Inverse Probability Of Treatment Weighting Research Articles

Real-world survival comparison of second-line treatment strategies for patients with RAS/RAF wild-type, right-sided metastatic colorectal cancer.

73 Background: For patients with RAS/RAF wild type metastatic colorectal cancer (mCRC), systemic therapy usually includes fluoropyrimidine-based chemo + anti-VEGF or anti-EGFR targeted therapy. The PARADIGM trial established tumor sidedness as an important predictive biomarker for patients with RAS/RAF wild-type disease; in right-sided tumors, there was no survival difference between first-line chemo + anti-EGFR vs. chemo + anti-VEGF. However, there is no comparative data to guide second-line treatment decisions in this population. We aim to compare the effectiveness of second-line chemo + anti-EGFR versus chemo + anti-VEGF therapy for patients with RAS/RAF wild-type, right-sided mCRC who received first-line chemo + anti-VEGF. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data obtained from ~280 cancer clinics and curated via technology-enabled abstraction. Patients ≥18 years old with RAS/RAF wild-type, right-sided mCRC who received first-line therapy consisting of chemotherapy ((FOLFIRI or FOLFOX or CAPEOX) + anti-VEGF and initiated second-line chemotherapy with either anti-EGFR or anti-VEGF targeted therapy between January 2013-May 2024 were included. Multiple imputation with chained equations imputed missing values for sidedness, RAS/RAF status, and propensity score covariates (age, gender, year of diagnosis, synchronous/metachronous disease, MMR/MSI status, ECOG score, CEA level, and first-line therapy duration). Cox proportional hazards modeling with stabilized inverse probability of treatment weighting (IPTW) assessed the association of anti-EGFR vs anti-VEGF treatment with overall survival. Results: 4,444 patients received appropriate first-line treatment and received chemo + anti-EGFR or chemo + anti-VEGF in the second line. Across 25 imputations, an average of 444 patients met inclusion criteria: 175 patients received chemo + anti-EGFR and 269 patients received chemo + anti-VEGF. Following IPTW, baseline characteristics were balanced between treatment groups. Patients who received chemotherapy + anti-EGFR had a 24% increased hazard of death when compared with patients who received chemotherapy + anti-VEGF, though this was not statistically significant (HR 1.24, 95% CI 0.96 – 1.61, p=0.097). Conclusions: Among patients with RAS/RAF wild-type, right-sided mCRC who received first-line chemotherapy + anti-VEGF, there is some evidence to support continuing anti-VEGF therapy vs. switching to anti-EGFR therapy in the second line, though the result was not statistically significant. Future studies should explore predictive biomarkers for EGFR vs VEGF-directed treatment for this population to determine the patients most likely to benefit from anti-EGFR therapy during their disease course.

Propensity score matching analysis of valve-sparing versus aortic root replacement in type A aortic dissection patients

This study compared long-term survival and reintervention rates between Valve-Sparing Root Replacement (VSRR, n = 244) and Aortic Root Replacement (ARR, n = 499) in 743 patients undergoing Type A acute aortic dissection (AAD), given the lack of prospective comparative data. Multivariable analysis is identifying advanced age, high Body Mass Index (BMI), Marfan syndrome, severe aortic regurgitation, bicuspid aortic valve, increased aortic root diameter, and reduced aortic cross-clamp time (ACC) as significant factors associated with ARR. After Propensity Score Matching (PSM), VSRR is showing significantly higher 5-year survival rates than ARR (80.2% vs. 64.1%, P = 0.001), validated by Inverse Probability of Treatment Weighting (IPTW) analysis. Reintervention rates are being found comparable, with endocarditis more prevalent in ARR and aortic regurgitation in VSRR. Subgroup analysis indicated that patients aged less than 60 years and those with a BMI greater than 24 in the VSRR group exhibited significantly improved survival probabilities compared to the ARR group. These findings support the wider utilization of valve-sparing root replacement (VSRR) in appropriately selected patients, highlighting its potential advantages for suitable candidates.

Abstract TMP83: Endovascular Therapy Vs. Medical Management In Isolated Posterior Cerebral Artery Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Weighted Study

Introduction: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo. Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications. Results: A total of 177 patients were analyzed (88 MM and 89 EVT). Baseline characteristics were balanced using Inverse Probability of Treatment Weighting (IPTW). EVT showed a statistically significant improvement in 90-day mRS scores (OR=0.55, 95% CI=0.30 to 1.00, P=0.048), functional independence (OR=2.52, 95% CI=1.02 to 6.20, P=0.045), and a reduction in 90-day mortality (OR=0.12, 95% CI=0.03 to 0.54, P=0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups. Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. These findings emphasize on the potential benefits of EVT in this understudied patient group, highlighting the need for randomized controlled trials to further validate these results.

Adjuvant capecitabine in resected biliary tract cancers: Real life data from a multicenter study (PRODIGE83-ACABi-PRONOBIL).

