Background & Aims Hepatitis C virus (HCV)-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated ...efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir + ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy. Methods This was a phase II, multicenter, open-label, single-arm study in treatment-naïve or peginterferon/ribavirin treatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine ± naloxone. Patients received 12 weeks of co-formulated ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) and dasabuvir (250 mg twice daily) + weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12 weeks post-treatment. Results Thirty-eight non-cirrhotic patients on chronic methadone (n = 19) or buprenorphine (n = 19) were enrolled. A total of 37 patients (97.4%) had a sustained virologic response 12 weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations <10 g/dl. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required. Conclusions The interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir + ribavirin for 12 weeks was well tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use.
Lively biographies of British artists, with material to instruct and entertain were – as Horace Walpole regretted in 1762 – difficult to construct from the limited materials available to biographers ...of British art. By the early years of the nineteenth century the situation had changed, with many anecdotes, loosely based on traditional European topoi, becoming both a functioning unit and a battleground in the histories that were being constructed of British art. Allan Cunningham’s Lives of the Most Eminent Artists of 1828-31 was the most influential attempt to date to effectively integrate detailed anecdotes of artists into a narrative of British art that placed ‘Nation’ and ‘Nature’ at its heart. This article examines Cunningham’s varied use of anecdote in the Lives of British Sculptors (vol 3). These stories function within the context of his grand narrative of Nation and Nature, and his lionisation of Chantrey. Sometimes his strategies involved the undermining of known anecdotes told of Roubiliac, Bacon and Damer. Elsewhere he creates new, and usually ironic, versions of recognisable topoi of childhood genius, transcendent inspiration, imitation of the ancients, and the taming of Nature. These anecdotes, and anti-anecdotes, can be contrasted with the un-ironic use of established classic anecdotal forms in the accounts that he gave of Francis Chantrey.
Posttraumatic stress disorder (PTSD) is a mental health condition with greater prevalence in military veterans. Caregivers and those providing support to individuals with PTSD may experience unique ...challenges due to this illness. This article includes a review of PTSD's core symptoms
and treatment options, and discusses considerations for older individuals providing care and support to a veteran with PTSD. Familiarity with communication pitfalls, issues in long-term care, and resources available to caregivers should help prepare an individual to provide care to a veteran
with PTSD.
Abstract
In our introduction, we establish the original conference context of the 15 following position papers, emphasizing that the papers represent a conversation between participants, each of whom ...had been allocated a single monument from St Paul’s Cathedral in the period between c. 1796 and 1913, to think about the memorial’s visual and material richness and complexity, as well as its immediate and wider cathedral location, and broader discursive contexts. We map out the historiographical contexts of the papers, within the contexts of sculpture studies, studies of church monuments, interdisciplinary studies of the nineteenth century, and histories of Victorian Christianity – and especially Anglicanism – as it intersects with other world religions, and seeks to evangelize both at home and abroad.
Introduction
Despite high efficacy of current direct‐acting antiviral agents (DAAs) in treating chronic hepatitis C virus (HCV) infection, a small portion of patients fail treatment. QUARTZ‐I was a ...phase 2, open‐label, multicenter, two‐part study that assessed the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) with dasabuvir (DSV) with or without the addition of sofosbuvir (SOF) and/or ribavirin (RBV) in DAA treatment‐experienced adults with chronic HCV GT1 infection.
Materials and Methods
Genotype 1 HCV‐infected patients with or without compensated cirrhosis had prior treatment failure to any DAA (part 1) or ledipasvir/SOF (part 2). Patients received OBV/PTV/r + DSV ± SOF with or without RBV for 12 or 24 weeks. The primary endpoint of this study is the percentage of patients achieving sustained virologic response at post‐treatment week 12 (SVR12).
Results
In part 1 of the study, 95.5% (21/22) of patients achieved SVR12, and in part 2, the SVR12 rate was 85.7% (6/7). Most adverse events (AEs) were mild and moderate in severity. Two serious AEs occurred and were assessed as not being related to study drug, of which one resulted in study drug discontinuation. Two patients experienced grade 3 elevations of serum alanine aminotransferase, and no other grade ≥3 laboratory abnormalities were observed.
Conclusion
The multi‐targeted regimen of OBV/PTV/r + DSV ± SOF with or without RBV was effective in the treatment of patients who failed previous DAA regimens including NS3/4A protease and NS5A and NS5B polymerase inhibitors. These results provide a promising outcome for patients that traditionally had limited treatment options.
Transcranial magnetic stimulation (TMS) is a neuro-modulation technique for treatment-resistant major depressive disorder (MDD). Standard TMS protocols for MDD involve once-daily treatment for 6 to 9 ...weeks. We report a case series of an accelerated TMS protocol for outpatient MDD treatment.
From July 2020 through January 2021, patients deemed appropriate candidates for TMS treatment were offered an accelerated TMS protocol consisting of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex, localized by the Beam F3 method, and consisting of 5 treatments daily for 5 days. Assessment scales were obtained as part of standard clinical care.
A total of 19 veterans received the accelerated protocol and 17 completed treatment. Statistically significant mean reductions from baseline to end of treatment were observed across all assessment scales. Remission and response rates, as defined by changes in Montgomery-Åsberg Depression Rating Scale scores, were 47.1% and 64.7%, respectively. Treatments were well tolerated without unexpected or serious adverse events.
This case series details the safety and efficacy of an accelerated iTBS TMS protocol consisting of 25 treatments over 5 days. Improved depressive symptoms were observed, with remission and response rates similar to standard TMS protocols of daily TMS for ≥6 weeks.
Summary Objectives To examine the safety and efficacy of ombitasvir and ABT-450 with ritonavir (ABT-450/r) ± ribavirin (RBV) in treatment-naïve, non-cirrhotic adults with chronic HCV genotype 1–3 ...infection. Methods Patients in this open-label, exploratory, phase 2, multicenter study received ombitasvir (25 mg QD) and ABT-450/r (200/100 mg QD) ± RBV for 12 weeks. Primary efficacy endpoint was HCV RNA < lower limit of quantitation (LLOQ) from week 4 through 12. Sustained virologic response 12 weeks post-treatment (SVR12 ) was a secondary endpoint. Results Sixty-one patients were enrolled. Among genotype 1-, 2-, and 3-infected patients, respectively, HCV RNA was<LLOQ from week 4 through 12 in 10 (100%; 95% CI 69–100), 9 (90%; 56–100), and 7 (70%; 35–93) receiving the RBV-containing regimen and 9 (90%; 56–100), 8 (80%; 44–97), and 2 (18%; 2–52) receiving the RBV-free regimen. Among genotype 1-, 2-, and 3-infected patients, respectively, SVR12 was achieved by 10 (100%), 8 (80%), and 5 (50%) receiving the RBV-containing regimen, and 6 (60%), 6 (60%), and 1 (9%) receiving the RBV-free regimen. The most common adverse events were fatigue, nausea, and headache. One patient discontinued due to an adverse event. Conclusions In this study, ombitasvir and ABT-450/r ± RBV regimens were generally well-tolerated. Sustained virologic response was achieved in most patients with HCV genotype 1 or 2 infection, but low SVR rates were observed in HCV genotype 3-infected patients.
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