Large US Database Research Articles

Concomitant Use of Oral Anticoagulants with Oral Dipeptidyl Peptidase-4 Inhibitors and Serious Bleeding Events.

In a prior screening study, saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP-4is and serious bleeding in a large US database, using self-controlled case series (SCCS) and case-crossover (CCO) designs. The study population was eligible Medicare beneficiaries co-exposed to a DPP-4i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016-2020. For the SCCS, we used conditional Poisson regression to estimate adjusted rate ratios (RRs) between each co-exposure (vs. not) and serious bleeding and divided the RR by the adjusted RR for the corresponding lisinopril + precipitant pair to obtain ratios of RRs (RRRs). For the CCO, we estimated the adjusted odds ratios (ORs) of exposure to the precipitant in the focal window vs. referent window using multivariable conditional logistic regression and divided the ORs in the object drug-exposed cases over the ORs in negative object drug-exposed cases to obtain the ratios of ORs (RORs). The adjusted RRRs for serious bleeding ranged from 0.32 (0.05-1.91) for apixaban/lisinopril + saxagliptin to 3.49 (1.29-9.48) for warfarin/lisinopril + linagliptin. The adjusted RORs ranged from 0.01 (0.00-0.20) for rivaroxaban/lisinopril + saxagliptin to 2.99 (0.74-12.11) for apixaban/lisinopril + linagliptin. While we could not confirm previously identified signals because of statistical imprecision, several numerically elevated estimates still warrant caution in concomitant use and further examination.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

Contemporary management of ischemic priapism: A 12-year population-based analysis from a large US database.

Priapism is a urological condition characterized by a persistent erection. The management varies based on its subclassifications. Despite established clinical guidelines for ischemic priapism, there is a lack of large-scale research focused on patient characteristics and management strategies. To analyze the contemporary management of ischemic priapism in the US, exploring patient demographics and clinical characteristics, as well as predictors of erectile dysfunction (ED) and penile prosthesis implantation (PPI). We performed a retrospective analysis of the PearlDiver Mariner database, reviewing records from 2010-2021. Adult males diagnosed with ischemic priapism were included. Data analysis covered demographic, clinical variables, and management strategies. Predictors of de novo ED and PPI were evaluated using multivariable logistic regression analysis. Of 36,120 patients, most (93%) received only medical management, and a minority underwent surgical interventions (penile shunt surgery [PSS], PPI or both). Medical management was typically effective, as 67.08% of the patients in this group experienced only one episode of priapism. However, de novo ED occurred in 16.57% of these patients. The majority of patients undergoing PPI had an inflatable prosthesis (81%). Older age (odds ratio, OR 1.02), the presence of metabolic diseases (OR 1.39), neurogenic disorders (OR 1.72), solid pelvic malignancies (OR 1.09), and multiple episodes of priapism were identified as significant predictors of de novo ED (all p<0.05). Similarly, age (OR 1.03), the presence of metabolic diseases (OR 1.23), solid pelvic malignancies (OR 1.99), and multiple episodes of priapism were associated with higher likelihood of PPI (all p<0.05). Most cases of ischemic priapism are managed with the medical therapy. Less than 3% of patients with ischemic priapism receive PPI, and when this occurs an inflatable prosthesis is favored. Age, specific comorbidities, and multiple episodes of priapism appear to be significant predictors of ED and PPI.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events

Background This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. Methods Adults with gMG and without MG were identified from a large US database (2017–2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. Results The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. Conclusions gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

A Comparison of Adverse Short-Term Outcomes After Forefoot Amputation Based on Patient Height.

The objective of this investigation was to evaluate adverse short-term outcomes after partial forefoot amputation with a specific comparison performed based on patient height. The American College of Surgeons National Surgical Quality Improvement Program database was analyzed to select patients with a 28805 Current Procedural Terminology code (amputation, foot; transmetatarsal) who underwent the procedure with "all layers of incision (deep and superficial) fully closed." This resulted in 11 patients with a height of 60 inches or less, 202 with a height greater than 60 inches and less than 72 inches, and 55 with a height of 72 inches or greater. Results of the primary outcome measures found no significant differences among groups with respect to the development of a superficial surgical site infection (0% versus 6.4% versus 5.5%; P = .669), deep incisional infection (9.1% versus 3.5% versus 10.9%; P = .076), or wound disruption (0% versus 5.4% versus 5.5%; P = .730). In addition, no significant differences were observed among groups with respect to unplanned reoperations (9.1% versus 16.8% versus 12.7%; P = .630) or unplanned hospital readmissions (45.5% versus 23.3% versus 20.0%; P = .190). The results of this investigation demonstrate no differences in short-term adverse outcomes after partial forefoot amputation with primary closure based on patient height. Although height has previously been described as a potential risk factor in the development of lower-extremity pathogenesis, this finding was not observed in this study from a large US database.