596 Background: Biliary tract cancers (BTCs) are rare and heterogeneous tumors with a poor survival even in early-stage patients treated with a curative surgery. Since 2019 the current standard of care in the adjuvant setting is oral chemotherapy (CT) with capecitabine for 6 months, as an option following BILCAP phase III trial results. Nevertheless, outside of this trial, real-world data are lacking. Methods: We conducted a French, retrospective, multicenter study from the ACABi-PRONOBIL cohort. Eligible patients had intrahepatic, perihilar, distal cholangiocarcinoma or gallbladder carcinoma treated by surgery with curative intent without prior therapy. Two groups were compared, patients who received capecitabine (Cape group) as adjuvant CT and patients without adjuvant treatment before 2017 (surveillance group). The primary endpoint was overall survival (OS). Secondary endpoints were disease-free survival (DFS) and toxicity. Results: 324 patients were included, 200 in the Cape group and 124 in the surveillance group. The median OS was 43.5 months (CI95%= 35.4-48.0) and 44.6 months (CI95% 37.7-54.8) in the Cape and surveillance group, respectively. ECOG performance status ≥ 2, pT3 stage, vascular and node invasion were associated with a poorer OS. The DFS was 15.8 months (CI95%= 14.1-20.3) in the Cape group and 13.3 months (CI95%= 10.1-17.5) in the surveillance group. In inverse probability of treatment weighting (IPTW) analysis we observed a significant statistical association between Cape group and DFS (IPTW HR (CI95%) Cape group vs surveillance group = 0.76 (0.60-0.96), pvalue=0.0224) but not with OS. In the Cape group, 49% of patients had at least one dose reduction, 35% had to discontinue treatment due to toxicity (mainly gastrointestinal,13.3% of grade 3-4; and cutaneous, 27% of grade 3-4). Conclusions: In this retrospective analysis, adjuvant capecitabine appears to increase DFS without statistically significant impact on OS in patients undergoing surgery for BTC, confirming in real life the BILCAP study results.

A 20-year population-wide cohort study on association of aspirin and risk of gastrointestinal and non-gastrointestinal cancer.

830 Background: Aspirin has been shown to reduce the risk of various gastrointestinal (GI) and non-GI cancers 1,2 . However, little was known about at what age aspirin should be started for maximal chemoprotective better on GI cancer. Furthermore, the randomised controlled trial on aspirin for primary prevention use in healthy elderly (ASPREE) showed no association between aspirin and cancer incidence despite the limitation of short follow-up duration 3 . The current study aims to investigate the 20-year risk of cancer using aspirin in a territory-wide Hong Kong population cohort. Methods: The study included all aspirin users from 2000 to 2019, and non-aspirin users matched by age and sex at a ratio of 1:2. Enrolled subjects with a history of cancer at enrolment, cancer incidence or death within 6 months were excluded. The incidence of individual GI and non-GI cancer was presented as the primary outcome. Baseline characteristics between aspirin and non-aspirin users were adjusted in the survival analysis by inverse probability of treatment weighting (IPTW). The fine-grey model has been used to address bias from competing risk of death. The sub-distribution hazard ratio was presented for the association of aspirin use and risk of GI and non-GI cancers. Results: The current study included 538,147 aspirin users and 968,378 non-users with a mean age of 64.8 years. A total number of 36,683 cases of GI cancer (2.4%) and 47,196 cases of non-GI cancers (3.1%) were observed. Aspirin was associated with a lower risk of several common individual GI cancers, including colorectal cancer (SHR 0.78, 95% CI 0.76-0.81), liver cancer (SHR 0.67, 95% CI 0.64-0.70), stomach cancer (SHR 0.79, 95% CI 0.75-0.84) and pancreatic cancer (SHR 0.85, 95% CI 0.79-0.91), but not oesophageal cancer. On the other hand, aspirin was associated with a lower risk of prostate cancer (SHR 0.95, 95% CI 0.91-1.00) and breast cancer (SHR 0.76, 95% CI 0.73-0.79), but not lung cancer and kidney cancer. In overall, aspirin was associated with a 24% lower risk of GI cancers (SHR 0.76, 95% CI 0.74-0.78) and a 3% lower risk of non-GI cancers (SHR 0.97, 95% CI 0.95-0.99). Conclusions: Aspirin was associated with a lower risk of most GI cancers, including colorectal cancer, liver cancer, stomach cancer and pancreatic cancer, but not most non-GI cancers. In general, results on the effect of aspirin on GI cancer prevention were consistent with the previously presented 10-year cohort. 1. Bosetti C, Santucci C, Gallus S, Martinetti M, La Vecchia C. Aspirin and the Risk of Colorectal and Other Digestive Tract Cancers: An Updated Meta-analysis through 2019. Ann Oncol. 2020;31(5):558-568. 2. Santucci C, Gallus S, Martinetti M, La Vecchia C, Bosetti C. Aspirin and the risk of nondigestive tract cancers: An updated meta-analysis to 2019. Int J Cancer. 2021;148(6):1372-1382. 3. McNeil JJ, Gibbs P, Orchard SG, et al. Effect of Aspirin on Cancer Incidence and Mortality in Older Adults. J Natl Cancer Inst. 2021;113(3):258-265.

Diminished salivary cortisol response to mental stress predict all-cause mortality in general population.

