Outpatient Diagnosis Research Articles

P-2033. Patient Characteristics and Management of COVID-19 Diagnosed in the Outpatient Setting

Abstract Background The clinical profile of outpatient COVID-19 continues to evolve. Our research objective was to characterize patients diagnosed with COVID-19 in the outpatient setting and describe antiviral treatment patterns. Methods The HealthVerity database (includes chargemaster, electronic health record, and claims data) was queried for individuals age ≥12 y with an outpatient COVID-19 diagnosis between 12/1/2021 and 5/31/2023. We examined patient characteristics, including demographics, Charlson Comorbidity Index (CCI), and medication prescription history. Any hospitalization ≤30 days postdiagnosis and potential drug-drug interactions (DDIs) 90 days prior to diagnosis were captured. Antiviral therapy ≤90 days postdiagnosis was also captured, though antivirals were only available under emergency use authorization during the study period. Results Over the study period, 5,339,778 patients met the entry criteria, of whom 62.5% were women and 11.2% were age ≥65 y. In addition, 2.7% had an immunosuppressive condition, 11.3% were prescribed an antiviral (10.4% molnupiravir, 89.9% nirmatrelvir/ritonavir), and 37.1% had a potential DDI to nirmatrelvir/ritonavir (Table 1). Among patients with a CCI score ≥3, 13.8% received antiviral treatment compared to 11.1% of patients with a CCI score < 3. Of patients age ≥65 y, 19.2% received antivirals compared to 10.3% of those age < 65 y. Prevalence of potential DDIs was high in patients age ≥65 y and in those with immunosuppressive conditions (Tables 2 and 3). Overall, 1.0% of patients treated for COVID-19 were hospitalized ≤30 days postdiagnosis, compared to 1.9% of those untreated (Table 4). Conclusion Outpatient antiviral therapy for COVID-19 was underutilized, though there was a considerable percent of patients without comorbidities whom clinicians may have considered low-risk for serious disease progression. A high proportion of patients age ≥65 y and/or with immunosuppressive conditions were prescribed antivirals and were more likely to have potential associated DDIs. The proportion of patients who were hospitalized approximately doubled when the patient was not treated, though future adjustments will be needed to allow for subgroup comparisons, including matching of treated and untreated patients according to confounding effects. Disclosures Mark Berry, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Christian B. Ramers, MD MPH, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Viiv: Advisor/Consultant|Viiv: Honoraria Amos Lichtman, MPH, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Ching-Yi Chuo, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Anand Chokkalingam, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company)

P-1566. Healthcare Resource Use and Costs of Acute Uncomplicated Cystitis in Japan

Abstract Background Acute uncomplicated cystitis (AUC) is an area of interest for outpatient antimicrobial stewardship in Japan due to the high prevalence of community antibiotic use. Literature on the cost burden of AUC in Japan is limited. We aimed to quantify real-world healthcare resource utilization (HCRU) and costs of treating AUC in Japan. Methods This retrospective cohort study used Japanese Medical Data Center (JMDC) claims data (1 October 2015−30 November 2021). Eligible patients (≥ 18 to < 75 years) had an outpatient AUC diagnosis claim in the same month as ≥ 1 oral antibiotic prescription (date of prescription = index date). Continuous health plan enrolment, with medical and pharmacy benefits, was required ≥ 12 months pre index (baseline period) and ≥ 12 months post index (follow-up period). Patients with complicated cystitis or pyelonephritis were excluded. The index AUC episode was defined as 28 days from index date and was extended an additional 28 days if treatment failure (TF) was observed (within 28 days from date of TF). Patients were stratified based on evidence of TF or AUC recurrence (full definitions in Table 1). AUC-related costs (Japanese Yen [¥]) and HCRU, per episode, were compared within subgroups. Results Overall, 71,467 patients were included, of whom 3742 (5%) had evidence of TF and 3206 (4%) had recurrent AUC. The mean (standard deviation [SD]) cost of any AUC episode was ¥14,905 (¥31,344) (Table 2), with 1.22 (0.46) outpatient claims and 1.07 (0.27) pharmacy prescription claims per episode (Table 3). Patients with evidence of TF had significantly higher mean (SD) pharmacy (¥2078 [¥2295]) and total costs (¥25,932 [¥64,494]), and a higher number of pharmacy prescription claims (2.03 [0.45]) per episode versus patients without TF (all p< 0.001). Patients with recurrent AUC had higher mean (SD) total costs (¥16,514 [¥35,241]) and higher outpatient claims (1.10 [0.34]) per episode versus patients without recurrence (¥14,830 [¥31,148]) total costs and (¥1037 [¥1281]) outpatient claims; (p=0.008 and p< 0.001, respectively). Conclusion TF rates and recurrence of AUC in Japan were modest; however, the economic burden of AUC was greater in patients who had evidence of TF or recurrence. Disclosures Meg Franklin, PharmaD, PhD, Franklin Pharmaceutical Consulting: Owner and President|Franklin Pharmaceutical Consulting: Ownership Interest|PRECISIONheor (who received funding from GSK to complete this study): Advisor/Consultant Maia R. Emden, BA, PRECISIONheor: Previous employee of PRECISIONheor, who received funding from GSK to complete this study Elise Bauer, MS, PRECISIONheor: Previous employee of PRECISIONheor, who received funding from GSK to complete this study Naomi Sacks, PhD, PRECISIONheor: Previous employee of PRECISIONheor, who received funding from GSK to complete this study Fanny S. Mitrani-Gold, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company) Shinyoung Ju, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Ashish V. Joshi, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Yoshiaki Kawano, MD, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Shinya Kawamatsu, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Madison T. Preib, MPH, GSK: Employee|GSK: Stocks/Bonds (Public Company)

