Effectiveness, Safety, and Costs of Thromboprophylaxis with Enoxaparin or Unfractionated Heparin Among Medical Inpatients With Chronic Obstructive Pulmonary Disease or Heart Failure.

Background: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are risk factors for venous thromboembolism (VTE). Enoxaparin and unfractionated heparin (UFH) help prevent hospital-associated VTE, but few studies have compared them in COPD or HF. Objectives: To compare effectiveness, safety, and costs of enoxaparin vs UFH thromboprophylaxis in medical inpatients with COPD or HF. Methods: This retrospective cohort study included adults with COPD or HF from the Premier PINC AI Healthcare Database. Included patients received prophylactic-dose enoxaparin or UFH during a >6-day index hospitalization (the first visit/admission that met selection criteria during the study period) between January 1, 2010, and September 30, 2016. Multivariable regression models assessed independent associations between exposures and outcomes. Hospital costs were adjusted to 2017 US dollars. Patients were followed 90 days postdischarge (readmission period). Results: In the COPD cohort, 114 174 (69%) patients received enoxaparin and 51 011 (31%) received UFH. Among patients with COPD, enoxaparin recipients had 21%, 37%, and 10% lower odds of VTE, major bleeding, and in-hospital mortality during index admission, and 17% and 50% lower odds of major bleeding and heparin-induced thrombocytopenia (HIT) during the readmission period, compared with UFH recipients (all P <.006). In the HF cohort, 58 488 (58%) patients received enoxaparin and 42 726 (42%) received UFH. Enoxaparin recipients had 24% and 10% lower odds of major bleeding and in-hospital mortality during index admission, and 13%, 11%, and 51% lower odds of VTE, major bleeding, and HIT during readmission (all P <.04) compared with UFH recipients. Enoxaparin recipients also had significantly lower total hospital costs during index admission (mean reduction per patient: COPD, 1280;HF,2677) and readmission (COPD, 379;HF,1024). Among inpatients with COPD or HF, thromboprophylaxis with enoxaparin vs UFH was associated with significantly lower odds of bleeding, mortality, and HIT, and with lower hospital costs. Conclusions: This study suggests that thromboprophylaxis with enoxaparin is associated with better outcomes and lower costs among medical inpatients with COPD or HF based on real-world evidence. Our findings underscore the importance of assessing clinical outcomes and side effects when evaluating cost-effectiveness.

Trends in Patient Transfers From Overall and Caseload-Strained US Hospitals During the COVID-19 Pandemic.

Importance: Transferring patients to other hospitals because of inpatient saturation or need for higher levels of care was often challenging during the early waves of the COVID-19 pandemic. Understanding how transfer patterns evolved over time and amid hospital overcrowding could inform future care delivery and load balancing efforts. Objective: To evaluate trends in outgoing transfers at overall and caseload-strained hospitals during the COVID-19 pandemic vs prepandemic times. Design, Setting, and Participants: This retrospective cohort study used data for adult patients at continuously reporting US hospitals in the PINC-AI Healthcare Database. Data analysis was performed from February to July 2023. Exposures: Pandemic wave, defined as wave 1 (March 1, 2020, to May 31, 2020), wave 2 (June 1, 2020, to September 30, 2020), wave 3 (October 1, 2020, to June 19, 2021), Delta (June 20, 2021, to December 18, 2021), and Omicron (December 19, 2021, to February 28, 2022). Main Outcomes and Measures: Weekly trends in cumulative mean daily acute care transfers from all hospitals were assessed by COVID-19 status, hospital urbanicity, and census index (calculated as daily inpatient census divided by nominal bed capacity). At each hospital, the mean difference in transfer counts was calculated using pairwise comparisons of pandemic (vs prepandemic) weeks in the same census index decile and averaged across decile hospitals in each wave. For top decile (ie, high-surge) hospitals, fold changes (and 95% CI) in transfers were adjusted for hospital-level factors and seasonality. Results: At 681 hospitals (205 rural [30.1%] and 476 urban [69.9%]; 360 [52.9%] small with <200 beds and 321 [47.1%] large with ≥200 beds), the mean (SD) weekly outgoing transfers per hospital remained lower than the prepandemic mean of 12.1 (10.4) transfers per week for most of the pandemic, ranging from 8.5 (8.3) transfers per week during wave 1 to 11.9 (10.7) transfers per week during the Delta wave. Despite more COVID-19 transfers, overall transfers at study hospitals cumulatively decreased during each high national surge period. At 99 high-surge hospitals, compared with a prepandemic baseline, outgoing acute care transfers decreased in wave 1 (fold change -15.0%; 95% CI, -22.3% to -7.0%; P < .001), returned to baseline during wave 2 (2.2%; 95% CI, -4.3% to 9.2%; P = .52), and displayed a sustained increase in subsequent waves: 19.8% (95% CI, 14.3% to 25.4%; P < .001) in wave 3, 19.2% (95% CI, 13.4% to 25.4%; P < .001) in the Delta wave, and 15.4% (95% CI, 7.8% to 23.5%; P < .001) in the Omicron wave. Observed increases were predominantly limited to small urban hospitals, where transfers peaked (48.0%; 95% CI, 36.3% to 60.8%; P < .001) in wave 3, whereas large urban and small rural hospitals displayed little to no increases in transfers from baseline throughout the pandemic. Conclusions and Relevance: Throughout the COVID-19 pandemic, study hospitals reported paradoxical decreases in overall patient transfers during each high-surge period. Caseload-strained rural (vs urban) hospitals with fewer than 200 beds were unable to proportionally increase transfers. Prevailing vulnerabilities in flexing transfer capabilities for care or capacity reasons warrant urgent attention.

