Absolute Standardized Differences Research Articles

A simulation-based bias analysis to assess the impact of unmeasured confounding when designing non-randomized database studies.

Unmeasured confounding is often raised as a source of potential bias during the design of non-randomized studies but quantifying such concerns is challenging. We developed a simulation-based approach to assess the potential impact of unmeasured confounding during the study design stage. The approach involved generation of hypothetical individual-level cohorts using realistic parameters including a binary treatment (prevalence 25%), a time-to-event outcome (incidence 5%), 13 measured covariates, a binary unmeasured confounder (u1, 10%), and a binary measured 'proxy' variable (p1) correlated with u1. Strength of unmeasured confounding and correlations between u1 and p1 were varied in simulation scenarios. Treatment effects were estimated with, a) no adjustment, b) adjustment for measured confounders (Level 1), c) adjustment for measured confounders and their proxy (Level 2). We computed absolute standardized mean differences in u1 and p1 and relative bias with each level of adjustment. Across all scenarios, Level 2 adjustment led to improvement in balance of u1, but this improvement was highly dependent on the correlation between u1 and p1. Level 2 adjustments also had lower relative bias than Level 1 adjustments (in strong u1 scenarios: relative bias of 9.2%, 12.2%, 13.5% at correlations 0.7, 0.5, and 0.3, respectively versus 16.4%, 15.8%, 15.0% for Level 1, respectively). An approach using simulated individual-level data was useful to explicitly convey the potential for bias due to unmeasured confounding while designing non-randomized studies and can be helpful in informing design choices.

#462 Initiation of SGLT2i vs GLP1-RA and incidence of AKI in persons with type 2 diabetes mellitus

Abstract Background and Aims Adverse kidney outcomes, including acute kidney injury (AKI), are frequent complications in people with diabetes mellitus type 2. In large placebo-controlled randomized trials, both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown efficacy in reducing the risk of kidney outcomes; however, no trial has compared the kidney protective effects of these drug classes head-to-head. We therefore conducted an emulated target trial to compare the effect of SGLT2i to that of GLP1-RA on the incidence of AKI. Method Using routinely collected data from nationwide Danish population-based registries, we included all adults with diabetes mellitus type 2 initiating SGLT2i or GLP1-RA in 2015-2020. Patients with prevalent kidney failure (defined as eGFR < 15 mL/min/1.73m2, dialysis, or kidney transplant), and patients initiating GLP1-RA marketed specifically for treatment of obesity were excluded. We assessed demographic and diabetes-related baseline characteristics along with comorbidities and comedication. We used propensity scores, estimated by logistic regression, to compute stabilized inverse probability of treatment weights, which were applied in all analyses to reduce confounding. Using an intention to treat approach, we followed patients from treatment initiation until the first of death, emigration, or end of follow-up (31 December 2021). Using creatinine measurements from in- and outpatient settings, we applied the KDIGO definition of AKI to record each episode of AKI during follow-up. We estimated the risk of a first AKI episode over time using the Aalen-Johansen estimator. Furthermore, to estimate the mean number of AKIs over time, i.e., including recurrent AKIs, we used the mean cumulative count estimator. Both estimators account for the competing risk of death. Comparing SGLT2i to GLP1-RA, we reported differences in risks and counts at 1, 3 and 5 years of follow-up. Finally, we estimated all-cause mortality using the Kaplan-Meier estimator. We used bootstrapping to obtain 95% confidence intervals (95% CI). Results We included 68 010 individuals, of which 44 034 (65%) initiated SGLT2i, and 23 976 (35%) initiated GLP1-RA. Initiators of SGLT2i were slightly older (median age 63 vs 62 years) and more often male (63% vs 56%) than initiators of GLP1-RA, but with similar diabetes duration (7 vs 7 years). The annual number of initiators of each drug in Denmark increased over the study period. Compared to GLP1-RA, initiators of SGLT2i generally had better estimated glomerular filtration rate (eGFR) at baseline (9% vs 18% had eGFR < 60 mL/min/1.73m2), more frequently used metformin (91% vs 84%), but less frequently insulin (11% vs 28%). Initiators of SGLT2i had a lower prevalence of hospital-diagnosed retinopathy (7% vs 9%), neuropathy (5% vs 6%), and obesity (13% vs 23%) than initiators of GLP1-RA. After inverse probability of treatment weighting, each variable was well balanced with absolute standardized mean differences below 0.02. During a median follow-up of 2.8 years, the weighted absolute risks of first time AKI at 1, 3, and 5 years were 4.8%, 11.2%, and 17.0% for initiators of SGLT2i, and 5.4%, 12.3%, and 19.1% for initiators of GLP1-RA, resulting in AKI risk differences of −0.6% (95% CI: −1.0% to −0.3%), −1.0% (95% CI: −1.7% to −0.5%), and −2.0% (95% CI: −3.0% to −1.1%). The mean cumulative counts showed a similar pattern, with SGLT2i initiators experiencing slightly fewer AKI episodes than GLP1-RA initiators on average (Fig. 1). After 5 years, an estimated 10.3% of SGLT2i initiators and 9.6% of GLP1-RA initiators had died, resulting in a risk difference of 0.7% (95% CI: -0.1% to 1.5%). Conclusion People with diabetes mellitus type 2 who initiated SGLT2i had slightly lower weighted incidence of AKI over 5 years than those initiating GLP1-RA.