Inpatient versus outpatient diagnosis of heart failure across the spectrum of ejection fraction: a population cohort study

BackgroundEarly heart failure (HF) diagnosis is crucial to ensure that optimal guideline-directed medical therapy (GDMT) is administered to reduce morbidity and mortality. Limited access to echocardiography could lead to a...

Adverse Pregnancy Outcomes and Long-Term Risk of HeartFailure in Women: National Cohort and Co-Sibling Study.

Adverse pregnancy outcomes, such as preterm delivery and hypertensive disorders of pregnancy, may be associated with higher future risks of heart failure (HF). However, the comparative effects of different adverse pregnancy outcomes on long-term risk of HF, and their potential causality, are unclear. The authors sought to examine 5 major adverse pregnancy outcomes in relation to long-term risk of HF in a large population-based cohort. A national cohort study was conducted of all 2,201,638 women with a singleton delivery in Sweden in 1973-2015, followed up for HF identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute HRs for HF associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, while adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. In 48 million person-years of follow-up, 667,774 women (30%) experienced an adverse pregnancy outcome, and 19,922 women (0.9%) were diagnosed with HF (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with long-term increased risk of HF. With up to 46 years of follow-up after delivery, adjusted HRs for HF associated with specific adverse pregnancy outcomes were: gestational diabetes, 2.19 (95%CI: 1.95-2.45); preterm delivery, 1.68 (95%CI: 1.61-1.75); other hypertensive disorders, 1.68 (95%CI: 1.48-1.90); preeclampsia, 1.59 (95%CI: 1.53-1.66); and small for gestational age, 1.35 (95%CI: 1.31-1.40). All HRs remained significantly elevated (1.3- to 3.0-fold) even 30 to 46 years after delivery. These findings were only partially explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk (eg, up to 46 years after delivery, adjusted HRs associated with 1, 2, or≥3 adverse pregnancy outcomes were 1.51 [95%CI: 1.47-1.56], 2.31 [95%CI: 2.19-2.45], and 3.18 [95%CI: 2.85-3.56], respectively). In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for HF up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term clinical care to reduce the risk of HF.

Characterization of SARS-CoV-2 Diagnostic Tests and Liver Function Tests Among Patients With COVID-19 Diagnosed in Outpatient Settings Using Administrative Healthcare Data and Data From Commercial Laboratories.

To characterize select laboratory tests ordered versus reported for patients diagnosed with COVID-19 in administrative healthcare and commercial laboratory data. Among patients with an outpatient COVID-19 diagnosis claim in HealthVerity data (01/01/2021-12/31/2022), this study described baseline characteristics and descriptively compared SARS-CoV-2 diagnostic tests and liver function tests from administrative healthcare (insurance claims and hospital billing data) and commercial laboratories, overall and by code type (e.g., CPT, LOINC). Select liver function tests were also described by method-specific and methodless LOINC. Among 214 998 patients with COVID-19, 46.1% had a SARS-CoV-2 molecular diagnostic test recorded within 7 days of diagnosis (in either administrative or laboratory data); 44.5% had a corresponding CPT in medical claims, while only 10.0% had a corresponding LOINC in laboratory data. In contrast, the six most common liver function tests (albumin, aspartate aminotransferase, total protein, alkaline phosphatase, alanine aminotransferase, and total bilirubin) were identified in 55.7%-56.6% of patients via LOINC, but only in 3.2%-4.2% via CPT claims. Of the total count of select liver function tests performed in the laboratory data, 99.7% of aspartate aminotransferase, 96.1% of direct bilirubin, and 82.9% of lactate dehydrogenase were reported by methodless LOINC rather than method-specific LOINC. Important differences were identified between orders for SARS-CoV-2 diagnostic tests and liver function tests, as well as missingness of LOINC method, highlighting challenges related to completeness of laboratory data in real-world data sources. These challenges underscore a need to improve data quality when considering the utility of laboratory data for research.

Epidemiology and treatment of Adamantiades-Behçet's disease in Germany: A healthcare claims database study.

