Cost-utility analysis of using paliperidone palmitate in schizophrenia in China.

Objective: Long-acting injections (LAIs) of paliperidone palmitate have been shown to improve medication adherence and relieve psychotic symptoms. However, the specific cost-utility analysis of these LAIs in schizophrenia in China remains unclear. Methods: A multi-state Markov model was constructed to simulate the economic outcomes of patients with schizophrenia in China who received paliperidone palmitate 1-month formulation (PP1M), paliperidone palmitate 3-month formulation (PP3M), and paliperidone extended-release (ER). A cost-utility analysis was conducted, mostly derived from published literature and clinical databases. All costs and utilities were discounted at a rate of 5% per annum. The primary outcome measure was the incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were also applied. Results: After 20 years, compared to ER, using PP1M resulted in an increased discounted cost from $36,252.59 to $43,207.28. This increased cost was associated with a gain in quality-adjusted life years (QALYs) from 8.60 to 9.45. As a result, the ICER for PP1M was estimated to be $8,247.46/QALY, which was lower than the willingness-to-pay (WTP) threshold of $12,756.55/QALY. When using PP3M instead of ER, the incremental cost was $768.81 and the incremental utility was 0.88 QALYs, projecting an ICER of $873.13/QALY, which was also lower than the WTP threshold of $12,756.55/QALY. The univariate sensitivity analysis showed that the costs of PP1M, PP3M, and ER had the greatest impact on ICERs. The probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,756.55/QALY, the probability of PP1M and PP3M being cost-effective was 59.2% and 66.0%, respectively. Conclusion: From the Chinese healthcare system perspective, PP3M and PP1M are both more cost-effective compared to ER, and PP3M has notable cost-utility advantages over PP1M.

TNF-α (G-308A) Polymorphism, Circulating Levels of TNF-α and IGF-1: Risk Factors for Ischemic Stroke-An Updated Meta-Analysis.

Objective: Accumulated studies have explored gene polymorphisms and circulating levels of tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1 in the etiology of ischemic stroke (IS). Of the numerous etiopathological factors for IS, a single-nucleotide polymorphism (SNP) rs1800629 located in the TNF-α gene promoter region and increased levels of TNF-α were found to be associated with IS in different ethnic backgrounds. However, the published results are inconsistent and inconclusive. The primary objective of this meta-analysis was to investigate the concordance between rs1800629 polymorphism and IS. A secondary aim was to explore circulating levels of TNF-α and IGF-1 with IS in different ethnic backgrounds and different sourced specimens. Methods: In this study, we examined whether rs1800629 genetic variant and levels of TNF-α and IGF-1 were related to the etiology of IS by performing a meta-analysis. Relevant case-control studies were retrieved by database searching and systematically selected according to established inclusion criteria. Results: A total of 47 articles were identified that explored the relationship between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS risk susceptibility. Statistical analyses revealed a significant association between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS pathogenesis. Conclusion: Our findings demonstrated that the TNF-α rs1800629 polymorphism, the increased levels of TNF-α, and decreased levels of IGF-1 were involved in the etiology of IS.

Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder.

Major depressive disorder is a common chronic emotional disorder, and cyclic adenosine monophosphate response element binding protein 1 (CREB1) is hypothesized to play a role in its pathogenesis. The aim of the present study was to investigate the associations between major depressive disorder and relevant single nucleotide polymorphisms (SNPs) in the CREB1 gene. A total of 1,038 subjects of Han Chinese descent were recruited, including 456 patients with major depressive disorder (case group) and 582 healthy volunteers (control group). The frequency distributions of the genotypes and alleles were estimated in the case and control groups, and analyzed for any correlation with major depressive disorder. Three relevant SNP sites in CREB1 were analyzed using quantitative polymerase chain reaction, and statistical analyses were performed to estimate their use as risk factors for major depressive disorder. The analyses revealed that rs2254137 and rs16839883 in CREB1 showed polymorphisms in the sample population, and the genotype and allele frequencies of rs16839883 differed significantly when comparing the patients and healthy controls (P<0.05). No statistically significant differences were detected in the two SNP sites between the male and female patients (P>0.05). Furthermore, no statistically significant differences were detected in rs2254137 genotype and allele distribution when comparing the male and female patients with their corresponding control groups (P>0.05). However, statistically significant differences were observed in the genotype and allele frequencies of rs16839883 when the male and female patients were compared with their respective controls (P<0.05). Therefore, the results demonstrated that there is a close correlation between the rs16839883 polymorphism in CREB1 and major depressive disorder, which suggests that this SNP site should be further studied as a potential biomarker for major depressive disorder.

