Direct evidence of surface exposed water ice in the lunar polar regions.

Water ice may be allowed to accumulate in permanently shaded regions on airless bodies in the inner solar system such as Mercury, the Moon, and Ceres [Watson K, et al. (1961) J Geophys Res 66:3033-3045]. Unlike Mercury and Ceres, direct evidence for water ice exposed at the lunar surface has remained elusive. We utilize indirect lighting in regions of permanent shadow to report the detection of diagnostic near-infrared absorption features of water ice in reflectance spectra acquired by the Moon Mineralogy Mapper [M (3)] instrument. Several thousand M (3) pixels (∼280 × 280 m) with signatures of water ice at the optical surface (depth of less than a few millimeters) are identified within 20° latitude of both poles, including locations where independent measurements have suggested that water ice may be present. Most ice locations detected in M (3) data also exhibit lunar orbiter laser altimeter reflectance values and Lyman Alpha Mapping Project instrument UV ratio values consistent with the presence of water ice and also exhibit annual maximum temperatures below 110 K. However, only ∼3.5% of cold traps exhibit ice exposures. Spectral modeling shows that some ice-bearing pixels may contain ∼30 wt % ice that is intimately mixed with dry regolith. The patchy distribution and low abundance of lunar surface-exposed water ice might be associated with the true polar wander and impact gardening. The observation of spectral features of H2O confirms that water ice is trapped and accumulates in permanently shadowed regions of the Moon, and in some locations, it is exposed at the modern optical surface.

Does Emergency Medical Services Transportation Mitigate Post-stroke Discharge Disability? A Prospective Observational Study.

BACKGROUND: Whether emergency medical services (EMS) transport improves disability outcomes compared with other transport among acute ischemic stroke (AIS) patients is unknown. OBJECTIVE: To study severity-adjusted associations of hospital arrival mode (EMS vs. other transport) with in-hospital and discharge disability outcomes. DESIGN: Prospective observational study. PARTICIPANTS: AIS patients discharged April 2016 to October 2017 from a safety-net hospital in South Carolina. MAIN MEASURES: National Institutes of Health Stroke Scale (NIHSS) change at discharge (admission NIHSS score minus discharge NIHSS, continuous variable), 24-h NIHSS change (attaining high improvement, admission NIHSS minus 24-h NIHSS being 75th percentile or higher), door to neuroimaging (DTI) time, and IV alteplase receipt. NIHSS change was assessed within stroke severity groups, mild, moderate, and severe (admission NIHSS 0-5, 6-14, and ≥ 15, respectively). KEY RESULTS: Of 1168 patients, 838 were study-eligible (52% male, 52.4% Black, 72.2% EMS arrivals, 56.6% mild strokes). Severe and moderate stroke patients were more likely than mild stroke patients to use EMS (adjusted odds ratios, AOR [95% CI] 11.7 [5.0, 27.4] and 4.0 [2.6, 6.3], respectively). EMS arrival was associated with shorter DTI time (adjusted difference - 88.4 min) and higher likelihood of alteplase administration (AOR 5.3 [2.5, 11.4]), both key mediating variables in disability outcomes. High 24-h NIHSS improvement was more likely for EMS arrivals vs. other arrivals among moderate strokes (AOR 3.4 [1.1, 10.9]) and severe strokes (AOR > 999). EMS arrivals had substantially higher NIHSS improvement at discharge within the severe stroke group (adjusted NIHSS change at discharge, 5.9 points higher, p = 0.01). Alteplase recipients showed higher discharge NIHSS improvement than non-recipients (by 2.8 and 1.9 points among severe and moderate strokes, respectively; p = 0.01, 0.02). CONCLUSIONS: The findings offer evidence for including stroke education as a standard of care in the primary care management of patients with stroke-risk comorbidities/lifestyle in order to minimize post-stroke disability.

Why acute ischemic stroke patients in the United States use or do not use emergency medical services transport? Findings of an inpatient survey.

