Inverse Probability Of Treatment Weighting Research Articles

Predictors of the effectiveness to first-line CTLA4-Ig in patients with rheumatoid arthritis: the FIRST registry.

This study aimed to elucidate which bio-naïve patients with rheumatoid arthritis (RA) are suitable for treatment with CTLA4-Ig. This study enrolled 953 patients with RA who were administered their first biological disease-modifying antirheumatic drug (CTLA4-Ig, n = 328; tumour necrosis factor inhibitor [TNFi], n = 625) from July 2013 to August 2022. The primary outcome was the Clinical Disease Activity Index (CDAI) remission rate at week 24 in each group, adjusted using Propensity Score-based Inverse Probability of Treatment Weighting (PS-IPTW). After minimizing selection bias using PS-IPTW, the CDAI remission showed no significant difference between the CTLA4-Ig and TNFi groups (p= 0.464). Multivariable logistic regression analysis identified low baseline Health Assessment Questionnaire-Disability Index (HAQ-DI) scores as a contributing factor to the CDAI remission rate at week 24 in both groups, along with high baseline anti-citrullinated peptide antibody (ACPA) levels in the CTLA4-Ig group. However, among patients with high baseline HAQ-DI scores and low baseline ACPA levels (≦57.2), the CDAI remission rate was significantly higher in the TNFi group (29.8%) compared with the CTLA4-Ig group (5.9%, p< 0.0001). Among patients with high baseline HAQ-DI scores and ACPA levels (>57.2), the CDAI remission rate was significantly higher in the CTLA4-Ig group (35.6%) compared with the TNFi group (22.1%, p= 0.0057). Bio-naive RA patients with low HAQ-DI scores showed high treatment efficacy with no significant difference between CTLA4-Ig and TNFi. Among patients with high baseline HAQ-DI scores, TNFi and CTLA4-Ig were more likely to be effective in those with lower and higher baseline ACPA levels, respectively.

Impact of gastrectomy on efficacy and safety of second‐line chemotherapy patients with advanced gastric cancer: Exploratory analysis of two randomized phase III trials

AbstractAimsSecond‐line chemotherapy (SLC) improves survival in advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear.Patients and MethodsThe objective was to evaluate the impact of gastrectomy on SLC for AGC. A total of 290 eligible patients registered in two randomized phase III trials evaluating SLC for patients with AGC was classified into the prior gastrectomy group (PGG; n = 187) or the no gastrectomy group (NGG; n = 103). We compared overall survival (OS), progression‐free survival (PFS), overall response rate (ORR), disease control rate (DCR), and safety between these two groups. Adjusted OS and adjusted PFS were estimated using inverse probability of treatment weighting (IPTW).ResultsThe PGG had better performance status (p = 0.001), more prior platinum agent (p &lt; 0.001), and more frequent peritoneal metastasis (p = 0.006) than the NGG. The PGG had significantly better OS (13.8 vs. 9.3 mo; hazard ratio [HR]: 0.59; p &lt; 0.001) and PFS (4.7 vs. 2.8 mo; HR: 0.58; p &lt; 0.001) than the NGG. The PGG had significantly better adjusted OS (13.8 vs. 10.0 mo; IPTW HR: 0.66; p = 0.01) and adjusted PFS (4.3 vs. 3.2 mo; IPTW HR: 0.71; p = 0.027) than the NGG. No significant differences were observed in ORR and DCR. The incidence of Grade 3 or worse adverse events did not differ between the two groups except for a high incidence of anemia and diarrhea in the NGG.ConclusionPatients with previous gastrectomy are expected to have better survival outcomes when receiving second‐line irinotecan (IRI)‐based chemotherapy for AGC.

Safety and efficacy of endoscopic submucosal dissection with gel immersion technique for superficial esophageal neoplasms.

