Propensity Score Methods Research Articles

Impact of Masticatory Performance and the Tongue-Lip Motor Function on Incident Adverse Health Events in Patients with Metabolic Disease.

The present study aimed to determine whether decreased masticatory performance and tongue-lip motor function are associated with an increased incidence of adverse health events in patients with metabolic disease. One thousand patients with metabolic diseases including diabetes, dyslipidemia, hypertension, and hyperuricemia were recruited. Masticatory performance was assessed using a gummy jelly test, wherein glucose elution from chewed gummy jelly was measured. The tongue-lip motor function was measured using repeatedly pronounced syllables per second. Their association with the incidence of adverse health events (a composite of all-cause death, cardiovascular disease, bone fracture, malignant neoplasm, pneumonia, and dementia) was investigated using the generalized propensity score (GPS) method. During a median follow-up period of 36.6 (interquartile range, 35.0-37.7) months, adverse health events were observed in 191 patients. The GPS adjusted dose-response function demonstrated that masticatory performance was inversely associated with the incidence of adverse health events. The 3-year incidence rate was 22.8% (95% confidence interval, 19.0-26.4%) for the lower quartile versus 13.6% (10.5-16.7%) for the upper quartile (P＜0.001). Similarly, the tongue-lip motor function was inversely associated with the incidence of adverse health events, with a 3-year incidence rate of 23.6% (20.0-27.0%) for the lower quartile versus 13.2% (10.4-15.9%) for the upper quartile (P＜0.001). Decreased masticatory performance and tongue-lip motor function were associated with an increased incidence of adverse health events in patients with metabolic disease.

Comparing Machine Learning and Advanced Methods with Traditional Methods to Generate Weights in Inverse Probability of Treatment Weighting: The INFORM Study.

Observational research provides valuable insights into treatments used in patient populations in real-world settings. However, confounding is likely to occur if there are differences in patient characteristics associated with both the exposure and outcome between the groups being evaluated. One approach to reduce confounding and facilitate unbiased comparisons is inverse probability of treatment weighting (IPTW) using propensity scores. Machine learning (ML) and entropy balancing can potentially be used in generating propensity scores for IPTW, but there is limited literature on this application. We aimed to assess the feasibility of applying these methods for reducing confounding in observational studies. These methods were assessed in a study comparing cardiovascular outcomes in adults with type 2 diabetes and established atherosclerotic cardiovascular disease taking once-weekly glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors. We applied advanced methods to generate the propensity scores compared to the original logistic regression method in terms of covariate balance. After calculating weights, a weighted Cox proportional hazards model was used to calculate the sample average treatment effect. Support Vector Classification, Support Vector Regression, XGBoost, and LightGBM were the ML models used. Entropy balancing was also performed on features identified in the original cardiovascular outcomes study. Accuracy (range: 0.71 to 0.73), area under the curve (0.77 to 0.79), precision (0.53 to 0.60), recall (0.66 to 0.68), and F1 score (0.60 to 0.64) were similar between all of the advanced propensity score methods and traditional logistic regression. Among ML models, only XGBoost achieved balance in all measured baseline characteristics between the two treatment groups, closely approximating the performance of the original logistic regression. Entropy balancing weights provided the best performance among all models in balancing baseline characteristics, achieving near perfect balancing. Among the advanced methods examined, entropy balancing weights performed the best for optimizing balancing and can produce similar results compared to traditional logistic regression.

Comparisons of Percutaneous Ablation, Open or Laparoscopic Liver Resection for Barcelona Clinic Liver Cancer Stage 0-A Hepatocellular Carcinoma: A Concurrent Generalized Propensity Score Analysis.

Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients. This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences. Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population. In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.

Trajectories of Treatment Burden Among Primary Care Patients with Long-Term Conditions in Southern China: A Latent Class Growth Analysis.

Treatment burden is a patient-centred, dynamic concept. However, longitudinal data on the changing pattern of treatment burden among patients with one or more long-term conditions (LTCs) are relatively scanty. We aimed to explore the longitudinal trajectories of treatment burden and associated risk factors in a large, patient population in primary care settings. We analysed data from 5573 primary care patients with long-term conditions (LTCs) recruited using a multistage sampling method in Shenzhen, southern China. The treatment burden was assessed by the Mandarin Chinese version of the Treatment Burden Questionnaire (TBQ). We used latent class growth mixture modelling (LCGMM) to determine trajectories of treatment burden across four time points, ie, at baseline, and at 6, 12, and 18 months. Predictors of trajectory classes were explored using multivariable logistic regression analysis. The mean TBQ scores of patients with a single LTC (n = 2756), 2 LTCs (n = 1871), 3 LTCs (n = 699), and ≥4 LTCs (n = 247) were 18.17, 20.28, 21.32, and 26.10, respectively, at baseline. LCGMM identified three discrete classes of treatment burden trajectories over time, ie, a high-increasing class, a low-stable class, and a high-decreasing class. When controlling for individual-level factors including age, education, monthly household income per head, smoking, alcohol consumption, and attendance in health education, patients who had a clinical diagnosis of 3 LTCs (adjusted odds ratio [aOR] = 1.49, 95% CI = 1.21-1.86, P < 0.001) or ≥4 LTCs (aOR = 1.97, 95% CI = 1.44-2.72, P < 0.001) were more likely to belong to the high-increasing class. Sensitivity analysis using propensity score methods obtained similar results. Our study revealed the presence of discrete patterns of treatment burden over time in Chinese primary care patients with LTCs, providing directions for tailored interventions to optimise disease management. Patients with 3 or more LTCs should receive close attention in healthcare delivery as they tend to experience a greater treatment burden.

