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      • HCV : PE-134 ; Hemoglobin decline during peginterferon Alfa-2B (PEG-2B)/ribavirin (RBV) treatment in real-life is associated with favorable SVR rates in difficult-to-treat patients with HCV genotype 1 (G1) infection

        ( G Teuber ),( S Mauss ),( D Huppe ),( E Zehnter ),( M P Manns ),( T Dahhan ),( U Meyer ),( T Witthoft ),( B Moller ),( N Dikopoulos ),( J Brack ),( B Stade ),( M Bilzer ),( Bng Hepatitis Study Group 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

        Background and Aims: Recently, it has been shown for the overall G1 population that anemia as well as the maximal hemoglobin (Hb) decline during peginterferon/RBV treatment is associated with higher SVR rates. We here investigated whether the maximal Hb decline influences SVR rates in difficult-to-treat patients undergoing Peg2b/RBV therapy for HCV G1 infection in real-life. Methods: Data of patients treated for G1 infection within the German Peg2b/RBV observational study were retrospectively analyzed. In this real-life cohort study G1 infection was treated with Peg2b 1.5 μg/kg/wk + weight-based RBV (800-1200 mg/day) for up to 48 wks at 285 sites. Subjects who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as undetectable serum HCV-RNA 24 wks after EOT response. Only one patient received erythropoietin treatment for anemia. Results: 1851 patients had baseline and at least one Hb measurement during therapy. Overall SVR rate was 42.6% (789/1851). SVR rates were only slightly higher for subjects with an absolute Hb decline >3 g/dL (44.3%, 493/1114) compared to those with maximum Hb declines <3 g/dL (40.2%, 296/737) (p=0.08). In contrast, a significant (p=0.0004) difference in SVR rates was obtained by comparing subjects with Hb declines >2 g/dL (44.6%, 673/1510) with those who experienced Hb declines <2 g/dL (34.0%, 116/341). Similar SVR rates of 46.1% (164/356) and 44.1% (509/1154) in patients with Hb declines >2 g/dL even if they did/did not become anemic (Hb<10 g/dL) strongly support Hb decline, and not anemia, as primary beneficial mechanism improving SVR. As summarized in the table, Hb declines >2 g/dl were significantly associated with higher SVR rates in difficult-to-treat patients, such as subjects elder than 50 years or subjects with high baseline viral load >600.000 IU/ml. Interestingly no beneficial effect was observed in patients with low platelet count (<150/nL), an indicator of advanced fibrosis/cirrhosis. Patients who first developed a Hb decline >2 g/dL during weeks 0-4 were likely to achieve similar SVR (41.3%, 365/883) than those who developed a Hb decline <2 g/dL (44.9%, 386/859). In contrast, a Hb decline >2 g/dL compared to <2 g/dL during weeks 0-4 was associated with a 2-3 fold higher risk of anemia in female (16.6% vs 40.5%) and male patients (7.3% vs 19.0%) when compared with a Hb decline <2 g/dL. Conclusions: Patients with HCV genotype 1 infection and in particular the subgroup of difficult-to-treat patients elder than 50 years or with HVL, achieve up to 15% higher SVR rates when they develop a Hb decline >2 g/dL during Peg2b/RBV therapy. However, patients with low platelet count <150/nL do not achieve this beneficial virologic effect.

      • HCV, Alcoholic : PE-134 ; Hemoglobin decline during peginterferon Alfa-2B (PEG-2B)/ribavirin (RBV) treatment in real-Life is associated with favorable SVR rates in difficult-to-treat patients with HCV genotype 1 (G1) infection

        ( G Teuber ),( S Mauss ),( D Huppe ),( E Zehnter ),( M P Manns ),( T Dahhan6 ),( U Meyer ),( T Witthoft ),( B Moller9,),( N Dikopoulos ),( J Brack ),( B Stade ),( M Bilzer ),( The Bng Hepatitis Study 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

