Electronic Health Record Database Research Articles

Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study

Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease (eGFR <30ml/min per 1.73m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30ml/min per 1.73m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days-0.09%, 95% CI:-0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI:-0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI:-0.03 to 0.09%), ischaemic stroke (ARR at 90 days-0.06%, 95% CI:-0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI:-0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

Long-term QT interval analysis for real world patients with Insertable cardiac monitors taking antiarrhythmic drugs

Abstract Background The QT interval serves as a surrogate biomarker for ventricular repolarization. Variance in QT intervals can clinically lead to pro-arrhythmia and sudden cardiac death. An insertable cardiac monitor (ICM) device capable of continuously monitoring the QT interval over a long period can provide diagnostic value for evaluating physiologic or drug induced variations in QT interval. Objective To analyze feasibility of continuous QTc interval monitoring in patients with ICM and evaluate the QTc interval changes in patients taking antiarrhythmic drugs. Methods Patients QT intervals detected from daily ICM ECG data from real-world patients taking antiarrhythmic drugs such as sotalol, amiodarone and dofetilide during hospitalization while implanted with ICM were analyzed from the de-identified Electronic Health Record (EHR) database linked with ICM device data warehouse. The ICM ECG was processed through the previously defined QT detection algorithm which calculates the QTc interval for every beat to generate continuous long term QTc trends. A patient contributed to the prescription group if they were prescribed antiarrhythmics drugs prior to hospitalization in the EHR database otherwise they contributed to the non-prescription group. Patients from the prescription group who were administered antiarrhythmic drugs via injection or IV during hospitalization were removed from the analysis. A 30-day median QTc interval from 30-60 days prior to hospitalization was used as baseline. Wilcoxon signed-rank test was used to compare the paired difference from days 1-5, 1-10, 30-60, and 60-90 after hospitalization to their respective baseline. Results 441 patients (avg. age: 70±11, 50.5% female) were included with 220 prescription and 221 non-prescription. The baseline QTc intervals were 414 and 417.3 msec for non-prescription and prescription groups, respectively. There was a significant increase in QTc on days 1-5, 1-10, 30-60, and 60-90 after hospital admission compared to the baseline (all p &amp;lt; 0.001) for the non-prescription group. The prescription group showed increase in QTc only on days 30-60 after hospitalization when compared to baseline (p&amp;lt;0.05). A larger QTc increase was observed in non-prescription receiving anti-arrhythmic loading on days 1-5 after hospitalization compared to patients on prescription prior to hospitalization (P&amp;lt;0.05). Conclusion Utilizing a QT interval detection algorithm from an ICM can provide long term QT trends for patients with an ICM. Continuous monitoring of QT can help to detect sudden changes in QT due to antiarrhythmic drugs which may lead to increased risk of arrhythmias or cardiac arrest.

BOLD: Blood-gas and Oximetry Linked Dataset

Pulse oximeters measure peripheral arterial oxygen saturation (SpO2) noninvasively, while the gold standard (SaO2) involves arterial blood gas measurement. There are known racial and ethnic disparities in their performance. BOLD is a dataset that aims to underscore the importance of addressing biases in pulse oximetry accuracy, which disproportionately affect darker-skinned patients. The dataset was created by harmonizing three Electronic Health Record databases (MIMIC-III, MIMIC-IV, eICU-CRD) comprising Intensive Care Unit stays of US patients. Paired SpO2 and SaO2 measurements were time-aligned and combined with various other sociodemographic and parameters to provide a detailed representation of each patient. BOLD includes 49,099 paired measurements, within a 5-minute window and with oxygen saturation levels between 70–100%. Minority racial and ethnic groups account for ~25% of the data – a proportion seldom achieved in previous studies. The codebase is publicly available. Given the prevalent use of pulse oximeters in the hospital and at home, we hope that BOLD will be leveraged to develop debiasing algorithms that can result in more equitable healthcare solutions.

Comparing penalization methods for linear models on large observational health data.