To characterize individuals with a diminished salivary cortisol response to mental stress, assess its association with all-cause mortality, and quantify the mediating effects of the most relevant and modifiable factors to identify potential target for prevention. Data from MIDUS II study with a 16-year follow-up, were used to categorize 1129 participants as responders or non-responders based on the existence of increase in salivary cortisol under mental stress. LASSO-logistics analysis identified the most relevant factors. Cox regression models and restricted cubic splines evaluated the prognostic impact. Further analyses examined the mediating effects of identified factors on prognosis. After employing Inverse Probability of Treatment Weighting to adjust for demographic differences between groups, individuals with diminished cortisol responses were found to have higher levels of depressive symptoms (p=0.050), increased inflammation (IL-6, 2.30 [1.41, 3.79] vs. 1.96[1.33, 3.31], p=0.011), and were less likely to regularly exercise (74.3% vs. 79.9%, p=0.030). IL-6 (OR: 1.25 [1.04, 1.52]，p=0.021) and regularly exercising (OR 0.71 [0.51, 0.97], p=0.032) emerged as significant modifiable factors in multivariate analysis. A notable prognostic association of diminished cortisol response with all-cause mortality (HR=1.33 [1.01-1.76], p=0.046) was observed, consistent across various subgroups and supported by non-linear model analysis. Approximately 13% of the mortality risk associated with diminished cortisol response was mediated by increased IL-6 levels (p=0.043). Diminished salivary cortisol response is linked to an increased risk of all-cause mortality, significantly mediated by elevated IL-6. This study offers a new perspective on prognostic prediction while highlighting potential avenues for intervention.

Outcomes and Perceptions of Masculinizing Mammoplasty Among Transgender Men in Brazil.

Transgender men often experience body image dissatisfaction due to incongruence between their gender identity and physical appearance. Masculinizing mammoplasty (MM) aligns physical appearance with gender identity; however, its impact on body image satisfaction in Brazil has not been comprehensively assessed using validated tools. To evaluate satisfaction with chest appearance, nipple aesthetics, and body investment among transgender men in Brazil, comparing those who have undergone MM with those who have not, using validated tools, such as the BODY-Q Chest, BODY-Q Nipple, and Body Investment Scale. This cross-sectional study included 90 transgender men aged ≥18 years recruited between June and September 2024. Participants were allocated to two groups: those who had undergone MM (n=45) and those eligible but had not yet undergone surgery (n=45). Inverse probability of treatment weighting and regression models adjusted for age, BMI, and education level were used. Participants had a mean age of 32.2 years (SD ± 8.1, range: 19-62) and BMI of 27.9 kg/m² (SD ± 4.8). The MM group had a mean time since surgery of 40 months (SD ± 29.2). After adjustment, MM was associated with significantly greater satisfaction with chest appearance (ATE, 60.98; 95% CI 53.02-68.93), nipple aesthetics (ATE, 50.61; 95% CI 38.99-62.23), and body investment (ATE, 11.02; 95% CI 5.66-16.38). Chest binding was significantly reduced in the MM group (P < 0.001). Transgender men in Brazil who underwent MM reported higher body image satisfaction and quality of life, supporting the role of this procedure in enhancing mental health.

Effectiveness and safety of tofacitinib versus calcineurin inhibitor in interstitial lung disease secondary to anti-MDA5-positive dermatomyositis: a multi-centre cohort study.

To compare the effectiveness and safety of tofacitinib (TOF) versus calcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5+DM-ILD). Adult Chinese patients with newly-diagnosed MDA5+DM-ILD (ILD course<3 months) from five tertiary referral centres between April 2014 and January 2023 were included for this retrospective cohort study. The primary effectiveness endpoint was lung transplantation-free survival within 1 year. Propensity score-based inverse probability of treatment weighting (IPTW) was applied for adjustment in this real-world study. In the eligible cohort, a total of 94 (32.4%) and 105 (46.7%) patients died or underwent lung transplantation within 1 year in the TOF group (n=290) and the CNI group (n=225), respectively. After adjustment by IPTW, patients' lung transplantation-free survival rate within 1 year was significantly higher in the TOF group compared to the CNI group (log-rank p=0.013). Multivariable Cox analysis performed in the IPTW dataset revealed the hazard ratio of TOF versus CNI for 1-year survival was 0.72 (95% CI, 0.56 to 0.94, p=0.013). The adjusted difference of survival rate was 9.3% (95%CI 2.8% to 15.8%). Alternative analytic strategies yielded consistent results in sensitivity analyses. Patients less than 60 years old, without RPILD, or with baseline PaO2/FiO2 ≥300 mmHg might benefit more from TOF. Opportunistic infection was the major treatment-related serious adverse event, with generally comparable incidence (42.4% versus 45.3%). In this large multi-centre cohort study, tofacitinib showed significantly more benefits for 1-year lung transplantation-free survival than calcineurin inhibitors in MDA5+DM-ILD.

Comparison of postoperative oxygenation in children receiving sugammadex versus neostigmine for reversal of neuromuscular blockade: a retrospective cohort study.

Residual neuromuscular blockade can impair postoperative respiratory mechanics, promoting hypoxemia and pulmonary complications. Sugammadex, with its unique mechanism of action, may offer a more effective reversal of neuromuscular blockade and respiratory function than neostigmine. We sought to test the primary hypothesis that children undergoing noncardiac surgery exhibit better initial recovery oxygenation when administered sugammadex than those administered neostigmine. Furthermore, we aimed to investigate if children administered sugammadex experience fewer in-hospital pulmonary complications. In a retrospective cohort study, we analyzed data from children aged 2-17yr who underwent noncardiac surgery with general anesthesia and received neostigmine or sugammadex between January 2017 and April 2023 at the Cleveland Clinic Main Campus. Our primary outcome was postoperative oxygenation defined by the mean SpO2/FIO2 ratio during the initial hour in the postanesthesia care unit. The secondary outcome was a composite of postoperative pulmonary complications during the hospital stay. Among 3,523 cases, 430 (12.5%) involved sugammadex and 3,081 (87.5%) involved neostigmine. The median [interquartile range] of the mean SpO2/FIO2 ratio during the first postoperative hour was 403 [356-464] in the sugammadex group and 408 [357-462] in the neostigmine group, resulting in an estimated difference in means of -6.2 (95% confidence interval, -12.8 to 0.41; P = 0.07) after inverse probability of treatment weighting. Overall, 22/1,916 (1.1%) inpatients experienced postoperative pulmonary complications; 2.0% of patients given sugammadex and 1.0% of patients administered neostigmine developed postoperative pulmonary complications (P = 0.19). In this retrospective cohort study, postoperative oxygenation was similar in children after reversal of neuromuscular blockade with sugammadex versus neostigmine.

