Longitudinal Management of Cardiovascular Risk Factors Among Postpartum Women.

Background: Pregnancy-related cardiovascular (CV) conditions, including hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM), are associated with increased long-term CV risk. Methods: This retrospective cohort study defined the prevalence of HDP and GDM within a large, academic health system in the southeast United States between 2012 and 2015 and described health care utilization and routine CV screening up to 1-year following delivery among those with pregnancy-related CV conditions. Rates of follow-up visits and blood pressure, hemoglobin A1c (HbA1c), and lipid screening in the first postpartum year were compared by provider type and pregnancy-related CV condition. Results: Of the 6027 deliveries included, 20% were complicated by HDP and/or GDM. Rates of pre-pregnancy CV risk factors were high, with a significantly higher proportion of pre-pregnancy obesity among women with HDP than in normal pregnancies. Those with both HDP/GDM had the highest rates of follow-up by 1-year postpartum, yet only half of those with any pregnancy-related CV condition had any follow-up visit after 12 weeks. Although most (70%) of those with HDP had postpartum blood pressure screening, less than one-third of those with GDM had a repeat HbA1c by 12 months. Overall, postpartum lipid screening was rare (<20%). Conclusion: There is a high burden of pregnancy-related CV conditions in a large U.S. academic health system. Although overall rates of follow-up in the early postpartum period were high, gaps in longitudinal follow-up exist. Low rates of CV risk factor follow-up at 1 year indicate a missed opportunity for early CV prevention.

An Analysis of Linker-Dependent Effects on the APC Activation and In Vivo Immunogenicity of an R848-Conjugated Influenza Vaccine.

Subunit or inactivated vaccines comprise the majority of vaccines used against viral and bacterial pathogens. However, compared to their live/attenuated counterparts, these vaccines often demonstrate reduced immunogenicity, requiring multiple boosters and or adjuvants to elicit protective immune responses. For this reason, studies of adjuvants and the mechanism through which they can improve inactivated vaccine responses are critical for the development of vaccines with increased efficacy. Studies have shown that the direct conjugation of adjuvant to antigen promotes vaccine immunogenicity, with the advantage of both the adjuvant and antigen targeting the same cell. Using this strategy of direct linkage, we developed an inactivated influenza A (IAV) vaccine that is directly conjugated with the Toll-like receptor 7/8 agonist resiquimod (R848) through a heterobifunctional crosslinker. Previously, we showed that this vaccine resulted in improved protection and viral clearance in newborn nonhuman primates compared to a non-adjuvanted vaccine. We subsequently discovered that the choice of linker used to conjugate R848 to the virus alters the stimulatory activity of the vaccine, promoting increased maturation and proinflammatory cytokine production from DC differentiated in vitro. With this knowledge, we explored how the choice of crosslinker impacts the stimulatory activity of these vaccines. We found that the linker choice alters signaling through the NF-κB pathway in human monocyte-derived dendritic cells (moDCs). Further, we extended our analyses to in vivo differentiated APC present in human peripheral blood, replicating the linker-dependent differences found in in vitro differentiated cells. Finally, we demonstrated in a mouse model that the choice of linker impacts the amount of IAV-specific IgG antibody produced in response to vaccination. These data enhance our understanding of conjugation approaches for improving vaccine immunogenicity.

Generalizability of an EHR-network dataset to the United States for cardiovascular disease conditions: Comparison of Cerner real world data with the national inpatient sample.