        Background and Aims: Recently, it has been shown for the overall G1 population that anemia as well as the maximal hemoglobin (Hb) decline during peginterferon/RBV treatment is associated with higher SVR rates. We here investigated whether the maximal Hb decline influences SVR rates in difficult-to-treat patients undergoing Peg2b/RBV therapy for HCV G1 infection in real-life. Methods: Data of patients treated for G1 infection within the German Peg2b/RBV observational study were retrospectively analyzed. In this real-life cohort study G1 infection was treated with Peg2b 1.5 μg/kg/wk + weight-based RBV (800-1200 mg/day) for up to 48 wks at 285 sites. Subjects who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as undetectable serum HCV-RNA 24 wks after EOT response. Only one patient received erythropoietin treatment for anemia. Results: 1851 patients had baseline and at least one Hb measurement during therapy. Overall SVR rate was 42.6% (789/1851). SVR rates were only slightly higher for subjects with an absolute Hb decline >3 g/dL (44.3%, 493/1114) compared to those with maximum Hb declines <3 g/dL (40.2%, 296/737) (p=0.08). In contrast, a significant (p=0.0004) difference in SVR rates was obtained by comparing subjects with Hb declines >2 g/dL (44.6%, 673/1510) with those who experienced Hb declines <2 g/dL (34.0%, 116/341). Similar SVR rates of 46.1% (164/356) and 44.1% (509/1154) in patients with Hb declines >2 g/dL even if they did/did not become anemic (Hb<10 g/dL) strongly support Hb decline, and not anemia, as primary beneficial mechanism improving SVR. As summarized in the table, Hb declines >2 g/dl were significantly associated with higher SVR rates in difficult-to-treat patients, such as subjects elder than 50 years or subjects with high baseline viral load >600.000 IU/ml. Interestingly no beneficial effect was observed in patients with low platelet count (<150/nL), an indicator of advanced fibrosis/cirrhosis. Patients who first developed a Hb decline >2 g/dL during weeks 0-4 were likely to achieve similar SVR (41.3%, 365/883) than those who developed a Hb decline <2 g/dL (44.9%, 386/859). In contrast, a Hb decline >2 g/dL compared to <2 g/dL during weeks 0-4 was associated with a 2-3 fold higher risk of anemia in female (16.6% vs 40.5%) and male patients (7.3% vs 19.0%) when compared with a Hb decline <2 g/dL. Conclusions: Patients with HCV genotype 1 infection and in particular the subgroup of difficult-to-treat patients elder than 50 years or with HVL, achieve up to 15% higher SVR rates when they develop a Hb decline >2 g/dL during Peg2b/RBV therapy. However, patients with low platelet count <150/nL do not achieve this beneficial virologic effect.

      • SCISCIESCOPUS

        Non-ideality of polymer melts confined to nanotubes

        Lee, N.-K.,Farago, J.,Meyer, H.,Wittmer, J. P.,Baschnagel, J.,Obukhov, S. P.,Johner, A. Editions de Physique 2011 Europhysics letters Vol.93 No.4

        <P>Corrections to chain ideality have been demonstrated recently for polymer melts in the bulk and in ultrathin films. It has been shown that the effect of incomplete screening is stronger in the latter. We show here that the deviation from ideality is even stronger in thin capillaries. Describing the crossover from the free bulk to the confined regime as the radius of the capillary decreases below the typical coil radius we make connection to the so far disconnected work by Brochard and de Gennes (<A HREF='http://dx.doi.org/10.1051/jphyslet:019790040016039900'><I>J. Phys. (Paris), Lett.</I>, <B>40</B> (1979) 399</A>) predicting chain segregation in very thin capillaries. Due to the generalized Porod scattering of the segregated chains, the Kratky representation of the intrachain structure factor reveals a plateau for all regimes although the chains become swollen with increasing confinement.</P>

      • Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase ½ dose escalation and expansion trial

        El-Khoueiry, A.B.,Sangro, B.,Yau, T.,Crocenzi, T.S.,Kudo, M.,Hsu, C.,Kim, T.Y.,Choo, S.P.,Trojan, J.,Welling, T.H.,Meyer, T.,Kang, Y.K.,Yeo, W.,Chopra, A.,Anderson, J.,dela Cruz, C.,Lang, L.,Neely, J. J. Onwhyn ; Elsevier Science Ltd 2017 The Lancet Vol.389 No.10088