Emergent Carotid Stenting During Thrombectomy in Tandem Occlusions Secondary to Dissection: A STOP-CAD Secondary Study.

Background: The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients with tandem occlusion secondary to cervical carotid artery dissection. Methods: This was a secondary analysis of patients treated with EVT for AIS due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study. We compared patients with and without emergent stenting. The primary efficacy and safety outcomes were 90-day functional independence (modified Rankin Scale 0-2) and symptomatic intracranial hemorrhage (sICH) within 24h after EVT. Procedural outcome was successful intracranial recanalization (mTICI 2b/3). We used mixed-effect logistic regression adjusting for site, age, and NIHSS. In additional analyses, we used inverse probability of treatment weighting and adjusted for ASPECTS. Results: Of the 4023 patients enrolled in STOP-CAD, 328 presented with anterior circulation AIS due to tandem occlusion and underwent EVT. The median age was 51 years (interquartile range 44-58), and 96 patients (29.3%) were female. One hundred fifty patients (45.7%) underwent emergent stenting. There was no significant association between stenting and 90-day functional independence (62.0% vs 59.7%; aOR 1.23, 95% CI 0.82-1.86, p=0.315) or sICH (7.3% vs 7.9%; aOR OR 0.95, 95% CI 0.41-2.2, p=0.913). Emergent carotid stenting was associated with successful intracranial recanalization (81.8% vs 76.6% aOR 2.62, 95% CI 1.52-4.5, p<0.001). Results did not meaningfully change in additional analyses. Conclusion: In patients presenting with an acute anterior circulation tandem occlusion secondary to cervical carotid artery dissection, emergent stenting was associated with a higher likelihood of successful intracranial recanalization but not improved functional outcomes or increased sICH. It remains unclear whether emergent stenting led to successful intracranial recanalization or patients with successful intracranial recanalization were more likely to be stented. Randomized trials are warranted.

Balloon-mounted versus self-expandable stent in failed neurothrombectomy: a post hoc analysis of the SAINT study

BackgroundPrevious studies have shown that when thrombectomy has failed, rescue intracranial stenting is associated with better clinical outcomes compared with failed reperfusion. However, comparative data regarding stent type are lacking.ObjectiveTo...

P-1010. Clinical and Economic Burden of Changing Initial Antifungal Regimens in Invasive Aspergillosis: A Hospital Perspective

Abstract Background Initial antifungal (AF) regimens (AFR) for Invasive Aspergillosis (IA) are often changed due to treatment failure, intolerability, or drug-drug interactions. We compared outcomes among IA patients who did and did not change their initial IA AFR.Table 1.Adjusted Baseline Characteristics of Patients Who Changed or Did Not Change Their IA Antifungal Regimen*CCI=Charlson comorbidity index; COPD=chronic obstructive pulmonary disease; IA= invasive Aspergillosis; SD=standard deviation*The following covariates were used to calculate propensity scores for Inverse probability of treatment weighting: age group, geographic region, payer type, year of index, asthma, autoimmune conditions, bacteremia, COPD, pneumonia, immunodeficiencies, myelodysplastic syndrome, transplant history, immunosuppressants, cancer, neutropenia, and total healthcare costs.||All covariates were well balanced as indicated by an SMD &amp;lt;0.1 except corticosteroids which was marginally imbalanced with an SMD of 0.108†Solid organ or hematopoietic cell transplant#Partial years data available in IQVIA New Data Warehouse⁋Azathioprine, cyclophosphamide, cyclosporine, methotrexate, mycophenolate, tacrolimus, voclosporin Methods This retrospective cohort study identified US adults with an index hospitalization for IA (ICD-10: B44.0, B44.1, B44.7) between Oct 2015 and Nov 2022 in IQVIA’s New Data Warehouse (pharmacy, outpatient and hospital claims). Patients were placed into two cohorts based on whether they changed AFRs, defined as starting a new AFR with or without discontinuing initial therapy at any subsequent point. Inverse probability of treatment weighting minimized confounding due to baseline differences between patients who changed vs. did not change their AFR. Inpatient length of stay (LOS), all-cause costs (in 2023 US$) and all-cause mortality in IA patients who did and did not change their initial AFR were reported as medians with interquartile ranges (IQR) or frequencies and compared.Table 2.Adjusted* Outcomes of Patients Who Changed or Did Not Change Their IA Antifungal RegimenLOS=length of stay; IA= invasive Aspergillosis; ICU=intensive care unit; IQR=interquartile range; SD=standard deviation*Inverse probability of treatment weighted Results Among 1,192 IA patients, 707 (59.3%) changed their initial AFR (Table 1). Most patients started therapy on an -azole (87% among those who changed vs 95% in those who did not change regimens). Duration of initial AFR for those who did and did not change their regimen was a median of 5 days (IQR=7) vs. 11 days (IQR=24), respectively. Hospital and ICU LOS were longer in the AFR change than the no change cohort (Table 2). Median costs associated with the index hospitalization, including pharmacy costs, were also significantly higher for those who changed AFR compared with those who did not. No statistical difference was seen in inpatient mortality during the index hospitalization between cohorts. Conclusion In this large contemporary cohort of patients with IA, most patients changed AFRs, with many doing so within 1-2 weeks of treatment initiation. Changing regimens was associated with significantly longer hospital and ICU LOS as well as higher inpatient costs. Further study is needed to understand reasons for changing AFRs and to understand changes that might be avoided. New and improved AFs that reduce the need for regimen changes offer the opportunity to reduce the economic and clinical burden associated with changing AFRs. Disclosures Barbara D. Alexander, MD, Basilea: Advisor/Consultant|F2G: Advisor/Consultant|F2G: Grant/Research Support|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Scynexis: Grant/Research Support|TFF Pharmaceuticals: Advisor/Consultant Mark Bresnik, MD, F2G Ltd: Employee Ruthwik Anupindi, PhD, F2G Ltd: Grant/Research Support|IQVIA: Employee Lia Pizzicato, MPH, F2G Ltd: Grant/Research Support|IQVIA: Employee Mitchell DeKoven, PhD, F2G Ltd: Grant/Research Support|IQVIA: Employee Belinda Lovelace, PharmD, MS, MJ, F2G, Inc.: Employee Craig I. Coleman, PharmD, F2G Ltd: Advisor/Consultant|F2G Ltd: Grant/Research Support Melissa D. Johnson, PharmD MHS AAHIVP, Biomeme: Licensed Technology|Scynexis, Inc: Grant/Research Support|UpToDate: Author Royalties

