17 research outputs found

    National reimbursement listing determinants of new cancer drugs: a retrospective analysis of 58 cancer treatment appraisals in 2007–2016 in South Korea

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    <p><b>Background:</b> Since the positive-list system was introduced, concerns have been raised over restricting access to new cancer drugs in Korea. Policy changes in the decision-making process, such as risk-sharing agreement and the waiver of pharmacoeconomic data submission, were implemented to improve access to oncology medicines, and other factors are also involved in the reimbursement for cancer drugs. The aim of this study is to investigate the reimbursement listing determinants of new cancer drugs in Korea.</p> <p><b>Methods:</b> All cancer treatment appraisals of Health Insurance Review and Assessment during 2007–2016 were analyzed based on 13 independent variables (comparative effectiveness, cost-effectiveness, drug-price comparison, oncology-specific policy, and innovation such as new mode of action). Univariate and multivariate logistic analyses were conducted.</p> <p><b>Results:</b> Of 58 analyzed submissions, 40% were listed in the national reimbursement formulary. In univariate analysis, four variables were related to listing: comparative effectiveness, drug-price comparison, new mode of action, and risk-sharing agreement. In multivariate logistic analysis, three variables significantly increased the likelihood of listing: clinical improvement, below alternative’s price, and risk-sharing arrangement. Cancer drug’s listing increased from 17% to 47% after risk-sharing agreement implementation.</p> <p><b>Conclusion:</b> Clinical improvement, cost-effectiveness, and RSA application are critical to successful national reimbursement listing.</p

    MCP-1-deficiency decreased CD11c-expressing cells via impairing the production of ROS and decreased activation of PLCγ2, Akt, and ERK upon M-CSF stimulation in BMM.

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    <p>BMMs from WT (open bar) and MCP-1-KO mice (oblique-lined bar) were incubated in the presence of M-CSF (30 ng/ml) with U73122 (10 µM), Akt inhibitor IV (0.3 µM), PD098059 (5 µM), DPI (50 nM), NAC (3 mM), or H<sub>2</sub>O<sub>2</sub> (300 µM) for 4 d (A). *, <i>P</i><0.05; ***, <i>P</i><0.001 compared with vehicle-treated WT cells. There was no significant difference between WT and MCP-1-KO cells except upon vehicle treatment. Treatment with U73122, Akt inhibitor IV, PD98059, DPI, NAC, or H<sub>2</sub>O<sub>2</sub> abolished the decrease in CD11cF4/80 observed in MCP-1-KO cells. BMMs were serum-starved for 8 h and stimulated with M-CSF for 1, 2, or 3 d (B). Phosphorylation of PLCγ2 was determined by Western blotting. Total protein level served as the loading control. Relative ratios of phosphorylated forms to total forms were plotted. **, <i>P</i><0.01; ***, <i>P</i><0.001 compared with WT cells. Intracellular levels of ROS upon stimulation in the presence of M-CSF (M) or/and MCP-1 with control IgG (3 µg/ml) or anti-MCP-1 Ab (3 µg/ml) for 2 d were determined in WT cells and MCP-1-KO cells using H2DCFDA (C, D). ROS levels were quantified by flow cytometry. *, <i>P</i><0.05; **, <i>P</i><0.01 compared with M-stimulated WT cells. No significant difference between WT and MCP-1-KO cells stimulated with M+MCP-1 (C). *, <i>P</i><0.05; ***, <i>P</i><0.001 compared with IgG-treated WT cells. No significant difference between IgG- and anti-MCP-1 Ab-treated MCP-1-KO cells (D). BMMs were transfected with sip47<sup>phox</sup> or scRNA. Downregulation of p47<sup>phox</sup> by siRNA was confirmed by RT-PCR and qPCR (E). The expression level obtained from scRNA-treated cells was set to be 1. After 24 h of transfection with siRNA, cells were stimulated with M-CSF for 2 d (mRNA) or 4 d (FACS) in order to determine CD11c (F) and for 2 d to measure ROS (G). *, <i>P</i><0.05; **, <i>P</i><0.01; ***, <i>P</i><0.001 compared with scRNA-transfected WT cells. No significant difference was found in MCP-1-KO cells (F, G). Similar results were obtained in three independent experiments.</p

    The absence of MCP-1 reduced fat mass and improved metabolic perturbation induced by OVX.

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    <p>WT mice (open bar) and MCP-1-KO (oblique-lined bar) mice were subjected to OVX or sham surgery, and then held for 12 weeks. Whole body weight change up to 12 weeks after surgery (A) and average daily food intake (B) were measured. *, <i>P</i><0.05; WT OVX vs. MCP-1-KO OVX mice. Adipocyte volume was calculated from photograph of hematoxylin-eosin staining of visceral fat, assuming that an adipocyte is a sphere (magnification, ×200). Scale bar, 100 µm (C). Glucose clearance (D) and insulin sensitivity (E) were determined 12 weeks after sham or OVX, following an intraperitoneal injection of glucose (1 mg/kg) and insulin (0.75 munits/kg), respectively. AUC was measured for each group for D and E. *, <i>P</i><0.05, ***, <i>P</i><0.001; WT OVX vs. MCP-1-KO OVX. Data are expressed as mean ± SEM. Differences between groups were analyzed by two-way ANOVA, followed by Bonferroni post-tests (C, D) (adipocyte volume; <i>P</i><0.001, AUC for glucose tolerance; <i>P</i><0.01, effect of surgery. adipocyte volume; <i>P</i><0.001, AUC for glucose tolerance; <i>P</i><0.05, effect of MCP-1). *, <i>P</i><0.05; ***, <i>P</i><0.001 compared with WT OVX mice. Similar results were obtained in three independent experiments.</p

    MCP-1-deficiency decreased OVX-induced immune cell infiltration in AT.

