This study is aimed to evaluate the association between statin therapy and intermediate-term survival in critically ill patients with heart failure (HF). Using a real-world retrospective cohort from the MIMIC-IV database, we assessed all-cause mortality at 90 and 180 days following ICU admission. To reduce confounding factors, we applied a triangulated analytic framework incorporating propensity score matching, inverse probability of treatment weighting and standardized mortality ratio weighting. Survival outcomes were additionally examined across different statin types, including atorvastatin, rosuvastatin, simvastatin and pitavastatin, using stratified Kaplan–Meier analysis. Among over 8,000 eligible patients, statin use during hospitalization was consistently associated with reduced mortality at both time points across all models. Stratified survival curves showed comparable trends among the different statin types. These findings suggest a potential class-wide survival benefit of statin therapy in the ICU setting for HF patients and highlight the need for further studies to determine whether specific statin selection offers additional clinical advantages.

Association of aspirin use with mortality in critically ill patients with chronic obstructive pulmonary disease: A retrospective propensity score-matched cohort study.

The study objective was to compare long-term treatment persistence between patients initiating guselkumab vs 3 commonly prescribed biologics in the United States. Adult plaque psoriasis patients enrolled in the CorEvitas Psoriasis Registry initiating guselkumab, adalimumab, secukinumab, or ixekizumab (July 2017 - January 2022) were divided into biologic-naïve and biologic-experienced cohorts. The primary outcome measure was average 2-year treatment persistence, estimated as restricted mean survival time (RMST), comparing guselkumab with adalimumab, secukinumab, and ixekizumab. Standardized mortality ratio weighting was used to adjust for confounding. 1,007 biologic-naïve and 1,584 biologic-experienced treatment initiations were included. For biologic-naïve initiators, the weighted-average treatment persistence for guselkumab was 20.3 months (95% CI: 19.4, 21.3), 14.6 months (13.5, 15.7) for adalimumab; 17.5 months (16.5, 18.6) for secukinumab, and 18.9 months (17.8, 20.1) for ixekizumab. The RMST difference for guselkumab was 24.9 weeks (95% CI: 18.4, 31.3) vs adalimumab, 12.1 weeks (5.9, 18.2) vs secukinumab and 6.0 weeks (0.4, 12.4) vs ixekizumab. For biologic-experienced initiators, the weighted-average treatment persistence for guselkumab was 17.6 months (95% CI: 16.9, 18.4), 13.5 months (11.6, 15.5) for adalimumab, 16.5 months (15.7, 17.3) for secukinumab, and 16.9 months (16.1, 17.8) for ixekizumab. The RMST difference for guselkumab was 17.7 weeks (95% CI: 8.7, 26.7) vs adalimumab, 5.0 weeks (0.2, 9.1) vs secukinumab and 2.9 weeks (-1.9, 7.7) vs ixekizumab. In both biologic-naïve and biologic-experienced cohorts in this real-world study, average treatment persistence was significantly longer for guselkumab compared to adalimumab and secukinumab and numerically longer compared to ixekizumab.

Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a major health concern worldwide, particularly in China. Surgical resection is still considered the primary curative treatment for this disease. However, the effect of different surgical methods-traditional hand-sewn anastomosis and modern mechanical anastomosis-remains controversial. A retrospective study was thus performed to elucidate how these two techniques affected the clinical prognosis of patients. Data were retrospectively collected from the comprehensive Esophageal Cancer Case Management Database of Sichuan Cancer Hospital and Institute (Chengdu, China), covering the period from 2010 to 2017. The cohort consisted of patients who underwent esophagectomy for ESCC, divided into two groups based on the suturing technique used: Manual suturing (MS) and mechanical suturing (MeS). A total of four causal inference methods for retrospective studies, namely inverse probability of treatment weighting, standardized mortality ratio weighting, overlap weighting and propensity score matching analysis, were used to minimize potential selection bias. The primary outcome evaluated was overall survival (OS), allowing for a direct comparison of the long-term efficacy of the two suturing methods. In a retrospective analysis of 2,510 patients undergoing esophagectomy, significant differences in OS were observed between the MeS group and the MS group (hazard ratio: 0.84; 95% confidence interval: 0.75-0.95; P=0.004). However, after matching or weighting based on causal inference analyses, no significant differences in survival outcomes between groups were obtained. The equivalence in outcomes suggests that either suturing method may be equally viable in clinical practice, offering flexibility in surgical decision-making without compromising OS.

