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Background & Aims Coronavirus disease 2019 (COVID-19) pandemic lockdown and restrictions had significant disruption to patient care. We aimed to evaluate the impact of COVID-19 restrictions on hospitalizations of patients with alcoholic and nonalcoholic cirrhosis as well as alcoholic hepatitis (AH) in Alberta, Canada. Methods We used validated International Classification of Diseases (ICD-9 and ICD-10) coding algorithms to identify liver-related hospitalizations for nonalcoholic cirrhosis, alcoholic cirrhosis, and AH in the province of Alberta between March 2018 and September 2020. We used the provincial inpatient discharge and laboratory databases to identify our cohorts. We used elevated alanine aminotransferase or aspartate aminotransferase, elevated international normalized ratio, or bilirubin to identify AH patients. We compared COVID-19 restrictions (April–September 2020) with prior study periods. Joinpoint regression was used to evaluate the temporal trends among the 3 cohorts. Results We identified 2916 hospitalizations for nonalcoholic cirrhosis, 2318 hospitalizations for alcoholic cirrhosis, and 1408 AH hospitalizations during our study time. The in-hospital mortality rate was stable in relation to the pandemic for alcoholic cirrhosis and AH. However, nonalcoholic cirrhosis patients had lower in-hospital mortality rate after March 2020 (8.5% vs 11.5%; P = .033). There was a significant increase in average monthly admissions in the AH cohort (22.1/10,000 admissions during the pandemic vs 11.6/10,000 admissions before March 2020; P Conclusions Before and during COVID-19 monthly admission rates were stable for nonalcoholic and alcoholic cirrhosis; however, there was a significant increase in AH admissions. Because alcohol sales surged during the pandemic, future impact on alcoholic liver disease could be detrimental.

Background & Aims Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based studies to explore the changing temporal trends of acute pancreatitis incidence globally. Methods We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were independently assessed to identify applicable papers for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CI). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map. Results Forty-four studies reported the temporal incidence of acute pancreatitis (online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC = 3.07%; 95% CI: 2.30, 3.84; n=34). Increasing incidence was observed in North America (AAPC = 3.67%; 95% CI: 2.76, 4.57; n=4) and Europe (AAPC = 2.77%; 95% CI: 1.91, 3.63; n=23). The incidence of acute pancreatitis was stable in Asia (AAPC = −0.28%; 95% CI: −5.03, 4.47; n=4). Conclusion This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last 56 years and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa, and Latin America.

Background Immune-related adverse events can occur after treatment with immune checkpoint inhibitors (ICI), limiting treatment persistence. We aimed to evaluate the clinical course of ICI-mediated hepatitis (IMH) associated with combination ipilimumab and nivolumab treatment. Methods A retrospective cohort study including consecutive patients with metastatic melanoma treated with ipilimumab and nivolumab between 2013 and 2018 was conducted at two tertiary care centres. IMH was defined by the Common Terminology Criteria for Adverse Events (CTCAE). We determined the proportion of patients developing IMH, and compared the duration, treatment patterns and outcomes, stratified by hepatitis severity. Kaplan–Meier survival analysis was used to evaluate time to hepatitis resolution, and a linear mixed-effects model was used to compare longitudinal outcomes by treatment. Results A total of 63 patients were included. Thirty-two patients (51%) developed IMH (34% Grade 1–2, 66% Grade 3–4), at a median of 34 days (IQR 20 to 43.5 days) after the first dose. Baseline FIB4 index ≥1.45 was associated with IMH (OR 3.71 [95% CI: 1.03 to 13.38], P = 0.04). Ninety-four per cent (30/32) of patients had liver enzyme normalization after a median duration of 43 days (IQR 26 to 70 days). Corticosteroid use was not associated with faster IMH resolution or less ICI discontinuation. A total of 24 patients died during the study; no deaths were attributable to hepatitis-related complications. Fifty-three per cent (17/32) of patients resumed anti-PD-1 monotherapy and three patients developed IMH recurrence. Conclusions Approximately half of the patients treated with combination ipilimumab and nivolumab developed IMH in this cohort. However, most patients experienced uncomplicated IMH resolution.

