At-risk Patients Research Articles

Abstract 16504: Hospital Frailty Risk Score (HFRS) Predicts Adverse Events in Patients Undergoing Elective Percutaneous Left Atrial Appendage Closure (LAAC) With WATCHMAN Device

Introduction: Frailty and its association with adverse events are well-known in transcatheter aortic valve replacement. However, this association has not been well-studied in patients undergoing Left Atrial Appendage Closure (LAAC). Hypothesis: Frailty predicts adverse events in patients undergoing elective LAAC with WATCHMAN device. Methods: Patients aged ≥65 years who underwent elective LAAC with WATCHMAN device were identified using ICD-10 procedure code 02L73DK from the 2016-2018 HCUP-NIS Database. Hospital Frailty Risk Score (HFRS) was calculated for each patient based on 109 ICD-10 diagnosis codes and classified into non-frail (HFRS < 5) and frail (HFRS score ≥ 5) groups. In-hospital major adverse event (MAE) was defined as the composite of mortality, stroke (ischemic or hemorrhagic) or TIA, bleeding or transfusion, vascular complications, myocardial infarction, systemic embolization, and pericardial effusion or tamponade requiring pericardiocentesis or surgery. Multivariate regression and receiver operating characteristic (ROC) analyses were used to assess the relationship between the HFRS and MAE. Results: 28,050 patients (Age = 77.3 ± 6.4 years; Female = 42.6%) were included, and 4.7% experienced in-hospital MAE. Frail patients (HFRS score ≥ 5) constituted 12.5% of the cohort. Frail patients were older and had a more significant proportion of women. Rates of MAE were significantly greater in frail patients (4% vs. 9.7%; p<0.001). Increasing Hospital Frailty Risk Score was associated with a greater risk of in-hospital MAE. The AUC - ROC was 0.63 (Figures: A and B). Conclusions: HFRS predicts adverse events after LAAC. HFRS could be implemented in hospital information systems to facilitate the identification of at-risk patients.

Abstract 12144: The Association Between High Cardiac Index and Mortality

Background: Elevated cardiac index (CI) is implicated in the pathophysiology of heart failure. However, data on the CI hemodynamic spectrum that is associated with adverse outcome are lacking. We hypothesized that elevated CI is associated with increased mortality in patients referred for right heart catheterization (RHC). Methods and Results: We retrospectively assembled data for patients undergoing RHC at Vanderbilt University (1998-2013) with ≥ 1 yr follow-up, excluding patients with low CI (<2.2 L/min/m 2 ) which is known to be associated with increased mortality (N=2,548; age median 60 IQR [50-69] yrs; male, 50%; body mass index [BMI], 29 [25-35] kg/m 2 ). Univariate Cox-regression was used to assess the association between CI (measured by thermodilution) octile and all-cause mortality (N=925 [36%] events, time to event 4.7 [3.1-8.8] yrs). All-cause mortality was 31% higher in the highest CI octile (N=317; 4.1 [3.9-4.7] L/min/m 2 ; HR=1.31 [95%CI: 1.01-1.71], P=0.046) compared to the CI octile with lowest mortality risk (N=311; 3.1 [3.0-3.2] L/min/m 2 ). Patients with CI >4.1 L/min/m 2 were younger (54 [46-63] vs. 60 [49-67] yrs, P<0.001) and had lower BMI (28 [24-34] vs. 31 [26-36] kg/m 2 , P<0.001), pulmonary vascular resistance (1.4 [0.9-2.4] vs. 1.8 [1.3-2.7] WU, P<0.001), and hemoglobin (11.9 [10.3-13.7] vs. 12.7 [11.1-13.8] g/dL, P=0.003); similar mean pulmonary arterial pressure (27 [19-35] vs. 26 [20-36] mmHg, P=0.556), pulmonary arterial wedge pressure (13 [8-18] vs. 13 [9-18] mmHg, P=0.352), frequency of hemodialysis (11% vs. 9%, P=0.259) and hyperthyroidism (2% vs. 1%, P=0.491); but significantly higher frequency of liver cirrhosis (18% vs. 7%, P<0.001) compared to the low risk CI group. The mortality association for CI >4.1 L/min/m 2 remained significant after adjusting for age, sex, liver cirrhosis and hemodialysis (HR 1.34 [95%CI 1.03-1.76], p=0.032). Conclusion: Cardiac index >4.1 L/min/m 2 is associated with a significant increase in all-cause mortality among patients referred for RHC, even after adjusting for established risk factors for high-output heart failure. These data expand the mortality continuum related to CI and support further studies that clarify the clinical phenotype of at-risk patients.