Ivacaftor (IVA) has been shown to change the trajectory of cystic fibrosis (CF) disease progression by slowing the rate of lung function decline in clinical studies. Long-term real-world data help to confirm the durability of this response. This non-interventional, longitudinal study used data from the US CF Foundation Patient Registry to describe the annualized rate of change in lung function in people with CF receiving IVA. The IVA-treated cohort included people with CF aged ≥ 6years who had ≥ 1 CF transmembrane conductance regulator (CFTR)-gating mutation and initiated IVA between 31 January 2012 and 31 December 2018. An age-matched comparator cohort included people with CF heterozygous for the F508del-CFTR mutation and a minimal function mutation (R117H excluded) and had not received CFTR modulator therapy. Baseline characteristics were balanced using standardized mortality ratio (SMR) weights computed from estimated propensity scores. The annualized rate of change in percent predicted forced expiratory volume in 1s (ppFEV1) was estimated over 5years and used to calculate the relative annualized rate of change in lung function in the IVA-treated versus comparator cohorts. In the 5-year follow-up period, 548 people were in the IVA-treated and 541 in the comparator cohorts after SMR weighting. The annualized rate of change in ppFEV1 over 5years was -1.23 (95% CI -1.45, -1.03) and -2.03 (-2.16, -1.90) percentage points in the IVA-treated and comparator cohorts, respectively. There was a 39% reduction (95% CI: 28, 50) in the rate of lung function decline in the IVA-treated versus comparator cohort over 5years. Findings were generally consistent with those of shorter follow-up periods. IVA showed a durable clinical benefit by slowing the rate of lung function decline over 5years. Results support a sustained and consistent impact of IVA on lung function trajectory in people with CF. Word count: 300 (limit: 300 words).

Introduction: Acute respiratory distress syndrome (ARDS) remains a challenging disease with limited prevention and treatment options. The usage of beta-blockers may have potential benefits in different critical illnesses. This study aimed to investigate the correlation between beta-blocker therapy and mortality in patients with ARDS. Materials and methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care (MIMIC) IV database and focused on patients diagnosed with ARDS. The primary outcome of the study was 30-day mortality. To account for confounding factors, a multivariable analysis was performed. Propensity score matching (PSM) was carried out on a 1:1 ratio. Robust assessments were conducted using inverse probability weighting (IPTW), standardized mortality ratio weighting (SMRW), pairwise algorithms (PA), and overlap weights (OW). Results: A total of 1,104 patients with ARDS were included in the study. Univariate and multivariate Cox regression analyses found that the 30-day mortality for 489 patients (23.7%) who received beta-blockers was significantly lower than the mortality rate of 615 patients (35.9%) who did not receive beta-blockers. After adjusting for potential confounders through PSM and propensity score, as well as utilizing IPTW, SMRW, PA, and OW, the results remained robust, with the hazard ratios (HR) ranging from 0.42 to 0.58 and all p-values < 0.001. Evaluation of the E-values indicated the robustness of the results even in the presence of unmeasured confounding. Conclusion: The findings suggest a potential association between beta-blocker usage and reduced mortality in critically ill patients with ARDS. However, further validation of this observation is needed through randomized controlled trials.

An Updated Comparison of Clinical Outcomes from 4-Year Follow-up of Zuma-5 (Axicabtagene Ciloleucel) and the International Scholar-5 External Control Cohort in Relapsed/Refractory Follicular Lymphoma

Favorable effect of CD26/DPP-4 inhibitors on postoperative outcomes after lung transplantation: A propensity-weighted analysis

BackgroundExtrathyroidal extension is a major risk factor for poor prognosis in papillary thyroid cancer. However, the effect of different degrees of extrathyroidal extension on prognosis remains controversial. We performed a retrospective study to elucidate how the extent of extrathyroidal extension in papillary thyroid cancer affected the clinical prognosis of patients and its covariates.MethodsThe study included 108,426 patients with papillary thyroid cancer. We categorized the extent of extension into none, capsule, strap muscles, and other organs. Three causal inference methods for retrospective studies, namely, inverse probability of treatment weighting, standardized mortality ratio weighting, and propensity score matching analysis, were used to minimize potential selection bias. Kaplan–Meier analysis and univariate Cox regression analyses were applied to analyze the precise effect of ETE on survival in papillary thyroid cancer patients.ResultsIn the Kaplan–Meier survival analysis, only extrathyroidal extension into or beyond the strap muscles was statistically significant for both overall survival (OS) and thyroid cancer-specific survival (TCSS). In univariate Cox regression analyses before and after matching or weighting based on causal inference, extrathyroidal extension into soft tissues or other organs is a high-risk factor for both overall survival and thyroid cancer-specific survival. Sensitivity analysis revealed that lower overall survival was observed in patients with older age (≥55) and larger tumor size (>2 cm) of papillary thyroid cancer with extrathyroidal extension into or beyond the strap muscles.ConclusionsOur study indicates that extrathyroidal extension into soft tissues or other organs is a high-risk factor in all papillary thyroid cancer. Even though invasion into the strap muscles did not seem to be a marker for poor prognosis, it still impaired the overall survival of patients with older age (≥55 years old) or larger tumor size (>2 cm). Further investigation is needed to confirm our results and to clarify further risk factors independent of extrathyroidal extension.

BackgroundSepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients.MethodsWe included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60–65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results.ResultsA total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60–65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60–0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission.ConclusionsAfter risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis.

ABSTRACT Background In the ZUMA-5 trial (Clinical trials identification: NCT03105336), axicabtagene ciloleucel (axi-cel; a chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients and clear superiority relative to the SCHOLAR-5 external control cohort. We update this comparison using the ZUMA-5 24-month data. Research design and methods The SCHOLAR-5 cohort is comprised of r/r FL patients who initiated ≥3rd line of therapy after July 2014 and meeting ZUMA-5 eligibility criteria. Groups were balanced for patient characteristics through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. The overall response rate was compared using a weighted logistic regression. Time-to-event outcomes were evaluated using a Cox regression. Results For SCHOLAR-5, the sum of weights for the 143 patients was 85 after SMR weighting, versus 86 patients in ZUMA-5. The median follow-up was 29.4 months and 25.4 months for ZUMA-5 and SCHOLAR-5, respectively. The hazard ratios for overall survival and progression-free survival were 0.52 (95% confidence interval (CI): 0.28–0.95) and 0.28 (95% CI: 0.17–0.45), favoring axi-cel. Conclusion This updated analysis, using a longer minimum follow-up than a previously published analysis, shows that the improved efficacy of axi-cel, relative to available therapies, in r/r FL is durable. .

A 3-Year Follow-up Comparison of Clinical Outcomes from Zuma-5 (Axicabtagene Ciloleucel) and the International Scholar-5 External Control Cohort in Relapsed/Refractory Follicular Lymphoma (R/R FL)

Selective serotonin reuptake inhibitors and the risk of type 2 diabetes mellitus in youths

Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma

To evaluate the effectiveness and safety of apixaban versus rivaroxaban among patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes mellitus (T2DM). Using the United Kingdom's Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository, and the Office for National Statistics database, we identified a cohort of patients with NVAF and T2DM newly treated with apixaban or rivaroxaban between 2013 and 2020. Propensity scores with standardized mortality ratio weighting were used to control for confounding. We used weighted Cox proportional hazards models to estimate separately the hazard ratios (HRs) with 95% confidence intervals (CIs) of ischemic stroke, major bleeding, and major adverse limb events associated with the use of apixaban compared with rivaroxaban. We also evaluated whether the risk was modified by age, sex, duration of diabetes, microvascular and macrovascular complications of diabetes, nephropathy, CHA2DS2-VASc and HAS-BLED scores, and by dose (standard vs. low dose). The cohort included 11,561 apixaban and 8,265 rivaroxaban users. Apixaban was associated with a similar risk of stroke (HR: 0.99, 95% CI: 0.79-1.23), and a 32% reduced risk of major bleeding (HR: 0.68, 95% CI: 0.59-0.78), compared with rivaroxaban. The risk of major adverse limb events was similar between apixaban and rivaroxaban (HR: 0.75, 95% CI: 0.54-1.04). Overall, the risk of ischemic stroke and major bleeding was consistent in stratified analyses. Among patients with NVAF and T2DM, apixaban was associated with a similar risk of stroke and a lower risk of major bleeding compared with rivaroxaban.

Despite the known involvement of depression in chronic pain, the association between persistence with and adherence to antidepressant medication and onset of chronic pain in patients with depression remains unclear. This retrospective cohort study used a Japanese claims database to extract data for adult patients with depression who were prescribed antidepressants between April 2014 and March 2020. Patients were divided into groups according to duration of continuous prescription of antidepressants (≥6 months [persistent group] and <6 months [nonpersistent group]) and medication possession ratio (≥80% [good adherence group] and <80% [poor adherence group]). The outcome was onset of chronic pain, which was defined as continuous prescription >3 months of analgesics and diagnosis of pain-related condition after discontinuation of the first continuous antidepressant prescription. The risk of onset of chronic pain was compared between the paired groups. A total of 1859 patients were selected as the study population and categorized as the persistent (n = 406) and nonpersistent (n = 1453) groups, and good adherence (n = 1551) and poor adherence (n = 308) groups. Risk of onset of chronic pain was significantly lower in the persistent group than in the nonpersistent group after controlling for confounding via standardized mortality ratio weighting (hazard ratio, 0.38; 95% confidence interval, 0.18-0.80; P = 0.011). There was no significant difference between the good and poor adherence groups. Antidepressant persistence for ≥6 months is recommended and may reduce the onset of chronic pain in patients with depression.