This study evaluates regularization variants in logistic regression (L1, L2, ElasticNet, Adaptive L1, Adaptive ElasticNet, Broken adaptive ridge [BAR], and Iterative hard thresholding [IHT]) for discrimination and calibration performance, focusing on both internal and external validation. We use data from 5 US claims and electronic health record databases and develop models for various outcomes in a major depressive disorder patient population. We externally validate all models in the other databases. We use a train-test split of 75%/25% and evaluate performance with discrimination and calibration. Statistical analysis for difference in performance uses Friedman's test and critical difference diagrams. Of the 840 models we develop, L1 and ElasticNet emerge as superior in both internal and external discrimination, with a notable AUC difference. BAR and IHT show the best internal calibration, without a clear external calibration leader. ElasticNet typically has larger model sizes than L1. Methods like IHT and BAR, while slightly less discriminative, significantly reduce model complexity. L1 and ElasticNet offer the best discriminative performance in logistic regression for healthcare predictions, maintaining robustness across validations. For simpler, more interpretable models, L0-based methods (IHT and BAR) are advantageous, providing greater parsimony and calibration with fewer features. This study aids in selecting suitable regularization techniques for healthcare prediction models, balancing performance, complexity, and interpretability.

Implications of trial eligibility in patients with heart failure with mildly reduced or preserved ejection fraction.

Clinical trials in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) commonly have detailed eligibility criteria. This may contribute to challenges with efficient enrolment and questions regarding the generalizability of trial findings. Patients with HFmrEF/HFpEF from a large US healthcare system were identified through a computable phenotype applied in linked imaging and electronic health record databases. We evaluated shared eligibility criteria from five recent/ongoing HFmrEF/HFpEF trials (PARAGON-HF, EMPEROR-Preserved, DELIVER, FINE-ARTS, and SPIRRIT-HFpEF) and compared clinical and echocardiographic features as well as outcomes between trial-eligible and trial-ineligible patients. Among 5552 patients with HFpEF/HFmrEF, 792 (14%) were eligible for trial consideration, having met all criteria assessed. Causes of ineligibility included lack of recent loop diuretics (37%), significant pulmonary disease (24%), reduced estimated glomerular filtration rate (17%), recent stroke/transient ischaemic attack (13%), or low natriuretic peptides (12%); 53% of ineligible patients had >1 reason for exclusion. Compared with eligible patients, ineligible patients were younger (age 71 vs. 75years, P<0.001) with higher rates of coronary artery disease (66% vs. 59%, P<0.001) and peripheral vascular disease (40% vs. 33%, P<0.001), but less mitral regurgitation, lower E/e' ratio, and smaller left atrial sizes. Both eligible and ineligible patients demonstrated high rates of structural heart disease consistent with HFpEF [elevated left atrial size or left ventricular (LV) hypertrophy/increased LV mass], although this was slightly higher among eligible patients (95% vs. 92%, P=0.001). The two cohorts demonstrated similar LV global longitudinal strain along with a similar prevalence of atrial fibrillation/flutter, hypertension, and obesity. Ineligible patients had similar all-cause mortality (33% vs. 33% at 3years) to those eligible but lower rates of heart failure hospitalization (20% vs. 28% at 3years, P<0.001). Among patients with HFmrEF/HFpEF from a large health system, approximately one in seven were eligible for major trials based on key criteria applied through a clinical computable phenotype. These findings highlight the large proportion of patients with HFmrEF/HFpEF ineligible for contemporary trials for whom the generalizability of trial findings may be questioned and further investigation would be beneficial.

Systemic Anticancer Therapy and Overall Survival in Patients With Very Advanced Solid Tumors

Two prominent organizations, the American Society of Clinical Oncology and the National Quality Forum (NQF), have developed a cancer quality metric aimed at reducing systemic anticancer therapy administration at the end of life. This metric, NQF 0210 (patients receiving chemotherapy in the last 14 days of life), has been critiqued for focusing only on care for decedents and not including the broader population of patients who may benefit from treatment. To evaluate whether the overall population of patients with metastatic cancer receiving care at practices with higher rates of oncologic therapy for very advanced disease experience longer survival. This nationwide population-based cohort study used Flatiron Health, a deidentified electronic health record database of patients diagnosed with metastatic or advanced disease, to identify adult patients (aged ≥18 years) with 1 of 6 common cancers (breast cancer, colorectal cancer, non-small cell lung cancer [NSCLC], pancreatic cancer, renal cell carcinoma, and urothelial cancer) treated at health care practices from 2015 to 2019. Practices were stratified into quintiles based on retrospectively measured rates of NQF 0210, and overall survival was compared by disease type among all patients treated in each practice quintile from time of metastatic diagnosis using multivariable Cox proportional hazard models with a Bonferroni correction for multiple comparisons. Data were analyzed from July 2021 to July 2023. Practice-level NQF 0210 quintiles. Overall survival. Of 78 446 patients (mean [SD] age, 67.3 [11.1] years; 52.2% female) across 144 practices, the most common cancer types were NSCLC (34 201 patients [43.6%]) and colorectal cancer (15 804 patients [20.1%]). Practice-level NQF 0210 rates varied from 10.9% (quintile 1) to 32.3% (quintile 5) for NSCLC and 6.8% (quintile 1) to 28.4% (quintile 5) for colorectal cancer. No statistically significant differences in survival were observed between patients treated at the highest and the lowest NQF 0210 quintiles. Compared with patients seen at practices in the lowest NQF 0210 quintiles, the hazard ratio for death among patients seen at the highest quintiles varied from 0.74 (95% CI, 0.55-0.99) for those with renal cell carcinoma to 1.41 (95% CI, 0.98-2.02) for those with urothelial cancer. These differences were not statistically significant after applying the Bonferroni-adjusted critical P = .008. In this cohort study, patients with metastatic or advanced cancer treated at practices with higher NQF 0210 rates did not have improved survival. Future efforts should focus on helping oncologists identify when additional therapy is futile, developing goals of care communication skills, and aligning payment incentives with improved end-of-life care.