BACKGROUND: Patients with acute ischemic stroke (AIS) who use emergency medical services (EMS) receive quicker reperfusion treatment which, in turn, mitigates post-stroke disability. However, nationally only 59% use EMS. We examined why AIS patients use or do not use EMS. METHODS: During 2016-2018, a convenience sample of AIS patients admitted to a primary stroke center in South Carolina were surveyed during hospitalization if they were medically fit, available for survey when contacted, and consented to participate. The survey was programed into EpiInfo with skip patterns to minimize survey burden and self-administered on a touchscreen computer. Survey questions covered symptom characteristics, knowledge of stroke and EMS importance, subjective reactions, role of bystanders and financial factors. Descriptive and multiple regression analyses were performed. RESULTS: Of 108 inpatients surveyed (out of 1179 AIS admissions), 49% were male, 44% African American, mean age 63.5 years, 59% mild strokes, 75 (69%) arrived by EMS, 33% were unaware of any stroke symptom prior to stroke, and 75% were unaware of the importance of EMS use for good outcome. Significant factors that influenced EMS use decisions (identified by regression analysis adjusting for stroke severity) were: prior familiarity with stroke (self or family/friend with stroke) adjusted odds ratio, 5.0 (95% confidence interval, 1.6, 15.1), perceiving symptoms as relevant for self and indicating possible stroke, 26.3 (7.6, 91.1), and bystander discouragement to call 911, 0.1 (0.01,0.7). Further, all 27 patients who knew the importance of EMS had used EMS. All patients whose physician office advised actions other than calling EMS at symptom onset, did not use EMS. CONCLUSION: Systematic stroke education of patients with stroke-relevant comorbidities and life-style risk factors, and public health educational programs may increase EMS use and mitigate post-stroke disability.

To Treat or Not to Treat?

Background and Purpose- The 2015 updated US Food and Drug Administration alteplase package insert altered several contraindications. We thus explored clinical factors influencing alteplase treatment decisions for patients with minor stroke. Methods- An expert panel selected 7 factors to build a series of survey vignettes: National Institutes of Health Stroke Scale (NIHSS), NIHSS area of primary deficit, baseline functional status, previous ischemic stroke, previous intracerebral hemorrhage, recent anticoagulation, and temporal pattern of symptoms in first hour of care. We used a fractional factorial design (150 vignettes) to provide unconfounded estimates of the effect of all 7 main factors, plus first-order interactions for NIHSS. Surveys were emailed to national organizations of neurologists, emergency physicians, and colleagues. Physicians were randomized to 1 of 10 sets of 15 vignettes, presented randomly. Physicians reported the subjective likelihood of giving alteplase on a 0 to 5 scale; scale categories were anchored to 6 probabilities from 0% to 100%. A conjoint statistical analysis was applied. Results- Responses from 194 US physicians yielded 156 with complete vignette data: 74% male, mean age 46, 80% neurologists. Treatment mean probabilities for individual vignettes ranged from 6% to 95%. Treatment probability increased from 24% for NIHSS score =1 to 41% for NIHSS score =5. The conjoint model accounted for 25% of total observed response variance. In contrast, a model accounting for all possible interactions accounted for 30% variance. Four of the 7 factors accounted jointly for 58% of total relative importance within the conjoint model: previous intracerebral hemorrhage (18%), recent anticoagulation (17%), NIHSS (13%), and previous ischemic stroke (10%). Conclusions- Four main variables jointly account for only a small fraction (<15%) of the total variance related to deciding to treat with intravenous alteplase, reflecting high variability and complexity. Future studies should consider other variables, including physician characteristics.

Real-World Outcomes of Acute Ischemic Stroke Treatment with Intravenous Recombinant Tissue Plasminogen Activator.

BACKGROUND AND PURPOSE: In clinical trials, intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) reduces the likelihood of disability if given within 3 hours of acute ischemic stroke. This study compared real-world outcomes between patients treated and patients not treated with IV rt-PA. METHODS: In this retrospective study, United States-based neurologists randomly selected eligible acute ischemic stroke patients from their charts who were and were not treated with IV rt-PA. Mortality, hospital readmission, and independence were compared between patients treated and patients not treated with IV rt-PA using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. RESULTS: A total of 1026 charts were reviewed with a median follow-up time of 15.5 months. Pretreatment stroke severity, as measured by the National Institutes of Health Stroke Scale, was comparable between cohorts (IV rt-PA =11.7; non-rt-PA = 11.3; P = .165). IV rt-PA patients experienced significantly longer survival (P = .013), delayed hospital readmission (P = .012), and shorter time to independence (P < .001) compared with patients not treated with rt-PA. After adjusting for baseline characteristics, IV rt-PA patients had significantly lower mortality (hazard ratio [95% confidence interval] = .52 [.30, .90]) and greater rates of independence (hazard ratio [95% confidence interval] = 1.42 [1.17, 1.71]) than patients not treated with rt-PA. CONCLUSIONS: This real-world study indicated that acute ischemic stroke patients treated with IV rt-PA experience long-term clinical benefits in survival and functional status.

