Abstract

Background People who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use–related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown. Methods In this prospective, open-label, observational trial at a harm reduction organization’s drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR. Results Eighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P < .001) and receiving OAT at week 24 (P = .01). Of 67 patients not already receiving OAT at baseline, 53 (79%) started OAT. At week 24, 68 (68%) patients were receiving OAT. Receipt of OAT was associated with fewer opiate-positive urine drug screens (P = .003), lower human immunodeficiency virus risk-taking behavior scores (P < .001), and lower rates of opioid overdose (P = .04). Conclusions The Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use. Clinical Trials Registration NCT03221309.

Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.

PurposeThe traditional prone positioning of percutaneous nephrolithotomy (PCNL) is associated with various anesthetic and logistic difficulties. We aimed to compare the surgical outcomes of PCNLs performed using our modified supine position with those performed in the standard prone position.Materials and MethodsA prospective group of 236 renal units (224 patients) undergoing PCNL were included in this 2 site study: 160 were performed in the modified supine position were compared with 76 undergoing PCNL in the prone position. The outcomes of radiation dose, radiation time, stone free rate, body mass index (BMI), stone size, operative time, length of stay (LOS), in hospital and complications were compared. Chi-square and t-tests were used.ResultsThere were no significant differences in mean radiation time, radiation dose or stone size between the modified supine and prone groups. The supine group had a higher mean BMI (31 kg/m2 vs. 28 kg/m2, p=0.03), shorter mean surgical time (93 minutes vs. 123 minutes, p<0.001), shorter mean LOS (2 days vs. 3 days, p=0.005) and higher stone free rate (70% vs. 50%, p=0.005). There were no differences in septic or bleeding complications but the prone group had a higher rate of overall complications.ConclusionsModified supine PCNL has significantly lower operative time, shorter LOS and higher stone-free rate compared with prone in our series, while remaining a safe procedure.