The Impact of Palliative Care Consultation on Aggressive Medical Interventions in End-of-life Among Patients with Metastatic Breast Cancer: Insights from the U.S. National Patient Sample.

Advancement in treatment has led to prolonged survival and a rising number of women living with metastatic breast cancer (MBC) in the United States. Due to its high symptom burden, it is recommended that palliative care be integrated into the standard care to help improve quality of life. However, little is known about the use of palliative care among MBC patients in the nation. To determine utilization of palliative care consult (PCC) after metastasis and the influence of PCC on healthcare utilization in the end of life among women living with MBC in the US. This retrospective cohort study examined a national electronic health record database to quantify the PCC use after metastasis diagnosis until death and the associations of PCC with Emergency Department (ED), Intensive Care Unit (ICU), and chemotherapies in the end-of-life women (age ≥ 18 years) living with MBC. From a cohort of 2615 deceased MBC patients, 37% received PCC in the last 6 months of life. Patients who had received PCC in the end-of-life were more likely to be hospitalized, admitted to ED and ICU, and receive chemotherapies in the last 60 days before death. However, patients who had received end-of-life PCC had less hospital and ED visits and received less chemotherapies after PCC initiated. While PCC can reduce end-of-life aggressive interventions, it was underutilized among patients with MBC in the end-of-life. A myriad of clinical and patient factors may still challenge timely consultation. We urge for future endeavors in developing strategies to remove barriers in the implementation, especially earlier in the disease course, to assure timely PC treatments and reduce discomfort amid aggressive interventions for MBC.

Taipei Medical University Clinical Research Database: a collaborative hospital EHR database aligned with international common data standards

ObjectiveThe objective of this paper is to provide a comprehensive overview of the development and features of the Taipei Medical University Clinical Research Database (TMUCRD), a repository of real-world data...

Development and Implementation of a Digital Quality Measure of Emergency Cancer Diagnosis.

Missed and delayed cancer diagnoses are common, harmful, and often preventable. Automated measures of quality of cancer diagnosis are lacking but could identify gaps and guide interventions. We developed and implemented a digital quality measure (dQM) of cancer emergency presentation (EP) using electronic health record databases of two health systems and characterized the measure's association with missed opportunities for diagnosis (MODs) and mortality. On the basis of literature and expert input, we defined EP as a new cancer diagnosis within 30 days after emergency department or inpatient visit. We identified EPs for lung cancer and colorectal cancer (CRC) in the Department of Veterans Affairs (VA) and Geisinger from 2016 to 2020. We validated measure accuracy and identified preceding MODs through standardized chart review of 100 records per cancer per health system. Using VA's longitudinal encounter and mortality data, we applied logistic regression to assess EP's association with 1-year mortality, adjusting for cancer stage and demographics. Among 38,565 and 2,914 patients with lung cancer and 14,674 and 1,649 patients with CRCs at VA and Geisinger, respectively, our dQM identified EPs in 20.9% and 9.4% of lung cancers, and 22.4% and 7.5% of CRCs. Chart reviews revealed high positive predictive values for EPs across sites and cancer types (72%-90%), and a substantial percent represented MODs (48.8%-84.9%). EP was associated with significantly higher odds of 1-year mortality for lung cancer and CRC (adjusted odds ratio, 1.78 and 1.83, respectively, 95% CI, 1.63 to 1.86 and 1.61 to 2.07). A dQM for cancer EP was strongly associated with both mortality and MODs. The findings suggest a promising automated approach to measuring quality of cancer diagnosis in US health systems.