Effectiveness, safety, and costs of thromboprophylaxis with enoxaparin or unfractionated heparin in inpatients with obesity.

Background: Obesity is a frequent and significant risk factor for venous thromboembolism (VTE) among hospitalized adults. Pharmacologic thromboprophylaxis can help prevent VTE, but real-world effectiveness, safety, and costs among inpatients with obesity are unknown. Objective: This study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH). Methods: A retrospective cohort study was performed using the PINC AI™ Healthcare Database, which covers more than 850 hospitals in the United States. Patients included were ≥18 years old, had a primary or secondary discharge diagnosis of obesity [International Classification of Diseases (ICD)-9 diagnosis codes 278.01, 278.02, and 278.03; ICD-10 diagnosis codes E66.0x, E66.1, E66.2, E66.8, and E66.9], received ≥1 thromboprophylactic dose of enoxaparin (≤40 mg/day) or UFH (≤15,000 IU/day) during the index hospitalization, stayed ≥6 days in the hospital, and were discharged between 01 January 2010, and 30 September 2016. We excluded surgical patients, patients with pre-existing VTE, and those who received higher (treatment-level) doses or multiple types of anticoagulants. Multivariable regression models were constructed to compare enoxaparin with UFH based on the incidence of VTE, pulmonary embolism (PE)---------related mortality, overall in-hospital mortality, major bleeding, treatment costs, and total hospitalization costs during the index hospitalization and the 90 days after index discharge (readmission period). Results: Among 67,193 inpatients who met the selection criteria, 44,367 (66%) and 22,826 (34%) received enoxaparin and UFH, respectively, during their index hospitalization. Demographic, visit-related, clinical, and hospital characteristics differed significantly between groups. Enoxaparin during index hospitalization was associated with 29%, 73%, 30%, and 39% decreases in the adjusted odds of VTE, PE-related mortality, in-hospital mortality, and major bleeding, respectively, compared with UFH (all p < 0.002). Compared with UFH, enoxaparin was associated with significantly lower total hospitalization costs during the index hospitalization and readmission periods. Conclusions: Among adult inpatients with obesity, primary thromboprophylaxis with enoxaparin compared with UFH was associated with significantly lower risks of in-hospital VTE, major bleeding, PE-related mortality, overall in-hospital mortality, and hospitalization costs.

Treatment patterns, healthcare resource use, and costs associated with uncomplicated urinary tract infection among female patients in the United States.

BACKGROUND: We evaluated associations between antibiotic prescription and healthcare resource use and costs (Part A), and between antibiotic switching and healthcare resource use, costs, and uncomplicated urinary tract infection recurrence (Part B) in female patients with uncomplicated urinary tract infection in the United States. METHODS: This retrospective cohort study of linked Optum and Premier Healthcare Database data included female patients ≥12 years old with an uncomplicated urinary tract infection diagnosis (index date), who were prescribed antibiotics during an outpatient/emergency department visit between January 1, 2013 and December 31, 2018. In Part A, patients were stratified by antibiotic prescription appropriateness: appropriate and optimal (compliant with Infectious Diseases Society of America 2011 guidelines for drug class/treatment duration) versus inappropriate/suboptimal (inappropriate drug class/treatment duration per Infectious Diseases Society of America 2011 guidelines, and/or treatment failure). In Part B, patients were stratified by treatment pattern (antibiotic switch vs no antibiotic switch). Healthcare resource use and costs during index episode (within 28 days of index date) and 12-month follow-up were compared. RESULTS: Of 5870 patients (mean age 44.5 years), 2762 (47.1%) had inappropriate/suboptimal prescriptions and 567 (9.7%) switched antibiotic. Inappropriate/suboptimal prescriptions were associated with higher healthcare resource use (mean number of ambulatory care and pharmacy claims [both p < 0.001]), and higher total mean cost (inpatient, outpatient/emergency department, ambulatory visits, and pharmacy costs) per patient ($2616) than appropriate and optimal prescriptions ($649; p < 0.001) (Part A). Antibiotic switching was associated with more pharmacy claims and higher total mean costs (p ≤ 0.01), and a higher incidence of recurrent uncomplicated urinary tract infection (18.9%) than no antibiotic switching (14.2%; p < 0.001) (Part B). CONCLUSIONS: Inappropriate/suboptimal prescriptions and antibiotic switching were associated with high costs, ambulatory care, and pharmacy claims, suggesting a need for improved uncomplicated urinary tract infection prescribing practices in the United States.