BACKGROUND AND AIMS The effect of major depression and antidepressant use on patient survival in chronic liver disease is unknown. We evaluated the impact of major depressive disorder (MDD) and antidepressants on survival among patients with alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS The Health Improvement Network database, the largest medical database in the United Kingdom, was used to identify incident ALD (n = 4148) and NAFLD (n = 19 053) in patients between 1986 and 2017. Our primary outcome was development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models as time-varying covariates. Models were adjusted for age, sex, socio-economic status and comorbidities. RESULTS MDD rate was higher among patients with ALD (22.8%) compared to those with NAFLD (16.1%), P

Due to shared modes of exposure, HIV-HBV co-infection is common worldwide. Increased knowledge of the demographic and clinical characteristics of the co-infected population will allow us to optimize our approach to management of both infections in clinical practice. The Canadian Hepatitis B Network Cohort was utilized to conduct a cross-sectional evaluation of the demographic, biochemical, fibrotic and treatment characteristics of HIV-HBV patients and a comparator HBV group. From a total of 5996 HBV-infected patients, 335 HIV-HBV patients were identified. HIV-HBV patients were characterized by older median age, higher male and lower Asian proportion, more advanced fibrosis and higher anti-HBV therapy use (91% vs. 30%) than the HBV-positive / HIV seronegative comparator group. A history of reported high-risk exposure activities (drug use, high-risk sexual contact) was more common in HIV-HBV patients. HIV-HBV patients with reported high-risk exposure activities had higher male proportion, more Caucasian ethnicity and higher prevalence of cirrhosis than HIV-HBV patients born in an endemic country. In the main cohort, age ≥60 years, male sex, elevated ALT, the presence of comorbidity and HCV seropositivity were independent predictors of significant fibrosis. HIV seropositivity was not an independent predictor of advanced fibrosis (adj OR 0.75 [95%CI: 0.34-1.67]). In conclusion, Canadian co-infected patients differed considerably from those with mono-infection. Furthermore, HIV-HBV-infected patients who report high-risk behaviours and those born in endemic countries represent two distinct subpopulations, which should be considered when engaging these patients in care.

INTRODUCTION The incidence of peptic ulcer disease (PUD) has been decreasing over time with Helicobacter pylori eradication and use of acid-suppressing therapies. However, PUD remains a common cause of hospitalization in the United States. We aimed to evaluate contemporary national trends in the incidence, treatment patterns, and outcomes for PUD-related hospitalizations and compare care delivery by hospital rurality. METHODS Data from the National Inpatient Sample were used to estimate weighted annual rates of PUD-related hospitalizations. Temporal trends were evaluated by joinpoint regression and expressed as annual percent change with 95% confidence intervals (CIs). We determined the proportion of hospitalizations requiring endoscopic and surgical interventions, stratified by clinical presentation and rurality. Multivariable logistic regression was used to assess independent predictors of in-hospital mortality and postoperative morbidity. RESULTS There was a 25.8% reduction (P < 0.001) in PUD-related hospitalizations from 2005 to 2014, although the rate of decline decreased from -7.2% per year (95% CI: 13.2% to -0.7%) before 2008 to -2.1% per year (95% CI: 3.0% to -1.1%) after 2008. In-hospital mortality was 2.4% (95% CI: 2.4%-2.5%). Upper endoscopy (84.3% vs 78.4%, P < 0.001) and endoscopic hemostasis (26.1% vs 16.8%, P < 0.001) were more likely to be performed in urban hospitals, whereas surgery was performed less frequently (9.7% vs 10.5%, P < 0.001). In multivariable logistic regression, patients managed in urban hospitals were at higher risk for postoperative morbidity (odds ratio 1.16 [95% CI: 1.04-1.29]), but not death (odds ratio 1.11 [95% CI: 1.00-1.23]). DISCUSSION The rate of decline in hospitalization rates for PUD has stabilized over time, although there remains significant heterogeneity in treatment patterns by hospital rurality.

BACKGROUND The burden of cirrhosis on the healthcare system is substantial and growing. Our objectives were to estimate the readmission rates and hospitalization costs as well as to identify risk factors for 90-day readmission in patients with cirrhosis. METHODS We conducted a weighted analysis of the 2014 Nationwide Readmission Database to identify adult patients with cirrhosis-related complications in the United States and assessed readmission rates at 30, 60 and 90 days post-index hospitalization. Predictors of 90-day readmissions were identified using weighted regression models adjusting for patient and hospital characteristics; the national estimate of hospitalization costs was also calculated. RESULTS Of the 58 954 patients admitted with cirrhosis-related complications in 2014, 14 910 (25%) were readmitted within 90 days because of cirrhosis-related complications. The main causes of readmission were ascites (56%), hepatic encephalopathy (47%) and bleeding oesophageal varices (9%). Independent predictors of 90-day readmissions were male sex (adjusted OR [aOR]: 1.08, 95% CI, 1.04-1.13), age

ObjectiveDepression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD.DesignThe Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn’s disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA).ResultsWe identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC.ConclusionPatients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn’s disease and UC. These results may impact counselling and management of depression and IBD.