Adamantiades-Behçet's disease (ABD) is a rare, chronic, relapsing, multisystem vasculitis, with a reported prevalence of 0.9 out of 100,000 population in Germany in 2012. However, more recent epidemiological data are lacking. To estimate the prevalence and incidence of ABD in Germany and assess associated comorbidities and current treatment patterns. This retrospective cohort study used claims data from the anonymized Institute for Applied Health Research Berlin (InGef) research database. Cohorts were formed for the observation years 2016, 2017 and 2018, using data from 2013 to 2018 (allowing for a 3-year baseline period for incidence data). The study population included patients ≥18 years old with a diagnosis of ABD (ICD-10 diagnostic code M35.2), covered under the statutory health insurance system and in the InGef research database, with continuous insurance in the observation year and baseline period. We descriptively evaluated prevalence (≥2 outpatient ABD diagnoses in different quarters/≥1 main inpatient diagnosis in the observation year), incidence (no confirmed outpatient/inpatient diagnosis in the baseline period), comorbidities reported during the study and ABD-related medications. We identified 300, 303 and 329 patients diagnosed with ABD in 2016, 2017 and 2018, respectively, with fewer than half (122/300 [40.7%], 127/303 [41.9%] and 150/329 [45.6%]) prescribed ≥1 disease-related medication. In the treated population, ABD prevalence was 3.9 (2016), 4.1 (2017) and 4.7 (2018) per 100,000 population; annual ABD incidence was 0.5 per 100,000 population in 2016 and 2017 and 0.6 per 100,000 population in 2018. The most commonly reported comorbidities in patients diagnosed with ABD were dorsalgia (an indicator of possible misdiagnosis), disorders of refraction and accommodation, and essential (primary) hypertension. Prednisolone, colchicine and azathioprine were the most commonly prescribed treatments for ABD, with approximately 15% of patients taking >1 medication for ABD. The reported data provide evidence that ABD remains a rare disease in Germany.

The one-step outpatient diagnosis and treatment of congenital Mullerian anomalies – Class U1 and U2 according ESHRE/ESGE classification

The one-step outpatient diagnosis and treatment of congenital Mullerian anomalies – Class U1 and U2 according ESHRE/ESGE classification

Hospitalization Following Outpatient Diagnosis of Respiratory Syncytial Virus in Adults

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections among adults and is estimated to cause approximately 159 000 hospitalizations among adults aged 65 years and older in the US each year. Estimates of hospitalization among adults with outpatient medically attended RSV (MA-RSV) infections are required to design interventional studies that aim to prevent hospitalization. To assess absolute risk of 28-day, all-cause hospitalization following outpatient MA-RSV infections in adults. In this cohort study, data from 3 different deidentified databases containing electronic health records (EHR) linked to closed claims data (Optum's deidentified Integrated Claims-Clinical dataset, TriNetX Linked, and Veradigm Network EHR [VNEHR] database linked with claims) were analyzed separately across 6 RSV years (October 1, 2016, to September 30, 2022) in adults with commercial or government insurance. Outpatient (eg, clinics and emergency departments) MA-RSV infections were identified based on clinical laboratory data or RSV-specific International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes. Data were analyzed from March 2023 to April 2024. The main outcome was all-cause 28-day hospitalization following outpatient MA-RSV infections among all adults and a high-risk subgroup (defined as age ≥65 years or with asthma, chronic obstructive pulmonary disease [COPD], or congestive heart failure [CHF]). In this cohort study of 67 239 MA-RSV infections in adults (2771 from Optum, 7442 from TriNetX, and 57 026 from VNEHR), most occurred among females (62%-67%) and comorbidity prevalences were 20.0% to 30.5% for COPD, 14.6% to 24.4% for CHF, 14.6% to 24.4% for asthma; 14.0% to 54.5% of individuals were aged 65 years or older. The proportion hospitalized was 6.2% (95% CI, 5.3%-7.1%) in Optum, 6.0% (95% CI, 5.4% to 6.5%) in TriNetX, and 4.5% (95% CI, 4.3%-4.6%) in VNEHR. Among the high-risk subgroup, the proportion hospitalized was 7.6% (95% CI, 6.5%-8.9%) in Optum, 8.5% (95% CI, 7.6%-9.4%) in TriNetX, and 6.5% (95% CI, 6.2%-6.8%) in VNEHR. In this cohort study of adults with outpatient MA-RSV infections from 3 large deidentified US databases across 6 RSV seasons, approximately 1 in 20 adults experienced all-cause hospitalization within 28 days. The results of this study highlight the public health need for RSV prevention and treatment.

Virtual Mental Health Care and Suicide-Related Events

The rising suicide rates in the US emphasize the need for effective prevention. While telehealth has transformed access to mental health care, the impact of telehealth on suicide outcomes is unknown. To evaluate the association of virtual mental health services with individual-level suicide-related events (SREs). This retrospective cohort study using broadband access as an instrumental variable assessed a national sample of Veterans Health Administration patients who received mental health care between March 1, 2020, and December 31, 2021. Participants were recently separated (ie, discharged or released from active duty) veterans who completed their active duty service between March 1, 2019, and December 31, 2020, and who received at least 2 outpatient or inpatient diagnoses related to major depressive disorder, substance use disorder, or posttraumatic stress disorder within the year before their most recent separation date. Data were analyzed May 1 to October 31, 2023. Percentage of a patient's total mental health visits that were conducted virtually by psychiatrists, psychologists, or social workers within a calendar month. Binary measure indicating whether the patient had experienced an SRE (defined as a nonfatal suicide attempt, intentional self-harm, or suicide death) in a specific month and year as evaluated an instrumental variable probit model. The sample included 66 387 data points from 16 236 unique recently separated veterans. Among these entries, 44 766 were for male veterans (67.4%), the mean (SD) age across the sample was 32.9 (8.9) years, and the sample was representative of the US veteran population. There were 929 SREs (1.4%). Virtual mental health visits comprised a mean (SD) of 44.6% (46.1%) of all mental health visits. In instrumental variable probit analyses accounting for factors simultaneously associated with use of virtual mental health care and SRE risk, a 1% increase in the probability of virtual mental health visits was associated with a 2.5% decrease in SREs. Findings from this cohort study using a retrospective quasi-experimental design found that an increase in virtual mental health visits relative to total visits was associated with a statistically significant decrease in SREs, suggesting that providing virtual mental health services may reduce suicide-related outcomes.

