Propensity Score Model Research Articles

Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy.

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer Institute comorbidity index. Weighted Cox regressions with robust standard error were used to assess the hazard ratio (HR) and 95% confidence interval (CI). We found that among comparable advanced cancers, first-line ICI (n = 1823) and first-line chemo (n = 6345) had similar rates of VTE (8.49% for ICI and 8.36% for chemo at 6 months). The weighted HR was 1.06 (95% CI 0.88-1.26) for ICI versus chemo. In a subgroup analysis restricted to lung cancers, first-line ICI/chemo (n = 828), ICI monotherapy (n = 428), and chemo monotherapy (n = 4371) had similar rates of VTE (9.60% for ICI/chemo, 10.04% for ICI, and 8.91% for chemo at 6 months). The weighted HR was 1.05 (95% CI 0.77-1.42) for ICI versus chemo, and 1.08 (95% CI 0.83-1.42) for ICI/chemo versus chemo. In conclusion, ICI as a systemic therapy has a similarly elevated risk as cytotoxic chemo for VTE occurrence in cancer patients. This finding can inform future prospective studies exploring thromboprophylaxis strategies.

Model Misspecification and Robustness of Observed-Score Test Equating Using Propensity Scores

This study explores the usefulness of covariates on equating test scores from nonequivalent test groups. The covariates are captured by an estimated propensity score, which is used as a proxy for latent ability to balance the test groups. The objective is to assess the sensitivity of the equated scores to various misspecifications in the propensity score model. The study assumes a parametric form of the propensity score and evaluates the effects of various misspecification scenarios on equating error. The results, based on both simulated and real testing data, show that (1) omitting an important covariate leads to biased estimates of the equated scores, (2) misspecifying a nonlinear relationship between the covariates and test scores increases the equating standard error in the tails of the score distributions, and (3) the equating estimators are robust against omitting a second-order term as well as using an incorrect link function in the propensity score estimation model. The findings demonstrate that auxiliary information is beneficial for test score equating in complex settings. However, it also sheds light on the challenge of making fair comparisons between nonequivalent test groups in the absence of common items. The study identifies scenarios, where equating performance is acceptable and problematic, provides practical guidelines, and identifies areas for further investigation.

Evaluating the Performance of High-Dimensional Propensity Scores Compared with Standard Propensity Scores for Comparing Antihypertensive Therapies in the CPRD GOLD Database.

Propensity score (PS) matching is widely used in medical record studies to create balanced treatment groups, but relies on prior knowledge of confounding factors. High-dimensional PS (hdPS) is a semi-automated algorithm that selects variables with the highest potential for confounding from medical databases. The objective of this study was to evaluate performance of hdPS and PS when used to compare antihypertensive therapies in the UK clinical practice research datalink (CPRD) GOLD database. Patients initiating antihypertensive treatment with either monotherapy or bitherapy were extracted from the CPRD GOLD database. Simulated datasets were generated using plasmode simulations with a marginal hazard ratio (HRm) of 1.29 for bitherapy versus monotherapy for reaching blood pressure control at 3months. Either 16 or 36 known covariates were forced into the PS and hdPS models, and 200 additional variables were automatically selected for hdPS. Sensitivity analyses were conducted to assess the impact of removing known confounders from the database on hdPS performance. With 36 known covariates, the estimated HRm (RMSE) was 1.31 (0.05) for hdPS and 1.30 (0.04) for PS matching; the crude HR was 0.68 (0.61). Using 16 known covariates, the estimated HRm (RMSE) was 1.23 (0.10) and 1.09 (0.20) for hdPS and PS, respectively. Performance of hdPS was not compromised when known confounders were removed from the database. With 49 investigator-selected covariates, the HR was 1.18 (95% CI 1.10; 1.26) for PS and 1.33 (95% CI 1.22; 1.46) for hdPS. Both methods yielded the same conclusion, suggesting superiority of bitherapy over monotherapy for time to blood pressure control. HdPS can identify proxies for missing confounders, thereby having an advantage over PS in case of unobserved covariates. Both PS and hdPS showed superiority of bitherapy over monotherapy for reaching blood pressure control.

Humidified atmosphere in a time-lapse embryo culture system does not improve ongoing pregnancy rate: a retrospective propensity score model study derived from 496 first ICSI cycles.