The Evolution of a Spacecraft-Generated Lunar Exosphere.

Understanding how spacecraft alter planetary environments can offer important insights into key physical processes, as well as being critical to planning mission operations and observations. In this context, it is important to recognize that almost any powered lunar landing will be an active volatile release experiment, due to the release of exhaust gases during descent. This presents both an opportunity to study the interaction of volatiles with the lunar surface, and a need to predict how non-indigenous gases are dispersed, and how long they persist in the lunar environment. This work investigates these questions through numerical simulations of the transport of water vapor during a nominal lunar landing and for two lunar days afterwards. Simulation results indicate that the water vapor component of spacecraft exhaust is globally redistributed, with a significant amount reaching permanently shadowed regions (cold traps) near the closest pole, where temperatures are sufficiently low that volatiles may remain stable over geological timescales. Exospheric evolution and surface deposition patterns are highly sensitive to desorption activation energy, providing a means to constrain this critical parameter through landed or orbital measurements during future missions. Contamination of cold traps by exhaust gases is likely to scale with exhaust mass and proximity of the landing site to the poles. Exhaust propagation is perhaps the most widespread and long-lived impact of spacecraft operations on a nominally airless solar system body, and should be a key consideration in mission planning and in interpreting measurements made by landed lunar missions, particularly at near-polar regions. PLAIN LANGUAGE SUMMARY: There has been increasing interest lately in learning more about the origin and distribution of water on the Moon. However, whenever a spacecraft descends to land on the lunar surface, it releases water vapor and other gases into the lunar environment, complicating the situation. In this work, we use computer simulations to understand what happens to the water released by a spacecraft during a typical landing. The simulated landing creates a temporary, very thin atmosphere all around the Moon. The behavior of this atmosphere depends on how strongly water sticks to the lunar surface, such that comparing simulations to measurements of water in the lunar environment during and after future lunar landings could help us figure out the "stickiness" of the lunar surface - something that we don't yet accurately know, but is important to understanding the past, present and future distribution of water on the Moon. Our simulations also show that some spacecraft-delivered water travels to regions near the poles that are cold enough to trap water for very long periods of time. If the spacecraft is heavier, or lands closer to the poles, its influence on the lunar surface and atmosphere may be more significant.

Widespread hematite at high latitudes of the Moon.

Hematite (Fe2O3) is a common oxidization product on Earth, Mars, and some asteroids. Although oxidizing processes have been speculated to operate on the lunar surface and form ferric iron-bearing minerals, unambiguous detections of ferric minerals forming under highly reducing conditions on the Moon have remained elusive. Our analyses of the Moon Mineralogy Mapper data show that hematite, a ferric mineral, is present at high latitudes on the Moon, mostly associated with east- and equator-facing sides of topographic highs, and is more prevalent on the nearside than the farside. Oxygen delivered from Earth's upper atmosphere could be the major oxidant that forms lunar hematite. Hematite at craters of different ages may have preserved the oxygen isotopes of Earth's atmosphere in the past billions of years. Future oxygen isotope measurements can test our hypothesis and may help reveal the evolution of Earth's atmosphere.

Impact of primary prophylaxis on febrile neutropenia within community practices in the US.

OBJECTIVE: To determine if granulocyte-colony-stimulating factor (G-CSF) primary prophylaxis is associated with a lower risk of febrile neutropenia (FN) than non-primary prophylaxis. METHODS: This was a retrospective, cohort study of medical records from a random sample of patients with solid tumours and lymphomas treated in 99 community oncology practices in 2003 (n=5319). Consecutively-sampled patients treated with chemotherapy and either filgrastim (Neupogen), pegfilgrastim (Neulasta) or no G-CSF were included (n=3123). Multivariate logistic regression estimated the odds of FN in patients receiving G-CSF primary prophylaxis (within 3 days of first chemotherapy cycle) compared with non-primary prophylaxis (delayed or no G-CSF). RESULTS: Patients receiving primary prophylaxis were less likely to develop FN than patients receiving non-primary prophylaxis (OR=0.49, 95% CI 0.34-0.71, p<0.001). Chemotherapy characteristics were associated with development of FN including, receipt of at least three chemotherapy drugs versus one (OR=2.13, 95% CI 1.17-3.89, p=0.014) and regimens with at least one myelosuppressive drug (OR=2.37, 95% CI 1.19-4.73, p=0.014). CONCLUSION: Patients receiving G-CSF primary prophylaxis had significantly lower odds of developing FN than those receiving non-primary prophylaxis. Incidence of FN may be underestimated, as care not recorded in the medical oncologist's chart was not captured.

