QALYs and medical costs saved from prevention of a cancer: Analysis of nation-wide real-world data of Taiwan with lifetime horizon.

BACKGROUND/PURPOSE: To quantify savings of loss-of-QALE (quality-adjusted life expectancy) and lifetime medical costs from prevention of different cancers. METHODS: We collected nation-wide data on 808,700 new cancer cases of 14 different organ systems and followed them from 1998 to 2014 in Taiwan. We also collected 13,005 cancer patients from a medical center and 47,320 repeated measurements of quality of life (QoL) of EQ-5D to obtain utility values and multiplied them with the corresponding survival rates to calculate QALE. With Kaplan-Meier estimation to survival function to the end of follow-up, we extrapolated to lifetime through a rolling over algorithm on the logit transform of the survival ratio between the index cohort and age-, sex, and calendar year matched referents simulated from vital statistics. Lifetime costs for each cancer were estimated by multiplying survival with average monthly costs after adjustment with annual discount rate. The loss-of-QALE was estimated by the difference in QALE between the index cancer cohort and corresponding referents. RESULTS: The dynamic changes and weighted averages of the QoL utility values of 14 different cancers ranged from 0.82 to 0.95. Successful prevention of liver, lung, esophagus, or nasopharynx cancer would save more than 10 quality-adjusted life years and more than 21,000 USD per case for both genders. Since the saving of loss-of-QALE was adjusted for different age, sex, and calendar-year distributions, it could be used in cost effectiveness evaluation. CONCLUSION: Savings of loss-of-QALE and lifetime costs could be used for comparison of prevention, diagnosis, treatment and rehabilitation from a lifetime horizon.

Power and sample size calculation for paired recurrent events data based on robust nonparametric tests.

The purpose of this paper is to develop a formula for calculating the required sample size for paired recurrent events data. The developed formula is based on robust non-parametric tests for comparing the marginal mean function of events between paired samples. This calculation can accommodate the associations among a sequence of paired recurrent event times with a specification of correlated gamma frailty variables for a proportional intensity model. We evaluate the performance of the proposed method with comprehensive simulations including the impacts of paired correlations, homogeneous or nonhomogeneous processes, marginal hazard rates, censoring rate, accrual and follow-up times, as well as the sensitivity analysis for the assumption of the frailty distribution. The use of the formula is also demonstrated using a premature infant study from the neonatal intensive care unit of a tertiary center in southern Taiwan. Copyright © 2017 John Wiley & Sons, Ltd.

Estimation of Quality-Adjusted Life Expectancy of Patients With Oral Cancer: Integration of Lifetime Survival With Repeated Quality-of-Life Measurements.

BACKGROUND: Quality-adjusted life year is widely applied nowadays, which consider both survival and quality of life (QoL). When most diseases are becoming chronic, it is imperative to quantify the overall health impact of a disease in lifetime perspective. OBJECTIVE: The purpose of this study is to introduce methods for estimating quality-adjusted life expectancy (QALE) and loss of QALE in patients with a disease or specific conditions. METHODS: The QALE of an index cohort can be represented as the integration of the product of lifetime survival function and mean QoL function. We introduce a robust extrapolation approach for estimating lifetime survival function and propose an approach for estimating lifetime mean QoL function for studies with limited follow-up. The best part of the proposed method is that the survival data and QoL data can be collected separately. A cohort of patients with a specific condition can be identified by databases that regularly collect data for the control of diseases, and their survival status is verified by linking to a mortality registry. Although nationwide QoL data are not available, researchers can implement a relative short-term follow-up interview on a random sample of patients to collect QoL data. For demonstration, we applied the proposed methods to estimate QALE and loss of QALE of oral cancer patients. RESULTS: The estimates (95% confidence interval) of QALE for oral cancer patients were 11.0 (10.5-11.6) and 14.2 (12.7-15.5) quality-adjusted life years (QALYs) for men and women, respectively. The estimates of loss of QALE for the male and female patients with oral cancer were 14.4 (13.8-14.9) and 7.5 (6.2-9.0) QALYs, respectively. CONCLUSIONS: The methods for estimating QALE and loss of QALE can be applied to economic evaluation of cancer control, including screening.

Cost-effectiveness analysis of the oral cancer screening program in Taiwan.

OBJECTIVES: We assess the incremental cost-effectiveness ratio (ICER) of the oral cancer (OC) screening program in Taiwan. MATERIALS AND METHODS: We interlinked the Cancer Registry, Mortality Registry, National Vital Statistics, reimbursement database of National Health Insurance, and the National Oral Cancer Screening database of Taiwan. A total of 40,092 pathologically verified OC patients were identified and followed during 2002-2014. After stratification by stages, lifetime survival curves were estimated by a rolling extrapolation algorithm to obtain life expectancy (LE), expected years of life lost (EYLL), and lifetime medical costs (LMC). RESULTS: The LE for stages I-IV were 19.5, 14.0, 11.9, and 7.7 life-years, respectively, while those of EYLL were 7.3, 12.2, 15.4, and 18.7 life-years, respectively. The LMC for stages I-IV were US$ 65,752, 60,086, 53,675, and 47,570, respectively. We assumed no life loss for stage 0 with LMC of US$ 5380 spent for the first year after diagnosis. During 2010-2013, 967 out of the 28,018 cases detected with abnormal oral pathology by screening were found to develop OC. The ICER of the screening program was US$ 28,516 per life-year saved, which could be improved to US$ 5579 per life-year saved if all cancers transformed from abnormal oral pathology were detected before stage I. CONCLUSION: The ICER of the current OC screening program in Taiwan slightly exceeds 1 GDP (gross domestic product) per capita per life-year saved. Intensive follow-up and treatment for all patients with abnormal oral pathology would improve screening efficiency and effectiveness of prevention.