Machine learning evaluation of inequities and disparities associated with nurse sensitive indicator safety events.

To use machine learning to examine health equity and clinical outcomes in patients who experienced a nurse sensitive indicator (NSI) event, defined as a fall, a hospital-acquired pressure injury (HAPI) or a hospital-acquired infection (HAI). This was a retrospective observational study from a single academic hospital over six calendar years (2016-2021). Machine learning was used to examine patients with an NSI compared to those without. Inclusion criteria: all adult inpatient admissions (2016-2021). Three approaches were used to analyze the NSI group compared to the No-NSI group. In the univariate analysis, descriptive statistics, and absolute standardized differences (ASDs) were employed to compare the demographics and clinical variables of patients who experienced a NSI and those who did not experience any NSIs. For the multivariate analysis, a light grading boosting machine (LightGBM) model was utilized to comprehensively examine the relationships associated with the development of an NSI. Lastly, a simulation study was conducted to quantify the strength of associations obtained from the machine learning model. From 163,507 admissions, 4643 (2.8%) were associated with at least one NSI. The mean, standard deviation (SD) age was 59.5 (18.2) years, males comprised 82,397 (50.4%). Non-Hispanic White 84,760 (51.8%), non-Hispanic Black 8703 (5.3%), non-Hispanic Asian 23,368 (14.3%), non-Hispanic Other 14,284 (8.7%), and Hispanic 30,271 (18.5%). Race and ethnicity alone were not associated with occurrence of an NSI. The NSI group had a statistically significant longer length of stay (LOS), longer intensive care unit (ICU) LOS, and was more likely to have an emergency admission compared to the group without an NSI. The simulation study results demonstrated that likelihood of NSI was higher in patients admitted under the major diagnostic categories (MDC) associated with circulatory, digestive, kidney/urinary tract, nervous, and infectious and parasitic disease diagnoses. In this study, race/ethnicity was not associated with the risk of an NSI event. The risk of an NSI event was associated with emergency admission, longer LOS, longer ICU-LOS and certain MDCs (circulatory, digestive, kidney/urinary, nervous, infectious, and parasitic diagnoses). Machine learning methodologies provide a new mechanism to investigate NSI events through the lens of health equity/disparity. Understanding which patients are at higher risk for adverse outcomes can help hospitals improve nursing care and prevent NSI injury and harm.

Dysphagia and Functional Limitations Among Adults in the United States: Findings from the 2022 National Health Interview Survey.

Dysphagia or swallowing dysfunction is associated with reduced quality of life and poor long term outcomes. While standard dysphagia treatment focuses on improving swallowing function, it is not clear if people with dysphagia also have difficulties performing daily tasks. This study aimed to determine if individuals with dysphagia had difficulties with participating in daily tasks requiring physical function, as compared to those with no dysphagia. We conducted a secondary data analysis using the responses of 24,107 adults aged 18years or older who completed the 2022 National Health Interview Survey. The independent variable was report of swallowing problem during the past 12months, and the dependent variables were report of difficulty in physical function tasks (e.g., self-care, mobility, working, social participation). We utilized propensity score methods to balance demographic and clinical variables between groups, and examined if individuals with dysphagia had more difficulties with the physical function tasks. The propensity score methods balanced the demographic and clinical variables (absolute standardized differences < 0.1). People with dysphagia had significantly higher odds ratios (ranged from 1.23 to 1.70, all p < 0.05) of having difficulties in physical function tasks than those without dysphagia. The findings revealed an association between experiencing dysphagia and encountering difficulties in self-care, mobility, working, and social participation in the general adult population in the US. Results of our study indicate that during the course of rehabilitation, healthcare professionals should consider the potential impact of dysphagia symptoms on clients' ability to partake in independent activities in their community settings.

Postoperative outcomes and costs of laparoscopic versus robotic distal pancreatectomy: a propensity-matched analysis.