Short- and Long-Term Renal Function After Partial Nephrectomy: Comparison of Solitary and Multifocal Renal Masses.

Multifocal partial nephrectomy (MPN) is a critical management strategy for extirpation of multiple distinct renal masses; however, its short- and long-term impact on renal function remains poorly described. Herein we compared absolute glomerular filtration rate (GFR) and change from baseline at multiple time points after MPN and standard partial nephrectomy (SPN). Perioperative and pathologic characteristics of 1307 partial nephrectomies performed from 2009 to 2020 were identified. 3:1 propensity score methods were used to match MPN and SPN cohorts based on preoperative characteristics known to impact renal function. Differences in GFR, perioperative outcomes, and overall and recurrence-free survival were assessed. Absolute and relative change from baseline GFR was compared at 5 time points for 36 months after partial nephrectomy. After propensity score matching, 192 SPNs and 64 MPNs with a median GFR of 80.2 mL/min were compared. MPN was associated with a greater decline in GFR of between 11% and 18% for the first year compared to a decline of 7% to 10% for SPN. This difference stabilized after 24 months. However, no differences in overall survival or recurrence-free survival were observed. Median follow-up time was 46.7 months. Long-term renal function after MPN remains similar to SPN despite greater declines in the first year after excision of multifocal renal masses.

Overall survival from tebentafusp versus nivolumab plus ipilimumab in first-line metastatic uveal melanoma: a propensity score-weighted analysis

Tebentafusp demonstrated a superior overall survival (OS) benefit [hazard ratio (HR) 0.51] compared to investigator's choice (82% pembrolizumab) in a randomized, phase III trial (IMCgp100-202; N= 378) in untreated metastatic uveal melanoma (mUM). The 1-year OS rates for tebentafusp and pembrolizumab were 73% and 59%, respectively. In the single-arm GEM1402 (N= 52), the 1-year OS rate for nivolumab plus ipilimumab (N+I) in mUM was 52%. Due to limitations in conducting randomized trials in mUM, we compared OS on tebentafusp or pembrolizumab (IMCgp100-202) to N+I (GEM1402) in untreated mUM using propensity scoring methods. Analyses were adjusted using propensity score-based inverse probability of treatment weighting (IPTW), balancing age, sex, baseline lactate dehydrogenase (LDH), baseline alkaline phosphatase, disease location, Eastern Cooperative Oncology Group status, and time from primary diagnosis to metastasis. OS was assessed using IPT-weighted Kaplan-Meier and Cox proportional hazard models. Sensitivity analyses using alternative missing data and weights methods were conducted. The primary IPTW analysis included 240 of 252 patients randomized to tebentafusp from IMCgp100-202 and 45 of 52 N+I-treated patients from GEM-1402. Key baseline covariates, including LDH, were generally well balanced before weighting. The IPTW-adjusted OS favored tebentafusp, HR 0.52 [95% confidence interval (CI) 0.35-0.78]; 1-year OS was 73% for tebentafusp versus 50% for N+I. Sensitivity analyses showed consistent superior OS for tebentafusp with all IPTW HRs ≤0.61. IPTW analysis of pembrolizumab versus N+I showed no significant difference in OS (HR 0.72; 95% CI 0.50-1.06). Tebentafusp was previously shown to provide an OS benefit compared to checkpoint inhibitors or chemotherapy in untreated mUM. Propensity score analysis demonstrated a similar OS benefit for tebentafusp compared with N+I. These data further support tebentafusp as the standard of care in previously untreated human leukocyte antigen (HLA)-A∗02:01+ adult patients with mUM.

Modifiable Risk Factors in High-Risk Groups of Colorectal Cancer Screening: A Cross-Sectional Study with Propensity Score Method

Modifiable Risk Factors in High-Risk Groups of Colorectal Cancer Screening: A Cross-Sectional Study with Propensity Score Method

Impact of children’s appropriate work participation in cocoa farms on household welfare: Evidence from Ghana

This study examines how children engaged in cocoa farming in Ghana affect household welfare. Data was gathered from 384 cocoa producers using a multistage sampling technique and analysed employing the Cragg double hurdle and propensity score method. The study found that only 2.3 % of cocoa farmers highly used children for cocoa activities. Additionally, household size, cooperative membership, and credit access were found to have significant impacts on both the use and extent of use of children on cocoa farms. Moreover, cocoa farmers who used children experienced improvements in their income, food security and assets compared to those who did not use children. The study also confirms the reality of the practice of employing children on cocoa plantations in Ghana. Harnessing the considerable advantages of credit access and cooperative membership, we emphasize the importance of extension agents sensitizing cocoa farmers about the merits of forming cooperatives. This approach could serve as a means of obtaining group/individual credits to support cocoa production. Furthermore, in light of the notable improvements in the welfare of cocoa farmers, it is imperative for COCOBOD to take decisive action in invigorating the regulation against child labor and instead embrace agricultural technologies as viable alternatives.

Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma.

Modern treatment guidelines recommend multimodal therapy with at least chemotherapy and surgery for patients with potentially resectable epithelioid mesothelioma. This study evaluated guideline compliance for patients with stage I-III epithelioid mesothelioma and tested the hypothesis that guideline-concordant therapy improved survival. The National Cancer Database was queried for patients with stage I-III epithelioid malignant pleural mesothelioma between 2004 and 2016. The impact of therapy was evaluated using logistic regression, Kaplan-Meier analysis, Cox-proportional hazards analysis, and propensity-scoring methods. During the study period, guideline-concordant therapy was used in 677 patients (19.1%), and 2,857 patients (80.8%) did not have guideline-concordant therapy. Younger age, being insured, living in a census tract with a higher income, clinical stage, and being treated at an academic or research program were all predictors of receiving guideline-concordant therapy in multivariable analysis. Guideline-concordant therapy yielded improved median survival [24.7 (22.4-26.1) vs. 13.7 (13.2-14.4) months] and 5-year survival [17.7% (14.7-21.3%) vs. 8.0% (7.0-9.3%)] (P<0.001), and continued to be associated with better survival in both multivariable analysis and propensity-matched analysis. In the patients who received guideline therapy, median survival [24.9 (21.9-27.2) vs. 24.5 (21.7-28.1) months] and 5-year survival [14.9% (10.9-20.2%) vs. 20.1% (16.0-25.4%)] was not significantly different between patients who underwent induction (n=304) versus adjuvant (n=373) chemotherapy (P=0.444). Guideline-concordant therapy for potentially resectable epithelioid mesothelioma is associated with significantly improved survival but used in a minority of patients. The timing of chemotherapy with surgery in this study did not have a significant impact on overall survival.

MSR158 Successful Use of Propensity Score Methods for HTA in Germany: A Near-Impossible Task?

MSR158 Successful Use of Propensity Score Methods for HTA in Germany: A Near-Impossible Task?

Abstract C013: Importance of statistical considerations in multi-center, transatlantic cancer disparity studies: Lessons learned from the CaPTC prostate cancer familial cohort study

Abstract The CaPTC prostate cancer (CaP) Familial Cohort study (CaPFCS) was launched in 2017 to explore the CaP risk factors of African Black men (ABM). The study design is a prospective study that observes and follows healthy ABM and ABM diagnosed with CaP. Aim: The specific aim is to provide recommendations on statistical considerations for cohort studies focused on cancer disparities, based on lessons learned from the CaPTC CaPFCS. Methodology: Study participants were ABM in Cameroon, Nigeria, and the US. Using validated measures, data were collected mostly by self-administered or research assistant administered survey using paper survey (especially in Cameroon and Nigeria) with the responses transferred to REDCap by research coordinators. The statistical analysis for the CaPTC CaPFCS focused on the baseline epidemiological, behavioral, clinical and anthropometric measures of Black men. A total of 819 participants were included in the analyses. Statistical analyses included descriptive statistics (sample median, range, frequency and percentages) and unadjusted logistic regression models. Results: Data collection for the CaPTC CaPFCS were by multiple investigators/research coordinators at multiple sites in Cameroon, Nigeria, and the US. In preparation for the data analyses, we noted data entry errors and/or misinterpretation of data entry, which required extensive cleaning of the database prior to the analyses. The biostatisticians spent significant effort cleaning and ensuring data validity prior to the analyses. Confounding variables is another statistical consideration for cohort studies, such as the CaPTC CaPFCS. There was variability observed across age, education levels, employment status, household income and CaP diagnosis based on country of residence. CaP diagnosis was not reported by any of the ABM in the US, which may be due to the fact that they were all recruited within the community and no recruitment took place in the clinic. Finally, the CaPTC CaPFCS has several variables. Performing a lot of statistical tests may result in false-positive findings at P&amp;lt;0.05.Conclusion: The advantage of the CaPFCS is that it allows the CaPTC investigators to study epidemiological, behavioral, clinical and anthropometric variables associated with CaP over time. Being a longitudinal cohort study, investigators can track the changes in exposure and outcomes over time.However, statistical considerations need to be at the fore-front of multi-center, transatlantic cancer disparity studies such as the CaPTC CaPFCS, from data collection to data entry. The use of web-based survey with the ability to enter data directly into REDCaP will significantly reduce (if not totally eliminate) the need for database cleaning. There are multiple strategies that can be used to reduce confounder effect, including statistical adjustment and multivariate analysis to adjust for the confounders. The use of propensity score methods have especially been found to be effective in controlling baseline confounding factors. Citation Format: Daniel Lee, CaPTC Investigators, Jennifer Crook, Ruth Enuka, Fathi Parisa, Emeka Iweala Iweala, Oluwole Kukoyi, Ernest Kaninjing, Oluwaseyi Toye, Paul Jibrin, Folakemi Odedina. Importance of statistical considerations in multi-center, transatlantic cancer disparity studies: Lessons learned from the CaPTC prostate cancer familial cohort study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C013.

