Search

e17534 Background: Limited tx options exist for pts with A/R EC who progress on/after platinum-based chemotherapy (PBCT). This study compared survival outcomes of pts with A/R mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) EC receiving dostarlimab in Cohort A1 of the single-arm, Phase I GARNET trial, with an equivalent real-world (RW) cohort receiving current tx in England. The primary objective compared second-line (2L) overall survival (OS) between cohorts; a secondary objective was time to tx discontinuation (TTD; proxy for progression-free survival). Methods: An overall-2L-tx RW cohort was established using National Cancer Registration and Analysis Service data. Five tx-specific RW cohorts were identified (tx received at 2L in > 5% of pts) (Table). Clinical outcomes between GARNET and RW cohorts were compared using MAICs. Relevant prognostic variables were used to create 3 matching scenarios (SC): SC1: grade, histology, PBCT number; SC2: histology, PBCT number; SC3: race/ethnicity, stage at diagnosis, histology, prior surgery (MMR/MSI status not considered). OS was time from first dostarlimab dose (GARNET) or 2L RW tx (RW cohorts) to any-cause death; MAIC-adjusted hazard ratios (HR, 95% confidence interval [CI]) were estimated by weighted Cox proportional-hazards models. TTD after MAIC was summarized descriptively. Results: Effective sample size (ESS) assessed matching capacity; lower ESS in SC1 reduced its robustness (Table). Following matching, distributions of baseline characteristics were similar between cohorts. Across most matching scenarios, there was a lower risk of death in pts treated with dostarlimab compared to the overall RW cohort and for tx-specific RW cohorts (Table). Median TTD (months, 95% CI) was longer for pts treated with dostarlimab across all matching scenarios (SC1: 7.8 [4.1, not estimable (NE)]; SC2: 9.7 [5.5, NE]; SC3: 14.0 [6.4, 17.9]) than the overall RW cohort (3.4 [3.2, 3.4]). Conclusions: Results suggest that pts in GARNET with dMMR/MSI-H A/R EC receiving dostarlimab had better OS and longer TTD compared with pts receiving current 2L tx in England. Funding: GSK (217216; scott.r.goulden@gsk.com).[Table: see text]

OBJECTIVES This analysis assessed the safety of intravenous immunoglobulin (IVIg) in the treatment of patients with neuroimmunological and immunological disorders in a home-based setting. METHODS Adverse reactions (ARs) were assessed in a retrospective review of 1176 patients receiving 28,677 home-based IVIg infusions between 1996 and 2013. RESULTS Of 1176 patients, 648 (55.1%) experienced IVIg-related ARs; 536 (45.6%) were mild, 78 (6.6%) moderate, and 34 (2.9%) severe. Thirty-seven (3.1%) patients were hospitalized because of ARs; of these, headache was most common (51.4%). Mean number of ARs per patient increased from 1.4 (low dose) to 3.6 (high dose). Incidence of ARs increased from 41% in the first 5-year moving average in 2003 to 65% in 2008. The number of ARs correlated with the number of infusions (ρ = 0.24; P < 0.001) and the average IVIg dose (ρ = 0.10; P < 0.001). CONCLUSIONS Low- and high-dose IVIg were safe and well tolerated with a few serious ARs in patients with neuroimmunological and immunological disorders.

Background Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD). To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes. Methods A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015. Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint. Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group). Each association was assessed at 6 months and study end. Results Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation. Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p

Evaluate literature to assess response rate as a surrogate endpoint of survival in ovarian cancer (OC).Systematic review consistent with PRISMA criteria, identified randomized, controlled trials reporting overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in recurrent OC. MEDLINE® and Embase® searches (year 2000-March 23, 2015) were augmented by bibliographic screening. Proposed surrogate measures (independent variables) were ORR and disease control rate. True clinical outcomes (dependent variables) were median OS and PFS. Analyses were performed on unweighted and weighted data using correlation analysis, linear regression, and surrogate threshold effect (STE). Smaller STE indicates greater predictive precision with magnitude of STE dependent on variance of prediction.Thirty-nine studies were included for review, representing 9223 platinum-sensitive and resistant patients. Objective response rate (r=0.82; P0.001) was a better predictor than disease control rate (r=0.58; P0.001) and strongly correlated with PFS (r=0.85; P0.0001). Weighted-regression analysis demonstrated that for each 10% increase in ORR, PFS increased by 1.20months and OS by 2.83months. Regression analysis of treatment effects (odds ratio of response, hazard ratio of survival) suggests that a 10% increase in odds ratio of ORR would result in 2.5% reduction in the hazard ratio of OS. Based on weighted data, STE indicated that an ORR of ≥1% is needed to achieve nonzero OS benefit.This systematic review supports ORR as a possible surrogate clinical trial endpoint for OS in recurrent OC with at least second-line therapy.

