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Background Multiple guidelines regarding risk stratification for venous thromboembolism (VTE) incidence following cesarean delivery have been promulgated. Objective To estimate the percentage of cesarean delivery patients for which pharmacologic VTE would be recommended and subsequent incidence of VTE, based on several guidelines. Patients/methods This retrospective cohort study used data from the Nationwide Readmissions Database from October 2015 through December 2017. Diagnosis and procedure codes were used to identify patients undergoing cesarean delivery, incidence of VTE, and risk factors used to stratify risk in the existing guidelines. Time-to-event analysis was used to analyze data, stratified by risk categorization in 2011 American College of Gynecology and Obstetrics (ACOG), 2012 American College of Chest Physician (ACCP), 2015 Royal College of Obstetricians and Gynecologists (RCOG) and 2018 American Society for Hematology (ASH) guidelines. Results/conclusions In a cohort of 1,235,149 cesarean deliveries, VTE incidence was 2.1 per 1,000 deliveries at 330 days following delivery (95% confidence interval: 2.0 - 2.2). Proportions of patients that would be recommended for pharmacologic prophylaxis ranged from 0.2% in 2018 ASH guidelines to 73.4% in 2015 RCOG criteria. Among groups considered at elevated risk for VTE for which pharmacologic prophylaxis would be recommended, VTE incidence varied from 35.2 per 1,000 deliveries based on 2018 ASH criteria to 2.5 per 1,000 in 2015 RCOG criteria. In a large cohort of cesarean deliveries in the United States, application of different risk stratification guidelines identified widely different proportions at risk of VTE following delivery, with implications for being categorized as having elevated risk.

Objectives This study was designed to: (1) characterize stay duration following cesarean delivery, (2) ascertain whether facility variation exists, and (3) determine whether shorter stays are associated with rates of readmission or costs. Study Design The 2017 Nationwide Readmissions Database was used to identify uncomplicated cesarean deliveries. Hierarchical logistic regression was used to assess for facility variation in percentage of patients discharged within 2 days. Similar models were used to assess for associations between probability of readmission within 30 days and facility-level rates of discharge within 2 days. Results In total, 456,312 patients from 1,535 hospitals were included. The median facility discharged 46.8% of patients within 2 days, with the 25th percentile of hospitals 23.7% and the 75th percentile 71.2%. In adjusted regression, there was significant facility heterogeneity (p

Objective Pyelonephritis is the most common nonobstetric cause for hospitalization during pregnancy. The maternal and obstetric complications associated with antepartum pyelonephritis are well described. However, it is not clear whether these risks extend into the postpartum period. The primary objective of this study was to describe the morbidity associated with postpartum pyelonephritis, by comparing the morbidity associated with pyelonephritis in the postpartum period to morbidity seen during pregnancy or delivery. Methods A retrospective cohort study was performed using the Nationwide Readmissions Database (NRD), an all-payor sample of discharges from approximately 60% of U.S. hospitalizations. Discharges between October 2015 and December 2018 were included. Maternity-associated hospitalizations, diagnosis of pyelonephritis, comorbid conditions, and incidence of severe maternal morbidity were identified using International Classification of Disease-10th Revision (ICD-10) diagnosis and procedure codes. Bivariate statistics, weighted to account for the complex survey methods in the NRD, were used to evaluate the association between antepartum, delivery, and postpartum hospital stays associated with pyelonephritis and maternal morbidity. Weighted regression models were used to evaluate the association between admission timing and maternal outcomes. Results A total of 32,850 pyelonephritis admissions were identified, corresponding to a national estimate of 61,837 admissions. Of these, 1,465 (2.4%) were postpartum, 55,056 (89.0%) were antepartum, and 5,317 (8.6%) involved a delivery stay. Rates of severe maternal morbidity were higher in the postpartum group than the antepartum or delivery hospitalization groups (59.5 vs. 12.9 and 15.8%, respectively, p Conclusion Though relatively uncommon, postpartum hospitalizations for pyelonephritis are associated with higher rates of severe maternal morbidity, driven by differential rates of sepsis, than are antepartum or delivery-associated hospitalizations.

Background Infective endocarditis (IE) is a rare but serious infection that complicates pregnancy. Little is known about IE management and outcomes in this population. Methods The National Readmissions Database was used to obtain data between October 2015 and October 2018. Billing codes identified admissions for IE in female patients of reproductive age. Demographic characteristics, comorbidities, and outcomes were compared between patients with maternity-associated and nonmaternity-associated IE and obstetric patients who delivered with and without IE. Weighted regressions were used to examine outcomes in adjusted models. Results We identified 12 602 reproductive-aged female patients with a diagnosis of IE, of which 382 (weighted national estimate, 748) were maternity-associated. Of these cases, 117 (weighted national estimate, 217) occurred during a delivery admission. Compared with patients with nonmaternity-associated IE, maternity-associated infection was associated with younger age (mean, 29.0 vs 36.6 years; P < .001), Medicaid coverage (72.5% vs 47.2%; P < .001), and drug use (76.2% vs 59.8%; P < .001). Mortality was comparable (8.1% vs 10.6%; adjusted rate ratio [aRR], 1.03; 95% confidence interval [CI]: .71–1.48). Compared with patients who delivered without IE, IE complicating delivery was associated with worse maternal and fetal outcomes, including maternal mortality (17.2% vs Conclusions Maternity-associated IE does not appear to confer additional risk for adverse outcome over nonmaternity-associated infection. Patients who deliver with IE have worse maternal and fetal outcomes than those whose deliveries are not complicated by IE.

BACKGROUND In the Northern Hemisphere, influenza season typically starts in December and lasts through March. Pregnant people are at increased risk for influenza-related morbidity and mortality. Potentially, new viral strains or reduced provider suspicion leading to delayed diagnosis of late-season influenza could result in an increased risk of severe infection. OBJECTIVE This study aimed to assess the incidence and morbidity associated with late-season influenza in pregnancy, compared with influenza in other seasons. STUDY DESIGN This was a retrospective cohort study using the 2007–2018 National Inpatient Sample. Pregnant patients with discharge diagnosis codes consistent with influenza infection were compared on the basis of hospital admission quarter (quarter 1: October to December; quarter 2: January to March; quarter 3: April to June; quarter 4: July to September), with quarter 3 defined as “late-season.” The primary outcome was the severe maternal morbidity composite defined by the Centers for Disease Control and Prevention. The secondary outcomes included sepsis, shock, acute renal failure, acute heart failure, temporary tracheostomy, and invasive mechanical ventilation. Associations between outcomes and quarter of infection were adjusted for age, hospitalization type (antepartum, delivery, or postpartum), and comorbid conditions using relative risk regression, weighted to reflect the National Inpatient Sample design. RESULTS Of 7355 hospitalizations, corresponding to a weighted national estimate of 36,042, 2266 (30.8%) occurred in quarter 1, 4051 (55.0%) in quarter 2, 633 (8.6%) in quarter 3, and 405 (5.5%) in quarter 4. A nonsignificant trend toward higher rates of severe maternal morbidity was seen in the “late-season” compared with other quarters (13.9% [quarter 3] vs 10.5% [quarter 1] vs 12.1% [quarter 2] vs 13.6% [quarter 4]; P=.07). Moreover, sepsis was more common in patients with late-season influenza (8.0% [quarter 3] vs 4.8% [quarter 1] vs 5.8% [quarter 2] vs 5.9% [quarter 4]; P=.03). In the adjusted analyses, patients with late-season influenza had a 1.34 (95% confidence interval, 1.01–1.78) higher risk of severe maternal morbidity and 1.57 (95% confidence interval, 1.06–2.32) higher risk of sepsis than patients with influenza in quarter 1. CONCLUSION Influenza infection between April and June, that is, late-season influenza, is associated with a higher risk of severe maternal morbidity and sepsis in pregnant patients. Obstetrical providers must continue to have awareness and suspicion for influenza infection during these months.

