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When simultaneous comparisons are performed, a procedure must be employed to control the overall level (also known as the Type I Error rate). Hochberg’s stepwise testing procedure is often used and here determination of the sample size needed to achieve a specified power for two pairwise comparisons when observations follow a normal distribution is addressed. Three different scenarios are considered: subsets defined by a baseline criterion, two treatments compared to a control, or one set of subjects nested within the other. The solutions for these three scenarios differ and are examined. The sample sizes for the differences in success probabilities for binomial distributions are presented using the asymptotic normality. The sample sizes and power using Hochberg’s procedure are compared to the corresponding results using the Bonferroni approach.

A survey of the United States and Canadian governmental agencies investigated the environmental impact and relative invasiveness of free-roaming domestic non-native carnivores—dogs, cats, and ferrets. Agencies represented wildlife, fish, game, natural or environmental resources, parks and recreation, veterinary and human health, animal control, and agriculture. Respondents were asked to document the number and frequency of sightings of unconfined animals, evidence for environmental harm, and the resulting “degree of concern” in their respective jurisdictions. Results confirmed the existence of feral (breeding) cats and dogs, documenting high levels of concern regarding the impact of these animals on both continental and surrounding insular habitats. Except for occasional strays, no free-roaming or feral ferrets were reported; nor were there reports of ferrets impacting native wildlife, including ground-nesting birds, or sensitive species. This is the first study to report the relative impact of free-roaming domestic carnivores. Dogs and cats meet the current definition of “invasive” species, whereas ferrets do not. Differences in how each species impacts the North American environment highlights the complex interaction between non-native species and their environment. Public attitudes and perceptions regarding these species may be a factor in their control and agency management priorities.

A prerandomization assessment of an efficacy variable is often used as a covariate in the analysis to perform between-treatment comparisons. Such assessments may be made more than once. The variable to be used as the covariate must be chosen prior to any analyses. This choice may be the use of both assessments as covariates. The impact of the choice is examined here.

Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.

The determination of the appropriate sample size is an important aspect of planning a clinical trial. In recent years, procedures for estimation of a nuisance parameter to adjust the sample size if necessary have been examined. Here, it is assumed that the clinical trial is conducted for the comparison of two treatments, where the observations are assumed to have normal distributions with a common unknown variance. For sample size determination, the variance is assumed known and the resulting sample size is sensitive to misspecification of the variance. An estimate of the variance, obtained while the clinical trial is ongoing, can often be used to assess the appropriateness of the assumed variance. The use of a blinded estimate of the variance to potentially adjust the sample size is examined.

Students in graduate school experience stress associated with a fear of failure. Heightened stress responses typically occur in situations where students are required to absorb a vast quantity of information in a limited time. Student reports of stress induced anxiety and depression are further exacerbated by an inability to satisfy basic social, recreational, family and financial needs. Outdoor experiential training (OET) activities as a component of student development initiatives have been designed to assist students with the stress caused by the demands of college. The purpose of this study was to examine the effect of a one-day OET experience on graduate students' perceptions of stress. Using a quasi-experimental design, the results of this study indicated that several mood states, including anxiety-tension, vigor-activity, and depression-dejection, were significantly reduced by a one-day OET experience.

CF101, an orally bioavailable A3 adenosine receptor (A3AR) agonist, demonstrated very good safety and anti-inflammatory effect in Phase II clinical studies in patients with rheumatoid arthritis (RA) and psoriasis. A3AR expression level in peripheral blood mononuclear cells has been defined as a biological predictive marker, based on a significant correlation found in a former RA Phase II study between its over expression at baseline and positive patients' response to CF101 treatment. 79 patients were enrolled to a phase II, multicenter, randomized, double-blind, Placebo controlled, parallel-group study designed to assess the efficacy and safety of CF101 1mg vs. placebo, administered orally twice daily to patients with active RA for 12 weeks. Primary efficacy endpoint was ACR20 response at week 12 and secondary efficacy included ACR 50/70. Patients were enrolled based on A3AR mRNA expression level, utilized as an inclusion criterion. (NCT # NCT01034306) CF101 was found to be safe and well tolerated. CF101 achieved ACR20 of 48.6%, statistically significantly higher than that of the placebo group (25.0%) at week 12 (P=0.0352). CF101 showed superiority in ACR50 and ACR70 values vs. placebo. Interestingly, ACR20, ACR50 and ACR70 response rate at week 12 in a subpopulation with no prior systemic therapy was impressively higher (ACR20 75%) compared to the response of the whole patient population treated with CF101. CF101 reached the primary endpoint in the current study demonstrating clear evidence of efficacy and safety when given orally as monotherapy for 12 weeks in patients with active RA.

Objective: To investigate changes in fecal flora and multiple‐dose pharmacokinetics with the oral antibiotics ceftibuten 400 mg daily and cefpodoxime proxetil (CPX) 200 mg every 12 h, compared to amoxycillin/clavulanate 500/125 mg every 8 h during and following 1 week of medication. Methods: In an open randomized triple crossover design, 18 (nine female, nine male) healthy volunteers received each drug for 7 days, followed by a ‘washout’ period of 4 weeks. Serum and urine levels of the substances were determined by bioassay, and for ceftibuten isomers by high‐pressure liquid chromatography. Statistical analysis of quantitative aerobic and anaerobic cultures of feces was performed, and β‐lactamase activity was determined. Results: Ceftibuten showed a mean Cmax of 18.9 (SD 3.0) mg/L, a terminal half‐life of 2.89 h, and an AUCtot of 100 (21.8) mg.h/L; protein binding was 63.7 (5.1)%, and accumulation was marginal. Cefpodoxime proxetil had a Cmax of 1.92 (0.61) mg/L, a terminal half‐life of 1.97 (0.42) h and an AUCtot of 10.8 (3.3) mg.h/L; no accumulation was seen. Amoxycillin and clavulanate had Cmax values of 7.15 (2.16) mg/L and 3.39 (1.31) mg/L, terminal half‐life values of 1.03 (0.15) h and 0.93 (0.17) h, AUCtot values of 20.0 (4.2) mg.h/L and 8.87 (3.10) mg.h/L, and there was no accumulation. Statistical analysis for ech microorganism in fecal samples showed significant differences between amoxycillin/clavulanate and the two third‐generation cephalosporins, but virtually no differences between ceftibuten and cefpodoxime proxetil. Eleven of 12 volunteers reported loose stools (days 2–7, mean duration 4.4 (SD 2.7) days) with amoxycillin/clavulanate, but nobody during ceftibuten administration and one volunteer during cefpodoxime proxetil administration. Conclusions: Ceftibuten showed excellent and cefpodoxime favorable pharmacokinetic properties, with significantly less pronounced fecal flora changes and intestinal side effects compared to amoxycillin/clavulanate. The multiple crossover design allows powerful microbiological statistical analysis and pharmacokinetic parameter comparisons.