From the perspective of health economics, the evaluation of drug-related cost effectiveness and clinical utility is crucial. We conducted a cost-utility analysis of two first-line drugs, tenofovir ...alafenamide (TAF) and entecavir (ETV), in the treatment of chronic hepatitis B (CHB) patients. We performed inverse probability of treatment weighting (IPTW) to match the independent variables between the two treatment groups. The incremental cost effectiveness ratio (ICER) of the two treatment groups was simulated using a decision tree with the Markov annual-cycle model. A total of 54 patients treated with TAF and 98 with ETV from January 2016 to December 2020 were enrolled. The total medical cost in the TAF group was NT$76,098 less than that in the ETV group, and TAF demonstrated more effectiveness than ETV by 3.19 quality-adjusted life years (QALYs). When the time horizon was set at 30 years, the ICER of the TAF group compared with the ETV group was -NT$23,878 per QALY, suggesting more cost savings for TAF. Additionally, with the application of TAF, over NT$366 million (approximately US$12 million) can be saved annually. TAF demonstrates cheaper medical costs and more favorable clinical QALYs than ETV. To balance health insurance benefits and cost effectiveness, TAF is the optimal treatment for CHB.
The gold standard of antituberculosis susceptibility testing is based on culture method which takes weeks. Rapid detection of resistance to isoniazid (INH) and rifampin (RIF) to avoid inappropriate ...regimens and to prevent transmission of resistant strains are important. A membrane array (BluePoint MTBDR) was developed to identify Mycobacterium tuberculosis complex (MTBC) and the genetic mutations responsible for resistance to RIF and INH. We aimed to evaluate the performance of this array for diagnosing drug‐resistant MTBC. A total of 261 acid‐fast bacilli positive sputum specimens, 1025 positive mycobacteria growth indicator tube (MGIT) cultures and 544 clinical isolates were analyzed. Antituberculosis susceptibility testing was the gold standard and was performed on MTBC isolated from positive MGIT cultures and on 544 clinical isolates. The sensitivity and specificity of the array to detect MTBC were 62.2% and 88.1% for sputum specimens, 100% and 97.9% for MGIT cultures. For detection of drug‐resistant MTBC in positive MGIT tubes, the sensitivities of the array were 100% for RIF and 97.1% for INH, while the specificities were 99.7% and 100%, respectively. Interestingly, we noticed four genotypically RIF‐resistant but phenotypically RIF‐susceptible isolates and eight genotypically INH resistant but phenotypically INH‐susceptible isolates. Comparing with conventional culture methods for species identification and drug susceptibility testing, the BluePoint MTBDR assay demonstrated to be a rapid test with high sensitivity and specificity to identify MTBC and to detect isoniazid and rifampin resistance when it is applied to broth culture specimens and clinical isolates.
AIM:To evaluate the influence of multiple samplings during esophagogastr oduodenoscopy(EGD) on the accuracy of the rapid urease test,and the validity of newly developed rapid urease tests,HelicotecUT ...plus test and HelicotecUT test,CLO test and ProntoDry test.METHODS:A total of 355 patients undergoing EGD for dyspepsia were included.Their Helicobacter pylori(H.pylori) treatment status was either nave or eradicated.Six biopsy specimens from antrum and gastric body,respectively,were obtained during EGD.Single...
Objectives: The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole‐based quadruple therapy for Helicobacter pylori ...infection after failure of standard triple therapies.
Patients and Methods: From January 2007 to March 2009, 1055 H. pylori‐infected patients received standard triple regimens (proton‐pump inhibitor (PPI), clarithromycin, and amoxicillin). Helicobacter pylori eradication was achieved in 865 (81.9%) subjects. One hundred ninety eradication‐failure patients were enrolled and randomly assigned to receive a 7‐day eradication therapy. Ninety‐six patients were treated with esomeprazole‐based quadruple rescue therapies (EB), while 94 patients were treated with rabeprazole‐based quadruple rescue therapies (RB). Follow‐up endoscopy was done 16 weeks later to assess the treatment response. Patients’ responses, CYP2C19 genotypes, and antibiotics resistances were also examined.