Background The epidemiology, and outcome of infective endocarditis (IE) among solid organ transplant (SOT) recipients is unknown. Methods We used data from the 2013-2018 Nationwide Readmissions Database (NRD). IE- and SOT-associated hospitalizations were identified using diagnosis and procedure codes. Outcomes included inpatient mortality, length of stay, and inpatient costs. Adjusted analyses were performed using weighted regression models. Results A total of 99,052 IE-associated hospitalizations, corresponding to a weighted national estimate of 193,164, were included for analysis. Of these, 794 (weighted n = 1,574) were associated with transplant history (SOT-IE). Mortality was not significantly different between SOT-IE and non-SOT-IE (17.2% vs. 15.8%, adjusted relative risk [aRR]: 0.86, 95% confidence interval [CI] [0.71, 1.03]), and fewer SOT-IE patients underwent valve repair or replacement than non-SOT-IE (12.5% vs. 16.2%, aRR 0.82, 95% CI [0.71, 0.95]). We then compared outcomes of patients diagnosed with IE during their index transplant hospitalization (index-SOT-IE) to patients without IE during their transplant hospitalization (index-SOT). Index-SOT-IE occurred most frequently among heart transplant recipients (45.1%), and was associated with greater mortality (27.1% vs. 2.3%, aRR 6.07, 95% CI [3.32, 11.11]). Conclusion Dual diagnosis of SOT and IE was associated with worse outcomes among SOT recipients during index hospitalization, but not overall among patients with IE.

Objective The aim of the study is to compare maternal and neonatal outcomes among patients who are normotensive, hypertensive by Stage I American College of Cardiology-American Heart Association (ACC-AHA) criteria, and hypertensive by American College of Obstetricians and Gynecologists (ACOG) criteria. Study Design Secondary analysis of a prospective first trimester cohort study between 2007 and 2010 at three institutions in Baltimore, MD, was conducted. Blood pressure at 11 to 14 weeks' gestation was classified as (1) normotensive (systolic blood pressure [SBP] Results Among 3,422 women enrolled, 2,976 with delivery data from singleton pregnancies of nonanomalous fetuses were included. In total, 20.2% met hypertension criteria (Stage I ACC-AHA n = 254, 8.5%; ACOG n = 347, 11.7%). The Stage I ACC-AHA group's risk for developing preeclampsia was threefold higher than the normotensive group (adjusted relative risk [aRR] 3.70, 95% confidence interval [CI] 2.40–5.70). The Stage I ACC-AHA group had lower preeclampsia risk than the ACOG group but the difference was not significant (aRR 0.87, 95% CI 0.55–1.37). The Stage I ACC-AHA group was more likely than the normotensive group to deliver preterm (aRR 1.44, 95% CI 1.02–2.01) and deliver an SGA neonate (aRR 1.51, 95% CI 1.07–2.12). The Stage I ACC-AHA group was less likely to deliver preterm compared with the ACOG group (aRR 0.65, 95% CI 0.45–0.93), but differences in SGA were not significant (aRR 1.31, 95% CI 0.84–2.03). Conclusion Pregnant patients with Stage I ACC-AHA hypertension in the first trimester had higher rates of preeclampsia, preterm birth, and SGA neonates compared with normotensive women. Adverse maternal and neonatal outcomes were numerically lower in the Stage I ACC-AHA group compared with the ACOG group, but these comparisons only reached statistical significance for preterm birth. Optimal pregnancy management for first trimester Stage I ACC-AHA hypertension requires active study. Key Points

Background Little is known about infective endocarditis (IE) occurring during pregnancy. In this analysis, we sought to define the patient characteristics, risk factors, and outcome of maternity-associated IE (maIE). Methods The National Readmissions Database was used to identify admissions for IE in female patients aged 12 – 55 years discharged between Oct. 2015 and Dec. 2017. Demographics, comorbidities, and outcomes were obtained. Differences between groups were analyzed using weighted Chi-squared test for categorical variables and weighted linear regression for continuous variables. Weighted multivariate regressions adjusted for demographics, hospital, etiologic organism, and comorbid conditions to assess the association between maternity status and outcomes. Results Out of 10,271 identified IE admissions (corresponding to a national estimate of 19,626 admissions), maIE accounted for 320 (national estimate 617) (3.1%). Of these maIE admissions, 41.2% were antepartum admissions, 26.3% resulted in delivery, 18.3% were postpartum, and 11.3% were an early or abnormal pregnancy. Patients with maIE were younger (28.4 ± 3.9 vs. 36.6 ± 8.0, P < 0.001) and more likely insured by Medicaid (73.3% vs. 46.6%, P < 0.001). Although generally healthier, patients with maIE had higher rates of drug abuse (75.7% vs. 58.5%, P < 0.001). In unadjusted comparisons maIE was associated with lower rates of 60-day mortality and thromboembolic events. In adjusted analysis only differences between rates of thromboembolic events were significant (adjusted incremental difference: -17.1%, 95% confidence interval: -22.7% to -11.6%). Differences in rates of valve procedures, mechanical ventilation, length of stay, and inpatient costs were not statistically significant (Figure). Regression-adjusted Outcomes Conclusion Compared with other reproductive aged female IE patients, patients with maIE are younger, healthier, more likely insured by Medicaid, and report higher rates of drug abuse. After adjustment, they receive similar management and do not appear to be at higher risk for adverse outcomes including mortality. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Background: The necessity for rapid evaluation and treatment of acute ischemic stroke with intravenous tPA (tissue-type plasminogen activator) may increase the risk of administrating tPA to patients presenting with noncerebrovascular conditions that closely resemble stroke (stroke mimics). However, there are limited data on thrombolysis safety in stroke mimics. Methods and Results: Using data from the Get With The Guidelines–Stroke Registry, we identified 72 582 patients with suspected ischemic stroke treated with tPA from 485 US hospitals between January 2010 and December 2017. We documented the use of tPA in stroke mimics, defined as patients who present with stroke-like symptoms, but after workup are determined not to have suffered from a stroke or transient ischemic attack, and compared characteristics and outcomes in stroke mimics versus those with ischemic stroke. Overall, 3.5% of tPA treatments were given to stroke mimics. Among them, 38.2% had a final nonstroke diagnoses of migraine, functional disorder, seizure, and electrolyte or metabolic imbalance. Compared with tPA-treated true ischemic strokes, tPA-treated mimics were younger (median 54 versus 71 years), had a less severe National Institute of Health Stroke Scale (median 6 versus 8), and a lower prevalence of cardiovascular risk factors, except for a higher prevalence of prior stroke/transient ischemic attack (31.3% versus 26.1%, all P Conclusions: In this large cohort of patients treated with tPA, relatively few patients who received tPA for presumed stroke were ultimately not diagnosed with a stroke or transient ischemic attack. The complication rates associated with tPA in stroke mimics were low. Despite the potential risk of administering tPA to stroke mimics, opportunity remains for continued improvement in the rapid and accurate diagnosis and treatment of ischemic stroke.

