abatacept or rituximab compared with those who received TNF inhibitors (TNFi) and compared with biological DMARDs (bDMARD)-naïve RA patients.

Nationwide registry-based cohort study of RA patients who initiated bDMARD treatment with tocilizumab/sarilumab, abatacept, rituximab, and TNFi, as well as bDMARD-naive patients who initiated their second type of conventional synthetic DMARD. Patients were identified in the Danish Rheumatology Quality Register (DANBIO) and followed for cancer from 2006 to 2020. Patients could contribute multiple treatments, with person years, deaths and cancers allocated to each treatment group in a 'latest type of treatment' manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept and rituximab group compared with TNFi-treated and bDMARD-naïve groups, respectively.

In total, 21 982 treatment initiations, 96 475 person years and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept or rituximab treatment groups (HRs ranged from 0.7 to 1.1). More than 5 years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% CI 0.74-2.71). For haematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi-treated (HR 0.09; 95% CI 0.00-2.06) and bDMARD-naïve (HR 0.13; 95% CI 0.00-1.89).

Treatment with tocilizumab/sarilumab, abatacept or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.

Better data are necessary to determine whether baseline level of kidney function affects the rate of progressive kidney disease following pregnancy.

The objective was to determine whether the baseline (pre-pregnancy) estimated glomerular filtration rate (eGFR) modifies the association between becoming pregnant and the subsequent rate of progressive kidney disease.

Population-based cohort study using provincial administrative health care databases in Ontario and Alberta, Canada.

The sample will be accrued from April 1, 2007, to March 31, 2023, in Ontario and from April 1, 2012, to March 31, 2023, in Alberta. Follow-up for study outcomes will occur until March 31, 2024.

The pregnant group will include adult female residents of Ontario or Alberta with a record of a pregnancy of 20 to 46 weeks' gestation during the accrual period, and the non-pregnant group will include adult female residents with no prior record of pregnancy. The cohort entry dates in those in the pregnant group will be the estimated date of conception; the entry dates for those in the non-pregnant group will be randomly assigned following the distribution of dates in the pregnant group. To be eligible, individuals must be between 18 and 45 years old at cohort entry. They require at least 1 serum creatinine measurement within 2 years before entry and should not have received maintenance dialysis or a prior kidney transplant. Both groups will be categorized into one of 3 levels of baseline eGFR (≥60, 45-59, and <45 mL/min per 1.73 m2). Inverse probability of treatment weighting on a propensity score will be used to balance the pregnant and non-pregnant groups on baseline characteristics (including age, proteinuria, hypertension, and diabetes) within the 3 categories of baseline eGFR.

The primary outcome, progressive kidney disease, will be defined as a composite of a persistent ≥40% drop in eGFR from the baseline value, a new persistent eGFR <15 mL/min per 1.73 m2, receipt of maintenance dialysis, or receipt of a kidney transplant. The secondary outcomes will be the components of the primary composite outcome examined separately and the annualized change in eGFR in mL/min per 1.73 m2 from baseline.

We will test for statistical interaction to determine whether the baseline category of eGFR modifies the rate of long-term progressive kidney disease after pregnancy. We hypothesize that a statistical interaction will be present. We will present weighted cause-specific hazard ratios (HRs) and cumulative incidence function (CIF) curves for up to 10 years of follow-up for the pregnant and non-pregnant groups stratified by each eGFR category. We will perform additional pre-specified analyses to confirm whether the findings are robust and examine associations that account for baseline proteinuria.

Based on a feasibility analysis using ICES data in Ontario, we expect the cohort to include over 400 000 pregnant females and 1.2 million non-pregnant females. This includes at least 395 000 pregnant females with baseline eGFR ≥60 mL/min/1.73 m2, 300 with eGFR 45 to 59 mL/min/1.73 m2, and 110 with eGFR <45 mL/min/1.73 m2. The median follow-up is anticipated to be 5 years (range = 1-17 years) with minimal loss to follow-up.

Measures of kidney function will be obtained as part of routine care (not according to a research schedule). Measures of baseline proteinuria are frequently missing from routine care data, even in up to 15% of those with an eGFR <45 mL/min per 1.73 m2.

This study will investigate whether the level of baseline eGFR modifies the rate of progressive kidney disease after pregnancy and will estimate the cumulative incidence of progressive kidney disease in pregnant and non-pregnant females across 3 categories of baseline eGFR.

