Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice.

BACKGROUND: Findings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (MBC) treated in routine clinical practice in the USA. PATIENTS AND METHODS: This was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed. RESULTS: After sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2-34.9) in the palbociclib group and 23.3 months (IQR, 12.7-34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9 months; hazard ratio [HR], 0.58; 95% CI, 0.49-0.69; P < 0.0001). Median OS was not reached in the palbociclib group and was 43.1 months with letrozole alone (HR, 0.66; 95% CI, 0.53-0.82; P = 0.0002). The 2-year OS rate was 78.3% in the palbociclib group and 68.0% with letrozole alone. A propensity score matching analysis showed similar results. CONCLUSIONS: In this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting. TRIAL REGISTRATION: Clinicaltrials.gov; NCT04176354.

Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC).

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan-Meier survival curves were used to assess survival. RESULTS: Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25-44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. CONCLUSIONS: AS occurs frequently (32%) in real-world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients.

Using Artificial Intelligence With Natural Language Processing to Combine Electronic Health Record's Structured and Free Text Data to Identify Nonvalvular Atrial Fibrillation to Decrease Strokes and Death: Evaluation and Case-Control Study.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) affects almost 6 million Americans and is a major contributor to stroke but is significantly undiagnosed and undertreated despite explicit guidelines for oral anticoagulation. OBJECTIVE: The aim of this study is to investigate whether the use of semisupervised natural language processing (NLP) of electronic health record's (EHR) free-text information combined with structured EHR data improves NVAF discovery and treatment and perhaps offers a method to prevent thousands of deaths and save billions of dollars. METHODS: We abstracted 96,681 participants from the University of Buffalo faculty practice's EHR. NLP was used to index the notes and compare the ability to identify NVAF, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category (CHA2DS2-VASc), and Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage (HAS-BLED) scores using unstructured data (International Classification of Diseases codes) versus structured and unstructured data from clinical notes. In addition, we analyzed data from 63,296,120 participants in the Optum and Truven databases to determine the NVAF frequency, rates of CHA2DS2­VASc ≥2, and no contraindications to oral anticoagulants, rates of stroke and death in the untreated population, and first year's costs after stroke. RESULTS: The structured-plus-unstructured method would have identified 3,976,056 additional true NVAF cases (P<.001) and improved sensitivity for CHA2DS2-VASc and HAS-BLED scores compared with the structured data alone (P=.002 and P<.001, respectively), causing a 32.1% improvement. For the United States, this method would prevent an estimated 176,537 strokes, save 10,575 lives, and save >US $13.5 billion. CONCLUSIONS: Artificial intelligence-informed bio-surveillance combining NLP of free-text information with structured EHR data improves data completeness, prevents thousands of strokes, and saves lives and funds. This method is applicable to many disorders with profound public health consequences.

Effectiveness and safety of direct oral anticoagulants compared to warfarin in treatment naïve non-valvular atrial fibrillation patients in the US Department of defense population.

BACKGROUND: Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are at least non-inferior to warfarin in reducing the risk of stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF), but the comparative risk of major bleeding varies between DOACs and warfarin. Using US Department of Defense (DOD) data, this study compared the risk of stroke/SE and major bleeding for DOACs relative to warfarin. METHODS: Adult patients with ≥1 pharmacy claim for apixaban, dabigatran, rivaroxaban, or warfarin from 01 Jan 2013-30 Sep 2015 were selected. Patients were required to have ≥1 medical claim for atrial fibrillation during the 12-month baseline period. Patients with a warfarin or DOAC claim during the 12-month baseline period were excluded. Each DOAC cohort was matched to the warfarin cohort using propensity score matching (PSM). Cox proportional hazards models were conducted to evaluate the risk of stroke/SE and major bleeding of each DOAC vs warfarin. RESULTS: Of 41,001 identified patients, there were 3691 dabigatran-warfarin, 8226 rivaroxaban-warfarin, and 7607 apixaban-warfarin matched patient pairs. Apixaban was the only DOAC found to be associated with a significantly lower risk of stroke/SE (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.39, 0.77; p < 0.001) and major bleeding (HR: 0.65; 95% CI: 0.53, 0.80; p < 0.001) compared to warfarin. Dabigatran and rivaroxaban initiation were associated with similar risk of stroke/SE (dabigatran: HR: 0.68; 95% CI: 0.43, 1.07; p = 0.096; rivaroxaban: HR: 0.83; 95% CI: 0.64, 1.09; p = 0.187) and major bleeding (dabigatran: HR: 1.05; 95% CI: 0.79, 1.40; p = 0.730; rivaroxaban: HR: 1.07; 95% CI: 0.91, 1.27; p = 0.423) compared to warfarin. CONCLUSION: Among NVAF patients in the US DOD population, apixaban was associated with significantly lower risk of stroke/SE and major bleeding compared to warfarin. Dabigatran and rivaroxaban were associated with similar risk of stroke/SE and major bleeding compared to warfarin.

Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population.

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) VS warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban-warfarin, 18,131 dabigatran-warfarin, and 55,359 rivaroxaban-warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59-0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73-0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72-1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57-0.67; NCO: HR: 0.64; 95% CI 0.60-0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71-0.89; NCO: HR: 0.84; 95% CI 0.76-0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02-1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99-1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Detecting Atrial Fibrillation in the Emergency Department in Patients with Cardiac Implantable Electronic Devices.

BACKGROUND: Clinical guidelines emphasize identifying atrial fibrillation (AF) as a strategy to reduce stroke risk. Cardiac implantable electronic device (CIED) interrogation at the point of care may facilitate AF detection, increasing opportunities to identify patients at high risk for stroke. OBJECTIVES: This study sought to quantify AF prevalence and assess stroke risk in patients with a CIED who presented to the emergency department (ED). METHODS: This noninterventional, retrospective observational study included adult patients who presented at a single facility ED that incorporated device interrogation as a routine standard practice for all patients with a CIED. Interrogations were conducted in 494 unique patients, and relevant demographic/clinical information was captured from electronic medical records. RESULTS: AF was detected via CIED interrogation in 54.8% (271/494) of the unique patient population that presented to the ED. Device interrogation detected the presence of AF in 110 patients without a documented past history or current diagnosis of AF, representing 22.3% (110/494) of total unique patients. Based on CHA2DS2-VASc (Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65-74 years, Sex category [female]) risk scoring methodology, over three-quarters of these newly detected AF patients (78.2%, 86/110) were classified in a high stroke risk category that reflected a > 2.2% annualized risk, and over half (57.3%, 63/110) presented to the ED for reasons unrelated to cardiac/dysrhythmia problems. CONCLUSIONS: The use of technology-assisted device interrogation of CIEDs at the point of care has promise in identifying patients with asymptomatic AF. Results suggest consideration of routine device interrogation of CIEDs in the ED, regardless of reason for admission or history of AF.

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients.

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Ischemic Stroke in Nonvalvular Atrial Fibrillation at Warfarin Initiation: Assessment via a Large Insurance Database.

BACKGROUND AND PURPOSE: Stroke risk may increase shortly after warfarin initiation in nonvalvular atrial fibrillation patients. Because of the brief period and limited number of events, large samples are needed to study this effect. We compared 30-day rates of ischemic stroke between nonvalvular atrial fibrillation patients initiating warfarin to nonwarfarin comparators using an insurance claims database. METHODS: We identified nonvalvular atrial fibrillation patients via 1 inpatient/2 outpatient diagnosis claims from the MarketScan database, January 1, 2009, to December 31, 2010. We studied patients initiating warfarin using prescription claims and 1:1 matched 22 669 initiators to comparators based on age, sex, diagnosis date, and warfarin propensity score. Follow-up began on initiation date; patients were censored at discontinuation/switch of therapy, disenrollment, or end of the study. The median follow-up was 415 days. Cox regression was used to study differences in ischemic stroke risks between warfarin initiators and comparators while controlling for important prognostic factors. RESULTS: Warfarin initiators were generally similar to comparators in clinical features but had higher CHADS2 scores (1.26 versus 1.19). The first 30-day ischemic stroke rate was higher among warfarin initiators than comparators (1.47%/y (27/1836) versus 0.98%/y (18/1837); P=0.18) but lower subsequently (0.81%/y [134/16 543] versus 1.09%/y [406/37 248]; P=0.002). Multivariable regression confirmed a significant interaction between follow-up and warfarin use with the adjusted hazard ratios (95% confidence intervals) for warfarin/comparator as 1.46 (0.80-2.65) in the first 30 days and 0.70 (0.57-0.85) afterward. CONCLUSIONS: Warfarin effect was qualitatively different in the first 30 days after initiation than subsequently. This is consistent with a modest increase in stroke risk occurring briefly after starting warfarin.

