Inverse Propensity Score Weighting Research Articles

Parent-Child Mismatch in Educational Expectations and Depressive Symptoms among Chinese Adolescents.

The roles of both parents' and children's educational expectations in shaping adolescent depressive symptoms have increasingly been discussed, yet in a separate manner. To date, few studies have associated parent-child mismatch in educational expectations with depressive symptoms, and less is known about the variation in the association across gender (male vs. female), educational level (primary vs. secondary), and region status (urban vs. rural) in the Chinese educational setting. Respondents were from a nationally representative sample of adolescent students in China (sample size: 1844; age range: 10-15 years). Parent-child mismatch in educational expectations included three categories: (1) "match", (2) "mismatch-parent higher", and (3) "mismatch-parent lower". Regression analysis with inverse propensity-score weighting was employed to estimate the effect of parent-child mismatch as to educational expectations on depressive symptoms, and stratified analysis was used to examine the variation of the effect by gender, educational level, and region. Compared with the "match" group, the "mismatch-parent higher" group had significantly higher levels of depressive symptoms. Furthermore, the pattern remained consistent between boys and girls, but differed significantly by adolescents' educational level and region status. Specifically, the pattern was more pronounced in the primary school and urban subsamples. Findings in this study indicated that educators and policymakers can develop tailored strategies to alleviate depressive symptoms among the "mismatch-parent higher" group, and especially for those children from primary schools and urban areas.

Unemployment’s long shadow: the persistent impact on social exclusion

This paper studies the long-term consequences of unemployment on different dimensions of social exclusion. Based on longitudinal linked survey and administrative data from Germany and an event study analysis combined with inverse propensity score weighting, I document that becoming unemployed has lasting adverse effects on both individuals’ material well-being and their subjective perception of social status and integration, persisting even after four years. An examination of effect heterogeneity underscores that the enduring effects of job loss are more pronounced for individuals confronted with challenging labor market conditions, those with a history of repeated unemployment, and individuals with lower levels of educational attainment.

Complete versus incomplete revascularization in patients with a non-ST-elevation myocardial infarction: Analysis from the e-ULTIMASTER registry

BackgroundIncomplete revascularization (ICR) has been associated with a worse prognosis after a percutaneous coronary intervention (PCI). In NSTEMI patients with multivessel disease (MVD) however, the benefit of a complete revascularization (CR) remains unclear. MethodsPatients presenting with an NSTEMI and MVD were selected from the global e-ULTIMASTER registry and grouped according to completeness of revascularization at index hospitalization discharge. The primary endpoint was the patient oriented composite endpoint (POCE) defined as all death, any myocardial infarction, and any revascularization at 1 year. Target lesion failure (TLF) was defined as the composite of cardiac death, target vessel related myocardial infarction and clinically driven target lesion revascularization. Inverse propensity score weighting (IPSW) was performed to harmonize the patient's baseline characteristics between the groups. ResultsCR was achieved in 1800 patients (47.0 %) and ICR in 2032 patients (53.0 %). The incidence of POCE at 1 year was lower in the CR group compared to the ICR group: 7.0 % vs. 12.9 %, p < 0.0001. Similarly for TLF at 1 year: 3.6 % vs. 5.5 %, p < 0.01. After IPSW, the incidence of POCE was 7.7 % vs. 12.0 %, p < 0.0001, due to a lower all-cause mortality: 2.7 % vs. 4.2 %, p = 0.02 and less revascularizations: 4.9 % vs. 7.9 %, p < 0.001. The incidence of TLF was no longer statistically significant: CR 3.9 % vs. IR 5.0 %, p = 0.10. ConclusionsPatients with a NSTEMI and multi vessel disease undergoing a percutaneous coronary revascularization with a complete revascularization during index hospitalization have better 1-year clinical outcomes. Randomized studies are warranted to confirm these results.