Minimally invasive distal pancreatectomy (MIDP) has established advantages over the open approach. The costs associated with robotic DP (RDP) versus laparoscopic DP (LDP) make the robotic approach controversial. We sought to compare outcomes and cost of LDP and RDP using propensity matching analysis at our institution. Patients undergoing LDP or RDP between 2000 and 2021 were retrospectively identified. Patients were optimally matched using age, gender, American Society of Anesthesiologists status, body mass index, and tumor size.Between-group differences were analyzed using the Wilcoxon signed-rank test for continuous data, and the McNemar's test for categorical data. Outcomes included operative duration, conversion to open surgery, postoperative length of stay, pancreatic fistula rate, pseudocyst requiring intervention, and costs. 298 patients underwent MIDP, 180 (60%) were laparoscopic and 118 (40%) were robotic. All RDPs were matched 1:1 to a laparoscopic case with absolute standardized mean differences for all matching covariates below 0.10, except for tumor type (0.16). RDP had longer operative times (268 vs 178min, p < 0.01), shorter length of stay (2 vs 4days, p < 0.01), fewer biochemical pancreatic leaks (11.9% vs 34.7%, p < 0.01), and fewer interventional radiological drainage (0% vs 5.9%, p = 0.01). The number of pancreatic fistulas (11.9% vs 5.1%, p = 0.12), collections requiring antibiotics or intervention (11.9% vs 5.1%, p = 0.12), and conversion rates (3.4% vs 5.1%, p = 0.72) were comparable between the two groups. The total direct index admission costs for RDP were 1.01 times higher than for LDP for FY16-19 (p = 0.372), and 1.33 times higher for FY20-22 (p = 0.031). Although RDP required longer operative times than LDP, postoperative stays were shorter. The procedure cost of RDP was modestly more expensive than LDP, though this was partially offset by reduced hospital stay and reintervention rate.

The impact of COVID‐19 lockdown on mortality rate in memory clinic patients

AbstractBackgroundPeople with (pre‐)dementia were particularly at risk for mortality during the COVID‐19 pandemic due to severe outcome of a COVID‐19 infection and the negative consequences of restrictive measures. Here we study whether patients during the COVID‐19 pandemic had a higher mortality rate compared to historical controls.MethodIn this case‐control study, we included patients from the Amsterdam Dementia Cohort: 1) Pandemic patients (n = 1022) with a baseline visit between January 2017 and December 2018 and 2) Historical controls (n = 930) with a baseline visit between January 2015 and December 2016. Both groups were followed for three years (pandemic patient until 2021 and historical controls until 2019). Absolute standardized mean differences were analyzed in order to determine whether groups were well‐balanced in terms of demographics and cognition at baseline. Cox proportional hazards analyses were performed to compare mortality rate during COVID‐19 pandemic with historical controls. Age, sex, diagnosis, MMSE score, education level, and comorbidity were added as covariates to the model.ResultBoth groups were well‐balanced, as mean age of the pandemic patients was 63±9 years, n = 423 (41%) were female and mean MMSE score was 24.5±5.0. Mean age of the historical controls was 63±8 years, n = 404 (43%) were female and MMSE score was 24.2±5.2. The absolute standardized mean differences were under 0.1 for all selected covariates. Among the pandemic patients, n = 180 (18%) patients died during the previously described follow‐up time. In the historical control group, n = 131 (14%) patients died. Cox proportional hazards models showed that pandemic patients had higher risk for mortality than historical controls (HR [95%‐CI] = 1.27 [1.02‐1.59]). Results remained significant after adjusting for covariates age, sex, diagnosis, MMSE score, education level, and comorbidity (HR [95%‐CI] = 1.37 [1.09‐1.72]).ConclusionMemory clinic patients had increased risk on mortality during times of COVID‐19 lockdown compared to historical controls. This indicates that COVID‐19 lockdown regulations have accelerated disease. Even though the cause of mortality is unknown, it is likely that the excess mortality is not only due to COVID‐19 infections, but also caused by the restrictive measure of the COVID‐19 lockdown restrictions (e.g. social isolation and loss of structure).

Representativeness of the American Spine Registry: a comparison of patient characteristics with the National Inpatient Sample.

The American Spine Registry (ASR) is a collaborative effort between the American Academy of Orthopaedic Surgeons and the American Association of Neurological Surgeons. The goal of this study was to evaluate how representative the ASR is of the national practice with spinal procedures, as recorded in the National Inpatient Sample (NIS). The authors queried the NIS and the ASR for cervical and lumbar arthrodesis cases performed during 2017-2019. International Classification of Diseases, 10th Revision and Current Procedural Terminology codes were used to identify patients undergoing cervical and lumbar procedures. The two groups were compared for the overall proportion of cervical and lumbar procedures, age distribution, sex, surgical approach features, race, and hospital volume. Outcomes available in the ASR, such as patient-reported outcomes and reoperations, were not analyzed due to nonavailability in the NIS. The representativeness of the ASR compared to the NIS was assessed via Cohen's d effect sizes, and absolute standardized mean differences (SMDs) of < 0.2 were considered trivial, whereas > 0.5 were considered moderately large. A total of 24,800 arthrodesis procedures were identified in the ASR for the period between January 1, 2017, and December 31, 2019. During the same time period, 1,305,360 cases were recorded in the NIS. Cervical fusions comprised 35.9% of the ASR cohort (8911 cases) and 36.0% of the NIS cohort (469,287 cases). The two databases presented trivial differences in terms of patient age and sex for all years of interest across both cervical and lumbar arthrodeses (SMD < 0.2). Trivial differences were also noted in the distribution of open versus percutaneous procedures of the cervical and lumbar spine (SMD < 0.2). Among lumbar cases, anterior approaches were more common in the ASR than in the NIS (32.1% vs 22.3%, SMD = 0.22), but the discrepancy among cervical cases in the two databases was trivial (SMD = 0.03). Small differences were illustrated in terms of race, with SMDs < 0.5, and a more significant discrepancy was identified in the geographic distribution of participating sites (SMDs of 0.7 and 0.74 for cervical and lumbar cases, respectively). For both of these measures, SMDs in 2019 were smaller than those in 2018 and 2017. The ASR and NIS databases presented a very high similarity in proportions of cervical and lumbar spine surgeries, as well as similar distributions of age and sex, and distribution of open versus endoscopic approach. Slight discrepancies in anterior versus posterior approach among lumbar cases and patient race, and more significant discrepancies in geographic representation were also identified, yet decreasing trends in differences suggested the improving representativeness of the ASR over the course of time and its progressive growth. These conclusions are important to underline the external validity of quality investigations and research conclusions to be drawn from analyses in which the ASR is used.