Highlights • Solitary fibrous tumors are typically indolent tumors of the pleura. • Primary origin in the female reproductive organs is rare, as are aggressive forms. • We report a case of a vulvar solitary fibrous tumor, notable for extensive spinal metastasis.

Background With over 30,000 solid organ transplants (SOT) performed annually the United States alone, there is an urgent need to understand the risks and outcomes of infective endocarditis (IE) in SOT recipients. Methods We used data from the 2013–2017 Nationwide Readmissions Database (NRD). Hospitalizations associated with IE were identified using diagnosis and procedure codes. The cohort included all patients with IE, stratified by history of solid organ transplant (heart, liver, kidney, lung, intestines, pancreas). Outcomes included 60-day rates of mortality, (extracorporeal membrane oxygenation) ECMO deployment, thromboembolic events, length of stay, and inpatient costs. Regression models, weighted to account for the NRD sample design, were used to model associations between outcomes and transplant history, adjusting for patient age, sex, facility characteristics, comorbid conditions, and potential IE organism. Results A total of 175,682 hospitalizations associated with IE, corresponding to a national estimate of 345,236, were included. Of these, 1,299 (weighted estimate = 2,511) were associated with history of transplant. Transplant recipients were younger (54.2 vs. 59.4 years, p < 0.001), less likely to be female (33.2% vs. 40.1%), had higher rates of renal and liver disease (93.1% vs. 39.2% and 16.2% vs. 8.6%, respectively, p < 0.001 for both). The most common SOT organ (allowing for multiple organs) was kidney (75%) followed by liver (11.5%) and heart (10.5%). Compared to non-SOT patients with IE, SOT recipients with IE were associated with lower risk of mortality [adjusted relative risk (aRR): 0.74, 95% confidence interval (CI) (0.61, 0.89)], lower risk of prolonged mechanical ventilation [aRR 0.80 (0.68, 0.93)], 2.2 fewer inpatient days (-3.5 to -0.8) and $7,000 lower charges (-$9,700, -$4,300), after adjustment. Conclusion IE complicated by SOT history was associated with paradoxically better outcomes than IE in patients without SOT history. The selection process underlying receipt of transplant may partially explain these differences in outcomes. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Background The prevalence and impact of infective endocarditis (IE) on organ transplant recipients is unknown. We used a large cohort of transplant recipients to assess the impact of IE on outcomes during index transplant hospitalization. Methods We used data from the 2013-2017 Nationwide Readmissions Database (NRD). Hospitalizations associated with solid organ transplantation procedures (heart, liver, kidney, lung, intestines, pancreas) were included. Outcomes included 60-day rates of mortality, ECMO deployment, thromboembolic events, length of stay, and inpatient costs. For data obtained October 2015 and later, rates of graft rejection and graft failure were also measured. Regression models, weighted to account for the NRD sample design, were used to model associations between outcomes and transplant procedure, adjusting for patient age, sex, facility characteristics, comorbid conditions, and organs transplanted. Results A total of 75,069 hospitalizations for organ transplantation, corresponding to a national estimate of 160,368, were included. A diagnosis of IE was associated with 416 (weighted estimate = 898). IE cases were less likely to be female (22.2% vs. 37.9%, p< 0.001), and had higher rates of underlying pulmonary disease. The most common organ transplanted in the hospitalization during which IE was diagnosed (allowing for multiple organs) was heart (84.5%) followed by kidney (8.9%) and liver (7.9%), (p< 0.001). IE was associated with higher mortality [adjusted relative risk (aRR): 1.70, 95% confidence interval (CI) (1.09, 2.66)], prolonged ventilation (aRR 1.32 [1.06, 1.65], 4.6 additional inpatient days (CI: 1.5, 7.6) and $28,300 more inpatient cost (CI: $12,000, $44,700) (Table). 60-Day Outcomes, Stratified by IE During Index Transplant Hospitalization Conclusion IE complicating hospitalization for organ transplantation is associated with higher rates of morbidity and mortality. IE during index transplant hospitalization occurs most frequently in heart transplant recipients. Understanding the high rate of IE in heart recipients in the early post-transplant period requires further study. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Background Infective endocarditis (IE) is a rare but serious complication of pregnancy. Its impact on delivery outcomes is unknown. In this study, we use a national administrative database to compare outcomes of deliveries complicated by IE to non-IE deliveries. Methods The National Readmissions Database was used to identify discharges between Oct. 2015 and Dec. 2017 for deliveries in patients aged 12 – 55 years with concomitant IE, which were compared to those deliveries without IE. Demographics, comorbidities, and outcomes were obtained. Differences between groups were analyzed using weighted Chi-squared test for categorical variables and weighted linear regression for continuous variables. Weighted multivariate regression models adjusted for demographic, facility, and comorbidity conditions were used to evaluate the association between IE and delivery outcomes. Results We identified 88 individuals with IE complicating their delivery hospitalization, corresponding to a national estimate of 162 admissions during the study period, who were compared to 4,401,879 delivery hospitalizations not complicated by IE (weighted national estimate 8,375,536). Patients with IE were more likely to reside in ZIP codes with median incomes in the lowest national quartile (46.3% vs. 28.1%, P = 0.003) and were more likely to be insured by Medicaid (76.5% vs. 42.1%, P < 0.001). Rates of pre-existing cardiac valve disease (39.9% vs. 0.2%, P < 0.001) and congenital heart disease (6.6% vs 0.1%, P < 0.001) were higher in those with IE, as well as drug abuse (69.3% vs. 2.6%, P < 0.001). Unadjusted analyses demonstrated higher rates of in-hospital mortality for IE-associated admissions (12.1% versus 0.005%), along with high rates of severe maternal morbidity, stillbirth, preterm birth, and cesarean birth, and longer lengths of stay and total hospital costs. These differences persisted despite adjustment using multivariate methods (Table). Clinical and Resource Utilization Outcomes Conclusion The presence of IE during an admission for delivery is associated with poorer outcomes for both pregnant patients and their fetuses. The occurrence of IE during pregnancy was associated with lower income, a history of cardiac disease, and drug abuse. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Actavis (Grant/Research Support)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Research Grant or Support)Affinium (Consultant)Allergan (Grant/Research Support)Ampliphi Biosciences (Consultant)Basilea (Consultant, Research Grant or Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Research Grant or Support)Contrafect (Consultant, Research Grant or Support)Cubist (Grant/Research Support)Debiopharm (Consultant)Destiny (Consultant)Durata (Consultant)Forest (Grant/Research Support)Genentech (Consultant, Research Grant or Support)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Research Grant or Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)Medimmune (Consultant, Research Grant or Support)Merck (Consultant, Research Grant or Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Research Grant or Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Research Grant or Support)Tetraphase (Consultant)Theravance (Consultant, Research Grant or Support)Trius (Consultant)xBiotech (Consultant)

