BackgroundIt 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).MethodsWe 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.ResultsThe 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.ConclusionsThis 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.

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.

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 a-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.

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