Real-world data on polysomnography- and patient-reported outcomes in hypoglossal nerve stimulation and auto-titrating positive airway pressure therapy for obstructive sleep apnea

BackgroundFew data are available comparing first-line positive airway pressure (PAP) therapy of obstructive sleep apnea (OSA), especially auto-adjusting PAP (aPAP), with second-line hypoglossal nerve stimulation (HGNS) therapy. The aim of this study was to directly compare these therapeutic options by standard polysomnography (PSG)-related parameters and patient-reported outcomes in comparable groups. Methods20 patients (aged 57.30 ± 8.56 years; 6 female) were included in the HGNS and 35 patients (aged 56.83 ± 9.20 years; 9 female) were included in the aPAP group. In both groups participants had to fit the current guideline criteria for HGNS treatment. Groups were compared by analysis of covariance (ANCOVA) using inverse propensity score weighting. ResultsPropensity scores did not differ between groups. Pre-therapeutic AHI (HGNS: 40.22 ± 12.78/h; aPAP: 39.23 ± 12.33/h) and ODI (HGNS: 37.9 ± 14.7/h, aPAP: 34.58 ± 14.74/h) were comparable between the groups. After 413.6 ± 116.66 days (HGNS) and 162.09 ± 140.58 days (aPAP) of treatment AHI (HGNS: 30.22 ± 17.65/h, aPAP group: 4.71 ± 3.42/h; p < 0.001) was significantly higher in the HGNS group compared to the aPAP group. However, epworth sleepiness scale (ESS) was post-interventionally significantly lower in the HGNS group compared to the aPAP group (pretherapeutic: HGNS: 13.32 ± 5.81 points, aPAP: 9.09 ± 4.71 points; posttherapeutic: HGNS: 7.17 ± 5.06 points; aPAP: 8.38 ± 5.41 points; p < 0.01). ConclusionThese are novel real-world data. More research on the key parameters regarding titration of the HGNS neurostimulation parameter tuning and on the impact of factors influencing HGNS adherence is needed.

Oral ethanol prescribing for alcohol withdrawal syndrome: initial findings and future directions following implementation within a United Kingdom National Health Service setting

Introduction Prescribing of ethanol may be an alternative to benzodiazepines for managing alcohol withdrawal syndrome. We present our experience of oral ethanol prescribing within an acute United Kingdom National Health Service setting. Methods A retrospective review of patients presenting with alcohol withdrawal who were managed with oral ethanol or benzodiazepines was performed from data collected across two acute care settings. Ethanol prescribing inclusion: high risk of delirium tremens, or a history of harmful alcohol consumption (typically ≥30 units/day; in which 1 unit = 8 grams of alcohol; one standard United States drink = 14 grams of alcohol) or known to have a history of severe alcohol withdrawal, alcohol-related seizures or delirium tremens. Inverse propensity score weighting was used to partially account for variance between the two patient populations. Results Fifty (82 per cent male; average age 50.9 years) and 93 (84 per cent male; average age 46.5 years) patients in receipt of benzodiazepines or ethanol, respectively, were included. The likelihood of hospital admission was significantly reduced when individuals were managed with ethanol (odds ratio 0.206 (95 per cent confidence interval; 0.066-0.641), Wald chi-square P = 0.006). In those not admitted, the treatment type had no significant impact on length of stay or the number of occasions a pharmacological agent was required. In those admitted, treatment had no significant effect on length of stay. Discussion We offer preliminary evidence to support a role of oral ethanol in the management of patients with alcohol withdrawal. We have implemented a robust and translatable guideline. Despite limitations in the data set the impact of ethanol in reducing the likelihood of admission remained significant. Conclusions In individuals at significant risk of severe alcohol withdrawal, prescribing ethanol as part of a comprehensive care plan, may reduce unplanned admissions. The preliminary findings presented here warrant further assessment through prospective studies.

The effects of hoof health and hoof trimming on farm profitability

Animal diseases pose a significant threat to the global livestock industry, with severe economic consequences. To minimize this impact, farmers employ various preventative measures, with hoof trimming being the most common method for addressing hoof disorders. This study analysed the economic effects of hoof trimming on dairy farms, using a panel dataset containing three years of hoof health data across Finland. This was an observational study that also addressed the issue with unavoidable confounders. To reduce bias, inverse propensity score weighting (IPW) was used, which assigned weights based on the probability density function of treatment frequency. By reweighting the data, this study improved the validity of the causal inference in the presence of confounding unobserved variables. The results of the study indicated that both infectious and non-infectious hoof disorders were notable on dairy farms in Finland. Furthermore, frequency of hoof trimming was influenced by several factors, including hoof health, farm characteristics, and management decisions. The analysis suggested a U-shaped relationship between hoof trimming and farms' profitability. Although the profitability ratio initially decreased, it increased after reaching a hoof trimming level of 97 %. The study highlighted how important systematic and regular hoof trimming is to maintain profitability.

Metformin Use in Type 2 Diabetics and Delirium After Noncardiac Surgery: A Retrospective Cohort Analysis.

