Citations

ABSTRACT Background Systemic infections are a leading cause of hospitalization and death among patients with cirrhosis. Timely and accurate infection identification is essential for both clinical care and the development of predictive models. However, existing methods such as ICD-10 coding are unreliable, and manual chart review is resource-intensive and difficult to scale. This study aimed to develop and validate an automated large language model (LLM)-based approach for infection classification and subtyping in patients with cirrhosis presenting to the emergency department (ED). Method We developed INFEHR (INfection identification and subtyping using Free-text EHR analysis), an LLM-powered pipeline utilizing Claude 3.5 Sonnet to analyze clinical notes from the first 72 hours of admission. Model outputs were compared against a physician-adjudicated gold standard in a cohort of 1,000 encounters from patients with cirrhosis who presented to the ED. Performance was benchmarked against ICD-10 code–based labeling and CDC Adult Sepsis Event criteria. Results INFEHR achieved 94.7% overall accuracy, with 99.5% sensitivity and 92.8% positive predictive value for identifying infection presence, outperforming ICD-10–based classification across all metrics ( p < 0.0001). The model also demonstrated strong performance in classifying pathogen type and infection site. This pipeline processed notes within seconds, offering improvements in efficiency and scalability over manual review. Conclusion INFEHR offers a scalable, reproducible, and accurate method for infection phenotyping in cirrhosis. By overcoming limitations of traditional coding and manual review, it supports high-throughput infection surveillance, improves cohort construction for clinical research, and enables future integration into real-time decision-support tools in hepatology.

Abstract Background: Obstructive sleep apnea (OSA) is associated with obesity and cardiovascular risk. Results from the SURMOUNT-OSA studies demonstrated significant reduction of a number of cardiometabolic risk measures in participants with OSA and obesity following treatment with tirzepatide. Objectives: Systematically analyze all tirzepatide treatment related changes of cardiometabolic risk measures in SURMOUNT-OSA studies and investigate to what extent these changes were mediated by reductions in weight and/or OSA-related measures. Methods: The SURMOUNT-OSA master protocol comprised two 52-week, randomized, double-blind, placebo-controlled Phase 3 studies. Study 1 (N=234) and 2 (N=235) included participants with moderate-to-severe OSA and obesity, who at screening reported not using, or using positive airway pressure (PAP) therapy, respectively. The design and rationale of the studies have been published previously (1). The current analysis investigated the association of treatment with tirzepatide or placebo with SURMOUNT-OSA pre-specified cardiometabolic risk measures including blood pressure, and levels of high-sensitivity C-reactive protein (hsCRP), HDL-C, non-HDL-C, triglycerides, fasting insulin. Further analyses included change in HOMA-IR with tirzepatide compared to placebo, and mediation analysis to determine the proportion of observed changes attributable to reductions in body weight, apnea-hypopnea index (AHI) and sleep apnea-specific hypoxic burden (SASHB). Results: In Study 1, participants experienced greater difference in change from baseline with tirzepatide compared to placebo in SBP (-7.9 mmHg; 95% CI -11.0 to -4.9; p<0.001), and DBP (-3.2 mmHg; 95% CI -5.4 to -1.0; p=0.005) at 48 weeks, and hsCRP (-28.9±8.2%; p=0.003), HDL-C (7.2±2.1%; p<0.001), non-HDL-C (-13.0±3.1%; p<0.001), triglycerides (-32.2±3.7%; p<0.001), fasting insulin (-41.4±5.0%; p<0.001), and HOMA-IR (-48.0±4.9%; p<0.001) at 52 weeks. In Study 2, participants experienced greater differences in change from baseline following tirzepatide compared to placebo in SBP (-4.3 mmHg; 95% CI -7.3 to -1.2; p=0.007) at 48 weeks, and hsCRP (-45.1±8.0%; p<0.001), HDL-C (10.0±2.8%; p<0.001), non-HDL-C (-14.3±2.5%; p<0.001), triglycerides (-31.5±3.7%; p<0.001), fasting insulin (-45.4±5.4%; p<0.001), and HOMA-IR (-54.8±5.0%; p<0.001) at 52 weeks. Statistically significant independent mediation effect of changes in OSA metrics was observed on hsCRP, HOMA-IR and triglycerides. In addition, the combination of changes in weight and OSA metrics, but not weight or OSA improvements alone, had a significant mediation effect on non-HDL-C. There was no significant mediation effect of weight or OSA metrics observed on DBP. Conclusions: In the SURMOUNT-OSA program trials, tirzepatide appeared to have significant cardiometabolic benefits for patients with moderate-to-severe OSA and obesity. Based on the mediation analysis, treating both sleep-disordered breathing and obesity is likely required to optimize cardiometabolic benefits for patients with OSA and obesity.