Factors associated with COVID-19 vaccination during June-October 2021: A multi-site prospective study.

Vaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership. In June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analyses assessed predictors of subsequent vaccination among those initially unvaccinated. In June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9%) became vaccinated by October 31, 2021. In June, unvaccinated participants were less likely to feel "very concerned" about getting COVID-19 than vaccinated participants (10.6% vs. 43.3%, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5% reported vaccination before study end. Two latent factors predicted subsequent vaccination-being 'more receptive' was derived from motivation to protect one's own or others' health and resume usual activities; being 'less receptive' was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention. This study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions.

PD44-08 BENEFIT OF WHOLE-PELVIS RADIATION FOR PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER: AN INVERSE PROBABILITY TREATMENT WEIGHTED ANALYSIS

PD44-08 BENEFIT OF WHOLE-PELVIS RADIATION FOR PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER: AN INVERSE PROBABILITY TREATMENT WEIGHTED ANALYSIS

Medications for alcohol use disorder improve survival in patients with hazardous drinking and alcohol-associated cirrhosis.

Medications for alcohol use disorder (MAUD) are highly effective in achieving and maintaining abstinence in patients with alcohol use disorder (AUD). Our aim was to evaluate the effect of MAUD on all-cause mortality in patients with alcohol-associated cirrhosis and active alcohol use. This was a retrospective cohort study of patients with alcohol-associated cirrhosis and high-risk alcohol use disorder in the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) database. Propensity score matching for exposure to MAUD (acamprosate or naltrexone) within a year after cirrhosis diagnosis was performed to account for potential confounders, and the association between MAUD and all-cause mortality was subsequently evaluated using Cox regression analysis. A total of 9131 patients were included, of whom 886 (9.7%) were exposed to MAUD (naltrexone: 520, acamprosate: 307, both medications: 59). The duration of MAUD exposure was >3 months in 345 patients (39%). The strongest positive predictor of MAUD prescription was an inpatient diagnosis code for AUD, followed by a concurrent diagnosis of depression; the strongest negative predictor was a history of cirrhosis decompensation. After propensity score matching (866 patients in each group) with excellent covariate balance (absolute standardized mean differences <0.1), MAUD exposure was associated with improved survival, with an HR of 0.80 relative to no MAUD exposure (95% CI: 0.67-0.97, p = 0.024). MAUD are underutilized in patients with alcohol-associated cirrhosis with high-risk alcohol use behavior but are associated with improved survival after adjustment for confounders such as the severity of liver disease, age, and engagement in the healthcare system.

Elevated body mass index in modified natural cycle frozen euploidembryo transfers is not associated with live birth rate.

To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos. This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes. 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders. While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR.

Pregnancy and neonatal outcomes of letrozole versus natural cycle frozen embryo transfer of autologous euploid blastocyst.

To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET). Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5mg of daily letrozole for 5days starting on cycle day 2 or 3. Outcomes were compared using absolute standardized differences (ASD), in which a larger ASD signifies a larger difference. Multivariable regression models adjusted for confounders: maternal age, BMI, nulliparity, embryo grade, race, infertility diagnosis, and endometrial thickness. The demographic and clinical characteristics were overall similar. A greater proportion of the letrozole cohort was multiparous, transferred high-graded embryos, and had ovulatory dysfunction. The cohorts had similar pregnancy rates (67.1% LTZ vs 62.1% NC; aOR 1.31, P = 0.21) and live birth rates (60.9% LTZ vs 58.6% NC; aOR 1.17, P = 0.46). LTZ-FET neonates on average were born 5.7days earlier (P < 0.001) and had higher prevalence of prematurity (18.6% vs. 8.0%NC, ASD = 0.32) and low birth weight (10.4% vs. 5.0%, ASD = 0.20). Both cohorts' median gestational ages (38weeks and 1day for LTZ; 39weeks and 0day for NC) were full term. There were similar rates of pregnancy and live birth between LTZ-FET and NC-FET cycles. However, there was a higher prevalence of prematurity and low birth weight among LTZ-FET neonates. Reassuringly, the median gestational age in both cohorts was full term, and while the difference in gestational length of almost 6days does not appear to be clinically significant, this warrants larger studies.