Combination of Venetoclax and Azacytidine As First-Line Induction Therapy for Acute Myeloid Leukemia in Patients Younger Than 60 Years: A Tertiary Care Center Experience from Our Low Middle Income Country

INTRODUCTION: Anthracycline- and cytarabine-based “7+3” induction chemotherapy has been the frontline treatment option for acute myeloid leukemia (AML) in the non-elderly and fit patient population. Sixty percent of these patients (pts) achieve Complete remission (CR). However, an estimated 30-40% of pts relapse (Tara L. Lin &amp; Livio Pagano et al., Expert Review of Hematology, 2021). In addition, based on a large US database study and studies from India, the “7+3” regimen is associated with high rates of induction mortality, intensive care unit (ICU) admission, and duration of hospital stay. BCL2 inhibition with venetoclax has been a new paradigm for the treatment of AML. Herein, we present our institutional experience in treating AML in pts younger than 60 years (yrs) old with a combination of venetoclax (ven) and azacytidine (aza). METHODS: We conducted a retrospective review of patients aged 18-60 who were newly diagnosed with AML between May 2020 and May 2023, and in this study, we included all pts, who met the WHO criteria for AML, did not have APML, had no prior history of treatment for other malignancies, and had not received prior induction treatment. Pts received aza 75 mg/m2 on days 1-7 and ven, which escalated from 100 to 200 to 400 mg on days 1-3. Ven continued at 400 mg without posaconazole or 100 mg with posaconazole from days 4-28, and bone marrow aspiration and biopsy were performed after day 28. Patients who achieved morphological remission without count recovery had up to 14 days off therapy before subsequent cycles. Non-responders received up to 1-2 additional cycles. Post-response (defined as a complete remission [CR] ), and patients with measurable residual disease (MRD) negative by multiparameter flow cytometry (MFC) with the residual blast cutoff being &amp;lt; 0.1% proceeded to further cycles. The primary objective of the study is to focus on the induction mortality rate and complete remission in younger, newly diagnosed AML pts who received aza and ven in the induction period. Responses to induction and subsequent post-remission therapy were recorded. RESULTS: A total of 17 patients with AML aged ≥ 18 years and ≤60 years were treated with a combination of aza and ven from May 2020 to May 2023. The median patient age was 47 yrs (interquartile range [IQR]: 30-56 yrs, 52.9% age &amp;lt;50 yrs ), and 52.9% of the pts were males. According to the European Leukemia Network (ELN) guidelines for 2022, using FISH and next-generation sequencing (NGS), 5 out of 17 pts (41.2%) were categorized as having favorable risk, 3 out of 17 patients (17.6%) were categorized as having intermediate risk, and 9 out of 17 pts (41.2%) were categorized as having adverse risk. During their inpatient stay, none of the pts required renal replacement therapy (RRT), and 1 out of 17 (5.8%) pts required mechanical ventilation. The dose of ven was 400 mg in 8 out of 17 patients (47%). One pt was on sertraline and received 200mg of ven. The remaining pts (8/17) received 100 mg of ven with posaconazole, which reduced the cost of the treatment to 50%. The median pretreatment white cell count (WCC) was 11.49 x 10^9/L (IQR: 6.25 to 39.74 x 10^9/L). The platelet count took a median of 31 days to recover above 50 x 10^9/L (IQR: 28-43 days), while the median time for the absolute neutrophil count (ANC) to recover above 1 x 10^9/L was 52 days (IQR: 47-60 days). 11 out of 17 (64%) of our patients achieved complete remission (CR1) after the first cycle. Additionally, 5 out of 17 (29.4%) were MRD-negative when compared to a large US study database and an Indian study (see table1). The median duration of hospital stay was 16 days (IQR: 10-20 days), and the induction mortality rate was 1/17 (5.8%) (see table1). This death occurred in a patient with adverse risk. CONCLUSIONS: The response to induction therapy with venetoclax and azacytidine in young adults with AML was similar to the standard “7+3” induction therapy, with around 64% of pts achieving CR after the first cycle. The median duration of hospital stay, frequency of ICU admission, and especially induction mortality have been lower than the “7+3” regimen. BCL2 inhibition has indeed resulted in a paradigm shift in the treatment of AML. Therefore, it may be the right time to consider the combination of ven and aza as the standard first-line induction therapy for all pts with AML.