Gel immersion (GI) endoscopy provides a good visual field in endoscopic submucosal dissection (ESD); however, its clinical outcomes are poorly understood. This study aimed to compare the treatment outcomes between esophageal gel immersion endoscopic submucosal dissection (GI-ESD) and conventional ESD (C-ESD) to determine the safety and efficacy of GI-ESD. The data of 71 consecutive patients who underwent esophageal ESD between April 2021 and March 2023 at a Japanese tertiary center were retrospectively reviewed. GI was achieved using an additional irrigation tube. The treatment outcomes between the GI-ESD and C-ESD groups were compared using inverse probability of treatment weighting (IPTW) to control for confounding factors. A total of 75 superficial esophageal epithelial neoplasms (41 in the C-ESD and 34 in the GI-ESD groups) were treated using ESD. The mean procedure time in the GI-ESD group was significantly shorter than that in the C-ESD group (59.2±36.2 vs 85.3±45.7min, P=0.008). After IPTW adjustment, the mean procedural times were 62.6±36.6 and 82.9±41.7min in the GI-ESD and C-ESD groups, respectively (P=0.037), and the incidence rate of muscle layer damage was 4.2% in the GI-ESD group and 30.6% in the C-ESD group (P=0.001). In the multivariate analysis, specimen size ≥30mm (odds ratio [OR]: 9.44, 95% confidence interval [CI]: 2.46-36.30, P=0.001) was positively correlated with longer procedural time (≥90min), whereas GI-ESD (OR: 0.19, 95%CI: 0.05-0.68, P=0.011) showed a negative association. Esophageal GI-ESD may be useful in terms of safety and time efficiency. The GI technique could be an option for esophageal ESD.

Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans.

Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization. Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest. Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations. Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.

Real-World Effectiveness of All-Oral Direct-Acting Antivirals in Patients With Hepatitis C Virus-Related HCC.

The association between direct-acting antiviral (DAA) treatment and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is currently unclear. Hence, we aim to assess the association between DAA treatment and mortality rate among Medicare beneficiaries with HCV-related HCC. This retrospective cohort study screened 19,813 adults in 2013-2019 Surveillance, Epidemiology, and End Results data linked with Medicare data. Patients with HCV-related HCC initiating DAA therapy after their first HCC diagnosis were compared with patients with HCV-related HCC who received no HCV treatment. After inverse probability treatment weighting, multivariable Cox proportional hazards models compared mortality rates between the groups. Subgroup and sensitivity analyses were based on HCC stage (early vs. advanced), type of HCC treatment (curative, palliative, none), and DAA treatment duration. In total 3,777 patients with HCV-related HCC were identified (mean age: 68.2 years, 75.2% male, 61.8% White), of whom 19% initiated DAA therapy. Crude incidence mortality rates were 17.9 and 90.7 deaths per 100 person-years in the DAA and HCV-untreated groups, respectively. Cox regression models indicated that DAA therapy was associated with decreased risk of all-cause mortality (adjusted hazard ratio, 0.33; 95% CI 0.31-0.36). Median survival time was 45.7 (95% CI 40.9-57.9) months in the DAA group and 7.7 (95% CI 7.3-8.2) months in the HCV-untreated group (P < 0.001). All subgroup and sensitivity analyses were consistent with the main analyses. DAA therapy was associated with survival benefits for patients with HCV-related HCC regardless of the stage or type of HCC treatment and should not be withheld from this population of Medicare beneficiaries.

Whether Primary Bone-Only Oligometastatic Nasopharyngeal Carcinoma Patients Benefit From Radiotherapy to the Bones on the Basis of Palliative Chemotherapy Plus Locoregional Radiotherapy?-A Large-Cohort Retrospective Study.

Whether to perform local radiotherapy on metastatic bone for primary bone-only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment. We studied 308 primary bone-only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log-rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups. The best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45-0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre-treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low-risk group while 153 were in high-risk group. Before and after IPTW, the high-risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42-0.67, p < 0.001; unadjusted HR = 0.59, 95% CI: 0.42-0.83, p = 0.007), while the low-risk group did not (adjusted HR = 0.79, 95% CI: 0.56-1.11, p = 0.345; unadjusted HR = 0.65, 95% CI: 0.37-1.14, p = 0.309). Best outcomes of the whole cohort were seen with PCT + LRRT + bRT. Our study identified age, N stage, pre-treatment LDH levels, and EBV DNA levels as independent prognostic factors for OS. The high-risk group demonstrated a longer OS when treated with PCT + LRRT + bRT, whereas the low-risk group did not benefit from the combinatorial treatment.