BACKGROUND: Electronic Health Record (EHR) data from health systems are increasingly being combined for clinical research purposes. Yet, it remains unclear whether these large EHR data sources provide a representative assessment of national disease prevalence and treatment. To evaluate this, we compared Cerner RealWorldData (CRWD), a large EHR data source, to those seen in the National Inpatient Sample (NIS) for 3 cardiovascular conditions (myocardial infarction (MI), congestive heart failure (CHF), and stroke. METHODS: Adult patients (age ≥18 years) hospitalized with MI, CHF, and stroke were identified in both CRWD (86 health systems) and the NIS (4,782 hospitals). Patient demographics, comorbidities, procedures, outcomes (length of stay and in-hospital mortality) and hospital type (teaching or nonteaching) were compared between NIS and CRWD patients. RESULTS: Of 86 health systems participating in CRWD, 33 were excluded for potential data quality issues which accounted for about 11% of hospitalizations in the dataset, leaving 53 for inclusion in analysis which accounted for about 89% of hospitalizations in the dataset. Between January 1, 2017 and December 31, 2018, 116,956 MI, 188,107 CHF, and 93,968 stroke hospitalizations were identified in CRWD vs 2,245,300 MI, 4,310,745 CHF, and 1,333,480 stroke hospitalizations in the NIS. Patient demographics were similar among patients in CWRD and the NIS for all 3 cardiovascular groups except for ethnicity, with underrepresentation of Hispanic individuals in CRWD vs the NIS. Patients hospitalized in CRWD had a slightly higher proportion of coded co-morbidities compared with NIS hospitalizations due to a longer potential look-back period. For patients with MI, hospital mortality, length of stay, coronary artery bypass graft (CABG) rates, and percutaneous coronary intervention (PCI) rates were similar between CRWD and NIS. Additionally, there was similar in hospital mortality and length of stay for those with CHF and stroke hospitalizations between CRWD and NIS. CONCLUSIONS: On aggregate, characteristics of hospitalizations for MI, CHF, and stroke using EHR data from one nationwide EHR-derived database, CRWD, appears similar to characteristics of hospitalizations in the nationally representative NIS. Important limitations of CRWD include lack of geographic representativeness, under-representation of Hispanic adults, and the need to exclude health systems for missing data.

Uptake of non-statin lipid-lowering therapies for secondary prevention in community practice.

Nearly two-thirds of individuals with atherosclerotic cardiovascular disease (ASCVD) do not reach target low-density lipoprotein cholesterol despite statin therapy. Three novel lipid-lowering therapies have proven to further reduce ASCVD beyond statins, including: ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and icosapent ethyl. This study evaluated the use of these three agents in 728,423 individuals with ASCVD from 89 US health systems from 01/2018 through 03/2021 using the electronic health record. As of 2021, only 6.0% of ASCVD patients were on ezetimibe, 1.6% were on a PCSK9i, and 1.3% on icosapent ethyl, with utilization only marginally increasing over the study period. Addressing the underutilization of non-statin lipid-lowering therapy for secondary prevention is a critical step in improving the treatment gap of patients with residual risk of ASCVD.

Bending the Cardiovascular Event Curve by Evaluating the Potential Impact of Achieving Low-Density Lipoprotein Cholesterol Goal Across a Large Health System Among Secondary Prevention Patients.

Guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) lowering in patients with atherosclerotic cardiovascular disease (ASCVD). However, the recommended threshold of LDL-C ≤70 mg/dL is often not achieved. We used data from the Duke University Health System electronic health record to characterize patterns of lipid levels and lipid management in patients with ASCVD to estimate the number of clinical events that could be prevented by achieving LDL-C ≤70 mg/dL . A multivariable logistic regression model was developed to predict the 1-year composite of all-cause mortality, myocardial infarction, stroke, or coronary revascularization and was validated through bootstrapping. The number needed to treat to prevent an event was then determined. Among 56,230 patients with ASCVD, the median (quartile 1, quartile 3) age was 68.6 years (59.9, 76.2), 47% were women, and 27% were non-Hispanic Black. LDL-C was >70 mg/dL in 39,566 of patients (70%); these patients were more frequently female (51% vs 36%), non-Hispanic Black (28% vs 23%), and less frequently on statin therapy (67% vs 91%) than those with LDL-C ≤70 mg/dL . A predictive model with reasonable discrimination (c-index 0.77, 95% confidence interval 0.760 to 0.77) and calibration (slope 0.99) determined that if the overall population achieved an LDL-C ≤70 mg/dL, 734 clinical events (455 myocardial infarctions, 186 strokes, and 93 coronary revascularizations) could be prevented in a year. Achieving LDL-C ≤70 mg/dL in patients with ASCVD across a health system could prevent significant clinical events within a single year. In conclusion, this study quantifies the potential benefit of a system-wide effort to achieve guideline-based LDL-C goals.

Use of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagonlike Peptide-1 Receptor Agonists in Patients With Diabetes and Cardiovascular Disease in Community Practice.