Racial-ethnic disparities in concurrent rates of peripapillary & macular OCT parameters among a large glaucomatous clinical population.

To compare rates of change in peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) parameters among different race-ethnicities from a large electronic health record database of subjects with or suspected of glaucoma. In this retrospective cohort study, rates of change were obtained using joint longitudinal linear mixed models for eyes with ≥3 visits and ≥1 year of follow-up, adjusting for age, sex, intraocular pressure, central corneal thickness, and baseline pRNFL and mGCIPL thickness. Best linear unbiased predictor estimates of various parameters were stratified by baseline glaucoma severity and analysed by racial-ethnic group. A total of 21,472 spectral domain optical coherence tomography (OCT) pRNFL scans and 14,431 mGCIPL scans from 2002 eyes were evaluated. A total of 200 (15.6%) and 601 (46.8%) subjects identified as non-Hispanic Black (NHB) and Hispanic, respectively. NHB eyes exhibited faster rates of change in pRNFL among glaucoma suspect (global pRNFL -0.57 ± 0.55 µm/year vs. -0.37 ± 0.62 µm/year among Hispanics, p < 0.001), mild glaucoma (superior pRNFL quadrant -1.20 ± 1.06 µm/year vs. -0.75 ± 1.51 µm/year among non-Hispanic Whites (NHW), p = 0.043), and moderate glaucoma eyes (superior pRNFL quadrant -1.31 ± 1.49 µm/year vs. -0.52 ± 1.26 µm/year among Hispanics, p = 0.003). NHB eyes exhibited faster rates of mGCIPL loss corresponding to pRNFL rates. Global pRNFL and mGCIPL rates were strongly correlated (R2 = 0.70). Adjusted rates of pRNFL and mGCIPL loss significantly differed between racial-ethnic groups when stratified by glaucoma severity, with faster rates among NHB patients. These differences highlight key racial-ethnic disparities in adjusted rates of glaucoma OCT parameters.

Abstract PO2-09-06: Interaction of racial disparities on outcomes and toxicities associated with treatment of HER2+Breast Cancer- a TrinetX Database study

Abstract Objective: Investigate the interaction of racial disparities on outcomes and toxicities associated with treatment of HER2+BrCa (Breast Cancer)- a TrinetX Database study Background: HER2+BrCa is an aggressive subtype accounting for about 1/3rd of all BrCa, for which Trastuzumab based therapy remains the mainstay of treatment. While we are starting to understand the breadth of racial disparities in BrCa , the knowledge about outcomes and toxicities in relation to treatment of HER2+ BrCa is still limited. Design/Methods: In this propensity score-matched cohort study we used the TriNetX Research Network, a multi-health care organization de-identified electronic health record (EHR) database, to compare the 1-, 3-, and 5-year mortality of HER2+BrCa non-Hispanic African American (NHAA) women to a corresponding non-Hispanic White cohort (NHW). Qualification into the two race based HER2+BrCa cohorts required the presence of a C50 ICD-10-CM diagnosis code and at least one proxy for HER2 positivity such as Trastuzumab administration (index event). Cohorts were matched for age, BMI, comorbidities (HTN, DM ), and lab values using 1:1 matching with a greedy nearest neighbor search. Toxicity outcomes of interest such as cardiomyopathy, neuropathy, diarrhea, rashes, leg swelling/edema, and fatigue as well as the frequency of emergency room visits were also compared between the cohorts. The associations of observed outcome frequencies in the two cohorts were tested for significance using the chi-square test. The odds ratios and p-values, corrected for multiple hypothesis testing using the Benjamini-Hochberg procedure, are reported as an effect size and significance estimation. Results: 15983 patients met the inclusion criteria for HER2+BrCa (13611-NHW and 2372-NHAA). The mean age at the index event was 55.6 ± 12.6 years for NHAA and 57.2 ± 13.3 years for NHW. After matching the two sub-cohorts, 2303 patients remained in each. NHAA women were found to have significantly increased odds of neuropathy and cardiomyopathy for 1, 3, and 5-year time intervals after the HER2+BrCa index date, as compared to the reference NHW women (abbreviated results given in Table 1). In addition, the odds of an emergency room visit (for any reason) was found to be increased by as much as 79% in NHAA women as compared to the NHW women. The odds of experiencing fatigue/malaise, diarrhea/nausea, and rash, were reduced for NHAA women across all time intervals investigated. Odds ratios for mortality and leg swelling did not meet the significance threshold (p-value &amp;lt; 0.05). Conclusion: This study, which examined racial disparities in outcomes and toxicities associated with HER2+BrCa, revealed significant findings. NHAA women with HER2+BrCa treated with Trastuzumab based therapy demonstrated increased odds of experiencing neuropathy and cardiomyopathy compared to their NHW counterparts. Additionally, NHAA women had a higher likelihood of emergency room visits for any reason. Conversely, NHAA women exhibited decreased odds of fatigue/malaise, diarrhea/nausea, and rash. These findings underscore the importance of considering the impact of race on HER2+BrCa outcomes and treatment toxicities and suggest the need for further research and targeted interventions to address disparities and thus enhance treatment outcomes in diverse populations. Table 1: Representative significant Odds ratios and corrected p-values for outcomes comparing the NHAA and NHW cohorts. Citation Format: Monali Vasekar, Justin Petucci, Avnish Katoch, Vasant Honavar. Interaction of racial disparities on outcomes and toxicities associated with treatment of HER2+Breast Cancer- a TrinetX Database study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-06.