The cardio-protective effect of cardiomyopeptidin in critically ill patients with myocardial injury: a retrospective cohort study

In order to investigate the association between the use of cardiomyopeptidin (CMP) and outcomes in critically ill patients with myocardial injury, we conducted a retrospective cohort study in Nanfang hospital, Southern Medical University. Clinical data of patients with myocardial injury were collected retrospectively and adjusted for possible confounders by propensity score weighting. The main outcome was the in-hospital mortality. Secondary outcomes included the major adverse cardiovascular events (MACE) occurring during the hospital, the individual components of MACEs, changes in high sensitive troponin T (hsTnT) levels, length of stay (LOS) in ICU and hospital. A Cox proportional hazards model was constructed to examine the association between the application of CMP and in-hospital mortality. Logistic regression and linear regression are used to analyze secondary outcomes. In total, 339 critically ill patients with myocardial injury were included in the analysis. After inverse probability of treatment weighting (IPTW), the use of CMP was associated with reduced in-hospital mortality (HR: 0.64, 95%CI: 0.43–0.96, P = 0.03). No significant differences were found in change of hsTnT, the occurrence of MACE and LOS in ICU as well as hospital after IPTW. The association was more significant in the subgroup with hsTnT > 3URL (HR: 0.41, 95%CI: 0.23–0.71, P < 0.001) and APACHE II score < 25 (HR: 0.13, 95%CI: 0.17–0.59, P < 0.001). Cardiomyopeptidin was associated with reduced in-hospital mortality in critically ill patients with myocardial injury. Our study provides initial clinical basis for the application of CMP with cardio-protective effect in critically ill patients. These results need to be confirmed in future randomized controlled trails.

Intravenous immunoglobulin‑based adjuvant therapy for severe fever with thrombocytopenia syndrome: A single‑center retrospective cohort study.

Intravenous immunoglobulin (IVIG) is frequently administered to patients with severe fever with thrombocytopenia syndrome (SFTS), particularly those with severe manifestations, although its efficacy remains controversial. The study retrospectively analyzed the effects of IVIG administration on SFTS patients in both mild and severe groups. The primary outcome measure was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. A total of SFTS patients with complete data enrolled from January 1, 2015, to August 1, 2023. Death at 28 days occurred for 68 (17.5%) patients. By unadjusted analysis, no difference was observed for 28-day mortality between the IVIG and non-IVIG groups in both the mild and severe groups. Similar results were found by propensity score matching and by IPTW analysis. Although IVIG is frequently used as adjuvant therapy for severe SFTS patients, no significant association was observed between IVIG treatment and reduced mortality in this patient population.

Dexamethasone regime and clinical outcomes in children hospitalized with croup: A cohort study.

High-quality trial evidence supports the use of one dose of dexamethasone in the outpatient management of croup; however, there are no inpatient trials, and the optimal treatment regimen for the inpatient management of croup remains uncertain. Significant practice variability exists in the corticosteroid treatment of children hospitalized for croup. To evaluate the association of dexamethasone treatment regimen (1 vs. >1 dose) with hospital length of stay (LOS) and 30-day return to emergency department (ED) visits among children hospitalized for croup. A cohort study of children hospitalized for croup at a children's hospital between 2010 and 2022. Children less than 10 years old, without known airway anomalies and who received dexamethasone for croup treatment were included. Children who received 1 dose versus >1 dose of dexamethasone were compared. Propensity score analyses, using inverse probability of treatment weighting, were conducted to estimate the treatment effects of dexamethasone regimen on hospital LOS and all-cause 30-day return to ED visit. Of 471 children hospitalized for croup, 229 (49%) received 1 dose of dexamethasone; 242 (51%) received >1 dose. In the propensity-weighted analyses, children receiving >1 dose of dexamethasone had a longer mean LOS by 59.6 h (95% CI 44.8-74.5, p < .001) compared with those receiving >1 dose. There was no statistically significant difference in the odds of all-cause 30-day return to ED visit; OR 1.30, (95% CI 0.76-2.22, p = .33). Among children hospitalized for croup, children who received >1 dose of dexamethasone had a longer LOS compared with children who received 1 dose of dexamethasone; however, there was no statistically significant difference in the 30-day return to ED visits. Randomized clinical trials are needed to determine the optimal dexamethasone treatment regimen for children hospitalized with croup.