Inverse probability of treatment weighting (IPTW) using the propensity score allows estimation of the effect of treatment in observational studies. We had three objectives: first, to describe methods for using IPTW to estimate the effects of treatments in settings with competing risks; second, to illustrate the application of these methods using empirical analyses; and third, to conduct Monte Carlo simulations to evaluate the relative performance of three methods for estimating time-specific risk differences and time-specific relative risks in settings with competing risks. In doing so, we provide guidance to applied biostatisticians and clinical investigators on the use of IPTW in settings with competing risks. We examined three estimators of time-specific risk differences and relative risks: the weighted Aalen-Johansen estimator, an estimator that combines IPTW with inverse probability of censoring weights (IPTW-IPCWs), and a double-robust augmented IPTW estimator combined with IPCW (AIPTW-IPCW). The design of our simulations reflected clinically realistic scenarios. Our simulations found that all three estimators tended to result in unbiased estimations of time-specific risk differences and time-specific relative risks. However, the weighted Aalen-Johansen estimator and the AIPTW-IPCW estimator tended to result in estimates with greater precision compared to the IPTW-IPCW estimator. In our empirical analyses, we illustrated the application of these methods by estimating the effect of statin prescribing on the risk of subsequent cardiovascular death in patients discharged from the hospital with a diagnosis of acute myocardial infarction.

In patients with type 2 diabetes mellitus and chronic kidney disease (CKD), sodium-glucose cotransporter 2 (SGLT2) inhibitors improve renal outcomes, but may transiently affect biochemical markers of CKD-mineral and bone disorders (CKD-MBD). We sought to evaluate the long-term risk of CKD-MBD associated with use of SGLT2 inhibitors in this patient population.

We conducted a retrospective cohort study, employing a target trial emulation framework and using electronic medical records of patients from 9 hospitals in Taiwan (2016-2023). We included adults with type 2 diabetes mellitus and stage 1-3 CKD who had newly started either an SGLT2 inhibitor or, as a comparison group, a glucagon-like peptide-1 receptor agonist (GLP-1 RA). The primary outcome was a composite of incident biochemical abnormalities (serum phosphate > 1.5 mmol/L, serum calcium < 2.1 mmol/L, serum intact parathyroid hormone [iPTH] > 6.9 pmol/L, or serum 25-hydroxyvitamin D < 49.9 nmol/L).

The cohort included 13 379 patients receiving SGLT2 inhibitors (n = 11 920) or GLP-1 RAs (n = 1459) with a median follow-up of 3.3 years. Compared with GLP-1 RAs, SGLT2 inhibitors were associated with a lower cumulative incidence of the composite primary outcome (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.79-0.86), hyperphosphatemia (HR 0.83, 95% CI 0.76-0.91), hypocalcemia (HR 0.82, 95% CI 0.78-0.86), high serum iPTH levels (HR 0.66, 95% CI 0.57-0.78), and low serum 25-hydroxyvitamin D levels (HR 0.65, 95% CI 0.47-0.90).

Use of SGLT2 inhibitors was associated with a lower incidence of biochemical abnormalities related to CKD-MBD than GLP-1 RAs. These agents may be considered to reduce risk of CKD-MBD in patients with type 2 diabetes mellitus and stage 1-3 CKD.

Uncomplicated urinary tract infection (UTI) is a common indication for outpatient antimicrobial therapy. National guidelines for the management of uncomplicated UTI were published in 2011, but the extent to which they align with current practices, patient diversity, and pathogen biology, all of which have evolved greatly in the time since their publication, is not fully known.

To reevaluate the effectiveness and adverse event profile for first-line antibiotics, fluoroquinolones, and oral β-lactams for treating uncomplicated UTI in contemporary clinical practice.

This retrospective, population-based cohort study used a claims dataset from Independence Blue Cross, which contains inpatient, outpatient, laboratory, and pharmacy claims that occurred between 2012 and 2021, formatted into the Observational Medical Outcomes Partnership (OMOP) common data model. Participants were nonpregnant female individuals aged 18 years or older with a diagnosis of uncomplicated, nonrecurrent UTI at an outpatient setting. Patients must also have been treated with first-line (nitrofurantoin or trimethoprim-sulfamethoxazole), fluoroquinolone (ciprofloxacin, levofloxacin, or ofloxacin), or oral β-lactam (amoxicillin-clavulanate, cefadroxil, or cefpodoxime) antibiotics. Data analysis was performed from November 2021 to August 2024.

Patients exposed to first-line antibiotics were assigned to the treatment group, and those exposed to fluoroquinolone or β-lactam treatments were assigned to control groups.

The primary outcome was a composite end point for treatment failure, defined as outpatient or inpatient revisit within 30 days for UTI, pyelonephritis, or sepsis. Secondary outcomes were the risk of 4 common antibiotic-associated adverse events: gastrointestinal symptoms, rash, kidney injury, and Clostridium difficile infection.