Ulcerative Colitis Treatment Patterns and Cost of Care.

OBJECTIVES: To examine treatment patterns, dosing, health care resource utilization, and cost of tumor necrosis factor inhibitors (TNFi), adalimumab (ADA) and infliximab (IFX), among patients enrolled in US Humana insurance plans who have been diagnosed with ulcerative colitis (UC). METHODS: This retrospective cohort study identified the first pharmacy or medical claim for ADA or IFX (from January 1, 2007, to December 31, 2014) in patients with continuous enrollment for 6 months or more preindex and 12 months or more postindex, with one or more UC diagnosis claim 6 months pre- or postindex. TNFi discontinuation was defined as a therapy gap of 56 days or more for ADA and 112 days or more for IFX. TNFi switch was defined as nonindex TNFi initiation. Health care resource utilization and costs were characterized quarterly according to treatment patterns. RESULTS: The study population comprised 295 patients: mean age 50.9 years, 50.5% females, and 61.7% in southern United States. At the index date, 17% of patients received ADA and 83% received IFX. Treatment discontinuation was observed in 52% of ADA and 45% of IFX users through 12 months postindex (mean time 19 and 22 weeks, respectively). Among discontinuers, 46% of ADA and 68% of IFX users did not restart/switch TNFi. ADA and IFX showed mean times to switch of 18 and 30 weeks, respectively. TNFi discontinuers had the lowest mean quarterly total health care cost ($3,935) versus patients who initiated/switched TNFi ($15,004). Nevertheless, discontinuers had higher UC-related hospitalization versus patients receiving therapy. CONCLUSIONS: Approximately half of ADA and IFX users discontinued, with approximately half of discontinuers not restarting/switching therapies. Further investigation of treatment patterns and outcomes after TNFi discontinuation is required.

Using Random Forest Models to Identify Correlates of a Diabetic Peripheral Neuropathy Diagnosis from Electronic Health Record Data.

Objective: To identify variables correlated with a diagnosis of diabetic peripheral neuropathy (DPN) using random forest modeling applied to electronic health records. Design: Retrospective analysis. Setting: Humedica de-identified electronic health records database. Subjects: Subjects ≥ 18 years old with type 2 diabetes from January 1, 2008-September 30, 2013 having continuous data for 1 year pre- and postindex with DPN (n = 35,050) and without DPN (n = 288,328) were identified. Methods: Demographic, clinical, and health care resource utilization variables (e.g., inpatient and outpatient encounters, medications, and procedures) were input into a random forest model to identify the most important correlates of a DPN diagnosis. Random forest modeling is a computationally extensive, robust data mining technique that accommodates large sets of variables to identify associated factors using an ensemble of classifications trees. Accuracy of the model was evaluated using receiver operating characteristic curves (ROC). Results: The final random forest model consisted of the following variables (importance) associated with a DPN diagnosis: Charlson Comorbidity Index score (100%), age (37.1%), number of pre-index procedures and services (29.7%), number of pre-index outpatient prescriptions (24.2%), number of pre-index outpatient visits (18.3%), number of pre-index laboratory visits (16.9%), number of pre-index outpatient office visits (12.1%), number of inpatient prescriptions (5.9%), and number of pain-related medication prescriptions (4.4%). ROC analysis confirmed model performance, with an area under the curve of 0.824 and accuracy of 89.6% (95% confidence interval 89.4%, 89.8%). Conclusions: Random forest modeling can determine likelihood of a DPN diagnosis. Further validation of the random forest model may help facilitate earlier diagnosis and enhance management strategies.