Importance: Recent national guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD); yet, there are limited data on the use of these agents in contemporary community practice. Objective: To evaluate the use of SGLT2i and GLP-1 RA in adults with T2D and ASCVD across a diverse sample of health care systems in the US. Design, Setting, and Participants: This multicenter, retrospective cohort study used electronic health record data from 88 US health care systems participating in Cerner Real World Data between January 2018 to March 2021. Adults with ASCVD and T2D taking at least 1 glucose-lowering medication, had end-stage kidney disease, or had stage 5 chronic kidney disease were excluded. Main Outcomes and Measures: Treatment with SGLT2i or GLP-1 RA. Results: A total of 321 304 patients were identified with T2D and ASCVD ASCVD (130 280 female [40.5%]; median [IQR] age, 70.9 [62.9-78.0] years) who were potentially eligible for SGLT2i and/or GLP-1 RA, including 37 754 Black individuals (11.8%), 51 522 Hispanic individuals (16.0%), and 256 008 White individuals (11.8%). From January 2018 to March 2021, the use of SGLT2i increased from 5.8% (11 285 of 194 264) to 12.9% (11 058 of 85 956), GLP-1 RA increased from 6.9% (13 402 of 194 264) to 13.8% (11 901 of 85 956), and use of either agent increased from 11.4% (22 069 of 194 264) to 23.2% (19 909 of 85 956). Those taking an SGLT2i or GLP-1 RA were younger, less frequently hospitalized in the year prior, and more likely to be taking additional secondary prevention medications. Treated and nontreated populations were similar in terms of race, ethnicity, and outpatient health care utilization. Sulfonylureas and dipeptidyl peptidase 4 inhibitors remained more commonly used than SGLT2i or GLP-1 RA through 2021. Conclusions and Relevance: In this study, uptake of SGLT2i and GLP-1 RA in adults with T2D and ASCVD increased modestly after guideline recommendations, although less than a quarter of persons with ASCVD and T2D receiving medical therapy were taking either. Further efforts are necessary to maximize the potential population benefit of these therapies in this high-risk population.

Predictive Utility of a Validated Polygenic Risk Score for Long-Term Risk of Coronary Heart Disease in Young and Middle-Aged Adults.

BACKGROUND: Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies. METHODS: Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20-39 years [median, 30 years] of age), early midlife (FOS, 40-59 years [median, 43] years of age), and late midlife (ARIC, 45-59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared to assess discrimination for each model individually and together with the optimism-corrected C index (95% CI). RESULTS: Among 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08-3.27], 2.09 [95% CI, 1.83-2.40], and 2.11 [95% CI, 1.96-2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70-2.30], 1.64 [95% CI, 1.47-1.84], and 1.22 [95% CI, 1.15-1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70-0.78], 0.70 [95% CI, 0.67-0.72], and 0.72 [95% CI, 0.70-0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69-0.78], 0.66 [95% CI, 0.62-0.69], and 0.66 [95% CI, 0.64-0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001-0.05), 0.02 (95% CI, -0.002 to 0.037), and 0.002 (95% CI, -0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively. CONCLUSIONS: Despite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.

Cardiovascular Events and Long-Term Risk of Sudden Death Among Stabilized Patients After Acute Coronary Syndrome: Insights From IMPROVE-IT.

Background Unlike patients with low ejection fraction after an acute coronary syndrome (ACS), little is known about the long-term incidence and influence of cardiovascular events before sudden death among stabilized patients after ACS. Methods and Results A total of 18 144 patients stabilized within 10 days after ACS in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) were studied. Cumulative incidence rates (IRs) and IRs per 100 patient-years of sudden death were calculated. Using Cox proportional hazards, the association of ≥1 additional postrandomization cardiovascular events (myocardial infarction, stroke, and hospitalization for unstable angina or heart failure) with sudden death was examined. Early (≤1 year after ACS) and late sudden deaths (>1 year) were compared. Of 2446 total deaths, 402 (16%) were sudden. The median time to sudden death was 2.7 years, with 109 early and 293 late sudden deaths. The cumulative IR was 2.47% (95% CI, 2.23%-2.73%) at 7 years of follow-up. The risk of sudden death following a postrandomization cardiovascular event (150/402 [37%] sudden deaths; median 1.4 years) was greater (IR/100 patient-years, 1.45 [95% CI, 1.23-1.69]) than the risk with no postrandomization cardiovascular event (IR/100 patient-years, 0.27 [95% CI, 0.24-0.30]). Postrandomization myocardial infarction (hazard ratio [HR], 3.64 [95% CI, 2.85-4.66]) and heart failure (HR, 4.55 [95% CI, 3.33-6.22]) significantly increased future risk of sudden death. Conclusions Patients stabilized within 10 days of an ACS remain at long-term risk of sudden death with the greatest risk in those with an additional cardiovascular event. These results refine the long-term risk and risk effectors of sudden death, which may help clinicians identify opportunities to improve care. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial.

