Outcomes for nighttime bracing in adolescent idiopathic scoliosis based on brace wear adherence.

BACKGROUND: This study determined brace wear adherence for patients treated with nighttime braces and evaluated the effect of brace adherence on curve progression. METHODS: One hundred twenty-two patients with AIS ages 10-16 years, Risser stages 0-2, major curves 20°-40° treated with Providence nighttime braces prescribed to be worn at least 8 h per night were prospectively enrolled and followed until skeletal maturity or surgery. Brace adherence was measured using iButton temperature sensors after 3 months of brace initiation and at brace discharge. RESULTS: Curve types were single thoracolumbar/lumbar (62%, n = 76), double (36%, n = 44), and single thoracic (2%, n = 2). Brace adherence averaged 7.8 ± 2.3 h after 3 months (98% adherence) and 6.7 ± 2.6 h at brace discharge (84% adherence). Curves that progressed ≥ 6° had decreased brace adherence than non-progressive curves after 3 months (7.0 h vs. 8.1 h, p = 0.010) and at brace discharge (5.9 h vs. 7.1 h, p = 0.017). Multivariate logistic regression analysis showed that increased hours of brace wear [odds ratio (OR) 1.23, 95% confidence interval (CI) 1.06-1.46], single curves (OR 3.11, 95% CI 1.35-7.53), and curves < 25° (OR 2.61, 95% CI 1.12-6.44) were associated with non-progression at brace discharge. CONCLUSIONS: Patients treated with nighttime bracing have a high rate of brace adherence. Lack of curve progression is associated with increased brace wear. Nighttime bracing is effective at limiting curve progression in AIS single thoracolumbar/lumbar and double curves. LEVEL OF EVIDENCE: Prognostic Level 2.

Stratospheric ozone, UV radiation, and climate interactions.

This assessment provides a comprehensive update of the effects of changes in stratospheric ozone and other factors (aerosols, surface reflectivity, solar activity, and climate) on the intensity of ultraviolet (UV) radiation at the Earth's surface. The assessment is performed in the context of the Montreal Protocol on Substances that Deplete the Ozone Layer and its Amendments and Adjustments. Changes in UV radiation at low- and mid-latitudes (0-60°) during the last 25 years have generally been small (e.g., typically less than 4% per decade, increasing at some sites and decreasing at others) and were mostly driven by changes in cloud cover and atmospheric aerosol content, caused partly by climate change and partly by measures to control tropospheric pollution. Without the Montreal Protocol, erythemal (sunburning) UV irradiance at northern and southern latitudes of less than 50° would have increased by 10-20% between 1996 and 2020. For southern latitudes exceeding 50°, the UV Index (UVI) would have surged by between 25% (year-round at the southern tip of South America) and more than 100% (South Pole in spring). Variability of erythemal irradiance in Antarctica was very large during the last four years. In spring 2019, erythemal UV radiation was at the minimum of the historical (1991-2018) range at the South Pole, while near record-high values were observed in spring 2020, which were up to 80% above the historical mean. In the Arctic, some of the highest erythemal irradiances on record were measured in March and April 2020. For example in March 2020, the monthly average UVI over a site in the Canadian Arctic was up to 70% higher than the historical (2005-2019) average, often exceeding this mean by three standard deviations. Under the presumption that all countries will adhere to the Montreal Protocol in the future and that atmospheric aerosol concentrations remain constant, erythemal irradiance at mid-latitudes (30-60°) is projected to decrease between 2015 and 2090 by 2-5% in the north and by 4-6% in the south due to recovering ozone. Changes projected for the tropics are ≤ 3%. However, in industrial regions that are currently affected by air pollution, UV radiation will increase as measures to reduce air pollutants will gradually restore UV radiation intensities to those of a cleaner atmosphere. Since most substances controlled by the Montreal Protocol are also greenhouse gases, the phase-out of these substances may have avoided warming by 0.5-1.0 °C over mid-latitude regions of the continents, and by more than 1.0 °C in the Arctic; however, the uncertainty of these calculations is large. We also assess the effects of changes in stratospheric ozone on climate, focusing on the poleward shift of climate zones, and discuss the role of the small Antarctic ozone hole in 2019 on the devastating "Black Summer" fires in Australia. Additional topics include the assessment of advances in measuring and modeling of UV radiation; methods for determining personal UV exposure; the effect of solar radiation management (stratospheric aerosol injections) on UV radiation relevant for plants; and possible revisions to the vitamin D action spectrum, which describes the wavelength dependence of the synthesis of previtamin D3 in human skin upon exposure to UV radiation.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2021.

