Date Of Diagnosis Research Articles

Abstract A062: Glycemic control and risk of total and advanced prostate cancer in Veterans with diabetes: analysis of disparities by race/ethnicity

Abstract Introduction Access to quality healthcare is considered a key driver in the multifactorial process giving rise to racial inequities in two of the most common complex diseases in adult men in the US - prostate cancer and diabetes. Whether inequities in diabetes treatment and outcomes, and/or related metabolic and hormone signaling pathways contribute to racial differences in prostate cancer outcomes in an equal access setting is unknown. Our objective is to determine if associations between glycemic control assessed by routine clinically measured hemoglobin A1c (A1c), among men with diabetes and risk of total and advanced prostate are similar in Black and White men receiving care from the Veterans Health Administration (VHA). Methods We used clinical data from the VHA to construct a longitudinal cohort of male Veterans >=45 years of age with diagnosed diabetes free of any cancer from 01/01/2010 to 12/31/2019. We classified men with total prostate cancer if the date of prostate cancer diagnosis preceded any other cancer diagnosis. Advanced prostate cancer was classified as prostate cancer diagnosis with Gleason score >=8, or PSA >=100 ng/mL, or metastasis, or death from prostate cancer. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for time-updated annual mean A1c (<7% [ref]; 7-8%; >8%) and total and advanced prostate cancer risk adjusted for age; marital status; rurality, smoking; annual primary care visits; service-connected disability; comorbidities; statin use; and oral diabetes medication use for non-Hispanic Black (NHB) and non-Hispanic White (NHW) men separately. Results Among 736,964 Veterans with diabetes, we observed 31,330 prostate cancer events including 6,779 advanced prostate cancers. For NHW men, poor glycemic control (A1c >8%) and moderate control (A1c 7-8%) were associated with a 19% (HR=0.81; 95%CI=0.78-0.84) and 8% lower risk (HR=0.92; 95%CI=0.89-95) of total prostate cancer incidence (p-trend<0.001). Among NHB men, inverse associations were attenuated for poor (HR=0.90; 95% CI=0.86-0.95) and moderate (HR=1.01; 95% CI=0.96-1.06) glycemic control and total prostate cancer risk (p-trend <0.001). For advanced prostate cancer, associations were inverse for poor (HR=0.90; 95% CI=0.83-0.97) and moderate glycemic control (HR=0.90; 95% CI=0.84-0.97) and advanced prostate cancer risk in NHW men, while non-statistically significant associations were observed in NHB men with poor HR=1.06; 95%CI=0.96-1.18) and moderate glycemic control (HR=1.04; 95%CI=0.94-1.16). Conclusion In the largest equal access healthcare system in the US, inverse associations for glycemic control and risk of total and advanced prostate cancer varied by race/ethnicity with stronger inverse associations observed in NHW men compared to NHB men. Whether the racial differences in diabetes treatment and care contribute to the observed disparities in total and advanced prostate cancer risk could inform precision public health efforts aimed at reducing inequities in both diabetes and prostate cancer outcomes. Citation Format: Michael T. Marrone, Kinfe G. Bishu, Neal Axon, Hermes Florez, Robert L. Grubb, Mulugeta Gebregziabher. Glycemic control and risk of total and advanced prostate cancer in Veterans with diabetes: analysis of disparities by race/ethnicity [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A062.

Clinical, electrocardiographic, and diagnostic imaging features and outcomes in cats with electrocardiographic diagnosis of ventricular pre-excitation: a retrospective study of 23 cases (2010–2022)

