RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non-small-cell lung cancer ...(NSCLC).
The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS).
Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm
12.1% and 17.4% in the HD arm, respectively (
= .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7
20.3 months (
= .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% (
= .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms.
A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.
H-terminated Si nanocrystals undergo room temperature hydrosilylation with bifunctional alkenes with distal polar moietiesethyl ester, methyl ester, or carboxylic acidswithout the aid of light or ...added catalyst. The passivated Si nanocrystals exhibit bright photoluminescence (PL) and disperse in polar solvents, including water. We propose a reaction mechanism in which ester or carboxylic acid groups facilitate direct nucleophilic attack of the highly curved Si surface of the nanocrystals by the alkene.
Abstract Purpose Published prospective trials have questioned the role of post-lumpectomy radiotherapy in older women with early-stage, estrogen-receptor (ER) positive breast cancer. As the ...population with ER negative tumors may be at greater risk for relapse, particularly given that endocrine therapy is not effective, we hypothesize the addition of radiation would benefit in patients age ≥ 70. Methods and Materials The SEER database was queried from 1998 to 2011 for patients age ≥ 70 years receiving breast conserving surgery for T1, ER negative invasive ductal carcinoma. Patients were separated into two cohorts: those treated with and without adjuvant radiotherapy. Chi-square analysis, unpaired t-test and Kaplan-Meier log-rank were used to compare patient and tumor characteristics as well as overall and cancer-specific survival between the cohorts. Results Overall, 3,685 patients received radiation and 1,493 patients received lumpectomy alone. Patients treated with adjuvant radiation were younger (median age 76 versus 78 years, p<0.0001). Patients who received radiation had improved overall survival, with 5-year survival rates of 81.0% versus 61.7% without radiation (p<0.0001). Cancer-specific survival was also improved with radiotherapy, with 5-year cancer-specific survival rates of 93.1% versus 85.0% (p<0.0001). Conclusions This analysis of the SEER database demonstrates that women ages 70 and older treated with lumpectomy and radiotherapy for ER negative, early-stage breast cancer have improved overall survival and breast cancer-specific survival compared with patients treated with lumpectomy alone. This information may help in the decision making process for this patient population.
Exacerbations account for the greatest proportion of costs associated with chronic obstructive pulmonary disease (COPD). Here we aimed to evaluate, from the US payer perspective, the costs associated ...with moderate and severe COPD exacerbation events for patients treated with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) compared with FF/VI or UMEC/VI.
This post hoc, within-trial economic analysis used data derived from the InforMing the PAthway of COPD Treatment (IMPACT) study (NCT02164513).
Treatment groups within the IMPACT trial received either triple therapy with FF/UMEC/VI (100/62.5/25 mcg) or dual therapy (FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg). The primary end point for this IMPACT post hoc analysis was cost differences between the treatment arms related to 1-year on-treatment combined moderate and severe COPD exacerbation events.
The final study sample for this within-trial analysis consisted of 10,355 patients, 49% of whom experienced an on-treatment moderate or severe exacerbation during the study. The mean 1-year on-treatment cost estimate associated with combined moderate and severe exacerbations was highest with UMEC/VI and lowest with FF/UMEC/VI ($6205 vs $4913, respectively). Mean cost differences were statistically significant for all pairwise comparisons of FF/UMEC/VI with FF/VI or UMEC/VI (-$549 95% CI, -$565 to -$533 and -$1292 95% CI, -$1313 to -$1272, respectively; both P <.0001).
Treatment with FF/UMEC/VI compared with FF/VI or UMEC/VI in the US healthcare system resulted in lower exacerbation-related costs for combined moderate/severe exacerbation events, as well as moderate and severe exacerbations separately.
Suboptimal treatment of exacerbations is a major concern in management of chronic obstructive pulmonary disease (COPD). The Pharmacotherapy Management of COPD Exacerbation (PCE) Healthcare ...Effectiveness Data and Information Set (HEDIS) measure is a quality measure included by the National Committee for Quality Assurance that focuses on appropriate use of steroids and bronchodilators during an acute COPD exacerbation. There is limited evidence evaluating predictors of this quality measure, as well as its association with hospital readmission and cost outcomes.
To (a) describe characteristics of patients hospitalized for COPD, (b) evaluate factors associated with appropriate receipt of pharmacotherapy upon discharge, and (c) evaluate factors associated with the rate of readmission.
