Novel direct-acting antivirals (DAAs) are now the standard of care for the management of hepatitis C virus (HCV) infection. Branded DAAs are associated with high sustained virological response at 12 weeks post-completion of therapy (SVR12), but are costly. We aimed to assess the efficacy of generic oral DAAs in a real-life clinical scenario. Consecutive patients with known HCV infection who were treated with generic-oral DAA regimens (May 2015 to January 2017) were included. Demographic details, prior therapy and SVR12 were documented. Four hundred and ninety patients (mean age: 38.9 ± 12.7 years) were treated with generic DAAs in the study time period. Their clinical presentations included chronic hepatitis (CHC) in 339 (69.2%) of cases, compensated cirrhosis in 120 (24.48%) cases and decompensated cirrhosis in 31 (6.32%) cases. Genotype 3 was most common (n = 372, 75.9%) followed by genotype 1 (n = 97, 19.8%). Treatment naïve and treatment-experienced (defined as having previous treatment with peginterferon and ribavirin) were 432 (88.2%) and 58 (11.8%), respectively. Generic DAA treatment regimens included sofosbuvir in combination with ribavirin (n = 175), daclatasvir alone (n = 149), ribavirin and peginterferon (n = 80), ledipasvir alone (n = 43), daclatasvir and ribavirin (n = 37), and ledipasvir and ribavirin (n = 6). Overall SVR12 was 95.9% (470/490) for all treatment regimens. SVR12 for treatment naïve and experienced patients was 97.0% (419/432) and 87.9% (51/58), respectively, P = .005. High SVR12 was observed with various regimens, irrespective of genotype and underlying liver disease status. There were no differences in SVR12 with 12 or 24 weeks therapy. No major adverse event occurred requiring treatment stoppage. Generic oral DAAs are associated with high SVR rates in patients with HCV infection in a real-life clinical scenario.
Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000–10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.
Various methods of skin closure exist in joint replacement surgery. Although subcuticular skin closure techniques offer an aesthetic advantage over conventional skin stapling, no measurable differences have been reported. Furthermore, newer barbed sutures, such as the V-Loc absorbable suture (Covidien, Mansfield, Massachusetts), theoretically distribute tension evenly through the wound and help decrease knot-related complications. The purpose of this study was to evaluate whether wound complication rates were (1) lower in V-Loc closure cases as theoretically suggested, (2) lower for subcuticular closure vs staples, and (3) significantly different for knee and hip joint reconstruction.A retrospective chart review was conducted of 278 consecutive cases of primary joint reconstruction performed by a single surgeon (L.P.). The study group comprised 106 men and 161 women. Average patient age at surgery was 63 years (range, 18-92 years), and average body mass index of the cohort was 33.7 kg/m(2) (range, 25-51 kg/m(2)). Skin was closed via staple gun or subcuticular stitch (3-0 Biosyn [Covidien] vs V-Loc). Seven (3.9%) wound complications occurred in 181 cases closed with staples. Four (7.8%) wound complications occurred in 51 cases closed via subcuticular Biosyn suture. Six (13.0%) wound complications occurred in 46 cases closed with V-Loc suture. The staple group had a lower rate of complications when compared with the suture group as a whole (P=.033) and when compared specifically with the V-Loc suture group (P=.017).
Background and Study Aims: Endoscopic ultrasound-directed transgastric ERCP (EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. Aims of this study were 1) to determine rates of long-term adverse events (AEs) after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; 2) identify predictors of persistent fistula; 3) assess outcomes of endoscopic closure when persistent fistula is encountered. Patients and Methods: This was a multicenter, retrospective study involving 13 centers between 1/2014 and 3/2019. AEs were defined according to ASGE lexicon. Persistent fistula was defined as upper GI series or EGD showing evidence of fistula. Results: A total of 178 patients (mean age 58 years, 79% F) underwent EDGE. Technical success was achieved in 98% of cases (175/178) with a mean procedure time of 92 min. Periprocedural AEs occurred in 28 patients (15.7%; mild 10.1%, moderate 3.3%, severe 2.2%). The 4 severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10% of those sent for objective testing (9/90). Following identification of fistula, 5/9 patients underwent endoscopic closure procedures, which were successful in all cases. Conclusions: The EDGE procedure is associated with high clinical success rates, and an acceptable risk profile. Persistent fistula after lumen apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistula are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.
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