Shortened hospital length of stay and lower costs associated with rivaroxaban in patients with pulmonary embolism managed as observation status.

BACKGROUND: Unlike rivaroxaban, treatment of patients with pulmonary embolism (PE) with warfarin requires parenteral bridging and coagulation monitoring that may prolong length-of-stay (LOS) and increase hospital costs. AIMS: The aim of this study was to compare LOS, hospital costs and readmissions in PE patients managed through observation stays treated with rivaroxaban or parenterally bridged warfarin. METHODS: Premier Hospital claims data from November 2012 to March 2015 were used to identify patients with a primary diagnosis code for PE managed through an observation stay and with ≥1 claim for a PE-related diagnostic test on day 0-2. Rivaroxaban users, allowing ≤2 days of prior parenteral therapy, were 1:1 propensity-score matched to patients receiving parenterally bridged warfarin. LOS, the proportion of encounters lasting >2 midnights, total hospital costs of the index visit and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between matched cohorts using multivariable regression. RESULTS: A total of 312 rivaroxaban users were matched to 312 patients receiving parenterally bridged warfarin. Rivaroxaban was associated with an average of 0.27-day shorter LOS, a 52% decreased odds of an encounter lasting >2 midnights and a $403 mean reduction in costs vs parenterally bridged warfarin (P≤.002 for all). The readmission rate for VTE during the same or subsequent 2 months following the index PE was similar between cohorts (P=.75). No patient in either cohort was readmitted for major bleeding. CONCLUSION: Rivaroxaban was associated with shortened LOS and lowered cost vs parenterally bridged warfarin in PE observation stay patients, without increases in the short-term rate of complications or readmission.

Observation management of pulmonary embolism and agreement with claims-based and clinical risk stratification criteria in United States patients: a retrospective analysis.

BACKGROUND: Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. METHODS: Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). RESULTS: We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each <4.5%), but 7.8% were >80 years-of-age and 19.4% had chronic lung disease. CONCLUSION: Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

Vitamin K antagonist use: evidence of the difficulty of achieving and maintaining target INR range and subsequent consequences.

Vitamin K antagonists (VKAs) are effective oral anticoagulants that are titrated to a narrow therapeutic international normalized ratio (INR) range. We reviewed published literature assessing the impact of INR stability - getting into and staying in target INR range - on outcomes including thrombotic events, major bleeding, and treatment costs, as well as key factors that impact INR stability. A time in therapeutic range (TTR) of ≥65 % is commonly accepted as the definition of INR stability. In the real-world setting, this is seldom achieved with standard-of-care management, thus increasing the patients' risks of thrombotic or major bleeding events. There are many factors associated with poor INR control. Being treated in community settings, newly initiated on a VKA, younger in age, or nonadherent to therapy, as well as having polymorphisms of CYP2C9 or VKORC1, or multiple physical or mental co-morbid disease states have been associated with lower TTR. Clinical prediction tools are available, though they can only explain <10 % of the variance behind poor INR control. Clinicians caring for patients who require anticoagulation are encouraged to intensify diligence in INR management when using VKAs and to consider appropriate use of newer anticoagulants as a therapeutic option.

External validation of prognostic rules for early post-pulmonary embolism mortality: assessment of a claims-based and three clinical-based approaches.