Impact of neutropenic complications on short-term disability in patients with cancer receiving chemotherapy.

OBJECTIVES: The study examined the impact of chemotherapy-induced neutropenic complications (CINC), defined as neutropenia with fever or infection, on short-term disability (STD) among cancer patients receiving chemotherapy. METHODS: The key outcome metrics were average monthly STD days and associated indirect costs. Patients with and without CINC were propensity score (PS) matched. Multivariate regressions were conducted on PS-matched cohorts to estimate the marginal impact of CINC. RESULTS: A total of 280 patients with CINC were PS-matched to 280 patients without CINC. Compared with matched patients, patients with CINC on average experienced 0.9 more STD day (3.2 vs. 2.3, p=0.046) and $155 more in indirect costs ($549 vs. 394, p=0.050) per month. After multivariate adjustment, patients with CINC experienced 1.0 more STD day (p=0.029), and incurred $200 more in indirect cost (p=0.016) per month. CONCLUSIONS: Patients with CINC experience significantly greater STD leave than patients with no neutropenic complications from cancer chemotherapy. The overall study sample only included patients from large self-insured employers in the US and may not reflect the work loss experience of all employed patients in the US or other countries. Indirect costs associated with absenteeism and presenteeism were not measured.

A Retrospective, Longitudinal, Claims-Based Comparison of Concomitant Diagnoses Between Individuals with and Without Down Syndrome.

BACKGROUND: Individuals with Down syndrome (DS) experience various comorbidities in excess of the prevalence seen among the non-DS population. However, the extent of the excess burden of comorbidities specifically within commercially and publicly insured DS populations aged < 21 years is not currently known. OBJECTIVES: To (a) describe the most common diagnoses among individuals with DS who have either commercial or Medicaid insurance and (b) compare the prevalence of those diagnoses between DS cases and non-DS controls. METHODS: This was a longitudinal, retrospective study using health care claims of commercially insured and Medicaid-insured individuals in the Truven Health MarketScan Databases from 2008 to 2015. Individuals aged < 2, 2-5, 6-11, and 12-20 years with a DS diagnosis (cases; commercial: n = 15,948; Medicaid: n = 11,958) were matched to individuals without DS (controls; commercial: n = 47,844; Medicaid: n = 35,874) using a 1:3 ratio. The annual number of diagnoses was compared between cases and controls within age groups using t-tests, and the prevalence of the most common diagnoses was compared using chi-square tests. RESULTS: Cases in all age groups in both databases had more diagnoses annually than controls (mean =9-17 per year vs. 4-10 per year, P < 0.001), and the number of diagnoses decreased with age for cases and controls. Among the most common case diagnoses were upper respiratory infections (28.9%-59.1% vs. 19.5%-52.9%); suppurative otitis media (25.1%-56.8% vs. 8.7%-51.2%); nutrition/metabolic/developmental symptoms (37.9%-50.4% vs. 7.7%-10.6%); delays in development (22.8%-52.8% vs. 4.1%-10.9%); and general symptoms (35.1%-47.2% vs. 22.1%-37.2%), and the prevalence of each was greater among cases versus controls in all age groups in both databases (P < 0.001). The most common diagnoses among controls included some of the same as among cases, as well as acute pharyngitis (18.7%-31.8% vs. 19.2%-30.5%); allergic rhinitis (19.9%-24.3% vs. 15.3%-20.7%); viral/chlamydial infections (24.2%-26.6% vs. 17.7%-23.5%); and joint disorders (11.6% vs. 16.6%), and most were significantly more prevalent among cases (P < 0.05). CONCLUSIONS: Commercially insured and Medicaid-insured individuals aged < 21 years with DS experience a greater number and prevalence of concomitant diagnoses compared with non-DS individuals. Awareness of these common diagnoses could help facilitate the optimal care of these individuals by the pediatric health care community. DISCLOSURES: This study was sponsored and funded by Genentech. Truven Health Analytics, an IBM Company, receives payment from Genentech to conduct research, including the research for this study. Truven Health Analytics also receives payment from other pharmaceutical companies to conduct research. Kong and Evans are employed by Truven Health Analytics. Csoboth is employed by Genentech. Brixner reports fees paid to the University of Utah by Truven Health Analytics on her behalf for work related to this study. Hurley reports fees from Genentech for work on this study and for work outside of this study. At the time of this study, Visootsak was employed by F. Hoffman-LaRoche Pharmaceuticals, parent company of Genentech. All authors, including those affiliated with the study sponsor, were involved in the design of the study, interpretation of the data, writing of the manuscript, and the decision to submit the manuscript for publication. Study concept and design were contributed by Kong, Hurley, and Brixner, along with Evans. Kong and Evans collected the data, and data interpretation was performed by Csoboth, Visootsak, Brixner, and Hurley, with assistance from Kong. The manuscript was written by Evans, Kong, Hurley, and Brixner and revised by Kong, Hurley, Evans, and Brixner, with assistance from Csoboth and Visootsak.