Background Electronic medical records (EMRs) contain large amounts of rich clinical information. Developing EMR-based case definitions, also known as EMR phenotyping, is an active area of research that has implications for epidemiology, clinical care, and health services research. Objective This review aims to describe and assess the present landscape of EMR-based case phenotyping for the Charlson conditions. Methods A scoping review of EMR-based algorithms for defining the Charlson comorbidity index conditions was completed. This study covered articles published between January 2000 and April 2020, both inclusive. Embase (Excerpta Medica database) and MEDLINE (Medical Literature Analysis and Retrieval System Online) were searched using keywords developed in the following 3 domains: terms related to EMR, terms related to case finding, and disease-specific terms. The manuscript follows the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA) guidelines. Results A total of 274 articles representing 299 algorithms were assessed and summarized. Most studies were undertaken in the United States (181/299, 60.5%), followed by the United Kingdom (42/299, 14.0%) and Canada (15/299, 5.0%). These algorithms were mostly developed either in primary care (103/299, 34.4%) or inpatient (168/299, 56.2%) settings. Diabetes, congestive heart failure, myocardial infarction, and rheumatology had the highest number of developed algorithms. Data-driven and clinical rule–based approaches have been identified. EMR-based phenotype and algorithm development reflect the data access allowed by respective health systems, and algorithms vary in their performance. Conclusions Recognizing similarities and differences in health systems, data collection strategies, extraction, data release protocols, and existing clinical pathways is critical to algorithm development strategies. Several strategies to assist with phenotype-based case definitions have been proposed.

Background: Healthcare systems worldwide have adopted the electronic medical record (EMR). EMRs are an efficient method of interprofessional communication, and can improve data availability for secondary research purposes. The discharge summary (DS) is a crucial document for both interprofessional communication, and coding of data for research purposes. We aimed to assess the completeness of our EMRs by assessing the presence of a DS in the EMR. Additionally, we evaluated the presence of indicators for a missing DS. Method: A retrospective chart review was conducted on 3,011 inpatient charts from 3 hospitals in Calgary, Alberta Canada. 893 charts were missing an electronic DS. A 10% sample was drawn to assess for presence of a paper DS. A list of variables was compiled to assess for association between patient and hospital characteristics, patient comorbidities, and the absence of an electronic DS. A Chi-square test, Fisher’s test and logistic regression were conducted to assess for associations. Results: The univariate analyses showed that age, being a surgical patient, a Charlson Comorbidity Index (CCI) of

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.

OBJECTIVES To conduct a systematic review and meta-analysis that defines the worldwide incidence of celiac disease (CD) and examines temporal trends. METHODS MEDLINE and EMBASE were searched for population-based studies reporting the incidence of CD in the overall population, children, or adults. No limits were placed on year or language of publication. Studies solely examining at-risk populations (e.g., patients with type 1 diabetes) were excluded. Random-effects models were performed to meta-analyze sex- and age-specific incidence in the 21st century. Temporal trend analyses assessed the average annual percent change in CD incidence over time. RESULTS Of 11,189 citations, 86 eligible studies were identified for inclusion, of which 50 were deemed suitable for analyses. In the 21st century, the pooled female incidence of CD was 17.4 (95% confidence interval [CI]: 13.7, 21.1) (I = 99.5%) per 100,000 person-years, compared with 7.8 (95% CI: 6.3, 9.2) (I = 98.6%) in males. Child-specific incidence was 21.3 per 100,000 person-years (95% CI: 15.9, 26.7) (I = 99.7%) compared with 12.9 (95% CI: 7.6, 18.2) (I = 99.9%) in adults. Pooling average annual percent changes showed the incidence of CD to be increasing by 7.5% (95% CI: 5.8, 9.3) (I = 79.6%) per year over the past several decades. DISCUSSION Incidence of CD is highest in females and children. Overall, the incidence has been significantly rising in the latter half of the 20th century and into the 21st century throughout the Western world. Population-based studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of CD.