BACKGROUND: Studies show the In-hospital Mortality for Pulmonary embolism using Claims daTa (IMPACT) rule can accurately identify pulmonary embolism (PE) patients at low-risk of early mortality in a retrospective setting using only claims for the index admission. We sought to externally validate IMPACT, Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI) and Hestia for predicting early mortality. METHODS: We identified consecutive adults admitted for objectively-confirmed PE between 10/21/2010 and 5/12/2015. Patients undergoing thrombolysis/embolectomy within 48 h were excluded. All-cause in-hospital and 30 day mortality (using available Social Security Death Index data through January 2014) were assessed and prognostic accuracies of IMPACT, PESI, sPESI and Hestia were determined. RESULTS: Twenty-one (2.6 %) of the 807 PE patients died before discharge. All rules classified 26.1-38.3 % of patients as low-risk for early mortality. Fatality among low-risk patients was 0 % (sPESI and Hestia), 0.4 % (IMPACT) and 0.6 % (PESI). IMPACT's sensitivity was 95.2 % (95 % confidence interval [CI] = 74.1-99.8 %), and the sensitivities of clinical rules ranged from 91 (PESI)-100 % (sPESI and Hestia). Specificities of all rules ranged between 26.8 and 39.1 %. Of 573 consecutive patients in the 30 day mortality analysis, 33 (5.8 %) died. All rules classified 27.9-38.0 % of patients as low-risk, and fatality occurred in 0 (Hestia)-1.4 % (PESI) of low-risk patients. IMPACT's sensitivity was 97.0 % (95%CI = 82.5-99.8 %), while sensitivities for clinical rules ranged from 91 (PESI)-100 % (Hestia). Specificities of rules ranged between 29.6 and 39.8 %. CONCLUSION: In this analysis, IMPACT identified low-risk PE patients with similar accuracy as clinical rules. While not intended for prospective clinical decision-making, IMPACT appears useful for identification of low-risk PE patient in retrospective claims-based studies.

Outcomes associated with observation stays versus inpatient admissions for pulmonary embolism.

Changes in reimbursement policies have led to an increased use of observation stays in the United States (US). We sought to compare outcomes among pulmonary embolism (PE) patients managed through observation stays or inpatient admissions.The Premier Perspective Comparative Hospital Database was used to identify patients with a primary International Classification of Diseases, ninth-edition diagnosis of PE (415.1×) from 11/2012-3/2015. Patients were required to have claims for ≥1 diagnostic tests for PE on days 0-2 and evidence of PE treatment. Patients managed through observation stays were 1:1 propensity score matched to those undergoing inpatient admissions. We compared length-of-stay (LOS), hospital costs (2015US$) and rates of hospital-acquired conditions and readmission between the cohorts. A total of 1105 PE observation stays were matched to 1105 inpatient admissions. The baseline characteristics of the cohorts were well-balanced (no standardized differences >10 %). Mean ± standard deviation LOS and hospital costs were 3.6 ± 2.6 days and $5423 ± $5770, respectively. LOS was shorter for observation stays 2.3 ± 1.3 days) vs. inpatient admissions (4.9 ± 3.0 days, p < 0.001). This corresponded to a mean $4390 lower treatment costs for observation stays (p < 0.001). Hospital-acquired conditions were less common among observation stay patients vs. inpatients (p < 0.001); driven predominantly by reductions in bacterial pneumonia and Clostridium difficile infection. Readmission for venous thromboembolism or major bleeding in the same or subsequent 2-months did not differ between the cohorts (p ≥ 0.16 for both).Compared with inpatient admissions, observation stays were associated with reduced LOS, costs and hospital-acquired conditions, without increased risk of readmission.

External validation of a multivariable claims-based rule for predicting in-hospital mortality and 30-day post-pulmonary embolism complications.

BACKGROUND: Low-risk pulmonary embolism (PE) patients may be candidates for outpatient treatment or abbreviated hospital stay. There is a need for a claims-based prediction rule that payers/hospitals can use to risk stratify PE patients. We sought to validate the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) prediction rule for in-hospital and 30-day outcomes. METHODS: We used the Optum Research Database from 1/2008-3/2015 and included adults hospitalized for PE (415.1x in the primary position or secondary position when accompanied by a primary code for a PE complication) and having continuous medical and prescription coverage for ≥6-months prior and 3-months post-inclusion or until death. In-hospital and 30-day mortality and 30-day complications (recurrent venous thromboembolism, rehospitalization or death) were assessed and prognostic accuracies of IMPACT with 95 % confidence intervals (CIs) were calculated. RESULTS: In total, 47,531 PE patients were included. In-hospital and 30-day mortality occurred in 7.9 and 9.4 % of patients and 20.8 % experienced any complication within 30-days. Of the 19.5 % of patients classified as low-risk by IMPACT, 2.0 % died in-hospital, resulting in a sensitivity and specificity of 95.2 % (95 % CI, 94.4-95.8) and 20.7 % (95 % CI, 20.4-21.1). Only 1 additional low-risk patient died within 30-days of admission and 12.2 % experienced a complication, translating into a sensitivity and specificity of 95.9 % (95 % CI, 95.3-96.5) and 21.1 % (95 % CI, 20.7-21.5) for mortality and 88.5 % (95 % CI, 87.9-89.2) and 21.6 % (95 % CI, 21.2-22.0) for any complication. CONCLUSION: IMPACT had acceptable sensitivity for predicting in-hospital and 30-day mortality or complications and may be valuable for retrospective risk stratification of PE patients.