Introduction/ObjectivesVentricular pre-excitation (VPE) occurs when atrial electrical impulses prematurely excite the ventricles through an aberrant muscle bundle known as an accessory pathway (AP). Orthodromic atrioventricular reciprocating tachycardia is a re-entrant, narrow complex supraventricular tachycardia (SVT), maintained through retrograde conduction over an AP. The study aimed to describe patient signalments, clinical signs, electrocardiographic (ECG) and diagnostic imaging features, treatments, prognostic variables, and outcomes in cats with ECG diagnosis of VPE. AnimalsTwenty-three cats diagnosed with VPE between January 2010 and August 2022 were included in this study. Materials and MethodsThis was a multicenter, retrospective study with twenty-three cats diagnosed with VPE between January 2010 and August 2022. Ventricular pre-excitation diagnosis was based on ECG evidence of shortened PR interval, delta wave, and prolonged QRS duration. The median survival time (MST) was estimated by the Kaplan-Meier curve. Log-rank tests were performed to assess for an association between clinical signs or presence of structural heart disease on the MST. ResultsFourteen (60.8%) cats with VPE also had SVT documented on ECG, with 7 of 14 with ECG confirmation of orthodromic atrioventricular reciprocating tachycardia. Four (17.4%) cats had suspected AP-mediated tachyarrhythmia based on associated clinical signs. Common presenting signs included collapse (15/23; 65.2%) and respiratory distress (14/23; 60.8%). Five (21.7%) cats were asymptomatic. Heart rate during SVT ranged from 310 to 420 bpm (median: 375 bpm). Initial treatment included atenolol (10/18), sotalol (5/18), diltiazem (2/18), and amiodarone (1/18). From the date of diagnosis, MST was 1872 days (5.1 years). ConclusionsThe majority of cats with VPE also had symptomatic SVT. The prognosis for cats with VPE is considered good with an MST of greater than five years.

Abstract B020: DNA methylation and pancreatic cancer in select gene promoter regions: A repeated measures case-control study of US military service members

Abstract Introduction: Pancreatic cancer (PC) is a devastating disease, its etiology is not fully understood, and there is a paucity of non-invasive biomarkers for early diagnosis. While DNA methylation (DNAm) holds promise, associations between DNAm and PC risk are poorly understood, especially regarding temporal changes in associations. Therefore, we aimed to evaluate potential associations between DNAm in pre-diagnostic serum on 9 genes (BNIP3, CDKN1C, CLDN4, LCN2, p16, RASSF1, SFN, SPARC, and TFPI-2) and 2 repetitive elements (Alu and LINE-1) and PC risk in a US Department of Defense cohort. Methods : The study population included 82 PC cases, diagnosed 1991 - 2007, and 229 controls individually- matched on age (within 5 years), sex, race, and serum draw time period. Cases had up to 3 pre- diagnostic serum samples. Controls had 1 serum sample collected 0-10 years before their selection date (date of case diagnosis). DNA was extracted from serum and the percentage of cytosines at a given CpG site that were methylated was quantified via Pyrosequencing. For serum samples within a time window (<2, 2-<5, and 5-10 years pre-diagnosis), we computed odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of each CpG site with PC risk (66 sites in total across all genes and repetitive elements) with conditional logistic regression models. DNAm was evaluated as both a binary variable and a continuous variable. Results : In samples collected 5-10 years before diagnosis, those with no DNAm (0% DNAm) had increased odds of PC compared to those with DNAm (>0% DNAm) in the promoter region of BNIP3 (Chr10:131982293 OR, 95% CI: 5.63, 1.16 – 27.28) and those with lower DNAm (<median) had increased odds of PC compared to those with higher DNAm (≥median) in the promoter regions of CDKN1C (Chr11:2886398 OR, 95% CI: 4.07, 1.16 – 14.31; Chr11:2886388 OR, 95% CI: 3.51, 1.24 – 9.96) and RASSF1 (Chr3:50340841 OR, 95% CI: 3.98, 1.15 – 17.45). Similarly, in samples collected 2 - <5 years before diagnosis, lower DNAm (<median) was associated with increased odds of PC compared to those with higher DNAm (≥median) in the promoter region of TFPI-2 (Chr7:93890717 OR, 95% CI: 3.82, 1.20 – 12.15). In models with DNAm as a continuous measure and in samples collected <2 years before diagnosis, a 1% increase in DNAm in the promoter region of SFN was associated with increased odds of PC (Chr1:26863188 OR, 95% CI: 1.23, 1.01 – 1.51). There was no evidence of associations between DNAm on Alu, CLDN4, LCN2, LINE-1, p16, or SPARC and PC risk. Conclusions : Our findings of increased risk of PC associated with lower DNAm on BNIP3, CDKN1C and TFPI-2 and higher DNAm on SFN genes suggest there may be molecular patterns occurring prior to PC diagnosis that could be considered further for developing non-invasive biomarkers for early diagnosis of this aggressive carcinoma. The opinions and assertions expressed herein do not reflect the official policy or position of the Uniformed Services University, the Department of Defense, or the National Cancer Institute. Citation Format: Jordan McAdam, Ruth M Pfeiffer, Alexander P Keil, Ann Meyer, Anwar E Ahmed, Dechang Chen, Jennifer Rusiecki. DNA methylation and pancreatic cancer in select gene promoter regions: A repeated measures case-control study of US military service members [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B020.