Treatment Patterns and Attrition With Lines of Therapy for Advanced Urothelial Carcinoma in the US

The treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC. To delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample. This retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis. Frequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 [PD-1/PD-L1] inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line. Of the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 [73.9%] men; median age at the start of first-line treatment, 73 [IQR, 66-80] years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 [30.9%]), followed by PD-1/PD-L1 inhibitors (2174 [29.9%]). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 [52.0%] and 258 of 857 [30.1%], respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 [8.1%] and 159 of 857 [18.6%], respectively), erdafitinib (39 of 2714 [1.4%] and 28 of 857 [3.3%], respectively), and sacituzumab govitecan (14 of 2714 [0.5%] and 34 of 857 [4.0%], respectively). The findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor-based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.

Abstract PS04-02: BRCA testing and PARP inhibitor utilization in real-world HER2-negative metastatic breast cancer

Abstract Background: PARP inhibitors (PARPi) have demonstrated progression-free survival benefits vs. chemotherapy in patients (pts) with metastatic breast cancer (mBC) and germline BRCA mutations (gBRCAm). NCCN guidelines recommend that all pts with mBC are offered gBRCAm testing to aid in systemic treatment decisions with PARPi. Understanding real-world gBRCAm testing patterns and PARPi use would be beneficial for improving clinical outcomes of pts with gBRCAm mBC. Methods: This retrospective cohort study identified pts ≥ 18 years old with HER2-negative mBC, diagnosed from 2014 to 2022 (US Flatiron Electronic Health Record database). gBRCAm testing patterns in mBC over time were examined by BC subtype (hormone receptor-positive [HR+] or triple-negative breast cancer [TNBC]) and disease stage at diagnosis [de novo or recurrent]). Timing of gBRCAm testing and subsequent initiation of first-line or later PARPi in pts with gBRCAm HR+ and TNBC mBC was assessed in pts diagnosed after 2018 when PARPi were approved in mBC. Prevalence of gBRCAm was calculated overall and by mBC subtype. Demographic and clinical characteristics were described by gBRCAm testing and PARPi initiation (yes/no). Real-world overall survival (OS) by PARPi use since mBC diagnosis was estimated using the Kaplan-Meier method and a log-rank test. Results: Of 15,006 total pts, 4654 (31.0%) had a gBRCAm test. Compared with pts who were not tested, gBRCAm-tested pts were younger at initial mBC diagnosis (median age: 53.5 vs. 62.0 years), had a shorter median disease-free interval before mBC diagnosis (821 vs. 959 days), and were less likely to have de novo mBC (28.0% vs. 31.2%). gBRCAm testing prevalence was 6.1% in the HR+ group (n=11,945) and 8.9% in the TNBC group (n=2430). gBRCAm testing rates mostly increased from 2014 to 2022 and were lowest in HR+ tumor subtypes; &amp;lt; 2/3 of all pts had a gBRCAm test from 2020 onwards (Table). Most pts with recurrent mBC (HR+: 68.3%; TNBC: 76.1%) were gBRCAm tested before diagnosis, whereas pts with de novo mBC were tested at a later timepoint ( &amp;gt; 60 days after mBC diagnosis – HR+: 48.3%; TNBC: 38.4%). Of all pts with gBRCAm diagnosed from 2018 onwards (n=187), 44.4% initiated PARPi. A higher proportion of pts with gBRCAm in the TNBC group initiated PARPi (52.9%) than in the HR+ group (42.4%). Pts with gBRCAm in the TNBC group received PARPi earlier than pts with gBRCAm in the HR+ group (mean days from mBC diagnosis to first PARPi use: 173 and 411 days, respectively). Fewer pts with de novo mBC (35.7%) initiated PARPi than pts with recurrent mBC (50.8%). With a median follow-up of 15.3 months, pts with gBRCAm initiated on PARPi had numerically longer median OS (32.3 months [95% CI: 24.2–47.4]) than PARPi non-initiators (21.4 months [95% CI:18.4–43.5]). OS results should be regarded with caution due to the small sample size (n=187). Conclusions: Despite NCCN guideline gBRCAm-testing recommendations, &amp;lt; 2/3 of pts with HER2-negative mBC in our study were gBRCAm tested from 2020 onwards. gBRCAm testing was lower in pts with HR+ disease and was performed at a later timepoint for pts with de novo disease. Wider and timelier implementation of gBRCAm testing to identify pts that could benefit from PARPi is warranted. Fewer pts with gBRCAm who had HR+ tumors or de novo disease received PARPi than pts with TNBC. Our data suggest that pts who initiated PARPi had numerically longer OS than PARPi non-initiators; further research into OS trends and PARPi use in gBRCAm mBC would be of interest. Editorial acknowledgment: Medical writing assistance was provided by Leigh-Ann Booth, Ph.D. from BOLDSCIENCE Inc., funded by AstraZeneca and Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, US Legal entity responsible for the study: AstraZeneca. Funding: This study was supported by AstraZeneca and Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, US, who are codeveloping olaparib. Table. gBRCAm testing rates over time in pts with HER2-negative mBC HER2-negative mBC is defined as IHC 0, or 1-positive, or IHC2-positive/ISH-negative. *Olaparib approved in mBC; †Olaparib approved in eBC. eBC, early breast cancer; gBRCAm, germline breast cancer gene mutation; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IHC, immunohistochemistry; ISH, in situ hybridization; mBC, metastatic breast cancer; pt, patient; TNBC, triple-negative breast cancer. Citation Format: Siddhartha Yadav, Sam Hillman, Linlin Luo, Weiyan Li, Jagadeswara Earla, Xiaoqing Xu. BRCA testing and PARP inhibitor utilization in real-world HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS04-02.