There currently exists a paucity of data on whether pre-admission anticoagulants use may have benefits among COVID-19 patients by preventing COVID-19 associated thromboembolism. The aim of this study was to assess the association between pre-admission anticoagulants use and COVID-19 adverse outcomes. We conducted a population-based cohort studying using the Health Insurance Review and Assessment Service (HIRA) claims data released by the South Korean government. Our study population consisted of South Koreans who were aged 40 years or older and hospitalized with COVID-19 between 1 January 2020 through 15 May 2020. We defined anticoagulants users as individuals with inpatient and outpatient prescription records in 120 days before cohort entry. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, and mechanical ventilation use. Individual components of the primary endpoint were secondary endpoints. We compared the risk of endpoints between the anticoagulants users and non-users by logistic regression models, with the standardized mortality ratio weighting (SMRW) adjustment. In our cohort of 4,349 patients, for the primary endpoint of mortality, mechanical ventilation and ICU admission, no difference was noted between anticoagulants users and non-users (SMRW OR 1.11, 95% CI: 0.60-2.05). No differences were noted, among individual components. No effect modification was observed by age, sex, history of atrial fibrillation and thromboembolism, and history of cardiovascular disease. When applying the inverse probability of treatment weighting (IPTW) and SMRW with doubly robust methods in sensitivity analysis, anticoagulants use was associated with increased odds of the primary endpoint. Pre-admission anticoagulants were not determined to have a protective role against severe COVID-19 outcomes.

Propensity score analysis has been widely used in observational studies to make a causal inference. This study introduces three assumptions for causal inferences-conditional exchangeability, positivity, and consistency-and five steps for propensity score (PS) analysis-1) construct appropriate PS models, 2) check overlap in PS, 3) apply appropriate weighting (inverse probability of treatment weighting, standardized mortality ratio weighting, matching weights, and overlap weights) or matching methods according to the target of inference, 4) check the balance of covariates, and 5) estimate the effect of exposure appropriately. Finally, the advantages of PS analyses over conventional multivariable regression are discussed.

PurposeThe efficacy of local treatments (LTs) in selected patients with metastatic prostate cancer (mPCa) had been demonstrated. However, the comparative effectiveness between LTs is unclear. Here, we compared the impact of radical prostatectomy (RP) and brachytherapy (RT) on the survival outcomes of mPCa patients.Materials and MethodsmPCa patients who received RT or RP between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable Cox proportional hazards analysis was used to evaluate the comparative risk of prostate cancer-specific mortality (CSM) and all-cause mortality (ACM) between LTs. A 1:1 propensity score matching (PSM) and adjusted standardized mortality ratio weighting (SMRW) were performed to balance the clinicopathological characteristics of the groups.ResultsOf 684 mPCa patients, 481 underwent RP and 203 received RT. After PSM, both groups included 148 cases, and RT resulted in comparable CSM versus RP [CSM: hazard ratio (HR) = 0.77, p = 0.325; ACM: HR = 0.73, p = 0.138], which was consistent with the SMRW model [CSM: HR = 0.83, p = 0.138; overall survival (OS): HR = 0.75, p = 0.132]. However, RP was associated with a lower CSM in the T1–2 subgroup (HR = 0.42, p = 0.048) and a lower ACM in the T1–2 (HR = 0.55, p = 0.031) and prostate-specific antigen (PSA) ≤20ng/ml (HR = 0.48, p = 0.022) subgroups. Besides, the results showed that the mortality risk was similar between the two groups in the T3–4, Gleason score (GS) >7, PSA >20 ng/ml, and all metastatic subgroups (all p > 0.100).ConclusionsRP could confer better survival outcomes than could RT in mPCa patients with favorable primary tumor features, but not in those with advanced primary tumor features. Moreover, the metastatic substage has limited impact on the comparative effectiveness between RP and RT. Further clinical trials are necessary to confirm the present results.

A Comparison of Clinical Outcomes from Updated Zuma-5 (Axicabtagene Ciloleucel) and the International Scholar-5 External Control Cohort in Relapsed/Refractory Follicular Lymphoma (R/R FL)