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    <p>SVCs from visceral fat were extracted from WT (open bar) and MCP-1-KO mice (oblique-lined bar) 12 weeks after sham or OVX surgery. SVCs were labeled with conjugated Abs to CD11bF4/80 (A), CD11cF4/80 (B), CD4 (C), and CD8 (D) and quantified by flow cytometry. Data are expressed as mean ± SEM. Differences between groups were analyzed by two-way ANOVA, followed by Bonferroni post-tests (CD11bF4/80, CD11cF4/80, CD4; <i>P</i><0.01, CD8; <i>P</i><0.05, effect of surgery. CD11cF4/80; <i>P</i><0.05, effect of MCP-1). *, <i>P</i><0.05; **, <i>P</i><0.01; ***, <i>P</i><0.001 compared with WT OVX mice. Similar results were obtained in three independent experiments.</p

    Physiological measurements of sham and OVX of WT and MCP-1-KO mice 12 weeks after operation.

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    <p>Data are expressed as mean ± SEM. ND, non-detectible. Differences between groups were analyzed by two-way ANOVA, followed by Bonferroni post-tests (Increased body weight, subcutaneous fat, visceral fat, serum H<sub>2</sub>O<sub>2</sub>, and blood insulin; <i>P</i><0.001, serum M-CSF; <i>P</i><0.01, blood glucose; <i>P</i><0.05, effect of surgery. Increased body weight, subcutaneous fat, and visceral fat; <i>P</i><0.001, serum M-CSF and blood insulin; <i>P</i><0.01, serum ROS; <i>P</i><0.05, effect of MCP-1). WT OVX vs. MCP-1-KO OVX;</p>*<p><i>P</i><0.05,</p>**<p><i>P</i><0.01,</p>***<p><i>P</i><0.001.</p

    A Comment on Moyn’s Christian Human Rights, ‘From Communist to Muslim: Religious Freedom and Christian Legacies’

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    <p>(A) Semi-quantitative analysis of the number of ED-1 positive cells, (B) fractional mesangial area, and (C) fibrotic area in kidney tissue. *<i>P</i> < 0.05, OL-C vs. other groups; †<i>P</i> < 0.05, LT vs. other groups; ‡<i>P</i> < 0.05, OL-DA vs. OL-VO. Values are expressed as means ± SE.</p

    Remote Ischemic Preconditioning for the Prevention of Contrast-Induced Acute Kidney Injury in Diabetics Receiving Elective Percutaneous Coronary Intervention

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    <div><p>Objective</p><p>Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI.</p><p>Methods</p><p>This randomized, double-blind, sham-controlled study enrolled patients with diabetes scheduled for elective PCI with eGFR ≤60 ml/min/1.73 m<sup>2</sup> or urinary albumin creatinine ratio of >300 mg/g to receive either RIPC or the sham ischemic preconditioning.</p><p>Results</p><p>One hundred and two patients (68.9 ± 8.2 years old, 47.1% men) were included. Baseline eGFR, creatinine and serum NGAL was similar between RIPC and control groups (48.5 ± 12 ml/min vs. 46.6 ± 10 ml/min, <i>p</i> = 0.391; 1.42 ± 0.58 mg/dl vs. 1.41 ± 0.34 mg/dl, <i>p</i> = 0.924; and 136.0 ± 45.0 ng/ml vs. 137.6 ± 43.3 ng/ml, <i>p</i> = 0.961, respectively). CI-AKI occurred in 13.7% (14/102) of the total subjects, with both RIPC and control groups having an equal incidence of 13.7% (7/51). No significant differences were seen in creatinine, NGAL, cardiac enzymes (troponin T, CKMB) and hs-CRP between the groups post-procedure.</p><p>Conclusions</p><p>In this study, RIPC applied prior to elective PCI was not effective in preventing CI-AKI in patients with diabetes with pre-existing CKD.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02329444" target="_blank">NCT02329444</a></p></div

    The expression of type IV collagen and total collagen content in renal tissues.

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    <p>(A) Representative immunoblot of type IV collagen, (B) quantitative analyses of the expression of type IV collagen and (C) the amount of hydroxyproline in renal tissue in LETO (LT) and OLETF rats with saline (OL-C), dapagliflozin (OL-DA) or voglibose (OL-VO) treatment. *<i>P</i> < 0.05, OL-C vs. other groups; †<i>P</i> < 0.05, LT vs. other groups; ‡<i>P</i> < 0.05, OL-DA vs. OL-VO; §<i>P</i> < 0.05, OL-C vs. OL-DA. Values are expressed as means ± SE.</p

    The expressions of RAS and antioxidant enzymes in renal tissues.

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    <p>(A) Representative immunoblots of AT1R, Cu/ZnSOD, MnSOD and catalase. Quantitative analyses of the expression of AT1R (B), Cu/ZnSOD (C), MnSOD (D), catalase (E) in LETO (LT) and OLETF rats with saline (OL-C), dapagliflozine (OL-DA) or voglibose (OL-VO) treatment. *<i>P</i> < 0.05, OL-C vs. other groups; †<i>P</i> < 0.05, LT vs. other groups; ‡<i>P</i> < 0.05, OL-DA vs. OL-VO. Values are expressed as means ± SE. AT1R, Ang II type I receptor</p
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