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.

Using the health belief model to assess racial/ethnic disparities in cancer-related behaviors in an NCI-designated comprehensive cancer center catchment area.

BACKGROUND: Racial and ethnic minorities experience well-documented disparities across the cancer trajectory. However, factors underlying these disparities may vary regionally. The Health Belief Model (HBM) was developed to explain and predict health-related prevention and early detection behaviors, particularly uptake of health services. Our goal was to use the HBM to guide an exploration of factors that contribute to racial/ethnic health disparities in the catchment area of a large National Cancer Institute-designated Comprehensive Cancer Center in the Southeastern United States. METHODS: We conducted a secondary analysis of data collected by the cancer center for its triennial Community Health Needs Assessment, which sampled adults from the center's 15-county catchment area. White non-Hispanics (WNHs; n = 887), Black non-Hispanics (BNHs; n = 78), Hispanics/Latinxs (H/Ls; n = 185), and those identifying as another race/ethnicity ("Others"; n = 39) were compared across key HBM variables, including demographic/psychosocial information, perceived benefits and barriers to preventive health behaviors, risk perception, and health behavior outcomes. RESULTS: Controlling for annual household income, relationship status, and age (for certain screening behaviors), significant differences were seen in information-seeking behaviors, risk perception, community attributes, discrimination, and distress. Non-WNH groups reported worse community attributes, higher everyday discrimination, lower health literacy, less confidence in their ability to get health information, and lower perceived risk of cancer. CONCLUSION: This analysis presents a better understanding of how HBM factors may influence health disparities in the cancer center's catchment area. Results describe the needs of community members from racial and ethnic minority groups, which will inform future research, education, outreach, and service activities.

Incidence of nephrotoxicity with prolonged aminoglycoside exposure in patients with cystic fibrosis.

Cystic fibrosis (CF) patients, with Pseudomonas aeruginosa infection, often require repeated aminoglycoside courses for the management of acute pulmonary exacerbations (APEs). Acute kidney injury (AKI) due to aminoglycosides has been reported; little data exist regarding long-term nephrotoxicity with repeated exposure. The objective of this study was to describe the incidence of acute and chronic nephrotoxicity due to cumulative intravenous (IV) aminoglycoside exposure. This is a retrospective, observational study of pediatric and adult CF patients admitted to an academic medical center between January 1, 2006 and October 1, 2018 for APE management. Patients were eligible for inclusion if they received at least five courses of an IV aminoglycoside for at least 7 days each. Cumulative weight-based aminoglycoside dose was reported in milligrams per kilogram. For each admission, baseline and highest serum creatinine were collected to assess the incidence of AKI. The baseline and final estimated glomerular filtration rate (eGFR) were calculated to assess long-term effects on renal function. Sixty-six patients, representing greater than 700 courses, were included in the final analysis. The median cumulative weight-based aminoglycoside dose was 1183 mg/kg of tobramycin or tobramycin equivalent. Twenty percent of courses resulted in AKI; 86% were Stage 1. A repeated measure multivariate model showed colistin, piperacillin/tazobactam, vancomycin, and age were significant AKI risk factors. There was no correlation between cumulative aminoglycoside dose and change in eGFR. AKI from IV aminoglycoside exposure occurred in 20% of courses. Cumulative exposure to IV aminoglycosides in APE management was not correlated with long-term renal dysfunction.

Environmental effects of stratospheric ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2019.

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.

Ozone-climate interactions and effects on solar ultraviolet radiation.