Incident atrial fibrillation prediction using ECG-based deep learning at a specialized tertiary cardiac care center

Abstract Background Deep learning (DL) applied to electrocardiograms (ECG) is an emerging modality in the prediction of incident atrial fibrillation or atrial flutter (AF). The generalizability of such methods to a tertiary heart center (THC) population has not yet been formally explored. Purpose Evaluate the performance of DL in predicting 5-year incident AF using a resting 12-lead ECG in sinus rhythm acquired at a THC. Methods In a retrospective study, we examined 1.4 million ECGs acquired from over 250,000 adults at a THC between 2004 and 2022. ECGs were excluded if they were performed within 30 days of cardiac surgery, captured a rhythm other than sinus rhythm, or were acquired in patients with pre-existing AF. Incident AF at 5 years was modelled as a binary outcome and was determined on the basis of available outpatient and inpatient clinical databases and ECG diagnoses. Included ECGs were randomly split by distributing patients into training (70%), validation (10%), and test (20%) sets. A ResNet-50 model was trained using the training set. Hyperparameters were optimized using the validation set. The tuned model's performance is reported on the test set. The results at the patient level were derived by averaging the model's probability outputs for ECGs grouped according to both their AF outcome and the patient's identity. Bootstrapping was used to report confidence intervals (CI). Sensitivity and specificity are reported at a classification threshold based on the Matthews correlation coefficient. Saliency maps were used to enhance the model’s explainability. Results A total of 669,782 ECGs (47% of the screened ECGs) were included among 145,323 patients. Mean age was 63±15 years and 62% were male. The 5-year incident AF outcome was observed in 12% of ECGs and 16% of patients. The performance of the tuned model was first evaluated at the ECG level on the test set demonstrating an area under the receiver operating curve (AUC) of 0.75 (95% CI: 0.745-0.753) and an integrated calibration index of 0.009 (95% CI: 0.008-0.011). When testing the model at the patient level to simulate a deployment scenario, the AUC improved to 0.78 (95% CI: 0.768-0.783) with a sensitivity of 50% (95% CI: 49-52) and specificity of 87% (95% CI: 86.5-87.3). Stratified results by sex showed a better AUC in females, 0.81 (95% CI: 0.80-0.82), compared to males, 0.75 (95% CI: 0.74-0.76). Subgroup analyses revealed a trend of improved performance at the patient level with an increasing number of ECGs. Saliency maps highlighted the P-wave area as having the highest influence on the model’s prediction, thereby enhancing the model’s plausibility and explainability. Conclusion A unimodal ECG-based deep learning model showed promising 5-year incident AF prediction performance in a cohort of all-comer patients at a tertiary heart center. Further studies could explore the use of multimodal prediction models that integrate ECGs with other clinical and imaging data.

A flattening systolic blood pressure response at the end of ramp exercise testing is not associated with all-cause mortality

Abstract Purpose Systolic blood pressure (SBP) is expected to rise linearly during ramp exercise, but sometimes plateaus before the end of exercise. We aimed to examine the predictive value of a plateauing SBP response at the end of a cycle exercise test. Methods We analyzed 9,001 consecutive patients aged ≥18 years with maximal cycle ergometer ramp tests, after excluding subjects with valvulopathy, pacemaker, arrhythmia during the test, or body mass index (BMI) >40kg/m², as well as tests with resting SBP <80mmHg or >200mmHg, exercise SBP <100 mmHg, <2 SBP measurements during the second half of the test or a test duration <4 minutes. The data were cross-linked with nationwide registries for mortality and in- and outpatient hospital diagnoses. The difference in SBP between the two last SBP measurements was standardized to the difference in Watts between the same time points, categorized as i) an SBP decrease (drop), ii) an SBP increase of <2.5 mmHg per 10 Watts increase (flat), iii) an SBP increase of 2.5-15 mmHg/10 Watts (intermediate), and iv) an SBP increase >15 mmHg/10 Watts representing the 97.5th percentile (steep). Hazards ratios (HR, [95% confidence interval, CI]) for all-cause mortality were calculated, stratified for exercise capacity (peak Watt % of predicted) with the intermediate SBP response as reference. Adjustments were made for age, sex, BMI, resting SBP, baseline diagnosis of ischemic heart disease, heart failure, chronic obstructive pulmonary disease, and the use of beta-blockers or anti-hypertensive medication. Results Decreasing, flat, intermediate, and steep SBP responses at the end of exercise were present in 1.1%, 25.6%, 70.8% and 2.5% of patients respectively (Table 1). During median follow-up 8.6 years (interquartile range 5.9–11.6 years) there were 844 deaths. When compared to an intermediate SBP response, a flat SBP response was not associated with all-cause mortality in any of the exercise capacity strata: lowest tertile of Wmax%pred unadjusted HR 0.88 (95% CI 0.69–1.11), middle tertile HR 0.91 (95% CI 0.66–1.24), and highest tertile HR 0.95 (95% CI 0.64–1.41), with HRs remaining non-significant after adjustment for covariates (Table 2). Conclusion In patients referred for exercise testing, a flattening SBP response at the end of exercise was not associated with increased all-cause mortality risk compared to an intermediate SBP response, consistent across the different exercise capacity strata.