Risk factors, resource use, and cost of postoperative low cardiac output syndrome.

OBJECTIVE: Low cardiac output syndrome complicates recovery after cardiac surgery. We examined the incidence and risk factors for low cardiac output syndrome and its association with postoperative mortality, morbidity, resource use, and cost. METHODS: This cross-sectional retrospective observational study examined patients having cardiac surgery captured in the Premier Healthcare Database. Low cardiac output syndrome was defined as the requirement for postoperative mechanical circulatory support and/or hemodynamic instability requiring prolonged inotropic support. Incidence, risk factors, and association of low cardiac output syndrome with postoperative outcomes, including mortality, hospital and intensive care unit length of stay, hospital readmission, and cost at 30 days, 90 days, and 6 months, were examined. RESULTS: Among 59,810 patients from 164 hospitals having cardiac surgery between July 1, 2012, and June 30, 2014, low cardiac output syndrome developed in 6067 (10.1%) patients. Patients presenting in cardiogenic shock or systolic (± diastolic) heart failure were at greatest risk. Risk-adjusted in-hospital mortality was 12-fold greater with low cardiac output syndrome (odds ratio, 12.0; 95% confidence interval, 10.6-13.5). Risk-adjusted hospital costs (2019$; median [Q1, Q3]) were $64,041 [21,439] in patients who developed low cardiac output syndrome versus $48,086 [16,098] without; P < .001. Increased costs were driven by longer risk-adjusted hospital stay (10.1 [4.5] vs 8.5 [3.8] days); P < .001, intensive care unit (5.5 [2.5] vs 3.3 [1.5] days; P < .001) stay, and all-cause 30-day adjusted hospital readmission rates (mean [SD] 16.6 [8.2]% vs 13.9 [7.2]%; P < .001). CONCLUSIONS: Cardiac surgical patients who develop postoperative low cardiac output syndrome suffer greater mortality and have greater resource use, health care costs, and all-cause readmission, which informs perioperative decision making, and impacts hospital performance metrics and federal priority to reduce health care costs.

Epidemiology of Invasive Escherichia coli Infection and Antibiotic Resistance Status Among Patients Treated in US Hospitals: 2009-2016.

BACKGROUND: Published data is limited on the prevalence and risk of recurrence of extraintestinal invasive Escherichia coli infections (IEIs) in the United States. METHODS: The analysis included all inpatient and hospital-based outpatient visits occurring between 2009 and 2016 at hospitals with continuous microbiology data submission to the Premier Healthcare Database for 90 days before and 12 months after the admission or visit. IEI was defined as having positive E. coli culture from a normally sterile site (eg, blood, cerebrospinal fluid). The prevalence of IEI, 12-month risk of recurrent IEI, and antibiotic resistance were assessed. RESULTS: Overall, 144 944 725 hospital visits among 37 207 510 patients were analyzed, and 71 909 IEI events occurred in 67 583 patients, corresponding to an IEI prevalence of 0.50 events per 1000 visits and 1.82 events per 1000 patients. Recurrence was common: 26.9 per 1000 patients had a recurrent IEI in the 12 months after their infection. Most infections were community acquired (66.4%), and urosepsis was most common clinical syndrome (66.0%). The 30-day risk of IEI among patients undergoing transrectal ultrasound-guided prostate biopsy was high: 5.03 events per 1000 patients. Among all IEI cases with antibiotic susceptibility testing, 9.18% were resistant to extended-spectrum cephalosporins, 28.22% to fluoroquinolones, and 0.14% to carbapenems. Resistance to extended-spectrum cephalosporins increased from 5.46% to 12.97% during the 8-year study period. CONCLUSIONS: This real-world study indicates a substantial burden of IEI and recurrent IEI exists in the United States, as well as increasing resistance to extended-spectrum cephalosporins. Future research should explore risk factors of recurrent IEI aiming to effectively prevent such infections.

Comparative Effectiveness and Costs of Enoxaparin Monotherapy Versus Unfractionated Heparin Monotherapy in Treating Acute Coronary Syndrome.