African American patients have a higher probability of cognitive impairment after incident stroke: An analysis of national electronic health record data

BackgroundCognitive impairment (CI) and stroke are diseases with significant disparities in race and geography. Post stroke cognitive impairment (PSCI) can be as high as 15-70% but few studies have utilized large administrative or electronic health records (EHR) to evaluate trends in PSCI. We utilized an EHR database to evaluate for disparities in PSCI in a large sample of patients after first recorded stroke to evaluate for disparities in race. MethodsThis is a retrospective cohort analysis of Cerner Health Facts® EHR database, which is comprised of EHR data from hundreds of hospitals/clinics in the US from 2009-2018. We evaluated patients ≥40 years of age with a first time ischemic stroke (IS) diagnosis for PSCI using ICD9/10 codes for both conditions. Patients with first stroke in the Cerner database and no pre-existing cognitive impairment were included, we compared hazard ratios for developing PSCI for patient characteristics ResultsA total of 150,142 IS patients with follow-up data and no pre-existing evidence of CI were evaluated. Traditional risk factors of age, female sex, kidney injury, hypertension, and hyperlipidemia were associated with PSCI. Only African American stroke survivors had a higher probability of developing PSCI compared to White survivors (HR 1.347, 95% CI (1.270, 1.428)) and this difference was most prominent in the South. Among those to develop PSCI, median time to documentation was 1.8 years in African American survivors. ConclusionIn a large national database, African American stroke survivors had a higher probability of PSCI five years after stroke than White survivors.