BACKGROUND: Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined. OBJECTIVES: The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters. METHODS: This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters. RESULTS: Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684). CONCLUSIONS: In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. METHODS: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). RESULTS: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar. CONCLUSIONS: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01471522.

Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy. METHODS: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory­interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). RESULTS: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61­1.30]; severe ischemia HR, 0.83 [95% CI, 0.57­1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86­1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98­1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06­6.98]) and MI (HR, 3.78 [95% CI, 1.63­8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%­12.4%]), but 4-year all-cause mortality was similar. CONCLUSIONS: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup.

Lipoprotein(a) Testing Patterns in a Large Health System.

Lipoprotein (a) [Lp(a)] is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). As directed therapy for Lp(a) emerges, it is important to understand patterns of Lp(a) testing in routine clinical practice. We set out to characterize Lp(a) testing across a large academic health system. Using electronic health record (EHR) data from 2014 to 2019, we compared patients who underwent Lp(a) testing to date-matched peers who had low density lipoprotein (LDL-C) assessment alone. We analyzed ordering provider characteristics and rates of initiation of new lipid lowering therapy (LLT) within 12 months after testing. Of 1,296 adults with Lp(a) test results, 629 (48.5%) had prior history of ASCVD and 667 (51.4%) did not. Compared with those with LDL-C testing alone, individuals who underwent Lp(a) testing were more like to have a myocardial infarction or ischemic stroke at a young age and multiple prior cardiovascular events. Though the majority of Lp(a) tests were ordered in outpatient encounters, a higher proportion of Lp(a) tests compared with LDL-C tests were performed in the inpatient setting. Neurology and psychiatry were the most common specialty to order Lp(a) tests in our cohort. There was a significantly increased initiation of LLT after Lp(a) testing compared with LDL-C testing across all medication types. Consistent with guidelines, Lp(a) testing is used in those with early onset ASCVD, and among those with multiple cardiovascular events. Lp(a) testing is associated with more aggressive LLT in following year. Further research is needed to characterize Lp(a) testing across larger populations.

Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure.

BACKGROUND: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial. METHODS AND RESULTS: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139). CONCLUSIONS: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

The importance of weight stabilization amongst those with overweight or obesity: Results from a large health care system.

Data on patterns of weight change among adults with overweight or obesity are minimal. We aimed to examine patterns of weight change and associated hospitalizations in a large health system, and to develop a model to predict 2-year significant weight gain. Data from the Duke University Health System was abstracted from 1/1/13 to 12/31/16 on patients with BMI ≥ 25 kg/m2 in 2014. A regression model was developed to predict patients that would increase their weight by 10% within 2 years. We estimated the association between weight change category and all-cause hospitalization using Cox proportional hazards models. Of the 37,253 patients in our cohort, 59% had stable weight over 2 years, while 24% gained ≥ 5% weight and 17% lost ≥ 5% weight. Our predictive model had reasonable discriminatory capacity to predict which individuals would gain ≥ 10% weight over 2 years (AUC 0.73). Compared with stable weight, the risk of hospitalization was increased by 37% for individuals with > 10% weight loss [adj. HR (95% CI): 1.37 (1.25,1.5)], by 30% for those with > 10% weight gain [adj. HR (95% CI): 1.3 (1.19,1.42)], by 18% for those with 5-10% weight loss [adj. HR (95% CI): 1.18 (1.09,1.28)], and by 10% for those with 5-10% weight gain [adj. HR (95% CI): 1.1 (1.02,1.19)]. In this examination of a large health system, significant weight gain or loss of > 10% was associated with increased all-cause hospitalization over 2 years compared with stable weight. This analysis adds to the increasing observational evidence that weight stability may be a key health driver.

Unanticipated Respiratory Compromise and Unplanned Intubations on General Medical and Surgical Floors.