Abstract 18229: The Effectiveness of a Student-Delivered Weight Loss Program in a High-Risk Urban Practice

Introduction: Obesity is a global epidemic contributing to CVD, the leading cause of death worldwide. Diet, exercise, and lifestyle are crucial to CVD prevention and treatment. The Healthy Eating Index (HEI) is a 13-component dietary analysis tool based on the Dietary Guidelines for Americans, with higher scores associated with lower CVD risk. Calculating the HEI involves a 24-hour food recall and complex scoring. The Diet Risk Score (DRS), a 9-question, efficient alternative screening tool, has been validated against the HEI. JeffWLP, a unique low-cost, long-term student-delivered nutrition education program, evaluates improvement in DRS. Hypothesis: JeffWLP participants in JeffWLP would demonstrate significant weight loss, increased physical activity, and improved DRS in urban at-risk patients. Methods: In this randomized controlled trial, 30 obese adults from an underserved urban population were randomized to intervention (n=18) or control/usual care (n=12) groups. Mean age was 46 +/- 13 years. 80% were African American, and 90% were female; mean baseline BMI was 38 +/- 5. Mean socioeconomic status, self-assessed using the MacArthur Scale, was 6 (maximum 10). JeffWLP includes 12 core weekly group and individual nutrition education counseling sessions, meal replacements, and an exercise component, followed by unlimited bimonthly maintenance counseling. Vitals were obtained pre, mid, and post-core intervention. Results: JeffWLP participants achieved mean weight loss of 6.1 +/- 7.8 lbs (p=0.01), or 2.7 +/- 3.3% body weight (p < 0.01) in 12 weeks. Mean DRS improved by 7 +/- 6 points (p <0.001). Number of weekend steps walked increased by 3500 +/- 3150 (p = 0.016). Pilot JeffWLP patients (n=7), sustained weight loss of 4.8 +/- 8.1 lbs, 285 days after enrollment (p = 0.17). Conclusions: Our study demonstrates the cost-effectiveness of JeffWLP for improving weight loss, exercise, and dietary risk in 12 weeks. We anticipate additional sustained improvements in this ongoing study with double the sample size; this additional data will be available at the AHA meeting. JeffWLP empowers medical students to improve health outcomes in disadvantaged, at-risk underserved populations affordably, addressing critical health disparities.

Abstract 19050: Polysomnography and Sleep Symptom-Based Patient Profiles Associated With Atrial Fibrillation Development

Introduction: Although sleep disorders are linked to atrial fibrillation (AF), the complex interplay remains unclear. Investigating sleep-based profiles associated with AF can deepen understanding and identify at-risk patients. Hypothesis: We hypothesized discrete phenotypes of symptoms and polysomnography (PSG)-based data differ in relation to incident AF. Methods: This retrospective cohort study of Cleveland Clinic patients (age>18) who underwent PSG 11/27/2004-12/30/2015 identified patient clusters using latent class analysis of 23 sleep-related symptoms, Epworth Sleepiness Scale (ESS) score, and 24 PSG measures of sleep disordered breathing and architecture. Cox proportional hazards models with cluster membership as the independent variable and incident AF as the dependent variable were adjusted for age, sex, race, BMI, cardiopulmonary disease and risk factors, anti-arrhythmic medication, and positive airway pressure with follow up 7.6±3.4 years. Results: Of the sample (n=43,433, age 52±15, 52% male, 74% White) 9% developed AF. Five clusters were identified: 1) Hypoxic + Sleepy (n=3,245): highest % time SaO 2 below 90%, highest ESS, 2) Apneas + Arousals (n=4,592): highest AHI, highest arousal index, 3) Short sleep + Low %REM (n=6,126): shortest sleep duration, longest REM latency, lowest %REM, 4) Hypopneas (n=2,661): most hypopneas, 5) Long sleep + High %REM (n=26,809): longest sleep duration, shortest REM latency, highest %REM (reference). Compared to reference, Hypoxic + Sleepy had 48% (HR=1.48, 95%CI=1.34-1.64), Apneas + Arousals had 22% (HR=1.22, 95%CI=1.11-1.35), and Short Sleep + Low %REM had 11% (HR=1.11, 95%CI=1.01-1.22) higher risk of AF development. Internal validation indicated reasonable predictive accuracy. Sensitivity analysis excluding split night studies confirmed the associations observed. Conclusions: Of 5 patient profiles identified, Hypoxic + Sleepy conferred the strongest AF risk. Consistent with prior evidence of hypoxia as an AF driver and cardiovascular risk of the sleepy phenotype, this constellation of symptoms and physiology illustrates risk in the clinical setting, providing potential value as a risk prediction tool. Future investigation will focus on external validation of these findings.

