Cost Trend Analysis of Initial Cancer Treatment in Taiwan

Background

Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment.

Methodology/Principal Findings

The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI) system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05). Hospitalization costs comprised the largest portion of payments for all cancers. During 1996–2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05). In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share.

Conclusions/Significance

In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit from these expensive treatments.     

Psoriasis and the Risk of Pneumonia: A Population-Based Study

Background

Psoriasis is a prevalent autoimmune disorder. Various studies have reported on the relationship between psoriasis and chronic diseases but very few have explored the association between psoriasis and subsequent acute infection. This retrospective cohort study aimed to compare the risk of pneumonia between subjects with and those without psoriasis.

Methods

The medical records of 14,022 patients with psoriasis and 14,022 without psoriasis were obtained from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was followed-up for a three-year period. Cox proportional hazard regressions were performed to compare difference of subsequent pneumonia incidence between subjects with and those without psoriasis.

Results

There were 206 (1.47%) subjects with psoriasis and 138 (0.98%) without psoriasis hospitalized for pneumonia. By Cox proportional hazard regressions analysis, the HR (hazard ratio) of pneumonia requiring hospitalization for patients with psoriasis was 1.50 (95% confidence interval [CI]: 1.21–1.86) compared to patients without psoriasis. The adjusted HR was 1.40 (95% CI: 1.12–1.73). The adjusted HR of pneumonia hospitalization for subjects with mild and severe psoriasis was 1.36 (95% CI: 1.09–1.70) and 1.68 (95% CI: 1.12–2.52), respectively, compared to those without psoriasis.

Conclusions

Patients with psoriasis have significantly higher incidence of pneumonia compared to those without psoriasis.     

Prolonged Seasonality of Respiratory Syncytial Virus Infection among Preterm Infants in a Subtropical Climate

Objective

There is limited epidemiological data on the seasonality of respiratory syncytial virus (RSV) infection in subtropical climates, such as in Taiwan. This study aimed to assess RSV seasonality among children ≤24 months of age in Taiwan. We also assessed factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with RSV-associated hospitalization in preterm infants to confirm the appropriateness of the novel Taiwanese RSV prophylactic policy.

Study Design

From January 2000 to August 2010, 3572 children aged ≤24-months were admitted to Taipei Mackay Memorial Hospital due to RSV infection. The monthly RSV-associated hospitalization rate among children aged ≤24 months was retrospectively reviewed. Among these children, 378 were born preterm. The associations between GA, CA, and BPD and the incidence of RSV-associated hospitalization in the preterm infants were assessed.

Results

In children aged ≤24 months, the monthly distribution of RSV-associated hospitalization rates revealed a prolonged RSV season with a duration of 10 months. Infants with GAs ≤32 weeks and those who had BPD had the highest rates of RSV hospitalization (P<0.001). Preterm infants were most vulnerable to RSV infection within CA 9 months.

Conclusions

Given that Taiwan has a prolonged (10-month) RSV season, the American Academy of Pediatrics'' recommendations for RSV prophylaxis are not directly applicable. The current Taiwanese guidelines for RSV prophylaxis, which specify palivizumab injection (a total six doses until CA 8–9 months) for preterm infants (those born before 28^6/7 weeks GA or before 35^6/7 weeks GA with BPD), are appropriate. This prophylaxis strategy may be applicable to other countries/regions with subtropical climates.     

In Vitro Study of a Novel Nanogold-Collagen Composite to Enhance the Mesenchymal Stem Cell Behavior for Vascular Regeneration

Novel nanocomposites based on type I collagen (Col) containing a small amount (17.4, 43.5, and 174 ppm) of gold nanoparticles (AuNPs, approximately 5 nm) were prepared in this study. The pure Col and Col-AuNP composites (Col-Au) were characterized by the UV-Vis spectroscopy (UV-Vis), surface-enhanced raman spectroscopy (SERS) and atomic force microscopy (AFM). The interaction between Col and AuNPs was confirmed by infrared (IR) spectra. The effect of AuNPs on the biocompatibility of Col, evaluated by the proliferation and reactive oxygen species (ROS) production of mesenchymal stem cells (MSCs) as well as the activation of monocytes and platelets, was investigated. Results showed that Col-Au had better biocompatibility than Col. Upon stimulation by vascular endothelial growth factor (VEGF) and stromal derived factor-1α (SDF-1α), MSCs expressed the highest levels of αvβ3 integrin/CXCR4, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), and Akt/endothelial nitric oxide synthase (eNOS) proteins when grown on the Col-Au (43.5 ppm) nanocomposite. Taken together, Col-Au nanocomposites may promote the proliferation and migration of MSCs and stimulate the endothelial cell differentiation. These results suggest that Col-Au may be used to construct tissue engineering scaffolds for vascular regeneration.     