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival

Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown. To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer. This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models. OS, from diagnosis date and from start of first-line chemotherapy. The study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P <.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P <.001; and 0.86; 95% CI, 0.81-0.92; P <.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P <.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; < 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%). This single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and the molecular pathogenesis of colorectal cancer with chemotherapy response is needed.

Successful surgical treatment of metachronous carcinoma of the appulla of Vater and ductal carcinoma of the distal parts of the pancreas

Background. Currently, there is a steady trend towards an increase in the incidence of both synchronous and metachronous multiple primary malignant tumors (MPMT). However, metachronous polyneoplasia of the pancreatobiliary tract is relatively rare, and there have been very few reports on successful treatment of this malignancy. Case presentation. In September 2014, the patient K. was diagnosed with adenocarcinoma of the ampulla of Vater (T2N0M0, stage Ib) and underwent gastropancreatoduodenal resection with the creation of pancreatic-gastric anastomosis at the Abdominal Department of Cancer Research Institute of Tomsk National Research Medical Center. There were no complications in the postoperative period. At a 6.5-year followup, no evidence of disease progression was found. In April 2021, a follow-up examination conducted at the Cancer Research Institute revealed a large lesion on the distal part of the pancreatic stump with no clinically significant manifestations. Diagnosis of MPMT was confirmed by transgastric endoscopic ultrasound-guided biopsy. Histological and immunohistochemical examinations revealed undifferentiated ductal carcinoma of the pancreas. Considering the metachronous tumor localization, pancreatic stump extirpation with resection of the posterior wall of the stomach and splenectomy was performed. No complications occurred in the postoperative period. The patient received replacement therapy for exocrine pancreatic insufficiency and individual correction of carbohydrate metabolism. At a 15-month follow-up, liver metastases were detected, and palliative chemotherapy was administered. The patient died 6 months later due to disease progression. The survival time was 99 months after the first surgery and 21 months after the second surgery. Conclusion. We report a rare case of metachronous cancers of the ampulla of Vater and pancreatic stump developed with an interval of 6.5 years. The patient underwent successful curative resections consecutively. The overall survival time from the date of diagnosis was 99 months.

Socio-demographic variations in prostate cancer diagnosis recording: Primary care compared to the Cancer Registry in England

IntroductionIn the UK, primary care data are often used for cancer-related research, but the accuracy of cancer information is uncertain. ObjectiveWe investigated socio-demographic variation based on the recording date of prostate cancer diagnosis between primary care and the National Cancer Registry (CR). ApproachWe utilised a data extract of 1,600,000 patients over 65 years from Clinical Practice Research Datalink (CPRD). We extracted prostate cancer diagnoses using Read and SNOMED-CT codes from primary care, and ICD-10 from CR. Initial code entry determined diagnosis dates. We categorised recording timing differences as earlier, same-day or later in primary care than CR and used the chi-squared test and logistic regression (adjusted for recording year) to compare these discrepancies across age, deprivation, and ethnicity. ResultsWe included 26,875 men with prostate cancer diagnoses commonly recorded in both sources during 2000-2016 (1,030 excluded with missing ethnicity). Compared to CR, 1,747 (7%) had diagnoses recorded on the same day in primary care, while 20,615 (77%) had later recordings with a median delay of 21 days (IQR: 13-38). Age at diagnosis was associated with recording discrepancies (p&lt;0.001); older men were more likely to have earlier/same-day recordings. Adjusted ORs for age groups were 1.4 (95%CI: 1.3-1.5) for 60-69, 1.3 (1.2-1.5) for 70-79, and 0.9 (0.8-1.0) for ≥80 compared to &lt;60. No associations were found between deprivation (p=0.096) or ethnicity (p=0.067) and recording differences. Conclusion/ ImplicationsThe discrepancy in prostate cancer information between primary care and CR underscores potential biases in studies relying solely on one data source.