Recurrent hospitalization and healthcare resource use among patients with deep vein thrombosis and pulmonary embolism: findings from a multi-payer analysis.

The objective of this study was to assess deep vein thrombosis and pulmonary embolism (DVT/PE) recurrence rates and resource utilization among patients with an initial DVT or PE event across multiple payer perspectives. Retrospective analyses were performed using a software tool that analyzes health plan claims to evaluate treatment patterns and resource utilization for various cardiovascular conditions. Six databases were analyzed from three payer perspectives (Commercial, Medicare, and Medicaid). Patients were ≥18 years old with a primary diagnosis of DVT or PE associated with an inpatient and/or emergency room claim, had received an antithrombotic within 7 days before or 14 days after index, and had no diagnosis of atrial fibrillation during follow-up. Outcomes were assessed over a 1 year period following index. More PE patients were hospitalized for their index event than DVT patients (42-59 % DVT and 69-86 % PE) and had longer mean length of stay (2.35-2.95 days DVT and 3.26-3.76 days PE). Recurrent event rates among PE patients (12-32 %) were higher than those for DVT patients (6-16 %) across all payers. The highest rate of recurrence was observed among the Medicaid population [23 % overall (VTE); 16 % DVT; 32 % PE]. All-cause hospitalization in the year following their VTE episode occurred in 23-67 % DVT patients and 30-68 % PE patients. Medicaid had the highest proportion of patients with hospitalizations and ER visits. Recurrent VTE events and all-cause hospitalizations are relatively common, especially for patients who had a PE, and among those in the Medicaid payer population.

Quality of vitamin K antagonist control and outcomes in atrial fibrillation patients: a meta-analysis and meta-regression.

BACKGROUND: Atrial fibrillation (AF) patients frequently require anticoagulation with vitamin K antagonists (VKAs) to prevent thromboembolic events, but their use increases the risk of hemorrhage. We evaluated time spent in therapeutic range (TTR), proportion of international normalized ratio (INR) measurements in range (PINRR), adverse events in relation to INR, and predictors of INR control in AF patients using VKAs. METHODS: We searched MEDLINE, CENTRAL and EMBASE (1990-June 2013) for studies of AF patients receiving adjusted-dose VKAs that reported INR control measures (TTR and PINRR) and/or reported an INR measurement coinciding with thromboembolic or hemorrhagic events. Random-effects meta-analyses and meta-regression were performed. RESULTS: Ninety-five articles were included. Sixty-eight VKA-treated study groups reported measures of INR control, while 43 studies reported an INR around the time of the adverse event. Patients spent 61% (95% CI, 59-62%), 25% (95% CI, 23-27%) and 14% (95% CI, 13-15%) of their time within, below or above the therapeutic range. PINRR assessments were within, below, and above range 56% (95% CI, 53-59%), 26% (95% CI, 23-29%) and 13% (95% CI, 11-17%) of the time. Patients receiving VKA management in the community spent less TTR than those managed by anticoagulation clinics or in randomized trials. Patients newly receiving VKAs spent less TTR than those with prior VKA use. Patients in Europe/United Kingdom spent more TTR than patients in North America. Fifty-seven percent (95% CI, 50-64%) of thromboembolic events and 42% (95% CI, 35 - 51%) of hemorrhagic events occurred at an INR <2.0 and >3.0, respectively; while 56% (95% CI, 48-64%) of ischemic strokes and 45% of intracranial hemorrhages (95% CI, 29-63%) occurred at INRs <2.0 and >3.0, respectively. CONCLUSIONS: Patients on VKAs for AF frequently have INRs outside the therapeutic range. While, thromboembolic and hemorrhagic events do occur patients with a therapeutic INR; patients with an INR <2.0 make up many of the cases of thromboembolism, while those >3.0 make up many of the cases of hemorrhage. Managing anticoagulation outside of a clinical trial or anticoagulation clinic is associated with poorer INR control, as is, the initiation of therapy in the VKA-naïve. Patients in Europe/UK have better INR control than those in North America.