The cause of postoperative delirium is unknown, but it is thought to result at least in part from inflammation. Metformin, besides its hypoglycemic properties, demonstrates anti-inflammatory effects systemically and in the brain. We tested the primary hypothesis that chronic metformin use in adults with type 2 diabetes is associated with less delirium during the first 5 days after major noncardiac surgery. Secondary outcomes were a composite of serious complications (myocardial infarction, cardiac arrest, stage 2-3 acute kidney injury [AKI], and mortality) and time to discharge alive. We considered adults with type 2 diabetes who did or did not routinely use metformin daily and had noncardiac surgery. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or brief Confusion Assessment Method (bCAM) for 5 postoperative days. Postoperative AKI was defined by Kidney Disease Improving Global Guidelines. Logistic regression and generalized estimating equation models accounted for within-patient correlation across multiple surgeries and explored the association between metformin use and postoperative delirium and complications. Inverse propensity score weighting and propensity score calibration (PSC) adjusted for confounding variables. No significant difference was observed in the incidence of postoperative delirium between the 2 groups, with 260 of 4744 cases (5.5%) among metformin users and 502 of 5918 cases (8.5%) cases in nonmetformin users, for an odds ratio of 0.88 (95% confidence interval [CI], 0.73-1.05; P = .155), number-needed-to-expose = 118 patients. Similarly, there were fewer composite complications in metformin users (3.3%) than in nonusers (11.7%); However, the common-effect odds ratio of 0.67 was not statistically significant (97.5% CI, 0.39-1.17; P = .106). Discharge from the hospital was significantly faster in patients who took metformin (3 [interquartile range, IQR, 1-5] days for metformin users and 3 [IQR, 2-6] days for nonmetformin users), with a hazard ratio of 1.07 for early discharge, and tight CIs (1.01-1.13). Chronic metformin use was associated with slightly and nonsignificantly less delirium. However, patients who used metformin had clinically meaningfully fewer major complications, mostly stage 2 to 3 kidney injury. While not statistically significant, the reduction was substantial and warrants further investigation because there is currently no effective preventive measure for perioperative renal injury. Benefit would be especially meaningful if it could be produced by acute perioperative treatment. Finally, metformin was associated with faster hospital discharge, although not by a clinically meaningful amount.

Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry

PurposeWe used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the two pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the two monthly treatment arms from the clinical trial. DesignRetrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data SubjectsAll treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for one year from either the CATT or the IRIS Registry MethodsPatients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all non-imaging based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity. ResultsWe identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n= 281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n=261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (Exact Matching: 1.9 letters +/- 14.0 vs. IPSW: 2.8 letters +/- 15.0 letters, p=0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (Exact Matching: 2.4 letters +/- 15.4 vs. IPSW: 2.1 letters +/- 16.0 letters, p=0.79). ConclusionsBoth exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared to the clinical trial.

Approximate balancing weights for clustered observational study designs.

In a clustered observational study, a treatment is assigned to groups and all units within the group are exposed to the treatment. We develop a new method for statistical adjustment in clustered observational studies using approximate balancing weights, a generalization of inverse propensity score weights that solve a convex optimization problem to find a set of weights that directly minimize a measure of covariate imbalance, subject to an additional penalty on the variance of the weights. We tailor the approximate balancing weights optimization problem to the clustered observational study setting by deriving an upper bound on the mean square error and finding weights that minimize this upper bound, linking the level of covariate balance to a bound on the bias. We implement the procedure by specializing the bound to a random cluster-level effects model, leading to a variance penalty that incorporates the signal-to-noise ratio and penalizes the weight on individuals and the total weight on groups differently according to the the intra-class correlation.