Prognostic impact of cardiac events in asymptomatic mitral regurgitation

Abstract Background Mitral regurgitation (MR) is the most common valvular heart disease in adults and is associated with increased morbidity and mortality. Treatment recommendations of degenerative MR have been liberalized, however, the role of asymptomatic patients is still insufficiently defined. Purpose The purpose of this study were to evaluate the prevalence of cardiac events in a large asymptomatic MR cohort, based on health insurance data analysis, in comparison with healthy propensity score-matched general population and to define the prognostic impact of such cardiac events on ten-year survival. Methods We retrospectively analyzed health insurance claims data from Germany’s second largest health insurance fund, which maintains longitudinal data on outpatient and inpatient medical services for 8.7 million German residents. We included all patients with an outpatient diagnosis of MR (I34.0) in a minimum of two quarters during a calendar year and first recorded diagnosis between 2008 and 2011. To identify an asymptomatic MR cohort (study group), all patients with at least one complication attributable to MR / mitral valve intervention during the incidence quarter of MR were excluded. Ten-year outcomes were compared between study group vs. age- and sex-matched healthy control group. Cardiac events of interest were new congestive heart failure, new-onset atrial fibrillation, pulmonary hypertension, or cardiac decompensation. Results A total of 56.577 (62.7%) asymptomatic MR patients were identified from the whole cohort of 90.245 individuals with a newly diagnosed MR in the BARMER database. During a ten-year follow-up, 26.282 (46.5%) patients in the study group experienced at least one cardiac event vs. 11.763 (20.8%) individuals in the control group (OR: 3.31, 95%CI: 0.251-0.262, P<0.0001). The occurrence of at least one cardiac event (i.e., congestive heart failure, new-onset atrial fibrillation, pulmonary hypertension or cardiac decompensation) in the study group was associated with a significantly worse ten-year survival as compared to the control group. The risk of cardiac events was age- and sex-dependent, while female patients with an asymptomatic MR had a lower risk as compared to males in all age groups (OR: 0.38, 95%CI: -1.193- -0.754, P<0.0001). Only 1.530 (2.7%) patients underwent mitral valve (MV) intervention in the study group during ten-year follow-up. Conclusions Our study reveals high incidence of asymptomatic MR in a representative cohort of health insurance claims data in Germany. Every second patient with an asymptomatic MR experiences at least one cardiac event during a ten-year follow-up period that is associated with a significantly worse survival. The definition of asymptomatic MR cohort at risk of developing cardiac events may potentially improve early treatment strategies and lead to better outcome in the future.Abstract picture

Racial and ethnic disparities in the incidence of stroke and mortality in atrial fibrillation: a US nationwide study

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia globally and is associated with increased risks of cardiovascular mortality and ischemic stroke. Prior research has demonstrated racial/ethnic disparities in AF outcomes yet this work has been limited to small cohorts and did not adjust for anticoagulant therapy. Purpose We compared incidence of ischemic stroke and death by race/ethnicity for patients with AF in the Veterans Health Administration (VA), the largest integrated, low-cost, national healthcare system in the US. Methods In this retrospective cohort study we identified those with an outpatient diagnosis of AF and a confirmatory diagnosis ≦ 180 days of their index AF diagnosis enrolled in VA from January 1, 2014 to December 31, 2021, with follow-up for outcomes from the index AF diagnosis date until May 31, 2022. To create a cohort of incident AF cases, we excluded patients with an AF diagnosis or anticoagulant therapy in the 2 years prior to their index AF diagnosis. We also excluded patients with pre-existing valvular heart disease, prior stroke, receiving hospice care or who died within 180 days of index AF diagnosis. We categorized our independent variable as race (i.e., non-Hispanic American Indian / Alaska Native [AI/AN], Asian, Black, or White [reference group]), and ethnicity (i.e., Hispanic). Our primary outcomes were incidence of stroke or death at any point within the study follow-up period. To compare these outcomes by race/ethnicity we conducted a survival analysis, adjusting for anticoagulant use as a time-varying covariate along with sociodemographic factors (age, sex, region, area deprivation index), clinical factors (CHADS2VA2Sc stroke risk and HAS-BLED bleeding risk), and facility type. Results There were 187,080 patients in the final cohort including 0.5% AI/AN, 1% Asian, 9% Black, 4% Hispanic, 85% White; mean age was 73 years. Over a mean study follow-up period of 4.43 years, 65,375 (34.9%) patients died and 24,910 (13.3%) developed stroke. The adjusted hazard ratio [95% CI] for death was lower for Hispanic (0.84 [0.78, 0.91]) and Black (0.94 [0.91, 0.97]) patients than White patients. In contrast, the adjusted hazard ratio for stroke incidence was higher for Black (1.21 [1.16, 1.27]) and Hispanic (1.10 [1.03, 1.17]) patients than White patients. There was no difference observed between AI/AN or Asian and White patients in either outcome. Conclusions In a national cohort of patients with incident AF, we identified significantly higher rates of stroke in Black and Hispanic than White patients even controlling for myriad factors including anticoagulant use. Conversely, racial/ethnic disparities in mortality appear to be eliminated in VA, counter to prior data. Understanding the factors, beyond anticoagulation, driving disparities in stroke outcomes and identifying factors reducing mortality among minority groups is critical to improving overall AF care in the largest integrated US health system.Adjusted Hazard Ratios of Study Outcomes