This report assesses the effects of stratospheric ozone depletion and anticipated ozone recovery on the intensity of ultraviolet (UV) radiation at the Earth's surface. Interactions between changes in ozone and changes in climate, as well as their effects on UV radiation, are also considered. These evaluations focus mainly on new knowledge gained from research conducted during the last four years. Furthermore, drivers of changes in UV radiation other than ozone are discussed and their relative importance is assessed. The most important of these factors, namely clouds, aerosols and surface reflectivity, are related to changes in climate, and some of their effects on short- and long-term variations of UV radiation have already been identified from measurements. Finally, projected future developments in stratospheric ozone, climate, and other factors affecting UV radiation have been used to estimate changes in solar UV radiation from the present to the end of the 21st century. New instruments and methods have been assessed with respect to their ability to provide useful and accurate information for monitoring solar UV radiation at the Earth's surface and for determining relevant exposures of humans. Evidence since the last assessment reconfirms that systematic and accurate long-term measurements of UV radiation and stratospheric ozone are essential for assessing the effectiveness of the Montreal Protocol and its Amendments and adjustments. Finally, we have assessed aspects of UV radiation related to biological effects and human health, as well as implications for UV radiation from possible solar radiation management (geoengineering) methods to mitigate climate change.

Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

A trial of nebulised heparin to limit lung injury following cardiac surgery.

Cardiac surgery with cardiopulmonary bypass triggers an acute inflammatory response in the lungs. This response gives rise to fibrin deposition in the microvasculature and alveoli of the lungs. Fibrin deposition in the microvasculature increases alveolar dead space, while fibrin deposition in alveoli causes shunting. We investigated whether prophylactic nebulised heparin could limit this form of lung injury. We undertook a single-centre double-blind randomised trial. Forty patients undergoing elective cardiac surgery with cardiopulmonary bypass were randomised to prophylactic nebulised heparin (50,000 U) or placebo. The primary endpoint was the change in arterial oxygen levels over the operative period. Secondary endpoints included end-tidal CO2, the alveolar dead space fraction and bleeding complications. We found nebulised heparin did not improve arterial oxygen levels. Nebulised heparin was, however, associated with a lower alveolar dead space fraction (P <0.05) and lower tidal volumes at the end of surgery (P <0.01). Nebulised heparin was not associated with bleeding complications. In conclusion, prophylactic nebulised heparin did not improve oxygenation, but was associated with evidence of better alveolar perfusion and CO2elimination at the end of surgery.

Ozone depletion and climate change: impacts on UV radiation.

We assess the importance of factors that determine the intensity of UV radiation at the Earth's surface. Among these, atmospheric ozone, which absorbs UV radiation, is of considerable importance, but other constituents of the atmosphere, as well as certain consequences of climate change, can also be major influences. Further, we assess the variations of UV radiation observed in the past and present, and provide projections for the future. Of particular interest are methods to measure or estimate UV radiation at the Earth's surface. These are needed for scientific understanding and, when they are sufficiently sensitive, they can serve as monitors of the effectiveness of the Montreal Protocol and its amendments. Also assessed are several aspects of UV radiation related to biological effects and health. The implications for ozone and UV radiation from two types of geoengineering methods that have been proposed to combat climate change are also discussed. In addition to ozone effects, the UV changes in the last two decades, derived from measurements, have been influenced by changes in aerosols, clouds, surface reflectivity, and, possibly, by solar activity. The positive trends of UV radiation observed after the mid-1990s over northern mid-latitudes are mainly due to decreases in clouds and aerosols. Despite some indications from measurements at a few stations, no statistically significant decreases in UV-B radiation attributable to the beginning of the ozone recovery have yet been detected. Projections for erythemal irradiance (UVery) suggest the following changes by the end of the 21(st) century (2090-2100) relative to the present time (2010-2020): (1) Ozone recovery (due to decreasing ozone-depleting substances and increasing greenhouse gases) would cause decreases in UVery, which will be highest (up to 40%) over Antarctica. Decreases would be small (less than 10%) outside the southern Polar Regions. A possible decline of solar activity during the 21(st) century might affect UV-B radiation at the surface indirectly through changes induced in stratospheric ozone. (2) The projected changes in cloud cover would lead to relatively small effects (less than 3%), except at northern high latitudes where increases in cloud cover could lead to decreases in UVery by up to 7%. (3) Reductions in reflectivity due to the melting of sea-ice in the Arctic would lead to decreases of UVery by up to 10%, while at the margins of the Antarctic the decreases would be smaller (2-3%). The melting of the sea-ice would expose the ocean surface formerly covered by ice to UV-B radiation up to 10 times stronger than before. (4) The expected improvement of air-quality and reductions of aerosols over the most populated areas of the northern hemisphere may result in 10-20% increases in UVery, except over China where even larger increases are projected. The projected aerosol effect for the southern hemisphere is generally very small. Aerosols are possibly the most important factor for future UV levels over heavily populated areas, but their projected effects are the most uncertain.