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors

Children undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As cancer survivors, they face a high burden of long-term adverse effects. The association between sepsis during anticancer therapy and long-term organ dysfunction in adult survivors of childhood cancer has not been examined. To determine whether severe sepsis during therapy for leukemia in childhood is associated with subsequent chronic health conditions in adult survivors. This cohort study included 644 adult survivors of childhood leukemia who were diagnosed between January 1, 1985, and July 19, 2010, and participated in the St Jude Lifetime Cohort Study. Participants were excluded if they received hematopoietic cell transplant or had relapsed leukemia. Data collection ended June 30, 2017. Data were analyzed from July 1, 2020, to January 5, 2024. Severe sepsis episodes, defined according to consensus criteria as septic shock, acute respiratory distress syndrome, or multiorgan dysfunction associated with infection occurring during anticancer therapy, were abstracted by medical record review for all participants. Common Terminology Criteria for Adverse Events-defined chronic health condition outcomes were independently abstracted. Associations between sepsis and cumulative incidence of chronic health conditions (eg, cardiovascular, pulmonary, kidney, neurological, and neurocognitive outcomes) were compared by adjusted hazard ratios from Cox proportional hazards logistic regression. Inverse propensity score weighting was used to adjust for potential confounders, including age, year of diagnosis, and leukemia type. The study sample consisted of 644 adult survivors of pediatric leukemia (329 women [51.1%] and 315 men [48.9%]; including 56 with a history of acute myeloid leukemia and 585 with a history of acute lymphoblastic leukemia) who were most recently evaluated at a median age of 24.7 (IQR, 21.2-28.3) years at a median time after leukemia diagnosis of 17.3 (IQR, 13.7-21.9) years. Severe sepsis during treatment of acute childhood leukemia occurred in 46 participants (7.1%). Participants who experienced severe sepsis during treatment were more likely to develop moderate to severe neurocognitive impairment (29 of 46 [63.0%] vs 310 of 598 [51.8%]; adjusted hazard ratio, 1.86 [95% CI, 1.61-2.16]; P < .001) significantly affecting attention, executive function, memory and visuospatial domains. Sepsis was not associated with long-term risk of cardiovascular, pulmonary, kidney, or neurological chronic health conditions. In this cohort study of long-term outcomes in survivors of pediatric leukemia, severe sepsis during anticancer therapy for leukemia was associated with a selectively increased risk for development of serious neurocognitive sequelae. Efforts to reduce the effects of anticancer therapy on long-term function and quality of life in survivors might include prevention of severe sepsis during therapy and early detection or amelioration of neurocognitive deficits in survivors of sepsis.

Effectiveness of a 5-year health empowerment programme on promoting cardiovascular health for adults from low-income families in Hong Kong

ObjectiveThis study aimed to evaluate the effectiveness of a health empowerment programme (HEP) to enhance cardiovascular health for adults from low-income families. MethodsA prospective cohort study (N = 219, Intervention group: n = 103, comparison group: n = 116) was conducted with participants recruited from January 2013 to November 2015 and followed up until January 2022. Throughout the study duration, intervention group were invited to participate in the HEP. The cardiovascular health status of both groups at baseline and follow-up were assessed using the adapted Ideal Cardiovascular Health Index (ICHI) defined by the American Heart Association. After inverse propensity score weighting, multiple linear regression and Poisson regression were employed to examine the effects of the HEP. ResultsThe HEP was associated with a greater increase in ICHI total score (B = 0.33, p < 0.001), and the increase of proportion of people achieving a normal blood pressure (Incidence rate ratio: 3.39, p < 0.05). ConclusionHEP can be an effective and sustainable strategy to reduce social disparities in cardiovascular health of adults from low-income families, as indicated by improvement in the ICHI total score and blood pressure status. Practical ImplicationsThe sustainable HEP in the community setting has potential for generalizability and scalability to other financially challenged families.

Association of Intravenous Neostigmine and Anticholinergics or Sugammadex with Postoperative Delirium: A Retrospective Cohort Study.

Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular blocks may precipitate delirium through impairment of central cholinergic transmission, which could be avoided by using sugammadex. Therefore, we tested the primary hypothesis that postoperative delirium is less common when neuromuscular block is reversed with sugammadex than with neostigmine combined with glycopyrrolate or atropine. We conducted a single-center retrospective cohort study, analyzing all adult patients having general anesthesia for noncardiac surgery who received neostigmine or sugammadex from January 2016 to March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for appropriate confounders. Our primary outcome was presence of delirium within the first 4 days after surgery, defined as at least 1 positive brief Confusion Assessment Method (bCAM) screening. The secondary outcome was the presence of early delirium within 24 hours of surgery. Among 49,468 cases in our analysis, 6881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ between the sugammadex and neostigmine groups, with an estimated odds ratio (95% confidence interval) of 1.33 (0.91-1.95), P = .147. A sensitivity analysis restricted to only include cases with at least 6 bCAM measurements over postoperative day (POD) 1 to 4 had consistent results, as sugammadex compared with neostigmine was associated with an estimated odds ratio for postoperative delirium of 1.20 (0.82-1.77), P = .346. Sugammadex was significantly associated with an increased incidence of early postoperative delirium, with an estimated odds ratio of 1.71 (1.07-2.72), P = .025. Further analysis showed no treatment-by-age interaction for either postoperative delirium (P = .637) or postoperative early delirium (P = .904). Compared to neostigmine, use of sugammadex for reversal of neuromuscular block was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Though sugammadex was associated with a statistically significant increased risk of postoperative early delirium, the difference was small and not clinically relevant, and may reflect the presence of unknown confounders.

Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: a nationwide cohort study from the French Health Insurance Database (SNDS)

ObjectiveTo assess the risk of serious infection associated with different targeted therapies for psoriatic arthritis (PsA) in real-world settings.MethodsThis nationwide cohort study used the administrative healthcare database of the French...

Association between the surgical approach and prognosis of spontaneous supratentorial deep intracerebral hemorrhage

The association between surgical approach and prognosis in patients with spontaneous supratentorial deep intracerebral hemorrhage is unclear. We aimed to explore the association between surgical approach and prognosis in these patients. A retrospective cohort of 311 patients from 3 centers who were treated with surgery 24 h after ictus was recruited. The surgical procedure involved removing the intracerebral hematoma using an aspirator through either the cortical approach or Sylvian fissure approach, assisted by an endoscope or microscope. The primary outcome was the one-year modified Rankin scale (mRS) score. The association between the surgical approach and the one-year mRS score was explored by using ordinal logistic regression and binary logistic regression. Baseline characteristics were balanced by propensity score matching and inverse propensity score weighting. In the adjusted analysis, compared with the cortex approach group, the Sylvian fissure approach group had better one-year mRS scores when analyzed as an ordinal variable (3.00 [2.00–4.00] vs. 4.00 [3.00–5.00]; adjusted odds ratio, 3.15; 95% CI, 1.78–5.58; p < 0.001) and a dichotomous variable (74.14% vs. 49.01%; adjusted odds ratio, 6.61; 95% CI, 2.75–15.88; p < 0.001). Surgical approach was not significantly associated with rebleeding (p = 0.88) or three-month mortality (p = 0.81). In univariate analysis after propensity score matching, there were significant differences in one-year mRS score between the two groups (p < 0.001), and there were no significant differences in rebleeding (Fisher’s exact test, p > 0.999) or three-month mortality (Fisher's exact test, p > 0.999). Inverse probability weighted regression analysis showed better one-year mRS scores when analyzed as an ordinal variable (adjusted odds ratio, 3.03; 95% CI, 2.17–4.17; p < 0.001) and a dichotomous variable (adjusted odds ratio, 3.11; 95% CI, 2.16–4.77; p < 0.001) in the Sylvian fissure approach group; the surgical approach was not significantly associated with rebleeding (p = 0.50) or three-month mortality (p = 0.60). In the surgical treatment of patients with spontaneous supratentorial deep intracerebral hemorrhage, the Sylvian fissure approach may lead to a better functional outcome compared with the cortex approach. Future prospective studies are warranted to confirm this finding.

Performance of modeling and balancing approach methods when using weights to estimate treatment effects in observational time-to-event settings

In observational studies weighting techniques are often used to overcome bias due to confounding. Modeling approaches, such as inverse propensity score weighting, are popular, but often rely on the correct specification of a parametric model wherein neither balance nor stability are targeted. More recently, balancing approach methods that directly target covariate imbalances have been proposed, and these allow the researcher to explicitly set the desired balance constraints. In this study, we evaluate the finite sample properties of different modeling and balancing approach methods, when estimating the marginal hazard ratio, through Monte Carlo simulations. The use of the different methods is also illustrated by analyzing data from the Swedish stroke register to estimate the effect of prescribing oral anticoagulants on time to recurrent stroke or death in stroke patients with atrial fibrillation. In simulated scenarios with good overlap and low or no model misspecification the balancing approach methods performed similarly to the modeling approach methods. In scenarios with bad overlap and model misspecification, the modeling approach method incorporating variable selection performed better than the other methods. The results indicate that it is valuable to use methods that target covariate balance when estimating marginal hazard ratios, but this does not in itself guarantee good performance in situations with, e.g., poor overlap, high censoring, or misspecified models/balance constraints.