Enhancing Risk Assessment in Patients Receiving Chronic Opioid Analgesic Therapy Using Natural Language Processing.

OBJECTIVES: Clinical guidelines for the use of opioids in chronic noncancer pain recommend assessing risk for aberrant drug-related behaviors prior to initiating opioid therapy. Despite recent dramatic increases in prescription opioid misuse and abuse, use of screening tools by clinicians continues to be underutilized. This research evaluated natural language processing (NLP) together with other data extraction techniques for risk assessment of patients considered for opioid therapy as a means of predicting opioid abuse. DESIGN: Using a retrospective cohort of 3,668 chronic noncancer pain patients with at least one opioid agreement between January 1, 2007, and December 31, 2012, we examined the availability of electronic health record structured and unstructured data to populate the Opioid Risk Tool (ORT) and other selected outcomes. Clinician-documented opioid agreement violations in the clinical notes were determined using NLP techniques followed by manual review of the notes. RESULTS: Confirmed through manual review, the NLP algorithm had 96.1% sensitivity, 92.8% specificity, and 92.6% positive predictive value in identifying opioid agreement violation. At the time of most recent opioid agreement, automated ORT identified 42.8% of patients as at low risk, 28.2% as at moderate risk, and 29.0% as at high risk for opioid abuse. During a year following the agreement, 22.5% of patients had opioid agreement violations. Patients classified as high risk were three times more likely to violate opioid agreements compared with those with low/moderate risk. CONCLUSION: Our findings suggest that NLP techniques have potential utility to support clinicians in screening chronic noncancer pain patients considered for long-term opioid therapy.

Evaluation of the Relationship Between Serum Uric Acid Levels and Cardiovascular Events in Patients With Gout: A Retrospective Analysis Using Electronic Medical Record Data.

OBJECTIVES: The aim of this study was to evaluate relationships between serum uric acid (SUA) and newly emergent acute myocardial infarction (AMI), congestive heart failure (CHF), coronary artery disease (CAD), composite cardiovascular (CV) events (AMI, CHF, CAD), hypertension, hyperlipidemia, and renal disease in gout patients. METHODS: Retrospective analysis of electronic medical records from Humedica identified adults (≥18 years) with 2 or more International Classification of Diseases, Ninth Revision, Clinical Modification codes for gout 30 days or more apart (first diagnosis = index event) having 1 or more SUA assessment on or after the index date, and at least 6 months preindex and at least 12 months postindex enrollment. Outcomes were measured during 12 months postindex; patients with preindex events were excluded from analysis of those events. The SUA level (0.01-4.00 mg/dL, 4.01-6.00 mg/dL, 6.01-8.00 mg/dL, and ≥8.01 mg/dL) was determined using the closest laboratory assessment before or on the date of the CV event. Tukey-Kramer comparisons were performed for pairs of SUA strata and Cox proportional model estimated hazard ratios. RESULTS: A significantly higher incidence of AMI, CHF, and renal disease was observed for patients with 8.01 mg/dL or greater relative to other SUA levels (P < 0.0001), and a significantly higher incidence of composite CV events (AMI, CHF, and CAD) was observed for hypouricemia (SUA, 0.01-4.00 mg/dL) compared with other SUA levels (P < 0.0001). Cox models confirmed the increased risk associated with SUA 8.01 mg/dL or greater; hazard ratios ranged from 1.16 for hypertension to 2.04 for renal disease. Hyperlipidemia and hypertension were diagnosed concurrently with gout in 24% and 28% of patients, respectively. CONCLUSIONS: Hyperuricemia and hypouricemia were associated with an increased risk of CV events.

Warfarin Discontinuation in Patients With Unprovoked Venous Thromboembolism: A Large US Insurance Database Analysis.

