Background & Aims The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Methods We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET—a prospective, observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, 836 patients with HCV genotype 1 infection began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment—a 2 week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. Results The overall rate of SVR rate was 84% (675/802 patients, 95% CI: 81–87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. Conclusions In a large, prospective observational cohort study, a 12 week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811

Mycetoma is a chronic infective condition of tropical and subtropical regions. It is commoner in males, especially those in their third or fourth decade who work on the land. The clinical triad of subcutaneous nodule, sinuses and discharge usually leads to diagnosis; the disease is commonly painless. Treatment is by extensive surgical excision of affected areas and may include limb amputation. Recurrence is common, rates ranging from 20 to 90 per cent. Medical treatment may be used on its own or as an adjunct to surgery. Although such therapy may cure over half of those with actinomycetoma (caused by bacteria, mainly aerobic actinomycetes), those affected by eumycetoma (caused by fungi) have a poorer prognosis and may require many years of drug therapy.

Background Data outside of clinical trials with direct acting antiviral (DAA) regimens with or without ribavirin as treatment of chronic HCV in solid organ transplant recipients is limited. Methods Liver transplant (LT), kidney transplant (KT) and dual liver kidney (DLK) transplant recipients from the HCV-TARGET database, a multicenter, longitudinal clinical care treatment cohort, treated with DAA regimens between January 1 2014 and February 15, 2016 were included to assess safety and efficacy. Results 443 post-transplant patients were included (KT=60, LT =347, DLK=36); 42% had cirrhosis, 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% G1a, 27% G1b, and 8% G1 no subtype) and were treated with sofosbuvir/ledipasvir (SOF/LDV) ± RBV (85%) followed by sofosbuvir + daclatasvir (SOF + DAC) ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir (PrOD) ± RBV (6%). SVR12 rates were available on 415 patients and 397 patients (95.7%) achieved SVR12: 96.3%, 94.6% and 90.9% among LT, KT and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher eGFR and lower creatinine. Female gender, baseline albumin ≥ 3.5 g/dL, baseline total bilirubin ≤ 1.2 mg/dL, the absence of cirrhosis and hepatic decompensation predicted SVR12. Six episodes of acute rejection (n=2 KT, 4 LT) occurred during HCV treatment in 4 and after cessation of treatment in 2. Conclusion In a large prospective observational cohort study, DAA therapy with SOF/LDV, PrOD and SOF plus DAC was efficacious and safe in, LT, KT, and DLK transplant recipients. Ribavirin did not influence SVR. Graft rejection was rare.

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