An Interplay between Health Equity and Disparity in Cognitive Decline

AbstractBackgroundCognitive decline may be an early indicator of Alzheimer diseases and related dementia (ADRD). To identify the intervention targets that ameliorate disparities in ADRD, it is critical to employ disparity measures that account for health equity. We aimed to investigate disparity estimates in cognitive decline built on three health equity measures.MethodThe study sample (n = 451) was derived from the bi‐ethnic community‐dwelling San Antonio Longitudinal Study of Aging (SALSA). The latent variable mixture model classified cognitive function trajectory strata based on four repeated measures of the Mini Mental Status Examination (MMSE) over 8.5±1.3 years of follow‐up. Three risk adjustments were employed to optimize equity in social determinants of health (SDoH: income, education, social interactions) between Hispanics and non‐Hispanics. 1) Average constrained regression adjustment minimized the impact of SDoH for Hispanics. 2) Covariance constrained adjustment derived estimates with a near independence between the residuals with ethnicity. 3) Net compensation penalized regression imposed a penalty for excess lower MMSE among Hispanics. Inverse propensity score weighting (IPSW) estimates of disparity further adjusted away confounding due to covariates (demographics, disease burdens) between ethnic groups.ResultTable 1 contrasted baseline characteristics of the study sample between Hispanics and non‐Hispanics. Two MMSE trajectory strata were identified: cognitive decline stratum (38%) with mean MMSE decreased from 23.9 to 21.2; and stable cognitive function stratum (62%) with mean MMSE around 28 throughout. Average constrained and covariance constrained risk adjustments attained optimal SDoH equity across three fairness metrics: predictive ratios, fair covariance, and net compensation (Table 2). Ethnic disparity in cognitive decline (Table 3) was strong conditioned on SDoH equity alone (log(aOR) = 4.27, p&lt;0.001). Balancing covariates alone via IPSW without equity in SDoH also fell short for parity (aOR = 1.16, p&lt;0.001). Parity in cognitive decline could be achievable under both SDoH equity and balanced covariates between ethnic groups (aOR = 0.85, p = 0.21).ConclusionOur study suggested that integrating equity metrices in ADRD disparity research could guide the paths to improve equity and reduce disparity. The field would be better served by identifying the causal drivers of disparities through the advancement in equity metrices and mediation analyses that delineate intricate interactions between SDoH and ADRD risk factors.

Metformin use and stroke risk in Hispanic and non‐Hispanic veteran men with type 2 diabetes

AbstractBackgroundStroke is a strong risk factor for dementia in the elderly. Traditional stroke risk factors such as hypertension and diabetes are also associated with the incidence and progression of dementia. There is a lack of data characterizing the effect of metformin use on stroke in racially/ethnically diverse cohorts. We sought to evaluate the impact of metformin as a preventative treatment in reducing the incidence of stroke risk in a cohort of older US veteran men with type 2 diabetes (T2D).MethodOur cohort included men with T2D, ≥65 years old, insulin/thiazolidinediones naïve, and without stroke history. Metformin use was defined as ≥180 days of prescription during 2002‐2003. Stroke incidence was identified by ICD9 codes 430‐438 (excluding TIA, 435) from inpatient/outpatient visits every year during 2004‐2012. Generalized estimating equations were used to estimate the odds ratios (OR) of stroke diagnosis over time associated with metformin use, where inverse propensity score weights (IPSW) for metformin use were incorporated to minimize confounding. Furthermore, the generalizability method was used to compare IPSW adjusted ORs between race/ethnicity groups after calibrating covariates between groups. Finally, inverse probability weights for survival were incorporated to project the adjusted ORs among the survivors.ResultAmong 19,705 men with T2D, 81.3% were non‐Hispanic White, 5.3% Hispanic White, and 13.4% were non‐Hispanic Black. Overall, 26.7% used metformin (35.2% of Hispanic Whites, 27% of non‐Hispanic Whites, and 21.4% of non‐Hispanic Blacks). Metformin use was associated with attenuating the temporal increase in stroke risk during 2009‐2012 (vs. 2004‐2008) among Hispanic White (log(aOR) = ‐0.05, p‐value = 0.02), This stroke risk attenuation effect by metformin use was marginally different between Hispanic White with non‐Hispanic Black (p = 0.056) and significantly different between Hispanic White and non‐Hispanic White (p = 0.02). The stroke risk attenuation effect of metformin was not significant conditioned on survival.ConclusionOur study suggests that metformin use is associated with a reduced distal stroke risk amongst men of Hispanic ethnicity compared to non‐Hispanics. Further studies are needed to elucidate the putative biological or pharmacological mechanism for this difference and to uncover the impact on dementia risk.