BACKGROUND: Unanticipated respiratory compromise that lead to unplanned intubations is a known phenomenon in hospitalized patients. Most events occur in patients at high risk in well-monitored units; less is known about the incidence, risk factors, and trajectory of patients thought at low risk on lightly monitored general care wards. The aims of our study were to quantify demographic and clinical characteristics associated with unplanned intubations on general care floors and to analyze the medications administered, monitoring strategies, and vital-sign trajectories before the event. METHODS: We performed a multicenter retrospective cohort study of hospitalized subjects on the general floor who had unanticipated, unplanned intubations on general care floors from August 2014 to February 2018. RESULTS: We identified 448 unplanned intubations. The incidence rate was 0.420 per 1,000 bed-days (95% CI 0.374-0.470) in the academic hospital and was 0.430 (95% CI 0.352-0.520) and 0.394 per 1,000 bed-days (95% CI 0.301-0.506) at our community hospitals. Extrapolating these rates to total hospital admissions in the United States, we estimate 64,000 events annually. The mortality rate was 49.1%. Within 12 h preceding the event, 35.3% of the subjects received opiates. All received vital-sign assessments. Most were monitored with pulse oximetry. In contrast, 2.5% were on cardiac telemetry, and only 4 subjects used capnography; 53.7% showed significant vital-sign changes in the 24 h before the event. However, 46.3% had no significant change in any vital signs. CONCLUSIONS: Our study showed unanticipated respiratory compromise that required an unplanned intubation of subjects on the general care floor, although not common, carried a high mortality. Besides pulse oximetry and routine vital-sign assessments, very little monitoring was in use. A significant portion of the subjects had no vital-sign abnormalities leading up to the event. Further research is needed to determine the phenotype of the different etiologies of unexpected acute respiratory failure to identify better risk stratification and monitoring strategies.

DIFFERENCES IN ACHIEVING HBA1C GOALS AMONG PATIENTS SEEN BY ENDOCRINOLOGISTS AND PRIMARY CARE PROVIDERS.

Objective: This study evaluated whether there is a difference in the proportion of patients with type 2 diabetes who achieve a hemoglobin A1c (HbA1c) <7% within one year following treatment by an endocrinologist or primary care physician (PCP). Methods: We conducted a retrospective, propensity-matched study of patients with type 2 diabetes that were not optimally controlled and seen within our health system from 2007-2016. We assessed differences in short term health outcomes for patients following an endocrinologist visit compared to a PCP visit. Results: Patients seen by endocrinologists obtained HbA1c control at a faster rate (hazard ratio = 1.226; 95% confidence interval = 1.01 to 1.488) than those seen by a PCP. Furthermore, 34.5% and 29.5% of those treated by endocrinologists and PCPs, respectively, obtained HbA1c control by one year. Endocrinologists were more likely to prescribe a new medication class within 90 days than PCPs (14.1% versus 10.3%, respectively, P = .043). There was no difference in the risk of hospitalization between groups; 24.4% and 24.1% of those treated by endocrinologists and PCPs, respectively, were hospitalized within one year. Conclusion: Patients treated by endocrinology specialists were more likely to achieve a target HbA1c of <7% (53 mmol/mol) than those treated by PCPs in our health-care system. The performance difference may be partially explained by a higher rate of adding new classes of diabetes medications to the patient's pharmacologic regimens within 90 days by endocrinologists compared with PCPs. The long-term impact of these differences is unknown but has the potential to have an unfavorable impact on the health of the population. Abbreviations: ACP = American College of Physicians; CI = confidence interval; DUHS = Duke University Health System; HbA1c = hemoglobin A1c; HR = hazard ratio; PCP = primary care physician; SMD = standard mean difference.

Adversarial Time-to-Event Modeling.

Modern health data science applications leverage abundant molecular and electronic health data, providing opportunities for machine learning to build statistical models to support clinical practice. Time-to-event analysis, also called survival analysis, stands as one of the most representative examples of such statistical models. We present a deep-network-based approach that leverages adversarial learning to address a key challenge in modern time-to-event modeling: nonparametric estimation of event-time distributions. We also introduce a principled cost function to exploit information from censored events (events that occur subsequent to the observation window). Unlike most time-to-event models, we focus on the estimation of time-to-event distributions, rather than time ordering. We validate our model on both benchmark and real datasets, demonstrating that the proposed formulation yields significant performance gains relative to a parametric alternative, which we also propose.