The Validity of a Synthetic Control Arm Derived from Historical Multiple Myeloma Clinical Trials

Introduction While randomized phase III clinical trials (RCTs) are the gold-standard for establishing drug efficacy in the United States, external control arms (ECAs) may be valuable for both early and late phase drug development. An ECA is a collection of patients with the disease of interest who were treated outside of a clinical trial of interest (ie, target trial) and whose outcomes are compared to those of the target trial patients' to evaluate comparative drug efficacy and/or safety. ECAs created through rigorous statistical non-experimental methods such as matching patient-level characteristics may provide early estimates of comparative efficacy in advance of RCTs and offset prospective enrollment of control patients in randomized studies. We evaluate the validity of using a matched ECA to estimate the comparative efficacy of an experimental drug in relapsed refractory multiple myeloma (r/r MM). Methods From the anonymized Medidata Enterprise Data Store (MEDS), we identified historic RCTs in r/r MM containing patients exposed to an experimental drug as well as an active control drug (ie, a corticosteroid). Arbitrarily, we selected one trial to serve as the “target trial”. For the remaining trials, we collapsed all corticosteroid control patients into a single pool to construct an ECA. Using propensity score (PS) optimal full matching, we identified corticosteroid ECA patients by selecting from the candidate patients those whose baseline demographic and clinical attributes were similar to patients receiving the experimental drug in the target trial. Using the Kaplan-Meier (KM) estimator and a Cox proportional hazards regression, we first compared overall survival time (OS) of patients in the experimental drug arm vs control arm in the target trial. We then compared the OS in the experimental drug arm vs the ECA. Results We found fewer than five historic clinical trials from MEDS which were open-label RCTs conducted from 2010-2017. They enrolled r/r MM patients aged ≥18 years who had received more than two prior lines of therapy, one of which was lenalidomide and bortezomib. The target trial contained 300 patients in the investigational drug arm and 152 patients in the control arm. Using the PS matching, we identified 183 patients from the control arms in pooled trials that were matched with 290 patients in the investigational drug arm in the target trial (i.e., ECA). These ECA patients were then upweighted to be matched with 290 patients in the investigational drug arm in the target trial. Full matching successfully attenuated baseline differences between the investigational drug and ECA arms. Figure 2 shows the KM curves of OS (investigational vs control) in the target trial. Median OS was 13.25 months vs. 8.52 months (log-rank p&amp;lt;0.01) and the investigational drug was associated with a 36% reduction in the hazard of death (HR 0.74, 95% CI: 0.60-0.92). Figure 2 shows the KM curves of OS, after full matching, using the ECA. Median OS was 13.51 months vs. 8.75 months (log-rank p&amp;lt;0.01) and the investigational drug was associated with a 36% reduction in the hazard of death (HR 0.74, 95% CI: 0.58-0.94). Conclusions In this methodologic validation study, we have demonstrated that it is possible to produce an ECA from historical clinical trials data using propensity score methods which replicates the comparative efficacy estimate from a target without introducing bias. That is, the ECA, which was well balanced with the investigational arm with respect to baseline patient attributes, returned nearly identical estimates of comparative efficacy as assessed by OS of both target trial control arm and ECA against the target trial experimental arm. This work illustrates that it is possible to create a valid ECA even when historical data size is limited and to do so without excessive exclusion of non-matched patients. That the treatment effect on OS estimated in comparison to the randomized control was very closely matched by that of the ECA suggests this approach to ECAs may be used to (1) estimate comparative efficacy of therapies that have only been studied in single arm settings and/or (2) augment or replace a randomized control arm in future trials when ethically or practically challenging. Figure 1A. Kaplan-Meier OS estimates of target trial experimental (N=300) vs. control arm (N=152) Figure 1B. Kaplan-Meier OS estimates of target trial experimental (N=290) vs. ECA (N=290)

Long-term outcomes and cost-effectiveness evaluation of robot-assisted stereotactic hematoma drainage for spontaneous intracerebral hemorrhage

