Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel.

The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), p<0.001] or SARS-non-HCP [24.50% (61/249), p<0.001], however, no difference was found between MERS-HCP and SARS-HCP [p = 0.181]. In terms of clinical period, the days from onset to death [13 (4~17) vs 14.5 (0~52), p = 0.045] and to discharge [11 (5~24) vs 24 (0~74), p = 0.010] and be hospitalized days [9.5 (3~22) vs 22 (0~69), p = 0.040] were much shorter in MERS-HCP than SARS-HCP. Similarly, days from onset to confirmation were shorter in MERS-HCP than MERS-non-HCP [6 (1~14) vs 10 (1~21), p = 0.044]. In conclusion, the severity of MERS-HCP and SARS-HCP was lower than that of MERS-non-HCP and SARS-non-HCP due to younger age and early confirmation in HCP groups. However, no statistical difference was found in MERS-HCP and SARS-HCP. Thus, prevention of nosocomial infections involving both novel Coronavirus is crucially important to protect HCP.

Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications.

Primary hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related death. It is important to identify new targets for early diagnosis and treatment of HCC. Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular cholesterol homeostasis via direct binding with free cholesterol. However, little is known about the significance of NPC2 in HCC tumorigenesis. In this study, we showed that NPC2 is abundantly expressed in normal liver, but is downregulated in human HCC tissues. The patients with NPC2 downregulation expressed much higher α-fetoprotein, multiple tumor type, vascular invasion, later pathological stage and shorter survival rate. Knockdown NPC2 in liver cancer cell lines promote cell proliferation, migration and xenograft tumorigenesis. In contrast, NPC2 overexpression inhibits HuH7 promoted tumor growth. Furthermore, administration of hepatotropic adeno-associated virus 8 (AAV8) delivered NPC2 decreased the inflammatory infiltration, the expression of two early HCC markers-glypican 3 and survivin and suppressed the spontaneous HCC development in mice. To identify the NPC2-dependent mechanism, we emphasized on the status of MAPK/ERK signaling. MEK1/2 inhibitor treatment demonstrated that the expression of NPC2 affected the activation of ERK1/2 but not MEK1/2. In addition, cholesterol trafficking inhibitor treatment did not alter the cell proliferation and the activation of MEK/ERK. In conclusion, our study demonstrates that NPC2 may play an important role in negatively regulate cell proliferation and ERK1/2 activation that were independent of cholesterol accumulation. AAV-NPC2 may thus represent a new treatment strategy for liver cancer.

Treatment of patients with dual hepatitis C and B by peginterferon α and ribavirin reduced risk of hepatocellular carcinoma and mortality.

OBJECTIVE: Whether peginterferon α and ribavirin combination therapy reduces risk of hepatocellular carcinoma (HCC) or improves survival in patients dual-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) is unknown. Since it is ethically impossible to conduct a randomised trial to learn the long-term efficacy, we rely upon the large database to explore the effectiveness of combination therapy among dual-infected patients. DESIGN: Data for this population-based retrospective cohort study were obtained from the treatment programme, Cancer Registry, National Health Insurance and death certification. We examined the risk of HCC, mortality and adverse events in 1096 treated and 18 988 untreated HCV-HBV dually-infected patients. Outcomes were analysed using the bias corrected inverse probability weighting (IPW) by propensity scores. Outcomes of HCV-HBV dually-infected and HCV mono-infected patients receiving the same treatment were compared using new user design with IPW estimators to adjust for confounding. RESULTS: After adjustment, combination therapy significantly reduced the risk of HCC (HR 0.76, 95% CI 0.59 to 0.97), liver-related mortality (HR 0.47, 95% CI 0.37 to 0.6) and all-cause mortality (HR 0.42, 95% CI 0.34 to 0.52). Nevertheless, the underlying HBV infection was still a risk factor for HCC and mortality after treatment. Treatment was associated with an increase in the incidence of thyroid dysfunction (HR 1.9, p<0.001) and mood disorders (HR 1.81, p=0.005). CONCLUSIONS: This is the first evidence showing that combination therapy decreased the risk of HCC and improved survival in HCV-HBV dually-infected patients despite a slight increase in the incidence of thyroid and mood disorders.