Cost-effectiveness analysis with surrogate endpoint: mobile targeted active case detection for early detection of tuberculosis

Abstract Objective This study aimed to determine cost-effectiveness analysis with the surrogate endpoint of mobile targeted active case detection (MTACD) programmes in the early detection of tuberculosis (TB) cases. Methods A cross-sectional study to determine the cost-effectiveness with the surrogate endpoint of MTACD as compared with passive case detection (PCD) from the provider’s perspective. Data were gathered on the costs and significant dates (TB screening date, first TB symptoms date, TB diagnosis date, and TB treatment starting date) for 904 patients from five Sabah districts in 2022. A combined step-down and activity-based costing method was used to estimate provider costs. The health outcome measures used were the time taken by the day to detect TB cases. Cost-effectiveness analysis with surrogate endpoint was assessed using cost per TB screening by MTACD and PCD, and the mean of the time taken by the day to detect TB cases. Key findings The total cost for a patient to be screened by MTACD was Malaysian Ringgit (MYR) 96.6 (MYR 1 = USD 0.22), while the cost by PCD was MYR 43.1. The MTACD generally costs MYR 1727.1 to detect a case of TB, compared with MYR 586.9 for PCD. However, MTACD used a shorter mean time to detect TB cases (52.7 days) than PCD (98.9 days). Conclusions Despite the higher costs per screening, MTACD may shorten the days of diagnosis from the onset of TB symptoms when compared with PCD. This study is beneficial when budgeting for TB programmes since MTACD can detect TB cases earlier and lead to early treatment.

O60 SURVIVAL DISPARITIES AMONG INDIGENOUS GROUPS WITH HTN LINKED TO THEIR POPULATION CONCENTRATION

Background and objective: The indigenous groups are considered minority populations, primarily residing in rural areas. Cardiovascular disease stands as the leading cause of mortality, affecting native populations as well. This study aims to compare the overall survival (OS) rates among patients diagnosed with hypertension (HTN) in four Colombian departments where the population concentration of indigenous groups is over 10% compared to departments where it is less than 1%. Methods: Longitudinal retrospective cohort study. Population: Indigenous adults diagnosed with HTN from July 1st, 2014, to June 30 th, 2015, from the National Registry of Chronic Kidney Disease (NRCKD). The follow-up period was until July 30, 2023. We grouped indigenous communities according to their population concentration calculated by the Observatory of the Colombian Presidential Program for Human Rights. The probability of global survival from the date of diagnosis was estimated using Kaplan-Meier analysis. An unadjusted Royston Parmar flexible regression model was fitted. Right-censoring was defined as abandonment or completion of follow-up without death occurring. Results: 67,353 indigenous prevalent cases were identified from July 1st, 2022 to June 30th, 2023, representing an HTN prevalence of 2.76%. Among them, 48.90% are in Cauca, Nariño, La Guajira, and Córdoba. Natives of Nariño registered a higher proportion of GFR stages 3 and 4, calculated using the CKD-EPI formula, compared to departments with a concentration of less than 1% (48.30% and 3.15% vs. 8.08% and 0.45% respectively). 2.600 cases were included in the survival analysis. Natives residents from Nariño and Cauca had the highest risk of all-cause mortality (HR = 7.66; 95% CI 3.33 – 17.59 and HR = 7.36; 95% CI 3.26 – 16.61) compared to groups living in departments with &lt;1% concentration. Conclusions: In the Colombian health system, the hazard of all-cause mortality is higher for indigenous individuals with HTN living in Nariño and Cauca compared to those living in departments with less than 1% of the indigenous population.