Abstract Central sleep apnea, a rare polysomnographic finding in the general population, is prevalent in certain cardiovascular conditions including systolic and diastolic left ventricular dysfunction, atrial fibrillation, coronary artery disease, carotid artery stenosis, stroke, and use of certain cardiac-related medications. Polysomnographic findings of central sleep apnea with adverse cardiovascular impacts include nocturnal hypoxemia and arousals, which can lead to increased sympathetic activity both at night and in the daytime. Among cardiovascular diseases, central sleep apnea is most prevalent in patients with left ventricular systolic dysfunction; a large study of more than 900 treated patients has shown a dose-dependent relationship between nocturnal desaturation and mortality. Multiple small randomized controlled trials have shown mitigation of sympathetic activity when central sleep apnea is treated with nocturnal oxygen, continuous positive airway pressure, and adaptive servoventilation. However, two early randomized controlled trials with positive airway pressure devices have shown either a neutral effect on survival or excess premature mortality in the active treatment arm, compared to untreated central sleep apnea. In contrast, the results of the most recent trial using an advanced adaptive servoventilation device showed improved quality of life and no signal for mortality suggesting that treatment of central sleep apnea was at least safe. In addition to positive airway pressure devices, multiple medications have been shown to improve central sleep apnea, but no long-term trials of pharmacologic therapy have been published. Currently, phrenic nerve stimulation is approved for the treatment of central sleep apnea, and the results of a randomized controlled trial showed significant improvement in sleep metrics and quality of life.

Background Obstructive sleep apnea (OSA) is common in heart failure with preserved ejection fraction (HFpEF). However, current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in HFpEF. This study assessed the association between adherence to PAP therapy and health care resource use in patients with OSA and HFpEF. Methods and Results Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to determine associations between PAP adherence and a composite outcome including hospitalizations and emergency room visits. One‐year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 4237 patients (54.0% female, mean age 64.1 years); 40% were considered adherent to PAP therapy (30% intermediate adherent, 30% nonadherent). In the matched cohort, PAP‐adherent patients had fewer health care resource use visits than nonadherent patients, a 57% decrease in hospitalizations, and a 36% decrease in emergency room visits versus the year before PAP initiation. Total health care costs were lower in adherent patients than nonadherent patients ($12 732 versus $15 610, P <0.001). Outcomes for intermediately adherent patients were most similar to those for nonadherent patients. Conclusions Treating OSA with PAP therapy in patients with HFpEF was associated with a reduction in health care resource use. These data highlight the importance of managing concomitant OSA in patients with HFpEF, and the need for strategies to enhance PAP adherence in this population.

Introduction: Obstructive sleep apnea (OSA) is common in heart failure, although the impact of OSA treatment remains unclear. We assessed the association between adherence to positive airway pressure (PAP) therapy and healthcare resource utilization in patients with OSA and heart failure with reduced ejection fraction (HFrEF). Methods: Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFrEF were used to measure the association of PAP adherence and a composite clinical outcome of hospitalization and emergency room (ER) visits. US Medicare defines PAP compliance as usage of the device for at least 4 hours/night for 70% of nights in a consecutive 30-day period over 90 days. PAP adherent patients met these criteria for all 4 90-day periods, while PAP non-adherent patients did not meet these criteria for any 90-day period over one year. Propensity score methods were used to create well matched groups with differing PAP adherence levels. Results: The study cohort consisted of 3,182 eligible patients (69.9% male, mean age 59.7 years) of whom 39% were considered adherent to PAP therapy (29% intermediate-adherent, 31% non-adherent). In the year after PAP prescription, after propensity score matching, PAP adherent patients had fewer hospital visits than non-adherent patients, driven by a 24% reduction in ER visits for adherent patients (Table 1a). These results remained consistent with inverse probability weighting and furthermore showed there were no statistically significant differences between intermediate-adherent and non-adherent patients for any outcome (Table 1b). Conclusions: Treating OSA with PAP therapy in patients with HFrEF is associated with a reduction in the composite outcome of hospitalization and ER visits, driven primarily by a reduction in ER visits. Consistent adherence to PAP therapy is required to realize these benefits.