BackgroundTo investigate the long-term follow-up and economic estimation outcomes of hematoma drainage for spontaneous intracerebral hemorrhage (SICH) with the assistance of neurosurgical navigation and positioning planning system (referred to as robot).MethodsData were retrospectively obtained from consecutive patients with SICH who were admitted to our single-center between March 2019 and March 2022. Different minimally invasive surgery (MIS) procedures were performed according to the inclusion/exclusion criteria. The different groups were sampled and matched using the propensity score method, with age, sex, history of stroke, hypertension, bleeding volume and site of bleeding as matching variables, and matched with inverse probability weighting using R statistical analysis software. From the time of discharge up until 1 year after the surgery, records were gathered on clinical results and medical expenditures. An analysis was conducted to compare the costs and health outcomes of both robot-assisted stereotactic hematoma drainage and neuro-endoscopic surgery, considering both short-term and long-term effects. Health outputs were measured using modified Rankin scale (mRS) and quality adjusted life years (QALYs).ResultsOf the 142 patients, there were 77 patients in the robotic surgery group and 65 patients in the neuro-endoscopic surgery group. Propensity score sampling was matched, resulting in a balanced and comparable group of 37 patients in each, with the robotic surgery group [mean age (57.29 ± 12.74) years, 27 males (72.97%), hematoma volume (44.54 ± 10.49 ml), 22 deep location (59.46%)] and the neuro-endoscopic surgery group [mean age (57.27 ± 11.12) years, 27 males (72.97%), hematoma volume (44.70 ± 10.86 ml), 23 deep location (62.16%)]. At both three-month and one-year postoperative follow-up, the proportion of mRS scores ≤3 was higher in the robotic surgery group (45.95%,70.27%) than in the neuro-endoscopic surgery group (35.14%, 62.16%), but there was no statistically significant difference (P = 0.344, 0.461). One year after surgery, the robotic group demonstrated cost savings of ¥36,862.14 per individual and a gain of 0.062 QALYs compared to the neuro-endoscopic group.ConclusionOur calculations based on a model for SICH suggest that robotic-assisted stereotactic drainage offers health economic benefits due to its lower cost and higher effectiveness. However, to confirm these findings, more data from multicenter, prospective randomized controlled trials with larger sample sizes are needed.

Influence of antibiotic therapy with hemodynamic optimization on 30-day mortality among septic shock patients cared for in the prehospital setting

BackgroundIn order to reduce septic shock mortality, international guidelines recommend early treatment implementation, antibiotic therapy (ABT) and hemodynamic optimisation, within 1-h.This retrospective multicentric study aims to investigate the relationship between prehospital ABT delivered within 1st hour and mean blood pressure (MAP) ≥ 65 mmHg at the end of the prehospital stage, and 30-day mortality among patients with septic shock. MethodsFrom May 2016 to December 2021, patients with septic shock requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To assess the relationship between 30-day mortality and prehospital ABT delivered within 1st hour and/or MAP ≥ 65 mmHg at the end of the prehospital stage, Inverse Probability Treatment Weighting (IPTW) propensity score method was performed. ResultsAmong the 530 patients included, 341 were male gender (64%) with a mean age of 69 ± 15 years. One-hundred and thirty-two patients (25%) patients received prehospital ABT, among which 98 patients (74%) were treated with 3rd generation cephalosporin.Suspected pulmonary, urinary and digestive infections were the cause of sepsis in respectively 43%, 25% and 17%. The 30-day overall mortality was 31%.A significant association was observed between 30-day mortality rate and (i) ABT administration within the first hour: RRa = 0.14 [0.04–0.55], (ii) ABT administration within the first hour associated with a MAP ≥ 65 mmHg: RRa = 0.08 [0.02–0.37] and (iii) ABT administration within the first hour in the prehospital setting associated with a MAP < 65 mmHg at the end of the prehospital stage: RRa = 0.75 [0.45–0.85]. Patients who received prehospital ABT after the first hour have also a 30-day mortality rate decrease: RRa = 0.87 [0.57–0.99], whereas patients who did not received ABT had an increased 30-day mortality rate: RRa = 2.36 [1.89–2.95]. ConclusionIn this study, we showed that pre-hospital ABT within the first hour and MAP≥65 mmHg at the end of prehospital stage are both associated with 30-day mortality decrease among patients suffering from septic shock cared for by a MICU. Further prospective studies are needed to confirm these preliminary results.

BIOS-01. EFFICACY AMONG THERAPEUTICALLY EFFECTIVE ABSORBED DOSE PATIENTS IN RESPECT-GBM PHASE I OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOBLASTOMA (RGBM) COMPARED TO AN EXTERNAL CONTROL ARM (ECA)

Abstract BACKGROUND ReSPECT-GBM is a Phase 1/2 study of 186RNL administered by convection enhanced delivery (CED) in patients with rGBM. In Phase I, 15 of 24 patients have achieved a therapeutic absorbed dose defined as &amp;gt; 100 Gy. Based on prior work establishing the comparability of a bevacizumab (Bev) comparator to inform early-phase CED study results, OS of the 15 TAD patients were compared to a Bev ECA. METHODS Recent Bev-treated rGBM clinical trial patients meeting the same eligibility criteria as patients in the ReSPECT-GBM study were identified from the Medidata Enterprise Data Store of aggregated and deidentified patient-level historical clinical trial data. Propensity score (PS) methods were used to select the ECA and align the baseline characteristics of the Bev patients to the ReSPECT TAD cohort. OS estimates were generated using the weighted Kaplan-Meier method and compared with a weighted 2-sample 2-sided log-rank test at α = 0.05 based on a data cut-off of December 2022. RESULTS Baseline characteristics of the ReSPECT TAD and ECA patients were well-aligned after PS modeling. Although not achieving statistical significance due to small sample sizes (median OS 12.2 vs 10.1 months, hazard ratio 0.63, 95% CI: 0.26, 1.52), comparison of OS between the ReSPECT TAD and ECA patients demonstrate consistently longer OS at each 6-month interval: 6 months: 85.1% vs 73.3%, 12 mos: 51.1% vs 30.3%, 18 months: 30.6% vs 25.4%, 24 months: 30.6% vs 3.5%. CONCLUSIONS Single-arm studies can be challenging to interpret. By comparing the ReSPECT-GBM outcomes to an ECA of similar patients with balanced baseline characteristics, we can better appreciate the treatment effect of 186RNL administered via CED. The current results are encouraging, and updated results reflecting current follow-up will be presented at the meeting.