In this retrospective, observational, event-based study of COPD-related hospital and ED visits, events were identified between 2007 and 2013 from a Central Texas health plan using administrative claims data. The index date was defined as the date of admission. Subjects were included if they were aged ≥ 40 years and had a medical claim with a primary diagnosis for COPD or a pharmacy claim for a COPD maintenance medication during the 1-year pre-index period. Study groups were identified based on the receipt of PCE within the time frame specified by HEDIS: (a) a systemic corticosteroid within 14 days of discharge (PCE-C) or (b) a bronchodilator within 30 days of discharge (PCE-D). Bivariate analyses of potential factors associated with the receipt of PCE were performed using t-tests for continuous data and chi-square tests for categorical data. Generalized estimating equations, including significant predictors from the bivariate analyses, were used to determine factors associated with receipt of PCE-C and/or PCE-D, as well association with COPD-related and all-cause readmission within 6 months of discharge.
Of 375 identified index admissions, 254 (68%) patients received PCE-C; 299 (80%) received PCE-D; and 229 (61%) received both. Patients were more likely to receive PCE with an index inpatient visit as compared with an ED visit (PCE-C: RR = 2.25, 95% CI = 1.21-4.17, P = 0.010; PCE-D: RR = 1.90, 95% CI = 1.01-3.58, P = 0.048). Those with previous use of rescue medication were also more likely to receive PCE (PCE-C: RR = 1.88, 95% CI = 1.12-3.17, P = 0.018; PCE-D: RR = 2.11, 95% CI = 1.16-3.83, P = 0.014). Patients with greater adherence (proportion of days covered PDC ≥ 75%) to COPD maintenance medication before admission (RR = 8.67, 95% CI = 1.60-46.78, P = 0.012) were also more likely to receive PCE-D. Older patients were more likely to have a COPD-related readmission (RR = 1.07, 95% CI = 1.01-1.13, P = 0.028), while use of maintenance medication before admission was associated with lower risk of an all-cause readmission (RR = 0.49, 95% CI = 0.30-0.79, P = 0.004). In addition, patients with higher medical and pharmacy costs before the index event were more likely to have all-cause readmission (RR = 1.01, 95% CI = 1.00-1.02, P = 0.013). Receipt of PCE was not shown to be a significant predictor of all-cause or COPD-related readmission.
The use of bronchodilators and systemic corticosteroids after a COPD-related inpatient or ED visit may be related to the severity of the index COPD exacerbation or patients' previous pattern of bronchodilator use. However, the use of maintenance medication before the index event was associated with a significant reduction in all-cause readmission, so proper treatment of the underlying disease may be an effective strategy in reducing readmission.
Funding for this study was provided by GlaxoSmithKline (HO-14-15081). Tran was a Fellow at Scott & White Health Plan (SWHP) during year 1 of this study and a Fellow at Novartis during year 2 of this study. Novartis did not have any input in this study nor did it contribute any funding or support for this research. Tran, Xiang, Godley, and Stock were employed by SWHP at the time of this study. Rascati is employed by the University of Texas at Austin and also by the Journal of Managed Care & Specialty Pharmacy and has received consulting fees from GlaxoSmithKline. Coleman, Bogart, and Stanford are GlaxoSmithKline employees and shareholders. Study design was created by Rascati, Tran, and Godley, with assistance from Stock, Coleman, Bogart, and Stanford. Tran and Xiang collected the data, with data analysis and interpretation performed by Stock and Rascati. The manuscript was written by Tran, Rascati, and Xiang and revised by Godley, Stock, Coleman, Bogart, and Stanford.
Metalorganic vapor phase epitaxy was used to grow 15
μm of Al
0.26Ga
0.74N on GaN that was patterned with trenches 10
μm wide and 1
μm deep. The top of the AlGaN showed 4-μm-wide areas on either side ...of the trench centerline that had low threading dislocation densities, measured to be less than ∼1.5×10
8
cm
−2. Cross-sectional transmission electron microscopy showed that in the early stages of growth, AlGaN grew at an angle from the corners of the trench and eventually coalesced over the center. These laterally propagating growth sections overgrew the vertical growth in the trench bottom, with the result that low dislocation-density areas formed at the top of the AlGaN. Detailed examination showed that the vertical dislocations from the trench bottom were bent by the angled growth toward the center of the trench where they annihilated with other dislocations, allowing the low dislocation-density areas to form above. Elemental analysis showed that the angled growth sections had slightly lower Al content. The low dislocation-density areas are sufficiently wide to permit optically emitting devices to be grown.
Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models ...will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM) 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model's structure and in silico "experimental" data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Northern leopard frogs (Rana pipiens) and green frogs (Rana clamitans) were evaluated at eight wetland sites, four of which were within apple orchards, to determine if environmental changes ...associated with orchard management affected measured biological parameters. Size, age, genetic variation, condition indices, levels of circulating steroid hormones, 7-ethoxyresorufin-O-deethylase activity (EROD), and organochlorine and organophosphorus residues in breeding males sampled at pond sites in orchards were compared to the same parameters measured in breeding males from reference sites. Also, the size and physiological condition of young-of-the-year captured in orchard and reference ponds were compared. No evidence of a reduction in genetic variation was found in populations of either species at any sites, but unexpectedly high average heterozygosity values (0.191-0.282) in concert with low overall fixation indices (0.012-0.059) in adults of both species did suggest that pond populations were interacting with neighboring populations in nonorchard habitats. Few significant differences in levels of circulating steroid hormones or condition indices of breeding males were found among sites. Significant EROD induction in male green frogs collected from one orchard site during one sampling event was the only indication that a metabolic challenge due to presence of cytochrome P450-inducing toxicants may have existed, whereas elevated concentrations of organochlorines (dichlorodiphenyltrichloroethane DDT- or endosulfan-related) in green frog tissues suggested that frogs at three orchard sites were taking up pesticides. Significant differences in size of equivalent-age male and juvenile leopard frogs and green frogs occupying different study sites suggested that suboptimal habitat characteristics existed at one or two of the four orchard sites. However, site-specific habitat deficiencies could not be related to orchard study sites in general, and, thus, wetlands in apple orcha...
This longitudinal, retrospective cohort study of patients with COPD describes baseline characteristics, adherence, and persistence following initiation of inhaled corticosteroids (ICS)/long-acting β
...-agonists (LABA)/long-acting muscarinic antagonists (LAMA) from multiple inhaler triple therapy (MITT).
Patients aged ≥40 years receiving MITT between January 2012 and September 2015 were identified from the IQVIA™ Real-world Data Adjudicated Claims-USA database. MITT was defined as subjects with ≥1 overlapping days' supply of three COPD medications (ICS, LABA, and LAMA). Adherence (proportion of days covered, PDC) and discontinuation (defined as a gap of 1, 30, 60, or 90 days of supply in any of the three components of the triple therapy) were calculated for each patient over 12 months of follow-up. In addition, analyses were stratified by number of inhalers.
In total, 14,635 MITT users were identified (mean age, 62 years). Mean PDC for MITT at 12 months was 0.37%. Mean PDC for the ICS/LABA and LAMA component at 12 months was 49% (0.49±0.31; median, 0.47) and 54% (0.54±0.33; 0.56), respectively. The proportion of adherent patients (PDC ≥0.8) at 12 months was 14% for MITT. Allowing for a 30-day gap from last day of therapy, 86% of MITT users discontinued therapy during follow-up.
Patients with COPD had low adherence to and persistence with MITT in a real-world setting. Mean PDC for each single inhaler component was higher than the mean PDC observed with MITT. Reducing the number of inhalers may improve overall adherence to intended triple therapy.
Stigma may differ depending on the timing of group-membership entry, whether a person was “born that way” or “became that way.” Disability, a highly understudied minority group, varies on this ...domain. Three studies demonstrated that congenital disability is more stigmatized than acquired disability and essentialism and blame moderate and mediate this effect. Congenital disability was more stigmatized than the acquired version of the same disability (Studies 1–2). People with congenital disability were more essentialized, but less blamed than people with acquired disability (Study 2). Manipulating onset and essentialism revealed that when disability was acquired, low essentialism predicted greater stigma through blame (Study 3). However, when disability was congenital, essentialism did not affect stigma through blame. For stigmatized groups unlikely to be blamed for their group membership, reducing essentialism could ameliorate stigma, but for groups that might be blamed for their group membership, increasing essentialism may be a tool to reduce stigma by reducing blame.
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