BACKGROUND: Enoxaparin and unfractionated heparin (UFH) are guideline-recommended anticoagulants for patients with acute coronary syndrome (ACS), including unstable angina (UA) and myocardial infarction with (STEMI) or without ST-segment elevation (NSTEMI). Prior efficacy and safety evidence are mainly from clinical trials. Economic data are insufficient. This study examined the differences in utilization, effectiveness, safety, and costs in treating ACS between enoxaparin and UFH monotherapy using real-world data. METHODS: Using data from 859 US hospitals, inpatients ≥ 18 years of age with a diagnosis of an initial episode of ACS between 2010 and 2016 were identified. Outcomes included 30-day risk of non-fatal myocardial infarction (MI), recurrent angina, in-hospital mortality, composite ischemic complication (having MI/recurrent angina/death), major bleeding, and costs. Multivariable regression was used to compare outcomes between enoxaparin and UFH monotherapy. RESULTS: Among 1,048,053 eligible patients (UA: 219,259; NSTEMI: 582,134; STEMI: 246,660), the prevalence of enoxaparin monotherapy was 12.0%, 13.9%, and 5.1%, and the prevalence of UFH monotherapy was 45.1%, 43.1% and 59.8%, for UA, NSTEMI, and STEMI patients, respectively. Enoxaparin was associated with a lower risk of ischemic complications and death among NSTEMI, but not in UA or STEMI patients, and with a lower risk of major bleeding in all patients. Cost savings per patient during index admission and 30-day follow-up for enoxaparin over UFH was $2972 for UA, $2475 for NSTEMI, and $3050 for STEMI. CONCLUSIONS: Enoxaparin was associated with a lower risk of ischemic complications (including death), lower costs, and better safety than UFH among NSTEMI patients. Improving upstream selection of anticoagulants in appropriate populations may help optimize clinical outcomes and costs.

Contemporary trend of acute kidney injury incidence and incremental costs among US patients undergoing percutaneous coronary procedures.

OBJECTIVES: To assess national trends of acute kidney injury (AKI) incidence, incremental costs, risk factors, and readmissions among patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) during 2012-2017. BACKGROUND: AKI remains a serious complication for patients undergoing CAG/PCI. Evidence is lacking in contemporary AKI trends and its impact on hospital resource utilization. METHODS: Patients who underwent CAG/PCI procedures in 749 hospitals were identified from Premier Healthcare Database. AKI was defined by ICD-9/10 diagnosis codes (584.9/N17.9, 583.89/N14.1, 583.9/N05.9, E947.8/T50.8X5) during 7 days post index procedure. Multivariable regression models were used to adjust for confounders. RESULTS: Among 2,763,681 patients, AKI incidence increased from 6.0 to 8.4% or 14% per year in overall patients; from 18.0 to 28.4% in those with chronic kidney disease (CKD) and from 2.4 to 4.2% in those without CKD (all p < .001). Significant risk factors for AKI included older age, being uninsured, inpatient procedures, CKD, anemia, and diabetes (all p < .001). AKI was associated with higher 30-day in-hospital mortality (ORadjusted = 2.55; 95% CI: 2.40, 2.70) and readmission risk (ORadjusted = 1.52; 95% CI: 1.50, 1.55). The AKI-related incremental cost during index visit and 30-day readmissions were estimated to be $8,416 and $580 per inpatient procedure and $927 and $6,145 per outpatient procedure. Overall excess healthcare burden associated with AKI was $1.67 billion. CONCLUSIONS: AKI incidence increased significantly in this large, multifacility sample of patients undergoing CAG/PCI procedures and was associated with substantial increase in hospital costs, readmissions, and mortality. Efforts to reduce AKI risk in US healthcare system are warranted.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice.

PURPOSE: Accumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted. METHODS: Data from two US private healthcare claims repositories were employed. The source population comprised adults who received "intermediate-risk" or "high-risk" chemotherapy regimens for solid cancers or non-Hodgkin's lymphoma and first-cycle pegfilgrastim prophylaxis. From the source population, all patients who did not receive second-cycle pegfilgrastim prophylaxis ("comparison patients") were matched (1:1) to those who received it ("pegfilgrastim patients") based on cancer, regimen, and propensity score. Odds ratios (OR) for FN-broad and narrow definitions-during the second chemotherapy cycle were estimated for comparison patients versus pegfilgrastim patients using generalized estimating equations. RESULTS: A total of 2245 comparison patients (5.3 % of source population) were matched to pegfilgrastim patients; cohorts were well-balanced on baseline characteristics. Second-cycle FN incidence proportions for comparison and pegfilgrastim patients were 3.8 versus 2.2 % based on broad definition and 2.6 versus 0.8 % based on narrow definition; corresponding OR were 1.7 (95 % CI 1.2-2.5, p = 0.002) and 3.5 (95 % CI 2.0-6.0, p < 0.001). Results were similar within cancer/regimen-subgroups and were robust when using alternative methods for confounding adjustment. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients who received first-cycle pegfilgrastim prophylaxis in US clinical practice, a clinically relevant minority did not receive second-cycle prophylaxis. Second-cycle FN odds among this subset were significantly higher than they were among those who continued prophylaxis.