O61 HYPERTENSION IN COLOMBIA: ETHNIC GROUP COMPARISONS IN CHARACTERIZATION AND SURVIVAL

Background and objective: Research has shown that ethnic minorities may be disproportionately affected by arterial hypertension. The aim of this study is to compare the overall survival (OS) HTN patients within the Colombian health system, by their ethnic group. Methods: Design: Longitudinal retrospective cohort study. Population: Adults diagnosed with HTN from June 1, 2014, to July 30, 2015, from the National Registry of Chronic Kidney Disease (NRCKD). The follow-up period was until July 30, 2023. Analysis: The probability of global survival from the date of diagnosis was estimated using Kaplan-Meier analysis. An unadjusted Royston Parmar flexible regression model was fitted. Right-censoring was defined as abandonment or completion of follow-up without death occurring. Results: 5,634,812 cases were identified from june 1st 2022 to july 30th 2023, and 299,161 incident cases were included in the survival analysis. 95.29% had no ethnic group, 1.20% were indigenous, 3.47% were Afro-descendant and 0.03% were Gypsy (ROMA). ROMA group had a higher proportion of residents in Bogotá, D.C. compared to other groups (13.96% vs ∼3%). Afro-descendant group had a higher proportion of obesity (30.61% vs. 27.86%) and diagnosis of Chronic Kidney Disease (27.31% vs. 15.69%) compared to cases with no ethnic group, while ROMA group had a higher occurrence of DM cases (23.46% vs. 21.66%). 9 years OS was higher in ROMA group (OS = 0.85; CI 95% 0.71 – 0.93) compared to indigenous (OS = 0.83; CI 95% 0.81 – 0.84) and afro-descendants (OS = 0.83; CI 95% 0.83 – 0.84). The probability of all-cause mortality was approximately 20% higher among afro-descendants and indigenous people (HR = 1.20; 95% CI 1.14 – 1.25 and HR = 1.22; 95% CI 1.12 – 1.32, respectively) compared to the non-ethnic group. In contrast, the ROMA did not present differences (p = 0.712). Conclusions: In the Colombian health system, differences in OS among afro-descendant and indigenous groups are observed compared to non-ethnic population.

P034 THE INFLUENCE OF SOCIODEMOGRAPHICAL CHARACTERISTICS AND COMORBIDITIES ON SURVIVAL IN ADULTS WITH HTN IN COLOMBIA

Background and objective: Awareness of the impact of hypertension (HTN) on health enables the implementation of effective measures to control the disease. This study characterizes the survival of the Colombian adult population with hypertension. Methods: This longitudinal retrospective cohort study included adults diagnosed with HTN from July 1, 2013, to june 30, 2014, from the National Registry of Chronic Kidney Disease (NRCKD). The primary outcome was the time from diagnosis to all-cause mortality. The probability of from the date of diagnosis was estimated using Kaplan-Meier analysis. Log-rank test evaluated differences in survivor functions. Patients were followed from baseline until death, abandonment, or the end of follow-up on July 30, 2023. Results: Baseline characteristics: The analysis included 285,418 cases. The mean age at diagnosis was 59.17 ± 14.58 years. 61.25% were females, 67.13% were affiliated with third-payer insurance, and 28.81% resided in the Central region. At baseline, 36.77% of the study population had comorbidities, including diabetes mellitus (DM) or chronic kidney disease (CKD) or both. 36,110 all-cause deaths were recorded during the follow-up period. Survival analysis: The 10-year overall survival (OS) rate was 0.84 (95% CI 0.84–0.84). The unadjusted log-rank comparisons revealed a lower probability of survival for men compared to women (0.81 vs. 0.86, respectively) and for individuals with state insurance compared to those with third-party insurance (0.80 vs. 0.86, respectively). The survival rates were found to be lower in individuals with HTA, DM, and HTN at baseline (0.68) compared to those with HTN and CKD (0.78), HTN and DM (0.81), or only HTN (0.88) (p &lt; 0.001). Conclusions: The survival of individuals with HTN is influenced by a variety of sociodemographic characteristics and can be further complicated by the presence of other comorbidities, which can potentially amplify the negative effects on an individual's health. These findings may be useful for decision-makers to focus on the identification of patients with different characteristics of risk.

249. OVERALL SURVIVAL OF PATIENTS WITH ESOPHAGEAL CANCER TREATED WITH DEFINITIVE CHEMORADIOTHERAPY: INSIGHTS FROM A RETROSPECTIVE STUDY