Adherence patterns for abiraterone acetate and concomitant prednisone use in patients with prostate cancer.

BACKGROUND: With the growing use of oral anticancer medications, understanding adherence patterns has become increasingly important. Abiraterone acetate (AA) is a prodrug of abiraterone, a novel androgen biosynthesis inhibitor. AA is approved for use in combination with prednisone for treatment of patients with metastatic castration-resistant prostate cancer. OBJECTIVE: To evaluate AA and concomitant prednisone utilization and adherence patterns for patients with prostate cancer in the United States. METHODS: This study used data from 2 administrative health care claims databases--Dataset 1: Truven Health Analytics MarketScan (December 2010 to August 2012) and Dataset 2: Symphony Health Solutions' ProMetis Lx (June 2009 to March 2013). To evaluate the consistency of medication-taking behavior, adherence was measured using medication possession ratio (MPR), which was calculated as the sum of days of supply divided by the days on therapy in patients with at least 2 AA prescriptions. Additional outcomes included the proportion of patients taking prednisone, mean and median daily dose of AA, and concomitant prednisone use. Adherence was also studied by age, health care plan type, or previous recent chemotherapy subgroups. RESULTS: 515 patients (mean age: 72.2) and 3,228 patients (mean age: 72.2) with at least 1 AA claim were selected from Dataset 1 and Dataset 2, respectively. The mean (median) daily AA dose per person per prescription was 998.8 (1,000) mg for Dataset 1 and 994.2 (1,000) mg for Dataset 2, which is within 1% of the recommended daily dose (1,000 mg). Mean (median) MPR was 93% (98%; n = 492) in Study Population 1 and 93% (100%; n = 2,449) in Study Population 2. The mean (median) daily prednisone dose per person per prescription was similar in both datasets with 10.1 (10.0; n = 488) mg and 10.6 (10.0; n = 2,425) mg in Dataset 1 and 2, respectively. Similar adherence patterns were observed for patients in different age groups, for patients with commercial health care plans versus patients with Medicare coverage, and for patients with recent chemotherapy compared with patients without. CONCLUSIONS: Results from 2 observational studies reported high levels of adherence to AA dosing and administration patterns consistent with prescribing information. These findings provide useful insights into the treatment patterns in patients with prostate cancer treated with AA and can contribute to the current discussion in oncologic research and practice.

The alpha band of the resting electroencephalogram under pulsed and continuous radio frequency exposures.

The effect of GSM-like electromagnetic fields with the resting electroencephalogram (EEG) alpha band activity was investigated in a double-blind cross-over experimental paradigm, testing the hypothesis that pulsed but not continuous radio frequency (RF) exposure would affect alpha activity, and the hypothesis that GSM-like pulsed low frequency fields would affect alpha. Seventy-two healthy volunteers attended a single recording session where the eyes open resting EEG activity was recorded. Four exposure intervals were presented (sham, pulsed modulated RF, continuous RF, and pulsed low frequency) in a counterbalanced order where each exposure lasted for 20 min. Compared to sham, a suppression of the global alpha band activity was observed under the pulsed modulated RF exposure, and this did not differ from the continuous RF exposure. No effect was seen in the extremely low frequency condition. That there was an effect of pulsed RF that did not differ significantly from continuous RF exposure does not support the hypothesis that "pulsed" RF is required to produce EEG effects. The results support the view that alpha is altered by RF electromagnetic fields, but suggest that the pulsing nature of the fields is not essential for this effect to occur.

