Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide.

Therapeutic administration of peptides may result in anti-drug antibody (ADA) formation, hypersensitivity adverse events (AEs) and reduced efficacy. As a large peptide, the immunogenicity of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide is of considerable interest. The present study assessed the incidence of treatment-emergent dulaglutide ADAs, hypersensitivity AEs, injection site reactions (ISRs), and glycaemic control in ADA-positive patients in nine phase II and phase III trials (dulaglutide, N = 4006; exenatide, N = 276; non-GLP-1 comparators, N = 1141). Treatment-emergent dulaglutide ADAs were detected using a solid-phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell-based assay derived from human endothelial kidney cells (HEK293). A total of 64 dulaglutide-treated patients (1.6% of the population) tested ADA-positive versus eight (0.7%) from the non-GLP-1 comparator group. Of these 64 patients, 34 (0.9%) had dulaglutide-neutralizing ADAs, 36 (0.9%) had native-sequence GLP-1 (nsGLP-1) cross-reactive ADAs and four (0.1%) had nsGLP-1 neutralization ADAs. The incidence of hypersensitivity AEs and ISRs was similar in the dulaglutide versus placebo groups. No dulaglutide ADA-positive patient reported hypersensitivity AEs. Because of the low incidence of ADAs, it was not possible to establish their effect on glycaemic control.

Gender differences in the perception of drug user treatment: assessing drug user treatment for youthful offenders.

The present study sought to determine whether gender-specific differences existed in the perception of drug user treatment services delivered at a residential substance misuse treatment program operated by a large youth correctional agency in the western United States. Hypothesized gender differences in perceptions of treatment services and treatment-related needs were confirmed in a number of areas such as treatment engagement, counseling needs, and postrelease concerns. Findings of this exploratory study underscore the need to consider gender-specific issues in correctional substance misuse treatment for young offenders.

The influence of gemcitabine and cisplatin schedule on response and survival in advanced non-small cell lung cancer.

PURPOSE: Gemcitabine-cisplatin combinations are among the most active for the treatment of non-small cell lung cancer. Previous reports have suggested that the day of cisplatin administration affects both toxicity and drug delivery. We undertook this retrospective analysis to determine whether it also affects response and survival. PATIENTS AND METHODS: This was a retrospective analysis of six studies of gemcitabine and cisplatin. Gemcitabine, 1000-1500 mg/m(2) was administered on days 1, 8, and 15 of a 28 day cycle. In four studies cisplatin 100 mg/m(2) was administered with mannitol diuresis every four weeks on either day 1, day 2 or day 15. In two studies cisplatin 25-30 mg/m(2) was administered on day 1, 8 and 15. Standard prognostic factors including age, gender, stage, performance status, and histologic subtype were analyzed along with day of cisplatin administration. Single variable Cox proportional hazards regressions were performed. This was followed by multiple variable Cox proportional hazards regression, beginning with a full model containing terms for gender, age, performance status and stage. The least statistically significant terms were subsequently dropped from the model to reach a final model with only statistically significant variables. A similar approach was followed to fit a multiple variable logistic regression model to overall response data. RESULTS: Overall response rates were highest (36-46%) in the three studies that administered cisplatin on days 2 or 15, and these studies had the highest 1-year survival rates (52-58%). Survival was better for patients who received cisplatin on day 2 or 15 compared to those treated on either day 1 or weekly on days 1, 8, 15 (P=0.020). In the final model of the Cox regression analysis, survival was better for cisplatin on days 2 or 15 (hazard ratio=0.69, P=0.008) and female gender (hazard ratio=0.72, P=0.036). Only cisplatin delivery on day 2 or day 15 predicted for significantly better response (42 vs. 29%, P=0.036). CONCLUSION: In a 28 day cycle in which gemcitabine is administered day 1, 8 and 15, the best therapeutic index is achieved with cisplatin administration on day 2 or 15.

Gemcitabine in the treatment of elderly patients with advanced non-small cell lung cancer.

Gemcitabine is active against non-small cell lung cancer (NSCLC), with single-agent response rates of 20% or more in previously untreated patients. Its mild toxicity profile suggests that it should be well tolerated by older patients. To assess the impact of age on the efficacy and tolerance of gemcitabine, the results of four phase II trials of single-agent gemcitabine for the treatment of NSCLC were analyzed retrospectively. Starting doses for gemcitabine ranged from 800 to 1,250 mg/m2/wk, and in all studies gemcitabine was administered weekly for 3 weeks followed by a 1-week rest period. Response rates, toxicity, and dose delivery were compared for two age groups, less than 65 years (255 patients) or > or = 65 years (105 patients). The pretreatment characteristics for both patient groups were well balanced. Overall response rates were 16% and 24% for the younger and older patients, respectively (P = .072). Median survival and 1-year survival rates were 8.1 months and 27% and 9.1 months and 36%, respectively, for patients aged less than 65 years and > or = 65 years. Hematologic and nonhematologic toxicities were similar for both age groups. The number of cycles associated with dose reductions or dose omissions and the mean number of treatment cycles administered were also similar. In summary, gemcitabine is active and well tolerated in elderly patients with NSCLC, and is a promising new alternative for the treatment of this patient population.

Role of visual richness in picture recognition memory.

25 fourth graders, 21 eighth graders, and 21 college students were shown slides of objects presented as color photographs, black-and-white photographs, simple outline drawings, or printed words. After an 8-wk. delay, students were asked to discriminate the study slides from similar distractor slides. No significant differences were found among the types of pictures. Recognition of black-and-white photographs was superior to words.