Morbidity and Mortality of the Transmetatarsal Amputation: A Comparative NSQIP Analysis

The objective of this investigation was to compare the morbidity and mortality of transmetatarsal amputation to other frequently performed surgical procedures utilizing a large US database. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was interrogated for the purposes of this investigation. We initially extracted data related to the Current Procedural Terminology (CPT) code 28805 (amputation, foot; transmetatarsal) and the variable labels “estimated probability of morbidity” and “estimated probability of mortality.” We subsequently performed a CPT code search for those procedures occurring at a frequency greater than 10,000 in the database, and additionally extracted data for estimated probability of morbidity and estimated probability of mortality for these procedures. This resulted in identification of 17 additional procedures. CPT code 28805 was associated with the highest estimated probability of morbidity of the cohort (0.1360 ± 0.0669), and this demonstrated statistical significance higher than all other CPT codes (p < .001). CPT code 28805 was associated with the second-highest estimated probability of mortality of the cohort (0.0327 ± 0.0596). This demonstrated statistical significance less than that of CPT code 27245 (0.0327 ± 0.0596 vs 0.0547 ± 0.0661; p < .0001), but statistical significance higher than all other CPT codes (p<0.001). The results of this investigation indicate that transmetatarsal amputation carries a substantial risk for morbidity and mortality in comparison to other commonly performed surgical procedures.

5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2yr) and longer-term (> 2yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

#2977 PROGRESSION AND REGRESSION OF CHRONIC KIDNEY DISEASE IN THE UNITED STATES USING ELECTRONIC MEDICAL RECORDS

Abstract Background and Aims Chronic kidney disease (CKD) is generally considered to be progressive and may lead to end-stage kidney disease (ESKD), or death. We aim to analyze a large US database and capture CKD progression, regression, ESKD and death over a 5-year follow-up, in a real-world setting. Method A retrospective cohort study was conducted using data from IBM® Explorys electronic medical records (&amp;gt;53 million patients) from 1 Jan 2010 to 31 Dec 2019. We created two main cohorts of patients with CKD: Cohort 1 and Cohort 2. Cohort 1 was based on diagnostic codes only (ICD 9/10, n = 810,987 unique patients), and Cohort 2 on KDIGO screening and staging criteria only (eGFR, UACR/UPCR values, n = 953,396). Within these cohorts, we created individual sub-cohorts for each CKD stage (1-5), though patient categorization was not mutually exclusive (one patient could contribute to multiple main and sub-cohorts). Patients in Cohort 1 were required to have an ICD code specific to a stage, and patients in Cohort 2 were required to have two consecutive laboratory test results within 3–18 months to determine KDIGO CKD stage. Index date was the date of diagnosis or second abnormal test with at least 12 months lookback period. Progression and regression were assessed for Cohort 1 using change in ICD codes and for Cohort 2, two test results (3-18 months apart) were required with a change in KDIGO eGFR stage and at least one of the values showing an increase or decrease by ≥25% in eGFR from baseline. We performed individual follow-up for progression and regression from each CKD stage to a progression or a regression event, death, loss to follow-up, or maximum 5 years, whichever came first. For ESKD, we followed up from each CKD stage to ESKD, death, loss to follow-up, or maximum 5 years. For death, we followed up from each CKD stage to death, loss to follow-up, or a maximum of 5 years. Results Most patients in Cohort 1 (ICD) and 2 (KDIGO) had stage 3 CKD at index. Mean age was 70y in Cohort 1 and 71y in Cohort 2, with 49% and 40% males, respectively. Both cohorts were predominantly Caucasian. The prevalence of cardiovascular diseases increased with CKD stage. The proportion of patients from Cohort 2 who had at least one CKD diagnosis increased from 34% in stage 1 to 86% and 83% in stage 4 and 5, respectively. CKD regression, ESKD and death increased progressively from stage 1–5 in both cohorts, except for stage 5 in Cohort 2. Progression in Cohort 1 decreased with stage and was variable in Cohort 2. The proportion of patients experiencing at least one event corresponding to CKD regression, progression, and ESKD was higher at all stages in Cohort 1 vs. Cohort 2, particularly ESKD which was markedly higher for stage 5 (91.4% vs. 13.6%). Proportion of death was similar in both cohorts and was the highest in stages 4–5. Conclusion Substantial differences in kidney outcomes were noted between CKD classifications derived from ICD codes vs. KDIGO criteria, except all-cause mortality which was comparable across both cohorts and increased notably with stage. Changes in kidney function, both progression, regression, and ESKD occurred more frequently in Cohort 1. Our analysis suggests ICD diagnosis and KDIGO criteria might not be used interchangeably in the context of utilizing real-world data sources.