Real-World Corticosteroid Utilization Patterns in Patients with Metastatic Castration-Resistant Prostate Cancer in 2 Large US Administrative Claims Databases.

BACKGROUND: Prostate cancer is the most common noncutaneous malignancy in men in the United States. Patients with metastatic castration-resistant prostate cancer (mCRPC) may be treated with secondary hormonal therapy or with chemotherapy, and potentially with concomitant corticosteroids. Corticosteroids can help manage the side effects of chemotherapy and secondary hormonal therapy and ameliorate prostate cancer-related symptoms, although corticosteroids are also associated with adverse effects. With an increasing number of available treatment options for mCRPC, evaluating the real-world concomitant use of corticosteroids in this patient population is important. OBJECTIVE: To evaluate the utilization patterns of corticosteroids for the treatment of patients with mCRPC based on real-world data from 2 large claim databases. METHODS: This retrospective analysis included medical and pharmacy claims from 2 large publicly available healthcare claims databases covering more than 31 million individuals to identify treatment patterns in adult patients with mCRPC. A total of 2593 patients with mCRPC were identified in data set 1 and 626 patients in data set 2 between 2005 and 2011. The appropriate treatment for castration-resistant prostate cancer (CRPC) was defined as chemotherapy, an antiandrogen, an adrenal androgen blocker, or estrogen. The index date was the date of the first CRPC treatment or the first metastasis diagnosis, whichever occurred later. The observation period spanned from the index date to the end of health insurance eligibility. Study end points included population characteristics, the distribution of mCRPC therapies, and corticosteroid utilization patterns. RESULTS: The study population came from the 2 data sets and included 3219 men who were treated for mCRPC. Bone and lymph nodes were the predominant metastatic sites. Bicalutamide was the most common secondary hormonal therapy, and docetaxel was the most common chemotherapy used for these patients. Overall, 73.4% of the patients in data set 1 received concomitant corticosteroids, as did 71.6% of patients in population 2 during the entire period from the index date to the end of eligibility date. In addition, 62.8% and 60.4% of patients, respectively, received concomitant corticosteroids during the secondary hormonal therapy period, and 93.8% and 95.1% of patients, respectively, received concomitant corticosteroids during the chemotherapy period. Similar patterns of corticosteroid use were observed across geographic areas of the United States. CONCLUSION: This study shows consistently similar utilization patterns of corticosteroids in patients with mCRPC in 2 large national databases. Using real-world data to inform concomitant corticosteroid use in the treatment of patients with mCRPC may assist healthcare providers with treatment selection and with sequencing decision. Future research is warranted to investigate evolving treatment options for patients with mCRPC.

Constitutive activation of STAT3 in Sézary syndrome is independent of SHP-1.

Constitutive and persistent activation of STAT3 has been implicated in the pathogenesis of many malignancies. Studies of CTCL cell lines have previously suggested that aberrant activation of STAT3 is mediated via silencing of the negative regulator SHP-1 by promoter methylation. In this study of ex vivo tumour cell populations from 18 Sézary syndrome (SS) patients, constitutive phosphorylation of STAT3, JAK1 and JAK2 was present in all patients, but was absent in comparative CD4+ T-cells from healthy controls. Furthermore, no loss or significant difference in SHP-1 expression was observed between patients and healthy control samples. Methylation-specific PCR analysis of the SHP-1 CpG island in 47 SS patients and 11 healthy controls did not detect any evidence of methylation. Moreover, small interfering RNA knockdown of SHP-1 had no effect on phosphorylation of STAT3. In contrast, treatment of SS tumour cells with the pan-JAK inhibitor pyridone 6 led to downregulation of phosphorylated STAT3 (pSTAT3), its target genes and induction of apoptosis. No evidence for common JAK1/JAK2-activating mutations was found. These data demonstrate that constitutive activation of STAT3 in SS is not due to the loss of SHP-1, but is mediated by constitutive aberrant activation of JAK family members.