A clinical pathway for community-acquired pneumonia: an observational cohort study.

BACKGROUND: Six hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost. METHODS: Data were collected for adults from six U.S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost. RESULTS: Overall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (p = 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, p < 0.01), lower mean hospital costs ($2,485 vs. $3,281, p = 0.02), and similar mean pharmacy costs ($356 vs. $442, p = 0.11). CONCLUSIONS: Pathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP.

Patients' assessment of the convenience of fentanyl HCl iontophoretic transdermal system (ITS) versus morphine intravenous patient-controlled analgesia (IV PCA) in the management of postoperative pain after major surgery.

The patient-controlled fentanyl HCl iontophoretic transdermal system (ITS) is a compact, self-contained, needle-free system that has been approved for acute postoperative pain management in hospitalized adults. The objective of the present analysis was to evaluate patients' assessment of fentanyl ITS and morphine intravenous patient-controlled analgesia (IV PCA) convenience on 7 different subscales, using a validated patient ease of care (EOC) questionnaire in 2 prospective, open-label, randomized, phase IIIb clinical trials. Patients received fentanyl ITS or morphine IV PCA (N = 1,305) for up to 72 h after total hip replacement surgery (THR study) or abdominal or pelvic surgery (APS study). For the majority of items on the patient EOC questionnaire, trends suggest that greater percentages of patients reported the most positive response for fentanyl ITS than they did for morphine IV PCA in both studies; differences were particularly noteworthy for items on the Movement subscale. In the THR study, more patients in the fentanyl ITS group were responders compared with those in the morphine IV PCA group for the subscales Confidence with Device, Pain Control, Knowledge/Understanding, and Satisfaction. In the APS study, responder rates for these subscales did not differ between treatment groups. These findings indicate that patients assessed the EOC associated with fentanyl ITS higher compared with morphine IV PCA for the management of acute postoperative pain and suggest that fentanyl ITS has the potential to improve acute postoperative pain care for patients and nurses.

Comparison of real-world outcomes in patients with nonvalvular atrial fibrillation treated with direct oral anticoagulant agents or warfarin.

PURPOSE: To compare patients with atrial fibrillation (AF) initiating direct oral anticoagulants (DOACs) versus warfarin on clinical outcomes including stroke, systemic embolism (SE), bleeding events, and cost of care. METHODS: This retrospective observational study used Medicare Advantage Prescription Drug and fully insured commercial claims from the Humana Research Database. Patients with AF who initiated a DOAC or warfarin from January 1, 2012, through September 30, 2015, were included. Date of the first prescription of DOAC or warfarin was the index date. Patients in the DOAC and warfarin groups were matched on propensity scores. Patients were censored at end of enrollment or study period, discontinuation, or switch of index medication. Clinical outcomes were compared in the matched groups using Cox proportional hazards models. Annualized costs and costs adjusted for censoring using Lin's interval method were also compared between the two cohorts. RESULTS: Patients on DOACs had a significantly lower risk of ischemic stroke (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.98), hemorrhagic stroke (HR, 0.65; CI, 0.46-0.92), SE (HR, 0.53; 95% CI, 0.43-0.65), and composite outcome of stroke or SE (HR, 0.78; 95% CI, 0.71-0.86) compared with patients on warfarin. Bleeding risk was not statistically significant (HR, 0.85; 95% CI, 0.71-1.01). While annualized pharmacy costs were higher, annualized medical and total costs were lower in the DOAC group compared with the warfarin group. CONCLUSION: The results of the study indicated that patients on DOACs had lower rates of ischemic stroke, hemorrhagic stroke, SE, and composite outcome of stroke or SE compared with patients on warfarin. No significant differences in bleeding rates between the DOAC and warfarin groups were observed, while total cost of care was lower in the DOAC group.

Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants.

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE (n = 1,340) and those with MB (n = 3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively (p < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively (p < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

System-related events and analgesic gaps during postoperative pain management with the fentanyl iontophoretic transdermal system and morphine intravenous patient-controlled analgesia.

BACKGROUND: Analgesic gaps (interruptions in analgesic delivery) contribute to ineffective postoperative pain management. In this analysis, we evaluated the incidence of analgesic gaps resulting from system-related events (SREs) for patients using the fentanyl iontophoretic transdermal system (ITS), a noninvasive patient-controlled analgesia (PCA) system, or morphine IV PCA for postoperative pain management. METHODS: Data were pooled from two open-label, randomized, active-controlled trials that evaluated the efficacy and safety of fentanyl ITS and morphine IV PCA after total hip replacement, abdominal, or pelvic surgery. The incidence and duration of analgesic gaps resulting from SREs were assessed, along with SRE resolution times. RESULTS: A total of 1305 patients received fentanyl ITS (n = 647) or morphine IV PCA (n = 658). Fentanyl ITS was associated with a significantly lower incidence of analgesic gaps per 100 patients compared with morphine IV PCA (5.87 vs 12.01, respectively; P < 0.001). Compared with patients receiving morphine IV PCA, patients receiving fentanyl ITS had both a numerically lower median total analgesic gap time (15.0 min vs 20.0 min) and a numerically lower median total SRE resolution time (11.0 min vs 20.0 min). Most fentanyl ITS SREs were resolved by applying a new system, whereas many different SRE resolution methods were used for morphine IV PCA. CONCLUSIONS: Fentanyl ITS was associated with a significantly lower incidence of analgesic gaps relative to morphine IV PCA. Fentanyl ITS may provide patients with fewer interruptions and more continuous analgesic delivery.

Is Rivaroxaban Associated With Shorter Hospital Stays and Reduced Costs Versus Parenteral Bridging to Warfarin Among Patients With Pulmonary Embolism?

OBJECTIVE: We sought to compare the length of stay (LOS) and total costs for patients with pulmonary embolism (PE) treated with either rivaroxaban or parenterally bridged warfarin. METHODS: This retrospective claims analysis was performed in the Premier Database from November 2012 to March 2015. Adult patients were included if they had a hospital encounter for PE (an International Classification of Diseases, Ninth Revision code = 415.1×) in the primary position, a claim for ≥1 diagnostic test for PE on day 0 to 2, and initiated rivaroxaban or parenteral anticoagulation/warfarin. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients receiving parenterally bridged warfarin. Length of stay, total costs, and readmission for venous thromboembolism (VTE) or major bleeding during the same or subsequent 2 months following the index event were compared between cohorts. Analysis restricted to patients with low-risk PE was also performed. RESULTS: Characteristics of the matched PE cohorts (n = 3466 per treatment) were well balanced. Rivaroxaban use was associated with a 1.36-day shorter LOS and $2304 reduction in total costs compared to parenterally bridged warfarin ( P < .001 for both). Rates of readmission for VTE were similar between cohorts (1.7% vs 1.6%; P = .64). No difference was observed between treatments for readmission for major bleeding (0.2% vs 0.2%; P > .99). In analyses restricted to low-risk patients (n = 1551 per treatment), rivaroxaban was associated with a 1.01-day and a $1855 reduction in LOS and costs, respectively ( P < .001 for both). Rates of readmission were again similar between treatments ( P > .56 for all). CONCLUSION: Rivaroxaban significantly reduced hospital LOS and costs compared to parenterally bridged warfarin, without increasing the risk of readmission.

External Validation of the Hestia Criteria for Identifying Acute Pulmonary Embolism Patients at Low Risk of Early Mortality.