Association between implanted cardioverter-defibrillator and mortality for patients with left ventricular ejection fraction near 35%

Abstract Background Consensus guidelines support the use of implanted cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death in patients with either non-ischemic or ischemic cardiomyopathy with left ventricular ejection fraction ≤ 35%. Despite that class 1 recommendation, evidence from trials for efficacy specifically for patients with left ventricular ejection fraction (LVEF) near 35% is weak. Past trials are underpowered for this population and future trials are unlikely to be performed. As such, we aimed to use a large longitudinal echocardiography database linked to mortality to assess the comparative effectiveness of ICD therapy near the conventional primary prevention LVEF threshold. Methods Patients with lowest LVEF between 33-38% without an ICD prior to the lowest-LVEF echo (defined as "time zero") were identified by querying echocardiography data from November 28, 2001 until July 9, 2020 at large general hospital-based echocardiography registry linked to ICD treatment status. These data were then linked to mortality and comorbidity data. After inclusion and exclusion criteria were applied, 6,144 patients remained for the analytic cohort. Given evidence of covariate imbalance around the LVEF = 35% threshold, fuzzy regression discontinuity methods were considered but not used. Instead, to assess the association between ICD and mortality, multiple propensity score methods including matching and inverse probability of treatment weighting (IPTW) were used to create synthetic reference groups. Survival was then assessed with Cox proportional hazards models considering treatment status as a time-dependent covariate. Results In bivariate unadjusted comparisons, patients who received ICDs were substantially more often male (85.6% vs. 64.9%, p &amp;lt; 0.0001), more often white (87.3% vs. 82.9%, p &amp;lt; 0.048), and more often had a history of ventricular tachycardia (41.1% vs. 12.1%, p &amp;lt; 0.0001) and myocardial infarction (42.1% vs. 34.7%, p = 0.008). In the propensity matched sample, after accounting for time-dependence, there was no association between ICD and mortality (HR 1.09, 95% CI 0.86-1.39, p = 0.474). In the IPTW analysis, there also was no association between ICD and mortality (HR 1.09, 95% CI 0.91-1.30, p = 0.3672). Conclusions ICD therapy was not associated with reduced mortality near the conventional LVEF threshold of 35%. Although this treatment design cannot definitively demonstrate lack of efficacy, our results are concordant with available prior trial data. A definitive, well-powered trial is needed to answer the common and important clinical question of primary prevention ICD efficacy near the threshold of LVEF = 35%.

Abstract 14605: Association of SGLT-2 Inhibition With Size of Myocardial Infarction in Patients With Type 2 Diabetes Mellitus

Introduction: Preclinical data suggest that sodium-glucose-cotransporter-2 inhibitors (SGLT-2i) reduce the size of myocardial infarction (MI). This study aimed to assess the association of SGLT-2i use with the size of MI and clinical outcome. Methods: In a retrospective single center cohort study, patients with diagnosed diabetes mellitus type 2 who were admitted for MI and treated with PCI between November 2015 and November 2022 were analyzed and grouped according to SGLT-2i use. Following PCI, serial high sensitivity troponin T (cTn, Roche) measurements were performed according to in-house protocol. The primary outcome was the size of MI determined by the peak cTn normalized on the endangered myocardial area (EMA) calculated according to culprit lesion localization and coronary arterial dominance. Secondary outcomes were in-hospital adverse events (i.e. in-hospital death or stroke) and length of intensive care unit (ICU) treatment. The propensity score method was used to assess the association with outcomes. Results: 631 patients were identified: 85 with ongoing SGLT-2i therapy and 537 with other antidiabetic medication. Patients using SGLT-2i were younger (median age [years]: 67 [interquartile range, IQR 59-73] vs. 73 [64-79], p&lt;0.01) and had a higher eGFR at admission (75 [57-91] vs. 68 [49-88] ml/min/1.73m 2 , p=0.03). The median cTn samples per patient was 6 (5-8). There was no significant difference in the peak cTn levels between the two groups (SGLT-2i use vs. no SGLT-2i use: 53 (12-173) vs. 65 (20-174) х the upper limit of normal [ULN], p=0.26). After augmented inverse-probability weighted propensity score matching, ongoing SGLT-2i therapy was significantly associated with a reduced MI size (difference between means: -2.19 [95% confidence interval, -4.07 to -0.31] x ULN/EMA (1/%), p=0.02). SGLT-2i use was associated with less in-hospital adverse events (-4.69 [-8.70 to -0.69] %, p=0.02) and with less days on ICU (-0.27 [-0.53 to -0.01] days, p=0.045). Conclusion: In this retrospective cohort study of patients with DM presenting with MI, prior prescription of SGLT-2i was associated with reduced MI size and fewer adverse events during hospitalization. This might indicate that SGLT2i reduces the size of MI.