Quantification of rare somatic single nucleotide variants by droplet digital PCR using SuperSelective primers

Somatic single-nucleotide variants (SNVs) occur every time a cell divides, appearing even in healthy tissues at low frequencies. These mutations may accumulate as neutral variants during aging, or eventually, promote the development of neoplasia. Here, we present the SP-ddPCR, a droplet digital PCR (ddPCR) based approach that utilizes customized SuperSelective primers aiming at quantifying the proportion of rare SNVs. For that purpose, we selected five potentially pathogenic variants identified by whole-exome sequencing (WES) occurring at low variant allele frequency (VAF) in at-risk colon healthy mucosa of patients diagnosed with colorectal cancer or advanced adenoma. Additionally, two APC SNVs detected in two cancer lesions were added to the study for WES-VAF validation. SuperSelective primers were designed to quantify SNVs at low VAFs both in silico and in clinical samples. In addition to the two APC SNVs in colonic lesions, SP-ddPCR confirmed the presence of three out of five selected SNVs in the normal colonic mucosa with allelic frequencies ≤ 5%. Moreover, SP-ddPCR showed the presence of two potentially pathogenic variants in the distal normal mucosa of patients with colorectal carcinoma. In summary, SP-ddPCR offers a rapid and feasible methodology to validate next-generation sequencing data and accurately quantify rare SNVs, thus providing a potential tool for diagnosis and stratification of at-risk patients based on their mutational profiling.

The importance of peri-anaesthetic temperature management: part 2

When considering patient temperature management under anaesthesia, hyperthermia is a rare complication. Associated risk factors, management and prevention of hyperthermia are considered in this article to ensure that veterinary nurses feel confident in dealing with these cases and identifying atrisk patients. This article is the second in a series dedicated to exploring the importance of temperature monitoring and management during the anaesthetic period.

Resistance to CD38 Antigen Targeted Therapy in Multiple Myeloma May Result from Underrecognized Chromosome 4 Gene Deletions

Anti-CD38 monoclonal antibodies (mAbs), daratumumab (dara) and isatuximab (isa), are approved to treat multiple myeloma (MM) in the first line and relapsed/refractory settings. Resistance portends a poor prognosis, yet underlying mechanisms have not been well characterized. Despite generally high CD38 expression on most malignant plasma cells (PCs), antigen density may impact the clinical efficacy of targeted therapy. Unfortunately, therapeutic anti-CD38 mAbs interfere with detection and quantification of CD38 surface level by most conventional clinical flow cytometry assays, limiting characterization of CD38 antigen escape. Tumor cell evasion of antigen specific therapeutics can occur with target loss or downmodulation, a phenomenon conventionally referred to as antigen escape. To elucidate mechanisms of CD38 antigen escape, we evaluated MM patients treated with anti-CD38 mAbs who underwent a marrow evaluation between 1/2017 and 10/2022 at a single institution. Eighty-one of 161 (50%) patients had become clinically refractory over their course. Among 82 (51%) patients with ≥1 chromosomal genomic array test (CGAT) performed, 10 (12%) were found to harbor a CD38 deletion ( Table). With a CGAT coverage of 31%, the estimated prevalence of CD38 deletions was 39%. The median interval from diagnosis to CD38 deletion was calculated as 6.7 years (IQR 2.8 to 11.6) for CD38-deleted patients and estimated as 12.9 years (95% CI 12 to NA; Figure) for all patients. The presence of a CD38 deletion was associated with an increasing number of chromosomal abnormalities on concurrent FISH (OR 2.00, 95% CI 1.33 to 3.29, p=0.002). Specific FISH and flow cytometry findings occurred in conjunction with a CD38 deletion. In 50% of patients, flow cytometry detected a bimodal distribution of CD38 fluorescence intensity, reflecting two populations of malignant plasma cells with distinct CD38 surface levels. No patient showed a uniform malignant plasma cell population with a normal surface CD38 level. When the CD38 (4p15.32) deletion was identified in the context of a large 4p deletion spanning the FGFR3 locus, the FGFR3 (4p16) probe could detect the relevant loss of 4p. This was seen in 6 of 8 patients with a concurrent FGFR3 deletion by CGAT. The proportion of clones harboring a CD38 deletion could be quantified by FISH over time when testing was performed on a CD138-enriched sample. Low-level CD38 deletions (≤25%) did not confer resistance to dara-containing multi-drug regimens. In two cases where such deletions were present at diagnosis, disease control is ongoing in response to dara-Pd and dara-Rd. We suggest that acquired CD38 gene deletions appear to be common, the proportion of patients harboring them increases over time irrespective of prior exposure to CD38 mAbs, and their presence facilitates tumor antigen escape. We demonstrate that CGAT can identify CD38 deletions. Conventional clinical flow cytometry assays are unable to quantify the CD38 surface level due to interference from anti-CD38 mAbs. However, we propose that the finding of a bimodal distribution of CD38 fluorescence by flow cytometry could serve as an initial screen to identify at-risk patients warranting confirmatory CD38 mutational analysis. Following characterization of a deletion, FISH could be used to monitor the clonal level longitudinally. Our suggestion that the presence of a CD38 deletion in >25% of malignant PC clones predicts for reduced CD38 mAb efficacy requires prospective validation.