Background and Purpose— Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non–vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods— A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results— We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5–14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0–2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12–2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08–1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45–14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions— These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

Objectives The aim of this study was to determine diagnostic testing patterns after percutaneous coronary intervention (PCI). Background Little is known about patterns of diagnostic testing after PCI in the United States or the relationship of these patterns to clinical outcomes. Methods Centers for Medicare and Medicaid Services inpatient and outpatient claims were linked to National Cardiovascular Data Registry CathPCI Registry data from 2005 to 2007. Hospital quartiles of the cumulative incidence of diagnostic testing use within 12 and 24 months after PCI were compared for patient characteristics, repeat revascularization, acute myocardial infarction, and death. Results A total of 247,052 patients underwent PCI at 656 institutions. Patient and site characteristics were similar across quartiles of testing use. There was a 9% and 20% higher adjusted risk for repeat revascularization in quartiles 3 and 4 (highest testing rate), respectively, compared with quartile 1 (lowest testing rate) (p = 0.020 and p Conclusions Although patient characteristics were largely independent of rates of post-PCI testing, higher testing rates were not associated with lower risk for myocardial infarction or death, but repeat revascularization was significantly higher at these sites. Additional studies should examine whether increased testing is a marker for improved quality of post-PCI care or simply increased health care utilization.

Background and Purpose— Rehabilitation is recommended after a stroke to enhance recovery and improve outcomes, but hospital’s use of inpatient rehabilitation facilities (IRFs) or skilled nursing facility (SNF) and the factors associated with referral are unknown. Methods— We analyzed clinical registry and claims data for 31 775 Medicare beneficiaries presenting with acute ischemic stroke from 918 Get With The Guidelines-Stroke hospitals who were discharged to either IRF or SNF between 2006 and 2008. Using a multilevel logistic regression model, we evaluated patient and hospital characteristics, as well as geographic availability, in relation to discharge to either IRF or SNF. After accounting for observed factors, the median odds ratio was reported to quantify hospital-level variation in the use of IRF versus SNF. Results— Of 31 775 patients, 17 662 (55.6%) were discharged to IRF and 14 113 (44.4%) were discharged to SNF. Compared with SNF patients, IRF patients were younger, more were men, had less health-service use 6 months prestroke, and had fewer comorbid conditions and in-hospital complications. Use of IRF or SNF varied significantly across hospitals (median IRF use, 55.8%; interquartile range, 34.8%–75.0%; unadjusted median odds ratio, 2.59; 95% confidence interval, 2.44–2.77). Hospital-level variation in discharge rates to IRF or SNF persisted after adjustment for patient, clinical, and geographic variables (adjusted median odds ratio, 2.87; 95% confidence interval, 2.68–3.11). Conclusions— There is marked unexplained variation among hospitals in their use of IRF versus SNF poststroke even after accounting for clinical characteristics and geographic availability. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02284165.

Measurement of the long-term impact of medical treatments on resource utilization is essential to health technology assessment. Whether such measurement is performed using a randomized trial or observational study, most cohorts include some patients who were alive at the end of their data availability but whose resource use was not measured for the entire period of interest; these patients are said to be censored at the point from which subsequent resource use is unknown. Even when censoring occurs at random, conventional survival analysis methods produce biased cost estimates due to heterogeneity in cost trajectories (Lin et al. 1997). Previous methods to address the issue of estimating resource use with censored data have notable limitations. Early approaches using survival-adjusted models were shown to produce biased estimates when death and censoring occurred continuously during the study period, rather than at predictable, discrete intervals such as every 30 days (Lin et al. 1997). Inverse probability weighting (IPW) approaches solve this limitation (Bang and Tsiatis 2000; Lin 2000), but they do not allow decomposition of a treatment's effect on resource use into an effect due to the treatment altering how long a patient lives (the survival effect) and an effect due to the treatment altering how many resources a surviving patient consumes (the intensity effect) (Basu and Manning 2010). Such decomposition, which is possible with survival-adjusted methodologies, is of interest in health technology assessment because it allows for more detailed examination of how treatments affect long-term costs of care. An extreme example of a treatment affecting both survival and resource use is highly active antiretroviral therapy (HAART) for human immunodeficiency virus infection. HAART dramatically improves survival, meaning a substantial survival effect due to prolonged life spans among patients receiving HAART is likely. In addition, there is also an important intensity effect associated with HAART usage, consisting of increased costs for antiretroviral medications, but lower costs due to prevention of opportunistic infections. However, most cost analyses of HAART have not considered potential survival effects (Schackman et al. 2006). Although most cost-effectiveness analyses do not consider survival effect-induced costs (Gold et al. 1996), failing to incorporate these effects may bias them in favor of therapies that extend life span versus therapies that improve quality of life (Meltzer 1997). Furthermore, if an analytic objective is to forecast long-term expenditures for a third-party payer, incorporation of survival effect-induced costs is essential. A recently developed approach extends the survival-adjusted methodology to produce consistent estimates for resource use, even when censoring and death occur continuously throughout the follow-up period. The approach also preserves the ability to decompose differences in resource use into survival and intensity effects (Basu and Manning 2010). In addition to these advantages, the authors identify an additional important and poorly appreciated limitation of IPW methods: the potential for considerable bias when IPW estimators are used to evaluate the costs of treatments that have both intensity and survival effects, as well as substantial precision loss. The authors show that this bias is eliminated with the use of their approach. We apply Basu and Manning's new methodology to compare the effects of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) on survival and resource use for elderly patients with symptomatic multivessel coronary artery disease. Clinical Context PCI and CABG are both treatments for coronary artery disease (CAD; blockages in the arteries that oxygenate the heart). PCI is performed by interventional cardiologists and involves reopening blocked arteries through the use of instruments threaded into the heart via catheters inserted in the patient's arm or leg. CABG is performed by cardiothoracic surgeons and involves sewing vessels from elsewhere in the patient's body onto the heart, allowing blood to bypass the blocked coronary arteries. PCI is less invasive than CABG and is increasingly the CAD procedure elderly patients receive (Sheridan et al. 2008). A systematic review of PCI versus CABG on survival from randomized trials published between 1996 and 2006 found similar overall survival after 1 and 5 years postrevascularization (Bravata et al. 2007). However, elderly patients were routinely excluded from many studies listed in the review, and results from recent randomized trials and observational studies suggest that among elderly patients with complex multivessel coronary disease, CABG provides a survival benefit over PCI (Sheridan et al. 2010; Kappetein et al. 2011; Weintraub et al. 2012). For this reason, a comparison of resource use between PCI and CABG must consider the possibility of differential survival between the two procedures. We use an innovative approach to determine how PCI differentially affects institutional days and resource use compared to CABG through decomposed survival and intensity effects. Specifically, we assess the effects of PCI versus CABG on survival, institutional (hospital or long-term care) days, and Medicare payments for up to 6 years of follow-up for a national sample of elderly Medicare beneficiaries treated with multivessel coronary revascularization.