Benefit of whole-pelvis radiation for patients with muscle-invasive bladder cancer: An inverse probability treatment-weighted analysis.

449 Background: Pelvic lymph node irradiation is still under debate for patients with muscle-invasive bladder cancer (MIBC) planned for curative-intent radiation-based therapy (RT). A previous randomized trial suggested bladder-only (BO)-RT was effective in reducing RT-related toxicity, while associated with non-inferior oncological outcomes – bladder preservation rates, disease-free survival, and overall survival (OS) – compared to whole-pelvis (WP)-RT. In this study, we sought to evaluate the impact of the radiation volume (BO-RT vs. WP-RT) on main oncological outcomes in patients with MIBC. Methods: This nationwide study included patients with urothelial MIBC (cT2-4aN0-2M0) who underwent curative RT at 10 academic centers across Canada. Patients clinically staged with pelvic or abdominal wall invasion (cT4b) or enlarged lymph nodes beyond the common iliac bifurcation (cN3) before RT were excluded. Patients were divided into two groups based on the RT volume: WP-RT vs. BO-RT. Inverse probability of treatment weighting (IPTW) and absolute standardized differences (ASDs) were used to balance baseline covariates across treatment groups. Regression models were used to assess the impact of the RT volume on the rates of complete response (CR) to treatment, cancer-specific survival (CSS), and OS while adjusting for potential confounding variables in the weighted cohorts. Results: A total of 599 patients were analyzed, out of whom 369 (61.6%) underwent WP-RT. Patients in the WP-RT group were younger (mean age 73.2 vs. 77.4; ASD 0.41), and more likely to have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (82.1% vs. 73.5%; ASD 0.21), clinical node-positive disease (12.5% vs. 2.2%; ASD 0.40), and lymphovascular invasion (26.3% vs. 16.1%; ASD 0.25), compared to BO-RT. In addition, WP-RT patients were more commonly treated with neoadjuvant chemotherapy (20.9% vs. 10.4%; ASD 0.29) and concurrent chemotherapy (76.7% vs. 56.5%; ASD 0.44), compared to BO-RT. In the IPTW cohort, age, gender, ECOG PS, clinical staging, the proportion of patients with carcinoma in situ, lymphovascular invasion, variant urothelial histologies, hydronephrosis, and whose tumours were completely resected before RT, treated with NAC, and treated with concurrent chemotherapy were well balanced across groups (all ASDs &lt; 0.10). In multivariable analysis, WP-RT did not impact CR rates post-RT (OR 1.14; p=0.526) but was associated with both CSS (HR 0.66; p=0.016) and OS (HR 0.68; p=0.002), independently of other prognostic factors (Table). Conclusions: Our study demonstrated a significant survival benefit with the use of WP-RT compared to BO-RT in patients with MIBC treated with curative intent. Additional randomized controlled trials are needed to confirm our findings.

The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease: A Secondary Analysis of the Age of Blood in Children in the PICU Trial.

Guidelines recommend against RBC transfusion in hemodynamically stable (HDS) children without cardiac disease, if hemoglobin is greater than or equal to 7 g/dL. We sought to assess the clinical and economic impact of compliance with RBC transfusion guidelines. A nonprespecified secondary analysis of noncardiac, HDS patients in the randomized trial Age of Blood in Children (NCT01977547) in PICUs. Costs analyzed included ICU stay and physician fees. Stabilized inverse propensity for treatment weighting was used to create a cohort balanced with respect to potential confounding variables. Weighted regression models were fit to evaluate outcomes based on guideline compliance. Fifty international tertiary care centers. Critically ill children 3 days to 16 years old transfused RBCs at less than or equal to 7 days of ICU admission. Six-hundred eighty-seven subjects who met eligibility criteria were included in the analysis. Initial RBC transfusions administered when hemoglobin was less than 7 g/dL were considered "compliant" or "non-compliant" if hemoglobin was greater than or equal to 7 g/dL. Frequency of new or progressive multiple organ system dysfunction (NPMODS), ICU survival, and associated costs. The hypothesis was formulated after data collection but exposure groups were masked until completion of planned analyses. Forty-nine percent of patients (338/687) received a noncompliant initial transfusion. Weighted cohorts were balanced with respect to confounding variables (absolute standardized differences < 0.1). No differences were noted in NPMODS frequency (relative risk, 0.86; 95% CI, 0.61-1.22; p = 0.4). Patients receiving compliant transfusions had more ICU-free days (mean difference, 1.73; 95% CI, 0.57-2.88; p = 0.003). Compliance reduced mean costs in ICU by $38,845 U.S. dollars per patient (95% CI, $65,048-$12,641). Deferring transfusion until hemoglobin is less than 7 g/dL is not associated with increased organ dysfunction in this population but is independently associated with increased likelihood of live ICU discharge and lower ICU costs.