Lifetime risks, loss of life expectancy, and health care expenditures for 19 types of cancer in Taiwan.

BACKGROUND: The mortality rates for different cancers are no longer an efficient tool for making national policy. The purpose of this study were to quantify the lifetime risks, life expectancies (LEs) after diagnosis, expected years of life lost (EYLL), and lifetime health care expenditures for 19 major cancers in Taiwan. METHODS: A total of 831,314 patients with 19 pathologically proven cancers were abstracted from the Taiwan Cancer Registry from 1998 to 2012. They were linked to the National Mortality Registry (1998-2014) and National Health Insurance reimbursement database (1998-2013) for survival and health care costs. We estimated the cumulative incidence rate for ages 0-79 years and the lifetime survival function for patients with different cancer sites. The EYLL was calculated by subtracting the LE of each cancer cohort from that of the age- and sex-matched referents simulated from national life tables. The estimated lifetime cost was calculated by adding up the product of survival probability and mean cost at the corresponding duration-to-date after adjustment for the inflation to the year of 2013. RESULTS: There were 5 cancers with a lifetime risk exceeding 4%: colorectal, liver, lung, and prostate in males, and breast and colorectal in females. Cancers with EYLL of >10 years were: esophageal, intrahepatic bile ducts, liver, pancreas, oral, nasopharyngeal, leukemia, lung, and gallbladder, extrahepatic bile ducts and biliary tract in males, and intrahepatic bile ducts, pancreas, nasopharyngeal, lung, esophageal, leukemia, liver, gallbladder, extrahepatic bile ducts and biliary tract, ovary, and stomach in females. Cancers with lifetime health care expenditures exceeding US$50,000 to the National Health Insurance were as follows: leukemia, kidney, testis, renal pelvis and ureter in males, and renal pelvis and ureter, leukemia, breast, urinary bladder, kidney, ovary, and nasopharyngeal in females. All these impacts should be considered in health policy decisions. CONCLUSION: The impacts of cancer in Taiwan are very large. Future studies must consider both quality of life and the entire impact from societal perspectives.

Stiffness Effects in Rocker-Soled Shoes: Biomechanical Implications.

Rocker-soled shoes provide a way to reduce the possible concentration of stress, as well as change movement patterns, during gait. This study attempts to examine how plantar force and spatio-temporal variables are affected by two rocker designs, one with softer and one with denser sole materials, by comparing them with the barefoot condition and with flat-soled shoes. Eleven subjects' gait parameters during walking and jogging were recorded. Our results showed that compared with barefoot walking, plantar forces were higher for flat shoes while lower for both types of rocker shoes, the softer-material rocker being the lowest. The plantar force of flat shoes is greater than the vertical ground reaction force, while that of both rocker shoes is much less, 13.87-30.55% body weight. However, as locomotion speed increased to jogging, for all shoe types, except at the second peak plantar force of the denser sole material rocker shoes, plantar forces were greater than for bare feet. More interestingly, because the transmission of force was faster while jogging, greater plantar force was seen in the rocker-soled shoes with softer material than with denser material; results for higher-speed shock absorption in rocker-soled shoes with softer material were thus not as good. In general, the rolling phenomena along the bottom surface of the rocker shoes, as well as an increase in the duration of simultaneous curve rolling and ankle rotation, could contribute to the reduction of plantar force for both rocker designs. The possible mechanism is the conversion of vertical kinetic energy into rotational kinetic energy. To conclude, since plantar force is related to foot-ground interface and deceleration methods, rocker-design shoes could achieve desired plantar force reduction through certain rolling phenomena, shoe-sole stiffness levels, and locomotion speeds.

Correction: Stiffness Effects in Rocker-Soled Shoes: Biomechanical Implications.

[This corrects the article DOI: 10.1371/journal.pone.0169151.].

Isatis indigotica induces hepatocellular cancer cell death via caspase-independent apoptosis-inducing factor translocation apoptotic pathway in vitro and in vivo.

Isatis indigotica is a biennial herbaceous cruciferous medical herb with antipyretic, antiviral, anti-inflammatory, and anti-endotoxin activity. This study explored the chemotherapeutic potential of I indigotica on human hepatoma cells and investigated the mechanism by which metabolites from I indigotica inhibit hepatoma cell growth. Antitumor activity was discovered in dried I indigotica leaf chloroform extracts (CEDLI). In nude mice xenotransplanted with human hepatoma cells, CEDLI supplementation inhibited tumor growth by ~40% compared with nonsupplemented animals without affecting body weight/food intake. CEDLI induced sub-G1 cell cycle arrest and apoptosis in hepatoma cells. Furthermore, CEDLI activates p53 and Bax, reduces Bcl-2 expression, and causes mitochondrial stress and the release of apoptosis-inducing factor into the cytosol followed by its translocation into the nucleus, resulting in hepatoma cell apoptosis. This study provides novel in vivo evidence of I indigotica's antitumor activity. The chemotherapeutic activity against human hepatoma tumorigenesis was because of a distinguished caspase-independent apoptotic pathway.