Introduction: The prevalence of obstructive sleep apnea (OSA) in heart failure (HF) patients varies from 30 to 50%. The differences in clinical characteristics, healthcare resource utilization (HCRU), and positive airway pressure (PAP) usage between HF with preserved ejection fraction (HFpEF) vs. HF with reduced ejection fraction (HFrEF) in OSA patients are not well known. Objective: To compare clinical characteristics, PAP usage, and HCRU in OSA patients with HFpEF vs HFrEF. Methods: Retrospective cohort study using US administrative claims data linked to objective PAP usage data over one year. HFpEF and HFrEF were identified by ICD-9/10 codes associated with healthcare encounters 1 year before starting PAP therapy. Pearson’s Chi-squared and Wilcoxon rank-sum tests were used as applicable to compare baseline characteristics and PAP usage, and the pre to post-PAP initiation difference in the number of health care encounters. Results: In total, 7,419 patients with HF and OSA were identified, of which 57% had HFpEF. HFpEF patients were majority female (54%) and older than those with HFrEF (64.1 ± 11.52 vs 59.7 ± 11.24 years, p<0.001). HFpEF had a higher overall comorbidity burden, although coronary artery disease, atrial fibrillation, and other arrhythmias were more prevalent in HFrEF. Both prior to and after PAP therapy, HCRU was higher in HFpEF patients compared to HFrEF (Table 2a). There were no differences in PAP usage between HFpEF and HFrEF (3.6 ± 2.9 vs 3.7 ± 3.0 hrs/night, p=0.070) over the first year of PAP therapy. There was a significant reduction in ER visits and all cause hospitalizations after 1 year of PAP therapy initiation, which was similar between groups (Table 2b). Conclusions: Although there were differences in clinical characteristics between HFpEF and HFrEF patients with OSA, and HFpEF is associated with greater HCRU, PAP therapy usage was similar, and both groups experienced a similar reduction in HCRU after the first year of PAP initiation.

Introduction: Heart failure patients with preserved ejection fraction (HFpEF) frequently have co-morbid obstructive sleep apnea (OSA), although the impact of OSA treatment remains unclear in this patient population. We assessed the association between adherence to positive airway pressure (PAP) therapy and healthcare resource utilization in patients with OSA and HFpEF. Methods: Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to measure the association of PAP adherence and healthcare resource utilization, defined by hospitalizations and emergency room (ER) visits. US Medicare defines PAP compliance as use for at least 4 hours/night for 70% of nights in a consecutive 30-day period over 90 days. PAP adherent patients met this criteria for all 4 90-day periods, while PAP non-adherent patients did not meet this criteria for any 90-day period over one year. Propensity score methods were used to create well matched groups with differing PAP adherence levels. Results: The study cohort consisted of 4,237 eligible patients (54.0% female, mean age 64.1 years), of whom 40% were considered adherent to PAP therapy (30% intermediate-adherent, 30% non-adherent). After propensity score matching on prior year covariates, during the year after PAP prescription, PAP adherent patients had fewer hospital visits than non-adherent patients, with a 57% reduction in hospitalizations and a 36% reduction in ER visits for PAP adherent patients (Table 1a). These results remained consistent with inverse probability weighting, and furthermore showed a significant difference in hospitalizations between intermediate-adherent and non-adherent patients, but no significant difference in ER visits (Table 1b). Conclusions: Treating OSA with PAP therapy in patients with HFpEF is associated with a reduction in hospitalizations and ER visits. Adherence to PAP therapy is required to realize these clinical benefits.

