Modelling the cost effectiveness of non-alcoholic fatty liver disease risk stratification strategies in the community setting.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Identifying high-risk patients is critical to best utilize limited health care resources. We established a community-based care pathway using 2D ultrasound shear wave elastography (SWE) to identify high risk patients with NAFLD. Our objective was to assess the cost-effectiveness of various non-invasive strategies to correctly identify high-risk patients.MethodsA decision-analytic model was created using a payer's perspective for a hypothetical patient with NAFLD. FIB-4 [≥1.3], NAFLD fibrosis score (NFS) [≥-1.455], SWE [≥8 kPa], transient elastography (TE) [≥8 kPa], and sequential strategies with FIB-4 or NFS followed by either SWE or TE were compared to identify patients with either significant (≥F2) or advanced fibrosis (≥F3). Model inputs were obtained from local data and published literature. The cost/correct diagnosis of advanced NAFLD was obtained and univariate sensitivity analysis was performed.ResultsFor ≥F2 fibrosis, FIB-4/SWE cost $148.75/correct diagnosis while SWE cost$276.42/correct diagnosis, identifying 84% of patients correctly. For ≥F3 fibrosis, using FIB-4/SWE correctly identified 92% of diagnoses and dominated all other strategies. The ranking of strategies was unchanged when stratified by normal or abnormal ALT. For ≥F3 fibrosis, the cost/correct diagnosis was less in the normal ALT group.ConclusionsSWE based strategies were the most cost effective for diagnosing ≥F2 fibrosis. For ≥F3 fibrosis, FIB-4 followed by SWE was the most effective and least costly strategy. Further evaluation of the timing of repeating non-invasive strategies are required to enhance the cost-effective management of NAFLD

Race and Ethnicity in Non-Alcoholic Fatty Liver Disease (NAFLD): A Narrative Review

Non-alcoholic fatty liver disease (NAFLD) is a significant public health concern worldwide with a complex etiology attributed to behavioural, environmental, and genetic causes. The worldwide prevalence of NAFLD is estimated to be 32.4% and constantly rising. Global data, however, indicate considerable heterogeneity among studies for both NAFLD prevalence and incidence. Identifying variables that affect the estimated epidemiological measures is essential to all stakeholders, including patients, researchers, healthcare providers, and policymakers. Besides helping with the research on disease etiology, it helps to identify individuals at risk of the disease, which in turn will outline the focus of the preventive measures and help to fittingly tailor individualized treatments, targeted prevention, screening, or treatment programs. Several studies suggest differences in the prevalence and severity of NAFLD by race or ethnicity, which may be linked to differences in lifestyle, diet, metabolic comorbidity profile, and genetic background, among others. Race/ethnicity research is essential as it can provide valuable information regarding biological and genetic differences among people with similar cultural, dietary, and geographical backgrounds. In this review, we examined the existing literature on race/ethnicity differences in susceptibility to NAFLD and discussed the contributing variables to such differences, including diet and physical activity, the comorbidity profile, and genetic susceptibility. We also reviewed the limitations of race/ethnicity studies in NAFLD

Causes and Outcomes of Medicolegal Proceedings Following Gastrointestinal Endoscopy in Canada

Background and Aims: Endoscopic procedures are frequently performed in Canada but can be associated with potential complications and medicolegal implications. This study aimed to identify potential medicolegal cases in Canada relating to upper and lower endoscopies as well as advanced endoscopic procedures. Methods: Westlaw Canada was searched for any cases regarding upper and lower endoscopies and advanced endoscopic procedures from inception to December 31, 2020. Cases were classified by type of case, procedure performed, patient and defendant demographics, outcome, and alleged reason for litigation/complaint. Results: Twenty-nine civil cases and 9 board and tribunal decisions for upper and lower endoscopies and 3 advanced endoscopic procedure cases were analyzed. The most frequent defendant specialties were family physician, general surgery, and gastroenterology. The plaintiff was successful in 12 cases involving upper or lower endoscopy with an average award of $243,934 (2021 CDN). The most alleged reasons for litigation were procedural error or negligence (n = 19). The plaintiff was successful in 1 advanced endoscopic procedure case with an award of$153,032. Conclusion: Medicolegal cases regarding gastrointestinal endoscopy in Canada occur infrequently. Endoscopy should be performed by skilled providers with appropriate informed consent from the patient, and careful consideration of whether procedures are indicated are key for endoscopic providers