To investigate whether high relative humidity conditions (HC), when using a time-lapse system (TLS) with sequential culture media, are beneficial to embryo culture, improving ongoing pregnancy rates. We included patients undergoing their first ICSI cycle treatment from April 2021 to May 2022. Patients assigned to dry conditions (DC) or HC were 278 and 218, respectively. We used a GERI TLS, three chambers configured in humidity conditions and three in dry conditions. The effect of HC on ongoing pregnancy rate was assessed by the propensity matched sample, to reduce potential differences between women undergoing either HC or DC and reduce biased estimation of treatment effect. After adjusting for several confounding variables and applying the propensity score (PS), no significant differences were observed in the rates of normal (2PN) and abnormal (1PN and 3PN) fertilization, blastulation, top-quality blastocysts, frozen blastocysts, ongoing pregnancies, and miscarriages. The 2-cell (t2) and 4-cell (t4) stages and cell divisions between such stages occurred earlier and were more synchronous in the in DC. These results suggest that HC conditions do not improve the rate of ongoing pregnancy and several embryological outcomes, under the conditions used in this study based on a time-lapse system and sequential culture with day 3 medium change-over.

MP-453089-1 DIGOXIN AND RISK OF VENTRICULAR TACHYARRHYTHMIA AND DEATH IN ICD RECIPIENTS

Digoxin continues to be used in patients with heart failure with reduced ejection fraction (HFrEF), especially among those with atrial fibrillation (AF) with difficult to control ventricular response. However, some studies have shown digoxin use to be associated with adverse outcomes including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in implantable cardioverter defibrillator (ICD) recipients. We sought to assess whether digoxin use would be associated with increased risk of VT/VF in patients with HFrEF who were implanted with a primary prevention ICD in landmark clinical trials. Our study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator (CRT-D) who were enrolled in the four landmark MADIT trials. Propensity score for digoxin at baseline was developed using a wide variety of baseline clinical measures with a logistic regression model stepwise variable selection approach. All potential variables which met a significance level <0.10 were included in the propensity score model. Additionally, a multivariate proportional hazards regression model was developed for the endpoint of VT/VF. This multivariate model was used along with propensity score quintile stratification for the endpoints of VT/VF, death and VT/VF/death. At baseline, 1155 of 4499 patients were on digoxin (26%). Propensity score variables are shown in Table 1. From statistical models using both multivariate adjustment and propensity score quintile stratification, patients prescribed digoxin exhibited a statistically significant 28% increased risk of VT/VF [HR 1.28 (1.10-1.50); p=0.002; Figure 1A], 38% increased risk of the composite of VT/VF or death [HR 1.38 (1.21-1.58); p<0.0001; Figure 1B]; and a 64% increased risk of death [HR 1.64; (1.32-2.04); p<0.0001]. Our findings suggest that digoxin use is associated with a significant increased risk of ventricular tachyarrhythmic events and death among ICD recipients. This adds to the growing evidence that digoxin use is associated with adverse outcomes in certain groups of patients and suggest a need for reconsideration on use of digoxin in HFrEF patients with an ICD.

Association of Single-Nucleotide Polymorphisms in the VDR Gene with Tuberculosis and Infection of Beijing Genotype Mycobacterium tuberculosis.

The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphism and tuberculosis susceptibility, as well as the potential interaction of host genetic factors with the heterogeneity of Mycobacterium tuberculosis in the population from Xinjiang, China. From January 2019 to January 2020, we enrolled 221 tuberculosis patients as the case group and 363 staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in the VDR were detected by sequencing. M. tuberculosis isolates were collected from the case group and identified as Beijing or non-Beijing lineage by multiplex PCR. Propensity score (PS), univariate analysis and multivariable logistic regression models were used to perform the analysis. Our results showed that the allele and genotype frequencies of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in VDR were not correlated with tuberculosis susceptibility or lineages of M. tuberculosis. Two out of six loci of the VDR gene formed one haplotype block, and none of the haplotypes was found to correlate with tuberculosis susceptibility or lineages of M. tuberculosis infected. Polymorphisms in the VDR gene may not indicate susceptibility to tuberculosis. There was also no evidence on the interaction between the VDR gene of host and the lineages of M. tuberculosis in the population from Xinjiang, China. Further studies are nonetheless required to prove our conclusions.