Real World Effectiveness of "7 + 3" Intensive Chemotherapy Vs Venetoclax and Hypomethylating Agent for Initial Therapy in Adult Acute Myeloid Leukemia

Introduction Initial treatment selection for older adults with AML remains challenging. Historically, clinicians and patients had to choose between intensive chemotherapy (7 + 3), low intensity therapy or best supportive care. Approval of venetoclax and a hypomethylating agent (ven/HMA, NCT02993523) for those ≥75 years or with major comorbidities has offered higher response rates and improved survival vs. low intensity therapy. Use has expanded to other groups like younger patients with high risk disease or patients with "borderline" induction fitness. Prospective comparisons have yet to complete, so we examined retrospective outcomes for older patients receiving either 7 + 3 or ven/HMA as initial therapy. Methods We included patients from both the University of Pennsylvania ("HUP", n=187) and the Flatiron Health electronic health record derived, de-identified database with incident AML diagnosed between January 2017 and 2021, and 7 + 3 (7 days of cytarabine and 3 days of anthracycline) or ven/HMA (azacitadine or decitabine) as initial therapy (n=621). Only patients presumably eligible for 7 + 3 were included (age 60-75, estimated glomerular filtration rate > 30 mL/min, alanine transaminase, aspartate transaminase, bilirubin < 1.5x upper limit of normal (ULN), no history of systolic heart failure). Primary endpoint of overall survival (OS) had 80% power for hazard ratio (HR) 0.74 with alpha 0.05. OS was analyzed by Kaplan-Meier method and compared using log-rank test. Pre-planned sensitivity analyses included multiple imputation (MI) with inverse-probability of treatment weighting (IPTW) to address missingness and balance baseline covariates. Results 305 patients received 7 + 3 and 503 received ven/HMA. Baseline covariates showed ven/HMA patients were older, sicker and had worse disease biology (table 1). Underscoring this imbalance in age and comorbidity, allogeneic transplant rates were 31% vs 16% for 7 + 3 and ven/HMA respectively (p<0.0005). More than 40% of initial 7 + 3 patients received second-line ven/HMA while less than 10% of ven/HMA patients received second line 7 + 3 or CPX-351. In unadjusted analysis, median OS (mOS) was 14 months for all patients and 22 months for 7 + 3 versus 10 months for ven/HMA (HR 0.52, 95% confidence interval CI 0.41-0.67, p-value <0.005, Fig 1). No subset had statistically significant higher OS with ven/HMA compared to 7 and 3; in multi-variate analysis controlling for all covariates with univariate p-value < 0.20 induction choice did not affect overall survival (limited to complete cases n=229, HR 0.72, p-value 0.21). Missing values in the HUP dataset were <5% for all baseline covariates; Flatiron dataset missing values ranged from 0-40% for covariates (e.g., sex and baseline LDH respectively). After balancing covariates and adjustment for missing values, survival remained superior in the 7+3 group (HR 0.71, p-value 0.026, 95% CI 0.53-0.94) (absolute standardized differences for all baseline variables were below 0.10). Regarding safety, early mortality was higher for ven/HMA (13% vs 6%, p=0.003). However, rates of febrile neutropenia and culture positive infection were higher for 7 + 3. Length of stay, including any admission prior to next cycle, was longer for 7 + 3 in the HUP cohort (among patients admitted for induction: average 25 days for ven/HMA vs 34 days for 7 and 3 p=0.0012; an additional 20% of ven/HMA patients were managed entirely outpatient). Conclusion In this large, multi-center real word study, of patients presumed to be eligible for either approach we found superior outcomes for 7 + 3. However, there was significant confounding by indication and imbalance between the groups. Adjusting for these differences, OS was still higher for 7 + 3 (p=0.026). In this real world dataset, the 7 + 3 cohort outperformed historical benchmarks (e.g., NCT02085408) in OS and early mortality, perhaps reflecting improved later lines of therapy and patient selection. Given the significant confounding by indication, uneven cross-over and greater lab-based AEs/longer length of stays for intensive chemotherapy, prospective studies (such as NCT04801797) must confirm superiority of intensive chemotherapy. Careful attention to factors predictive of response to non-7 + 3 based therapy may be as important as the characterization of side effects, quality of life and impact on allotransplant to select optimal therapies for all adult AML patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 13338: Clinical Profile of Patients Hospitalized for Heart Failure With Severely Reduced Ejection Fraction: From the GWTG-HF Registry