Biochemical recurrence (BCR) and outcomes in patients (pts) with prostate cancer (PC) following radical prostatectomy (RP).

e17112 Background: RP is often the primary treatment option for pts with clinically localized PC. Despite its frequent success, more than 30% of pts eventually present with BCR, defined as detectable prostate-specific antigen (PSA) after RP. BCR is associated with a higher risk of developing distant metastasis and ultimately death. Current patterns of BCR and the impact of BCR on treatment choice and clinical outcomes are not well characterized. Methods: This retrospective cohort study uses nationally representative Optum© Electronic Medical Records (EMR) data from 1/2010 to 9/2021. Eligible pts were adults who underwent RP after PC diagnosis, had ≥ 3 available PSA values after RP, and had EMR activity for at least 6 mo before and 12 mo after RP. Pts with prior malignancy except nonmelanoma skin cancers and pts with metastatic PC at baseline (BL) or within 3 months after RP were excluded. The BL period was 6 mo before RP. Primary outcome was frequency of BCR (defined as PSA ≥ 0.2 ng/mL); secondary analyses included % of pts who progressed to metastasis, castration-resistant PC (CRPC), and death after BCR, and factors associated with time to BCR. Results: 15,198 pts who underwent RP were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 63.0 (36-88) y, 85.9% of pts were White, and 10.0% were African American. Median (Q1-Q3) follow-up was 3.9 (2.4-5.7) y, and 14.3% of pts had subsequent adjuvant/salvage radiation therapy (RT). Overall, 19.8% of all pts and 61.4% of the subgroup of 2,178 pts with subsequent RT developed BCR. Among pts with BCR (n = 3,016), 16.3% had a PSA doubling time ≤ 10 mo, 17.1% developed metastasis, 13.8% developed CRPC, and 9.7% died. In multivariate Cox regression models (Table), the BL factors associated with an increased risk of developing BCR were PSA 10- &lt; 20 or ≥ 20 ng/mL, Charlson comorbidity index (CCI) &gt; 0, age ≥ 65, African American race, public insurance, and living in the US South region. Conclusions: This real-world (RW) study evaluates the occurrence of BCR in pts who underwent RP with a curative intent from a large US database. This study confirms BL PSA as an important prognostic marker for BCR. A considerable % of pts with BCR developed metastatic PC (17%) or died (10%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC among pts with high-risk localized disease. [Table: see text]

Biochemical recurrence (BCR) among patients (pts) with prostate cancer (PC) after radiation therapy (RT).

e17111 Background: RT is a frequent primary treatment for pts with clinically localized PC. Despite its frequent success, 30-50% of pts eventually present with BCR, defined as rising prostate-specific antigen (PSA). BCR is associated with a higher risk of developing distant metastasis and ultimately death from PC. Understanding BCR occurrence and its impact on clinical outcomes is important for optimizing diagnostic and therapeutic strategies for recurrent disease. Methods: This is a retrospective cohort study using nationally representative Electronic Medical Records (EMR) data from Optum© from 1/2010-9/2021. Eligible pts were adults who underwent RT after PC diagnosis, had ≥ 3 available PSA values after initiating RT, and had EMR activity for at least 6 mo before and 12 mo after RT. Pts with a history of prior malignancy except nonmelanoma skin cancers and pts with metastatic PC (mPC) at baseline (BL) or within 3 months after RT were excluded. The BL period was 6 mo before RT initiation. Primary outcome was frequency of BCR, defined as rising PSA (PSA ≥ nadir + 2 ng/mL); secondary analyses included % of pts who progressed to mPC, castration-resistant PC (CRPC), and death after BCR and factors impacting time to BCR. Results: 9,292 RT pts were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 69.0 (40-88) y, 83.2% of pts were White, and 13.4% were Black. Median PSA nadir was 0.11 ng/mL, 32.5% of pts had received androgen deprivation therapy (ADT) during BL period, and median (Q1-Q3) follow-up from RT initiation was 3.8 (2.4-5.7) y. Overall, 10.2% of pts developed BCR. Among BCR pts (n = 949), 51.2% had a PSA doubling time (PSADT) &lt; 6 mo and 16.9% had a PSADT between 6-10 mo; 35.0% developed mPC, 30.2% developed CRPC, and 23.4% died. In multivariate Cox regression models, the BL factor associated with the highest risk of developing BCR was PSA ≥ 20 ng/mL. Conversely, the risk of developing BCR was lower for pts who received ADT during BL. Conclusions: This real-world (RW) study evaluates BCR occurrence in pts who underwent RT with a curative intent from a large US database. The study confirms BL PSA as an important prognostic marker for BCR, while use of ADT before RT is associated with a lower risk of BCR. A considerable % of pts with BCR developed mPC (35%) or died (23%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC in pts with high-risk localized disease. [Table: see text]