The experiment was carried out to evaluate the effects of different levels life Saccharomyces cerevisiae and yeast cell wall individually or in combination on growth performance, of Ross unsexed broiler chicks from 0 – 36 days of age. There were 15 dietary treatments and control. The results indicated that weight gain, feed intake and feed conversion ratio were significantly influenced by the addition of Saccharomyces cerevisiae with or without yeast cell wall. The results suggest that supplementation of S. cerevisiae with or without yeast cell wall to diets have a positive influence for improving performance of broilers flock

Nonalcoholic fatty liver disease (NAFLD) is a rising epidemic worldwide and will be the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplant within the next decade. NAFLD is considered as the hepatic manifestation of metabolic syndrome. Behaviors, such as a sedentary lifestyle and consuming a Western diet, have led to substantial challenges in managing NAFLD patients. With no curative pharmaceutical therapies, lifestyle modifications, including dietary changes and exercise, that ultimately lead to weight loss remain the only effective therapy for NAFLD. Multiple diets, including low-carbohydrate, low-fat, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean (MD) diets, have been evaluated. NAFLD patients have shown better outcomes with a modified diet, such as the MD diet, where patients are encouraged to increase the consumption of fruits and vegetables, whole grains, and olive oil. It is increasingly clear that a personalized approach to managing NAFLD patients, based on their preferences and needs, should be implemented. In our review, we cover NAFLD management, with a specific focus on dietary patterns and their components. We emphasize the successful approaches highlighted in recent studies to provide recommendations that health care providers could apply in managing their NAFLD patients.

In forensic sciences to determine one's sex is quite important during the identity defining stage. The reliability of sex determination depends on the completeness of the remains and the degree of sexual dimorphism inherent in the population. Computed Tomography is the imaging modality of choice for two- and three-dimensional documentation and analysis of many autopsy findings.The aim of the present work was to assess the reliability of Three-dimensional Multislice Computed Tomography (3D MSCT) to determine sexual dimorphism from certain chest measurements; sternum and fourth rib using the 3D MSCT and to develop equations for sex determination from these bones among adult Egyptians sample.The present study was performed on 60 adult Egyptians. Their age ranged from 21 up to 74 years and they were equally divided between both sexes. Sixty virtual chests (reconstructed Multislice Computed Tomography 3D images) were examined for detection of Sternal measurements; Manubrium length (ML), Sternal body length (BL), Manubrium width (MW), Sternal body widths(BWaBWb), Sternal area (SA) [(ML + BL) × (MW + BWa + BWb)/3]and Fourth rib width (FRW).All the studied measurements were significantly higher in males than in females. Multiple regression analysis was used to and three significant regression equations were developed for predicting sex using the different studied chest measurements; the sternal measurements, the sternal area and the widths of the right and left fourth ribs with their accuracies 96.67%.95.0%.72.68% respectively.Sterunm and fourth rib width revealed significant metric sex differences with the use of Multislice Computed Tomography 3D images thus provide a great advantage in the analysis of skeletal remains and badly decomposed bodies.

Background Non-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. Methods A 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. Results For ≥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. Conclusions SWE 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.

Background A subset of patients with ulcerative colitis (UC) will require colectomy within a few years of diagnosis. Thus, our aim was to determine the clinical predictors of early colectomy among patients with UC who are hospitalized with an acute flare. Methods Using population-based surveillance (1996-2009), all adults (≥18 years) hospitalized for UC within 3 years of diagnosis (n = 489) were identified. The primary outcome was a colectomy within 3 years of diagnosis. All medical charts were reviewed. A logistic regression model evaluated clinical variables that predicted colectomy within 3 years of diagnosis, and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results Among patients admitted to hospital with UC within 3 years of diagnosis, 57.7% underwent colectomy, with the odds of colectomy decreasing by 12% per year. Early colectomy was more likely among patients aged 35 to 64 years versus 18 to 34 years (OR 2.18 [95% CI, 1.27-3.74]), males (OR 2.03 [95% CI, 1.24-3.34]), those with pancolitis (OR 5.38 [95% CI, 3.20-9.06]), and living in rural areas (OR 2.81 [95% CI, 1.49-5.29]). Prescription of infliximab before hospitalization increased odds of surgery (OR 5.12 [95% CI, 1.36-19.30]). Conclusions Patients hospitalized for UC have a high risk of early colectomy. This is particularly true in middle-aged men, those living in rural areas, and those without response to infliximab.