There were 57 585 episodes of UTI among 49 037 female patients (mean [SD] age, 51.7 [20.1]) years), with prescriptions for first-line antibiotics in 35 018 episodes (61%), fluoroquinolones in 21 140 episodes (37%), and β-lactams in 1427 episodes (2%). After adjustment, receipt of first-line therapies was associated with an absolute risk difference of -1.78% (95% CI, -2.37% to -1.06%) for having a revisit for UTI within 30 days of diagnosis vs fluoroquinolones. First-line therapies were associated with an absolute risk difference of -6.40% (95% CI, -10.14% to -3.24%) for 30-day revisit compared with β-lactam antibiotics. Differences in adverse events were similar between all comparators. Results were identical for models built with an automated OMOP feature extraction package.

In this cohort study of patients with uncomplicated UTI derived from a large regional claims dataset, national treatment guidelines published almost 14 years ago continue to recommend optimal treatments. These results also provide proof-of-principle that automated feature extraction methods for OMOP formatted data can emulate manually curated models, thereby promoting reproducibility and generalizability.

To compare the association between prostate-specific antigen (PSA) levels and prostate cancer-specific mortality (PCSM) and the effectiveness of local treatment in patients with high-grade and low-grade prostate cancer (PCa).

This retrospective cohort study enrolled patients diagnosed with clinically localized PCa (cT1-4N0M0) from January 2010 to December 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression analysis was conducted to generate cumulative incidence plots and estimate the hazard ratio (HR) and 95% CI of PCSM. Multivariable restricted cubic spline analysis was used to examine the nonlinear associations of continuous values of PSA levels with PCSM. Inverse probability of treatment weighting was employed to minimize imbalances in baseline characteristics between different local treatment cohorts.

A total of 392 083 eligible patients were included in the study, including 327 659 low-grade (Gleason score [GS]≤7) PCa and 64424 high-grade (GS≥8) PCa. In multivariate Fine-Gray competing risk regression analysis, using PSA levels of 4.1-10.0 ng/ml as the reference, the adjusted HR among high-grade patients with PSA levels ≤2.5 ng/ml, 2.6-4.0 ng/ml, 10.1-20.0 ng/ml and >20.0 ng/ml were 1.988 (95% CI: 1.677-2.358), 1.411 (95% CI: 1.194-1.668), 1.472 (95% CI: 1.351-1.603), and 2.506 (95% CI: 2.318-2.709), respectively. Among low-grade PCa, the adjusted HR were 0.985 (95% CI: 0.800-1.213), 0.727 (95% CI: 0.602-0.877), 1.844 (95% CI: 1.679-2.026), and 3.574 (95% CI: 3.220-3.966), respectively. Multivariable-adjusted restricted cubic spline analysis showed a U/J-shaped distribution relationship between PSA levels and PCSM in high-grade PCa, while there was a positive association between PSA levels and PCSM in low-grade PCa. As for local treatment effectiveness, radiation therapy (RT) provided better control of PCSM compared to radical prostatectomy (RP) and RP+RT in high-grade PCa, while RP provided better control of PCSM compared to RT and RP+RT in low-grade PCa.

Low PSA level (≤2.5 ng/ml) is significantly associated with a very high-risk of PCSM in high-grade localized PCa but not in low-grade localized PCa. High-grade localized PCa patients benefit more from RT in terms of PCSM control, while low-grade localized PCa patients benefit more from RP. High-grade localized PCa with low PSA level may be a unique subgroup that could benefit from novel risk stratification strategies in PCa, which requires further studies to investigate the potential of developing novel therapeutic strategies, prognostic tools, and clinical management approaches.

In elderly and frail patients, there is limited evidence on the therapeutic management of left main coronary artery (LM) disease. The objective of this study was to evaluate mid-term clinical outcomes in older adults undergoing percutaneous coronary intervention (PCI) of LM.

We conducted a retrospective study including all older patients (≥ 75 years) undergoing LM-PCI at a high-volume center between 2017 and 2021. The primary endpoint was a composite of major adverse cardiovascular events (MACE). Patients were grouped according to the presence of frailty based on the FRAIL scale. Inverse probability of treatment weighting was used to account for clinical differences between the 2 groups.

A total of 140 patients were included in the study (median age 80 [78-84]; 36% women). Of them, 49% met the criteria for frailty. After a median follow-up of 19 [5-35] months, 40 MACE (29%) were recorded. The all-cause death rate was 32%. There were no differences in the risk of MACE between frailty groups, but patients with frailty had an increased risk of all-cause mortality (HRadj, 1.95 [1.02-3.75]; P = .046).

LM-PCI in older adults with multiple associated comorbidities could be considered a feasible option in this special population. The rate of MACE at follow-up was acceptable. Frailty was associated with a worse prognosis in terms of all-cause mortality at follow-up.