INTRODUCTION: There are limited studies evaluating the ability of the Hestia criteria to accurately identify patients with acute pulmonary embolism (PE) at low risk of early mortality. We sought to externally validate the Hestia criteria for predicting in-hospital and 30-day post-PE mortality. METHODS: We retrospectively identified consecutive, adult, objectively confirmed PE patients presenting to the emergency department at our institution from November 21, 2010, to January 31, 2014. We ascertained the total number of Hestia criteria met for each patient, calculated the proportion of patients categorized as low risk (ie, no Hestia criteria met), and determined the accuracy of the Hestia criteria for predicting in-hospital and 30-day all-cause mortality. Mortality was determined through Social Security Death Index searches. RESULTS: A total of 577 patients with PE were included, of which 19 (3.3%) and 35 (6.6%) died in hospital or within 30 days of presentation. Both in-hospital and 30-day case fatality rates rose as the number of Hestia criteria increased. One-hundred forty nine (25.8%) patients were classified as low risk for early mortality, and none of these patients died within 30 days (negative predictive values of 100%). The Hestia criteria had excellent sensitivity (100%, 95% confidence interval [CI] = 79.1%-100% and 100%, 95% CI = 87.7%-100%) for predicting in-hospital and 30-day mortality but low specificity (<27.5% for both). The c-statistics for in-hospital and 30-day mortality were 83.5%, 95% CI = 77.1%-89.9% and 78.5%, 95% CI = 71.9%-85.1%. The predictive accuracy of the Hestia criteria remained acceptable in patients >80 years of age, with active cancer or chronic cardiopulmonary disease. CONCLUSION: The Hestia criteria have an acceptable predictive accuracy to identify patients with PE at low risk for in-hospital or 30-day mortality.

Hospital length-of-stay and costs among pulmonary embolism patients treated with rivaroxaban versus parenteral bridging to warfarin.

We sought to compare length-of-stay (LOS), total hospital costs, and readmissions among pulmonary embolism (PE) patients treated with rivaroxaban versus parenterally bridged warfarin. We identified adult PE (primary diagnostic code = 415.1x) patients in the Premier Database (11/2012-9/2015), and included those with ≥1 PE diagnostic test on days 0-2. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients parenterally bridged to warfarin. LOS, total costs, and readmission for venous thromboembolism (VTE) or major bleeding within the same or subsequent 2 months were compared between cohorts. Separate analyses were performed in low-risk PE patients. Rivaroxaban use was associated with a 1.4-day [95 % confidence interval (CI) -1.47 to -1.28] shorter LOS, and $2322 (95 % CI -$2499 to -$2146) reduction in costs compared to parenterally bridged warfarin (p < 0.001 for both). There was no difference in readmission for VTE (1.5 versus 1.7 %) or major bleeding (0.3 versus 0.2 %) between the rivaroxaban and parenterally bridged warfarin cohorts (p ≥ 0.27 for both). Results were similar in low-risk patients (0.2-1.0 day and $251-$1751 reductions in LOS and costs, respectively, p ≤ 0.01 for all). In patients with PE, rivaroxaban was associated with reduced LOS and costs, without increased risk of readmission versus parenterally bridged warfarin. Similar results were observed in low-risk PE patients.

Association between rivaroxaban use and length of hospital stay, treatment costs and early outcomes in patients with pulmonary embolism: a systematic review of real-world studies.

