Evaluation of machine learning methodology for the prediction of healthcare resource utilization and healthcare costs in patients with critical limb ischemia-is preventive and personalized approach on the horizon?

BACKGROUND: Critical limb ischemia (CLI) is a severe stage of peripheral arterial disease and has a substantial disease and economic burden not only to patients and families, but also to the society and healthcare systems. We aim to develop a personalized prediction model that utilizes baseline patient characteristics prior to CLI diagnosis to predict subsequent 1-year all-cause hospitalizations and total annual healthcare cost, using a novel Bayesian machine learning platform, Reverse Engineering Forward Simulation™ (REFS™), to support a paradigm shift from reactive healthcare to Predictive Preventive and Personalized Medicine (PPPM)-driven healthcare. METHODS: Patients ≥ 50 years with CLI plus clinical activity for a 6-month pre-index and a 12-month post-index period or death during the post-index period were included in this retrospective cohort of the linked Optum-Humedica databases. REFS™ built an ensemble of 256 predictive models to identify predictors of all-cause hospitalizations and total annual all-cause healthcare costs during the 12-month post-index interval. RESULTS: The mean age of 3189 eligible patients was 71.9 years. The most common CLI-related comorbidities were hypertension (79.5%), dyslipidemia (61.4%), coronary atherosclerosis and other heart disease (42.3%), and type 2 diabetes (39.2%). Post-index CLI-related healthcare utilization included inpatient services (14.6%) and ≥ 1 outpatient visits (32.1%). Median annual all-cause and CLI-related costs per patient were $30,514 and $2196, respectively. REFS™ identified diagnosis of skin and subcutaneous tissue infections, cellulitis and abscess, use of nonselective beta-blockers, other aftercare, and osteoarthritis as high confidence predictors of all-cause hospitalizations. The leading predictors for total all-cause costs included region of residence and comorbid health conditions including other diseases of kidney and ureters, blindness of vision defects, chronic ulcer of skin, and chronic ulcer of leg or foot. CONCLUSIONS: REFS™ identified baseline predictors of subsequent healthcare resource utilization and costs in CLI patients. Machine learning and model-based, data-driven medicine may complement physicians' evidence-based medical services. These findings also support the PPPM framework that a paradigm shift from post-diagnosis disease care to early management of comorbidities and targeted prevention is warranted to deliver a cost-effective medical services and desirable healthcare economy.

Adherence to Rivaroxaban Compared with Other Oral Anticoagulant Agents Among Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Adherence to oral anticoagulant (OAC) agents is important for patients with nonvalvular atrial fibrillation (NVAF) to prevent potentially severe adverse events. OBJECTIVE: To compare real-world adherence rates and time to discontinuation for rivaroxaban versus other OACs (apixaban, dabigatran, and warfarin) among patients with NVAF using claims-based data. METHODS: Health care claims from the IMS Health Real-World Data Adjudicated Claims database (July 2012-June 2015) were analyzed. Adherence rate was defined as the percentage of patients with proportion of days covered (PDC) ≥ 0.80 and ≥ 0.90. Discontinuation was defined as a gap of more than 30 days between the end of a dispensing days of supply and the start date of the next fill, if any. Patients were included if they had ≥ 2 dispensings of rivaroxaban, apixaban, dabigatran, or warfarin at least 180 days apart (the first was considered the index date), had > 60 days of supply, had ≥ 6 months of pre-index eligibility, had ≥ 1 atrial fibrillation (AF) diagnosis pre-index or at index date, and had no valvular involvement. A logistic regression model was used to evaluate adherence to OAC therapy, while a Cox model was used to compare time to discontinuation; both models adjusted for baseline confounders. RESULTS: A total of 13,645 rivaroxaban, 6,304 apixaban, 3,360 dabigatran, and 13,366 warfarin patients were identified. A significantly higher proportion of rivaroxaban users (80.1%) was adherent to therapy (PDC ≥ 0.80 at 6 months) versus apixaban (75.8%), dabigatran (69.2%), and warfarin users (64.5%). After adjustment, the proportion of patients adherent to therapy remained significantly higher for rivaroxaban users versus apixaban (absolute difference [AD] = 5.8%), dabigatran (AD = 9.5%), and warfarin users (AD = 13.6%; all P < 0.001). More pronounced differences were found with a PDC ≥0.90. In addition, rivaroxaban users were significantly less likely to discontinue therapy compared with other OACs after adjustments (all P < 0.05). CONCLUSIONS: Among NVAF patients, rivaroxaban was associated with significantly higher adherence rates relative to other OACs whether using either a PDC of > 0.80 or > 0.90. Such differences in adherence could translate into improved patient outcomes and lower health care costs. DISCLOSURES: This research was funded by Janssen Scientific Affairs. Ashton, Crivera, and Schein are employees and stockholders of Janssen Scientific Affairs. Laliberté, Germain, Wynant, and Lefebvre are employees of Analysis Group, a consulting company that received research grants from Janssen Scientific Affairs in connection with this study. McHorney is an employee of Evidera, a consulting company that received research grants from Janssen Scientific Affairs in connection with this study. Peterson received research grants from Janssen Scientific Affairs in connection with this study. All authors contributed to concept and design. The data were collected by Germain, Wynant, Laliberté, and Lefebvre and interpreted primarily by McHorney and Peterson, with the assistance of Lefebvre, Laliberté, Ashton, Crivera, and Schein. The manuscript was written primarily by Laliberté, Germain, and Lefebvre, with the assistance of Wynant. Revisions were made primarily by Ashton, Crivera, McHorney, Schein, and Peterson.