Abstract Background Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for patients with locally advanced esophageal cancer. However, definitive chemoradiotherapy (dCRT) may be considered as an alternative for those with unresectable disease, cervical location of the tumor or if a non-surgical approach is preferred based on the patient's condition. Heterogeneity in indications for dCRT makes it challenging to draw generalized conclusions regarding outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns in patients with specified homogeneous indications for dCRT. Methods Patients with esophageal cancer treated with dCRT (50.4 Gy radiotherapy concomitant with 6 cycles of carboplatin/paclitaxel) between 2012-2022 in a tertiary referral center were identified from our institutional database. Primary endpoint was OS calculated from date of diagnosis until date of death or last day of follow-up, using the Kaplan Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality following dCRT and disease recurrence. Results 162 patients were included, median follow-up was 74.6 months (IQR 46.2-99.3). The full dCRT regimen was completed by 116 (73.9%) patients. The 30- and 90-day mortality were 2.5% and 8.3%, respectively. The median OS was 23.7 months (95% CI 6.65-40.66) for cervical location of the tumor, 13.7 months (95% CI 7.92-29.8) for irresectable disease, 28.2 months (95% CI 12.10-44.22) for patients unfit for surgery and 20.6 months (95% CI 14.14-27.13) for those with preference for dCRT (p=0.15). Disease recurrence was observed in 74 patients (46%), located locoregional (46%), distant (19%) or both locoregional and distant (35%). Conclusion(s) Treatment with dCRT resulted in a 5-year OS of 35% and is associated with a high 90-day mortality. Disease recurrence was mostly locoregional located and was observed in 46% of patients. This emphasizes the critical necessity for enhanced treatment strategies centered on improving locoregional disease control.

404. REAL-WORLD TREATMENT PATTERN OF EOSINOPHILIC ESOPHAGITIS IN JAPAN

Abstract Background Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration in the esophageal epithelium that causes esophageal dysfunction-related symptoms. The treatment for EoE includes acid suppressants (proton pump inhibitors (PPIs) or potassium competitive acid blocker (P-CAB)), topical corticosteroid (TCS), and diet therapy. In addition, biologics (i.e. dupilumab) have been recently approved for EoE in the US. However, the appropriate initial and maintenance therapy for EoE have not been established yet. Therefore, the aim of the study was to investigate the treatment pattern of EoE and its association with fibrostenosis in Japan. Methods We investigated prescription pattern for EoE analyzing an employer-based health insurance claim database from 2005 to 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. The initial treatment of interest for EoE included PPIs, P-CAB, and TCS (swallowed inhaled CS). The initial treatment for EoE was defined as these drugs prescribed within two months from the index date of EoE diagnosis. The discontinuation rates of initial PPIs or P-CAB were analyzed using Kaplan-Meier method. The discontinuation of treatment was defined as no treatment following within 90 days from the prescription of the previous treatment. Results Overall, 984 EoE patients (45 years old [38-52], male 747 [75.9%]) were ultimately analyzed. Most of the initial treatment for EoE was acid suppressants (PPIs [323 54.9%], P-CAB [241, 41%]), followed by TCS (13, 2.2%) and combination therapy of PPIs or P-CAB and TCS (11, 1.9%). PPIs or P-CAB discontinued in approximately 50% and 70% of the cases at approximately 150 days and 720 days respectively from the start of the initial therapy. The switching to the second-line therapy from the initial PPIs or P-CAB rarely happened. During the observation period, no EoE patients developed esophageal stenosis. Conclusion PPIs or P-CAB were most prescribed as the initial treatment for EoE in Japan. In addition, more than half of EoE patients discontinued such initial therapy within 2 years without fibrostenotic complication. These findings indicate that EoE that can respond to initial acid suppressants therapy does not necessarily require the maintenance therapy to prevent esophageal fibrostenosis.

A Single-center Experience With >200 Lung Transplant Recipients With COVID-19 Infection.

Although COVID-19 is no longer a declared global health emergency, data remain limited on the impact of COVID-19 in lung transplant recipients. We identified lung transplant recipients who were diagnosed with COVID-19 from March 2020 through August 2022 in our institutional database and investigated clinical outcomes. We then analyzed outcomes based on date of COVID-19 diagnosis (first wave March 2020-October 2020; second wave November 2020-2021; third wave December 2021-September 2022) and compared these results. Of the 210 lung transplant recipients (median age 67; 67% men) enrolled, 140 (67%) required hospital admission. Among admitted recipients, 35 (25%) were intubated and 7 (5%) were placed on extracorporeal membrane oxygenation. Overall survival was 67.1% at 1 y and 59.0% at 2 y post-COVID-19 diagnosis. COVID-19 led to mortality in all 5 patients diagnosed during their index admission for lung transplantation. Although overall survival was significantly better in recipients with COVID-19 during the third wave, in-hospital mortality remained high (first wave 28%, second wave 38%, and 28% third wave). Vaccination (partially vaccinated versus none and fully vaccinated versus none) was the only significant protective factor for hospital admission, and age 70 y and older and partially vaccinated (versus none or fully vaccinated) were independent risk factors for in-hospital mortality. Overall survival after COVID-19 infection in lung transplant recipients continues to improve; however, in-hospital mortality remains remarkably high. Vaccination appears to have been impactful in preventing hospital admission, but its impact on in-hospital mortality is still unclear. Further research is needed to better identify lung transplant recipients at high risk for mortality from COVID-19.