Validation of test performance characteristics and minimal clinically important difference of the 6-minute walk test in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The 6-minute walk test distance (6MWD) has been shown to be a valid and responsive outcome measure in patients with idiopathic pulmonary fibrosis (IPF). The analyses were based, however, on a single phase 3 trial and require validation in an independent cohort. OBJECTIVE: To confirm the performance characteristics and estimates of minimal clinically important difference (MCID) of 6MWD in an independent cohort of patients with IPF. METHODS: Patients randomized to placebo in the phase 3 CAPACITY trials who had a baseline 6MWD measurement were included in these analyses. The 6MWD and other functional parameters (lung function, dyspnea, and health-related quality of life) were measured at baseline and 24-week intervals. Validity and responsiveness were examined using Spearman correlation coefficients. The MCID was estimated using distribution- and anchor-based methods. RESULTS: The analysis comprised 338 patients. Baseline 6MWD was significantly correlated with lung function measures, patient-reported outcomes, and quality-of-life measures (validity). Compared with baseline 6MWD, change in 6MWD (responsiveness) showed stronger correlations with change in lung function parameters and quality-of-life measures. Dyspnea measured by the University of California San Diego Shortness of Breath Questionnaire showed the strongest correlations with 6MWD (baseline: coefficient -0.35; 48-week change: coefficient -0.37; both p < 0.001). The distribution-based analyses of MCID using standard error of measurement yielded an MCID of 37 m, and distribution-based analyses by effect size resulted in 29.2 m. The MCID by anchor-based analysis using criterion referencing (health events of hospitalization or death) was 21.7 m. CONCLUSIONS: The 6MWD is a valid and responsive clinical endpoint, which provides objective and clinically meaningful information regarding functional status and near-term prognosis. These results confirm previous findings in an independent cohort of patients with IPF.

Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors.

PURPOSE: Although studies have evaluated the risk and consequences of febrile neutropenia (FN) among patients receiving cancer chemotherapy in US clinical practice, none have focused on a broad group of patients with metastatic disease. METHODS: A retrospective cohort design and health care claims (2006 to 2011) from private health plans covering a geographically diverse US population of > 30 million persons annually were used. The study population included adults who underwent myelosuppressive chemotherapy for metastatic cancer of the breast (MBC), colon/rectum (MCRC), lung (MLC), ovaries (MOC), or prostate (MPC). For each patient, the first chemotherapy course and each cycle therein, along with each episode of FN and the consequences thereof, were identified. RESULTS: The most common regimens, by cancer type, were paclitaxel (18% of 15,318 patients with MBC); oxaliplatin, fluorouracil, and leucovorin (23% of 16,923 patients with MCRC); carboplatin plus paclitaxel (23% of 21,999 patients with MLC); carboplatin plus paclitaxel (49% of 7,433 patients with MOC); and docetaxel (68% of 4,667 patients with MPC). Across cancers, FN occurred in 13.1% to 20.6% of patients during their chemotherapy course, most often required hospitalization (89% to 94%), and most often occurred in the first cycle (23% to 36%). Among hospitalized patients with FN, mean length of stay ranged from 7.0 to 7.5 days, and inpatient mortality ranged from 3.9% to 10.3%; mean FN-related costs during the cycle ranged from $16,291 to $19,456. CONCLUSION: Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, FN is a frequent complication, associated with significant morbidity, mortality, and economic costs, and should be given careful consideration in the treatment of this population.

Risk of febrile neutropenia in patients receiving emerging chemotherapy regimens.

