All-oral, interferon-free treatment for chronic hepatitis C: cost-effectiveness analyses.

Interferon-based standard of care treatments (SOC) for chronic hepatitis C are unable to provide high cure rates in certain subgroups of the infected population and can cause debilitating side effects. Clinical trials evaluating all-oral, interferon-free treatments have demonstrated high rates of sustained virologic response with no resistance or major adverse events in most populations. As these drug regimens move towards FDA approval, it will be important to assess their cost-effectiveness in addition to their clinical efficacy. A decision-analytic Markov model with a lifetime, societal perspective was used to evaluate the cost-effectiveness of a generalized all-oral drug regimen compared to SOC by modelling the progression of a 50-year-old, HCV-positive cohort through disease natural history and treatment. In base case analysis, all-oral treatment dominated SOC across a range of willingness-to-pay (WTP) thresholds with an incremental cost-effectiveness ratio (ICER) of US$44,514/quality-adjusted life year (QALY). In sensitivity analyses, the model was sensitive to all-oral drug costs as well as rates of SVR and treatment uptake among noncirrhotic subjects, but robust to variations in all other parameters. All-oral treatment was most cost-effective among genotype 1 subjects but remained cost-effective for genotypes 2 and 3 at WTP thresholds ≥$80,000/QALY. Quality-adjusted life years gained per dollar spent were maximized in younger treatment cohorts. Using this model, the degree of cost-effectiveness depended on the WTP threshold and the final cost set for approved drug combinations.

p53 expression and tumor proliferative activity in testicular germ-cell tumors.

We evaluated p53 expression and tumor proliferative activity (TPA) using monoclonal antibodies to Ki-67 and proliferating cell nuclear antigen (PCNA) in 26 patients with seminomatous and nonseminomatous testicular germ-cell tumors (GCTs). Correlation between p53 expression and TPA, as well as the clinical correlation with the expression of these proteins were also assessed. There were eight cases of pure seminoma and 18 cases of nonseminomatous GCTs, collectively consisting of 45 tumors or tumor components. The nonseminomatous GCTs were mixed or pure and included choriocarcinoma (CC), embryonal carcinoma (EC), immature teratoma (IMT), mature teratoma (MT), seminoma, and yolk sac tumor (YST). The ages of the patients with seminomatous GCTs ranged from 24 to 47 years (mean, 34 years) and those for patients with nonseminomatous GCTs ranged from 17 to 43 years (mean, 29 years). Sixteen (44%) of the 36 nonseminomatous GCTs or tumor components were positive for p53 protein. Ten (91%) of eleven ECs, three (38%) of eight YSTs, two (20%) of ten MTs, and the single case of CC were positive for p53 protein. All nine seminomas and three of six IMTs were only focally positive for p53 protein. The p53 expression in ECs and YSTs was significantly higher than that in IMTs, MTs, and seminomas (P=0.0001). TPA was present in the majority of the seminomatous and nonseminomatous GCTs, and was significantly higher in ECs and YSTs than in seminomas, MTs, and IMTs (Ki-67, P=0.0001; PCNA, P=0.0006). In the majority of the cases PCNA expression was higher than Ki-67 expression (P=0.0001). The mean TPA percentage was significantly higher in the p53-positive tumors or tumor components (EC and YST) when compared with the mean TPA percentage in those neoplasms that were focally positive or negative for p53 protein (Ki-67, P=0.003; PCNA, P=0.046). p53 expression was also associated with histologically aggressive tumors (ECs and YSTs) that also exhibit high TPA. No relationship appears to exist between the three tumor markers and the clinical stage or the patients' follow-up and outcome in this small series. Further studies are necessary to elucidate the roles of p53 and proliferation markers in testicular tumorigenesis and as prognostic markers.

Ovulation following unilateral ovariectomy in the California leaf-nosed bat (Macrotus californicus).

Ovulation occurred from the left ovary in all 5 bats that had had the right ovary removed and an implanting blastocyst was found in the left uterine horn in 2 of these bats. All ovulations in the control and sham-operated bats occurred from the right ovary.