Background— Patterns of noninvasive stress test (ST) and invasive coronary angiography (CA) utilization after percutaneous coronary intervention (PCI) are not well described in older populations. Methods and Results— We linked National Cardiovascular Data Registry CathPCI Registry data with longitudinal Medicare claims data for 250 350 patients undergoing PCI from 2005 to 2007 and described subsequent testing and outcomes. Between 60 days post-PCI and end of follow-up (median 24 months), 49% (n=122 894) received ST first, 10% (n=25 512) underwent invasive CA first, and 41% (n=101 944) had no testing. Several clinical risk factors at time of index PCI were associated with decreased likelihood of downstream testing (ST or CA, P P Conclusions— In this descriptive analysis, ST and invasive CA were common in older patients after PCI. Paradoxically, patients with higher risk features at baseline were less likely to undergo post-PCI testing. The revascularization yield was low on patients referred for ST after PCI, with only 9% undergoing revascularization within 90 days.

Importance There is increasing interest in performing comparative effectiveness analyses in large observational databases, yet these analyses must adjust for treatment selection issues. Objectives To conduct comparative safety and efficacy analyses of prasugrel vs clopidogrel bisulfate after percutaneous coronary intervention and to evaluate inverse probability of treatment weighting (a propensity score method) and instrumental variable methods. Design, Setting, and Participants This study used data from the Treatment With Adenosine Diphosphate Receptor Inhibitors–Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study. Included in the study were patients undergoing percutaneous coronary intervention for myocardial infarction, 26.0% of whom received prasugrel. The study dates were April 4, 2010, to October 31, 2012. Exposures Choice of initial antiplatelet agent (prasugrel or clopidogrel). Main Outcomes and Measures Safety and efficacy outcomes included 1-year composite major adverse cardiovascular events, moderate to severe bleeding, and stent thrombosis. Hospitalizations for pneumonia, bone fractures, and planned percutaneous coronary intervention were used as the falsification end points. Results The study cohort comprised 11 784 participants (mean [SD] age, 60.0 [11.6] years, and 28.0% were female). Using inverse probability of treatment weighting adjustment, prasugrel and clopidogrel had similar major adverse cardiovascular events (hazard ratio [HR], 0.98; 95% CI, 0.83-1.16) and bleeding outcomes (1.18; 0.77-1.80), but prasugrel had a lower rate of stent thrombosis (0.51; 0.31-0.85). Using instrumental variable methods, prasugrel use was associated with a lower rate of the major adverse cardiovascular event end point (HR, 0.68; 95% CI, 0.47-1.00) but nonsignificant differences in the rates of bleeding (0.95; 0.41-2.08) and stent thrombosis (0.67; 0.16-2.00). There was no significant treatment difference noted in any of the falsification end-point rates when analyses were performed using inverse probability of treatment weighting, although the bone fracture end point approached statistical significance. Nevertheless, a lower rate of pneumonia-related hospitalizations was noted in the prasugrel-treated patients when analyses were performed using instrumental variable methods. Conclusions and Relevance Conclusions regarding the safety and efficacy of antiplatelet therapy varied depending on analytic technique, and none were concordant with the results from randomized trials. In addition, both statistical strategies demonstrated concerning associations when tested in the falsification analyses. A high level of scrutiny and careful attention to assumptions and validity are required when interpreting complex analyses of observational data.

Background Clopidogrel's effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor. Objective To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents. Methods A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US$) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial. Results The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was $10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below $50,000 per QALY until a monthly ticagrelor price of $693 or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, universal ticagrelor was below $50,000 per QALY in 97.7% of simulations. Conclusion Prescribing ticagrelor universally increases quality-adjusted life years for ACS patients at a cost below a typically accepted threshold.

Aims: When patients choose percutaneous coronary intervention (PCI) over coronary artery bypass grafting (CABG), they accept an increased long-term risk of repeat revascularisation in exchange for short-term morbidity benefits. This paper quantifies the risk-benefit trade-off faced by patients with multiple vessel coronary artery disease. Methods and results: Data from the Arterial Revascularisation Therapies Study are used to generate risk-benefit acceptability curves for PCI versus CABG. Risks are measured by the long-term likelihood of repeat revascularisation while benefits are measured by short-term reductions in pain or improvements in health-related quality of life (HRQL). PCI patients faced a risk of 0.81 additional revascularisation events over three years in exchange for being pain-free at one month. A patient would need to be willing to tolerate a risk of 1.06 additional revascularisation events at three years, in exchange for being pain free at one month to be 95% confident that choosing PCI over CABG is risk-effective for him/her. Conclusions: The risk-benefit framework outlined in this study provides information to enable physicians to help their patients weigh directly each procedure's risks and benefits. While trade-offs are typically measured in quality-adjusted life years, using pain reduction to reflect benefits may provide a more tangible framework for patients.

BackgroundAlthough human immunodeficiency virus (HIV)-infected persons are at increased risk for major cardiovascular events, short-term prognosis after these events is unclear.MethodsTo determine the association between HIV infection and acute myocardial infarction (AMI) and stroke outcomes, we analyzed hospital discharge data from the Nationwide Inpatient Sample (NIS) between 2002 and 2012. Multivariable logistic regression was used to evaluate the association between HIV infection and in-hospital death after AMI or stroke.ResultsOverall, 18 369 785 AMI/stroke hospitalizations were included in the analysis. Patients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke (odds ratio, 3.03 [95% confidence interval {CI}, 1.71-5.38] for AMI and 2.59 [95% CI, 1.97-3.41] for stroke). Additionally, patients with AIDS were more likely than HIV-uninfected patients to be discharged to nonhospital inpatient facilities after admission for AMI (OR, 3.14 [95% CI, 1.72-5.74]) or stroke (OR, 1.45; 95% CI, 1.12-1.87). There was a minimal difference in either outcome between HIV-infected patients without a history of AIDS and uninfected patients.ConclusionsPatients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke. This disparity was not observed when infected patients without a history of AIDS were compared to uninfected patients, implying that preserving immune function may improve cardiovascular outcomes in HIV-infected persons.

Rationale, aims, and objectives Despite proven benefits for reducing incidence of major cardiac events, antihypertensive drug therapy remains underutilized in the United States. This analysis assesses antihypertensive drug adherence, utilization predictors, and associations between adherence and outcomes (a composite of cardiovascular events, Medicare inpatient payments, and inpatient days). Methods The sample consisted of Atherosclerosis Risk in Communities Study cohort participants reporting hypertension without prevalent cardiovascular disease during 2006 to 2007 annual follow-up calls. Atherosclerosis Risk in Communities records were linked to Medicare claims through 2012. Antihypertensive medication adherence was measured as more than 80% proportion days covered by using Medicare Part D claims. Standard and hierarchical regression models were used to evaluate adjusted associations between person characteristics and adherence and between adherence and outcomes. Results Among 1826 hypertensive participants with Part D coverage, 31.5% had no antihypertensive class with more than 80% proportion days covered in the 3 months preceding the report of hypertension in 2006 to 2007. After adjustment for confounders, positive predictors of use included female gender and diabetes; negative predictors were African-American race and current smoking. Adjusted association between receiving no therapy and a composite endpoint of cardiovascular outcomes through 2012 was not statistically significant (hazard ratio: 0.93; 95% confidence interval: 0.72, 1.22) nor was the adjusted association with Medicare inpatient days or payments (incremental difference at 48 months in payments: $1217; 95% CI: −$2030, $4463). Conclusions Despite having medical and prescription coverage, nearly a third of hypertensive participants were not adherent to antihypertensive drug therapy. Differences in clinical outcomes associated with nonadherence, though not statistically significant, were consistent with results from randomized trials. The approach provides a model framework for rigorous assessment of detailed data that are increasingly available through emerging sources.