P-1011. Real-World Antifungal Therapy Patterns in US Patients with Invasive Aspergillosis: It’s Complicated

Abstract Background The complexity of antifungal therapy (AFT) in Invasive Aspergillosis (IA) can complicate care. We sought to better understand AFT changes that occur in IA across both in- and outpatient settings of care.Table 1.Baseline Characteristics of Patients Who Changed or Did Not Change Their Invasive Aspergillosis Antifungal Therapy* CCI=Charlson comorbidity index; COPD=chronic obstructive pulmonary disease; IA= invasive Aspergillosis †Partial years data were available in IQVIA New Data Warehouse #Solid organ or hematopoietic cell transplant ¶Azathioprine, cyclophosphamide, cyclosporine, methotrexate, mycophenolate, tacrolimus, voclosporin *The following covariates were used to calculate propensity scores for Inverse probability of treatment weighting: age group, geographic region, payer type, year of index, asthma, autoimmune conditions, bacteremia, COPD, pneumonia, immunodeficiencies, myelodysplastic syndrome, transplant history, immunosuppressants, cancer, neutropenia, and total healthcare costs. ∥All covariates were well balanced as indicated by an SMD &amp;lt;0.1 except corticosteroids which was marginally imbalanced with an SMD of 0.108 Methods This retrospective study was performed using the IQVIA New Data Warehouse (hospital, outpatient, and prescription claims) from Oct 2015-Nov 2022. The index inpatient stay was identified by IA ICD-10 codes. Patients were followed from index hospitalization until end of the study period (Dec 31, 2022), lack of medical or pharmacy activity in the database, or death (whichever occurred first). Patients were stratified by whether they ‘changed’ (defined as discontinuation with restart of a non-first line (L) AFT, switch or modification) or ‘did not change’ their AFT during the post-index period. Inverse probability of treatment weighting was used to minimize confounding due to baseline differences between the change and no change cohorts. Data were reported as frequencies or median with interquartile range.Figure 1.Sankey Diagram of IA Patients Who Required Changes in Antifungal Therapy Results Among 1,192 IA adults, 707 (59.3%) experienced changes to their AFT (60% modified existing AFT, 22.1% stopped 1L AFT and initiated AFT for 2L, and 18% directly switched to a different AFT) (Table 1). Among those who changed AFT, mold active azole use predominated, with voriconazole the most used across all AFT lines (37.3-49.3%), followed by isavuconazole (19.3-26.7%) (Figure 1). Echinocandin use varied between 25.3%-33.6% over 1-4L and amphotericin B use steadily increased over the lines of therapy (13.4-20.7%). Among the 485 (40.6%) patients that completed AFT with no changes, most received azole (62.8% voriconazole, 15.2% isavuconazole) monotherapy. Patients who changed AFT had shorter time on treatment for 1-3L (5-8 days) than those who did not change (11-21 days) (p&amp;lt; 0.047). Conclusion Based on this snapshot of IA treatment patterns, managing AFT for patients with IA is complicated. Most patients require changes to their AFT. Future studies should examine challenges associated with IA treatment and which factors contribute to AFT changes, such as drug toxicities or interactions and refractory infection. Novel oral antifungals that reduce the need for AFT changes when IA patients have limited options are needed. Disclosures Barbara D. Alexander, MD, Basilea: Advisor/Consultant|F2G: Advisor/Consultant|F2G: Grant/Research Support|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Scynexis: Grant/Research Support|TFF Pharmaceuticals: Advisor/Consultant Melissa D. Johnson, PharmD MHS AAHIVP, Biomeme: Licensed Technology|Scynexis, Inc: Grant/Research Support|UpToDate: Author Royalties Mark Bresnik, MD, F2G Ltd: Employee Ruthwik Anupindi, PhD, F2G Ltd: Grant/Research Support|IQVIA: Employee Lia Pizzicato, MPH, F2G Ltd: Grant/Research Support|IQVIA: Employee Mitchell DeKoven, PhD, F2G Ltd: Grant/Research Support|IQVIA: Employee Belinda Lovelace, PharmD, MS, MJ, F2G, Inc.: Employee Craig I. Coleman, PharmD, F2G Ltd: Advisor/Consultant|F2G Ltd: Grant/Research Support