This study examined warfarin therapy discontinuation and its risk factors among patients with unprovoked venous thromboembolism (VTE) in the US clinical practice setting. Adult patients with unprovoked VTE were identified from the MarketScan claims database from January 1, 2006 to December 31, 2012. The index date was defined as the date of first VTE diagnosis. Patients were required to have no VTE diagnosis in the 6 months before index date and continuous health plan enrollment for 6 months before and 12 months after the index date. Warfarin discontinuation rates and adjusted hazard ratios (HRs) were reported. Of 21,163 eligible patients, 15,463 were diagnosed with deep vein thrombosis (DVT) only (73.1%), 5027 with pulmonary embolism (PE) only (23.7%), and 673 with DVT and PE (3.2%). The average duration of warfarin therapy was 5.2 months (SD = 3.0). During 1-year follow-up, 21.4% patients discontinued therapy within 3 months, 42.8% within 6 months, and 70.1% within 12 months. PE versus DVT [HR = 0.77, 95% confidence interval (CI) = 0.74-0.80], comorbid atrial fibrillation (HR = 0.73, 95% CI = 0.66-0.81), thrombophilia (HR = 0.62, 95% CI = 0.54-0.71), and age >40 years (41-65 years: HR = 0.86, 95% CI = 0.81-0.91; >65 years: HR = 0.82, 95% CI = 0.77-0.87) were significantly associated with reduced risk of warfarin discontinuation. Alcohol abuse/dependence (HR = 1.36, 95% CI = 1.20-1.55), cancer history (HR = 1.13, 95% CI = 1.07-1.19), bleeding (HR = 1.07, 95% CI = 1.01-1.15), and catheter ablation (HR = 1.10, 95% CI = 1.00-1.20) in the 6 months before index date were significantly associated with increased risk for warfarin discontinuation. In conclusion, nearly 1 of 4 patients with unprovoked VTE discontinued warfarin within 3 months. Three of 4 patients discontinued therapy within 1 year. Younger age and multiple clinical factors are associated with warfarin therapy discontinuation.

Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a "real-world" observational study in the United States.

BACKGROUND: Limited data are available about the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVES: To compare the major bleeding risk among newly anticoagulated non-valvular atrial fibrillation (NVAF) patients initiating apixaban, warfarin, dabigatran or rivaroxaban in the United States. METHODS AND RESULTS: A retrospective cohort study was conducted to compare the major bleeding risk among newly anticoagulated NVAF patients initiating warfarin, apixaban, dabigatran or rivaroxaban. The study used the Truven MarketScan(®) Commercial & Medicare supplemental US database from 1 January 2013 through 31 December 2013. Major bleeding was defined as bleeding requiring hospitalisation. Cox model estimated hazard ratios (HRs) of major bleeding were adjusted for age, gender, baseline comorbidities and co-medications. Among 29 338 newly anticoagulated NVAF patients, 2402 (8.19%) were on apixaban; 4173 (14.22%) on dabigatran; 10 050 (34.26%) on rivaroxaban; and 12 713 (43.33%) on warfarin. After adjusting for baseline characteristics, initiation on warfarin [adjusted HR (aHR): 1.93, 95% confidence interval (CI): 1.12-3.33, P=.018] or rivaroxaban (aHR: 2.19, 95% CI: 1.26-3.79, P=.005) had significantly greater risk of major bleeding vs apixaban. Dabigatran initiation (aHR: 1.71, 95% CI: 0.94-3.10, P=.079) had a non-significant major bleeding risk vs apixaban. When compared with warfarin, apixaban (aHR: 0.52, 95% CI: 0.30-0.89, P=.018) had significantly lower major bleeding risk. Patients initiating rivaroxaban (aHR: 1.13, 95% CI: 0.91-1.41, P=.262) or dabigatran (aHR: 0.88, 95% CI: 0.64-1.21, P=.446) had a non-significant major bleeding risk vs warfarin. CONCLUSION: Among newly anticoagulated NVAF patients in the real-world setting, initiation with rivaroxaban or warfarin was associated with a significantly greater risk of major bleeding compared with initiation on apixaban. When compared with warfarin, initiation with apixaban was associated with significantly lower risk of major bleeding. Additional observational studies are required to confirm these findings.

Cost Burden of Chronic Pain Patients in a Large Integrated Delivery System in the United States.