Immunotargeting with CD154 (CD40 Ligand) Enhances DNA Vaccine Responses in Ducks

Engagement of CD154 on activated T cells with CD40 on antigen-presenting cells (APCs) potentiates adaptive immune responses in mammals. Soluble multimeric forms of CD154 have been used as an adjuvant or in immunotargeting strategies to enhance vaccine responses. The objective of our study was to examine the ability of duck CD154 (DuCD154) to enhance DNA vaccine responses in the duck hepatitis B model. Constructs were generated to express the functional domain of DuCD154 (tCD154), truncated duck hepatitis B virus (DHBV) core antigen (tcore) and chimera of tcore fused to tCD154 (tcore-tCD154). Expression in LMH cells demonstrated that all proteins were secreted and that tCD154 and tcore-tCD154 formed multimers. Ducks immunized with the plasmid ptcore-tCD154 developed accelerated and enhanced core-specific antibody responses compared to ducks immunized with ptcore or ptcore plus ptCD154. Antibody responses were better sustained in both ptcore-tCD154- and ptcore plus ptCD154-immunized ducks. Core-specific proliferative responses of duck peripheral blood mononuclear cells were enhanced in ducks immunized with ptcore-tCD154 or ptcore alone. This study suggests that the role of CD154 in the regulation of adaptive immune responses had already evolved before the divergence of birds and mammals. Thus, targeting of antigens to APCs with CD154 is an effective strategy to enhance DNA vaccine responses not only in mammalian species but also in avian species

Factors Associated With Geographic Disparities in Gastrointestinal Cancer Mortality in the United States

Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. Data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010–2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer–related mortality. Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer–related death. [Display omitted] The highest rates of death from gastrointestinal cancers occur in rural counties and in the Southeastern United States, with differences in county-level mortality from esophagus, stomach, pancreas, and colon cancer being associated with higher rates of smoking, diabetes, and obesity

Long-Term Follow-up and Quantitative Hepatitis B Surface Antigen Monitoring in North American Chronic HBV Carriers

Introduction. Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV DNA may be useful for predicting chronic hepatitis B (CHB) activity and nucleoside analogue (NA) response.Material and methods. In this retrospective cohort study we evaluated qHBsAg levels according to CHB disease phase and among patients on treatment. Random effect logistic regression analysis was used to analyze qHBsAg change with time in the NA-treated cohort.Results. 545 CHB carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing. In the untreated group (44%), 8% were classified as immune tolerant, 10% immune clearance, 40% inactive, and 43% had HBeAg- CHB and the median HBsAg levels were 4.6 (IQR 3.4-4.9), 4.0 (IQR 3.4-4.5), 2.9 (IQR 1.4-3.8), and 3.2 log IU/mL (IQR 2.6-4.0), respectively; p < 0.001. In the NA-treated group (28% entecavir, 68% tenofovir, 4% lamivudine), no significant change in qHBsAg levels occured with time. However, 19% of patients on long-term NA had sustained qHBsAg < 2 log10 IU/mL.Conclusion. qHBsAg titers were associated with CHB phase and remained stable in those on long-term NA. A significant number of treated patients had low-level qHBsAg, of which some may be eligible for treatment discontinuation without risk of flare

The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis - a hybrid type I effectiveness-implementation trial

Abstract Background Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community. Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial which aims to address these gaps. The proposed intervention is initiated at the time of hospitalization through implementation of a clinical information system embedded electronic order set for delivering evidence-based best practices under real-world conditions. The overarching objective of the CCAB trial is to demonstrate effectiveness and implementation feasibility for use of the order set in routine patient care within eight hospital sites in Alberta. Methods A mixed methods hybrid type I effectiveness-implementation design will be used to evaluate the effectiveness of the order set intervention. The primary outcome is a reduction in 90-day cumulative length of stay. Implementation outcomes such as reach, adoption, fidelity and maintenance will also be evaluated alongside other patient and service outcomes such as readmission rates, quality of care and cost-effectiveness. This theory-based trial will be guided by Normalization Process Theory, Consolidated Framework on Implementation Research (CFIR) and the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) Framework. Discussion The CCAB project is unique in its breadth, both in the comprehensiveness of the multi-component order set and also for the breadth of its roll-out. Lessons learned will ultimately inform the feasibility and effectiveness of this approach in “real-world” conditions as well as adoption and adaptation of these best practices within the rest of Alberta, other provinces in Canada, and beyond. Trial registration ClinicalTrials.gov: NCT04149223, November 4, 2019