Double robust semi-supervised inference for the mean: selection bias under MAR labeling with decaying overlap

Abstract Semi-supervised (SS) inference has received much attention in recent years. Apart from a moderate-sized labeled data, $\mathcal L$, the SS setting is characterized by an additional, much larger sized, unlabeled data, $\mathcal U$. The setting of $|\mathcal U\ |\gg |\mathcal L\ |$, makes SS inference unique and different from the standard missing data problems, owing to natural violation of the so-called ‘positivity’ or ‘overlap’ assumption. However, most of the SS literature implicitly assumes $\mathcal L$ and $\mathcal U$ to be equally distributed, i.e., no selection bias in the labeling. Inferential challenges in missing at random type labeling allowing for selection bias, are inevitably exacerbated by the decaying nature of the propensity score (PS). We address this gap for a prototype problem, the estimation of the response’s mean. We propose a double robust SS mean estimator and give a complete characterization of its asymptotic properties. The proposed estimator is consistent as long as either the outcome or the PS model is correctly specified. When both models are correctly specified, we provide inference results with a non-standard consistency rate that depends on the smaller size $|\mathcal L\ |$. The results are also extended to causal inference with imbalanced treatment groups. Further, we provide several novel choices of models and estimators of the decaying PS, including a novel offset logistic model and a stratified labeling model. We present their properties under both high- and low-dimensional settings. These may be of independent interest. Lastly, we present extensive simulations and also a real data application.

Compared with conventional insemination, intracytoplasmic sperm injection provides no benefit in cases of nonmale factor infertility as evidenced by comparable euploidy rate

To evaluate if differences in euploidy rates exist between intracytoplasmic sperm injection (ICSI) and conventional insemination (CI) in non-male factor infertility cases. Retrospective cohort study. Single, academically affiliated infertility center in the U.S. A total of 3,554 patients who underwent in-vitro fertilization (IVF) cycles from January 2014 to December 2021. All cycles that had pre-implantation testing for aneuploidy (PGT-A) performed by trophectoderm biopsy and had a post preparation sperm concentration >4 million total motile sperm per milliliter were included. The primary outcome was embryo euploidy rate per embryo biopsied in the ICSI versus CI group. Secondary outcomes included fertilization rate and number of embryos biopsied. Generalized estimating equations with a Poisson distribution was used to estimate the euploid rate ratio (with total embryos biopsied as an offset), while accounting for multiple retrievals per patient. To adjust for confounding, a propensity score model was fit for ICSI using 14 baseline female and male characteristics. Oocytes retrieved and number of embryos biopsied were similar in both groups, while fertilization rate per oocyte retrieved was significantly lower with ICSI (0.64 vs 0.66, p=0.04). The proportion of euploid embryos in the ICSI group was significantly lower when compared to CI (0.47 vs 0.52), with a euploid rate ratio of 0.89 (p<0.001). Interestingly, when accounting for variation in PGT reference laboratories over the study time period, adjusting for date of procedure did not change the relationship between ICSI and euploid rate (RR=0.89, p<0.001); however, after adjusting for PGT reference laboratory, the relationship between ICSI and euploid rate was no longer significant (RR=0.97, p=0.07). In the setting of non-male factor infertility, ICSI resulted in a lower fertilization rate and an 11% lower embryo euploid rate compared to CI. Although the data is not statistically significant when adjusted for PGT reference laboratory, we can still conclude that ICSI does not provide any benefit. This data supports the recommendation that CI should be the preferred methodology of fertilization in non-male factor infertility cases.