OBJECTIVES: To estimate all-cause healthcare resource utilization and costs among chronic pain patients within an integrated healthcare delivery system in the United States. METHODS: Electronic medical records and health claims data from the Henry Ford Health System were used to determine healthcare resource utilization and costs for patients with 24 chronic pain conditions. Patients were identified by ≥ 2 ICD-9-CM codes ≥ 30 days apart from January to December, 2010; the first ICD-9 code was the index event. Continuous coverage for 12 months pre- and postindex was required. All-cause direct medical costs were determined from billing data. RESULTS: A total of 12,165 patients were identified for the analysis. After pharmacy, the most used resource was outpatient visits, with a mean of 18.8 (SD 13.2) visits per patient for the postindex period; specialty visits accounted for 59.0% of outpatient visits. Imaging was utilized with a mean of 5.2 (SD 5.5) discrete tests per patient, and opioids were the most commonly prescribed medication (38.7%). Annual direct total costs for all conditions were $386 million ($31,692 per patient; a 40% increase from the pre-index). Pharmacy costs comprised 14.3% of total costs, and outpatient visits were the primary cost driver. CONCLUSIONS: Chronic pain conditions impose a substantial burden on the healthcare system, with musculoskeletal conditions associated with the highest overall costs. Costs appeared to be primarily related to use of outpatient services. This type of research supports integrated delivery systems as a source for assessing opportunities to improve patient outcomes and lower the costs for chronic pain patients.

Prevalence of Chronic Pain in a Large Integrated Healthcare Delivery System in the U.S.A.

BACKGROUND: There is a paucity of published data on the prevalence of chronic pain conditions within large, integrated healthcare organizations in the U.S.A. Such data are essential to inform the development of appropriate treatment programs. METHODS: Twenty-five selected pain conditions were used to identify patients receiving care within the Henry Ford Health System (HFHS) who were enrolled in the Health Alliance Plan (HAP), a subsidiary of HFHS. Patients aged ≥ 18 years, enrolled in HAP in 2010, and having ≥ 2 encounters, ≥ 30 days apart, with an ICD-9-CM diagnosis code for a pain condition of interest during 2010 were counted. Variables included in the study were as follows: age, gender, body mass index (BMI), and Charlson comorbidity conditions and index score. RESULTS: Altogether, 14,784 persons (11.6% of the total adult population) met the criteria for having a chronic pain condition. Overall, the study population was 64.4% female and had mean age (SD) of 61.2 (15.6) years and mean BMI of 31.4 (7.2) kg/m(2) . Musculoskeletal pain conditions were the most common diagnoses, comprising 75.4% of all pain diagnoses. Diabetes and chronic pulmonary disease were the most common medical comorbidities. CONCLUSIONS: In this comprehensive analysis of 2 years of data from a large, vertically integrated metropolitan health system, chronic pain was identified in 12% of adult patients. Approximately 75% of chronic pain conditions were musculoskeletal. The triad of age ≥ 60 years, BMI ≥ 30, and female sex were the most salient demographic characteristics of patients with chronic pain conditions. These diagnostic and demographic data may be used to inform treatment program development.

Clinical and Economic Implications of Apixaban Versus Aspirin in the Low-Risk Nonvalvular Atrial Fibrillation Patients.