Effect of Hyponatremia in Preeclamptic Patients With Severe Features [ID 2683491

INTRODUCTION: Hyponatremia, although common in expectant women with preeclampsia, has not been well studied in a multicenter fashion, and it is unknown whether it is associated with adverse events related to severe preeclampsia. Our primary objectives are to assess the clinical characteristics and emergency therapy applied to participants diagnosed with preeclampsia. We hypothesize that hyponatremia present in preeclamptic patients with severe features is associated with greater use of emergency hypertensives, antenatal steroids, and cesarean delivery. METHODS: This is a retrospective cohort study utilizing a multicenter electronic health record database (TriNetX). We collected and evaluated the following data of participants aged 15–54 years with a diagnosis of preeclampsia with severe features: demographics, diagnostic codes, medication codes, procedure codes, deaths, and laboratory results. RESULTS: A total of 2,901 participants (215 [7.4%] with a sodium level below 134 mEq/L and 2,686 [92.6%] with a sodium level above 135 mEq/L) were included. A higher proportion of participants in the below 134 sodium group received emergency antihypertensives (165 [76.7%] versus 1,811 [67.4%]; P=.01), antenatal steroids (103 [47.9%] versus 953 [35.5%]; P=.001), and cesarean section (27 [12.6%] versus 97 [3.6%]; P&lt;.001). CONCLUSION: We found that hyponatremia may be associated with emergency antihypertensive use, antenatal steroid use, and cesarean section in patients with preeclampsia with severe features. Future research is needed to determine whether routine sodium levels assessed in preeclamptic subjects with severe features identify subjects at risk of receiving these treatments.

P051 Trends in consultations for musculoskeletal pain in children and young people presenting to United Kingdom primary care: an electronic health record study

Abstract Background/Aims Musculoskeletal pain in childhood increases the risk of such pain in adulthood but there is an absence of management guidance for this group, not helped by a lack of evidence on the extent and nature of pain in children. The aim was to determine the extent and patterns of consultations for musculoskeletal pain in children and young people (CYP) presenting to UK primary care. Methods Data were obtained from an anonymised nationally representative UK primary care electronic health record database (Clinical Practice Research Datalink, CPRD). The study population was patients aged 8-18 years between 2005-2021 with consultations for musculoskeletal pain. Consultation prevalence was calculated per 10,000 registered population for each calendar year, and by age (8-11, 12-15 and 16-18 years), gender and body site (prevalence presented for 2019 prior to COVID-19 pandemic). Results 1.12 million children and young people (48% female; median age 14 years) were recorded with musculoskeletal pain, with an annual consultation prevalence of over 9% (932/10,000, 95% CI 928-937). Consultation prevalence increased until 2015, stabilised until 2019, and was lower during 2020 due to the COVID-19 pandemic, but climbed slightly in 2021. Consultation prevalence in 2019 was highest for those aged 12-15 years (1105/10,000 vs 8-11 years 736/10,000 and 16-18 years 984/10,000) and for females. Age and gender differences were observed by body site with foot/ankle the most common site of pain in younger children (ages 8-11: females 277/10,000, males 229/10,000,), back the most common site in older females (ages 16- 18: 247/10,000) and knee the most common site in older males (ages 16-18: 178/10,000). Conclusion Musculoskeletal pain in CYP is common with almost one in ten consulting primary care annually, but pain sites vary by age and gender. Understanding the extent and nature of musculoskeletal pain in CYP presenting to primary care can help inform targeted and effective care, and underpin much needed intervention studies, potentially reducing risk of continued pain into adulthood. Disclosure K.J. Mason: None. K.P. Jordan: None. J. Bailey: None. A. Jöud: None. S. Jowett: None. J. Protheroe: None. F. Mughal: None. K.I.E. Snell: None. M. Thomas: None. K.M. Dunn: None.

P177 The prevalence and incidence of psoriasis and psoriatic arthritis in England from 2009-2019: an observational study using primary care data

Abstract Background/Aims Psoriasis (PsO) and psoriatic arthritis (PsA) greatly impact quality of life and result in substantial personal and societal costs. Complete and up-to-date data on the prevalence and incidence of these conditions and whether these change over time and vary by age is important for healthcare service planning so that specialist care and funding can be appropriately allocated. Objective to determine the prevalence and incidence of PsO and PsA in males and females from 2009-2019 across all age groups in England. Methods We used Clinical Practice Research Datalink AURUM, a primary care electronic health record database, including 20% of the English population. The codes used to identify patients with PsO and PsA were selected by rheumatologists and dermatologists and cross-checked with published code lists from other studies. All included patients must have data for at least 1 year before their diagnosis. The annual incidence and point prevalence were calculated from 2009-2019 and stratified by age/sex. The study period ended in 2019 to avoid COVID-19 pandemic affecting results. Results The prevalence of PsO and PsA in males and females has increased annually, peaking in 2019 (PsO males 2.41% [95% confidence interval (CI) 2.40, 2.42]; PsO females 2.60% [95% CI 2.59-2.61]; PsA males 0.20% [95% CI 0.20-0.20]; PsA females 0.21% [95% CI 0.21- 0.22]), as illustrated in Table 1. In 2019, the prevalence of PsO and PsA was highest in the over 65 years age group; PsO 4.25% [95% CI 4.22-4.28] and PsA 0.38% [95% CI 0.37-0.38]. The annual incidence (per 100,000 person years) of PsO has gradually decreased in males (from 168 [164-171] in 2009 to 148 [145-151] in 2019) but in females it has been stable with a slight annual decrease (from 180 [177-184] in 2009 to 173 [170-176]) in 2019. The annual incidence for PsA has increased in both males and females; 13 (12-14) in 2009 and 15 (14-16) in 2019 for males and 12 (11-13) in 2009 and 18 (17-19) in 2019 for females. Conclusion The increasing prevalence of PsO and PsA highlights the importance of organising healthcare services to meet this need, particularly in the elderly population. Disclosure A. Vivekanantham: None. E. Burn: None. M. Pineda Moncusi: None. S. Khalid: None. D. Prieto Alhambra: Consultancies; DP-A’s research group has received consultancy or speaker fees from Astellas, Amgen, AstraZeneca, and UCB Biopharma. Grants/research support; DP-A’s research group has received research grants from the European Medicines Agency; the Innovative Medicines Initiative; and Amgen, Chiesi, and UCB Biopharma. L.C. Coates: Grants/research support; LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer; worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene.

