Development and validation of nomograms for predicting survival probability of patients with advanced adenocarcinoma in different EGFR mutation status.

INTRODUCTION: Molecular markers are important variables in the selection of treatment for cancer patients and highly associated with their survival. Therefore, a nomogram that can predict survival probability by incorporating epidermal growth factor receptor mutation status and treatments for patients with advanced adenocarcinoma would be highly valuable. The aim of the study is to develop and validate a novel nomogram, incorporating epidermal growth factor receptor mutation status and treatments, for predicting 1-year and 2-year survival probability of patients with advanced adenocarcinoma. MATERIAL AND METHODS: Data on 13,043 patients between June 1, 2011, and December 31, 2014 were collected. Seventy percent of them were randomly assigned to the training cohort for nomogram development, and the remaining 30% assigned to the validation cohort. The most important factors for constructing the nomogram were identified using multivariable Cox regression analysis. The discriminative ability and calibration of the nomograms were tested using C-statistics, calibration plots, and Kaplan-Meier curves. RESULTS: In the training cohort, 1-year and 2-year OS were 52.8% and 28.5% in EGFR(-) patients, and 73.9% and 44.1% in EGFR(+) patients, respectively. In EGFR(+) group, factors selected were age, gender, congestive heart failure, renal disease, number of lymph node examined, tumor stage, surgical intervention, radiotherapy, first-line chemotherapy, ECOG performance status, malignant pleural effusion, and smoking. In EGFR(-) group, factors selected were age, gender, myocardial infarction, cerebrovascular disease, chronic pulmonary disease, number of lymph node examined, tumor stage, surgical intervention, radiotherapy, ECOG performance status, malignant pleural effusion, and a history of smoking. Two nomograms show good accuracy in predicting OS, with a concordance index of 0.83 in EGFR(+) and of 0.88 in EGFR(-). CONCLUSIONS: The survival prediction models can be used to make individualized predictions with different EGFR mutation status and a useful tool for selecting regimens for treating advanced adenocarcinoma.

Assessing the relationship between healthcare market competition and medical care quality under Taiwan's National Health Insurance programme.

Background: There is still significant uncertainty as to whether market competition raises or lowers clinical quality in publicly funded healthcare systems. We attempted to assess the effects of market competition on inpatient care quality of stroke patients in a retrospective study of the universal single-payer health insurance system in Taiwan. Methods: In this 11-year population-based study, we conducted a pooled time-series cross-sectional analysis with a fixed-effects model and the Hausman test approach by utilizing two nationwide datasets: the National Health Insurance Research Database and the National Hospital and Services Survey in Taiwan. Patients who were admitted to a hospital for ischemic or hemorrhagic stroke were enrolled. After excluding patients with a previous history of stroke and those with different types of stroke, 247 379 ischemic and 79 741 hemorrhagic stroke patients were included in our analysis. Four outcome indicators were applied: the in-hospital mortality rate, 30-day post-operative complication rate, 14-day re-admission rate and 30-day re-admission rate. Results: Market competition exerted a negative or negligible effect on the medical care quality of stroke patients. Compared to hospitals located in a highly competitive market, in-hospital mortality rates for hemorrhagic stroke patients were significantly lower in moderately (ß = -0.05, P < 0.01) and less competitive markets (ß = -0.05, P < 0.01). Conversely, the impact of market competition on the quality of care of ischemic stroke patients was insignificant. Conclusions: Simply fostering market competition might not achieve the objective of improving the quality of health care. Other health policy actions need to be contemplated.

Real-world cost-effectiveness of laparoscopy versus open colectomy for colon cancer: a nationwide population-based study.

BACKGROUND: Laparoscopic colectomy is increasingly being adopted for the treatment of colon cancer; however, the long-term effectiveness of this approach in a real-world clinical setting has yet to be verified. This study aims to compare the effectiveness and costs associated with laparoscopic and open colectomy from the perspective of the National Health Insurance (NHI) system in Taiwan. METHODS: A nationwide population-based colon cancer cohort was observed by linking the Taiwan Cancer Registry, claims data from NHI system, and the National Death Registry. Adult patients with Stage I to Stage III colon cancer who underwent primary cancer resection using either laparoscopy or open colectomy between 2009 and 2011 were included. A propensity score-matched cohort (1745 pairs) was applied to examine three clinical endpoints: overall survival, recurrence-free survival, and disease-free survival within 2 years after the operation. To comply with the perspective as well as the analytic horizon of the study, we limited the research to NHI claims from the study population for the corresponding time period. The health outcomes and net monetary benefits were verified by multivariate mixed-effect models. RESULTS: This analysis revealed that laparoscopy resulted in longer overall survival (adjusted difference 16.8 days, 95 % CI 7.3-26.2), recurrence-free survival (16.8 days, 5.0-28.6) and disease-free survival (26.4 days, 7.4-45.4), compared to open colectomy at 2 years post-op. Laparoscopy also led to a significantly shorter length of stay (3.2 days, 2.4-3.9) and lower index hospitalization costs (US$ 455, 181-729) than open colectomy; however, no differences in costs were observed over the long term. Overall, laparoscopy was more cost-effective than open colectomy under various willingness-to-pay thresholds in the setting of the Taiwan NHI. CONCLUSIONS: The continued adoption of laparoscopy in primary curable colon cancer resection is expected to reduce health care costs over the short term while providing considerable health benefits over the long term.

Cell adhesion as a novel approach to determining the cellular binding motif on the severe acute respiratory syndrome coronavirus spike protein.

