Beta-delayed proton emission from 20Mg

Beta-delayed proton emission from 20 Mg has been measured at ISOLDE, CERN, with the ISOLDE Decay Station (IDS) setup including both charged-particle and gamma-ray detection capabilities. A total of 27 delayed proton branches were measured including seven so far unobserved. An updated decay scheme, including three new resonances above the proton separation energy in 20 Na and more precise resonance energies, is presented. Beta-decay feeding to two resonances above the Isobaric Analogue State (IAS) in 20 Na is observed. This may allow studies of the 4032.9(2.4)keV resonance in 19 Ne through the beta decay of 20 Mg, which is important for the astrophysically relevant reaction 15O( $\alpha$ , $\gamma$ )19Ne . Beta-delayed protons were used to obtain a more precise value for the half-life of 20 Mg, 91.4(1.0)ms

Genetic Heterogeneity of Hepatitis C Virus in Association with Antiviral Therapy Determined by Ultra-Deep Sequencing

The hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail.Using a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) α2b plus ribavirin therapy.Ultra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, corresponding to a mean of more than 1000 clones in each specimen, and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. There was no significant difference in the level of viral complexity between immediate virologic responders and non-responders at baseline (p = 0.39). Immediate virologic responders (n = 8) showed a significant reduction in the genetic complexity spanning all the viral genetic regions at the early phase of IFN administration (p = 0.037). In contrast, non-virologic responders (n = 8) showed no significant changes in the level of viral quasispecies (p = 0.12), indicating that very few viral clones are sensitive to IFN treatment. We also demonstrated that clones resistant to direct-acting antivirals for HCV, such as viral protease and polymerase inhibitors, preexist with various abundances in all 27 treatment-naïve patients, suggesting the risk of the development of drug resistance against these agents.Use of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important implications regarding the treatment response and outcome of antiviral therapy

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Switching bipolar disorder patients treated with clozapine to another antipsychotic medication: a mirror image study

Petru Ifteni,1,2 Andreea Teodorescu,1,2 Marius Alexandru Moga,1 Alina Mihaela Pascu,1 Roxana Steliana Miclaus1,2 1Faculty of Medicine, Transilvania University of Brasov, Brasov, Romania; 2Clinical Hospital of Psychiatry and Neurology Brasov, Brasov, Romania Abstract: Bipolar disorder (BD) is associated with periodic symptom exacerbations, leading to functional impairment, and increased risk of suicide. Although clozapine has never been approved for the treatment of BD, it is occasionally used in severe mania. The aim of the study is to evaluate the risks and benefits of switching clozapine in remitted BD patients. This is an observational, mirror image study of 62 consecutive remitted BD outpatients treated with clozapine. Twenty-five patients were switched to another antipsychotic following a change in a drug reimbursement rule, while 37 continued on clozapine. The mean time in remission was shorter for the switched group (9.2&plusmn;4 months vs 13&plusmn;6 months, P=0.018), and the number of patients who relapsed was larger (n=21 vs n=8, P&lt;0.0001). The results suggest that switching from clozapine to another antipsychotic may increase the risk of relapses in remitted patients with BD. Keywords: clozapine, bipolar disorder, relapse, switch, cos

Effects and tolerability of betahistine in patients with vestibular vertigo: results from the Romanian contingent of the OSVaLD study

Ovidiu Băjenaru,1 Adina Maria Roceanu,2 Silviu Albu,3 Viorel Zainea,4 Alexandru Pascu,4 Mădălina Gabriela Georgescu,4 Sebastian Cozma,5 Luigi Mărceanu,6 Dafin Fior Mureşanu7 1Department of Neurology, Carol Davila University of Medicine and Pharmacy, 2Department of Neurology, University Hospital, Bucharest, 3IInd Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, 4Institute of Phono-Audiology and ENT Functional Surgery Prof Dr Dorin Hociota, Carol Davila University of Medicine and Pharmacy, Bucharest, 5ENT Department, University of Medicine and Pharmacy Grigore T Popa, Audiology and Vestibulogy Department, Rehabilitation Clinical Hospital, Iasi, 6Transilvania University, Faculty of Medicine, Department: Doctoral Program (PhD), Brasov, 7&quot;RoNeuro&quot; Institute for Neurological Research and Diagnostic Cluj-Napoca, University of Medicine and Pharmacy &quot;Iuliu Haţieganu&quot;, Department of Clinical Neurosciences, Cluj-Napoca, Romania Background and methods: An efficacy population of 245 patients with vertigo of peripheral vestibular origin was recruited in Romania as part of a 3-month multinational, post-marketing surveillance study of open-label betahistine 48 mg/day (OSVaLD). Endpoints were changes in the Dizziness Handicap Index (primary endpoint), Medical Outcome Study Short-Form 36 (SF-36v2&reg;), and the Hospital Anxiety and Depression Scale. Results: During treatment, the total Dizziness Handicap Index score improved by 41 points (on a 100-point scale). Statistically significant improvements of 12&ndash;14 points were recorded in all three domains of the Dizziness Handicap Index scale (P&lt;0.0001). Betahistine therapy was also accompanied by progressive improvements in mean Hospital Anxiety and Depression anxiety and depression scores (P&lt;0.0001) and significant improvements in both the physical and mental component summary of the SF-36v2 (P&lt;0.0001). Betahistine was well tolerated, with only one suspected adverse drug reaction recorded in the Romanian safety population (n=259). Conclusion: Betahistine 48 mg/day was associated with improvements in multiple measures of health-related quality of life and had a good tolerability profile in these Romanian patients with recurrent peripheral vestibular vertigo. Keywords: betahistine, vertigo, dizziness, anxiety, depression, Romani

Evolution of deformation in the neutron-rich krypton isotopes: The Kr-96 nucleus

The energy of the first excited 2+ state in 96Kr was measured as 241 keV. The nucleus was produced in the fission of 238U induced by a 954-MeV 136Xe beam and prompt \u3b3 rays were observed using the clover array CLARA in coincidence with fission products identified with the PRISMA spectrometer. The evolution of the quadrupole collectivity in the Kr isotopes with N\u2a7e50 is discussed by comparison with that from the Rb to Mo isotones and with predictions of various theoretical calculations