Diabetic foot ulcers: Retrospective comparative analysis from Sicily between two eras

Aim: The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008-2013 and 2014-2019. Methods: We compared the two eras, era1: 2008-13, era2: 2014-19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. Results: In the population hospitalized for DFU in 2008-2013, 59.1% of males and 40.9% of females died, whilst in 2014-2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07-2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37-2.95, p <0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51-5.34, p 0.001) were independently associated with risk of death. Conclusions: Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality

Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

Background and Goals:Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines.Methods:We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview.Results:HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30-98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority.Conclusions:Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines. © 2013 Thudi et al

Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication

Background & Aims: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients. Methods: Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death. Results: Included were 1000 patients with SVR. Median age was 52.7 (IQR 45.1–59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9–8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0–4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0–11.4) among those with cirrhosis (p = 0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0–5.5) among patients <45 years, 9.7% (95% CI 5.8–13.6) among patients from 45–60 years, and 12.2% (95% CI 5.3–19.1) among patients >60 years of age at start of therapy (p = 0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8 years 4.2% (95% CI 0.1–8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3–19.3) of patients with cirrhosis experienced clinical disease progression (p = 0.007). Conclusions: Patients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed. Lay summary: Patients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer. 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserve

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Backgrounds & Aims Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. Methods We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. Results We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. Conclusions This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. Lay summary Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC

Predicting implementation from organizational readiness for change: a study protocol

<p>Abstract</p> <p>Background</p> <p>There is widespread interest in measuring organizational readiness to implement evidence-based practices in clinical care. However, there are a number of challenges to validating organizational measures, including inferential bias arising from the halo effect and method bias - two threats to validity that, while well-documented by organizational scholars, are often ignored in health services research. We describe a protocol to comprehensively assess the psychometric properties of a previously developed survey, the Organizational Readiness to Change Assessment.</p> <p>Objectives</p> <p>Our objective is to conduct a comprehensive assessment of the psychometric properties of the Organizational Readiness to Change Assessment incorporating methods specifically to address threats from halo effect and method bias.</p> <p>Methods and Design</p> <p>We will conduct three sets of analyses using longitudinal, secondary data from four partner projects, each testing interventions to improve the implementation of an evidence-based clinical practice. Partner projects field the Organizational Readiness to Change Assessment at baseline (n = 208 respondents; 53 facilities), and prospectively assesses the degree to which the evidence-based practice is implemented. We will conduct predictive and concurrent validities using hierarchical linear modeling and multivariate regression, respectively. For predictive validity, the outcome is the change from baseline to follow-up in the use of the evidence-based practice. We will use intra-class correlations derived from hierarchical linear models to assess inter-rater reliability. Two partner projects will also field measures of job satisfaction for convergent and discriminant validity analyses, and will field Organizational Readiness to Change Assessment measures at follow-up for concurrent validity (n = 158 respondents; 33 facilities). Convergent and discriminant validities will test associations between organizational readiness and different aspects of job satisfaction: satisfaction with leadership, which should be highly correlated with readiness, versus satisfaction with salary, which should be less correlated with readiness. Content validity will be assessed using an expert panel and modified Delphi technique.</p> <p>Discussion</p> <p>We propose a comprehensive protocol for validating a survey instrument for assessing organizational readiness to change that specifically addresses key threats of bias related to halo effect, method bias and questions of construct validity that often go unexplored in research using measures of organizational constructs.</p

Classical HLA-DRB1 and DPB1 alleles account for HLA associations with primary biliary cirrhosis

Susceptibility to primary biliary cirrhosis (PBC) is strongly associated with human leukocyte antigen (HLA)-region polymorphisms. To determine if associations can be explained by classical HLA determinants, we studied Italian, 676 cases and 1440 controls, genotyped with dense single-nucleotide polymorphisms (SNPs) for which classical HLA alleles and amino acids were imputed. Although previous genome-wide association studies and our results show stronger SNP associations near DQB1, we demonstrate that the HLA signals can be attributed to classical DRB1 and DPB1 genes. Strong support for the predominant role of DRB1 is provided by our conditional analyses. We also demonstrate an independent association of DPB1. Specific HLA-DRB1 genes (08,11 and14) account for most of the DRB1 association signal. Consistent with previous studies, DRB108 (P=1.59 710-11) was the strongest predisposing allele, whereas DRB111 (P=1.42 710-10) was protective. Additionally, DRB114 and the DPB1 association (DPB103:01; P=9.18 710-7) were predisposing risk alleles. No signal was observed in the HLA class 1 or class 3 regions. These findings better define the association of PBC with HLA and specifically support the role of classical HLA-DRB1 and DPB1 genes and alleles in susceptibility to PBC