Impact Of Preoperative Risk Factors On 5-year Survival After Fenestrated/Branched Endovascular Aortic Repair

To investigate which preoperative factors most impact the 5-year survival of patients undergoing fenestrated/branched endovascular aortic repair (F/BEVAR) and to identify modifiable elements that, if time allows, should be actively managed and adequately controlled preoperatively. Patients treated for aortic aneurysms with complex anatomy using either a patient-specific company manufactured or an off-the-shelf F/BEVAR devices were included. The exposure of interest was aneurysm type (group I: types I-III thoracoabdominal aneurysms (TAAA) vs group II: type IV TAAA vs group III: juxtarenal or suprarenal aneurysms) and the primary outcome was 5-year risk of all-cause mortality. Generalized linear models were used to estimate each group's crude 5-year risk of death and the 5-year risk of death across groups. Each preoperative factor was added to the model individually and a change in estimate was calculated between the new risks and the crude risk. Preoperative factors with a change of estimate of ≥10% were utilized to create an inverse probability of treatment weights for multivariable analysis. Results: 408 F/BEVAR patients were included, who were 71.6% male (mean age: 72.0±7.9 years). Eleven of the 22 preoperative factors analyzed had a change in estimate ≥10%. The greatest changes in estimates were observed for history of congestive heart failure (CHF), arrhythmia, overweight, obesity, COPD. Almost 60% of patients with CHF in group I died within 5 years. Current smoking or overweight at the time of F/BEVAR increases the 5-year risk of death more significantly than having a history of myocardial infarction. After adjustment, patients in group I had a significantly higher risk of 5-year all-cause mortality compared to those in group III (log-rank p-value=0.0082). The present findings suggest that cardiac arrhythmias, CHF, overweight, obesity, COPD, and aneurysm diameter above 7 cm are the most relevant preoperative elements that impact the 5-year survival post F/BEVAR. More specifically, CHF and arrhythmias should be used to alter patient selection and identify those individuals more likely to benefit from repair. Moreover, modifiable risk factors such as weight loss and smoking cessation during the surveillance period before the F/BEVAR procedure, might improve survival in this population. Considering that preoperatively, many patients are periodically evaluated by a vascular surgery team until the aneurysm diameter meets criteria for repair, a multidisciplinary approach that could address these modifiable risk factors might be an impactful strategy.

Clinical effectiveness of baricitinib and abatacept in patients with rheumatoid arthritis.

The objective of this study was to compare the clinical effectiveness of baricitinib and abatacept in patients with rheumatoid arthritis (RA). This study included 274 patients treated with abatacept and 241 treated with baricitinib who were followed for >52 weeks. Potential treatment selection bias was addressed by using inverse probability of treatment weighting. The paired t-test was used to assess differences in Clinical Disease Activity Index (CDAI) score relative to baseline. A generalized estimating equation was used to compare the two treatment groups. The estimated mean CDAI score was 18.2 at baseline and significantly decreased to 12.6 at 4 weeks, 8.9 at 12 weeks, 7.4 at 24 weeks, and 6.1 at 52 weeks in the abatacept group. The estimated mean CDAI score was 18.6 at baseline and significantly decreased to 9.5 at 4 weeks, 6.5 at 12 weeks, 5.7 at 24 weeks, and 5.5 at 52 weeks in the baricitinib group. The baricitinib group had significantly lower CDAI scores at 4, 12, and 24 weeks compared to the abatacept group. Subgroup analyses revealed that this difference was evident among patients with high disease activity and without concomitant use of methotrexate but was less pronounced among those with remission to moderate disease activity status with methotrexate use. Both baricitinib and abatacept were effective in reducing disease activity in patients with RA. Baricitinib demonstrated potential advantages over abatacept in terms of early disease control, particularly in patients with high disease activity and without methotrexate use.

Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Liver Cirrhosis.

Comparing direct oral anticoagulants (DOACs) and warfarin's efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC). Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC. A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups. In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70). DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.

Impact of discontinuing disease-modifying therapies on health care utilization among midlife patients with multiple sclerosis in the United States.

Multiple sclerosis (MS) is a lifelong progressive neurological disease treated primarily with disease-modifying therapies (DMTs). Disease activity tends to decline as patients age. Midlife represents a crossroads where the risks of DMT may outweigh the benefits, prompting providers to consider DMT discontinuation to reduce treatment burden. However, real-world evidence on the impact of DMT discontinuation among midlife patients is lacking. To evaluate the association between DMT discontinuation and health care utilization among midlife patients with MS. Midlife patients with MS who received an injectable or oral DMT between 2001 and 2018 were identified from the MarketScan commercial claims database. DMT discontinuation, defined as a treatment gap exceeding 90 days in days supply, was the independent variable. Patients who discontinued DMTs had their index date set as the last gap day, whereas index dates for those who continued DMTs were matched based on the time distribution of index dates of discontinuers. Inpatient hospitalizations (all-cause, MS-related, and non-MS-related), emergency department (ED) visits (all-cause, MS-related, and non-MS-related), and relapse-related hospitalizations and outpatient visits were independently evaluated during the 365-day follow-up. Patients were observed until the occurrence of an event (depending on the model), deviation from the treatment group, disenrollment, death, end of follow-up, or data unavailability. Stabilized inverse probability of treatment weighting (sIPTW) was employed to balance the 2 groups. The associations between DMT discontinuation and each utilization outcome were estimated using Cox proportional hazard regression models with sIPTW. Of 149,721 midlife patients with MS, 22.8% discontinued DMTs and 77.2% continued DMTs. Patients who discontinued DMTs had a higher cumulative incidence for all utilization outcomes during the 365-day follow-up than those who continued DMTs. Cox regression showed that DMT discontinuation was associated with a 10.3% and 24.9% higher rate of all-cause and non-MS-related inpatient hospitalizations, respectively, with no significant association found for MS-related hospitalizations. Patients discontinuing DMTs exhibited higher utilization rates for ED visits, with an increase of 21.3% for all-cause, 23.0% for MS-related, and 20.9% for non-MS-related visits compared with those who continued DMTs. We also observed a 15.9% and 52.1% higher rate of relapse-related hospitalizations and outpatient visits associated with DMT discontinuation, respectively. This study revealed that DMT discontinuation was associated with higher health care services utilization among midlife patients with MS, especially relapse-related outpatient visits. DMT discontinuation during midlife may be premature, and DMTs may still be necessary to reduce health care utilization.

Comparison of Time to Next Treatment or Death Between Front-Line Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) Among Transplant-Ineligible Patients With Multiple Myeloma.