BACKGROUND: In the EINSTEIN-Pulmonary Embolism (PE) trial, subjects randomized to rivaroxaban versus enoxaparin bridging to vitamin K antagonist (VKA) therapy experienced a reduced index hospital length of stay (LOS). We sought to conduct a systematic review of real-world studies comparing LOS, costs and early outcomes among patients treated with rivaroxaban or parenterally bridged VKA in routine practice. METHODS: We searched Medline and Scopus from 1 January 2011 to 30 November 2016 to identify observational studies comparing acute PE patients anticoagulated with rivaroxaban or parenterally bridged VKA and reporting data on index hospital LOS, costs and/or early post-PE outcomes. Studies not using appropriate methods for minimizing confounding bias or not published in English were excluded. RESULTS: Five studies met inclusion criteria. Rivaroxaban use was associated with decreased index hospital LOS (range: 1.36-1.70 days) and treatment costs (range: $1818-$2688) during an index stay compared to parenterally bridged warfarin. No differences in early readmission for recurrent thrombosis were noted between anticoagulation strategies. Readmission for major bleeding was rare in both cohorts. Similar reductions in LOS (range: 0.23-4.3 days) and costs (range: $251-$7094) were observed with rivaroxaban in studies restricted to patients deemed low risk for early complications by clinical gestalt or by a clinical- or claims-based risk stratification tool. CONCLUSIONS: Regardless of patient predicted risk of post-PE complications, real-world studies suggest that rivaroxaban is associated with a reduced hospital LOS and costs versus parenterally bridged warfarin, without increasing readmission.

External validation of a claims-based and clinical approach for predicting post-pulmonary embolism outcomes among United States veterans.

The In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) rule can accurately identify pulmonary embolism (PE) patients at low risk of early complications using claims data. We sought to externally validate the IMPACT and simplified Pulmonary Embolism Severity Index (sPESI) tools for predicting all-cause mortality and readmission. We used Veteran Health Administration data (10/1/2010-9/30/2015) to identify adults with ≥1 inpatient diagnosis code for acute PE, ≥12 months continuous medical and pharmacy benefits prior to the index PE, ≥90 days of post-event follow-up (unless death occurred) and ≥1 claim for an anticoagulant during the index PE stay. Prognostic accuracies of IMPACT and sPESI for 30- and 90-day all-cause mortality and 90-day readmission were estimated. Of 6,746 PE patients, 7.5 and 12.6% died at 30 and 90 days. Within 90 days, 20.1% were readmitted for any reason. Hospitalization for recurrent VTE and major bleeding occurred in 5.6 and 1.7% of patients. IMPACT classified 15.2% as low risk, while 28.4% were low risk per sPESI. Both tools displayed sensitivity >90% and negative predictive values (NPVs) >97% for 30-day mortality, but low specificity (range 16.2-30.0) and positive predictive values (PPVs) (range 8.7-9.5); with similar results observed for 90-day mortality. IMPACT's sensitivity for all-cause readmission was numerically higher than sPESI (88.2 vs. 79.0%), but both had comparable NPVs (85.1 vs. 84.2%). Similar trends were observed for VTE or major bleeding readmissions. IMPACT classified patients for post-PE outcomes with similar accuracy as sPESI. IMPACT appears useful for identifying PE patients at low risk for early mortality or readmission in claims-based studies.

Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain. METHODS: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily. MAIN OUTCOME MEASURES: The co-primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity. RESULTS: Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo, overall (p

Estimated costs of prescription opioid analgesic abuse in the United States in 2001: a societal perspective.

OBJECTIVES: This study estimates the costs to society of prescription opioid analgesic (RxO) abuse in the United States. METHODS: Costs associated with RxO abuse were grouped into healthcare, criminal justice, and workplace categories. Costs were estimated by either (1) a quantity method that multiplies the number of RxO abusers derived from various national surveys by the estimated per abuser cost, or (2) an apportionment method that starts with overall (ie, prescription and nonprescription) drug abuse costs for a cost component (eg, police protection) and apportions the share of costs based on the prevalence of RxO abuse relative to overall drug abuse. Medical costs in excess of those for otherwise similar nonabusers were based on an analysis of a large administrative claims database for an employed population using multivariate regression methods. RESULTS: A lower bound estimate of the costs of RxO abuse in the United States was 8.6 billion dollars in 2001 (or 9.5 billion dollars in 2005 dollars). Of this amount, 2.6 billion dollarswere healthcare costs, 1.4 billion dollars were criminal justice costs, and 4.6 billion dollars were workplace costs. CONCLUSIONS: The costs of RxO abuse represent a substantial economic burden. Rising trends of RxO abuse suggest an escalating economic and public health burden in coming years in the United States, and potentially, elsewhere.