The use of endoscopic approaches for sinonasal malignancy resection has increased, but survival data are limited secondary to disease rarity and new surgical technique. Here we present a systematic review and meta-analysis of endoscopic endonasal resection of sinonasal malignancy.MEDLINE, PubMed Central, NCBI Bookshelf, Cochrane Library, clinicaltrials.gov, National Guideline Clearinghouse.PRISMA/MOOSE guidelines were followed. MeSH terms were "endoscopic" AND ("esthesioneuroblastoma" OR "sinonasal adenocarcinoma" OR "squamous cell carcinoma" OR "sinonasal undifferentiated carcinoma"). For studies in which individual-level data were available, results were obtained by direct pooling. For studies in which only summary Kaplan-Meier curves were available, numerical data were extracted, traced, and aggregated by fitting a Weibull model.Of 320 studies identified, 35 case series were included (n = 952 patients), with 15 studies analyzed via aggregate modeling and 20 studies analyzed via direct pooling. Two- and 5-year survival rates for patients in aggregate modeling were 87.5% and 72.3%, respectively (mean follow-up: 32.9 months). Two- and 5-year survival for patients in direct pooling were 85.8% and 83.5%, respectively (mean follow-up: 43.0 ± 19.5 months). Significant overall survival difference was found between low- and high-grade cancers (P = .015) but not between low- and high-stage cancers (P = .79).Overall 2- and 5-year survival rates are comparable and sometimes greater than those from open craniofacial resection. Survival rates significantly differ by cancer grade but not stage. Journals and investigators should be encouraged to publish retrospective and prospective case series with staged survival updates based on established guidelines.

Introduction: Accountable care and bundled payment initiatives have increased attention on inpatient post-acute care effectiveness. Empirical evidence for whether care at inpatient rehabilitation (IRF) or skilled nursing facilities (SNF) is associated with differential outcomes is limited. Methods: Data from the American Heart Association Get With The Guidelines-Stroke registry were linked with Medicare claims. We compared post-discharge mortality and a composite of all-cause rehospitalization or death for beneficiaries who received IRF or SNF care immediately after hospital discharge. Proportional hazards regression with inverse propensity weighting (IPW) was used to adjust for measured differences in demographic, clinical and hospital characteristics. Acknowledging the possibility of unmeasured differences between groups, an instrumental variable approach (IV=hospital-specific proportion of patients discharged to IRFs vs SNFs) was used to adjust for both measured and unmeasured confounding. Results: From 1,142 hospitals there were 34,574 AIS patients discharged to IRFs and 34,430 to SNFs. Patients receiving SNF vs IRF care were older (83 vs 79 years), had more comorbid illness, and higher unadjusted 7, 90, and 365 day mortality and rehospitalizations (Table). After IPW adjustment mortality and rehospitalization/mortality rates remained significantly better for patients with IRF vs SNF care (Table). Differences attenuated with IV analysis but IRF care continued to be associated with better outcomes (Table). Findings were similar in sensitivity analyses among patients with a NIHSS score. Conclusions: Receiving care at an IRF after AIS was associated with lower mortality and all-cause rehospitalization/death compared with SNF care even after rigorous adjustment for both measured and unmeasured differences in treatment selection. Further research is needed to discern the mechanisms for these potential differences between settings.

Reperfusion times for ST-elevation myocardial infarction (STEMI) occurring in outpatients have improved significantly, but quality improvement efforts have largely ignored STEMI occurring in hospitalized patients (inpatient-onset STEMI).To define the incidence and variables associated with treatment and outcomes of patients who develop STEMI during hospitalization for conditions other than acute coronary syndromes (ACS).Retrospective observational analysis of STEMIs occurring between 2008 and 2011 as identified in the California State Inpatient Database.STEMIs were classified as inpatient onset or outpatient onset based on present-on-admission codes. Patients who had a STEMI after being hospitalized for ACS were excluded from the analysis.Regression models were used to evaluate associations among location of onset of STEMI, resource utilization, and outcomes. Adjustments were made for patient age, sex, comorbidities, and hospital characteristics. The analysis allowed for the location of inpatient STEMI to have a multiplicative rather than an additive effect for resource utilization since these measures were highly skewed.A total of 62,021 STEMIs were identified in 303 hospitals, of which 3068 (4.9%) occurred in patients hospitalized for non-ACS indications. Patients with inpatient-onset STEMI were older (mean, 71.5 [SD, 13.5] years vs 64.9 [SD, 14.1] years; P .001) and more frequently female (47.4% vs 32%; P .001) than those with outpatient-onset STEMI. Patients with inpatient-onset STEMI had higher in-hospital mortality (33.6% vs 9.2%; adjusted odds ratio (AOR), 3.05; 95% CI, 2.76-3.38; P .001), were less likely to be discharged home (33.7% vs 69.4%; AOR, 0.38; 95% CI, 0.34-0.42; P .001), and were less likely to undergo cardiac catheterization (33.8% vs 77.8%; AOR, 0.19; 95% CI, 0.16-0.21; P .001) or percutaneous coronary intervention (21.6% vs 65%; AOR, 0.23; 95% CI, 0.21-0.26; P .001). Length of stay and inpatient charges were higher for inpatient-onset STEMI (mean length of stay, 13.4 days [95% CI, 12.8-14.0 days] vs 4.7 days [95% CI, 4.6-4.8 days]; adjusted multiplicative effect, 2.51; 95% CI, 2.35-2.69; P .001; mean inpatient charges, $245,000 [95% CI, $235,300-$254,800] vs $129,000 [95% CI, $127,900-$130,100]; adjusted multiplicative effect, 2.09; 95% CI, 1.93-2.28; P .001).Patients who had a STEMI while hospitalized for a non-ACS condition, compared with those with onset of STEMI as an outpatient, were less likely to undergo invasive testing or intervention and had a higher in-hospital mortality rate.

