Efficacy and safety of sofosbuvir-based regimens for treatment in chronic hepatitis C genotype 1 patients with moderately impaired renal function

BACKGROUND/AIMS: Treatment of chronic hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) is essential. The availability of sofosbuvir (SOF) has dramatically improved overall HCV cure rates, however there is insufficient data regarding its use in patients with CKD. We evaluated SOF in patients with hepatitis C genotype 1 (G1) and moderately impaired renal function. METHODS: We retrospectively reviewed all patients treated with a SOF-based regimen from December 2013 through September 2015 at Virginia Mason Medical Center. Data was then collected for HCV G1 patients with stage 3 CKD. RESULTS: A total of 28 patients with HCV G1 and stage 3 CKD were treated with a SOF-based regimen. Twenty-one patients had stage 3A CKD (estimated glomerular filtration rate [eGFR] 45–60 mL/min/1.73m2) and 7 patients had stage 3B CKD (eGFR 30–45 mL/min/1.73m2). The overall rate of sustained virologic response (SVR) 12 weeks after completion of therapy (SVR12) was 85.7% (24/28). SVR12 in stage 3A CKD patients was 81.0% (17/21) and in stage 3B CKD patients, SVR12 was 100% (7/7). Based on the treatment regimen used, the SVR12 was 81.8% (9/11), 92.3% (12/13), and 75.0% (3/4) for SOF/ledipasvir (LDV), SOF/simeprevir (SIM), and SOF/pegylated interferon (PEG)/ribavirin (RBV), respectively. Greater than 30% reduction eGFR was observed in 4 out of 28 patients. CONCLUSIONS: SOF-based regimens resulted in high SVR12 rates in patients with moderately impaired renal function. During therapy, HCV patients with CKD should be carefully monitored for worsening renal function.

Real-World Single-Center Experience with Sofosbuvir-Based Regimens for the Treatment of Chronic Hepatitis C Genotype 1 Patients

BACKGROUND/AIMS: The approval of sofosbuvir (SOF), a direct-acting antiviral, has revolutionized the treatment of chronic hepatitis C virus (HCV). METHODS: We assessed the sustained virological response (SVR) of SOF-based regimens in a real-world single-center setting for the treatment of chronic HCV genotype 1 (G1) patients. This was a retrospective review of chronic HCV G1 adult patients treated with a SOF-based regimen at Virginia Mason Medical Center between December 2013 and August 2015. RESULTS: The cohort comprised 343 patients. Patients received SOF+ledipasvir (LDV) (n=155), SOF+simeprevir (SIM) (n=154), or SOF+peginterferon (PEG)+ribavirin (RBV) (n=34). Of the patients, 50.1% (n=172) had cirrhosis. The SVR rate was 92.2% for SOF/LDV, 87.0% for SOF/SIM, and 82.4% for SOF/PEG/RBV. Compared with the cirrhotic patients, the patients without cirrhosis had a higher SVR (96.8% vs 85.5%, p=0.01, SOF/LDV; 98.2% vs 80.6%, p=0.002, SOF/SIM; 86.4% vs 75.0%, p=0.41, SOF/PEG/RBV). In this study, prior treatment experience adversely affected the response rate in subjects treated with SOF/PEG/RBV. CONCLUSIONS: In this single-center, real-world setting, the treatment of chronic HCV G1 resulted in a high rate of SVR, especially in patients without cirrhosis.

Book Review: The Virginia Tech Massacre: Strategies and Challenges for Improving Mental Health Policy on Campus and Beyond

No abstract available.

Outcomes and Use of Therapeutic Drug Monitoring in Multidrug-Resistant Tuberculosis Patients Treated in Virginia, 2009-2014 / 결핵및호흡기질환

BACKGROUND: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. METHODS: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges. RESULTS: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean C2hr, 16.6+/-10.2 microg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2+/-1.5 microg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5+/-14.0 microg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0+/-29.1 microg/mL; all within or above); linezolid in three (mean C2hr, 11.4+/-4.1 microg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3+/-3.7 microg/mL; 1 [50%] below); ethionamide in one (C2hr, 1.49 microg/mL, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. CONCLUSION: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

Effects of different pretreatments on germination of Prunus serotina seed sources.

Establishing intensive plantations of fast growing hardwood tree species that have high market values in the forest industry can narrow the gap between Turkey's demand and the supply of quality hardwood products. Black cherry (P. serotina Ehrh.) is a fast growing hardwood species with a high market value. Introducing and intensively growing black cherry (BC) in Turkey may significantly reduce the country's quality wood shortage. Adequate seed germination constitutes the first essential step for successful establishments. In this paper effects of different pretreatments, including artificial and natural stratification, on the seeds of different BC seed sources (SSs) were studied. Pretreatments had substantial effects on the dormancy breaking and germination behaviours of the SSs. Consecutive periods of complex warm and cold artificial stratification regimes longer than 90 days or natural stratification (where seeds were assumed to be naturally exposed to this complexity) resulted in best dormancy breaking and, in turn, germination among all pretreatments. Deeper dormancy and reduced germination rates of some BC seeds as the altitude of the source increases might suggest an ecological adaptive strategy of the species. BC may have deeper morphophysiological dormancy than is commonly believed. Seed size may have a positive effect on seed germination.

Liquid-Based Cytology Using MonoPrep2(TM) System in Cervicovaginal Cytology: Comparative Study with Conventional Pap Smear and Histology / 대한세포병리학회지

We compared the diagnostic accuracy of liquid-based cervicovaginal cytology using MonoPrep2(TM) system (Monogen, Herndon, Virginia, USA), a manual system based on membrane filtration method, with conventional Pap smear. Study population included 92 patients visiting the gynecologic department under the suspicion of uterine cervical disease. In thirty of them, surgical biopsy was performed. MonoPrep2(TM) system provided well-preserved monolayer specimen with good nuclear morphology. However, about 19% of specimens were inadequate to interpret due to low cellularity. The detection rate of abnormal cells more than ASCUS (atypical squamous cells of unknown significance) was 23.9% and higher than 19.4 % of conventional Pap smear. Diagnostic concordance rate with conventional Pap smear was 81%, and severe discordance rate influencing on the management of patient was 7.6 %. Among these seven cases, MonoPrep2(TM) system was more diagnostic only in four. In comparison with histology, the sensitivity of diagnosis of MonoPrep2(TM) system was 78.9% and slightly higher than 73.5% of conventional Pap smear. However, the specificity was 81.1% and lower than 90.9% of Pap smear. In conclusion, MonoPrep2(TM) system provided diagnostic accuracies similar to the conventional Pap smear. The inexpertness of slide preparation and the low cellularity were considered to endow a limitation in more accurate evaluation.