Up-Regulation of Nerve Growth Factor in Cholestatic Livers and Its Hepatoprotective Role against Oxidative Stress

The role of nerve growth factor (NGF) in liver injury induced by bile duct ligation (BDL) remains elusive. This study aimed to investigate the relationship between inflammation and hepatic NGF expression, to explore the possible upstream molecules up-regulating NGF, and to determine whether NGF could protect hepatocytes from oxidative liver injury. Biochemical and molecular detection showed that NGF was up-regulated in cholestatic livers and plasma, and well correlated with systemic and hepatic inflammation. Conversely, systemic immunosuppression reduced serum NGF levels and resulted in higher mortality in BDL-treated mice. Immunohistochemistry showed that the up-regulated NGF was mainly localized in parenchymal hepatocytes. In vitro mechanistic study further demonstrated that TGF-β1 up-regulated NGF expression in clone-9 and primary rat hepatocytes. Exogenous NGF supplementation and endogenous NGF overexpression effectively protected hepatocytes against TGF-β1- and oxidative stress-induced cell death in vitro, along with reduced formation of oxidative adducted proteins modified by 4-HNE and 8-OHdG. TUNEL staining confirmed the involvement of anti-apoptosis in the NGF-exhibited hepatoprotection. Moreover, NGF potently induced Akt phosphorylation and increased Bcl-2 to Bax ratios, whereas these molecular alterations by NGF were only seen in the H₂O₂-, but not TGF-β1-treated hepatocytes. In conclusion, NGF exhibits anti-oxidative and hepatoprotective effects and is suggested to be therapeutically applicable in treating cholestatic liver diseases.     

Induced Pluripotent Stem Cell Therapy Ameliorates Hyperoxia-Augmented Ventilator-Induced Lung Injury through Suppressing the Src Pathway

Background

High tidal volume (V_T) mechanical ventilation (MV) can induce the recruitment of neutrophils, release of inflammatory cytokines and free radicals, and disruption of alveolar epithelial and endothelial barriers. It is proposed to be the triggering factor that initiates ventilator-induced lung injury (VILI) and concomitant hyperoxia further aggravates the progression of VILI. The Src protein tyrosine kinase (PTK) family is one of the most critical families to intracellular signal transduction related to acute inflammatory responses. The anti-inflammatory abilities of induced pluripotent stem cells (iPSCs) have been shown to improve acute lung injuries (ALIs); however, the mechanisms regulating the interactions between MV, hyperoxia, and iPSCs have not been fully elucidated. In this study, we hypothesize that Src PTK plays a critical role in the regulation of oxidants and inflammation-induced VILI during hyperoxia. iPSC therapy can ameliorate acute hyperoxic VILI by suppressing the Src pathway.

Methods

Male C57BL/6 mice, either wild-type or Src-deficient, aged between 2 and 3 months were exposed to high V_T (30 mL/kg) ventilation with or without hyperoxia for 1 to 4 h after the administration of Oct4/Sox2/Parp1 iPSCs at a dose of 5×10⁷ cells/kg of mouse. Nonventilated mice were used for the control groups.

Results

High V_T ventilation during hyperoxia further aggravated VILI, as demonstrated by the increases in microvascular permeability, neutrophil infiltration, macrophage inflammatory protein-2 (MIP-2) and plasminogen activator inhibitor-1 (PAI-1) production, Src activation, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and malaldehyde (MDA) level. Administering iPSCs attenuated ALI induced by MV during hyperoxia, which benefited from the suppression of Src activation, oxidative stress, acute inflammation, and apoptosis, as indicated by the Src-deficient mice.

Conclusion

The data suggest that iPSC-based therapy is capable of partially suppressing acute inflammatory and oxidant responses that occur during hyperoxia-augmented VILI through the inhibition of Src-dependent signaling pathway.     