Abstract Introduction The prevalence of obstructive sleep apnea (OSA) is high in patients with systolic heart failure (HFrEF) and has been associated with poor prognosis in this patient population. The impact of positive airway pressure (PAP) therapy in patients with OSA and HFrEF remains unclear. This retrospective study sought to investigate the association between 1-year adherence to PAP therapy and healthcare resource utilization (HCRU) in patients with newly diagnosed OSA and comorbid HFrEF. Methods A national sample of administrative claims data linked to objective PAP therapy usage was used for this analysis. Included patients either had two healthcare encounters or one hospitalization with a systolic heart failure ICD-10 diagnosis code the year prior to being diagnosed with OSA and initiated on PAP therapy. HCRU was measured as a composite outcome of hospitalizations, and emergency room (ER) visits. Propensity score matching was used to create well-balanced groups with differing PAP adherence levels to assess the association with 1-year HCRU outcomes. Risk-adjusted models were used to generate the number needed to treat (NNT) that referred to the number of patients that need to become adherent to PAP from non-adherent to avoid 1 visit. Results We identified 3,182 patients with OSA and comorbid HFrEF, and after propensity score matching, 738 patients remained in each group (adherent vs. non-adherent). After 1 year of PAP therapy, adherent patients had fewer visits than non-adherent patients (0.92 vs. 1.15 visits per subject, p = 0.006), which was driven by a 24% reduction in ER visits for adherent patients. Composite hospitalization and ER visit costs were lower in adherent versus non-adherent patients ($3,500 vs. $5,879, p=0.03). The NNT for the entire cohort to avoid one visit was 1.5 patients. Conclusion HFrEF patients with comorbid OSA who were adherent to PAP therapy for 1 year have fewer composite hospitalizations and ER visits than patients that were not adherent. These results highlight the clinical and economic benefits of treating OSA in HFrEF patients. Support (if any) Funding Source: ResMed

Background Obstructive sleep apnea (OSA) is a common comorbidity in patients with heart failure, although current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in patients with heart failure. This study assessed the impact of adherence to PAP therapy on health care resource utilization in patients with OSA and heart failure with reduced ejection fraction. Methods and Results Administrative insurance claims data linked with objective PAP therapy use data from patients with OSA and heart failure with reduced ejection fraction were used to determine associations between PAP adherence and a composite outcome of hospitalizations and emergency room visits. One‐year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 3182 patients (69.9% male, mean age 59.7 years); 39% were considered adherent to PAP therapy (29% intermediate adherent, 31% nonadherent). One year after PAP initiation, adherent patients had fewer composite visits than matched nonadherent patients, driven by a 24% reduction in emergency room visits for adherent patients. Composite visit costs were lower in adherent versus nonadherent patients ($3500 versus $5879, P =0.031), although total health care costs were not statistically different ($13 028 versus $14 729, P =0.889). Conclusions PAP therapy adherence in patients with OSA with heart failure with reduced ejection fraction was associated with a reduction in health care resource utilization. This suggests that greater emphasis should be placed on diagnosing and effectively treating OSA with PAP in patients with heart failure with reduced ejection fraction.

Objectives: Lung cancer is an important cause of mortality in the United States. Targeted mutation analysis has the potential to alter mortality in those with non-small-cell lung cancer. As such, the importance of timely tissue turnaround time (TAT) is substantial. We evaluated TAT at Mayo Clinic Arizona and found it to be delayed relative to national standards. Material and Methods: We conducted a series of plan, do, study, and act (PDSA) cycles at a single institution to identify areas for improvement with our lung cancer genomic testing. We assembled a multidisciplinary team and held serial meetings to discuss data from each PDSA cycle. Results: Using PDSA cycles and multidisciplinary discussions, we were able to identify a number of process limitations slowing TAT. We were then able to generate enhanced and timely communication between providers and pathology, educate and enforce the order/requisition workflow, and establish pathology accessioning with lung cancer specimens top priority. Conclusion: We were able to generate and implement a standard operating procedure for genomic testing of lung cancer specimens at our institution, thereby reducing tissue TAT.