Introduction: Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (i.e., stage D HF). The clinical profile, outcomes, and management of these patients in US practice is not well described. Methods: We studied patients hospitalized for worsening chronic HF with reduced ejection fraction (HFrEF) ≤40% across 423 sites in the Get With The Guidelines® (GWTG)-HF registry admitted 2014 -2019. We excluded patients with heart transplantation or durable mechanical circulatory support, severe kidney disease (eGFR&lt;20 mL/min/1.73 m 2 or dialysis), or missing critical data elements. Patients were grouped by EF (≤30% vs. 31-40%) and data were compared using absolute standardized differences. Results: Among 113,348 patients with HFrEF ≤40%, 78,589 (69%) had an EF≤30%. Compared with EF 31-40%, patients with EF≤30% tended to be younger, were less likely to be female, and more likely to be Black (Table). Patients with EF ≤30% had lower systolic blood pressure, but modestly higher eGFR and lower rates of atrial fibrillation and diabetes. Rates of guideline-directed medical therapy (GDMT) use at discharge were generally higher among those with EF≤30%, including greater use of triple therapy (ACEI/ARB/ARNI + beta-blocker + MRA). Among 20,387 patients age ≥65 years linked to Medicare, compared with patients with EF 31-40%, patients with EF≤30% faced higher rates of 12-month mortality and HF hospitalization, but similar rates of all-cause hospitalization. Conclusions: Among patients hospitalized for worsening chronic HFrEF in US clinical practice, most patients have severely reduced EF≤30%. Despite modestly higher use of GDMT at discharge and younger age, patients with severely reduced EF face heightened post-discharge risk of death and HF hospitalization.

Comparison of Spleen-Preservation vs Splenectomy in Minimally Invasive Distal Pancreatectomy: A Propensity-Matched Analysis

Introduction: Spleen-preservation during minimally invasive distal pancreatectomy (MIDP) can be technically challenging and remains controversial. Our primary aim was to compare minimally invasive distal pancreatectomy and splenectomy (MDPS) with minimally invasive spleen-preserving distal pancreatectomy (MSPDP). Secondary, we compared 2 spleen-preserving techniques. Methods: Adults undergoing MSPDP or MDPS (2001-2021) were retrospectively included in this single-center study. Patients were optimally matched using age, gender, American Society of Anesthesiologists score, BMI, and tumor size using MatchIt. Intraoperative and postoperative outcomes were compared using the Mann-Whitney U test for continuous data, and Fisher’s exact test for categorical data. Results: Of the 296 patients who underwent MIDP, 173 (58%) had spleen-preservation via the Warshaw technique (129;75%) or vessel-preservation (44;25%). All MDPSs were matched 1:1 to a spleen-preserving case with absolute standardized mean differences for all matching covariates below 0.20. The MSPDP group had shorter length of stay (3 vs 4 days, p = 0.01), fewer conversions to open (1 vs 13, p < 0.01) and less blood loss (p < 0.01) compared with MDPS. Operative times were comparable (245 vs 214 minutes, p = 0.16). No differences were found between the two spleen-preserving techniques. At a median follow-up of 42 (interquartile range 18-19) months, only 2 (1.2%) patients after MSPDP had required splenectomy (1 Warshaw for abscess, 1 vessel-preserving for variceal bleeding). Conclusion: Spleen-preservation does not carry the price of greater risk of blood loss, longer hospital stay, conversion, nor lengthy operating room times. Late splenectomy is very rarely required. Given the immune consequences of splenectomy, spleen-preservation should be preferred in MIDP when oncologically appropriate.

Top Surgery and Chest Dysphoria Among Transmasculine and Nonbinary Adolescents and Young Adults

Transgender and nonbinary (TGNB) adolescents and young adults (AYA) designated female at birth (DFAB) experience chest dysphoria, which is associated with depression and anxiety. Top surgery may be performed to treat chest dysphoria. To determine whether top surgery improves chest dysphoria, gender congruence, and body image in TGNB DFAB AYA. This is a nonrandomized prospective cohort study of patients who underwent top surgery between December 2019 and April 2021 and a matched control group who did not receive surgery. Patients completed outcomes measures preoperatively and 3 months postoperatively. This study took place across 3 institutions in a single, large metropolitan city. Patients aged 13 to 24 years who presented for gender-affirming top surgery were recruited into the treatment arm. Patients in the treatment arm were matched with individuals in the control arm based on age and duration of testosterone therapy. Patients in the surgical cohort underwent gender-affirming mastectomy; surgical technique was at the discretion of the surgeon. Patient-reported outcomes were collected at enrollment and 3 months postoperatively or 3 months postbaseline for the control cohort. The primary outcome was the Chest Dysphoria Measure (CDM). Secondary outcomes included the Transgender Congruence Scale (TCS) and Body Image Scale (BIS). Baseline demographic and surgical variables were collected, and descriptive statistics were calculated. Inverse probability of treatment weighting (IPTW) was used to estimate the association of top surgery with outcomes. Probability of treatment was estimated using gradient-boosted machines with the following covariates: baseline outcome score, age, gender identity, race, ethnicity, insurance type, body mass index, testosterone use duration, chest binding, and parental support. Overall, 81 patients were enrolled (mean [SD] age, 18.6 [2.7] years); 11 were lost to follow-up. Thirty-six surgical patients and 34 matched control patients completed the outcomes measures. Weighted absolute standardized mean differences were acceptable between groups with respect to body mass index, but were not comparable with respect to the remaining demographic variables baseline outcome measures. Surgical complications were minimal. IPTW analyses suggest an association between surgery and substantial improvements in CDM (-25.58 points; 95% CI, -29.18 to -21.98), TCS (7.78 points; 95% CI, 6.06-9.50), and BIS (-7.20 points; 95% CI, -11.68 to -2.72) scores. Top surgery in TGNB DFAB AYA is associated with low complication rates. Top surgery is associated with improved chest dysphoria, gender congruence, and body image satisfaction in this age group.