Annonacin,a mono-tetrahydrofuran acetogenin,arrests cancer cells at the G1 phase and causes cytotoxicity in a Bax- and caspase-3-related pathway

Annonaceous acetogenins are a group of potential anti-neoplastic agents isolated from Annonaceae plants. In this study, we purified annonacin, a cytotoxic mono-tetrahydrofuran acetogenin, from the seeds of Annona reticulata and analyzed its biological effects. Herein, we have shown that annonacin caused significant cell death in various cancer cell lines. T24 bladder cancer cells at the S phase were more vulnerable to the cytotoxicity of annonacin. Furthermore, annonacin activated p21 in a p53-independent manner and arrested T24 cells at the G1 phase. It also induced Bax expression, enhanced caspase-3 activity, and caused apoptotic cell death in T24 cells. In summary, these results suggest that annonacin is potentially a promising anti-cancer compound.     

Differences in the fatty acid composition of larvae and metamorphosing sea lampreys, Petromyzon marinus

This study was designed to evaluate biochemical changes in the fatty acid (FA) compositions of selected lipid depot (kidney and liver) and absorption (intestine) organs in larvae and metamorphosing sea lamprey, Petromyzon marinus. Palmitic or stearic acids were generally the predominant saturated fatty acids (SFA) before and during metamorphosis, but the greatest proportion of myristic acid occurred in renal triacylglycerol (TG). Monoenes, dienes, and polyenes consist mainly of 16:1, 18:1, and 20:1, 18:2 and 20:2omega6, and 18:4omega3, respectively. Alterations in these predominant fatty acids occurred during lamprey metamorphosis, but depended on tissue, lipid class, and developmental status. During metamorphosis, kidney TG and phospholipid (PL) classes tended to mobilize SFA and enhance the fatty acid unsaturation, as indicated by increased unsaturated/saturated ratio, unsaturation index (USI), and total mean chain length (MCL). There was a tendency to increase saturation in the fatty acids of liver TG and PL classes and intestine TG, FA and monoacylglycerol (MG) classes, but to increase unsaturation in the fatty acids of liver cholesteryl ester (CE), FA and MG classes and intestine PL and CE classes from larva or stage 3 to stage 7. Increased polyunsaturated fatty acids in kidney TG and PL from larvae to stage 5 transformers and intestine PL and CE from stage 3 to stage 7 transformers may reflect an osmoregulatory pre-adaptation. The presence of branched-chain SFA (BCSFA) and the odd number of fatty acids (ONFA) indicated a significant role of detritivores in the benthic larvae. Decreased abundance of BCSFA, ONFA, and 18:2 dienes occurred in the transformed intestine TG as non-trophic metamorphosis proceeded. These data suggest that sea lamprey metamorphosis may proceed in a habitat, dietary, osmoregulatory, energetic, and developmental pre-adaptation of fatty acid composition from benthic filter-feeding larvae to pelagic parasitic juveniles.     

Accumbal 14-3-3ζ protein downregulation is associated with cocaine-conditioned memory

Cocaine-conditioned memory has been known to cause cocaine craving and relapse, while its underlying mechanisms remain unclear. We explored accumbal protein candidates responsible for a cocaine-conditioned memory, cocaine-induced conditioned place preference (CPP). Two-dimensional gel electrophoresis in conjunction with liquid chromatography mass spectrometry analysis was utilized to identify accumbal protein candidates involved in the retrieval of cocaine-induced CPP. Among the identified candidate proteins, a downregulated 14-3-3ζ protein was chosen and confirmed by Western immunoblotting. A polymer-mediated plasmid DNA delivery system was then used to overexpress 14-3-3 protein in mouse nucleus accumbens before the CPP retrieval tests. Overexpression of accumbal 14-3-3ζ protein was found to diminish conditioned cue/context-mediated cocaine-induced CPP. In contrast, another isoform of 14-3-3 protein, 14-3-3ε protein, did not affect conditioned cue/context-mediated cocaine-induced CPP. Overexpression of accumbal 14-3-3ζ protein did not produce motor activity-impairing effect or alter local dopamine metabolism. Moreover, overexpression of accumbal 14-3-3ζ protein did not affect food-induced CPP. These results, taken together, indicated that overexpressed accumbal 14-3-3ζ protein specifically decreased conditioned cue/context-mediated cocaine memory. Further understanding of the function of accumbal 14-3-3ζ protein may shed light on the treatment of cocaine craving and relapse.