P-1901. Statin Use and Severe/Critical/Fatal Outcomes in Individuals with COVID-19

Abstract Background There are conflicting results regarding the effects of statins upon outcomes in individuals with COVID-19. Several studies demonstrated a beneficial effect on survival, with others failing to demonstrate a beneficial effect, or even a higher risk of mortality, need for mechanical ventilation, and intensive care unit admissions among those who received statins. Statins in COVID_Fig 1 Methods We identified all individuals in the VA COVID-19 database with confirmed COVID-19. We excluded those with HIV, organ transplantation, cancer diagnosis, and any hospitalization within preceding 30 days. Among those, we created a pool of potential cases who had received a statin within +/- 7 days, and controls with no statins in the previous 365 days and up to 28 days after the index positive test date. Using an inverse probability of treatment weights (IPTW) based approach, we determined the rates of moderate/severe/critical disease within 28 days of the index COVID-19 diagnosis among statin-recipients and controls. Absolute risk differences (ARD) and Kaplan-Meier curves were generated for cases and controls. Statins in COVID_Fig 2 Results In IPTW-weighted matched analysis including 10,544 statin-recipients and 94,185 controls, statin-recipients were more likely to have an unfavorable outcome compared with controls (ARD 0.21 (95% CI 0.08,0.35) overall. In subgroup analyses, statin-recipients &amp;gt;60 years old and those with diabetes, cardiovascular disease, or chronic lung or kidney disease had more favorable outcomes compared with controls. Conclusion Individuals with COVID-19 who received statins were more likely to have poorer outcomes compared with controls not receiving statins. Subgroup analyses demonstrating a benefit among those at high risk of cardiovascular outcomes may be reflection of the beneficial effects of statins on the underlying comorbidities rather than a direct benefit against COVID-19. Disclosures Adeel A. Butt, MD, MS, Gilead Sciences: Grant/Research Support

P-727. Is there increased risk of RSV infection following SARS-CoV-2 infection in children? An EHR-based cohort study from the RECOVER Program

Abstract Background Pediatric populations experienced an unprecedented burden of respiratory infections in 2022, raising a hypothesis that SARS-CoV-2 infection could increase the susceptibility to subsequent respiratory infections. Our objectives were to compare the risk of RSV infection among children with and without a prior documented SARS-CoV-2 infection. Density landscapes of index infections for the comparison cohorts from March 1, 2022 to July 1, 2022, along with density landscapes of the outcome (RSV infection), for the cohort. Red shading indicates children with SARS-CoV-2 infection on the same day as their first documented RSV infection, and green shading indicates children with Influenza and RSV on the same day. Purple and blue show the density of influenza and SARS-CoV-2 index cases and subsequent RSV infections not occurring on the same day, respectively. Methods This retrospective cohort study utilized inpatient and outpatient Electronic Health Record (EHR) data from 40 PCORnet sites in the US of children &amp;lt; 5 years of age with SARS-CoV-2 infection (test or coded) between March 1, 2022 and July 1, 2022. Comparison groups included a) children with influenza infection (PCR confirmed or coded) and b) children with a respiratory infection and no evidence of SARS-CoV-2 or influenza infection. The primary outcome of interest was RSV infection in the subsequent 15-180 days (PCR-confirmed or coded). Inverse probability of treatment weighting (IPTW) controlled for factors associated with the difference in exposures, including race, ethnicity, age, and date of infection. A weighted logistic regression model produced odds ratios for RSV infection via doubly robust analyses, with sensitivity analyses accounting for different outcome windows. Odds ratios of weighted, adjusted, and completely unweighted or adjusted models evaluating RSV infection in the 3 windows of follow up (0-60 days, 1-60 days, and 15-180 days) following SARS-CoV-2 infection compared with RSV infection following influenza infection. Square and triangle shapes represent odds ratios, lines represent 95% confidence intervals. Each color represents a different model with varied time period of evaluation, weighting and adjustment. Results The cohort consisted of 21,537 children with SARS-CoV-2 infection, 8,317 with influenza infection, and 59,798 with another acute respiratory infection. Distributions of index and RSV infection dates are shown in Figure 1. In weighted analyses, we found a 30% higher risk of RSV infection in the 0-60 days following SARS-CoV-2 infection; however, this increase was driven by co-infections (of the 3.06% of SARS-CoV-2 patients with RSV in the subsequent 0-60 days, two thirds had RSV/SARS-CoV-2 coinfection). When assessing the evaluation period of 1-60 days or 15-180 days, we did not find a significant difference in the risk of RSV infection (Figure 2). Conclusion Contrary to other studies which did not account for seasonal respiratory viral patterns or concurrent infections, we found an association of concurrent infection with RSV and SARS-CoV-2, but did not find a higher risk of subsequent RSV infection, compared with children seeking care for influenza and other respiratory illnesses during the RSV surge in 2022. Disclosures Asuncion Mejias, MD, PhD, MsCS, Astra-Zeneca: Advisor/Consultant|Astra-Zeneca: Honoraria|Enanta: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Honoraria