[M cell in vitro model and its application in oral delivery of macromolecular drugs].

The oral administration of bioactive macromolecular drugs such as proteins, peptides and nucleic acids represents unprecedented challenges from the drug delivery point of view. One key consideration is how to overcome the gastrointestinal tract absorption barrier. Recent studies suggest that microfold cell (M cell), a kind of specialized antigen-sampling epithelial cell which is characterized by a high endocytic rate and low degradation ability, may play an important role in macromolecule oral absorption. The development of an in vitro M cell coculture system and its modified models greatly advanced the study of M cells and the development of oral delivery system for macromolecular drugs. The special structure, function and formation characteristics, and biomarkers of M cell are summarized in this review. The applications of in vitro M cell models in developing oral delivery system ofbioactive macromolecular drugs are discussed.

Tyrosine hydroxylase, interleukin-1beta and tumor necrosis factor-alpha are overexpressed in peripheral blood mononuclear cells from schizophrenia patients as determined by semi-quantitative analysis.

The aim of this study is to profile the peripheral biomarkers (tyrosine hydroxylase, TH; interleukin-1beta, IL-1beta; and tumor necrosis factor-alpha, TNF-alpha) for schizophrenia and explore their relations with clinical symptoms. Thirty-nine patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS), and 25 siblings and 30 normal healthy subjects were used as controls. The mRNA expression levels of TH, IL-1beta and TNF-alpha in peripheral blood mononuclear cells, as determined with semi-quantitative reverse transcription-polymerase chain reaction, were all significantly increased in both patients (3-fold) and siblings (2-fold) as compared with normal control. Both IL-1beta and TNF-alpha were significantly correlated with scores on the general psychopathology subscale of the PANSS. A significant positive correlation between IL-1beta and TH expression was found in both sibling and normal controls, but not in patients, while a positive correlation between IL-1beta and TNF-alpha was significant in all the groups. These results suggest that TH, IL-1beta and TNF-alpha are overexpressed in the peripheral blood mononuclear cells of schizophrenia patients, perhaps due to the hereditary factors. IL-1beta and TNF-alpha may influence the symptoms of schizophrenia in the cognition dysfunction and anxiety/depression domains of the PANSS.

[The mRNA expression levels of IL-1beta, TNF-alpha and tyrosine hydroxylase in peripheral blood of paranoid schizophrenic patients].

AIM: To investigate the gene expression levels of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and tyrosine hydroxylase (TH) in peripheral blood of paranoid schizophrenic patients, and explore the neuroimmunological mechanism of paranoid schizophrenia. METHODS: The mRNA expression levels of IL-1beta, TNF-alpha and TH in the peripheral blood of 39 paranoid schizophrenic patients and 30 normal controls were measured with RT-PCR and semi-quantitative technique. RESULTS: The mRNA expression levels of IL-1beta, TNF-alpha and TH was higher in paranoid schizophrenic patients than those in normal controls (P<0.01). The correlation between the gene expression levels of IL-1beta and TH was found in normal controls (r=0.666, P<0.01), not in paranoid schizophrenic patients (P>0.05); and the correlation between the gene expression levels of IL-1beta and TNF-alpha was significant in all groups (r=0.847 for normal controls and 0.942 for patients, P<0.01, respectively). CONCLUSION: Pro-inflammation cytokines and catecholamines have been demonstrated to be overexpressed in the peripheral blood of paranoid schizophrenic patients. And the correlation between catecholamines and pro-inflammation cytokines, which exists in the controls, is broken in paranoid schizophrenic patients.