Impact of KRAS and NRAS mutations on outcomes in acute myeloid leukemia

The prognostic significance of RAS mutations in AML is poorly understood. In this ambispective cohort study of 239 newly-diagnosed AML patients at the University of Maryland, we assessed the median overall survival (mOS) and median event-free survival (mEFS) in RAS wild-type (WT) AML (n = 196), KRAS-mutated AML (n = 11), NRAS-mutated AML (n = 25), and KRAS/NRAS-mutated AML (n = 7). We used propensity score to adjust outcomes. NRAS-mutated AML had a similar response rate to first-line treatment and mOS compared to RAS-WT AML (57 vs. 54%, p = 0.8, 22.7 vs. 14.6 months, p = 0.7). The mOS of KRAS-mutated AML was shorter compared to RAS-WT AML (p = 0.049) and NRAS-mutated AML (p = 0.02). KRAS-mutated AML treated with anthracycline-based first-line regimens had a lower relative mortality compared to treatment with hypomethylating agents with venetoclax (HR <0.01, p = 0.04) and without venetoclax (HR <0.01, p = 0.04). This study demonstrates that KRAS but not NRAS mutations are associated with worse outcomes in AML. NOVELTY STATEMENT What is the new aspect of your work? The clinical significance of RAS mutations remains poorly defined and prior studies have yielded conflicting results. We used causal inferential methods, propensity score modeling, to determine the impact of KRAS and NRAS mutation on survival in newly diagnosed AML patients, independent of other risk factors. Moreover, we analyzed the outcomes of KRAS and NRAS-mutated AML patients receiving first-line therapy with hypomethylating agents and other non-anthracycline-based regimens. We provided a detailed description of RAS-mutated AML, including co-occurring mutations and cytogenetic abnormalities. What is the central finding of your work? KRAS mutations but not NRAS mutations in AML are directly linked to worse outcomes even after controlling for differences in AML type, co-occurring cytogenetic changes, treatment regimens, and comorbidities. KRAS-mutated AML has a higher relative mortality when treated with a hypomethylating agent-based first-line induction regimen compared to treatment with an anthracycline-based regimen. What is (or could be) the specific clinical relevance of your work? Our findings can help refine our genetic profiles of AML, improve prognostic models, and better stratify treatment regimens.

The prognostic impact of lymphovascular invasion for upper urinary tract urothelial carcinoma: A propensity score-weighted analysis.

Lymphovascular invasion (LVI) predicts poor survival in patients with pathologically localized or locally advanced upper urinary tract urothelial carcinoma (UT-UC). However, LVI is associated with high tumor grade, tumor necrosis, advanced tumor stage, tumor location, concomitant carcinoma in situ, lymph node metastasis, and sessile tumor architecture. These factors might interfere with the analysis of the impact of LVI on oncological prognosis. To address this, this study aimed to clarify the relationship between LVI and patient prognosis in UT-UC using propensity score weighting. Data were collected from 789 patients with UT-UC treated with radical nephroureterectomy without chemotherapy. We evaluated the significance of LVI in predicting metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) using propensity score weighting. All weighted baseline characteristics included in the propensity score model were balanced between the LVI (+) and LVI (-) groups. The MFS, CSS, and OS were all significantly poorer in the LVI (+) group. For patients without LVI, the 5-year MFS, CSS, and OS rates were 65.3%, 73.1%, and 67.3%, respectively, whereas the corresponding rates were 50.2%, 63.8 %, and 54.6%, respectively, for patients with LVI. (all P < .001). For patients without LVI, the 10-year MFS, CSS, and OS rates were 61.5%, 69.6%, and 59.2%, respectively, whereas those for patients with LVI were 44.5%, 57.0%, and 42.7%, respectively (all P < .001). LVI is an important pathological feature that predicts metastasis development and worse survival outcome after radical surgery in UT-UC patients.

Propensity score analysis with local balance.

Most propensity score (PS) analysis methods rely on a correctly specified parametric PS model, which may result in biased estimation of the average treatment effect (ATE) when the model is misspecified. More flexible nonparametric models for treatment assignment alleviate this issue, but they do not always guarantee covariate balance. Methods that force balance in the means of covariates and their transformations between the treatment groups, termed global balance in this article, do not always lead to unbiased estimation of ATE. Their estimated propensity scores only ensure global balance but not the balancing property, which is defined as the conditional independence between treatment assignment and covariates given the propensity score. The balancing property implies not only global balance but also local balance-the mean balance of covariates in propensity score stratified sub-populations. Local balance implies global balance, but the reverse is false. We propose the propensity score with local balance (PSLB) methodology, which incorporates nonparametric propensity score models and optimizes local balance. Extensive numerical studies showed that the proposed method can substantially outperform existing methods that estimate the propensity score by optimizing global balance, when the model is misspecified. The proposed method is implemented in the R package PSLB.