        Background: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. Methods: We did a phase ½, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous sorafenib treatment was allowed. A dose-escalation phase was conducted at seven hospitals or academic centres in four countries or territories (USA, Spain, Hong Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39 sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan). At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose-expansion phase, and an Eastern Cooperative Oncology Group performance status of 1 or less. Patients with HBV infection had to be receiving effective antiviral therapy (viral load <100 IU/mL); antiviral therapy was not required for patients with HCV infection. We excluded patients previously treated with an agent targeting T-cell costimulation or checkpoint pathways. Patients received intravenous nivolumab 0.1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion phase to patients in four cohorts: sorafenib untreated or intolerant without viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and HBV infected. Primary endpoints were safety and tolerability for the escalation phase and objective response rate (Response Evaluation Criteria In Solid Tumors version 1.1) for the expansion phase. This study is registered with ClinicalTrials.gov, number NCT01658878. Findings: Between Nov 26, 2012, and Aug 8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have completed treatment and follow-up is ongoing. During dose escalation, nivolumab showed a manageable safety profile, including acceptable tolerability. In this phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease progression. Incidence of treatment-related adverse events did not seem to be associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48 patients had grade ¾ treatment-related adverse events. Three (6%) patients had treatment-related serious adverse events (pemphigoid, adrenal insufficiency, liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for dose expansion. The objective response rate was 20% (95% CI 15-26) in patients treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28) in the dose-escalation phase. Interpretation: Nivolumab had a manageable safety profile and no new signals were observed in patients with advanced hepatocellular carcinoma. Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma. Funding: Bristol-Myers Squibb.

      • KCI등재

        Occupational Injuries Among Construction Workers by Age and Related Economic Loss: Findings From Ohio Workers' Compensation, USA: 2007–2017

        Kaur Harpriya,Steven J. Wurzelbacher,Bushnell P. Tim,Bertke Stephen,Meyers Alysha R.,Grosch James W.,Naber Steven J.,Lampl Michael 한국산업안전보건공단 산업안전보건연구원 2023 Safety and health at work Vol.14 No.4

        Background: This study examined age-group differences in the rate, severity, and cost of injuries among construction workers to support evidence-based worker safety and health interventions in the construction industry. Methods: Ohio workers' compensation claims for construction workers were used to estimate claim rates and costs by age group. We analyzed claims data auto-coded into five event/exposure categories: transportation incidents; slips, trips, and falls (STFs); exposure to harmful substances and environments; contact with objects and equipment (COB); overexertion and bodily reaction. American Community Survey data were used to determine the percentage of workers in each age group. Results: From 2007–2017, among 72,416 accepted injury claims for ∼166,000 construction full-time equivalent (FTE) per year, nearly half were caused by COB, followed by STFs (20%) and overexertion (20%). Claim rates related to COB and exposure to harmful substances and environments were highest among those 18–24 years old, with claim rates of 313.5 and 25.9 per 10,000 FTE, respectively. STFs increased with age, with the highest claim rates for those 55–64 years old (94.2 claims per 10,000 FTE). Overexertion claim rates increased and then declined with age, with the highest claim rate for those 35–44 years old (87.3 per 10,000 FTE). While younger workers had higher injury rates, older workers had higher proportions of lost-time claims and higher costs per claim. The total cost per FTE was highest for those 45–54 years old ($1,122 per FTE). Conclusion: The variation in rates of injury types by age suggests that age-specific prevention strategies may be useful.

      • KCI등재
      • KCI등재

        Dependence of Trap Concentrations in ZnO Thin Films on Annealing Conditions

        H. von Wenckstern,G. Biehne,M. Lorenz,M. Grundmann,F. D. Auret,W. E. Meyer,P. J. Janse van Rensburg,M. Hayes,J. M. Nel 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.53 No.5

        Electron traps in ZnO thin films were characterized by using thermal admittance and deep level transient spectroscopy. The samples were grown by using pulsed-laser deposition (PLD), and some of them were annealed in oxygen and nitrogen ambients, respectively, or in vacuum. We found that two closely lying defect levels existed in these PLD thin films with thermal activation energies of 300 meV and 370 meV, respectively. While the 300-meV electron trap had similar concentrations after annealing in different ambient, the 370 meV trap was abundant in the as-grown state and after oxygen annealing. Its concentration was considerably reduced after annealing in vacuum or in nitrogen, respectively.

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