BACKGROUND AND PURPOSE: Although recommended by guidelines, the benefits of treating patients with atrial fibrillation with a low-stroke risk score, with aspirin or anticoagulants, have not been clearly established. With advent of safer non-vitamin K antagonist oral anticoagulant, we assessed the clinical and economic implications of 5 mg BID of apixaban versus aspirin among patients with a relative low risk of stroke as assessed using the CHADS2 (congestive heart failure, hypertension, age>75, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke/transient ischemic attack, vascular disease) stroke risk classification. METHODS: A previously developed and validated Markov model was adapted. A secondary analysis of the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study was conducted to estimate event rates in different low-risk cohorts by treatment. Three cohorts (n=1000) with a CHADS2 score of 1, CHA2DS2-VASc score of 1, and CHA2DS2-VASc of score 2 to 4 were simulated to assess the number of clinical events avoided in terms of strokes and major bleeds, as well as life years gained, quality-adjusted life years gained, costs, and incremental costs per quality-adjusted life year gained. RESULTS: Apixaban was associated with fewer strokes and systemic embolism versus aspirin across all subgroups; however, it caused more major bleeding events. The reduction in systemic embolism offset the increase in major bleeding events leading to increased life expectancy and quality-adjusted life year gains, achieved at an increased cost that was lower than the UK threshold of $44,400 (ie, £30,000) per quality-adjusted life year gained across the 3 cohorts examined. CONCLUSIONS: Anticoagulant treatment with apixaban versus aspirin in low-risk patients, as identified using CHADS2 or CHA2DS2-VASc, is projected to increase life expectancy and provide clinical benefits that are cost effective.

Impact of Etanercept Therapy on Disease Activity and Health-Related Quality of Life in Moderate Rheumatoid Arthritis Patients Population from a National British Observational Cohort.

OBJECTIVES: To describe a population with moderate rheumatoid arthritis (RA) before biologic initiation and assess change in disease status, health-related quality of life (HRQOL), and adverse events in etanercept (ETN)-treated patients. METHODS: Data on adult patients with moderate RA (3.2 < Disease Activity Score in 28 Joints [DAS28] ≤ 5.1) were retrospectively analyzed from the British Society for Rheumatology Biologics Register comparing a nonbiologic-treated group (nBG) using at least one traditional disease-modifying antirheumatic drug to a biologic group (BG) treated with ETN. The HRQOL was assessed by using the Health Assessment Questionnaire disability index score. To mitigate confounding, we controlled for drivers of progression. Appropriate univariate, multivariate, and regression analyses were used. RESULTS: A total of 1754 patients with RA were assessed (211 BG and 1543 nBG). Compared with the nBG, the BG tended toward higher disease activity, such as significantly higher tender joints and DAS28. The BG compared with the nBG had 1) a greater reduction in DAS28 and Health Assessment Questionnaire scores; 2) disease remission occurring more often (odds ratio = 2.7; P = 0.006); and 3) progression occurring in fewer patients (odds ratio = 0.3; P = 0.002). BG patients had a higher incidence of "other serious infection" and "other central nervous system-related events," with no significant differences in associated hospitalization rates or deaths. CONCLUSIONS: Among patients with moderate RA from a clinical practice registry, ETN-treated patients had significantly higher disease activity at the time of biologic initiation but significantly reduced disease activity and better HRQOL after 6 months compared with nBG patients, although the possibility of unmeasured confounding remains. The ETN group reported significantly higher incidences of "other serious infections" and "other central nervous system-related events" without higher hospitalization rates.

Prescription opioid abuse and tampering in the United States: results of a self-report survey.

OBJECTIVE: The objective of this study is to estimate the prevalence and impact of prescription opioid abuse and tampering among US adults. METHODS: Participants from the US National Health and Wellness Survey were invited to complete an online survey assessing use, misuse, and abuse of prescription opioid medications in the preceding 3 months. A total of 25,864 adults were screened for self-reported opioid abuse. Prevalence was calculated using weights based on age, gender, race, and education. Respondents reporting abuse or medical use of prescription opioid medication in the prior 3 months (N = 1,242) completed a questionnaire assessing health care resource use and the Work Productivity and Activity Impairment questionnaire. RESULTS: The prevalence of prescription opioid abuse in the 3 months prior to the survey was estimated at 1.31% of US adults, with approximately half (0.67%) tampering during that time. Opioid abuse increased with younger age, male sex, minority race, psychiatric illness, alcoholism, cigarette smoking, being employed, and higher household income. Respondents abusing opioid medications reported greater impairment in work and nonwork activities and more health care use than nonusers. Tampering with opioid medication was associated with greater productivity loss and increased use of health care (all P < 0.05). CONCLUSIONS: Tampering with opioid medications to get high is associated with substantial loss of productivity and health care use. Technologies that reduce users' ability to tamper may reduce the burden of opioid abuse on the health care system.