Evaluation of US prescription patterns: Are treatment guidelines for cancer-associated venous thromboembolism being followed?

INTRODUCTION: Venous thromboembolism (VTE) is a common complication of cancer. Clinical practice guidelines recommend low-molecular-weight heparin (LMWH) for treatment of cancer-associated VTE, but it is unclear how frequently these are followed. This study assessed anticoagulation treatment patterns for VTE in newly diagnosed cancer patients in the United States. MATERIALS AND METHODS: MarketScan® claims records of more than 80 million insured members between January 1, 2009 and July 31, 2014 were retrospectively analyzed. Subjects were included if they were 18years of age or older, and had a diagnosis of cancer (9 solid tumor types) and VTE. Data were included for LMWH, warfarin, and other anticoagulants (fondaparinux and direct oral anticoagulants [DOACs]). Patients with anticoagulant treatment prior to cancer diagnosis were excluded. RESULTS: VTE developed in 6.2% of cancer patients (median, 181days after cancer diagnosis). VTE rates were highest for pancreatic (17.5%) and lung (12.6%) cancer and lowest for breast (4.2%) and prostate (4.1%) cancer. For patients for whom outpatient prescription data were available, warfarin was most commonly used (50.0%), followed by LMWH (40.0%) and other anticoagulants (10.0%). Over 6months, 13% of patients who initiated injectable anticoagulants remained on them compared with 30% of those who initiated oral anticoagulants. More patients switched from LMWH to warfarin and other anticoagulants (44%) versus those who switched from warfarin (28%). CONCLUSIONS: Warfarin was the most utilized anticoagulant for cancer-associated VTE despite guideline recommendations for LMWH. More patients remained on oral versus injectable agents, which may be related to self-injection burden and costs.

Patterns of international normalized ratio values among new warfarin patients with nonvalvular atrial fibrillation.

Limited information exists regarding the relationship between international normalized ratio (INR) control/stability and the discontinuation of warfarin therapy among patients with nonvalvular atrial fibrillation (NVAF). This study evaluated the association between INR stabilization and warfarin discontinuation and assessed INR patterns before and after INR stabilization among patients (≥18 years) with NVAF who newly initiated warfarin (Veterans Health Administration datasets; October 1, 2007 through September 30, 2012). Achievement of INR stabilization (≥3 consecutive in-range therapeutic INR measurements ≥7 days apart) was examined from warfarin initiation through the end of warfarin exposure. Proportion of time in therapeutic range during warfarin exposure was calculated (Rosendaal method) and categorized as at least 60% or less than 60%. Among 34 346 patients, 49.4% achieved INR stabilization (mean time to stabilization, 98 days). Approximately 40% of INR values were out-of-range, even after achieving stabilization. During 30 days following an INR 4.0 or higher, patients had more INR testing than the overall mean (2.51 vs. 1.67 tests). Warfarin discontinuation was 4.2 times more likely among patients without INR stabilization versus those with INR stabilization (P < 0.00001). Patients with poor INR control (time in therapeutic range <60%) were 1.76 times more likely to discontinue warfarin within 1 year (P < 0.0001). INR stabilization is a better predictor of warfarin discontinuation than poor INR control. Improved approaches are necessary to maintain appropriate anticoagulation levels among patients with NVAF.