Progression-Free Survival but Not Overall Survival Is Superior in Relapsed/Refractory Large B-Cell Lymphomas Treated with Axicabtagene Ciloleucel Compared to Tisagenlecleucel: Results of the CART-SIE Real Life Italian Study

Introduction The CART-SIE is a national prospective/retrospective observational study aimed at collecting the real-life data of all consecutive lymphoma patients treated with CAR-T cells in the Italian centers. Given the recognized efficacy of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) in relapsed/refractory large B-cell lymphoma (R/R LBCL) after at least two previous treatments, the best product in terms of efficacy and safety is still a matter of debate. Riedell reported comparable outcomes between axi-cel and tisa-cel in patients treated in 8 US centers; on the other hand, Bachy demonstrated, in a matched comparison, that axi-cel had a higher efficacy and a higher toxicity compared to tisa-cel. Methods On these bases, we conducted a subgroup analysis in the CART-SIE study, with the aim to evaluate the outcome (ORR, DoR, OS, PFS), and the safety (CRS, ICANS) of all R/R LBCL treated with different CAR-T (axi-cel versus tisa-cel) (primary mediastinal B-cell lymphoma, PMBCL, were excluded). A propensity score (PS) model estimated for the probability of being treated with tisa-cel (arbitrary) was performed. Variables used for the PS model (accordingly to Bachy, 2022) were: histology, age, sex, disease status (relapse vs. refractory), Ann Arbor stage (I/II vs. III/IV), IPI (&amp;lt; 3 vs. &amp;gt;=3), LDH, C reactive protein, bulky disease, N of previous treatments, ASCT, bridging therapy (no vs. yes with response vs. yes without response), time since last treatment and centers size (&amp;gt;=25 vs. &amp;lt; 25 cases contributed). Results From March 2019 to June 2023, 659 patients were leukapheresed; 562 were infused and 556 with adequate follow-up were analyzed: 419 LBCL (229 diffuse large B-cell lymphomas, DLBCL; 77 arising from indolent lymphoma, tFL; 113 high-grade B-cell, HGBCL), 70 PMBCL and 67 mantle cell lymphomas. Here, we analyzed the results of the 419 LBCL: 45% (190) received axi-cel, 55% (229) tisa-cel. Clinical characteristics for axi-cel vs. tisa-cel were: median age 57 years (IQR 50;65) vs. 61 (IQR 52;66), p 0.059; refractory to the last treatment 74% (141) vs. 64% (146), p 0.0309; intermediate-high/high risk IPI 39% (74) vs. 46% (105), p 0.1336. Bridging therapy was performed in 82% (156) patients candidate to receive axi-cel and in 85% (195) tisa-cel, p 0.4263; the ORR to bridging was 28% (53) in patients candidate to axi-cel vs. 30% (68) tisa-cel, p 0.1840. All grade CRS was observed in 88% (168) infused with axi-cel, and in 77% (177) with tisa-cel, p 0.0030. The severe (grade 3-4) CRS was registered in 8% (15) axi-cel and in 8% (18) tisa-cel. All grade ICANS was recorded in 32% (61) treated with axi-cel and in 9% (20) with tisa-cel, p 0.0001; severe ICANS was reported in 9% (18) axi-cel and in 3% (6) tisa-cel. Treatment related mortality was 2% (4) in axi-cel vs. 1% (3) tisa-cel. Median follow-up time for infused patients was 12.07 months (IQR: 6.05, 22.37). The ORR at 30-days after CAR-T was 74% (141) with 53% complete response (CR) in axi-cel; ORR 58% (133) with 39% CR in tisa-cel, p 0.001. DoR at 12-months was 56% (95% CI: 48-67) for axi-cel vs. 49% (95% CI: 40-59) for tisa-cel, p 0.2745. The 12-months OS was 71% (95% CI: 64-79) for axi-cel vs. 60% (95% CI: 53-67) for tisa-cel, p 0.1086. The 12-months PFS was 48% (95% CI: 41-57) for axi-cel vs. 32% (95% CI: 26-39) for tisa-cel, p 0.0003. In a multivariable model with all the clinically relevant variables, the OS for the two products was similar (HR tisa vs. axi: 1.23, 95% CI:0.86-1.75, p 0.2546), whereas the PFS was statistically superior for axi-cel compared to tisa-cel (HR: 1.65, 95% CI: 1.25-2.17, p 0.0004). The stabilized inverse propensity score weighting was applied to the subset of 277 LBCL (DLBCL, HGBCL, tFL) patients with complete data. The final population for weighted analysis included 201 patients, 100 treated with axi-cel and 101 with tisa-cel. The propensity score weighted analysis for tisa-cel vs. axi-cel was calculated; weighted log-rank test p-value for PFS was 0.0287 (Fig 1A), weighted log-rank test p-value for OS was 0.1547 (Fig 1B). Conclusions In the CART-SIE study, the outcome of patients treated with CAR-T was similar to those reported by pivotal trials and real-life studies, with manageable toxicities. At a median follow-up of 12 months, PFS for axi-cel was superior compared to PFS for tisa-cel; this advantage was confirmed in a propensity score analysis. The difference in PFS did not translate in a different OS, so far. CRS and ICANS were higher with axi-cel.

