Patterns of ambulatory care utilization in Taiwan

BACKGROUND: We used the insurance claims of a representative cohort to quantify the patterns of ambulatory care visits, especially the doctor-shopping phenomenon, in Taiwan. METHODS: The ambulatory visit files of the 200,000-person cohort datasets from the National Health Insurance Research Database in 2002 were analyzed. Only a visit with physician consultation would be considered. We computed the visit patterns both by visit count and by patient count. RESULTS: In 2002, there were 182,474 eligible people with 2,443,003 physician consultations. During the year, 87.4% of the cohort had visited physician clinics and 57.5% had visited hospital-based outpatient or emergency departments. On average, a person had 13.4 physician consultations and consulted 3.4 specialties, 5.2 physicians, and 3.9 healthcare facilities in a year. In 2002, 17.3% of the cohort had ever visited different healthcare facilities on the same day; 23.5% had ever visited physicians of the same specialty at different healthcare facilities within 7 days and the percentage of second visits was 3.8% of all visits. Besides, 7.6% of the cohort had visited two or more specialties at the same facility on the same day, and such visits make up 2.5% of all visits. CONCLUSION: The people in Taiwan did visit the physicians and outpatient departments frequently. Many patients not only consulted several physicians of different specialties and at different healthcare facilities during the year, but also switched the physicians and facilities quickly. An effective referral system with efficient data exchange between facilities might be the solution

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Application of Frequent Itemsets Mining to Analyze Patterns of One-Stop Visits in Taiwan

BACKGROUND: The free choice of health care facilities without limitations on frequency of visits within the National Health Insurance in Taiwan gives rise to not only a high number of annual ambulatory visits per capita but also a unique "one-stop shopping"phenomenon, which refers to a patient' visits to several specialties of the same healthcare facility in one day. The visits to multiple physicians would increase the potential risk of polypharmacy. The aim of this study was to analyze the frequency and patterns of one-stop visits in Taiwan. METHODOLOGY/PRINCIPAL FINDINGS: The claims datasets of 1 million nationally representative people within Taiwan's National Health Insurance in 2005 were used to calculate the number of patients with one-stop visits. The frequent itemsets mining was applied to compute the combination patterns of specialties in the one-stop visits. Among the total 13,682,469 ambulatory care visits in 2005, one-stop visits occurred 144,132 times and involved 296,822 visits (2.2% of all visits) by 66,294 (6.6%) persons. People tended to have this behavior with age and the percentage reached 27.5% (5,662 in 20,579) in the age group ≥80 years. In general, women were more likely to have one-stop visits than men (7.2% vs. 6.0%). Internal medicine plus ophthalmology was the most frequent combination with a visited frequency of 3,552 times (2.5%), followed by cardiology plus neurology with 3,183 times (2.2%). The most frequent three-specialty combination, cardiology plus neurology and gastroenterology, occurred only 111 times. CONCLUSIONS/SIGNIFICANCE: Without the novel computational technique, it would be hardly possible to analyze the extremely diverse combination patterns of specialties in one-stop visits. The results of the study could provide useful information either for the hospital manager to set up integrated services or for the policymaker to rebuild the health care system

Frequency-stabilization to 6x10^-16 via spectral-hole burning

We demonstrate two-stage laser stabilization based on a combination of Fabry- Perot and spectral-hole burning techniques. The laser is first pre-stabilized by the Fabry-Perot cavity to a fractional-frequency stability of sigma_y(tau) < 10^-13. A pattern of spectral holes written in the absorption spectrum of Eu3+:Y2SiO5 serves to further stabilize the laser to sigma_y(tau) = 6x10^-16 for 2 s < tau < 8 s. Measurements characterizing the frequency sensitivity of Eu3+:Y2SiO5 spectral holes to environmental perturbations suggest that they can be more frequency stable than Fabry-Perot cavities

Computers in Secondary Schools: Educational Games

This entry introduces educational games in secondary schools. Educational games include three main types of educational activities with a playful learning intention supported by digital technologies: educational serious games, educational gamification, and learning through game creation. Educational serious games are digital games that support learning objectives. Gamification is defined as the use of "game design elements and game thinking in a non-gaming context" (Deterding et al. 2011, p. 13). Educational gamification is not developed through a digital game but includes game elements for supporting the learning objectives. Learning through game creation is focused on the process of designing and creating a prototype of a game to support a learning process related to the game creation process or the knowledge mobilized through the game creation process. Four modalities of educational games in secondary education are introduced in this entry to describe educational games in secondary education: educational purpose of entertainment games, serious games, gamification, and game design