Tenecteplase Versus Alteplase for Acute Stroke: Mortality and Bleeding Complications

Intravenous thrombolysis with alteplase has been the foundation of initial treatment of acute ischemic stroke for several decades. Tenecteplase is a thrombolytic agent that offers logistical advantages in cost and administration relative to alteplase. There is evidence that tenecteplase has at least similar efficacy and safety outcomes compared with alteplase for stroke. In this study, we compared tenecteplase versus alteplase for acute stroke in a large retrospective US database (TriNetX) regarding the following 3 outcomes: (1) mortality, (2) intracranial hemorrhage, and (3) the need for acute blood transfusions. In this retrospective study using the US cohort of 54 academic medical centers/health care organizations in the TriNetX database, we identified 3,432 patients treated with tenecteplase and 55,894 patients treated with alteplase for stroke after January 1, 2012. Propensity score matching was performed on basic demographic information and 7 previous clinical diagnostic groups, resulting in a total of 6,864 patients with acute stroke evenly matched between groups. Mortality rates, the frequency of intracranial hemorrhage, and blood transfusions (as a marker of significant blood loss) were recorded for each group over the ensuing 7- and 30-day periods. Secondary subgroup analyses were conducted on a cohort treated from 2021 to 2022 in an attempt to determine whether temporal differences in acute ischemic stroke treatment would alter the results. Patients treated with tenecteplase had a significantly lower mortality rate (8.2% versus 9.8%; risk ratio [RR], 0.832) and lower risk of major bleeding as measured by the frequency of blood transfusions (0.3% versus 1.4%; RR, 0.207) than alteplase at 30 days after thrombolysis for stroke. In the larger 10-year data set of patients with stroke treated after January 1, 2012, patients receiving tenecteplase were not found to have a statistically different incidence of intracranial hemorrhage (3.5% versus 3.0%; RR, 1.185) at 30 days after the administration of the thrombolytic agents in patients. However, a subgroup analysis of 2,216 evenly matched patients with stroke treated from 2021 to 2022 demonstrated notably better survival and statistically lower rates of intracranial hemorrhage than the alteplase group. In our large retrospective multicenter study using real-world evidence from large health care organizations, tenecteplase for the treatment of acute stroke demonstrated a lower mortality rate, decreased intracranial hemorrhage, and less significant blood loss. The favorable mortality and safety profiles observed in this large study, taken together with previous randomized controlled trial data and operational advantages in rapid dosing and cost-effectiveness, all support the preferential use of tenecteplase in patients with ischemic stroke.