Comparison of different comorbidity measures for use with administrative data in predicting short- and long-term mortality.

BACKGROUND: It is important to find a comorbidity measure with better performance for use with administrative data. The new method proposed by Elixhauser et al. has never been validated and compared to the widely used Charlson method in the Asia region. The objective of this study was to compare the performance of three comorbidity measures using information from different data periods in predicting short- and long-term mortality among patients with acute myocardial infarction (AMI) and chronic obstructive pulmonary disease (COPD). METHODS: We conducted a retrospective cohort study using National Health Insurance claims data (2001-2002) in Taiwan. We constructed the Elixhauser, the Charlson/Deyo, and the Charlson/Romano methods based on the International Classification of Disease, 9th Revision, Clinical Modification codes in the claims data. Two data periods, including the index hospitalization as well as the index and prior 1-year hospitalizations, were used in the analysis. The performances were compared using the c-statistics derived from multiple logistic regression models that included age, gender, race, and whether the patient received surgery or not. The outcomes of interest were in-hospital and 1-year mortality. RESULTS: The performance was in the same rank order among both populations regardless of the outcome and data period: Elixhauser > Charlson/Romano > Charlson/Deyo. In predicting in-hospital mortality, the Elixhauser models using information from the index hospitalization performed best, even better than the Charlson/Deyo or Charlson/Romano models using information from the index and prior hospitalizations. Nevertheless, in predicting 1-year mortality, the Elixhauser models using information from the index and 1-year prior hospitalizations performed better than using information from the index hospitalization only. CONCLUSIONS: This is so far the first study to validate the Elixhauser method and compare it to other methods in the Asia region, and is the first to report its differences in data periods between short- and long-term outcomes. The comorbidity measurement developed by Elixhauser et al. has relatively good predictive validity, and researchers should consider its use in claims-based studies.

Establishing a nationwide emergency department-based syndromic surveillance system for better public health responses in Taiwan.

BACKGROUND: With international concern over emerging infectious diseases (EID) and bioterrorist attacks, public health is being required to have early outbreak detection systems. A disease surveillance team was organized to establish a hospital emergency department-based syndromic surveillance system (ED-SSS) capable of automatically transmitting patient data electronically from the hospitals responsible for emergency care throughout the country to the Centers for Disease Control in Taiwan (Taiwan-CDC) starting March, 2004. This report describes the challenges and steps involved in developing ED-SSS and the timely information it provides to improve in public health decision-making. METHODS: Between June 2003 and March 2004, after comparing various surveillance systems used around the world and consulting with ED physicians, pediatricians and internal medicine physicians involved in infectious disease control, the Syndromic Surveillance Research Team in Taiwan worked with the Real-time Outbreak and Disease Surveillance (RODS) Laboratory at the University of Pittsburgh to create Taiwan's ED-SSS. The system was evaluated by analyzing daily electronic ED data received in real-time from the 189 hospitals participating in this system between April 1, 2004 and March 31, 2005. RESULTS: Taiwan's ED-SSS identified winter and summer spikes in two syndrome groups: influenza-like illnesses and respiratory syndrome illnesses, while total numbers of ED visits were significantly higher on weekends, national holidays and the days of Chinese lunar new year than weekdays (p < 0.001). It also identified increases in the upper, lower, and total gastrointestinal (GI) syndrome groups starting in November 2004 and two clear spikes in enterovirus-like infections coinciding with the two school semesters. Using ED-SSS for surveillance of influenza-like illnesses and enteroviruses-related infections has improved Taiwan's pandemic flu preparedness and disease control capabilities. CONCLUSION: Taiwan's ED-SSS represents the first nationwide real-time syndromic surveillance system ever established in Asia. The experiences reported herein can encourage other countries to develop their own surveillance systems. The system can be adapted to other cultural and language environments for better global surveillance of infectious diseases and international collaboration.