Estimating the long-term clinical impact of cervical cancer vaccination in Taiwan.

The high burden of human papillomavirus (HPV) infection and subsequent cervical cancer in the presence of screening in Taiwan suggests the need for further prevention strategies. Epidemiology and screening practices vary considerably between countries, and specific analyses are required to estimate the impact of HPV vaccination. This study adapted a computer-based health economic model to Taiwan to project the clinical impact of the introduction of a prophylactic vaccine against persistent HPV 16/18 infection on cervical disease. A Markov model based on the natural history of HPV and cervical cancer was developed to simulate transitions between health states (normal, HPV, cervical intraepithelial neoplasia [CIN] stages I to III, cervical cancer stages I to IV, and death) in the presence of screening. The model was calibrated to Taiwan epidemiological end points including age-specific HPV prevalence, prevalence of CIN lesions, and predicted cervical cancer incidence and mortality. Taiwanese screening and treatment practices were modeled, and published clinical trial data were used to estimate vaccine efficacy. With 100% vaccine coverage in a 13-year-old cohort of females, there is estimated to be a 71% reduction in cervical cancer cases and deaths due to all HPV types and substantial reductions in the prevalence of precancerous lesions and screening outcomes. Removing the risk of HPV infection of a large proportion of Taiwanese females, with a high underlying cervical cancer incidence rate, would be expected to have dramatic effects on the health care system and mortality in Taiwan.

Comparison of detailed and succinct cohort modelling approaches in a multi-regional evaluation of cervical cancer vaccination.

Mathematical models have been used extensively in the evaluation of chronic diseases and in exploring the health economics of vaccination. In this study, we examine the value of having two different cohort models based on similar assumptions, one comprehensive and one simplified, which can be used to evaluate the impact of cervical cancer vaccination. To compare models, we ran cost-effectiveness analyses in four geographical regions (Italy, the UK, Taiwan and Canada). We show that the models produce comparable results and therefore can be used independently. However, as they require different complexities of data inputs, they are more suited to different circumstances depending on the level of data inputs available or the complexity of the research question asked.

Characterization of tetraethylammonium uptake across the basolateral membrane of the Drosophila Malpighian (renal) tubule.

Basolateral transport of the prototypical type I organic cation tetraethylammonium (TEA) by the Malpighian tubules of Drosophila melanogaster was studied using measurements of basolateral membrane potential (V(bl)) and uptake of [(14)C]-labeled TEA. TEA uptake was metabolically dependent and saturable (maximal rate of mediated TEA uptake by all potential transport processes, reflecting the total transport capacity of the membrane, 0.87 pmol.tubule(-1).min(-1); concentration of TEA at 0.5 of the maximal rate of TEA uptake value, 24 muM). TEA uptake in Malpighian tubules was inhibited by a number of type I (e.g., cimetidine, quinine, and TEA) and type II (e.g., verapamil) organic cations and was dependent on V(bl). TEA uptake was reduced in response to conditions that depolarized V(bl) (high-K(+) saline, Na(+)-free saline, NaCN) and increased in conditions that hyperpolarized V(bl) (low-K(+) saline). Addition of TEA to the saline bathing Malpighian tubules rapidly depolarized the V(bl), indicating that TEA uptake was electrogenic. Blockade of K(+) channels with Ba(2+) did not block effects of TEA on V(bl) or TEA uptake indicating that TEA uptake does not occur through K(+) channels. This is the first study to provide physiological evidence for an electrogenic carrier-mediated basolateral organic cation transport mechanism in insect Malpighian tubules. Our results also suggest that the mechanism of basolateral TEA uptake by Malpighian tubules is distinct from that found in vertebrate renal tubules.