Aspirin Use and Risk of Pancreatic Ductal Adenocarcinoma: A Large Case-Control Study.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate of approximately 5%. The incidence and mortality rates of PDAC are increasing, and the results of medical treatments remain unsatisfactory. Some conflicting evidence suggests that aspirin intake may reduce the risk of PDAC. This study aimed to evaluate the association between regular low-dose aspirin use (80-mg aspirin tablets, 5-7 tablets/week) and the risk of PDAC. This prospective, hospital-based, case-control study was performed on 470 PDAC patients (case group) and 526 sex and age-matched controls, in Tehran, Iran from 2011 to 2018. The participants were interviewed regarding the patterns of aspirin use. Data are expressed as mean±SD or frequency and percentage as appropriate. Differences in frequency between the case and control groups were evaluated based on the analysis of the contingency table (χ2 test and Fisher's exact test). Propensity score models were designed to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) for PDAC with respect to aspirin use, adjusted for age, sex, smoking status, opium use, diabetes mellitus, place of residence, and family history of cancer in first-degree relatives. About 60% of PDAC patients were male in this study. Also, 25.2% of PDAC patients had a family history of cancer in one of their first-degree relatives, 21.99% were smokers, 13.9% were opium users, and 11.7% had a history of diabetes. Aspirin was used by 22.77% of PDAC patients and 18.25% of the controls. Ever aspirin use (OR: 1.01, 95% CI: 0.89 - 1.14) was not associated with PDAC. Overall, aspirin use was not associated with a reduced risk of PDAC.

MP16-03 THE IMPACT OF TIMING OF DEFINITIVE INTERVENTION FOR PATIENTS WITH ACUTE RENAL COLIC: A POPULATION-BASED STUDY

You have accessJournal of UrologyCME1 Apr 2023MP16-03 THE IMPACT OF TIMING OF DEFINITIVE INTERVENTION FOR PATIENTS WITH ACUTE RENAL COLIC: A POPULATION-BASED STUDY Michael Ordon, Sarah Bota, Yuguang Kang, and Blayne Welk Michael OrdonMichael Ordon More articles by this author , Sarah BotaSarah Bota More articles by this author , Yuguang KangYuguang Kang More articles by this author , and Blayne WelkBlayne Welk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003236.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Little data exists on the optimal timing for intervention for symptomatic kidney stones, as such, our objective was to determine the impact of early intervention versus delayed intervention/expectant management for patients presenting to the emergency department (ED) with renal colic. METHODS: We conducted a population-based cohort study in the province of Ontario, utilizing linked administrative health data. Patients who presented to an ED with renal colic between April 1, 2010 to June 30, 2020 were included. Patients were divided into two groups. The early intervention (EI) group underwent shockwave lithotripsy (SWL), ureteroscopy (URS) or percutaneous nephrolithotomy (PCNL) within 2-weeks of presentation. The delayed intervention/expectant management (non-EI) group represented all other patients. Patients were followed forward in time for 3 months in the EI group and for 4 weeks post-intervention or 3 months (whichever was longer) in the non-EI group to assess for our outcomes. The outcomes included additional ED visits, hospitalizations or imaging studies, stent or nephrostomy insertion and urologist/primary care visits. These outcomes were compared across the two groups using matched propensity score modelling. RESULTS: There were 397,185 index renal colic events (EI=28,910, non-EI=368,275). The EI group was slightly older and more likely to have a history for stones, hypertension and diabetes (Table 1). The EI group had a lower risk for additional ED visits (RR 0.70 95% CI 0.68-0.72, p<0.001) and hospital admissions (RR 0.52, 95% CI 0.50-0.55, p<0.001) compared to the non-EI group. Similarly, the EI group had a lower risk for stent (RR 0.62, 95% CI 0.54-0.71, p<0.001) or nephrostomy insertion (RR 0.49, 95% CI 0.42-0.57, p<0.001), however there was no difference for additional imaging. The EI group had a slightly increased risk for urologist/primary care visit (RR 1.02, 95% CI 1.02-1.03, p<0.001). In the non-EI group, 17% underwent eventual intervention. CONCLUSIONS: Our population-based study suggests a benefit to EI for those presenting with renal colic to the ED, but potentially with the risk of exposing some patients to unneeded treatment. These findings could influence practice patterns and guideline recommendations moving forward. Source of Funding: Northeastern Section of the AUA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e202 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Ordon More articles by this author Sarah Bota More articles by this author Yuguang Kang More articles by this author Blayne Welk More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of splenectomy based on inverse probability weighting of the propensity score on Wilson's disease with hypersplenism: A retrospective cohort study.