8139 Examining the Association of GLP1-RA or DPP4i with Bullous Skin Diseases in Veterans

Abstract Disclosure: S. Saad-Omer: None. M. Kinaan: None. N. Sami: None. I. Mansi: None. Introduction: Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are Autoimmune Blistering Disorders (AIBDs). GLP-1 Receptor Agonists (GLP1-RA) and Dipeptidyl peptidase 4 inhibitors (DPP4i) have been noted in various case reports and case control studies to be linked with certain AIBDs; however, their overall role in these diseases is not completely understood, despite the exponential increase in use of these medications. This study aims to be the first study to investigate the association of DPP-4 inhibitors and GLP-1 agonists with incidence of AIBD, PV, and BP in a large cohort of American veterans. Methods: This retrospective cohort study of veterans enrolled in the Veterans Health Administration (VHA) used Corporate Data Warehouse (CDW). We extracted data of patients from fiscal years (FY) 2006 to end of FY 2021 who filled either GLP1-RA or DPP4i prescriptions. CDW is a comprehensive data source that encompasses vital status, demographic data, inpatient and outpatient diagnoses and procedure codes, vital signs, laboratory data, and pharmacy fill data. The study groups included: 1) GLP1-RA group: patients who initiated GLP1-RA; and 2) DPP4i group: patients who initiated DPP4i. Our primary outcome was the incidence of AIBDs. We compared baseline characteristics of patients who experienced the outcome and those who did not among GLP1-RA or DDP4i users. We, thereafter, examined factors associated with incidence of AIBD, PV, and BP among GLP1-RA users and DPP4i users. Results: The initial cohort of GLP1-RA or DPP4i users comprised a total of 415,895 patients, from which we excluded 397 (0.095%) patients with prior bullous skin diseases before starting GLP1-RA or DPP4i medications. Overall, a total of 154 patients developed PV/BP disease after initiation of either DPP4i or GLP1-RA. Of these 154 patients, 123 of these patients were on DPP4i and 31 of these patients were on GLP1-RA. The mean age (SD) of PV/BP patients was 72 (11) years compared to an average age of 66 (10) years in patients who did not develop PV/BP. Patients were also found to be predominately white (77.9%). Factors associated with increased risk of BP were use of DPP4i (Odds Ratio [OR] 1.90, 95% confidence interval [95% CI: 1.14-3.47, p=<0.01), and older age (OR: 1.07, 95%CI: 1.04-1.09, p<0.01). Use of GLP1-RA or DPP4i was not associated with PV incidence. (OR: 1.31, 95% CI: 0.65-2.62, p=<0.45). Conclusion: In conclusion, our study supports existing literature that DPP4i use is associated with an increased risk of developing BP. Our data does not find association with GLP-1 agonists nor DPP4 inhibitors in increasing the risk of PV. Presentation: 6/3/2024

Reductions in inpatient and outpatient mental health care in germany during the first year of the COVID-19 pandemic – What can we learn for a better crisis preparedness?

Background: During the COVID-19 pandemic, reports from several European mental health care systems hinted at important changes in utilization. So far, no study examined changes in utilization in the German mental health care inpatient and outpatient mental health care system comprehensively. Methods: This longitudinal observational study used claims data from two major German statutory health insurances, AOK PLUS and BKK, covering 162,905 inpatients and 2,131,186 outpatients with mental disorders nationwide. We analyzed changes in inpatient and outpatient mental health service utilization over the course of the first two lockdown phases (LDPs) of the pandemic in 2020 compared to a pre-COVID-19 reference period dating from March 2019 to February 2020 using a time series forecast model. Results: We observed significant decreases in the number of inpatient hospital admissions by 24–28% compared to the reference period. Day clinic admissions were even further reduced by 44–61%. Length of stay was significantly decreased for day clinic care but not for inpatient care. In the outpatient sector, the data showed a significant reduction in the number of incident outpatient diagnoses. Conclusion: Indirect evidence regarding the consequences of the reductions in both the inpatient and outpatient sector of care described in this study is ambiguous and direct evidence on treatment outcomes and quality of trans-sectoral mental healthcare is sparse. In line with WHO and OECD we propose a comprehensive mental health system surveillance to prepare for a better oversight and thereby a better resilience during future global major disruptions.