Validation of the multivariable In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) prediction rule within an all-payer inpatient administrative claims database.

OBJECTIVE: To validate the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) prediction rule, in a database consisting only of inpatient claims. DESIGN: Retrospective claims database analysis. SETTING: The 2012 Healthcare Cost and Utilization Project National Inpatient Sample. PARTICIPANTS: Pulmonary embolism (PE) admissions were identified by an International Classification of Diseases, ninth edition (ICD-9) code either in the primary position or secondary position when accompanied by a primary code for a PE complication. The multivariable IMPACT rule, which includes age and 11 comorbidities, was used to estimate patients' probability of in-hospital mortality and classify them as low or higher risk (≤1.5% deemed low risk). PRIMARY AND SECONDARY OUTCOME MEASURES: The rule's sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the receiver operating characteristic curve statistic for predicting in-hospital mortality with accompanying 95% CIs. RESULTS: A total of 34,108 admissions for PE were included, with a 3.4% in-hospital case-fatality rate. IMPACT classified 11, 025 (32.3%) patients as low risk, and low risk patients had lower in-hospital mortality (OR, 0.17, 95% CI 0.13 to 0.21), shorter length of stay (-1.2 days, p<0.001) and lower total treatment costs (-$3074, p<0.001) than patients classified as higher risk. IMPACT had a sensitivity of 92.4%, 95% CI 90.7 to 93.8 and specificity of 33.2%, 95% CI 32.7 to 33.7 for classifying mortality risk. It had a high NPV (>99%), low PPV (4.6%) and an AUC of 0.74, 95% CI 0.73 to 0.76. CONCLUSIONS: The IMPACT rule appeared valid when used in this all payer, inpatient only administrative claims database. Its high sensitivity and NPV suggest the probability of in-hospital death in those classified as low risk by IMPACT was minimal.

Medication persistence and discontinuation of rivaroxaban and dabigatran etexilate among patients with non-valvular atrial fibrillation.

OBJECTIVE: To compare real-world persistence and discontinuation among non-valvular atrial fibrillation (NVAF) patients on rivaroxaban and dabigatran in the US. METHODS: A large nationally representative US claims database was used to conduct a retrospective cohort analysis of patients with NVAF on rivaroxaban or dabigatran between October 2010 and March 2013. The index date was the date of the first prescription of rivaroxaban or dabigatran. All patients had ≥6 months of data prior to the index date and were followed until the earliest of inpatient death, end of continuous enrollment, or end of the study period. Rivaroxaban patients were matched 1:1 with dabigatran patients using the propensity score matching technique. Cox proportional hazards models were employed to estimate the adjusted hazard ratios (aHRs) of non-persistence and discontinuation. Persistence was defined as absence of a refill gap of ≥60 days. Discontinuation was defined as no additional refill for at least 90 days and until the end of follow-up. RESULTS: A total of 30,337 NVAF patients on rivaroxaban or dabigatran met the study criteria. All 7259 rivaroxaban patients were matched 1:1 to dabigatran patients. Compared with dabigatran users, rivaroxaban patients were 11% less likely to become non-persistent with therapy (aHR: 0.89, 95% CI 0.84-0.95) and 29% less likely to discontinue therapy (aHR: 0.71, 95% CI 0.66-0.77). LIMITATIONS: Claims data are subject to miscoding and inaccuracies. Refill data may not fully reflect actual medication taken. Confounding may remain even after propensity score matching and additional adjustments in model. Longer follow-up may produce more precise estimates of persistence and discontinuation. CONCLUSIONS: This matched cohort analysis indicated that, compared to dabigatran, rivaroxaban was associated with better persistence and lower rates of discontinuation.