Background— Many multicenter clinical trials use permuted-block randomization to create balanced treatment allocations within clinical centers. Unlike randomized trials, observational studies do not control treatment allocation, and statistical models are used to adjust for measured confounders. For many observational data analyses, the variability in the treatment selection process within clinical centers is ignored. Furthermore, there is no consensus on the best approach for dealing with variability in the treatment selection process across clinical centers. Methods and Results— Individuals aged ≥65 years receiving either drug-eluting stents or bare metal stents were included. A cohort of 262 700 patients from 650 CathPCI Registry sites was followed up for a median of 15 months. Propensity score models were estimated to describe the process used to select drug-eluting stents across the study population. Substantial variability in the use of drug-eluting stents at the clinical center level was observed—even after accounting for differences in patient and clinical center characteristics. By refitting and matching propensity scores within clinical centers, a balanced cohort on treatment allocation and prognostic factors was obtained. This approach generated an estimated hazard ratio that was qualitatively similar to standard regression models and other propensity score approaches. Conclusions— Substantial variability in treatment selection existed between clinical centers. Matching recalibrated propensity scores within clinical centers has the potential to reduce a source of bias in multicenter observational studies. This methodology cannot eliminate all potential for biases; however, it removes the potential bias from site-level factors.

Background Exercise testing with echocardiography or myocardial perfusion imaging is widely used to risk‐stratify patients with suspected coronary artery disease. However, reports of diagnostic performance rarely adjust for referral bias, and this practice may adversely influence patient care. Therefore, we evaluated the potential impact of referral bias on diagnostic effectiveness and clinical decision‐making. Methods and Results Searching PubMed and EMBASE (1990–2012), 2 investigators independently evaluated eligibility and abstracted data on study characteristics and referral patterns. Diagnostic performance reported in 4 previously published meta‐analyses of exercise echocardiography and myocardial perfusion imaging was adjusted using pooled referral rates and Bayesian methods. Twenty‐one studies reported referral patterns in 49 006 patients (mean age 60.7 years, 39.6% women, and 0.8% prior history of myocardial infarction). Catheterization referral rates after normal and abnormal exercise tests were 4.0% (95% CI , 2.9% to 5.0%) and 42.5% (36.2% to 48.9%), respectively, with odds ratio for referral after an abnormal test of 14.6 (10.7 to 19.9). After adjustment for referral, exercise echocardiography sensitivity fell from 84% (80% to 89%) to 34% (27% to 41%), and specificity rose from 77% (69% to 86%) to 99% (99% to 100%). Similarly, exercise myocardial perfusion imaging sensitivity fell from 85% (81% to 88%) to 38% (31% to 44%), and specificity rose from 69% (61% to 78%) to 99% (99% to 100%). Summary receiver operating curve analysis demonstrated only modest changes in overall discriminatory power but adjusting for referral increased positive‐predictive value and reduced negative‐predictive value. Conclusions Exercise echocardiography and myocardial perfusion imaging are considerably less sensitive and more specific for coronary artery disease after adjustment for referral. Given these findings, future work should assess the comparative ability of these and other tests to rule‐in versus rule‐out coronary artery disease.

Background Exercise stress testing is commonly obtained after percutaneous coronary intervention (PCI) performed for acute coronary syndromes (ACS). We compared the relationships between exercise echocardiography and nuclear testing after ACS-related PCI on outcomes and resource use. Methods Longitudinal observational study using fee-for-service Medicare claims to identify patients undergoing outpatient exercise stress testing with imaging within 15 months after PCI performed for ACS between 2003 and 2004. Results Of 63,100 patients undergoing stress testing 3 to 15 months post-PCI, 31,731 (50.3%) underwent an exercise stress test with imaging. Among 29,279 patients undergoing exercise stress testing with imaging, 15.5% received echocardiography. Echocardiography recipients had higher rates of repeat stress testing (adjusted hazard ratio [HR] 2.60, CI 2.19-3.10) compared with those undergoing nuclear imaging in the 90 days after testing, but lower rates of revascularization (adjusted HR 0.87, CI 0.76-0.98) and coronary angiography (adjusted HR 0.88, CI 0.80-0.97). None of these differences persisted subsequent to 90 days after stress testing. Rates of death and readmission for myocardial infarction rates were similar. Total Medicare payments were lower initially after echocardiography (incremental difference $498, CI 488-507), an effect attributed primarily to lower reimbursement for the stress test itself, but not significantly different after 14 months after testing. Conclusions In this study using administrative data, echocardiography recipients initially had fewer invasive procedures but higher rates of repeat testing than nuclear testing recipients. However, these differences between echo and nuclear testing did not persist over longer time frames.

Limited data are available on the use of coronary computed tomographic angiography (CCTA) in patients who have received percutaneous coronary intervention (PCI). To evaluate patterns of cardiac testing including CCTA after PCI, we created a retrospective observational dataset linking National Cardiovascular Data Registry CathPCI Registry baseline data with longitudinal inpatient and outpatient Medicare claims data for patients who received coronary stenting from November 1, 2005 through December 31, 2007. In 192,009 patients with PCI (median age 74 years), the first test after coronary stenting was CCTA for 553 (0.3%), stress testing for 89,900 (46.8%), and coronary angiography for 22,308 (11.6%); 79,248 (41.3%) had no further testing. Patients referred to CCTA first generally had similar or lower baseline risk than those referred for stress testing or catheterization first. Compared to patients with stress testing first after PCI, patients who underwent CCTA first had higher unadjusted rates of subsequent noninvasive testing (10% vs 3%), catheterization (26% vs 15%), and revascularization (13% vs 8%) within 90 days of initial testing after PCI (p0.0001 for all comparisons). In conclusion, despite similar or lesser-risk profiles, patients initially evaluated with CCTA after PCI had more downstream testing and revascularization than patients initially evaluated with stress testing. It is unclear whether these differences derive from patient selection, performance of CCTA compared to other testing strategies, or the association of early adoption of CCTA with distinct patterns of care.

The optimal use of stress testing after coronary revascularization remains unclear, and overuse of stress testing might increase the rates of repeat revascularization. We analyzed the association at both the patient and regional level between the use of stress testing and repeat revascularization for a cohort of Medicare beneficiaries receiving revascularization within 30 days of an admission for symptomatic coronary artery disease. The sample consisted of 219,748 Medicare beneficiaries aged >65 years who received percutaneous coronary intervention or cardiac bypass artery grafting after hospital admission for symptomatic coronary artery disease in 2003 to 2004. Medicare claims data through 2008 identified the use of stress testing and repeat revascularization. The associations between the cumulative incidence of stress testing and repeat revascularization were analyzed using linear regression analysis. Within 6 years of the initial revascularization, the cumulative incidence of events was 0.61 for stress testing and 0.23 for repeat revascularization. Most (53.1%) repeat revascularizations were preceded by a stress test. Only 10.3% of repeat revascularization procedures were preceded by myocardial infarction. The 4-year cumulative incidence of repeat revascularization and stress testing varied between the Hospital Referral Regions represented by the sample, and the positive correlation between the rates by the health referral region accounted for only a small portion of the total health referral region variation in revascularization rates. In conclusion, stress testing is commonly performed among Medicare patients after the initial revascularization, and most repeat procedures are performed for stable coronary artery disease. The variation in stress testing patterns only explained a modest fraction of the regional variation in the repeat revascularization rates.