Outcomes of erythropoiesis-stimulating agents in cancer patients with chemotherapy-induced anemia.

PURPOSE: To assess the clinical and economic outcomes among patients with chemotherapy-induced anemia (CIA) treated with United States Food and Drug Administration-approved fixed dosing regimens of erythropoiesis-stimulating agents (ESA). METHODS: Data were employed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) registry to evaluate CIA patients who were initiated on either epoetin alfa (EPO) 40,000 Units (U) or darbepoetin alfa (DARB) 500 micrograms (mcg) between January 1, 2006 and May 8, 2009. Study measurements included ESA treatment dose and dose ratio, changes in hemoglobin (Hb) levels from baseline, and cumulative ESA costs. RESULTS: Five hundred forty patients treated in 44 clinical centers were evaluated, of which 420 were initiated on EPO 40,000 U and 120 were initiated on DARB 500 mcg. Both cohorts had similar baseline characteristics, although EPO patients were less likely than DARB patients to have received iron supplementation before ESA initiation (11.4% EPO vs. 20.0% DARB, p = 0.015). The EPO-to-DARB dose ratio based on cumulative ESA dose was 169:1 (U EPO: mcg DARB). EPO patients showed statistically greater Hb improvement compared to DARB patients, and compared to EPO patients, a greater proportion of DARB patients required a blood transfusion (13.9% EPO vs. 22.5% DARB, p = 0.026). Mean cumulative ESA cost was significantly lower for EPO patients than DARB patients ($4,261 EPO vs. $8,643 DARB, p < 0.0001). CONCLUSIONS: These findings reported that patients with CIA achieved more favorable clinical and economic outcomes if initiated with EPO 40,000 U vs. DARB 500 mcg.

Utilization and cost comparison of erythropoiesis-stimulating agents in inpatient and outpatient hospital settings.

OBJECTIVE: To compare utilization and associated costs of epoetin alfa (EPO) and darbepoetin alfa (DARB), two erythropoiesis-stimulating agents (ESAs), in patients with cancer undergoing chemotherapy and patients with chronic kidney disease (CKD) not on dialysis in inpatient and outpatient hospital settings. METHODS: An analysis of medical claims recorded between January 2006 and December 2009 was conducted using the Premier Perspective Comparative Hospital database. Patients included were ≥18 years old with cancer and chemotherapy or with pre-dialysis CKD and with ≥1 claim for EPO or DARB during a hospital inpatient or outpatient treatment episode. Patients treated with both ESAs or who were receiving dialysis were excluded. Mean cumulative drug costs and dose ratios (units EPO: mcg DARB) were calculated using cumulative dose and April 2010 wholesale acquisition costs. RESULTS: Cancer chemotherapy: 13,832 inpatient stays (EPO: 10,454; DARB: 3378) and 5590 outpatient treatment episodes (EPO: 2856; DARB: 2734) were identified. The inpatient and outpatient populations reported ESA dose ratios of 230:1 and 238:1 with DARB cost premiums of 42% (EPO: $948; DARB: $1348) and 38% (EPO: $3358; DARB: $4627), respectively. CKD: 148,746 hospital stays (EPO: 116,017; DARB: 32,729) and 11,012 outpatient treatment episodes (EPO: 6921; DARB 4091) were identified. The inpatient and outpatient populations reported ESA dose ratios of 251:1 and 257:1 with DARB cost premiums of 30% (EPO: $566; DARB: $738) and 27% (EPO: $2077; DARB: $2642), respectively. LIMITATIONS: The lack of randomization may have led to confounding by indication. In addition, statistical significance must be interpreted with caution in studies involving large samples. CONCLUSIONS: This study of 19,422 patients with cancer receiving chemotherapy and 159,758 patients with pre-dialysis CKD reported ESA dose ratios ranging from 230:1-257:1 (units EPO: mcg DARB) and associated cost premiums of 27-42% for DARB.