Out-of-range INR values and outcomes among new warfarin patients with non-valvular atrial fibrillation.

BACKGROUND: Although efficacious in stroke prevention in non-valvular atrial fibrillation, many warfarin patients are sub-optimally managed. OBJECTIVE: To evaluate the association of international normalized ratio control and clinical outcomes among new warfarin patients with non-valvular atrial fibrillation. SETTING: Adult non-valvular atrial fibrillation patients (≥18 years) initiating warfarin treatment were selected from the US Veterans Health Administration dataset between 10/2007 and 9/2012. METHOD: Valid international normalized ratio values were examined from the warfarin initiation date through the earlier of the first clinical outcome, end of warfarin exposure or death. Each patient contributed multiple in-range and out-of-range time periods. MAIN OUTCOME MEASURE: The relative risk ratios of clinical outcomes associated with international normalized ratio control were estimated. RESULTS: 34,346 patients were included for analysis. During the warfarin exposure period, the incidence of events per 100 person-years was highest when patients had international normalized ratio <2:13.66 for acute coronary syndrome; 10.30 for ischemic stroke; 2.93 for transient ischemic attack; 1.81 for systemic embolism; and 4.55 for major bleeding. Poisson regression confirmed that during periods with international normalized ratio <2, patients were at increased risk of developing acute coronary syndrome (relative risk ratio: 7.9; 95 % confidence interval 6.9-9.1), ischemic stroke (relative risk ratio: 7.6; 95 % confidence interval 6.5-8.9), transient ischemic attack (relative risk ratio: 8.2; 95 % confidence interval 6.1-11.2), systemic embolism (relative risk ratio: 6.3; 95 % confidence interval 4.4-8.9) and major bleeding (relative risk ratio: 2.6; 95 % confidence interval 2.2-3.0). During time periods with international normalized ratio >3, patients had significantly increased risk of major bleeding (relative risk ratio: 1.5; 95 % confidence interval 1.2-2.0). CONCLUSION: In a Veterans Health Administration non-valvular atrial fibrillation population, exposure to out-of-range international normalized ratio values was associated with significantly increased risk of adverse clinical outcomes.

Out-of-range international normalized ratio values and healthcare cost among new warfarin patients with non-valvular atrial fibrillation.

BACKGROUND: Patients with out-of-range international normalized ratio (INR) values <2.0 and >3.0 have been associated with increased risk of thromboembolic and bleeding events. INR monitoring is costly, because of associated physician and nurse time, laboratory resource use, and dose adjustments. OBJECTIVES: This study assessed the healthcare cost burden associated with out-of-range INR among warfarin initiator patients diagnosed with non-valvular atrial fibrillation (NVAF) in the US Veterans Health Administration (VHA) population. METHODS: Adult NVAF patients (≥18 years) initiating warfarin were selected from the VHA dataset for the study period October 1, 2007-September 30, 2012. Only valid INR measurements (0.5 ≤ INR ≤ 20) were examined for the follow-up period, from the index date (warfarin initiation date) until the end of warfarin exposure or death. All-cause healthcare costs within 30 days were measured starting from the second month (31 days post-index date) to the end of the study period. Costs for inpatient stays, emergency room, outpatient facility, physician office visits, and other services were computed separately. Multiple regression was performed using the generalized linear model for overall cost analysis. RESULTS: In total, 29,463 patients were included in the study sample. Mean costs for out-of-range INR ranged from $3419 to $5126. Inpatient, outpatient, outpatient pharmacy, and total costs were significantly higher after patients experienced out-of-range results (INR < 2, INR > 3), compared with in-range INR (2 ≤ INR ≤ 3). When exposed to out-of-range INR, patients also incurred higher mean total costs within 2-6 months ($3840-$5820) than after the first 6 months ($2789-$3503) of warfarin therapy. CONCLUSION: In the VHA population, INR measures outside of the 2-3 range were associated with significantly higher healthcare costs. Increased costs were especially apparent when INR values were below 2, although INR measures above 3 were also associated with higher costs relative to in-range values.

Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation.

OBJECTIVES: To compare real-world persistence and discontinuation among non-valvular atrial fibrillation (NVAF) patients on rivaroxaban and warfarin in the US. RESEARCH DESIGN AND METHODS: A large nationally representative US claims database was used to conduct a retrospective cohort analysis of patients with NVAF treated with rivaroxaban or warfarin from 1 July 2010 through 31 March 2013. Index date was the date of the first prescription of rivaroxaban or warfarin. All patients were followed until the earliest of inpatient death, end of continuous enrollment, or end of study period. Rivaroxaban patients were matched 1:1 by propensity scores. Medication persistence was defined as absence of refill gap of ≥ 60 days. Discontinuation was defined as no additional refill for at least 90 days and until the end of follow-up. Cox proportional hazards models were estimated to examine the adjusted hazard ratios (aHRs) of rivaroxaban vs. warfarin on non-persistence and discontinuation. RESULTS: A total of 32,886 NVAF patients on rivaroxaban or warfarin met the study inclusion criteria. Each of the 7259 rivaroxaban patients identified were matched 1:1 to warfarin patients. Patients on rivaroxaban had a significantly better rate of persistence (aHR: 0.63, 95% CI 0.59-0.68) and lower rate of discontinuation (aHR: 0.54, 95% CI 0.49-0.58) compared to warfarin recipients. LIMITATIONS: Claims data may have contained inaccuracies and miscoding. Confounding may remain even after propensity score matching and additional adjustments in model. Refill data may not fully reflect actual medication use. Longer follow-up may produce more precise estimates of persistence and discontinuation. CONCLUSION: This matched cohort analysis indicated that rivaroxaban was associated with significantly higher medication persistence and lower discontinuation rates compared to warfarin.

Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients.

BACKGROUND: Rivaroxaban was shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) in a randomized controlled trial setting. OBJECTIVE: To assess real-world safety, effectiveness, and persistence associated with rivaroxaban and warfarin in nonvalvular AF patients. METHODS: Healthcare claims from Symphony Health Solutions' Patient Transactional Datasets from May 2011 to July 2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin, with ≥2 AF diagnoses (ICD-9-CM: 427.31) and a CHADS2 score ≥1 during the 180 day baseline period were included. Cohorts were matched 1:4 using propensity score methods. Study outcomes were major bleeding, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, composite stroke and systemic embolism, and venous thromboembolism (VTE) events. Cox proportional hazard models were used to compare event and persistence rates. RESULTS: The matched sample included 3654 rivaroxaban and 14,616 warfarin patients. Matching was adequate, with all standardized differences in patient characteristics <10%. No significant differences were observed for bleeding and composite stroke and systemic embolism outcomes, although rivaroxaban users were associated with significantly fewer VTE events (hazard ratio [HR] = 0.36, 95% confidence interval [CI]: 0.24-0.54, p < 0.0001) compared to warfarin users. Rivaroxaban was also associated with a significantly lower risk of treatment non-persistence (HR = 0.66; 95% CI: 0.60-0.72, p < 0.0001). LIMITATIONS: Claims data may have contained inaccuracies, and mortality and laboratory data were not available. Confounding may still have been possible even after propensity score matching. Early use pattern of medications may have changed over time. CONCLUSION: This analysis suggests that rivaroxaban and warfarin do not differ significantly in real-world rates of composite stroke and systemic embolism and major, intracranial, or GI bleeding. Rivaroxaban, however, was associated with significantly fewer VTE events and significantly better treatment persistence compared with warfarin.

Impact of co-morbidities and patient characteristics on international normalized ratio control over time in patients with nonvalvular atrial fibrillation.

This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as "lower" TTR. CHADS2 score of ≥2 was defined as "higher" CHADS2. Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS2 score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions.

Burden of comorbidities among patients with atrial fibrillation.