P-1534. The Impact of Broad-spectrum Antimicrobials in Patients with Community-onset Pneumonia at Low Risk of Drug-resistant Pathogens: A Historical Cohort Study

Abstract Background The administration of broad-spectrum antimicrobials has prevailed in the clinical management of community-onset pneumonia (COP). Growing evidence suggests that the use of unnecessary broad-spectrum antimicrobials for patients with COP leads to adverse events and poor outcomes. This study aims to understand the impact of broad-spectrum antipseudomonal β-lactam use on clinical outcomes and resource utilization in patients hospitalized for COP with a low risk for drug-resistant pathogens (DRPs). Methods This historical cohort study analyzed the hospital claims database in Japan from January to December 2018. The study includes patients aged 20 or older hospitalized with COP having intravenous antimicrobial therapy administration and excludes patients with a high risk for DRPs. Patients were selected into a broad-spectrum (antipseudomonal β-lactam therapy) and a narrow-spectrum (non-antipseudomonal β-lactam therapy) group based on the initial antimicrobial regimen. This study evaluates 30-day mortality as a primary outcome by inverse probability of treatment weighting (IPTW)and healthcare resource utilization as one of the secondary outcomes. Results A total of 15,617 patients met the inclusion criteria. This target population was divided into two groups: 2,627 patients in the broad-spectrum and 12,990 in the narrow-spectrum group. In the first group, the most commonly used antimicrobials were Piperacillin / Tazobactam (68%), and the 30-day mortality was 10.6 in contrast with 5.3% in the second group. Thus, the broad-spectrum group was associated with an increased 30-day mortality rate in contrast with the narrow-spectrum group after IPTW weighting (adjusted odds ratio 1.77, 95% confidence interval [1.52 to 2.06], &amp;lt; 0.001). This trend was observed regardless of pneumonia severity. The average inpatient cost was $6,139 USD for the broad-spectrum group against $5,184 USD for the narrow-spectrum group, with respective length of stay (LOS) figures of 23.1 and 19.8 days. Conclusion This study shows that the initial use of antipseudomonal β-lactams for COP with a low risk for DRPs is associated with higher poor outcomes, including death and higher healthcare resource utilization. Judicious selection of initial antimicrobials is warranted in the management of COP. Disclosures Junichi Hirayama, n/a, bioMerieux Japan: employee of bioMerieux, salary Rie Ueno, MD., BioMérieux Japan Ltd.: Employee of BioMérieux Japan Ltd. Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi &amp; Co., Ltd.: Advisor/Consultant|Shionogi &amp; Co., Ltd.: Grant/Research Support|Shionogi &amp; Co., Ltd.: Lecture fees

P-2243. Multiplex PCR Pneumonia Panel in Critically Ill Patients Did Not Modify Mortality. A Cohort Study

Abstract Background Severe pneumonia is a common cause of Intensive Care Unit (ICU) admissions. In critically ill patients, identification of the pathogen may allow timely adjustment of antibiotics and, therefore improve outcomes. The aim of this study was to assess whether performing a multiplex polymerase chain reaction (PCR) pneumonia panel in patients with pneumonia in ICU, has any effect on mortality, overall stay, ICU stay and duration of antimicrobial therapy. Methods A retrospective cohort study was conducted on adult patients with pneumonia who required ICU admission at 4 hospitals in Bogota Colombia, between November 2019 and June 2023. Patients who underwent multiplex PCR pneumonia panel testing were defined as exposed. Mortality at 30 days, length of hospital and ICU stay, duration of antibiotics and, their association with multiplex PCR pneumonia panel testing were evaluated using and Inverse Probability of Treatment Weighting (IPTW) to adjust for covariates and potential confounders. The infectious diseases specialist’s assessment and its effect on antibiotics adjustment was also determined. Mortality analysis Results 304 patients were included, 150 exposed, 154 non-exposed. Mean age 65.0 years (SD 14.6) and mean Charlson index 4.5 (SD 2.8). 186 (61.2%) patients had COVID-19 and 256 (84.2%) community acquired pneumonia. Length of hospital stay was 20.8 days (SD 17.0), ICU stay was 12.2 days (SD 10.9), total number of antibiotics administered was 2.7 (SD 1.7). No association was found between 30 days mortality and exposure HR 1.14 (CI95% 0.76-1.70), although infectious diseases specialist’s assessment is associated with a lower mortality HR 0.29 (CI95% 0.19-0.45). There was no association between exposure and antimicrobial therapy duration IRRa 1.17 (CI95% 0.90-1.54), hospital stay IRRa 1.02 (CI95% 0.75-1.38) or ICU stay IRRa 1.24 (CI95% 0.8-1.9). Adjusted outcomes Conclusion The use of multiplex PCR pneumonia panel was not associated with changes in mortality, antibiotics duration, hospital or ICU stay. Integrating this type of testing into antimicrobial stewardship programs is necessary to contribute to more rational decision-making. Disclosures Jorge Cortes, MD, Pfizer: Grant/Research Support Carlos Álvarez-Moreno, PhD, Pfizer: Grant/Research Support

The Effect of Isoniazid for Tuberculosis Prevention on Pregnancy Risk Among Women Living With HIV on Antiretroviral Treatment and Progestin-Based Hormonal Contraception.