Chronic periodontal disease is related with newly developing hypertension: a nationwide cohort study

BackgroundPeriodontal disease (PD) is a condition that can be treated and managed. This study aimed to determine if chronic PD status is associated with the risk of developing hypertension, utilizing data from the National Health Insurance Database of Korea.MethodsParticipants who received oral health examinations both in 2003 and in 2005–2006 were included. Those with a history of hypertension were excluded. Hypertension was defined as at least one outpatient or inpatient claim diagnosis (primary or secondary) of hypertension (International Classification of Diseases (ICD)-10 codes I10-I11) with prescription for antihypertensive medication or at least one incident of systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg during a health examination. Changes of PD status was determined during two oral examinations. Study participants were divided into 4 groups according to the changes of PD status: PD-free (those consistently free of disease in both exams), PD-recovered (individuals with disease initially but not in the second exam), PD-developed (no disease initially, but present in the second exam), and PD-chronic (disease throughout both exams). The incidence of hypertension after the second oral health examination (index date) was monitored. Participants were observed from the index date until the earliest occurrence of hypertension onset, mortality, or December 2020.ResultsThe study comprised 706,584 participants: 253,003(35.8%) in the PD-free group, 140,143(19.8%) in the PD-recovered group, 132,397(18.7%) in the PD-developed group, and 181,041(25.6%) in the PD-chronic group. Over a median follow-up duration of 14.3 years, 239,937 (34.0%) cases of hypertension were recorded. The PD-recovered group had a lower risk of hypertension compared to the PD-chronic group, while the PD-developed group had a higher risk of hypertension compared to the PD-free group.ConclusionChronic PD is associated with an increased risk of developing hypertension. Although the increase in risk is modest, recovery from PD may have beneficial effects in reducing hypertension risk. Further studies are needed to confirm the importance of regular dental examinations and effective management of PD to reduce hypertension risk.

Clinical utility and impact of a diagnostic oncology clinic.

74 Background: Oncologists have expertise in the work-up and management of patients with a suspected diagnosis of cancer. Patients diagnosed with cancer during acute care hospitalization often have poorer outcomes than those diagnosed as outpatients. For these patients, time to appropriate cancer diagnosis, management of cancer-related symptoms, and timely initiation of treatment are key to improved outcomes. Outpatient new diagnosis clinics may improve patient outcomes by improving access to subspecialty care. Methods: Patients seen by the inpatient oncology consult service over a two-month period (8/1/23-8/31/23 and 10/1/23-10/31/23) were included in this analysis. Inpatient management of disease was defined as an invasive procedure to treat the disease or a complication of the disease, initiation of systemic anti-neoplastic treatment, or radiation therapy. Surveys regarding perceived barriers to timely outpatient oncology care were distributed to oncology fellows and attendings. A Diagnostic Oncology Clinic (DOC) was started 2/1/2024 with the goal to decrease time to first outpatient oncology by a median of 12 days to less than 10 days, decrease hospital length of stay (LOS), improve outpatient management of cancer related symptoms, and improve time to treatment. Results: A total of 95 patients were evaluated. 74 (78%) of patients had a new diagnosis of cancer. Most patients had gastrointestinal cancer (n = 40, 42%) or thoracic cancer (n = 24, 25%). 51 patients (53.7%) had metastatic disease. 48 patients (50.5%) had an ECOG performance status of 0 or 1 at the time of consultation. The median hospital LOS was 11 days (IQR, 5-19). 13 patients (13.7%) had an inpatient PET scan and 43 patients (45.3%) required inpatient management of their disease or disease-related complication. 57 patients (60%) were discharged home, 21 (22%) to an extended care facility, and 17 (18%) expired or transitioned to hospice. 35 patients (37%) were seen as new outpatients with a median time to visit of 12 days (IQR 7-20). The median time to initiation of anti-neoplastic therapy as an outpatient was 24 days (IQR 18-33). There were 29 survey respondents corresponding to a response rate of 69%. 16 (55%) felt that about half the time or less patients will have timely follow-up with an oncologist after discharge, and 19 (65%) felt half the time or less patients will have appropriate cancer-related symptom management after discharge. Conclusions: Most patients seen by the inpatient oncology consult service with a new diagnosis of cancer have advanced and symptomatic disease. Historically, there has been significant time to outpatient care and cancer-specific management led by an oncologist. Creation of a diagnostic oncology clinic may shift some diagnostic testing and symptom management from the inpatient to outpatient setting, decrease time to first outpatient visit, and improve provider workflow for a vulnerable patient population. Analysis of this intervention is ongoing.

Incident Benzodiazepine and Z-Drug Use and Subsequent Risk of Serious Infections.