Peripheral artery disease and extracorporeal membrane oxygenation: Examining a high-risk cohort over time.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a resource-intensive approach for the management of refractory cardiogenic shock. Within this population exists a substantial cohort of patients with peripheral artery disease (PAD), which independently increases the risk of complications and all-cause mortality. We studied 10-year national trends of the impact of PAD among VA-ECMO recipients to better understand the prevalence of PAD and implications on outcomes in this vulnerable population. This 10-year retrospective, propensity score-matched study identified all adult patients (≥18) who underwent VA-ECMO between 2009 and 2018, from a large US database (National Inpatient Sample). Patients with an ICD diagnosis of PAD were identified. The primary endpoints of in-hospital mortality, bleeding complications and major limb loss (above- or below-knee amputation) were compared between patients with PAD to those without. A total of 6768 patients were identified, of which 342 (5.3%) had PAD. The median age at admission was significantly higher in PAD patients [64years vs. 55years; p < .01], as was male gender [71% vs. 64%; p < .01]. Patients with PAD had higher rates of smoking (38.9% vs. 23.3%), hypertension (71.1% vs. 50%), diabetes (37.4% vs. 27.0%), chronic kidney disease (30.1% vs. 18.0%), coronary artery disease (76.0% vs. 35.0%) and dyslipidemia (76.0% vs. 35.0); all p < .01. After propensity-matching 2:1 for comorbidities, PAD patients were found to have significantly greater overall complications, including in-hospital mortality, bleeding, surgical wound infections, pseudoaneurysms, and major adverse limb events [71.9% vs. 63.9%; p < .01]. Subgroup analysis revealed greater in-hospital mortality [62.2% vs. 55.3%; p < .05], major amputations [4.1% vs. 0.3%; p < .01] and blood transfusions [32.2% vs. 26.2%; p < .05] in PAD patients. Over 2014-2018, the non-PAD group demonstrated statistically discernable trends in a 51.1% decrease in overall complications and a 28.1% increase in survival to discharge (all p < .01). Over the same time period the PAD cohort experienced a modest, nonsignificant, decrease in complications [7.0%, p = .40] and a decrease in those surviving to discharge [47.1% vs. 40.5%, p = .91]. Patients with PAD on VA-ECMO are sicker at baseline and experience significantly greater major amputations and higher in-hospital mortality. They have not benefitted from the considerable decrease in complication rates and increase in survival to discharge over time as compared to their non-PAD counterparts. These findings demonstrate the substantial frailty of the PAD population within an already high-risk cohort, and highlight the need for better procedural approaches and innovative technologies.

Disparities in pediatric drug-resistant epilepsy care

IntroductionEpilepsy affects millions of children worldwide, with 20–40% experiencing drug-resistant epilepsy (DRE) who are recommended for epilepsy surgery evaluation and may benefit from surgical management. However, many patients live with DRE for multiple years prior to surgical epilepsy referral or treatment or are never referred at all.ObjectiveWe aimed to describe factors associated with referral for epilepsy surgery in the USA, in order to identify disparities in DRE, characterize why they may exist, and recognize areas for improvement.MethodsPediatric patients diagnosed with DRE between January 1, 2004 and December 31, 2020 were identified from the Pediatric Health Information System (PHIS) Database. Patients treated with antiseizure medications (ASMs) only, ASMs plus vagus nerve stimulation (VNS), and ASMs plus cranial epilepsy surgery were studied regarding access to epilepsy surgery and disparities in care. This study used chi-square tests to determine associations between treatment time and preoperative factors. Preoperative factors studied included epilepsy treatment type, age, sex, race/ethnicity, insurance type, geographic region, patient type, epilepsy type, and presence of pediatric complex chronic conditions (PCCCs).ResultsA total of 18,292 patients were identified; 10,240 treated with ASMs, 5019 treated with ASMs + VNS, and 3033 treated with ASMs + cranial epilepsy surgery. Sex was not found to significantly vary among groups. There was significant variation in age, census region, race/ethnicity, patient type, presence of PCCCs, diagnosis, and insurance (p < 0.001). Those treated surgically, either with VNS or cranial epilepsy surgery, were 2 years older than those medically treated. Additionally, those medically treated were less likely to be living in the Midwest (25.46%), identified as non-Hispanic white (51.78%), have a focal/partial epilepsy diagnosis (8.74%), and be privately insured (35.82%).ConclusionsWe studied a large administrative US database examining variables associated with surgical epilepsy evaluation and management. We found significant variation in treatment associated with age, US census region, race/ethnicity, patient type, presence of PCCCs, diagnosis, and health insurance type. We believe that these disparities in care are related to access and social determinants of health, and we encourage focused outreach strategies to mitigate these disparities to broaden access and improve outcomes in children in the USA with DRE.

S291 Demographic and Socio-Economic Trends in Colon Cancer Screening Rates Among Older Adults in the United States