Concomitant use of antiretroviral therapy (ART), hormonal contraception, and isonicotinic acid hydrazide (isoniazid) for tuberculosis prevention is common among women of reproductive age who are living with HIV in sub-Saharan Africa. We estimated the effect of isoniazid on 6-month pregnancy risk among Malawian women living with HIV in the Family Planning and Antiretroviral Therapy (FP-ART) prospective cohort study, overall and among subgroups defined by ART regimen type and hormonal contraceptive method. The analytic sample included visits contributed by participants who were currently using either efavirenz- or dolutegravir-based ART and either depot medroxyprogesterone acetate (DMPA) or levonorgestrel (LNG) implant contraception at the time of the visit. The exposure was self-reported, current isoniazid use (yes/no). The binary outcome measure, 6-month pregnancy, was defined as an estimated conception date 1-183 days after the study visit date. We used a marginal structural linear risk regression model with inverse probability of treatment weights, multiple imputation by chained equations, and bootstrapping to estimate risk differences (RD) and 95% confidence intervals (CI). The analytic sample included 4709 study visits occurring between September 2017 and June 2021. The weighted 6-month pregnancy risk among isoniazid use visits was 3.0% compared with 2.3% among non-use visits (RD 0.7%, 95% CI: -0.7%, 2.1%), and the results were qualitatively similar for all subgroup estimates. We did not find a clinically significant effect of isoniazid use on 6-month pregnancy incidence among women concomitantly using ART and either DMPA or LNG implant contraception.

P-1661. Characteristics and Outcomes Associated with Treatment of Asymptomatic Bacteriuria Among Patients with Neurogenic Bladder in a Statewide Hospital Database

Abstract Background Inappropriate treatment of asymptomatic bacteriuria (ASB) among hospitalized patients leads to longer length of stay (LOS) without improving outcomes. ASB is common in individuals with neurogenic bladder (NB); however, little is known about the epidemiology, treatment, and outcomes of inpatients with NB and ASB. Methods Between 1/1/2017-12/31/2023, abstractors collected deidentified data—including signs/symptoms of urinary tract infections (UTI) and 30-day outcomes—from inpatients with a positive urine culture (UC) at 46 hospitals. Due to poor documentation of NB, we defined NB using surrogates (Table 1). Patients without signs or symptoms of UTI were classified as ASB. Characteristics of patients a) with vs. without NB and b) with NB and ASB who were treated vs. untreated were compared using t or chi-squared tests. Finally, we compared 30-day outcomes of patients with NB and ASB treated vs. untreated using general estimating equation models adjusting for variables known to be associated with the outcomes via inverse probability of treatment weighting. Results Of 45,800 inpatients with a positive UC, 6% (2,769) had NB (Table 2). Compared to patients without NB, patients with NB were more often male (59% vs. 29% p&amp;lt; 0.001), younger (median age 69 vs. 76 p&amp;lt; 0.001), less likely to be white (64.6% vs. 77% p&amp;lt; 0.001) and more likely to use a catheter (76% vs. 17% p&amp;lt; 0.001). While ASB rates (25.7% vs. 25.2%, p=0.62) were similar, bacteremia from a presumed urinary source (4.6% vs. 7.2%, p&amp;lt; 0.001) was less common in patients with NB. 85.1% (605/711) of patients with NB with ASB received antibiotic therapy. Similar to patients without NB, altered mental status (AMS) was the main predictor of ASB treatment (23.8% vs. 13.3% p=0.017; Table 3). LOS after UC was longer among those with NB and ASB who were treated vs. untreated (4 vs. 3 days, aIRR: 1.538, 95% CI: 1.33-1.77 p&amp;lt; 0.001; Table 4). Conclusion Among inpatients with NB in a statewide dataset, ASB was common, more frequently treated with antibiotics, and treatment was associated with longer LOS. AMS was the main predictor of ASB treatment. Bacteremia was lower among patients with NB, suggesting UC overuse. Disclosures Barbara Trautner, MD, PhD, Abbott Laboratories: Stocks/Bonds (Public Company)|AbbVie: Stocks/Bonds (Public Company)|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Phiogen Pharma: Advisor/Consultant Elizabeth McLaughlin, MS, RN, Blue Cross Blue Shield of Michigan: Salary Support

Efficacy and Safety of Mechanical Thrombectomy in Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients on Low-Dose Aspirin.

Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (mRS 0-2). Secondary outcomes included excellent functional outcome at 90 days (mRS 0-1), mortality, and day-one post-MT NIHSS score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Among 1,354 patients, 150 were on pre-stroke low-dose aspirin. After applying Inverse Probability of Treatment Weighting (IPTW), Aspirin use was associated with significantly better functional outcomes (mRS 0-2: OR =1.89 , 95% CI, 1.14 to 3.12 ) and lower 90-day mortality (OR = 0.56, 95% CI, 0.32 to 1.00). The aspirin group had lower NIHSS scores on day one (β = -1.5, 95% CI, -2.8 to - 0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI, 0.60 to 1.43). Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.