Animal studies have suggested a link between benzodiazepine and related Z-drug (BZDR) use and immune dysfunction. Corresponding evidence in humans is limited and focuses mainly on pneumonia. This study aimed to assess the association of incident BZDR use with subsequent development of serious infections. This Swedish register-based study included a population-based demographically matched cohort, a co-twin control cohort, and an active comparator cohort. Out of 7,362,979 individuals aged below 65 years who were BZDR naïve by 2007, 713,896 BZDR recipients with incident dispensation of any BZDRs between 2007 and 2019 were 1:1 matched to 713,896 nonrecipients from the general population; 9197 BZDR recipients were compared with their 9298 unexposed co-twins/co-multiples; and 434,900 BZDR recipients were compared with 428,074 incident selective serotonin reuptake inhibitor (SSRI) recipients. The outcomes were identified by the first inpatient or specialist outpatient diagnosis of serious infections in the National Patient Register, or death from any infections recorded as the underlying cause in the Cause of Death Register. Cox proportional hazards regression models were fitted and controlled for multiple confounders, including familial confounding and confounding by indication. To study a possible dose-response association, the cumulative dosage of BZDRs dispensed during the follow-up was estimated for each BZDR recipient and modeled as a time-varying exposure with dose categories in tertiles [≤ 20 defined daily doses (DDDs), > 20 DDDs ≤ 65, and > 65 DDDs). The risk of infections was assessed in BZDR recipients within each category of the cumulative BZDR dosage compared to their demographically matched nonrecipients. In the demographically matched cohort (average age at incident BZDR use 42.8 years, 56.9% female), the crude incidence rate of any serious infections in BZDR recipients and matched nonrecipients during 1-year follow-up was 4.18 [95% confidence intervals (CI) 4.13-4.23] and 1.86 (95% CI 1.83-1.89) per 100 person-years, respectively. After controlling for demographic, socioeconomic, clinical, and pharmacological confounders, BZDR use was associated with 83% relative increase in risk of any infections [hazard ratio (HR) 1.83, 95% CI 1.79-1.89]. The risk remained increased, although attenuated, in the co-twin cohort (HR 1.55, 95% CI 1.23-1.97) and active comparator cohort (HR 1.33, 95% CI 1.30-1.35). The observed risks were similar across different types of initial BZDRs and across individual BZDRs, and the risks increased with age at BZDR initiation. We also observed a dose-response association between cumulative BZDR dosage and risk of serious infections. BZDR initiation was associated with increased risks of serious infections,even when considering unmeasured familial confounding and confounding by indication. The exact pathways through which BZDRs may affect immune function, however, remain unclear. Further studies are needed to explore the neurobiological mechanisms underlying the association between BZDR use and serious infections, as it can lead to safer therapeutic strategies for patients requiring BZDR.

A nationwide cohort study of inflammatory bowel disease, histological activity and fracture risk.

Individuals with inflammatory bowel disease (IBD) are at increased risk of fracture. It is unclear if this risk varies by recent histological activity. To determine the fracture risk in IBD during periods with and without histological inflammation. We studied a nationwide cohort of 54,591 individuals diagnosed with IBD in 1990-2016 with longitudinal data on ileo-colorectal biopsies. Fractures were identified by inpatient and hospital-based outpatient diagnoses. We derived Cox regression estimated hazard ratios (HRs) for fracture during 12 months following a histological inflammation (vs. histological remission) record after adjusting for socio-demographics, comorbidities, IBD duration, IBD-related surgery and hospitalization. We adjusted sensitivity analyses for medical IBD treatment including corticosteroids. Mean age of patients was 44.0 (SD = 18.3) and 45.5 (SD = 17.1) years at biopsy with histological inflammation and remission, respectively. For histological inflammation, there were 1.37 (95% CI 1.29-1.46) fractures per 100 years' follow-up versus 1.31 (95% CI 1.19-1.44) for remission (adjusted [a]HR 1.12; 95% CI 1.00-1.26; p = 0.04). HRs were similar with histological inflammation of Crohn's disease (1.11; 95% CI 0.91-1.36) and ulcerative colitis (1.18; 95% CI 1.02-1.36). Estimates were consistent across age groups. An overall small excess risk of any fracture remained after accounting for corticosteroids. A more prominently raised fracture risk was observed in corticosteroid-naïve IBD patients with histological inflammation versus histological remission (aHR 1.41; 95% CI 1.07-1.85). The aHR of hip fracture following histological inflammation was 1.29 (95% CI 0.87-1.92). Histological inflammation in IBD predicted a small increase in short-term fracture risk. Measures to reduce disease activity may reduce fracture risk in IBD.

Tree-based scan statistics to generate drug repurposing hypotheses: a test case using sodium-glucose cotransporter-2 inhibitors.

Most drug repurposing studies using real-world data focused on validating, instead of generating, hypotheses. We used tree-based scan statistics to generate repurposing hypotheses for sodium-glucose cotransporter-2 inhibitors (SGLT2i). We used an active-comparator, new-user design to create a 1:1 propensity-score matched cohort of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) initiators in the MerativeTM MarketScan® Research Databases. Tree-based scan statistics were estimated across an ICD-10-CM-based hierarchical outcome tree using incident outcomes identified from hospital and outpatient diagnoses. We used an adjusted P≤0.01 as the threshold for statistical alert to prioritize associations for evaluation as repurposing signals. We varied the analyses by tree size, scanning level, and clinical settings for outcomes. There were 80,510 matched SGLT2i-DPP4i initiator pairs with 215,333 outcomes among SGLT2i initiators and 223,428 outcomes among DPP4i initiators. There were 18 prioritized associations, which included chronic kidney disease (P=0.0001), an expected signal, and anemia (P=0.0001). Heart failure (P=0.0167), another expected signal, was identified slightly beyond the statistical alert threshold. Narrowing the outcome tree, scanning at different tree levels, and including outcomes from different clinical settings influenced the scan statistics. We identified signals aligning with recently approved indications of SGLT2i, plus potential repurposing signals supported by existing evidence but requiring future validation.