Exploring potential risk factors for lower limb amputation in people with diabetes-A national observational cohort study in Sweden.

Risk factors for lower limb amputation (LLA) in individuals with diabetes have been under-studied. We examined how 1/demographic and socioeconomic, 2/medical, and 3/lifestyle risk factors may be associated with LLA in people with newly diagnosed diabetes. Using the Swedish national diabetes register from 2007 to 2016, we identified all individuals ≥18years with an incident diabetes diagnosis and no previous amputation. These individuals were followed from the date of diabetes diagnosis to amputation, emigration, death, or the end of the study in 2017 using data from the In-Patient Register and the Total Population Register. The cohort consisted of 66,569 individuals. Information about demographic, socioeconomic, medical, and lifestyle risk factors was ascertained around the time of the first recorded diabetes diagnosis, derived from the above-mentioned registers. Cox proportional hazard models were used to obtain hazard ratios (HR) with 95% confidence intervals (CI). During the median follow-up time of 4years, there were 133 individuals with LLA. The model adjusting for all variables showed a higher risk for LLA with higher age, HR 1.08 (95% CI 1.05-1.10), male sex, HR 1.57 (1.06-2.34), being divorced, HR 1.67 (1.07-2.60), smokers HR 1.99 (1.28-3.09), insulin treated persons HR 2.03 (1.10-3.74), people with low physical activity (PA) HR 2.05 (1.10-3.74), and people with an increased foot risk at baseline HR>4.12. People with obesity had lower risk, HR 0.46 (0.29-0.75). This study found a higher risk for LLA among people with higher age, male sex, who were divorced, had a higher foot risk group, were on insulin treatment, had lower PA levels, and were smokers. No significant association was found between risk for LLA and education level, country of origin, type of diabetes, blood glucose level, hypertension, hyperlipidemia, creatinine level, or glomerular filtration rate. Obesity was associated with lower risk for LLA. Identified variables may have important roles in LLA risk among people with diabetes.

Accurately identifying incident cases of venous thromboembolism in the electronic health record: Performance of a novel phenotyping algorithm

BackgroundAccurate identification of incident venous thromboembolism (VTE) for quality improvement and health services research is challenging. The purpose of this study was to evaluate the performance of a novel incident VTE phenotyping algorithm defined using standard terminologies, requiring three key indicators documented in the electronic health record (EHR): VTE diagnostic code, VTE-related imaging procedure code, and anticoagulant medication code. MethodsRetrospective chart reviews were conducted to assess the performance of the algorithm using a random sample of phenotype(+) and phenotype(−) diagnostic encounters from primary care practices and acute care sites affiliated with five hospitals across a large integrated care delivery system in Massachusetts. The performance of the algorithm was evaluated by calculating the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity, using the phenotype(+) and phenotype(−) diagnostic encounters sample and target population data. ResultsBased on gold-standard manual chart review, the algorithm had a PPV of 95.2 % (95 % CI: 93.1–96.8 %), NPV of 97.1 % (95 % CI: 95.3–98.4 %), sensitivity of 91.7 % (95 % CI: 90.8–92.6 %), and specificity of 98.4 % (95 % CI: 98.1–98.6 %). The algorithm systematically misclassified a low number of specific types of encounters, highlighting potential areas for improvement. ConclusionsThis novel phenotyping algorithm offers an accurate approach for identifying incident VTE in general populations using EHR data and standard terminologies, and accurately identifies the specific encounter and date of diagnosis of the incident VTE. This approach can be used for measurement of incident VTE to drive quality improvement, research to expand the evidence, and development of quality metrics and clinical decision support to improve the diagnostic process.

Dispensed prescription medications and short-term risk of pulmonary embolism in Norway and Sweden

Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of drugs. We analysed the association between prescription drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004–2014) and 36,088 in Sweden (2005–2014). A case-crossover design was used to compare individual drugs dispensed 1–30 days before the date of pulmonary embolism diagnosis with dispensation in a 61–90 day time-window, while controlling for the receipt of other drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.