Abstract 11322: Comparative Outcomes of Impella and Intra-Aortic Balloon Pump for Left Ventricular Unloading Among Patients With Cardiogenic Shock on Veno-Arterial Extracorporeal Membrane Oxygenation

Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with CS. Although Impella or Intra-aortic balloon pump (IABP) is frequently used for left ventricular (LV) unloading for increased afterload during VA-ECMO therapy, there are scarce comparative outcomes data for these devices. Aims: To compare short-term outcomes of Impella and IABP in patients on VA-ECMO for CS. Methods: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes of CS patients requiring VA-ECMO based on multivariable regression and propensity score methods. Results: Of 15,980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4% patients, respectively. The proportion of patients managed with Impella for LV unloading significantly increased from 2016 to 2020 (6.5% vs. 25.8%; P-trend&lt;0.001). In-hospital mortality was higher in Impella group (54.8%) compared with ECMO only (50.4%) and IABP (48.4%) groups. After adjustment, LV unloading using IABP vs ECMO only was associated with lower in-hospital mortality (OR, 0.83; 95% CI, 0.70-0.98). LV unloading using Impella vs ECMO only had similar in-hospital mortality (OR, 1.09; 95% CI, 0.91-1.31) but was associated with more bleeding (OR, 1.21; 95% CI, 1.04-1.41) and more acute kidney injury (AKI) requiring hemodialysis (HD) (OR, 1.42; 95% CI, 1.13-1.77). LV unloading with Impella vs IABP was associated with greater risk of AKI requiring HD (OR, 1.49; 95% CI, 1.13-1.97), higher in-hospital mortality (OR, 1.32; 95% CI, 1.10-1.60), and high 40-day mortality (HR, 1.25; 95% CI, 1.17-1.32). Conclusions: LV unloading using Impella, compared with IABP, was not associated with improved survival at 40 days in patients treated with VA-ECMO for CS, but was associated with increased adverse events. These findings suggest a need for further studies to guide clinical practice of LV unloading in CS.

Salvage Transplant Versus CAR-T Cell Therapy for Relapsed Multiple Myeloma

Background: Ide-cel and cilta-cel received regulatory approval for the treatment of patients with relapsed or refractory multiple myeloma (MM) after ≥4 prior lines of therapy, and almost all eligible patients in the US and Europe have previously received at least one autologous hematopoietic cell transplant (autoHCT). Even for those who received upfront autoHCT, salvage transplant (either second autoHCT or allogeneic HCT) for patients with relapsed MM was shown to be effective and feasible. Therefore, comparing CAR-T cell therapy with salvage transplant could facilitate future selection of patients with relapsed MM, as eligibility for transplant (especially allogeneic HCT) differs significantly from that of CAR-T. Methods: We leveraged a large European dataset to identify relapsed MM patients who received either salvage autoHCT, allogeneic HCT, or CAR-T cell therapy. To minimize selection bias, we only included patients who received salvage treatment from 2018 onwards and who had documented time of relapse. Furthermore, to control for differences in patient characteristics, we applied propensity score (PS) matching for the comparison: CAR-T versus auto HCT and versus allogeneic HCT. We performed individual matching with the “nearest neighbour” method, using a caliper=0.2. The model for PS estimation included patient sex, MM classification at diagnosis, previous transplant history (single or tandem auto), interval between upfront transplant and relapse and between relapse and CAR-T/salvage transplant, age, performance status and disease status at CAR-T/salvage transplant. Endpoints of matched groups were compared by Log-Rank test or Gray test stratified on the pair. Primary endpoint was progression-free survival (PFS) at 1 year with 95% confidence interval (CI). Secondary endpoints constituted non-relapse mortality, incidence of relapse, and overall survival (OS). Results: We included 4292 patients, of whom 3858 received salvage autoHCT, 371 allogeneic HCT, and 63 CAR-T cell therapy (60% ide-cel, 33% cilta-cel, 7% other investigational). Median age at time of salvage treatment was 62 years for autoHCT, 54 years for allogeneic HCT, and 61 years for CAR-T cell therapy (P&amp;lt;0.001). More than 60% of patients were male in all groups, and IgG subtype of MM was present in 52% of autoHCT, 48% of allogeneic HCT, and 44% of CAR-T cell therapy. More patients receiving CAR-T cell therapy had a Karnofsky performance status &amp;lt;80% (41%) versus 32% of autoHCT and 29% of allogeneic HCT. In terms of response, complete response to treatment was observed in 40% for autoHCT, 63% for allogeneic HCT, and 44% for CAR-T cell therapy. Partial remission or very good partial remission was achieved 11%, 9%, and 35%, respectively (P&amp;lt;0.001). Median follow-up was 16.7 months for the entire cohort. The PS method could successfully match almost all patients for the comparison of CAR-T cell therapy versus salvage autoHCT (59 patient, respectively). The 1-year PFS for CAR-T cell therapy versus autoHCT was 68% (95% CI, 56-80%) versus 44% (95% CI, 28-59%; P=0.048; Figure 1). The 1-year non-relapse mortality was 9% (95% CI, 2-17%) versus 0% (P=0.31). Cumulative incidence of relapse at 1 year was 23% versus 57% (P=0.028), and 1-year overall survival was 81% versus 68% (P=0.059). The PS method matched 33 patients for the comparison of CAR-T cell therapy versus salvage allogeneic HCT. The 1-year PFS was 72% (95% CI, 56-88%) versus 39% (95% CI, 18-60%; P=0.346). Non-relapse mortality at 1-year was 13% (95% CI, 1-25%) versus 23% (95% CI, 7-43%; P=0.257). The 1-year cumulative incidence of relapse was 15% versus 36% (P=0.763), and the 1-year overall survival was 84% (95% CI, 71-97%) versus 60% (95% CI, 39-81%; P=0.083). Conclusion: This multicenter retrospective study compared CAR-T cell therapy with salvage transplantation strategies for relapsed MM. CAR- T cell therapy appeared to improve outcomes, especially in comparison with salvage autoHCT. The higher absolute rates of non-relapse mortality observed with CAR-T cell therapy may not counterbalance overall beneficial results, and rather highlights the need for careful selection of patients. Longer follow-up will be needed for definitive results.