Background Instrumental variable (IV) methods can correct for unmeasured confounding when using administrative (claims) data for cardiovascular outcomes research, but difficulties identifying valid IVs have limited their use. We evaluated the safety and efficacy of drug-eluting coronary stents (DES) compared with bare-metal stents (BMS) for Medicare beneficiaries with acute coronary syndromes using the rapid uptake of DES in clinical practice as an instrument. We compared results from IV with those from propensity score matching (PSM) and multivariable regression models. Methods This is a retrospective cohort study involving 62,309 fee-for-service beneficiaries 66 years and older treated with coronary stenting between May 2003 and February 2004. Outcomes were measured for 46 months after revascularization using claims data. Results Recipients of DES were younger, had a lower prevalence of myocardial infarction, and had fewer comorbidities compared with BMS recipients. Use of DES was associated with lower rates of mortality by PSM (hazard ratio [HR] 0.80, CI 0.77-0.83) but not by IV (HR 0.99, CI 0.87-1.11). Instrumental variable models estimated a larger reduction in repeat revascularization (HR 0.76, CI 0.63-0.89) than did PSM (HR 0.90, CI 0.87-0.93). Conclusions Based on IV analysis, the increased utilization of DES relative to BMS among Medicare beneficiaries with acute coronary syndrome is associated with reduced rates of repeat revascularization and no difference in mortality. Instrumental variable approaches provide a useful complement to conventional approaches to cardiovascular outcomes research with administrative data.

Comparative effectiveness of interventional treatment strategies for the very elderly with acute coronary syndrome remains poorly defined due to study exclusions. Interventions include percutaneous coronary intervention (PCI), usually with stents, or coronary artery bypass grafting (CABG). The elderly are frequently directed to PCI because of provider perceptions that PCI is at therapeutic equipoise with CABG and that CABG incurs increased risk. We evaluated long-term outcomes of CABG versus PCI in a cohort of very elderly Medicare beneficiaries presenting with acute coronary syndrome.Using Medicare claims data, we analyzed outcomes of multivessel PCI or CABG treatment for a cohort of 10,141 beneficiaries age 85 and older diagnosed with acute coronary syndrome in 2003 and 2004. The cohort was followed for survival and composite outcomes (death, repeat revascularization, stroke, acute myocardial infarction) for three years. Logistic regressions controlled for patient demographics and comorbidities with propensity score adjustment for procedure selection.Percutaneous coronary intervention showed early benefits of lesser morbidity and mortality, but CABG outcomes improved relative to PCI outcomes by three years (p0.01). At 36 months post-initial revascularization, 66.0% of CABG recipients survived (versus 62.7% of PCI recipients, p0.05) and 46.1% of CABG recipients were free from composite outcome (versus 38.7% of PCI recipients, p0.01).In very elderly patients with ACS and multivessel CAD, CABG appears to offer an advantage over PCI of survival and freedom from composite endpoint at three years. Optimizing the benefit of CABG in very elderly patients requires absence of significant congestive heart failure, lung disease, and peripheral vascular disease.

International audience; BACKGROUND: Coagulase-negative staphylococci (CoNS) are an infrequent cause of native valve endocarditis (NVE), and our understanding of NVE caused by CoNS is incomplete. METHOD: The International Collaboration on Endocarditis-Prospective Cohort Study includes patients with endocarditis from 61 centers in 28 countries. Patients with definite cases of NVE caused by CoNS who were enrolled during the period June 2000-August 2006 were compared with patients with definite cases of NVE caused by Staphylococcus aureus and patients with NVE caused by viridans group streptococci. Multivariable logistic regression was used to determine factors associated with death in patients with NVE caused by CoNS. RESULTS: Of 1635 patients with definite NVE and no history of injection drug use, 128 (7.8%) had NVE due to CoNS. Health care-associated infection occurred in 63 patients (49%) with NVE caused by CoNS. Comorbidities, long-term intravascular catheter use, and history of recent invasive procedures were similar among patients with NVE caused by CoNS and among patients with NVE caused by S. aureus. Surgical treatment for endocarditis occurred more frequently in patients with NVE due to CoNS (76 patients [60%]) than in patients with NVE due to S. aureus (150 [33%]; P=.01) or in patients with NVE due to viridans group streptococci (149 [44%]; P=.01). Despite the high rate of surgical procedures among patients with NVE due to CoNS, the mortality rates among patients with NVE due to CoNS and among patients with NVE due to S. aureus were similar (32 patients [25%] and 124 patients [27%], respectively; P=.44); the mortality rate among patients with NVE due to CoNS was higher than that among patients with NVE due to viridans group streptococci (24 [7.0%]; P=.01). Persistent bacteremia (odds ratio, 2.65; 95% confidence interval, 1.08-6.51), congestive heart failure (odds ratio, 3.35; 95% confidence interval, 1.57-7.12), and chronic illness (odds ratio, 2.86; 95% confidence interval, 1.34-6.06) were independently associated with death in patients with NVE due to CoNS (c index, 0.73). CONCLUSIONS: CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes.

Importance Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA. Objective To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA. Design, Setting, and Participants This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines–Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period. Exposures Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke. Main Outcomes and Measures Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]). Results Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16-1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in-hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, −0.01% [−0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50). Conclusions and Relevance Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy.

e15184 Background: Proton therapy (PT) has received much public attention due to its higher costs and lack of evidence of clinical benefit compared to intensity modulated radiation therapy (IMRT) for prostate cancer treatment. In this economic study, we performed a threshold analysis to assess the reduction in toxicity that PT would need to achieve compared with IMRT to be considered cost-effective for the treatment of localized prostate cancer. Methods: SEER-Medicare data was used to identify a cohort, aged 66 years or older, receiving IMRT as definitive radiation therapy (n=4,540). We assumed equal disease control efficacy between IMRT and PT and simulated toxicity outcomes and costs using an incidence-based Markov model. The relative risk of composite toxicity, comparing PT to IMRT, was the efficacy parameter studied. Rates of therapy-induced toxicity associated with IMRT were obtained from SEER-Medicare data. Utility values to calculate quality-adjusted life-years (QALY) and costs (in 2011 US dollars) were obtained from the literature and claims data, respectively. Deterministic threshold analysis using a payer perspective and analytic horizon of 4 years post radiation was performed to determine the relative risk thresholds that would result in incremental cost-effectiveness ratios (ICER) of $50,000 and $100,000/QALY for PT versus IMRT. One-way sensitivity analyses were performed with the lowest and highest treatment costs of PT and IMRT. Results: ComparingPT against IMRT, the threshold values for the relative risk of composite toxicity were 0.318 and 0.588 at cost-effectiveness levels of $50,000/QALY and $100,000/QALY, respectively. Sensitivity analyses showed that the relative risk needed to achieve an ICER of 100,000/QALY ranged from 0.79 and 0.40 for the low and high cost estimates of PT, and from 0.47 to 0.72, for the low and high cost estimates of IMRT. Conclusions: Assuming equal disease control, PT would need to result in a 41% reduction in composite toxicity to be considered cost-effective in the treatment of Medicare beneficiaries with localized prostate cancer at a cost-effectiveness threshold of $100,000/QALY.

Estimates of the incidence and impact of bacterial infective endocarditis (IE) have been limited by the infrequency of the disease. Administrative data analyses can provide important information across a broad range of hospitals and regions. We used a recent, nationally representative sample to estimate the incidence of hospitalizations for bacterial IE in the United States.