Emerging life threatening pathogens such as severe acute aspiratory syndrome-coronavirus (SARS-CoV), avian-origin influenzas H7N9, and the Middle East respiratory syndrome coronavirus (MERS-CoV) have caused a high case-fatality rate and psychological effects on society and the economy. Therefore, a simple, rapid, and safe method to investigate a therapeutic approach against these pathogens is required. In this study, a simple, quick, and safe cell adhesion inhibition assay was developed to determine the potential cellular binding site on the SARS-CoV spike protein. Various synthetic peptides covering the potential binding site helped to minimize further the binding motif to 10-25 residues. Following analyses, 2 peptides spanning the 436-445 and 437-461 amino acids of the spike protein were identified as peptide inhibitor or peptide vaccine candidates against SARS-CoV.

Erythropoiesis suppression is associated with anthrax lethal toxin-mediated pathogenic progression.

Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in high mortality in animals and humans. Although some of the mechanisms are already known such as asphyxia, extensive knowledge of molecular pathogenesis of this disease is deficient and remains to be further investigated. Lethal toxin (LT) is a major virulence factor of B. anthracis and a specific inhibitor/protease of mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality and induces certain anthrax-like symptoms, such as anemia and hypoxia, in experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream pathways of MAPKKs, and are important for erythropoiesis. This prompted us to hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic dysfunction. As revealed by colony-forming cell assays in this study, LT challenges significantly reduced mouse erythroid progenitor cells. In addition, in a proteolytic activity-dependent manner, LT suppressed cell survival and differentiation of cord blood CD34(+)-derived erythroblasts in vitro. Suppression of cell numbers and the percentage of erythroblasts in the bone marrow were detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked through treatments of erythropoietin, significantly ameliorating the anemia and reducing the mortality of LT-treated mice. These data suggested that suppressed erythropoiesis is part of the pathophysiology of LT-mediated intoxication. Because specific treatments to overcome LT-mediated pathogenesis are still lacking, these efforts may help the development of effective treatments against anthrax.

Can we accredit hospital ethics? A tentative proposal.

OBJECTIVES: The objective of this research was to develop ethics accreditation standards for hospitals. RESEARCH DESIGN: Our research methods included a literature review, an expert focus group, the Delphi technique and a hospital survey. The entire process was separated into two stages: (1) the development of a draft of hospital ethics accreditation standards; and (2) conducting a nationwide hospital survey of the proposed standards. RESULTS: This study produced a tentative draft of hospital ethics accreditation standards comprised of six chapters and 62 standards based on the expert focus group and Delphi technique. The six chapters are: Medical ethics policies, regulations and leadership; The establishment and operation of a medical ethics committee; The establishment and operation of research-related ethics committees; Medical ethics education; Organisational ethical climate; and Respect for patients' rights and establishment of good hospital-patient relationships. The hospital survey indicated that the concept of an organisational ethical climate was new to most hospital managers, most hospitals disliked the idea of having a separate hospital ethics accreditation system, and small hospitals were concerned about their ability to comply with all of the standards. CONCLUSIONS: Regardless of whether hospital ethics accreditation can be a stand-alone accreditation or just part of existing hospital accreditation programmes, we hope this draft can serve as a good reference for future endeavours by hospital accreditation authorities.

Assessing a population's need for scintigraphy: use under universal health insurance in Taiwan.

AIM: The aim of this study is to estimate how much scintigraphy the population will need in a well-developed healthcare system with fairly equitable access to healthcare. METHODS: This is a retrospective population-based study. The data used came from Taiwan's National Health Insurance reimbursement claims dataset, the National Account compiled by Taiwan's Statistical Bureau of the Directorate General of Budget, Accounting and Statistics, and the National Health Account by Taiwan's Department of Health from 2001 to 2005. Frequency and expenditure variables were derived from these datasets. RESULTS: The annual scintigraphy use rate in Taiwan was 13.57/1000 people from 2001-2005. On average, expenditures for scintigraphy accounted for 0.24% of National Health Insurance expenditures, 0.13% of the nation's total health expenditures and 0.00008% of the gross domestic product of Taiwan. The ratio of scintigraphy to computed tomography use was 0.37 and the scintigraphy to magnetic resonance imaging ratio was 1.14. The ratio of expenditures for scintigraphy and computed tomography was 0.23 and that for scintigraphy and magnetic resonance imaging was 0.36. CONCLUSION: A comparative approach is useful for assessing healthcare needs. Although the Taiwanese experience might not apply to all countries, the results of this study can serve as an international benchmark for assessing the need for scintigraphy in countries around the world.

Valuation of the economic benefits of human papillomavirus vaccine in Taiwan.

OBJECTIVES: The study aims to apply the contingent valuation method to elicit the willingness-to-pay (WTP), and measure the value of a statistic life (VSL), for human papillomavirus (HPV) vaccine in Taiwan. METHODS: A total of 512 questionnaires were completed on women aged 20 to 55 years with at least one daughter, during March through May 2007. The respondents' WTP for the vaccines was elicited by double-bounded binary-choice questions under two scenarios: one was to protect themselves from cervical cancer (CC) and the other was for their daughter(s). The WTP was modeled as a function of the respondents' knowledge score, attitudes toward CC and HPV vaccine, the vaccination outcome scenarios, and individual characteristics. A log-normal survival model was constructed and the maximum-likelihood method was used for estimation. RESULTS: The median regression-adjusted WTP was estimated at US$1098 to US$1233 (US$913-1004) for vaccinating the daughter (mother); and the VSL was estimated at approximately US$0.65 to US$4.09 (US$0.56-3.16) million for vaccinating the daughter (mother). CONCLUSIONS: The study results provided important evidences on the monetary value women placed on a HPV vaccine, and the differential benefits between vaccinating the women and their daughters.