OBJECTIVE: This study examined comorbidity prevalence and general medication use among individuals with atrial fibrillation in the United States to convey a more comprehensive picture of their total disease burden. METHODS: This was a retrospective, observational evaluation of responses to the 2009 wave of the annual Internet-based National Health and Wellness survey, which collects health data including epidemiologic data and information on medical treatment from a representative nationwide sample of adults in the United States. Responses were assessed to determine three measures of comorbidity: mean number of comorbidities, CHADS2 score reflecting stroke risk (0-6 points; low risk: 0; moderate risk: 1; high risk: ≥ 2), and scores on the Charlson Comorbidity Index, which is a measure of general comorbidity reflecting presence of a wide range of comorbidities. RESULTS: Of the overall sample, 1297 participants reported having been diagnosed with atrial fibrillation. Almost all (98%) of the predominantly male (65.1%) and older (≥ 65 years of age, 65.7%) population with atrial fibrillation had at least one additional comorbidity, and 90% had cardiovascular comorbidities. On the Charlson Comorbidity Index, 44.9% of the respondents had scores of 1-2 and 20.5% had scores of 3 or higher. High risk for stroke, demonstrated by a CHADS2 score of at least 2, was present in 45% and moderate risk (CHADS2 score 1) in 36%. Of the respondents with atrial fibrillation, 71% reported current use of medication to manage the condition, but only 48% of individuals at high risk for stroke reported use of anticoagulation therapy. Of those who reported having common risk factors for stroke, the majority reported receiving prescription therapy for these conditions. CONCLUSIONS: The health burden carried by patients often extends far beyond atrial fibrillation. Physicians should carefully consider comorbidities and concomitant medications when managing patients with atrial fibrillation.

Treatment failure rates and health care utilization and costs among patients with community-acquired pneumonia treated with levofloxacin or macrolides in an outpatient setting: a retrospective claims database analysis.

BACKGROUND: Macrolide antibiotics and fluoroquinolones are extensively used in the treatment of community-acquired pneumonia (CAP). OBJECTIVE: This analysis was conducted to compare treatment failure rates and health care utilization and cost outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient setting. METHODS: This was a retrospective analysis of claims data from a large US health plan. Patients were aged > or =18 years and had a primary diagnosis of CAP that was treated with oral levofloxacin or a macrolide in an outpatient setting (including physicians' offices, outpatient clinics, urgent care centers, and large ambulatory health centers). Patients were followed for 30 days after the index drug date to measure study outcomes. Multivariate regression analysis and a propensity score technique were used to compare rates of treatment failure and CAP-related health care utilization and costs. Two post hoc subgroup analyses were conducted in patients aged > or =50 and > or =65 years. RESULTS: Of the 7526 patients meeting the inclusion criteria, 2968 (39.4%) were treated with levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts, respectively. After adjustment for demographic characteristics, baseline comorbidities, and severity of illness, levofloxacin recipients were significantly less likely to experience treatment failure than macrolide recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood of treatment failure was significantly lower in levofloxacin recipients aged > or =50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and > or =65 years (OR = 0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of macrolide recipients. The magnitude of this difference was greatest in the subgroup aged > or =65 years, which had a 35% reduced risk of treatment failure compared with the corresponding group of macrolide-treated patients. The rate of CAP-related emergency department visits was significantly lower among patients receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no differences in CAP-related hospitalizations or total CAP-related health care costs between levofloxa-cin and macrolide recipients. CONCLUSIONS: Multivariate-adjusted rates of treatment failure in outpatients with CAP were significantly lower in those treated with levofloxacin relative to those treated with a macrolide. The lower rates of treatment failure with levofloxacin were consistently observed across all patients and in the subgroups aged > or =50 and > or =65 years. Rates of emergency department visits were also significantly lower among levofloxacin-treated patients, whereas overall CAP-related hospitali-zations and costs did not differ significantly between the 2 treatment groups.

Monitoring outcomes during long-term opioid therapy for noncancer pain: results with the Pain Assessment and Documentation Tool.