Real-World Evidence Application in Translational Medicine: Making Use of Prescription Claims to Inform Drug-Drug Interactions of a New Psoriasis Treatment.

Patients with psoriasis often take multiple medications due to comorbidities, raising concerns about drug-drug interactions (DDIs) during the development of new medicines. DDI risk assessments of a new small molecule showed risks of CYP3A4 autoinduction and being a sensitive CYP3A4 substrate. We conducted a real-world evidence (RWE) claims analysis to assess the frequency of prescription claims for up to 12 months from the date of the initial psoriasis diagnosis for drugs that may interact with CYP3A4 substrates. We used 2013 to 2018 patient data from the US Merative MarketScan Research Database. Among patients diagnosed with psoriasis, less than 1% had a claim for a moderate/strong inducer, but up to 15% had a claim for moderate/strong inhibitor. Most prescriptions for CYP3A4 inhibitors or inducers included antibiotics and anticonvulsants. While CYP3A4 inducers were rarely used, those treated received more than >90 days treatment. Then, these RWE data were used to inform the early translational medicine strategy for the new investigational drug by strategically integrating DDI evaluations into a first-in-human healthy volunteer trial prior to studies in patients with psoriasis. The resulting DDI substudy showed that the investigational small molecule did not induce midazolam clearance but was sensitive to CYP3A inhibition, leading to the decision to exclude concomitant use of strong CYP3A4 inducers or inhibitors from clinical trials.

Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.

Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). Target trial emulation study. Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders. Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. Ministry of Food and Drug Safety of South Korea.

Social and clinical drivers of stress responses in African American breast cancer survivors

Racial differences in breast cancer morbidity and mortality have been examined between Black/African American women and White women as part of efforts to characterize multilevel drivers of disease risk and outcomes. Current models of cancer disparities recognize the significance of physiological stress responses, yet data on stress hormones in Black/African American women with breast cancer and their social risk factors are limited. We examined cortisol levels in Black/African American breast cancer patients and tested their association with social and clinical factors to understand the relationship between stress responses and women’s lived experiences. Seventy-two patients who completed primary surgical treatment were included in this cross-sectional study. Data on sociodemographic characteristics and chronic diseases were obtained by self-report. Breast cancer stage and diagnosis date were abstracted from electronic health records. Cortisol levels were determined from saliva samples. Compared to those without hypertension, patients with hypertension were 6.84 (95% CI 1.33, 35.0) times as likely to have high cortisol (p = 0.02). The odds of having high cortisol increased by 1.42 (95% CI 1.03, 1.95, p = 0.03) times for every point increase in negative life events. Hypertension and negative life events are associated with high cortisol levels in Black/African American patients. These findings illustrate the importance of understanding the lived experiences of these patients to enhance cancer health equity.

Supraventricular tachycardia diagnosis in asthma patients is associated with adverse health outcomes.

Supraventricular tachycardia (SVT) can occur during treatment of an acute asthma exacerbation. There are, however, no data on the long-term outcomes of children who are diagnosed with both asthma and SVT. This study aims to analyze the impact of SVT in asthmatic children on mortality and/or cardiac arrest, hypothesizing asthmatic subjects with SVT have increased mortality and/or cardiac arrest compared to asthmatic subject with no-SVT. This was a retrospective cohort study, utilizing the TriNetX© electronic health record (EHR) database that included asthmatic subjects 2-18 years of age. The study population was divided into two groups (subjects with SVT diagnosis and no-SVT diagnosis). Data related to demographics, diagnostic, procedural, and medication codes were collected. The primary outcome was any death and/or cardiac arrest in a patient after the first asthma diagnosis date. This study included 91,066 asthmatic subjects (244 [0.27%] with SVT and 90,822 [99.73%] with no-SVT). Multivariable logistic regression analysis demonstrated that after controlling for demographic and clinical features, the odds of all-cause death and/or cardiac arrest after the first reported asthma exacerbation was significantly higher in asthmatic children with SVT compared to no-SVT (odds ratio [OR]: 4.30, confidence interval [CI]: 2.50-7.39, p < .001). Our large nationwide EHR study suggests that asthmatic pediatric patients with documented SVT diagnosis at any point in their EHR may be at increased risk of adverse health outcomes compared to no-SVT. Further studies are needed to determine the factors contributing to the increased risk of mortality and/or cardiac arrest in children with asthma and SVT.