Long-Term Outcomes of Pulmonary Embolism Requiring Intensive Care Unit (ICU) Admission

Introduction:Pulmonary embolism (PE) requiring intensive care unit (ICU) admission is associated with high in-hospital mortality, however data on long-term survival outcomes and associated contributors remains limited. We sought to further investigate this using a large binational dataset. Methods:Retrospective cohort study of adults aged >16 years admitted to an Australian or New Zealand (NZ) ICU between January 1, 2018 and December 31, 2022 with a primary admission diagnosis of PE using the Australian and NZ Intensive Care Society (ANZICS) Adult Patient Database (APD). Data were available on baseline characteristics - specifically age, gender, admission co-morbidities (active malignancy, chronic cardiovascular, respiratory, renal and liver disease and illness severity as per the Acute Physiology and Chronic Health Evaluation (APACHE) III scoring system. The need for ICU-specific supports (vasopressors or inotropes, invasive and non-invasive ventilation [NIV], extracorporeal membrane oxygenation [ECMO]) was also recorded. All-cause mortality from 30 days to 48 months after ICU admission was obtained. Descriptive analyses, Kaplan-Meier and Cox proportional hazards models were used to describe survival during this time period. Ethical approval was granted by the Alfred Hospital Human Research Ethics Committee (HREC). Results:6447 patients with PE who had been admitted to 193 ICUs across Australia and NZ were identified, representing 9136 patient-years of follow-up. Median age was 66.5 years (interquartile range [IQR], 53-75). 24.5% were admitted to a rural or regional ICU. Median ICU length of stay was 46.6 hours (IQR, 27-79). Median APACHE III score was 42 (IQR, 31-56). Admission co-morbidities included active malignancy (8.1%), chronic respiratory (7.0%), renal (1.4%) and liver (0.4%) disease. Systolic blood pressure was was ≤90 mmHg at time of ICU admission in 1482 patients (23.9% of those in whom this data was available). Vasopressors or inotropes were required in 986 patients (17.6%), NIV was used in 713 (12.6%), invasive ventilation in 453 (8.0%) and 24 patients (0.43%) received ECMO. The mean duration of invasive ventilation where this was required was 14.9 hours. Kaplan-Meier survival analysis is shown in Figure 1. Overall survival was 92.3% at 30 days (95% CI, 91.6-93.0%), 87.5% at 6 months (95% CI, 86.5-88.3%), 84.4% at 12 months (95% CI 83.4%-85.4%) and 73.0% at 48 months (95% CI, 71.0-74.9%). Active malignancy was the strongest independent predictor of mortality (hazard ratio [HR] 3.3, 95% CI 2.8-4.0). Other independent predictors were chronic liver (HR 2.8), renal (HR 1.7) and respiratory (HR 1.6) disease, immunosuppressive therapy (HR 1.5), and the need for NIV (HR 1.4) or vasopressor and inotropic support (HR 1.3). No significant difference in mortality was observed between rural/regional and tertiary/metropolitan ICUs, however improved survival was observed in patients admitted to Australian ICUs (n = 6032) compared to those in NZ (n = 415) (HR 0.5 [95% CI 0.4-0.8]). Conclusions:Nearly three-quarters of patients admitted to ICU due to PE remain alive 2 years later. The largest risk factor for late mortality is malignancy, along with other chronic diseases, which is similar to previous studies reporting long-term follow-up of PE survivors outside ICU, however patients who need advanced life supports (NIV, ECMO) were also at greater risk. Limitations of this study include retrospective design, broad heterogeneity in admission criteria across different ICUs due to variation in resources across both countries and lack of data therapies such as intravenous thrombolysis and anticoagulation. Further work is needed to understand if changes to acute management of at-risk patients might improve long-term survival outcomes.