Evaluating the comparability of osteoporosis treatments using propensity score and negative control outcome methods in UK and Denmark electronic health record databases.

Evidence on the comparative effectiveness of osteoporosis treatments is heterogeneous. This may be attributed to different populations and clinical practice, but also to differing methodologies ensuring comparability of treatment groups before treatment effect estimation and the amount of residual confounding by indication. This study assessed the comparability of denosumab vs oral bisphosphonate (OBP) groups using propensity score (PS) methods and negative control outcome (NCO) analysis. A total of 280 288 women aged ≥50years initiating denosumab or OBP in 2011-2018 were included from the UK Clinical Practice Research Datalink (CPRD) and the Danish National Registries (DNR). Balance of observed covariates was assessed using absolute standardised mean difference (ASMD) before and after PS weighting, matching, and stratification, with ASMD >0.1 indicating imbalance. Residual confounding was assessed using NCOs with ≥100 events. Hazard ratio (HR) and 95% confidence interval (CI) between treatment and NCO was estimated using Cox models. Presence of residual confounding was evaluated with two approaches1: >5% of NCOs with 95% CI excluding 1,2 >5% of NCOs with an upper CI <0.75 or lower CI >1.3. The number of imbalanced covariates before adjustment (CPRD 22/87; DNR 18/83) decreased, with 2-11% imbalance remaining after weighting, matching or stratification. Using approach 1, residual confounding was present for all PS methods in both databases (≥8% of NCOs), except for stratification in DNR (3.8%). Using approach 2, residual confounding was present in CPRD with PS matching (5.3%) and stratification (6.4%), but not with weighting (4.3%). Within DNR, no NCOs had HR estimates with upper or lower CI limits beyond the specified bounds indicating residual confounding for any PS method. Achievement of covariate balance and determination of residual bias were dependent upon several factors including the population under study, PS method, prevalence of NCO, and the threshold indicating residual confounding.

Retrospective Analysis of Burn Injuries in Children with Autism Spectrum Disorder.

Children with neurodevelopmental disorders are at risk for burn injury, but the clinical outcomes, particularly mortality, are unknown in this patient population in the United States (U.S.). The main objectives of this study are to evaluate (1) subject characteristics; (2) burn injury type; (3) clinical care provided; and (4) mortality in children with autism spectrum disorder (ASD), hypothesizing that this patient population has similar mortality and critical care management requirements when compared to children without ASD. This is a retrospective observational cohort study utilizing the TriNetX ® electronic health record database of subjects aged 0 to 18years with burn injury associated diagnostic codes. Data were analyzed for demographics, diagnostic, medication, procedural codes, and mortality. We analyzed 99,323 subjects (n, %) coded for a burn injury [3083 (3.1%) with ASD and 96,240 (96.9%) without ASD]. Children with ASD had a higher odds of 1-year all-cause mortality [1.9 (1.06, 3.40), p = 0.004], need for critical care services [1.88 (1.40, 2.52), p < 0.001], and mechanical ventilation [2.69 (1.74, 4.17), p < 0.001] compared to those without. Our study found that U.S. children with ASD who had a burn injury had a higher odds of mortality and critical care needs when compared to children without ASD. Future studies are needed to understand the impact of burn injuries and factors associated with mortality in this patient population.

Assessment of algorithms for identifying patients with triple-class refractory multiple myeloma using real-world data

Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.