BACKGROUND Intrathecal morphine (ITM) provides effective analgesia after posterior spinal fusion (PSF). Although most anesthetic drugs have well-characterized effects on evoked potentials, there is little data on the effects of ITM on transcranial electric motor-evoked potentials (tceMEPs). We performed this study to assess the effects of ITM on tceMEPs in the first 30 minutes after administration. We hypothesized that administration of ITM in doses currently used at our institution would not significantly affect mean tceMEP amplitudes and latencies of an ITM study group relative to control patients who did not receive the drug. METHODS tceMEPs were recorded before ITM injection and 5, 10, 20, and 30 minutes after injection in 14 subjects ages 11 through 18 years undergoing PSF. These recordings were compared to an age-matched control group undergoing PSF in which ITM was not injected. The effects of ITM on tceMEP amplitude and latency were compared between the 2 groups. RESULTS Fourteen subjects were enrolled in the ITM group and 16 served as controls. There were no significant differences in the baseline mean response amplitudes of the 2 groups for any of the 8 muscles studied. Mean response amplitudes over the 30-minute posttreatment period in the ITM group did not differ significantly from those of the control subjects. Average response amplitudes collapsed across all muscles for each subject were not significantly different during the baseline period (95% CI = -38% to 45%; P = 0.783), nor were they significantly different between the 2 groups during the posttreatment period (95% CI = -30% to 78%; P = 0.640). There also were no significant differences in the mean response latencies of the 2 groups in either the baseline or posttreatment periods. Average response latencies collapsed across all muscles for each subject were 4% larger for the ITM group than for controls during the baseline period (95% CI = -5% to 13%; P = 0.377), and 3% larger for the ITM group than for controls during the posttreatment period (95% CI = -4% to 12%; P = 0.359). CONCLUSIONS Administration of ITM in doses currently used at our institution did not cause more than a 70% attenuation of mean tceMEP amplitudes or latency changes of an ITM study group relative to control subjects during the 30-minute period after injection. Further studies are required to determine if there are delayed effects after this initial time period.

Background There is an increasing interest in the role of inflammatory mechanisms contributing to the development of stroke. Recent studies have reported an association between allele 2 of a variable number tandem repeat of the interleukin-1 receptor antagonist ( IL1RN ) gene in Caucasian patients with ischemic stroke. The purpose of this investigation is to independently confirm these results in our study population. Methods We recruited and genotyped 516 Caucasian patients with ischemic stroke and 380 matched controls. Tests of association were performed to estimate odds ratio (OR) for the IL1RN gene variable number tandem repeat polymorphism with case–control status. Genotype frequencies of IL1RN gene were compared by case–control and symptom status using χ 2 contingency tables and logistic regression models. Results No significant association was observed between any of the IL1RN gene genotypes and ischemic stroke. The unadjusted association model a, and the fully saturated model e, adjusted for age, gender, and stroke risk factors demonstrated no significant increase in risk associated with the IL1RN gene 2/2 genotype (a: OR, 1.11; 95% confidence interval [CI], .67-1.89; P = .615; and e: OR, .95; 95% CI, .46-1.94; P = .574). Analyses of genotypic and allelic frequencies of each Trial of Org 10172 in Acute Stroke Treatment subtype with control and pairwise comparison between stroke subtypes did not show any significant differences in their distributions, and all P values were greater than the significance level of .05. Conclusion Our results do not confirm an association between the gene and ischemic stroke in Caucasian patients.

Strong normality assumption is associated with widely used process capability indices such as cp, cpk. Violation of the assumption will mislead the interpretation in applications. A nonparametric method is proposed for density estimation of any unknown distribution. Kernels are used for density estimation and metropolis-hastings (M-H) algorithm is adopted to generate samples from the density. M-H sampling provides a tool to accommodate different kernel functions and flexibility of future extension to multivariate cases. Conformity (yield) based indices (yp, y) are adopted to replace cp, cpk. These indices can be conveniently assessed by the proposed kernel density based M-H algorithm (K-M-H). The method is validated by several simulation case studies.Copyright © 2012 by ASME