Symposium 06: Perioperative Neurocognitive Disorders With Considerations for Alzheimer’s Disease and Related Dementias

Summary AbstractLow- and high-risk surgical procedures are performed annually on more than half a million patients aged 65 and older. Yet, at least 20-35% of older patients undergoing surgery have undiagnosed signs of a mild to major neurocognitive disorder. These facts are alarming as older age, and preoperative memory/cognitive/affective vulnerabilities are significant predictors of postoperative cognitive complications such as delirium, cognitive decline, and mortality. Given the expected rate increase of neurodegenerative disorders in the populous, perioperative health care systems will face more significant numbers of individuals with undiagnosed Alzheimer’s disease and related dementias (ADRD) needing procedures with anesthesia due to severe health-related conditions (e.g., cardiac) or requesting surgeries for quality of life improvement (e.g., joint replacement). Through this symposium, attendees will learn from experts about the urgency of appreciating Perioperative Cognitive Disorders and the need for evidence-based perioperative ADRD assessment and intervention methods. Symposium speakers represent the International Society to Advance Alzheimer’s Research and Treatment’s “Perioperative Cognition and Delirium” Professional Interest Area. Lisbeth Evered, Ph.D., University of Melbourne, Australia, will begin the symposium by discussing the nomenclature for Perioperative Neurocognitive Disorders and the need to include neuropsychologists as part of the multidisciplinary diagnostic team. Robert Whittington, MD, University of California, Los Angeles, will present a bench-to-beside review of how tau protein is altered by perioperative factors and its potential relationship to cognition impairment after surgery and anesthesia. Miles Berger, M.D., Ph.D., Duke University, will present his team’s federally funded research showing how anesthesia is a stress test for the brain and the potential implications for incorporating intraoperative EEG monitoring into routine care. Kristin Hamlet, Ph.D., University of Florida, will round out the symposium by presenting a novel perioperative care environment where neuropsychologists identify at-risk undiagnosed ADRD patients before surgery for multidisciplinary care interventions. She will also highlight a cognitive “rescue” multidisciplinary intervention case. Attendees will leave the symposium with an improved understanding of Perioperative Neurocognitive Disorders and how neuropsychologists can work with other disciplines to advance evidence-based perioperative care for at-risk older adults electing surgery with anesthesia.

Association of Lower Extremity Lymphedema and Nonmelanoma Skin Cancers

ObjectiveTo determine whether patients with lymphedema of a lower extremity (LE) had a greater risk of skin cancer than those without lymphedema. Patients and MethodsThis retrospective cohort study included patients with LE lymphedema examined at Mayo Clinic in Rochester, MN, USA, from January 1, 2000, through December 31, 2020. All patients with the phrase “lower extremity lymphedema” and a diagnostic code for lymphedema present in their electronic health record, as well as their age-, race-, and sex-matched controls without lymphedema, were included in the study. A Kaplan-Meier curve was constructed to examine the time to development of the first skin cancer for the lymphedema cohort and the controls. A Cox proportional hazards regression model was used to calculate hazard ratios. ResultsIn total, 4437 patients had lymphedema within the study period. Compared with the matched control group, the lymphedema group had a significantly increased risk of skin cancer. For the subset of patients with unilateral lymphedema, the lymphedematous extremity was 2.65 times as likely as the nonlymphedematous LE to have skin cancer, particularly basal cell carcinoma. ConclusionLower extremity lymphedema appears to be a risk factor for squamous cell carcinoma, basal call carcinoma, and as expected, angiosarcoma. Clinicians caring for patients with LE lymphedema should be aware of this increased risk and monitor at-risk patients accordingly.

The genetics and disease mechanisms of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-β pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.

Prospective validation of machine learning-based approaches to predict potentially preventable emergency visits and hospitalizations.