Adalimumab, etanercept, and infliximab utilization patterns and drug costs among rheumatoid arthritis patients.

OBJECTIVES: To evaluate the utilization patterns of the anti-tumor necrosis factor (anti-TNF) agents Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab) in patients with rheumatoid arthritis (RA) and compare medication costs during the first year of treatment. (Humira is a registered trademark of Abbott Laboratories, IL; Enbrel is a registered trademark of Immunex Corporation, CA; and Remicade is a registered trademark of Janssen Biotech, Inc., PA). METHODS: This retrospective analysis of medical and pharmacy claims included patients who were aged ≥18 years, had ≥2 RA diagnosis codes, and had ≥365 days of persistence with the index anti-TNF. Patients excluded had claims for anti-TNF agents within 6 months before the index date. Refill patterns for adalimumab and etanercept, number of infliximab infusions, time between infusions, and dose per infusion were analyzed for 12 months. Direct anti-TNF medication costs were compared among anti-TNFs for the initial treatment year. RESULTS: Infliximab-treated patients (n = 457) were significantly older than adalimumab- (n = 337) or etanercept-treated patients (n = 902). Time between refills was longer than recommended for 28% and 30% of adalimumab and etanercept refill periods, respectively. Potential cumulative time without therapy was 33 days for adalimumab and 43 days for etanercept. Statistically significant differences in mean per-patient anti-TNF medication costs for the first year were reported for adalimumab, etanercept, and infliximab ($14,991, $13,361, and $18,139, respectively; p < 0.0001); however, a cost assessment using labeled dosing of the anti-TNF agents with optimal treatment compliance yielded comparable annual medication costs. LIMITATIONS: This analysis only evaluated utilization patterns for selected anti-TNF agents and was not inclusive of other medications that patients may have been using for RA. Absolute patient adherence could not be assessed due to lack of information on how patients were self-administering adalimumab and etanercept or if samples of the agents were made available. CONCLUSIONS: This study identified gaps in patients' refills compared with prescriber recommendations. The infliximab-treated group had infusion patterns consistent with prescribing information. Potential clinical and economic implications of dose attenuation with adalimumab and etanercept should be explored further.

Hematologic outcomes and blood utilization in cancer patients with chemotherapy-induced anemia (CIA) pre- and post-national coverage determination (NCD): results from a multicenter chart review.

PURPOSE: In July 2007, the Centers for Medicare and Medicaid Services (CMS) limited coverage of erythropoiesis-stimulating agents (ESAs) in cancer patients with chemotherapy-induced anemia (CIA) through a National Coverage Determination (NCD). The primary objective of this study was to compare transfusion rates in patients with CIA with lung, breast, or colorectal cancer before and after the NCD. METHODS: Adult Medicare patients with CIA treated at 49 community oncology clinics were selected from two time periods based on clinics' NCD implementation date. Chart data were abstracted for 12 weeks post-CIA episode start, defined as hemoglobin (Hb) level <11 g/dL while receiving chemotherapy or within 60 days of the last chemotherapy dose. Multivariate analyses were used to calculate the odds of transfusion and to assess the units of blood transfused, controlling for differences in demographics, clinical history, and chemotherapy. RESULTS: Eight hundred pre-NCD and 994 post-NCD patients from 49 sites were selected. Of the patients, 56% used ESAs post-NCD vs. 88% pre-NCD (p < 0.0001). The duration of ESA use decreased in the post-NCD (32.1 days) vs. pre-NCD (48.4 days, p < 0.0001) group. The post-NCD group reported significantly lower Hb levels, higher odds of receiving a transfusion (odds ratio: 1.41, 95% CI 1.05-1.89, p = 0.0238) and increased blood utilization of 53% (units transfused: OR 1.53, 95% CI 1.15-2.04, p = 0.0034). CONCLUSIONS: Decreased frequency and duration of ESA administration were reported in the post-NCD vs. pre-NCD period. Findings were accompanied by a modest but statistically significant increase in transfusions and a decrease in Hb values.