Daratumumab, lenalidomide, and dexamethasone (DRd) and bortezomib, lenalidomide, and dexamethasone (VRd) are the only preferred treatment regimens for patients with transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM). As there are no randomized head-to-head studies of DRd versus VRd, this analysis aimed to compare real-world time-to-next-treatment (TTNT) or death in this population. Patients with NDMM who received front-line (FL) DRd or VRd were identified from the Acentrus database (January 1, 2018 to May 31, 2023). Those with a record of a stem cell transplant or aged < 65 years were excluded to limit analysis to the TIE population. Inverse probability of treatment weighting was used to balance baseline patient characteristics. A doubly robust Cox proportional hazards model was used to compare TTNT or death between cohorts. A total of 149 and 494 patients who initiated DRd and VRd, respectively, were identified. After weighting (weighted NDRd = 302, weighted NVRd = 341), cohorts had similar baseline characteristics. Of these, 98 (32.4%) DRd and 175 (51.2%) VRd patients either received a subsequent line of therapy or died, with a median TTNT or death of 37.8 months in the DRd cohort and 18.7 months in the VRd cohort (hazard ratio: 0.58, 95% confidence interval: 0.35, 0.81; p < 0.001). Treatment of TIE NDMM patients with DRd led to a significantly longer TTNT or death compared to VRd, evidenced by a 42% risk reduction, supporting the effectiveness of DRd over VRd as FL treatment in this patient population.

The Effects of Prophylactic Laxative Use on Critically Ill Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study

Objective: To investigate the effects of prophylactic use of stimulant laxatives and/or docusate on the clinical outcomes in critically ill patients who required mechanical ventilation (MV). Methods: A single-center, retrospective, cohort study was conducted. Patients who received MV in the first 24 h after intensive care unit (ICU) admission were enrolled and divided into four groups: non-laxative, stimulant laxatives, docusate, and stimulant laxatives–docusate combination. The primary outcome was in-hospital mortality. The major secondary outcomes included ICU-free days and ventilator-free days at 28 days; the other outcomes were ventilation-associated pneumonia (VAP), enterobacterial infection, diarrhea, and electrolyte disturbances. Inverse probability treatment weighting (IPTW) was used to adjust for confounders. Results: A total of 2129 patients were included in this study, 263 of whom received stimulant laxatives, 253 received docusate, 368 received a combination, and 1245 did not receive any laxative. The prophylactic use of docusate was associated with a decreased risk of in-hospital mortality (OR: 0.59, 95% CI 0.42 to 0.83, p = 0.002) and VAP (OR: 0.62, 95% CI 0.47 to 0.81, p = 0.001). It was also associated with an increase in ICU-free days at 28 days (β: 0.89, 95% CI 0.83 to 0.95, p &lt; 0.001). Importantly, laxatives prophylaxis was not associated with increased risks of diarrhea, electrolyte disturbances, and enterobacterial infections. Conclusions: Prophylactic use of docusate may improve certain prognoses and does not demonstrate any adverse events. However, further research is necessary to determine the optimal regimen and dosage of prophylactic laxatives in this specific population.

Long-Term Outcomes of Induction Immunosuppression for Kidney Transplant Recipients With HIV Who Have Average Immunologic Risk: An Inverse Probability Treatment Weighting Analysis

We analyzed the Scientific Registry of Transplant Recipients (2004-2022) for primary kidney recipients with HIV who had average immunologic risk and were discharged on tacrolimus/mycophenolate mofetil (with or without corticosteroids). Recipients were grouped by induction type: rabbit antithymocyte globulin (r-ATG, n=688) and human interleukin-2 receptor antagonist (IL2Ra, n=467). Kaplan-Meier curves were generated to examine recipient and graft survival by induction type. We used mixed Cox proportional hazard models to determine associations between induction type and outcomes of interest, with adjustments for recipient and donor factors and transplant center as a random effect. Regression with propensity score weighting reduced selection bias from nonrandom induction allocation. The unadjusted 10-year survival rate was 57% for those receiving r-ATG and 64% for those receiving IL2Ra (P<.001). Adjusted risk of death was significantly lower for IL2Ra induction than r-ATG induction with Cox multivariable (hazard ratio, 0.65; 95% CI, 0.47-0.91; P=.01) and inverse probability treatment weighting (hazard ratio, 0.38; 95% CI, 0.29-0.50; P<.01) models. Death-censored kidney graft survival did not differ by induction type in either model. The 1-year rejection rate was 10.1% and 11.6% for r-ATG and IL2Ra recipients, respectively (P=.52). Overall, IL2Ra conferred better long-term survival than r-ATG without increased risk of graft loss.