404 Background: Patients undergoing cancer treatment are at risk for unplanned acute care. Early identification of at-risk patients could enable preventative interventions, reducing costs and treatment delays. To address this, the Centers for Medicare & Medicaid Services developed the Chemotherapy Measure (OP-35) to monitor potentially preventable acute care utilization during outpatient treatment. We previously developed machine-learning (ML) models using three approaches: least absolute shrinkage selection operator (LASSO), random forest (RF), and gradient boosted trees (GBT). The models predict risk of an OP-35 qualifying acute care event in the 30-days following a systemic therapy infusion and had good performance in the internal validation cohort, with GBT demonstrating the best predictive ability (receiver operating characteristic area under the curve (ROC-AUC) = 0.805). The aim of this study was to prospectively validate these models in patients undergoing systemic therapy at a single institution. Methods: All three models are being prospectively validated on systemic therapy infusions, including chemo, immuno, biologic, hormone, research and targeted therapies. Assuming a 2% event rate based on our prior data, with an alpha = 0.05 and 84% power, to detect an ROC-AUC of 0.75, validation will run for a total of 8000 infusions, from May 1 to August 21, 2023. We present early findings from May 1 to May 14, 2023 for this prospective validation. Model performance was assessed for calibration based on brier score and predictive ability based on ROC-AUC. Sensitivity and specificity were calculated for the model with the highest ROC-AUC based on a previously determined Youden’s J statistic. Results: This study included 1096 systemic therapy treatments across 957 patients. 21 (1.9%) infusions resulted in an OP-35 qualifying acute care event (3 emergency department visits and 18 hospitalizations). Most events were due to pain, anemia, sepsis, and/or dehydration. All models had good performance, with GBT demonstrating the greatest predictive ability (ROC-AUC = 0.78 [0.67 - 0.88], compared to LASSO (0.76 [0.65-0.85]) and RF (0.70 [0.56-0.81]). GBT also had good calibration (brier score = 0.017 [0.011 - 0.025]) followed closely by LASSO (0.018 [0.011-0.026]) and RF (0.019 [0.012-0.026]). Youden-based cut-off of 0.0249 corresponded to a validation sensitivity of 77.6% and specificity of 61.9%. Conclusions: Early prospective validation of ML models demonstrates accurate predictions of OP-35 qualifying acute care events on a per-infusion basis. The use of computational tools to identify patients at risk for unplanned acute care would enable preventative interventions, reducing costs and treatment disruptions. Prospective validation is ongoing and more comprehensive results will be presented at the meeting.

Heart rate variability as a marker and predictor of inflammation, nosocomial infection, and sepsis - A systematic review.

The autonomic nervous system interacts with the immune system via the inflammatory response. Heart rate variability (HRV), a marker of autonomic activity, is associated with inflammation, and nosocomial infections/sepsis, and has clinical implications for the monitoring of at-risk patients. Due to the vagal tone's influence on anti-inflammatory immune response, this association may predominately be reflected by vagally-mediated HRV indices. However, HRV's predictive significance on inflammation/infection remains unclear. 843 studies examining the associations/prognostic value of HRV indices on inflammation, and nosocomial infection/sepsis were screened in this systematic review. According to inclusion and exclusion criteria, 68 associative studies and 14 prediction studies were included. HRV and pro-inflammatory state were consistently associated in healthy subjects and patient groups. Pro-inflammatory state was related to reduced total power HRV including vagally- and non-vagally-mediated HRV indices. Similar, compared to controls, HRV reductions were observed during nosocomial infections/sepsis. Only limited evidence supports the predictive value of HRV in the development of nosocomial infections/sepsis. Reduced very low frequency power HRV showed the highest predictive value in adults, even with different clinical conditions. In neonates, an increased heart rate characteristic score, combining reduced total power HRV, decreased complexity, and vagally-dominated asymmetry, predicted sepsis. Pro-inflammatory state is related to an overall reduction in HRV rather than a singular reduction in vagally-mediated HRV indices, reflecting the complex autonomic-regulatory changes occurring during inflammation. The potential benefit of using continuous HRV monitoring for detecting nosocomial infection-related states, and the implications for clinical outcome, need further clarification.

Impact of the end of public health emergency oral dispensing flexibilities for at-risk patients in a community oncology practice.

209 Background: Many studies have shown the benefit of medically integrated pharmacies for cancer specialty oral drugs in improving patient adherence and reducing waste compared to external pharmacies. Anti-kickback regulations have limited practice’s ability to deliver prescriptions to patient’s homes from physician offices. During the Covid Public Health Emergency (PHE), flexibility for prescription delivery by a physician owned pharmacy was allowed leading many practices to deliver oral cancer therapies to patients who could not otherwise come to clinics to fill their medications. With the end of the PHE, CMS reversed this flexibility. We sought to determine the impact on patients with this change in CMS regulations. Methods: Utilizing the pharmacy database of prescriptions delivered to a patient’s home for a large statewide community oncology practice in Texas during the PHE, we identified patients with Medicare part D who would no longer be able to utilize their physician’s pharmacy for home delivery of their specialty medications. We determined the distance of those patient’s primary address to the nearest clinic and further matched them to the address deprivation index (ADI) a well-validated approach that rank orders zip codes in deciles from lowest to highest need. Results: We found 970 patients receiving home delivered prescriptions with traditional Medicare Part D. 687 or 71% of patients lived within 20 miles of the nearest clinic. 213 or 22% lived between 20 and 50 miles with 70 or 7% more than 50 miles from the nearest clinic. 60 addresses could not be matched to the ADI database. Focusing on those available addresses in the top half of the ADI at highest need, we found that 40% of patients living within 20 miles of the clinic are at significant risk of disparity vs 67% of those 20-50 miles and 61 % of those living more than 50 miles from the clinic. Conclusions: The removal of the PHE flexibility for home delivery of prescriptions from physician offices will significantly increase the burden on patients in Texas, forcing many to drive long distances to obtain drugs and disproportionately affecting those at greatest risk of disparity. We encourage revising policies to allow medically integrated pharmacies to allow home delivery of cancer specialty drugs to meet CMS stated goals of improving health equity.