Results: Intention‐to‐treat analysis revealed that RB had better eradication rates than EB (EB: 72.9%; 95% CI: 64.9–80.9% and RB: 78.7%; 95% CI 72.5–84.9%) (p value = .543). Per‐protocol results were EB = 75.3%; 95% CI: 70.3–80.3% and RB = 85.1%; 95% CI: 80.6–89.6% (p value = .0401). Both regimens had similar compliance (p value = 0.155) and adverse events (p value = 0.219). We also surveyed those patients without resistance of any antibiotics. RB still showed better outcome than EB. Our data showed that esomeprazole‐based regimen and CYP2C19 Hom EM genotype were important predictors for eradication failure.
Conclusions: In quadruple therapy, rabeprazole‐based regimens had better efficacy than esomeprazole‐based regimens. CYP2C19 polymorphism also played an important role in quadruple therapy. It seems advisable to change PPI to rabeprazole in second‐line quadruple therapy.
Aim: The aim of this study was to develop an in vitro human gastric stem and/or progenitor cell model that may be used to study the mechanism of gastric carcinogenesis induced by Helicobacter pylori ...infection.
Methods: Human gastric biopsy was minced and digested with collagenase and dispase and cultured in a low‐calcium medium (serum‐free keratinocyte medium; keratinocyte‐SFM) supplemented with N‐acetyl‐l‐cysteine and l‐ascorbic acid 2‐phosphate. Actively proliferating epithelial colonies with sustained growth were isolated and characterized for karyotype and phenotypes related to stem cell characteristics including proliferation and differentiation potential, ability of anchorage‐independent growth (AIG), gap junctional intercellular communication (GJIC) and the expression of Oct‐4, a transcription factor previously shown to be expressed in embryonic stem cells, adult stem cells and undifferentiated tumor cells. To study the carcinogenic effect of H. pylori infection, gastric stem and/or progenitor cells were incubated with H. pylori culture products and/or N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG), a chemical carcinogen, to see the telomerase activation.
Results: Multiple cell lines with stem cell features were isolated by this new cell culture method. The results based on detailed characterization of one cell clone, KMU‐GI2, revealed stem cell features of these cells. The initial clone contained mostly undifferentiated epithelial‐like cells, which, upon subculture and propagation, gave rise to a heterogeneous cell population. Single cell‐derived subclones, similar to the parental population, retained high differentiation potential and were capable of giving rise to many morphologically different cell types (i.e. epithelial‐like, glial or neuron‐like, round and various peculiar‐shaped cells). Although these cells were normal in karyotype and competent in GJIC, they had the ability to grow in soft agar. Cells expressing epithelial membrane antigen (EMA), mucin 5AC, glial fibrillary acidic protein (GFAP), cytokeratin‐18 (CK‐18), trefoil factor 1 (TFF‐1) and Oct‐4 were found in the cell culture, but not E‐cadherin‐, gastrin‐ or telomerase‐expressing cells. Furthermore, spontaneously immortalized non‐tumorigenic clones could be derived from the cell population. After treating these cell cultures with the chemical carcinogen, MNNG and H. pylori culture products for 5 days, telomerase activity and telomerase mRNA expression were significantly elevated, while treatment with either of them showed no effect.
Conclusion: The new cell culture method can be used to develop gastric epithelial cell clones with sustained growth from endoscopic biopsy. The gastric cell clone showed several stem and/or progenitor cell phenotypes (i.e. the ability of AIG, high differentiation capacity, high susceptibility to spontaneous immortalization and the expression of Oct‐4). The telomerase expression in these gastric stem and/or progenitor cells can be upregulated by exposure to H. pylori culture products and MNNG, an important step in neoplastic transformation. These results show that putative human gastric stem and/or progenitor cell clones can be developed by our method and these cells could be useful for studying the mechanisms of human gastric carcinogenesis including the mechanism of action of H. pylori, as well as the regulation of the proliferation and differentiation of human gastric mucosa.