Hypersplenism is a long-term complication of Wilson's disease (WD). Patients often have to stop copper excretion treatment due to the decrease in blood cell count aggravation of abnormal liver function, anaemia, bleeding caused by coagulation dysfunction. The present study aimed to explore the effect of splenectomy on serum, biochemical indicators and neurological function in patients with hypersplenism of WD to evaluate the impact of splenectomy on their survival and prognosis. Due to the non-randomness of splenectomy in patients with hypersplenism in WD in the present study, the propensity scoring model and inverse probability treatment weighting were used to evaluate the age, sex, duration of the disease. A total of 86 patients (40 with and 46 without splenectomy) were included in the present study. The baseline and preoperative data were adjusted by the inverse probability weighting method using the propensity score model. There was no significant difference in distribution of propensity scores between the two groups (P>0.05). There were significant differences in time-weighted PLT levels in patients with hypersplenism of WD [after adjustment, odd ratio (OR)=0.010; 95% CI, 0.0013-0.047; P<0.001]. The time-weighted Child-Pugh scores after adjustment also suggested a significant difference (OR=0.0684; 95% CI, 0.018-0.207; P<0.001). The time-weighted modified Young scale scores demonstrated no statistical significance (after adjustment, OR=0.294; 95% CI, 0.074-1.001; P>0.05). Survival data showed a mean survival time of 11.2±3.15 years with a 10-year survival rate of 64.97% for patients with non-splenectomy and 12.9±2.62 years with a 10-year survival rate of 92.11% for patients with splenectomy, which was statistically significant (P<0.05). Due to crossover of survival curves at a later stage, the data were analysed using landmark analysis. The results suggested that splenectomy decreased death rate within 10 years by 84% compared with the non-splenectomy group (HR=0.158; 95% Cl, 0.0198-1.2545; P<0.05), but the survival rate of the two groups was not statistically significant after 10 years. (HR=0.445; 95% Cl, 0.2463-0.8022; P>0.05). In conclusion, splenectomy significantly improved levels of PLT and liver function in patients with hypersplenism of WD, neurological function did not deteriorate and survival rate was improved.

Determining the survival benefit of postoperative radiotherapy in patients with pT1-3N1M0 rectal cancer undergoing total mesorectal excision: a retrospective analysis

BackgroundThe National Comprehensive Cancer Network guidelines recommend routine postoperative adjuvant radiotherapy and chemotherapy for patients with stage III rectal cancer who do not receive neoadjuvant therapy before surgery. The present study aimed to evaluate the value of postoperative radiotherapy in patients with low-risk disease (pT1-3N1M0) who did not receive neoadjuvant therapy prior to total mesorectal excision.MethodsWe used the Surveillance, Epidemiology, and End Results database (2004–2016) to retrospectively recruit patients with pT1-3N1M0 rectal cancer whose initial treatment was radical surgery with postoperative adjuvant chemotherapy. A propensity score model was used to balance the baseline covariates.ResultsOf the 2012 patients included in the present study, 1384 received adjuvant chemoradiotherapy (radio group), whereas the remaining 718 received chemotherapy alone (no-radio group). There was no significant difference in cancer-specific survival rate between the two groups (log-rank test χ2 = 2.372, P = 0.124) in the overall sample. Additionally, in the propensity score−matched cohort, adjuvant radiotherapy did not improve cancer-specific survival. Subgroup analysis showed that having three positive lymph nodes and a tumor > 50 mm, combined with postoperative adjuvant chemotherapy, could lead to an improved tumor-specific survival rate, while other cases did not benefit from postoperative radiotherapy.ConclusionsFor patients with pT1-3N1M0 rectal cancer who did not receive neoadjuvant therapy before surgery, postoperative radiotherapy in addition to adjuvant chemotherapy did not significantly improve survival rates. The number of positive nodes (n = 3) and tumor size (> 50 mm) were found to be potential screening indicators for postoperative adjuvant radiotherapy.

Association of preoperative COVID-19 and postoperative respiratory morbidity during the Omicron epidemic wave: the DROMIS-22 multicentre prospective observational cohort study