The increasingly common practice of long-term opioid therapy for chronic noncancer pain must be guided by ongoing assessment of four types of outcomes: pain relief, function, side effects, and drug-related behaviors. Our objective was to gather initial pilot data on the clinical application of a specialized chart note, the Pain Assessment and Documentation Tool (PADT), which was developed and tested with 27 physicians. This pilot test provided the means to collect cross-sectional outcome data on a large sample of opioid-treated chronic pain patients. Each of the physician volunteers (located in a variety of settings across the United States) completed the PADT for a convenience sample of personally treated chronic pain patients who had received at least three months of opioid therapy. Completion of the PADT required a clinical interview, review of the medical chart, and direct clinical observation. Data from the PADTs were collated and analyzed. The results suggested that the majority of patients with chronic pain achieve relatively positive outcomes in the eyes of their prescribing physicians in all four relevant domains with opioid therapy. Analgesia was modest but meaningful, functionality was generally stabilized or improved, and side effects were tolerable. Potentially aberrant behaviors were common but viewed as an indicator of a problem (i.e., addiction or diversion) in only approximately 10 percent of cases. Using the PADT physician ratings can be developed in four domains. In this sample, outcomes suggested that opioid therapy provided meaningful analgesia.

A new tool to assess and document pain outcomes in chronic pain patients receiving opioid therapy.

BACKGROUND: Opioid analgesics are the cornerstone of management for malignant pain. Their use in managing chronic, nonmalignant pain, albeit controversial, has increased in recent years. The decisions about whether to initiate opioid therapy or continue it over time should be guided by a comprehensive patient assessment. During long-term treatment, this assessment should focus on a broad range of outcomes, each of which should be documented in the medical record. OBJECTIVE: The goal of this study was to develop an instrument, the Pain Assessment and Documentation Tool (PADT), to focus on key outcomes and provide a consistent way to document progress in pain management therapy over time. METHODS: Items that assess 4 domains (pain relief, patient functioning, adverse events, and drug-related behaviors) were generated with input from a MEDLINE literature search and experts in pain and addiction management. The original tool was field tested by clinicians who applied it to the assessment of patients receiving long-term opioid therapy for the management of chronic, nonmalignant pain. Data analysis and debriefing telephone interviews with a formalized set of questions were then used to rephrase, delete, and refine items to create the final tool. RESULTS: A 6-member expert panel contributed to the initial development of the PADT. Twenty-seven clinicians completed the preliminary version of PADT for 388 patients. The original 59-item tool was modified to create a 41-item tool. The revised PADT was formatted for use as a chart note designed to assist clinicians in assessing and documenting 4 main outcome domains during long-term opioid use. CONCLUSIONS: In this study, the PADT appeared to be a useful tool for clinicians to guide the evaluation of several important outcomes during opioid therapy and provide a simple means of documenting patient care.

Comparison of resource utilization by patients treated with transdermal fentanyl and long-acting oral opioids for nonmalignant pain.

OBJECTIVE: To quantify resource utilization and costs incurred for patients who received transdermal fentanyl as their first long-acting analgesic for non-malignant pain, and to compare these with utilization and costs for similar patients dispensed other long-acting oral opioids. DESIGN: A retrospective matched cohort study using medical claims data from a large New England Insurer. PATIENTS: We identified 478 patients without cancer who received transdermal fentanyl during 1995-1998. We selected patients who had no previous long-acting opioid dispensings and were enrolled during the 180 days before and 30 days following the initial dispensing. We used propensity scores to identify a matched comparison group of 478 long-acting oral opioid users. RESULTS: Transdermal fentanyl and matched long-acting oral opioid users incurred identical median costs for outpatient medical services and prescriptions during 2 years of follow-up. A larger proportion of transdermal fentanyl patients were still taking their initial opioid analgesic at the end of the 2-year follow-up than were patients initially taking other long-acting opioids. Use of short-acting opioids tapered off more slowly among transdermal fentanyl patients than among long-acting opioid patients. In the first 6 months, the transdermal fentanyl patients had more hospital discharges than the long-acting oral opioid patients, but this difference appeared to reflect preexisting conditions. CONCLUSIONS: Users of fentanyl transdermal system and other long-acting opioids experienced essentially identical evolution of health services utilization and costs over a 2-year period. The choice of long-acting opioid analgesia does not appear to be a determinant of future medical costs.