The Comparative Effectiveness of Potent P2Y12 Inhibitors Versus Clopidogrel in Patients with Acute Myocardial Infarction Undergoing PCI: National Registry Data.

Dual antiplatelet therapy (DAPT), which is essential in AMI management, combines aspirin with a P2Y12 receptor antagonist. This study compared the effectiveness of potent P2Y12 inhibitors versus clopidogrel in AMI patients treated with percutaneous coronary intervention (PCI). Methods: 65,986 AMI patients included in a nationwide prospective registry who underwent PCI and received DAPT were studied. In total, 9,014 patients received potent P2Y12 inhibitors, and 56,074 received clopidogrel. This study focused on mortality, recurrent myocardial infarction, stroke, repeat revascularization, and major adverse cardiovascular events (MACE) over seven years. The analysis utilized unadjusted models and inverse probability of treatment weighting (IPTW) to compare prognosis, and decision curve analyses were constructed to aid clinical decision making. Results: Potent P2Y12 inhibitors significantly reduced mortality risk (unadjusted hazard ratio (HR): 0.58; IPTW HR: 0.68) and MACE (unadjusted HR: 0.66; IPTW HR: 0.78). Diabetic patients showed greater benefits (HR:0.45). In patients at high bleeding risk, the mortality rate was 13% (HR: 0.87, p = 0.08). For patients aged 75-79, the HR for mortality was 0.82, whereas for those aged >80 years, it was 0.79, indicating significant mortality risk reduction. Similar trends were observed for MACE. Conclusion: This study demonstrated that potent P2Y12 inhibitors are more effective than clopidogrel in reducing mortality and MACE in patients with AMI and underscored their potential role in improving outcomes across diverse patient subgroups. The trend was consistent even during the COVID-19 pandemic. These findings highlight the need for personalized DAPT strategies, particularly for high-bleeding-risk patients, and challenge current guidelines favoring clopidogrel use in older patients.

Sex differences in cardiovascular outcomes in patients with acute pancreatitis.

The risk of cardiovascular disease increases in patients with acute pancreatitis. However, it remains unknown whether this increase varies between males and females. To assess sex differences in cardiovascular outcomes among acute pancreatitis patients during long-term follow-up. Participants were recruited from the UK-biobank, which is a population-based cohort study consisting of 502 368 individuals aged 40-69 years old. Cardiovascular outcomes were defined as major cardiovascular and cerebrovascular adverse events (MACCE), encompassing all-cause death, myocardial infarction, and stroke. We compared sex difference in MACCE incidence using incidence rate per 1,000 person-years. The association between sex and MACCE risk was assessed using Cox proportional hazards models and win-ratio method, adjusted for demographic, lifestyle, metabolic factors and medication use. A total of 1371 participants with acute pancreatitis were included, 42.5% were male. Over a median follow-up of 13.9 years, 226 MACCE cases occurred. The incidence rate of MACCE for male was 16.44, compared to 9.80 in female. Multivariate Cox regression analysis indicated a higher risk of MACCE in male compared to female (HR 1.80 [95% CI 1.36-2.38]). Adjusted HR for all-cause mortality, myocardial infarction, and stroke were 1.49, 2.75, and 1.67, respectively. The adjusted win ratio by inverse probability of treatment weighting was 0.55 (P <0.001), suggesting a worse outcome in male acute pancreatitis patients. Male experienced more adverse cardiovascular outcomes than female in the long follow-up after acute pancreatitis, suggesting a need for sex-specific management strategies in acute pancreatitis patients.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies.