Preoperative COVID-19 has been associated with excess postoperative morbi-mortality. Consequently, guidelines were developed that recommended the postponement of surgery for at least 7 weeks after the infection. We hypothesised that vaccination against the SARS-CoV-2 and the large predominance of the Omicron variant attenuated the effect of a preoperative COVID-19 on the occurrence of postoperative respiratory morbidity. We conducted a prospective cohort study in 41 French centres between 15 March and 30 May 2022 (ClinicalTrials NCT05336110), aimed at comparing the postoperative respiratory morbidity between patients with and without preoperative COVID-19 within 8 weeks prior to surgery. The primary outcome was a composite outcome combining the occurrence of pneumonia, acute respiratory failure, unexpected mechanical ventilation, and pulmonary embolism within the first 30 postoperative days. Secondary outcomes were 30-day mortality, hospital length-of-stay, readmissions, and non-respiratory infections. The sample size was determined to have 90% power to identify a doubling of the primary outcome rate. Adjusted analyses were performed using propensity score modelling and inverse probability weighting. Of the 4928 patients assessed for the primary outcome, of whom 92.4% were vaccinated against the SARS-CoV-2, 705 had preoperative COVID-19. The primary outcome was reported in 140 (2.8%) patients. An 8-week preoperative COVID-19 was not associated with increased postoperative respiratory morbidity (odds ratio 1.08 [95% CI 0.48-2.13]; p=0.83). None of the secondary outcomes differed between the two groups. Sensitivity analyses concerning the timing between COVID-19 and surgery, and the clinical presentations of preoperative COVID-19 did not show any association with the primary outcome, except for COVID-19 patients with ongoing symptoms the day of surgery (OR 4.29 [1.02-15.8]; p=0.04). In our Omicron-predominant, highly immunised population undergoing general surgery, a preoperative COVID-19 was not associated with increased postoperative respiratory morbidity. The study was fully funded by the French Society of Anaesthesiology and Intensive Care Medicine (SFAR).

Abstract P4-06-10: Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting

Abstract Background: Breast cancer is the second most commonly diagnosed cancer in North American women. The administration of neoadjuvant chemotherapy (NAC) is the mainstay of treatment for individuals with high risk disease in an effort to reduce the extent of surgery, evaluate the role of additional adjuvant therapies (based on pathologic response to NAC), and improve disease-free and overall survival (OS). Anthracyclines have been shown to increase response rates leading to a greater likelihood of pathologic complete response compared to non-anthracycline regimens. However, for some individuals anthracyclines are omitted from the NAC regimen due to toxicities including greater immunosuppression, cardiac toxicity and risk of acute leukemia. We established a population-based cohort of individuals treated with NAC for breast cancer. We report the outcomes of women selected for treatment with non-anthracycline NAC compared to those treated with anthracyclines. Methods: This is a retrospective population-based cohort study using linked health administrative data held at the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada. We identified adult women diagnosed with stage I-III breast cancer (ICD-10 C50^) between 2012 and 2020 who received NAC. Administration of at least 50% of the planned chemotherapy regimen was required. We excluded patients with bilateral breast cancer, previous malignancy and male sex. NAC regimens were classified as anthracycline and non-anthracycline-containing regimens. To address confounding between those receiving anthracycline and other regimens, we built a propensity score model including patient and disease characteristics. The association with OS was calculated using Cox proportional hazards models, and breast cancer-specific survival (BCSS) was calculated using cause-specific Cox proportional hazards models. Models were adjusted for the propensity score, radiation treatment as a time-varying covariate, age, socioeconomic status, breast cancer stage and receptor sub-type, as well as Charlson comorbidity index. Results: A total of 4,180 women were identified with a median follow up of 62 months (IQR 44 – 85). Of these, 279 (6.7%) were treated with non-anthracycline regimens compared to 3,901 treated with anthracycline. Patients who received non-anthracyclines were older (median 62 years vs. 50 years; p &amp;lt; 0.001), and less likely to have stage III disease (33.0% vs. 48.7%; p &amp;lt; 0.001), and harbor triple-negative breast cancer (TNBC) (14.0% vs. 24.4%; p &amp;lt; 0.001). They were more likely to have no recorded comorbidities (89.2% vs. 96.5%; p &amp;lt; 0.001), undergo mastectomy (82.1% vs. 71.9%; p &amp;lt; 0.001), and sentinel lymph node biopsy (44.4% vs. 32.3%; p &amp;lt; 0.001). After propensity score and multivariable adjustment, women selected for treatment with non-anthracycline regimens had similar OS (HR 0.85, 95% CI 0.60-1.21) and BCSS (cause-specific HR 0.76, 95% CI 0.46-1.25) compared to those treated with anthracyclines. When stratified by stage, women treated with non-anthracycline regimens did not have significantly higher incidences of breast cancer death or death from any cause (stages I, II, and III Gray’s Test p-value all &amp;gt; 0.1). The mean OS was 7.2 years for women who received non-anthracycline regimens (95% CI 7.0 – 7.4) compared to 7.9 years for those who received anthracycline (95% CI 7.9 – 8.0) (log-rank p = 0.100). Conclusions: Women with stage I-III breast cancer treated with non-anthracycline NAC regimens are a highly selected population. These patients were older and healthier, with earlier stage disease and more favorable subtype (i.e. non-TNBC) when compared to those treated with anthracycline NAC. Our results demonstrate that women were well selected to omit anthracyclines and did not have worse survival outcomes. Further research is needed to better understand in whom anthracycline can be safely omitted. Citation Format: Danilo Giffoni M. M. Mata, Matthew Castelo, Rinku Sutradhar, Lena Nguyen, Neil Faught, Danielle Rodin, Ezra Hahn, Omolara Fatiregun, Cindy Fong, Sabina Trebinjac, Andrea Eisen, Lawrence Paszat, Katarzyna Jerzak, Eileen Rakovitch. Is Anthracycline Chemotherapy Essential in the Treatment of Women with Breast Cancer? – A Real World Comparison in the Neoadjuvant Setting [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-10.

