HCV compliance and treatment success rates are higher with DAAs in structured HCV clinics compared to general hepatology clinics.

The real-world cure rates for hepatitis C (HCV) with direct-acting antivirals (DAAs) based on intention-to-treat (ITT) analysis may be lower than reported in the literature because of non-compliance.To determine whether patients treated in a structured outpatient HCV clinic (SHC) had higher compliance and treatment success rates compared to those treated in general hepatology clinics (GHC).In this study, we compared the treatment and compliance success rates of 488 and 840 patients treated in the SHC and GHC, respectively. The SHC required a pre-treatment clinic visit when patients picked up their initial medication, and received detailed education of the treatment plan and follow-up. In the GHC, the medications were delivered to patients' homes, and there was less formal education. Compliance success was defined as a combination of treatment completion and obtaining at least 1 post-treatment viral load at week 4 or 12. Treatment success was defined as either SVR4 or SVR12.Fifty of 488 (10.3%) patients from the SHC and 163 of 840 (19.4%) patients from the GHC were lost to follow-up (P < .0001). sustained virological response (SVR) rates were similar in compliant patients in both the SHC (419/438, 95.6%) and GHC (642/677, 94.8%), but treatment success rates by intention to treat (ITT) (overall 79.9%) were higher in SHC compared to GHC (85.9% vs 76.4%, P < .0001). Multivariate analysis showed that female patients (P = .01), older age (P = .0005), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/simeprevir compared to sofosbuvir/ledipasvir had higher odds of compliance success; elbasvir/grazoprevir or dasabuvir/ombitasvir/paritaprevir/ritonavir had lower odds of compliance success compared to sofosbuvir/ledipasvir. Female patients (P = .02), older age (P < .0001), previous treatment (P = .03), treatment in SHC (OR 1.7, 95% CI 1.2, 2.3, P = .0008), and sofosbuvir/ledipasvir compared to sofosbuvir/velpatasvir, sofosbuvir, or elbasvir/grazoprevir had higher odds of treatment success. With 1:1 matching, the SHC group still had significantly higher odds than the GHC group of achieving treatment and compliance success.Our study shows that the effectiveness of HCV treatment could be improved by coordinating treatment in a structured HCV clinic.

Patient Non-adherence and Cancellations Are Higher for Screening Colonoscopy Compared with Surveillance Colonoscopy.

BACKGROUND: A significant proportion of the eligible population is non-adherent to colonoscopy for colorectal cancer (CRC) screening. AIMS: To define the demographic and clinical variables associated with non-adherence and multiple cancellations to scheduled colonoscopy within 1 year in a CRC screening and adenomatous polyp surveillance population. METHODS: This was an observational cohort study of 617 consecutive patients scheduled to undergo colonoscopy at an outpatient academic tertiary care center for CRC screening or adenomatous polyp surveillance from January 2012 to September 2012. RESULTS: Overall, 551 patients (89.3%) were adherent and 66 (10.7%) were non-adherent to scheduled colonoscopy at 1 year. The relative risk for non-adherence was 5.42 [95% confidence interval (CI) 2.74-10.75] in patients undergoing colonoscopy for screening compared to those for surveillance (16.7 vs. 3.5% non-adherence, respectively, P < 0.001). An indication of screening in comparison with surveillance was associated with non-adherence [odds ratio (OR) 12.69, 95% CI 4.18-38.51] and multiple cancellations (OR 2.33, 95% CI 1.27-4.31) by multiple regression analysis. CONCLUSIONS: Patients undergoing colonoscopy for CRC screening are significantly less likely to attend their scheduled procedure within a year and have more procedure cancellations than those undergoing surveillance colonoscopy.

Angiotensin II regulates the expression of monocyte chemoattractant protein-1 in pancreatic cancer cells.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal cancers with an overall median survival of less than 9 months and a 5-year survival rate of less than 5%. Increasing evidence indicates that inflammation facilitates PDA growth. DISCUSSION: Angiotensin II (AngII), the principal hormone of the renin-angiotensin system, is actively generated in the pancreas and has been proposed as a key mediator of inflammation. Monocyte chemoattractant protein (MCP)-1 is a chemokine that plays an important role in the recruitment of mononuclear cells into sites of inflammation. In this study, we investigated the potential proinflammatory role of AngII in PDA through studying its effect on MCP-1. AngII significantly increased the expression of MCP-1 mRNA and protein in PDA cells and induced its promoter activity. Constitutive and AngII-induced MCP-1 transcription was inhibited by an AngII type 1 receptor (AT1R) blocker, but was unchanged by an AT2R blocker. AngII activated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, but not p38 or c-Jun NH2-terminal mitogen-activated protein kinases. Inhibition of ERK1/2 activation reduced the AngII-induced MCP-1 synthesis. AngII induced the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB), an effect that was inhibited by AT1R blockade. Inhibition of NF-kappaB by pyrrolidine dithiocarbamate decreased the AngII-mediated increase in MCP-1 mRNA. Our data provide a novel insight into an AngII-initiated signal transduction pathway that regulates MCP-1 as a possible inflammatory mechanism in PDA and suggest that AngII blockade may regulate chemokine-induced signal transduction to prevent or reduce inflammation in PDA.

Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.

BACKGROUND: Both hereditary and sporadic forms of chronic pancreatitis are associated with an increased risk of developing pancreatic ductal adenocarcinoma (PDA). Inflammation has been identified as a significant factor in the development of solid tumour malignancies. We have recently shown that thymoquinone (Tq), the major constituent of Nigella sativa oil extract, induced apoptosis and inhibited proliferation in PDA cells. Tq also increased p21 WAF1 expression, inhibited histone deacetylase (HDAC) activity, and induced histone hyperacetylation. HDAC inhibitors have been shown to ameliorate inflammation-associated cancer. In this study, we evaluated the anti-inflammatory potential of Tq in PDA cells in comparison with that of a specific HDAC inhibitor, trichostatin A (TSA). METHODS: PDA cells were treated with or without Tq (25-75 microM), with or without pre-treatment of tumour necrosis factor (TNF)-alpha (25 ng/ml). The effect of Tq on the expression of different proinflammatory cytokines and chemokines was analysed by real-time polymerase chain reaction (PCR). Luciferase-labelled promoter studies evaluated the effect of Tq on the transcription of monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-kappaB (NF-kappaB). The effect of Tq on the constitutive and TNF-alpha-induced activation and nuclear translocation of NF-kappaB was examined by ELISA and immunohistochemistry. RESULTS: Tq dose- and time-dependently significantly reduced PDA cell synthesis of MCP-1, TNF-alpha, interleukin (IL)-1beta and Cox-2. At 24 h, Tq almost completely abolished the expression of these cytokines, whereas TSA had a less dramatic effect. Tq, but not TSA, significantly and dose-dependently reduced the intrinsic activity of the MCP-1 promoter. Tq also inhibited the constitutive and TNF-alpha-mediated activation of NF-kappaB in PDA cells and reduced the transport of NF-kappaB from the cytosol to the nucleus. CONCLUSIONS: Our data demonstrate previously undescribed anti-inflammatory activities of Tq in PDA cells, which are paralleled by inhibition of NF-kappaB. Tq as a novel inhibitor of proinflammatory pathways provides a promising strategy that combines anti-inflammatory and proapoptotic modes of action.