PURPOSE: Considerable evidence exists concerning the risk of febrile neutropenia (FN) associated with well-established, older chemotherapy regimens. Little is known, however, about the risks associated with many regimens that were introduced in the past decade and have become the predominant choice for certain cohorts of patients or are increasingly being used in clinical practice. METHODS: A retrospective cohort design and US healthcare claims data (2006-2011) were employed. Study subjects included adult patients receiving the following: docetaxel + cyclophosphamide (TC), 5-FU + epirubicin + cyclophosphamide (FEC), FEC followed by docetaxel (FEC → D), or docetaxel + carboplatin + trastuzumab (TCH) for non-metastatic breast cancer; TCH for metastatic breast cancer; 5-FU + leucovorin + irinotecan + oxaliplatin (FOLFIRINOX) for metastatic pancreatic cancer; and bendamustine (with rituximab [BR], without rituximab [B-Mono]) for non-Hodgkin's lymphoma (NHL). For each patient, the first qualifying chemotherapy course and each cycle therein were identified, as were the use of supportive care-colony-stimulating factors (CSF) and antimicrobials (AMB)-and unique FN episodes. RESULTS: The crude risk (incidence proportion) of FN during the chemotherapy course ranged from 8.8 (95 % CI 8.3-9.3) to 10.6 % (9.3-12.1) among the breast cancer regimens, was slightly higher for the NHL regimens (BR, 10.5 % [8.9-12.4]; B-Mono, 14.7 % [11.2-18.9]), and was markedly higher for FOLFIRINOX (24.7 % [17.9-33.1]). Most patients developing FN required inpatient care (range, 73-90 %). Use of CSF primary prophylaxis ranged from 17 (B-Mono) to 75 % (FEC → D); use of AMB primary prophylaxis ranged from 6 (FOLFIRINOX) to 13 % (B-Mono). CONCLUSION: The risk of FN among patients receiving selected emerging chemotherapy regimens is considerable, and most cases require inpatient care. Use of CSF and AMB prophylaxis, however, varies substantially across regimens.

Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: the importance of duration of prophylaxis.

BACKGROUND: To examine duration of daily filgrastim prophylaxis, and risk and consequences of chemotherapy-induced neutropenic complications (CINC) requiring inpatient care. METHODS: Using a retrospective cohort design and US healthcare claims data (2001-2010), we identified all cancer patients who initiated ≥1 course of myelosuppressive chemotherapy and received daily filgrastim prophylactically in ≥1 cycle. Cycles with daily filgrastim prophylaxis were pooled for analyses. CINC was identified based on hospital admissions with a diagnosis of neutropenia, fever, or infection; consequences were characterized in terms of hospital mortality, hospital length of stay (LOS), and CINC-related healthcare expenditures. RESULTS: Risk of CINC requiring inpatient care-adjusted for patient characteristics-was 2.4 (95% CI: 1.6-3.4) and 1.9 (1.3-2.8) times higher with 1-3 (N = 8371) and 4-6 (N = 3691) days of filgrastim prophylaxis, respectively, versus ≥7 days (N = 2226). Among subjects who developed CINC, consequences with 1-3 and 4-6 (vs. ≥7) days of filgrastim prophylaxis were: mortality (8.4% [n/N = 10/119] and 4.0% [3/75] vs. 0% [0/34]); LOS (means: 7.4 [N = 243] and 7.1 [N = 99] vs. 6.5 [N = 40]); and expenditures (means: $18,912 [N = 225] and $14,907 [N = 94] vs. $13,165 [N = 39]). CONCLUSIONS: In this retrospective evaluation, shorter courses of daily filgrastim prophylaxis were found to be associated with an increased risk of CINC as well as poorer outcomes among those developing this condition. Because of the limitations inherent in healthcare claims databases specifically and retrospective evaluations generally, additional research addressing these limitations is needed to confirm the findings of this study.

Retrospective Study of the Prevalence, Predictors, and Consequences of Nonadherence With Lapatinib in Women With Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab.

Background. Lapatinib is an oral small molecule dual tyrosine kinase inhibitor that has been shown to improve time to progression versus capecitabine in women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab. Objective. To describe extent, predictors, and consequences of nonadherence with lapatinib in women with MBC who were previously treated with trastuzumab. Methods. This was a retrospective observational study using data from a large health insurance claims databases spanning January 2000 to March 2010. Measures of lapatinib adherence included medication possession ratio (MPR), time to discontinuation (end of supply), time to first treatment interruption (gap during treatment of 30 days without supply), and duration of continuous therapy (time to gap of 30 days without supply or end of supply). Predictors of nonadherence to lapatinib and the association between nonadherence and outcomes, utilization, and costs were examined using multiple regression analysis. Results. A total of 666 patients met all inclusion criteria. Mean initial lapatinib dosage was 1161 mg daily; 63% received index lapatinib in combination with capecitabine. Mean MPR was 87%; 22% of patients had MPR < 80%. Median time to lapatinib discontinuation was 9.1 months (95% confidence interval = 8.0-10.2). Twenty-seven percent of patients had one or more treatment interruptions during follow-up. Median duration of continuous therapy was 5.9 months (95% confidence interval = 5.1-6.1). Concomitant therapy with a taxane was a predictor of nonadherence (odds ratio for MPR < 80% = 10.30; P < .001). There was a statistically significant association between nonadherence to lapatinib and greater number of outpatient visits (P = .028). Conclusions. In women with MBC who were previously treated with trastuzumab, mean adherence to lapatinib in typical clinical practice is relatively high overall, although there is a small group of patients with high nonadherence. Targeted efforts to improve adherence to lapatinib in this subgroup may be warranted.