Time toxicity in early-phase clinical trials.

104 Background: Early-phase clinical trials (EP-CTs) are designed to determine optimal dosing, tolerability, and preliminary activity of novel cancer therapeutics. However, little is known about the time that patients spend interacting with the healthcare system (e.g., time toxicity) while participating in these studies. Methods: We retrospectively reviewed the electronic health records of consecutive patients enrolled in EP-CTs from 2017-2019 to obtain baseline characteristics and number of healthcare-associated days, defined as all inpatient and outpatient visits while on trial. Encounters were reviewed by a trained coding team and categorized based on intention (required by study protocol versus unplanned oncology visits for disease-related or study-related complications versus non-oncologic, such as primary care visits). We used univariate and multivariable analyses to identify predictors of increased time toxicity, defined as the proportion of healthcare-associated days among total days on trial. For ease of interpretation, we created a dichotomous variable, with high time toxicity defined as 20% or more healthcare-associated days during time on trial, and used regression models to evaluate relationships among time toxicity and clinical outcomes. Results: Among 408 EP-CT participants (median age=60.5 years, 56.5% female), patients spent a median of 21.8% days on trial interacting with the healthcare system. Time toxicity was highest during the first month on trial, with an average of 6.76 healthcare-associated days (5.38 days required by protocol, 1.19 unplanned days, and 0.18 days not related to the cancer diagnosis). Time toxicity decreased after the initial months on trial, with an average of 2.98 healthcare-associated days per month after six months on trial. Patients with gastrointestinal (B=0.07, p=0.002), head and neck (B=0.09, p=0.004), and breast (B=0.06, p=0.015) cancers, as well as those with worse performance status (B=0.04, p=0.017) and those on trials studying targeted therapies (B=0.04, p=0.01) experienced higher time toxicity. Patients with breast cancer (B=0.03, p=0.1) and those receiving targeted therapies (B=0.02, p=0.2) had no increased risk of unplanned time toxicity. High time toxicity was associated with decreased clinical benefit (OR=0.09, p<0.001) and objective response (OR=0.07, p<0.001) as well as worse progression-free (HR=2.10, p<0.001) and overall (HR=2.16, p<0.001) survival. Conclusions: In this large cohort of EP-CT participants, patients spent one-fifth of their time interacting with the healthcare system. We identified characteristics associated with higher time toxicity, including both overall and unplanned time toxicity. We found that high time toxicity correlated with worse clinical outcomes. We show that time toxicity is a readily measurable metric that could help inform patient-clinician discussions, guide future trial design, and identify at-risk patients.

Timely PAH Identification in Adults With Repaired Congenital Heart Disease? The ACHD-QuERI Registry Insights

BackgroundThe Quality Enhancement Research Initiative (QuERI) in adults with congenital heart disease (ACHD) was developed to improve detection of pulmonary arterial hypertension (PAH) after repair of systemic-to-pulmonary arterial shunt lesions. ObjectivesThis study sought to standardize use of accepted criteria for PAH diagnosis and evaluate utility in at-risk patients with ACHD. MethodsPatients ≥18 years of age with ACHD repaired ≥1 year before enrollment and with additional risk factors for developing PAH were eligible. History, physical examination, electrocardiogram, transthoracic echocardiogram, World Health Organization functional class, and 6-minute walk distance were evaluated at baseline and yearly for 3 years. Pop-up reminders of patient-specific evidence-based recommendations for PAH detection appeared during data entry. ResultsAmong 217 eligible patients, mean age (enrollment) was 44.0 ± 15.9 years, 72.3% were women, and 82.0% were World Health Organization functional class I. Electrocardiogram was performed in >80% and TTE in >70% of patients annually; capture of required transthoracic echocardiography (TTE) measures and alignment between study- and core-center interpretation improved over time, with more frequent assessment of pulmonary arterial flow acceleration time and documentation of right ventricular outflow tract Doppler notching. Approximately 40% of patients had ≥2 high-risk features for PAH on TTE, but only 7% (6/82) underwent right heart catheterization (RHC). Using current definitions, 2 patients were confirmed by RHC to have a diagnosis of PAH (maximum follow-up 3 years). ConclusionsA structured protocol may improve screening for patients with repaired ACHD at risk of developing PAH. RHC may be underutilized in patients with ACHD with TTE findings suggestive of PAH. (Adult Congenital Heart Disease Registry [QuERI]; NCT01659411)

Primary care gatekeeping during the COVID-19 pandemic: a survey of 1234 Norwegian regular GPs.