Introduction: Colorectal cancer (CRC) screening decreases incidence and improves survival. Screening rates can be influenced by disparities in demographic, social and economic factors. Using a large US database, We aimed to study the demographic and socio-economic factors affecting colon cancer screening rates among older adults. Methods: We used the Behavior Risk Factor Surveillance System, a nationally representative health-related telephone survey in 2020, to compare reported colorectal cancer screening rates. We included all respondents over the age of 50 eligible for colon cancer screening. We performed binary logistic regression modeling to obtain adjusted odds ratios (aORs) adjusting for race, level of education, health care access limited by insurance coverage and cost. Weighted percentages were calculated as appropriate. Statistical analysis was performed using IBM SPSS version 25, IBM corp. Results: Of the 401,959 patients surveyed, 132,128 (72.39%) eligible patients had reported undergoing at least one of recommended CRC tests in the appropriate time interval, 43,570 (27.61%) had reported not undergoing any form of screening. Individuals with no cost issues related to access to a doctor in the past year, graduated high school, college attendance and Caucasian had a lower reported risk of lack of CRC screening (aOR 0.729, 0.699, 0.761 p< 0.001; aOR 0.829, 0.788, 0.872 p< 0.001; aOR 0.684, 0.651, 0.720, p< 0.001, aOR 0.731, 0.698, 0.765 p< 0.001 respectively). Individuals without insurance, minority races and females had a higher reported risk of lack of CRC screening (aOR 3.230, 3.082, 3.384 p< 0.001; aOR 1.459, 1.350, 1.576 p< 0.001; aOR 1.084, 1.059, 1.110 p< 0.001 respectively). (Table) Conclusion: In this large national survey, we found a modest increase in reported risk of lack of appropriate CRC screening in individuals without insurance, minority groups and females. Individuals with Caucasian race, no cost issues, high school or college education were associated with higher rates of appropriate CRC screening. Further studies on the influence of social determinants of health are required to study its effect on CRC screening rates. Table 1. - Logistic regression Modeling to obtain adjusted odds ratios (aORs) adjusting for race, level of education, health care access limited by insurance coverage and cost P value Adjusted Odds Ratio (aOR) 95% C.I. Lower Upper No cost issues < .001 .729 .699 .761 No insurance .000 3.230 3.082 3.384 Female < .001 1.084 1.059 1.110 Age 55 to 59 .000 .441 .426 .457 Age 60 to 64 .000 .370 .358 .384 Age 65 to 64 .000 .284 .273 .294 Age 65 to 69 .000 .234 .225 .244 Age 60 to 74 < .001 .260 .241 .281 Graduated high school < .001 .829 .788 .872 Attended College < .001 .684 .651 .720 Graduated College < .001 .535 .509 .563 Caucasian < .001 .731 .698 .765 African American < .001 1.459 1.350 1.576 American Indian < .001 1.295 1.190 1.409 Asian only .006 1.253 1.068 1.470 Other Race < .001 1.138 1.056 1.225

Inhaled Nitric Oxide vs Epoprostenol During Acute Respiratory Failure: An Observational Target Trial Emulation

The inhaled vasodilators nitric oxide and epoprostenol may be initiated to improve oxygenation in mechanically ventilated patients with severe acute respiratory failure (ARF); however, practice patterns and head-to-head comparisons of effectiveness are unclear. What are the practice patterns and comparative effectiveness for inhaled nitric oxide and epoprostenol in severe ARF? Using a large US database (Premier Healthcare Database), we identified adult patients with ARF or ARDS who were mechanically ventilated and started on inhaled nitric oxide, epoprostenol, or both. Leveraging large hospital variation in the choice of initial inhaled vasodilator, we compared the effectiveness of inhaled nitric oxide with that of epoprostenol by limiting analysis to patients admitted to hospitals that exclusively used either inhaled nitric oxide or epoprostenol. The primary outcome of successful extubation was modeled using multivariate Fine-Grey competing risk (death or hospice discharge) time-to-event models. Among 11,200 patients (303 hospitals), 6,366 patients (56.8%) received inhaled nitric oxide first, 4,720 patients (42.1%) received inhaled epoprostenol first, and 114 patients (1.0%) received both therapies on the same day. One hundred four hospitals (34.3%; 1,666 patients) exclusively used nitric oxide and 118 hospitals (38.9%; 1,812 patients) exclusively used epoprostenol. No differences were found in the likelihood of successful extubation between patients admitted to nitric oxide-only hospitals vsthose admitted to epoprostenol-only hospitals (subdistribution hazard ratio, 0.97; 95%CI, 0.80-1.18). Also no differences were found in total hospital costs or death. Results were robust to multiple sensitivity analyses. Large variation exists in the use of initial inhaled vasodilator for respiratory failure across US hospitals. Comparative effectiveness analyses identified no differences in outcomes based on inhaled vasodilator type.