Channeling of New Neuropsychiatric Drugs-Impact on Safety and Effectiveness Studies.

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005-2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies.

Impact of Hypoalbuminemia on Ceftriaxone Treatment Failure in Patients With Enterobacterales Bacteremia: A Propensity-Matched, Retrospective Cohort Study.

Ceftriaxone is frequently prescribed due to its convenience of dosing and robust antimicrobial activity. However, patients with hypoalbuminemia may experience suboptimal ceftriaxone exposure due to the high degree of protein binding. We aimed to evaluate the impact of hypoalbuminemia on treatment failure among hospitalized adults with Enterobacterales bacteremia who received ceftriaxone therapy. We conducted an observational cohort study among patients with Enterobacterales bacteremia who received >72 hours of ceftriaxone initiated within 48 hours of index culture. A propensity-score model was used to match and compare patients with hypoalbuminemia. The primary outcome was treatment failure, defined as a composite of (1) escalation from ceftriaxone to ertapenem or an intravenous antibacterial agent with activity against Pseudomonas aeruginosa, or (2) inpatient death. Secondary outcomes included hospital length of stay, duration of antibiotic therapy, and time to infection resolution. Of 260 patients included, the majority developed bacteremia from a urinary source (71.5%), and Escherichia coli was the most common pathogen identified (72.3%). Patients with hypoalbuminemia experienced numerically higher rates of treatment failure, although not reaching statistical significance (12.3% vs 7.7%; P = .21). Among patients receiving care in the intensive care unit, the impact of hypoalbuminemia on treatment failure was more pronounced (24.4% vs 7.3%; P = .07). Hypoalbuminemia may not have a significant impact on clinical outcomes among patients with Enterobacterales bacteremia treated with ceftriaxone. However, critically ill patients may be subject to higher incidence of treatment failure in the presence of hypoalbuminemia.

Clinical characteristics and outcomes of hospital-manifested COVID-19 among Brazilians

To analyze the clinical characteristics and outcomes of in-hospital patients with hospital- versus community-manifested COVID-19; and to evaluate the risk factors related to mortality in the first population. This retrospective cohort included consecutive adult COVID-19 patients, hospitalized between March and September/2020. Demographic data, clinical characteristics and outcomes were extracted from medical records. Patients with hospital-manifested COVID-19 (study group) and those with community-manifested COVID-19 (control group) were matched by the propensity score model. Logistic regression models were used to verify the risk factors for mortality in the study group. Among 7,710 hospitalized patients who had COVID-19, 7.2% developed symptoms while on admission for other reasons. Patients with hospital-manifested COVID-19 had a higher prevalence of cancer (19.2% vs. 10.8%) and alcoholism (8.8% vs. 2.8%), compared to patients with community-manifested COVID-19, as well as a higher rate of intensive care unit requirement (45.1% vs. 35.2%), sepsis (23.8% vs. 14.5%), and death (35.8% vs. 22.5%) (p<0.05 for all). The factors independently associated with increased mortality in the study group were increasing age, male sex, number of comorbidities, and cancer. Hospital-manifested COVID-19 was associated with increased mortality. Increasing age, male sex, number of comorbidities, and cancer were independent predictors of mortality among those with hospital-manifested disease.