In the Nordic healthcare systems, GPs regulate access to secondary health services as gatekeepers. Limited knowledge exists about the gatekeeper role of GPs during public health crises seen from the perspective of GPs. To document GPs' gatekeeper role and organisational changes during the initial COVID-19 lockdown in Norway. A cross-sectional online survey was addressed to all regular Norwegian GPs (n = 4858) during pandemic lockdown in spring 2020. Each GP documented how patients with potential COVID-19 disease were triaged and handled during a full regular workday. The survey also covered workload, organisational changes, and views on advice given by the authorities. A total of 1234 (25.4%) of Norway's GPs participated. Together, they documented nearly 18 000 consultations, of which 65% were performed digitally (video, text, and telephone). Suspected COVID-19 symptoms were reported in 11% of the consultations. Nearly all these patients were managed in primary care, either in regular GP offices (55.7%) or GP-run municipal respiratory clinics (40.7%), while 3.7% (n = 73) were admitted to hospitals. The GPs proactively contacted an average of 0.8 at-risk patients per day. While 84% were satisfied with the information provided by the medical authorities, only 20% were able to reorganise their practice in accordance with national recommendations. During the early stage of the COVID-19 pandemic in Norway, the vast majority of patients with COVID-19-suspected symptoms were handled in primary care. This is likely to have protected secondary health services from potentially detrimental exposure to contagion and breakdown of capacity limits.

EP04.06-01 Compliance with Lung Cancer Screening Guidelines Among At-Risk Patients at a Rural Teaching Hospital in West Texas

EP04.06-01 Compliance with Lung Cancer Screening Guidelines Among At-Risk Patients at a Rural Teaching Hospital in West Texas

Analisis Pelaksanaan Komunikasi Efektif SBAR Perawat dan Dokter

The aim of this research is to map research results related to the implementation of effective SBAR communication between nurses and doctors. The research method used, namely Scoping Review, was used to map the literature using PRISMA guidelines. The synthesis method uses PCC modification. Articles obtained from the Google Scholar search engine as well as the electronic databases PubMed and ScienceDirect. Search results, from 87 relevant articles with titles and abstracts, 6 articles were found that met the inclusion and exclusion criteria. The research results found that the analysis of the implementation of effective SBAR communication between nurses and doctors contained seven themes, namely patient safety and satisfaction, lack of self-confidence, environment, lack of interpersonal communication, lack of training, and work safety climate. In conclusion, effective communication and collaboration between doctors and nurses is very necessary in managing and limiting disturbances that can endanger patient safety and the continuity of safe care for at-risk patients.
 
 Keywords: Implementation Analysis, Effective Communication, SBAR

A targeted strategic peer support intervention to increase adherence to video teletherapy exposure and response prevention treatment for obsessive-compulsive disorder: a retrospective observational analysis.

Exposure and response prevention (ERP) therapy, a form of cognitive-behavioral therapy, is a first-line, evidence-based treatment for obsessive-compulsive disorder (OCD) for adults and children. It is effective for the majority of those who engage in it, but treatment adherence can be challenging for some due to the stress involved in the treatment as well as different life circumstances that arise. To help improve treatment adherence, NOCD, a provider of video teletherapy ERP, identifies those at risk of non-adherence using a prediction algorithm trained on a data set of N = 13,809 and provides targeted peer support interventions by individuals ("Member Advocates") who successfully completed ERP treatment for OCD. Member Advocates, using lived OCD experience as well as experience with ERP, engage at-risk patients through digital messaging to engage, educate, and encourage patients in the early stages of treatment. From June 2022 to August 2022, N = 815 patients deemed at risk were reached out to and n = 251 responded and engaged with the Member Advocates. In the at-risk patients who engaged, the intervention resulted in a significant mean 30.4% more therapy hours completed compared to those who did not engage. Additionally, engaged patients had greater reductions in OCD severity. These results have implications for how data science, digital interventions, and strategic peer-to-peer communication and support can be combined to enhance the effectiveness of treatment.