Background. It is urgent to find alternative agents due to increasing failure rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long-term effect of silver nanoparticles ...(AgNP) on H. pylori based on Mongolian gerbil’s model. Materials and Methods. Fifty gerbils were randomly allocated to six groups (A–F). Group (Gr) A: the gerbils were fed with broth; Gr B and D: the gerbils were fed with AgNP/clay complex (0.1% of weight); Gr C and E: the gerbils were fed with AgNP/clay complex(1% of weight); and Gr D, E, and F: the gerbils were inoculated with H. pylori. At the 20th experimental week, the gerbils were sacrificed. Histology was evaluated according to the classification of the Sydney system. P<0.05 was considered to be statistically significant. Results. The AgNP/clay has more obvious inhibitory effect on H. pylori in vitro. There was a trend of higher concentrations of AgNP with stronger inhibitory effect on H. pylori growth (P=0.071). There were no significant differences of inflammation among groups D, E, and F (P=0.688).Conclusion. AgNP/clay would be a potential and safe agent for inhibiting H. pylori. It should be helpful for eradication of H. pylori infection.
GOALStudy the mechanism of gastric tumor development.
BACKGROUNDWe have generated and characterized a novel human gastric cell line, KMU-CS12 (CS12), from an immortal cell line, KMU-CSN (CSN; ...formerly named as GI2CS) which was derived from putative human gastric stem cell/progenitor cell clone, KMU-GI2.
STUDYThe characterization of the CS12 cell line includes gene expression by immunocytochemical staining, cell proliferation and differentiation potential, cyotogenetic analysis by Giemsa banding and spectral karyotype analysis (SKY), and tumorigenicity in immune-deficient congenic inbred, nude mice (BALB/cAnN-Foxn1nu/CrlNarl). The Agilent Human 1A oligo-array and RT-PCR were also employed to analyze the expression of homeobox (HOX) genes.
RESULTSThe CS12 gastric cell line showed cancer cell phenotypes, i.e. the ability of anchorage-independent growth high frequency (44%) and to the expression of Oct-4, a transcription factor expressed in embryonic stem cells and many types of cancer cells, and tumor development in immune deficient mice. SKY analysis indicated a characteristic duplication of the short arm of chromosome 7 to chromosome 12. Agilent Human 1A oligo-array analysis showed that the expression of 1145 genes was upregulated while that of 890 genes was downregulated in CS12 cells. RT-PCR revealed that homeobox genes (HOXA4, HOXA5, HOXA7, HOXA9, and HOXA13) were highly expressed in CS12 cells in culture, as well as tumor tissues developed by CS12 cells in immunodeficient mice for six to eight weeks.
CONCLUSIONExcept for the duplication of the short arm of Chromosome 7 on Chromosome12, the karyotype of the tumorigenic CS12 cells is similar to the parental GI2 cells which are non-tumorigenic and normal in karyotype. This chromosomal change could be the cause for the high expression of HOXA genes and tumorigenicity of these cells found in this study. Thus HOXA genes might play an important role in gastric carcinogenesis.
Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration, gastric lymphoma and gastric cancer. Certain herbal remedies have been used to treat gastric disease. In this ...study, we examined the anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on
Helicobacter pylori-infected human gastric epithelial AGS cell. AGS cells were treated with
Helicobacter pylori at a bacterium/cell ratio of 300:1. mRNA expression and protein levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and western blot analysis, respectively. Interleukin-8 (IL-8) level and the translocation of nuclear factor kappa B (NF-κB) were measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked DNA–protein interaction assay (ELDIA), respectively. Nitric oxide production was measured by Griess reagent. We found that SHXT and baicalin inhibited
Helicobacter pylori-induced cyclooxygenase-2 (COX-2) enhancement and IκBα degradation in both mRNA and protein levels. SHXT and baicalin also inhibited
Helicobacter pylori-induced inducible nitric oxide synthase (iNOS) and IL-8 mRNA expression, and decreased NO and IL-8 production. Furthermore, SHXT and baicalin inhibited nuclear translocation of p50 subunit of NF-κB in
Helicobacter pylori-infected AGS cells. Based on the above findings, SHXT and baicalin might exert anti-inflammatory and gastroprotective effects in
Helicobacter pylori-induced gastric inflammation.
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