To emulate target trials comparing recurrence of nephrolithiasis among patients with pre-existing nephrolithiasis (overall and stratified by concomitant gout) initiating sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus an active comparator. Target trial emulation studies. Canadian population database, January 2014 to June 2022. 20 146 patients with nephrolithiasis and type 2 diabetes, including those with concomitant gout at baseline, a high risk group. Initiation of an SGLT-2 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist, with a dipeptidyl peptidase-4 (DPP-4) inhibitor as alternative comparator. The primary outcome was recurrent nephrolithiasis events ascertained from diagnoses during emergency department visits, hospital admissions, or outpatient visits. Secondary outcomes included nephrolithiasis resulting in hospital admission or emergency department visits and flare-up of gout, as well as a positive control outcome (genital infection) and negative control outcomes (osteoarthritis encounter and appendicitis). Poisson and Cox proportional hazards regression models were used (primary analyses), as well as overlap weighting. After inverse probability of treatment weighting, 1924 recurrent nephrolithiasis events occurred among the 14 456 weighted patients who used an SGLT-2 inhibitor (105.3 per 1000 person years), compared with 853 events among the 5877 weighted patients who used a GLP-1 receptor agonist (156.4 per 1000 person years). The adjusted rate ratio was 0.67 (95% confidence interval (CI) 0.57 to 0.79) and rate difference was -51 (95% CI -63 to -40) per 1000 person years, with a number needed to treat (NNT) of 20. Among those with recently active nephrolithiasis, the absolute rate difference was 219 per 1000 person years (NNT of 5). Protective associations persisted for nephrolithiasis events that required emergency department visits, hospital admissions, or procedures, and when an SGLT-2 inhibitor was compared with a DPP-4 inhibitor (rate ratio 0.73 (0.68 to 0.78), rate difference -38 (-46 to -29) per 1000 person years (NNT of 26)). Protective associations also persisted among patients with nephrolithiasis and concomitant gout, with a rate ratio of 0.67 (0.57 to 0.79) and rate difference of -53 (95% CI -78 to -27) per 1000 person years versus a GLP-1 receptor agonist (NNT of 19), and 0.63 (0.55 to 0.72) and-62 (-81 to -42) per 1000 person years, respectively, versus a DPP-4 inhibitor (NNT of 16). Furthermore, SGLT-2 inhibitor use was associated with a lower rate of gout flare-ups (rate ratio 0.72, 0.54 to 0.95, rate difference -16, -31 to -1 per 1000 person years) compared with GLP-1 receptor agonists (0.65, 0.52 to 0.82, and -21, -33 to -9 per 1000 person years) compared with DPP-4 inhibitors. SGLT-2 inhibitor initiators showed higher risk of genital infection (eg, hazard ratio 2.21, 95% CI 1.68 to 2.90, and rate difference 13 per 1000 person years), but no altered risk of osteoarthritis encounter (0.87, 0.68 to 1.1, and -2 per 1000 person years) or appendicitis (1.07, 0.69 to 1.67, and 1 per 1000 person years). Results were similar when propensity score overlap weighting was applied. The benefits associated with SGLT-2 inhibitor for patients with nephrolithiasis in these target trial emulations suggest they may be a useful addition to current treatments to simultaneously manage nephrolithiasis recurrence and comorbidities, including gout.

IPTW and DR Estimators: Advancing towards the Adoption of Methodologies for Estimating Causal Treatment Effects in Observational Studies

The propensity score refers to the likelihood of a subject being selected for intervention, given their observed baseline covariates. By assigning different weights to academic disciplines based on the reciprocal probability of receiving treatment, there will be a synthetic sample where the assignment of treatment is not influenced by baseline factors that were measured. Utilizing inverse probability of treatment weighting (IPTW) through the propensity score enables people to assemble unbiased or objective estimates regarding average treatment effects. In order to estimate the causal relationship between an exposure and an outcome, the second notion of doubly robust estimation combines an outcome regression with a propensity score model. Only when the statistical model is appropriately stated can unbiased estimates be obtained using the propensity score approach and outcome regression separately. However, even if only one of the two models is correctly specified, an unbiased estimator for the effect can be obtained by employing the doubly robust estimator. This introduction to inverse probability of treatment weighting and doubly robust estimators includes conceptual overviews, an application to students’ performance in high school, as well as discussions based on the project.