Use of Prephase Steroids in Older Patients Treated for Diffuse Large B-Cell Lymphoma

Background Treatment related morbidity and mortality (TRM) are significant contributors to overall morbidity and mortality for elderly patients with diffuse large B-cell lymphoma (DLBCL). Several studies have shown that TRM is greatest during the first two cycles of treatment. While attenuated doses of standard-of-care treatment regimens (such as R-mini-CHOP) are commonly used to reduce TRM, one additional strategy that has shown promise is the use of glucocorticoids prior to initiation of systemic chemoimmunotherapy (CIT). This approach, defined as prephase steroid use, has been evaluated in small studies, primarily single-center and retrospective in nature. However, older patients with comorbidities are both at greatest risk of TRM and less frequently included in clinical trials. Moreover, patient populations may differ across clinical settings. We conducted an analysis of prephase steroid use in a broader, real-world population treated across multiple centers. Methods We used longitudinal data from the US nationwide, Flatiron Health electronic health record-derived de-identified database. We included patients aged &amp;gt;60 with a diagnosis of DLBCL treated with CIT. This included high-grade B-cell lymphoma, but omitted diagnoses of Burkitt's or primary CNS lymphoma. We utilized a prespecified data analysis plan to determine whether outcomes differed by our exposure of interest, use of prephase steroids. The primary outcome measure was the combined endpoint of time to start of next treatment or death (real-world time to next treatment [rwTTNT]). The secondary outcome was real-world overall survival (rwOS). Outcomes were measured from frontline treatment start date. We also assessed rates of dose delays to evaluate whether prephase steroid use facilitates the maintenance of dose intensity. Prephase steroid use (the exposure) was defined as an order or administration for steroids occurring 5-21 days prior to the start of antineoplastic therapy (excluding steroids used as part of a standard treatment regimen). Patients were stratified by use of anthracycline-based CIT, with sensitivity analyses conducted limited to the anthracycline CIT group. To reduce confounding, we used propensity score-based inverse probability of treatment weighting (IPTW) for the primary analysis. Time to event endpoints were assessed using weighted Kaplan-Meier curves and log-rank tests. Odds of dose delays were assessed using weighted logistic regression. Results We included 3587 patients meeting our criteria, of whom 569 (15.9%) received prephase steroids prior to first-line CIT. A greater percentage of patients treated with anthracycline-based CIT received prephase steroids as compared to those treated with non-anthracyline CIT: 16.3% vs 12.4%, respectively (Table 1). In adjusted analysis using IPTW, there was no significant difference in the rwTTNT by prephase steroid use (p=0.807, Figure 1). Median rwTTNT was 41.2 months (95% CI, 34.6 to 52.4) vs 40.8 months (95% CI, 35.1 to 46.7) with and without prephase steroids, respectively. There was no difference in median rwOS by prephase steroid use: 65.7 months (95% CI, 52.4 to 84.8) vs 74.8 months (95% CI, 67.4 to 82.5) (p=0.707). No differences were seen in sensitivity analyses limiting to patients treated with anthracycline-based CIT. For dose delays, adjusted analysis showed a numerically lower odds of dose delay in patients administered prephase steroids in the total study population: 40.6% vs 50.7% (OR 0.796; p=0.0569). Discussion In this retrospective study of 3587 real-world, elderly patients with DLBCL, prephase steroid use within 21 days of induction CIT did not improve the rwTTNT or rwOS. There was a suggestion that use of prephase steroids may promote maintenance of dose intensity by reducing delays in CIT administration, though this finding did not reach statistical significance. The strengths of this analysis included use of a large, nationwide, real-world dataset and propensity score methods to control for confounding. Limitations include the retrospective nature of the study and potential for unmeasured confounding. In summary, in a real-world cohort of older patients with DLBCL, use of prephase steroids was not associated either with longer TTNT/death, or with longer OS. However, it may be associated with maintenance of CIT dose intensity. This finding is worth exploring in future studies.