Validation of an ovarian cancer line of therapy algorithm for real- world outcomes research in insurance claims (375)

Validation of an ovarian cancer line of therapy algorithm for real- world outcomes research in insurance claims (375)

Pregnancy, delivery, and neonatal outcomes among women with incarcerated uteri: A population-based study of a large US database

ObjectiveIncarcerated uterus occurs at a rate of 1:3000 pregnancies. Previous studies focused on risk factors and management options, providing limited information about pregnancy outcomes. This study evaluates the effect of incarcerated uterus on pregnancy, delivery, and neonatal outcomes. MethodsRetrospective study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 2004 to 2014. Incarcerated uterus was identified using ICD-9 code 654.3X. Multivariate logistic regression analysis was used to compare maternal and neonatal outcomes among women with and without incarcerated uterus while adjusting for confounders. ResultsIncarcerated uteri were identified in 370 pregnancies, and 9,096,418 pregnancies were control cases. Compared to controls, women with incarcerated uterus were more likely to be Caucasian, have smoked during pregnancy, have had a previous caesarean section, have thyroid disease, endometriosis, leiomyomas, pelvic inflammatory disease and adhesions, and ovarian cyst (P-value < 0.05 all). Women with incarcerated uterus were more likely to have placenta previa (aOR 3.1, 95% CI 1.3–7.4), deliver by caesarean section (aOR 2.4, 95% CI 1.8–3.1), have postpartum hemorrhage (aOR 2.8, 95% CI 1.8–4.4), and require blood transfusion (aOR 5.2, 95% CI 3.1–8.8). Hydronephrosis occurred more often in women with incarcerated uterus (0.8% versus 0.1%). Moreover, they were more likely to have infants with congenital anomalies (aOR 4.0, 95% CI 1.5–10.6). Rates of preeclampsia, preterm birth, and small for gestational age were similar between the two groups (P-value > 0.05, all). ConclusionWomen with incarcerated uterus were more likely to encounter adverse delivery and neonatal outcomes compared to the general population. These findings may help guide prenatal counseling and prenatal surveillance.

Independent External Validation of the METSSS Model Predicting Survival After Palliative Radiotherapy.

A validation of the recently published METSSS model (developed from a large US database) predicting survival after palliative radiotherapy was performed. METSSS includes age, sex, cancer type, localization of distant metastases, comorbidity, and radiotherapy site. Both 1- and 5-year survival was assessed in the validation cohort. Deviations between model-predicted and observed survival were analyzed. The METSSS model predicted a 1-year survival of 29% (cohort median, predicted probability 0-74% in individual patients). The observed 1-year survival rate was 33% (median survival 5.3 months). The corresponding figures for predicted 5-year survival were 0% and 0-46% (observed rate 3%). Statistical comparison of the survival curves was possible for two of three strata (insufficient number of low-risk patients) and the resulting p-value was 0.045. A complete validation was hampered by imbalances in group size. More than 90% of our patients were classified as high risk. If this distribution is representative for other countries, the METSSS model might need adjustment. However, its general ability to predict survival appears promising.

Modular Metal-Backed Tibial Components Provide Minimal Mid-Term Survivorship Benefits Despite Increased Cost and Frequency of Use: A Retrospective Review of the American Joint Replacement Registry Database

BackgroundPrevious studies have demonstrated equivalent survivorship of modular metal-backed tibial (MBT) and all-polyethylene tibial (APT) components. The purpose of this study is to compare the utilization and outcomes of APT and MBT components in a large US database. MethodsThe American Joint Replacement Registry was queried to identify all patients undergoing primary total knee arthroplasty (TKA) during the study period from 2012 to 2019. These patients were divided into cohorts based on tibial component (APT or MBT). Cohort demographics including gender, hospital size, hospital teaching status, region, age, and Charlson Comorbidity Index were reported with descriptive statistics. Overall reoperation rates and revisions for infection, aseptic loosening, periprosthetic fracture, manipulation under anesthesia, and revision for other reasons were identified using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes and compared across APT and MBT cohorts. Kaplan-Meir survival analysis was performed based on reason for reoperation for APT and MBT. ResultsDuring the study period, 703,007 TKAs were reported with 97.8% utilizing MBT and 2.2% utilizing APT components. Despite the introduction of alternative payment models during the study period, the utilization of APT decreased from 5.8% in 2012 to 1.7% in 2019. The survival of APT and MBT TKAs were similar across the study period: 98.1% vs 98.6% at 8 years. The rate of reoperation for all-causes was higher for APT compared to MBT (1.36% vs 1.00%; odds ratio 1.52). ConclusionDespite their paucity of use and lower cost APT remained within a 0.4% margin of survivorship when compared to MBT implants for up to 8 years. Level of EvidenceLevel III, retrospective.