Incidence, treatment, and consequences of chemotherapy-induced febrile neutropenia in the inpatient and outpatient settings.

OBJECTIVE: To examine the incidence, treatment, and consequences of febrile neutropenia across inpatient and outpatient care settings. METHODS: Data were obtained from Humedica's National Electronic Health Record-Derived Longitudinal Patient-Level Database (2007-2010). The study population included adult patients who received myelosuppressive chemotherapy for a solid tumor or non-Hodgkin's lymphoma. For each patient, each chemotherapy regimen course and each cycle within each regimen course was characterized. Febrile neutropenia episodes were identified on a cycle-specific basis based on any of the following: (1) absolute neutrophil count <1.0 × 10(9)/L and evidence of infection or fever; (2) inpatient diagnosis of neutropenia, fever, or infection; (3) outpatient diagnosis of neutropenia and non-prophylactic antimicrobial use; or (4) mention of febrile neutropenia in physician notes. Febrile neutropenia episodes were categorized as inpatient or outpatient based on the initial setting of care (i.e. acute-care inpatient facility vs. ambulatory care facility). Febrile neutropenia consequences included hospital length of stay and mortality (inpatient cases only), as well as number of febrile neutropenia-related outpatient encounters. RESULTS: Among the 2131 patients in this study, 401 experienced a total of 458 febrile neutropenia episodes. Risk of febrile neutropenia during the chemotherapy regimen course was 16.8% (95% CI: 15.3, 18.4). In cycle 1 alone, risk of febrile neutropenia was 8.1% (7.1, 9.3). Most febrile neutropenia episodes (83.2%) were initially treated in the inpatient setting; the hospital mortality rate was 8.1% (5.8, 11.1), and mean hospital length of stay was 8.4 days (7.7, 9.1). Among febrile neutropenia episodes initially treated in the outpatient setting (16.8%), the mean number of outpatient management encounters was 2.6 (2.1, 3.1), most of which were in the physician's office (69.2%) or emergency department (26.9%). CONCLUSIONS: Febrile neutropenia remains a common occurrence among patients receiving myelosuppressive chemotherapy and typically results in extended hospitalization and, for many patients, death. A minority of patients are, however, treated exclusively on an outpatient basis.

Risk and healthcare costs of chemotherapy-induced neutropenic complications in women with metastatic breast cancer.

BACKGROUND: The burden of chemotherapy-induced neutropenic complications (CINC) in women with metastatic breast cancer (MBC) is largely unknown and may differ across cancer populations due to variation in the characteristics of patients, their disease and their treatment. METHODS: This study employed a retrospective cohort design and US healthcare claims data (2003-2009). For each woman in the study database who received myelotoxic chemotherapy for MBC, the first observed course and each cycle within the course were characterized. Risk and healthcare costs of CINC - by care setting - were descriptively analyzed on an overall basis by chemotherapy cycle and chemotherapy regimen. RESULTS: Among 2,620 study subjects, most received chemotherapy with cyclophosphamide/doxorubicin (25%), docetaxel (20%) or paclitaxel (12%). Thirty-one percent of subjects received colony-stimulating factors (CSF) prophylactically in their first chemotherapy cycle and an additional 13% first received CSF prophylaxis after cycle one. CINC developed in 11% of subjects; among these subjects, 88% required inpatient care and 45% experienced CINC in the first cycle of chemotherapy. For CINC requiring inpatient care, costs averaged USD 12,869 (95% CI: USD 12,622-13,116), and for CINC requiring outpatient care only, USD 2,030 (CI: USD 1,925-2,135). CONCLUSION: CINC is a clinically and economically important threat among women with MBC, and should be an important consideration in the treatment of this population.

Incidence of reduced chemotherapy relative dose intensity among women with early stage breast cancer in US clinical practice.

Chemotherapy is widely used to treat early stage breast cancer (ESBC). Reductions and delays in dose administered--e.g., due to advanced age or febrile neutropenia (FN)--are generally believed to increase risk of disease progression and reduce survival. Little is known about incidence of reduced chemotherapy dose intensity among women with ESBC in the current era of US clinical practice. This study employed a retrospective cohort design and electronic medical records from > 65 community oncology/hematology clinics in > 35 states (2004-2010). The study population comprised adult women who received myelosuppressive chemotherapy for ESBC (stages I-IIIA). For each such woman, each unique cycle of chemotherapy within their first observed course was identified. Incidence of chemotherapy dose delays (≥ 7 days for any drug in ≥ 1 cycles), chemotherapy dose reductions (≥ 15% for any drug in ≥ 1 cycles), and low chemotherapy relative dose intensity (RDI <85% over the course) relative to published reference standards were descriptively analyzed for the seven most-frequently planned regimens in the study database. A total of 2,228 women (70% of the subjects who received chemotherapy for ESBC and met other selection criteria) initiated 1 of the 7 most-frequently planned regimens. Mean age of subjects was 54 years and 69% received primary prophylaxis against FN with a colony-stimulating factor. Incidence of dose delays, dose reductions, and low RDI was 31, 24, and 26%, respectively; low RDI typically was due to premature treatment discontinuation. For patients (n = 626) receiving the most common regimen (dose-dense AC-T: doxorubicin/cyclophosphamide, Q2 × 4 cycles, paclitaxel or docetaxel, Q2 × 4 cycles), incidence of dose delays, dose reductions, and low RDI was 42, 29, and 32%, respectively. In the current era of US clinical practice, chemotherapy dose delays and dose reductions are common among women with ESBC receiving frequently used myelosuppressive dose-dense, as well as conventional, chemotherapy regimens.

Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim as prophylaxis against hospitalization for neutropenic complications in patients with cancer receiving chemotherapy.

BACKGROUND: Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim in preventing hospitalization for febrile neutropenia (FN) during myelosuppressive chemotherapy has not been well characterized and is an important clinical question in oncology. METHODS: This study used a retrospective cohort design and US healthcare claims data. Source population included patients with solid tumors receiving filgrastim, pegfilgrastim, or sargramostim during their first observed course of chemotherapy between July 2001 and June 2007. For each patient, every unique chemotherapy cycle during the course was identified, along with each cycle in which filgrastim, pegfilgrastim, or sargramostim was administered by the fifth day of the cycle (ie, as prophylaxis). Risks of hospitalization for neutropenic complications (broad definition: admission with a diagnosis of neutropenia, fever, or infection; narrow definition: admission with a diagnosis of neutropenia) and for any reason were examined on a cycle-specific basis during all the cycles in which colony-stimulating factor prophylaxis was administered. Unadjusted and adjusted odds ratios (ORs) for hospitalization were estimated. RESULTS: Risk (unadjusted) of hospitalization for neutropenic complications (narrow definition) was 2.1% for filgrastim prophylaxis (n=8286), 1.1% for pegfilgrastim prophylaxis (n=67,247), and 2.5% for sargramostim prophylaxis (n=1736). Corresponding risks of hospitalization based on the broad definition were 4.0%, 2.6%, and 5.1%. Risks of all-cause hospitalization were 7.9%, 5.3%, and 9.6%, respectively. Adjusted odds of hospitalization were significantly higher for filgrastim [OR (range across the 3 alternative measures of hospitalization): 1.58-1.79; P<0.001] and sargramostim (OR: 1.89-2.68; P<0.001) versus pegfilgrastim. CONCLUSIONS: Risk of hospitalization for neutropenic complications during cancer chemotherapy is lower with pegfilgrastim prophylaxis than with filgrastim or sargramostim prophylaxis.

Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference.

RATIONALE: Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited. OBJECTIVES: To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF. METHODS: The study population included all 1,156 randomized patients in two clinical trials of IFN-γ1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID. MEASUREMENTS AND MAIN RESULTS: Correlation of percent-predicted FVC between measurements (mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%. CONCLUSIONS: FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference.

Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis.

RATIONALE: Several predictors of mortality in patients with idiopathic pulmonary fibrosis have been described; however, there is a need for a practical and accurate method of quantifying the prognosis of individual patients. OBJECTIVES: Develop a practical mortality risk scoring system for patients with idiopathic pulmonary fibrosis. METHODS: We used a Cox proportional hazards model and data from two clinical trials (n = 1,099) to identify independent predictors of 1-year mortality among patients with idiopathic pulmonary fibrosis. From the comprehensive model, an abbreviated clinical model comprised of only those predictors that are readily and reliably ascertained by clinicians was derived. Beta coefficients for each predictor were then used to develop a practical mortality risk scoring system. MEASUREMENTS AND MAIN RESULTS: Independent predictors of mortality included age, respiratory hospitalization, percent predicted FVC, 24-week change in FVC, percent predicted carbon monoxide diffusing capacity, 24-week change in percent predicted carbon monoxide diffusing capacity, and 24-week change in health-related quality of life. An abbreviated clinical model comprising only four predictors (age, respiratory hospitalization, percent predicted FVC, and 24-wk change in FVC), and the corresponding risk scoring system produced estimates of 1-year mortality risk consistent with observed data (9.9% vs. 9.7%; C statistic = 0.75; 95% confidence interval, 0.71­0.79). CONCLUSIONS: The prognosis for patients with idiopathic pulmonary fibrosis may be accurately determined using four readily ascertainable predictors. Our simplified scoring system may be a valuable tool for determining prognosis and guiding clinical management. Additional research is needed to validate the applicability and accuracy of the scoring system.