Abstract 12766: Assessing the Economic and Clinical Impact of Surgical Aortic Valve Replacement on Patients With Symptomatic Aortic Valve Regurgitation

Hypothesis: The purpose of this study was to estimate the differences in mortality, healthcare utilization, and annualized cost among patients with symptomatic aortic regurgitation (sAR) who underwent surgical valve replacement (SAVR) compared with those that were managed non-operatively within 12 months of their diagnosis. Methods: Using the Optum® United Health Care Database, we identified 132,317 patients from 2016 to 2021 with a diagnosis of clinically symptomatic aortic regurgitation (sAR) who had a minimum of 6 months of continuous enrollment prior to sAR and at least 12 months of continuous enrollment following sAR and no record of aortic stenosis or transcatheter aortic valve replacement. sAR was defined as ≥ 2 visits for either heart failure, angina, dyspnea, or syncope in the presence of aortic regurgitation. Outcomes were all-cause mortality, healthcare utilization, and annualized cost. Inverse propensity score weighting (IPW) was employed to adjust for baseline differences and included patient demographics and comorbidities measured by the Elixhauser Comorbidity Index. Cox proportional hazards were used to model survival and general linear models were estimated for annualized healthcare utilization and total costs. Results: Among 132,317 patients identified with sAR, only 400 (0.3%) underwent SAVR within the first 12 months of their sAR diagnosis. They were younger on average 65 vs. 75 years (p&lt;0.0001), more often male (71 vs 48%, p&lt;0.0001), and had a slightly higher Comorbidity Index (5.1 vs. 4.8, p=0.0527). After IPW, sAR patients who had SAVR had lower mortality (HR 0.384; 95% CI 0.375-0.394; P&lt;.0001), estimated annualized inpatient visits (0.33 versus 0.43; P=0.0039) and emergency department visits (0.54 versus 0.70; P=0.0002), hospital days (2.70 versus 3.14; P&lt;.0001), and annualized cost ($33,744 versus $41,399; P&lt;.0001). Conclusion: In this retrospective study, SAVR performed within 12 months of the diagnosis of symptomatic aortic regurgitation is associated with improved mortality and lower annualized healthcare utilization and costs. The clinical and economic benefits related to timely surgical management of aortic regurgitation should be considered when managing patients with symptomatic aortic regurgitation.

Mental health and care utilization in survivors of adolescent and young adult cancer.

Adolescent and young adult cancer survivors experience mental health challenges, yet little is known about the evolution of these difficulties. This study explored mental health symptoms and utilization among long-term adolescent and young adult cancer survivors. Using 30 432 respondents from the 2019 National Health Interview Survey, this study compared adults with a history of adolescent and young adult cancer (diagnosed when patients were between 15 and 39 years of age) to adults without adolescent and young adult cancer. Mental health symptom severity was measured using the Patient Health Questionnaire depression scale and 7-item Generalized Anxiety Disorder questionnaires. Care utilization constituted psychotherapy and mental health medication use. Inverse propensity score weights were used to balance demographics and combined with survey weights. Descriptive statistics, multivariable generalized linear models, and structural equation modeling with 2-sided tests were used for analysis. We compared 639 adolescent and young adult survivors with 29 793 controls. Survivors were, on average, 20.5 years (SE = 0.74) past their cancer diagnosis dates. After adjusting for survey and propensity score weights, adolescent and young adult survivors reported more severe depression (incidence rate ratio = 1.42, 95% confidence interval [CI] = 1.09 to 1.84, P < .01) and anxiety (incidence rate ratio = 1.85, 95% CI = 1.55 to 2.21, P < .001). They were more likely to use psychotherapy (odds ratio = 1.91, 95% CI = 1.16 to 3.17, P < .05) and mental health medications (odds ratio = 1.89, 95% CI = 1.15 to 3.11, P < .05). Time since diagnosis was negatively associated with symptoms and utilization. Structural equation modeling demonstrated mediation of utilization effect by symptom severity. Adolescent and young adult survivors experience worse mental health in late survivorship, despite small improvements over time. We highlight the importance of survivorship care that addresses the long-term mental health needs of these survivors.