The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis.

OBJECTIVE: Disease-modifying therapy (DMT) for multiple sclerosis (MS) can reduce relapses and delay progression; however, poor adherence and persistence with DMT can result in sub-optimal outcomes. The associations between DMT adherence and persistence and inpatient admissions and emergency room (ER) visits were investigated. METHODS: Patients with MS who initiated a DMT in a US administrative claims database were followed for 1 year. Persistence to initiated DMT was measured as the time from DMT initiation to discontinuation (a gap of >60 days without drug 'on hand') or end of 1-year follow-up. Adherence to initiated DMT was measured during the persistent period and was operationalized as the medication possession ratio (MPR). Patients with an MPR <0.80 were considered non-adherent. Claims during the 1-year follow-up period were evaluated for the presence of an all-cause inpatient admission or an ER visit. Adjusted odds ratios (AORs) for inpatient admission or ER visit comparing persistent vs non-persistent and adherent vs non-adherent patients were estimated using logistic regression models adjusted for patient characteristics. RESULTS: The final sample included 16,218 patients. During the 1-year follow-up period, 35.3% of patients discontinued their initiated DMT and 13.9% were not adherent while on therapy. During that same period, 10.0% of patients had an inpatient admission and 24.9% had an ER visit. The likelihoods of inpatient admission and ER visit were significantly decreased in persistent patients (AOR [95% CI] = 0.50 [0.45, 0.56] and 0.65 [0.60, 0.69], respectively) and in adherent patients (AOR [95% CI] = 0.83 [0.71, 0.97] and 0.86 [0.77, 0.95], respectively). CONCLUSIONS: Persistence and adherence with initiated DMT are associated with decreased likelihoods of inpatient admission or ER visit, which may translate to improved clinical outcomes.

Comparative effectiveness of colony-stimulating factors for febrile neutropenia: a retrospective study.