Very high PD-L1 expression as a prognostic indicator of overall survival among patients with advanced non-small cell lung cancer receiving anti-PD-(L)1 monotherapies in routine practice.

Programmed death or ligand-1 (PD-(L)1) pathway inhibitors confer improved survival as the first-line treatment for advanced non-small cell lung cancer (aNSCLC) in patients with PD-L1 expression (PD-L1 + e ≥ 50%) compared to platinum-doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients with PD-L1 + e of ≥50% receiving pembrolizumab monotherapy, very high levels of PD-L1 + e (≥90%) may be associated with better outcomes. We sought to assess whether very high PD-L1 + e (≥90%) compared to high PD-L1 + e (50%-89%) is associated with an overall survival benefit in aNSCLC patients receiving anti-PD-(L)1 monotherapies. We conducted a single-site retrospective cohort study of aNSCLC patients who initiated PD-(L)1 inhibitor monotherapy as the first-line treatment from October 24, 2016, to August 25, 2021, and had a PD-L1 + e ≥ 50%. The primary outcome was overall survival, measured from the start of the first-line PD-(L)1 inhibitor monotherapy (index date) to date of death or last confirmed activity prior to the cohort exit date. Propensity score-based inverse probability weighting (IPW) was used to control for confounding in Kaplan-Meier curves and Cox proportional hazard regression analysis. One hundred sixty-six patients with aNSCLC receiving PD-(L)1 inhibitor monotherapy met inclusion criteria. 54% were female, 90% received pembrolizumab, median age was 68 years, 70% had non-squamous cell carcinoma, 94% had a history of smoking, 29% had a KRAS mutation, and 37% had very high PD-L1 + e. Unweighted covariates at cohort entry were similar between groups (absolute standardized mean differences [SMDs] <0.1) except for race (SMD=0.2); age at therapy initiation (SMD=0.13); smoking status (SMD=0.13), and BRAF mutation status (SMD=0.11). After weighting, baseline covariates were well balanced (all absolute SMDs <0.1). In the weighted analysis, having a very high PD-L1 + e was associated with lower mortality (weighted hazard ratio 0.57, 95% CI 0.36-0.90) and longer median survival: 3.85 versus 1.49 years. Very high PD-L1 + e (≥90%) was associated with an overall survival benefit over high PD-L1 + e (50%-89%) in patients receiving the first-line PD-(L)1 inhibitor monotherapy in a model controlling for potential confounders. These findings should be confirmed in a larger real-world data set.

Treatment strategy of dabigatran etexilate following the availability of idarucizumab in Japanese patients with non-valvular atrial fibrillation: J-Dabigatran Surveillance 2

BackgroundIdarucizumab, a dabigatran-specific reversal agent, was launched in Japan in 2016. The J-Dabigatran Surveillance 2 study was designed to assess the characteristics and outcomes of dabigatran-treated patients after the launch of idarucizumab. MethodsPatient characteristics and outcomes, including thromboembolic and bleeding events, of dabigatran-naïve patients with non-valvular atrial fibrillation (NVAF) who received dabigatran etexilate [110 mg or 150 mg twice-daily (b.i.d.)] for the prevention of ischemic stroke and systemic embolism were investigated and presented descriptively. Absolute standardized differences (ASD) in baseline characteristics compared with the first J-Dabigatran Surveillance (J-Dabi1; 2011–2013) study were included. ResultsIn total, 5660 patients were enrolled and 5436 were analyzed in this study; 3516 and 1898 received 110 mg b.i.d. and 150 mg b.i.d. dabigatran, respectively; 22 received other doses. The overall duration of follow-up (mean ± standard deviation) was 287 ± 179 days. Baseline characteristics, including stroke/bleeding-risk scores, were typical of this patient population. Overall, paroxysmal, persistent, permanent, and symptomatic atrial fibrillation were observed for 53.2%, 27.1%, 13.7%, and 53.9% of patients, respectively (J-Dabi1 ASD: 0.2, 0.0, 0.3, and 0.2, respectively). Catheter ablation was selected in 27.9% of patients (J-Dabi1 ASD: 0.6).Rates of clinical outcomes were low in the study (mostly <2%/year). The incidence rate of major bleeding was 1.1%/year (n = 46) and stroke/transient ischemic attack/systemic embolism was 1.7%/year (n = 71). Twelve (0.2%) patients received idarucizumab, commonly for serious bleeding events, and most recovered. ConclusionsDabigatran continues to be safe and well tolerated in patients with NVAF for stroke and systemic embolism prevention and continues to be prescribed appropriately. Treatment outcomes have not changed since the availability of idarucizumab. Since the J-Dabi1 study, treatment guidelines for anticoagulation use in NVAF have been updated based on emerging clinical evidence, accounting for differences in patient characteristics, and making dabigatran a preference for distinct patient populations.