BACKGROUND: Granulocyte colony stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in cancer patients receiving myelosuppressive chemotherapy. There are two G-CSFs (pegfilgrastim and filgrastim) that differ in dosing schedules from which oncologists may prescribe. OBJECTIVES: This study aimed to compare the effectiveness of prophylactic pegfilgrastim and filgrastim on the risk of hospitalizations. The secondary objective was to compare the effectiveness of the timing of initiation (prophylactic versus delayed). METHODS: A retrospective study of administrative claims from US commercial payers included adult patients with Non-Hodgkin's lymphoma, breast, or lung cancer, treated with chemotherapy between July 2004 and January 2008. For these patients, the first course of chemotherapy and each unique cycle with use of G-CSF was identified and designated 'prophylaxis' if used within the first 5 days of each cycle, or 'delayed', if after day 5. The risk of neutropenia-related and all-cause hospitalization was evaluated for the pegfilgrastim and filgrastim prophylaxis cohorts and for the prophylaxis and delayed G-CSF initiation cohorts. RESULTS: Among 5,571 patient-cycles identified, 88.9% and 11.1% used pegfilgrastim and filgrastim respectively. The rate of neutropenic hospitalization was 1.1% for pegfilgrastim prophylaxis and 3.5% for filgrastim prophylaxis (P = 0.001). Compared to chemotherapy cycles with filgrastim prophylaxis, those with pegfilgrastim prophylaxis had decreased risk of neutropenia-related (adjusted odds ratio (OR) = 0.38, 95% confidence interval (CI) 0.17-0.83) and all-cause hospitalization (adjusted OR = 0.51, 95% CI 0.31-0.84). The neutropenic hospitalization rate was 1.2% for G-CSF prophylactic initiation and 3.7% for delayed G-CSF initiation (P < 0.001). Chemotherapy cycles with prophylactic initiation of either G-CSF had decreased risk of neutropenia-related (adjusted OR = 0.34, 95% CI 0.21-0.56) and all-cause hospitalization (adjusted OR = 0.67, 95% CI 0.49-0.91) compared with delayed initiation of G-CSF. CONCLUSIONS: Pegfilgrastim prescribed as prophylaxis resulted in lower risk of neutropenia-related and all-cause hospitalizations compared to filgrastim prophylaxis. This reduction was similar for prophylactic G-CSF initiation when compared to delayed G-CSF initiation.

LRO-LAMP observations of the LCROSS impact plume.

On 9 October 2009, the Lunar Crater Observation and Sensing Satellite (LCROSS) sent a kinetic impactor to strike Cabeus crater, on a mission to search for water ice and other volatiles expected to be trapped in lunar polar soils. The Lyman Alpha Mapping Project (LAMP) ultraviolet spectrograph onboard the Lunar Reconnaissance Orbiter (LRO) observed the plume generated by the LCROSS impact as far-ultraviolet emissions from the fluorescence of sunlight by molecular hydrogen and carbon monoxide, plus resonantly scattered sunlight from atomic mercury, with contributions from calcium and magnesium. The observed light curve is well simulated by the expansion of a vapor cloud at a temperature of ~1000 kelvin, containing ~570 kilograms (kg) of carbon monoxide, ~140 kg of molecular hydrogen, ~160 kg of calcium, ~120 kg of mercury, and ~40 kg of magnesium.

Use and cost of erythropoiesis-stimulating agents in patients with cancer.

OBJECTIVE: To compare the baseline characteristics, episodes of care, and cost of erythropoiesis-stimulating agents among cancer patients in a US managed-care population. RESEARCH DESIGN AND METHODS: Retrospective analysis of administrative claims data. Episodes of care for patients with cancer receiving erythropoiesis-stimulating agents between January 1, 2004 and January 17, 2006 included all claims for erythropoiesis-stimulating agents with < or = 42 days' gap between claims, plus the duration of therapeutic benefit based on median days between consecutive doses. MAIN OUTCOME MEASURES: Main outcome measures were average weekly dose of erythropoiesis-stimulating agents and costs of therapy. RESULTS: A total of 15,007 eligible episodes of care (darbepoetin alfa, 7769 episodes [5587 patients]; epoetin alfa 7238 episodes [5157 patients]) were identified. Fewer claims were observed per episode of care for darbepoetin alfa than for epoetin alfa (mean [SD] 3.7 [4.1] vs. 5.3 [6.4]). The median time between consecutive claims was 15 days (darbepoetin alfa) and 8 days (epoetin alfa). The mean (SD) weekly doses were 105 (56) microg (darbepoetin alfa) and 34,242 (28173) U (epoetin alfa), a dose-comparison ratio of 326 : 1. Dose-comparison ratios were sensitive to assumptions about duration of clinical benefit. The mean (95% CI) weekly costs were significantly lower for darbepoetin alfa ($560 [553-567]) than for epoetin alfa ($645 [630-659], p < 0.0001) when duration of clinical benefit was considered. CONCLUSIONS: Significant differences characterize patterns of use of erythropoiesis-stimulating agents. Duration of therapeutic benefit is an important variable in comparing darbepoetin alfa with epoetin alfa; incorporation of this variable in analyses of costs of therapy may have notable effects on calculated treatment costs. Limitations of the study include the potential for database errors or omissions, lack of detailed disease data, and lack of adjustment for differences in the ages and comorbidities of patients.