Malnutrition is an important predictor of morbidity and mortality among cirrhotic patients. Our objectives were to assess protein-calorie malnutrition (PCM) in cirrhotic pre-liver transplant patients and to study the correlation between subjective global assessment (SGA) and other objective measures of malnutrition.We recruited pre-liver transplant adult patients at our center between October 2012 and Oct 2015. Nutrition status was assessed via SGA. PCM was assessed by comparing recommended to actual protein and calorie intake. SGA was correlated with body mass index (BMI), dry BMI, handgrip strength by calibrated dynometer (HGS), and mid-arm circumference (MAC). We used non-parametric statistical methods in our analysis.Seventy patients were included in this study. Majority were males (n = 46, 66%) with a median age of 58 years (IQR: 50-61). Moderate to severe malnutrition was prevalent in our cohort (SGA-A: n = 15 (21.4%), SGA-B: n = 30 (42.9%) and SGA-C: n = 25 (35.7%). There was a significant difference in the recommended calories consumed between SGA groups (A 98.5% vs. C 79.2%, P = 0.03). A similar trend was observed for the recommended protein consumed (A 85.4%, C 62.5%; P = 0.09). SGA correlated with BMI (A = 26.4, C = 22.4; P0.01), Dry BMI (A = 25.9, C = 20.4; P0.01), HGS (A = 67.0, C = 47.0 PSI; P = 0.03), and MAC (A = 29.5 cm, C = 22.0 cm; P0.01). HGS and MAC were strongly correlated (Spearman correlation 0.49, P0.01).Cirrhotic patients have significant protein-calorie malnutrition. Multiple malnutrition tools including BMI, dry BMI, HGS and MAC were precisely able to assess malnutrition.

We would like to congratulate Mumtaz et al.1 for their important study attempting to develop and validate a risk score to predict 30-day hospital readmission in decompensated cirrhosis patients using the US nationwide readmission database (NRD). The identification of cirrhosis patients at high-risk for readmission is critical for developing processes to effectively address this problem. However, flaws in patient identification challenge the utility of the risk-score outlined in this study. This article is protected by copyright. All rights reserved.

A sensitive, accurate and reliable bioanalytical method for the enantioselective determination of metoprolol in plasma and saliva samples utilizing liquid chromatography-electrospray ionization tan ...

An Online post-column solvent-assisted ionization (OPSAI) method was developed for enhancing the ionization of the beta-blocker propranolol utilizing normal phase LC-MS/MS. Solvent-assisted electrospray ionization (SAESI) was studied by the introduction of the assistant solvents A: 0.5% Formic acid in Isopropanolol, B: 0.5% Formic acid in Isopropanolol-Water (1:1), and C: 0.5% Formic acid in water into the electrospray ionization chamber using a spray needle. Analyte molecules can be directly ionized by the aid of the assistant solvent spray. Both methods were applied to the chiral separation of propranolol enantiomers using normal phase analysis on cellulose-based chiral column. Interestingly, both methods are easy to handle and offer a wide range of assistant solvents that can be used in order to gain the optimum ionization of the analyte molecules. The both methods considerably improved the analyte signal and the peak area greatly increased. The propranolol average signal-to-noise (S/N) ratio was enhanced from 26±1 and 42±1 to 2341±61 and 1725±29 for R-propranolol and S-propranolol, respectively, when the post-column solvent method (OPSAI) was used with isopropanol-assistant solvent (A). While in case of solvent-assisted electrospray ionization method (SAESI) signal was enhanced from 26±1 and 42±1 to 2223±72 and 2155±58 for R-propranolol and S-propranolol, respectively, with water as an assistant solvent. The limit of detection was 10ng/mL and the method was linear in the range 50-2000ng/mL. The NPLC-MS method was applied for the determination of propranolol enantiomers in human plasma after microextraction by packed C18 sorbent.

Background & Aims In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), indicators for assessing colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between annual colonoscopy volume and ADR, CIR, AEs, or PCCRC. Methods We searched publication databases through March 2019 for studies assessing the relationship between annual colonoscopy volume and outcomes, including ADR, CIR, AEs, or PCCRC. Pooled odds ratios (ORs) were calculated using DerSimonian and Laird random effects models. Sensitivity analyses were performed to assess for potential methodological or clinical factors associated with outcomes. Results We performed a systematic review of 9235 initial citations, generating 27 retained studies comprising 11,276,244 colonoscopies. There was no association between procedural volume and ADR (OR, 1.00; 95% CI, 0.98–1.02 per additional 100 annual procedures). CIR improved with each additional 100 annual procedures (OR, 1.17; 95% CI, 1.08–1.28). There was a non-significant trend toward decreased overall AEs per additional 100 annual procedures (OR, 0.95; 95% CI, 0.90–1.00). There was considerable heterogeneity among most analyses. Conclusions In a systematic review and meta-analysis, we found higher annual colonoscopy volumes to correlate with higher CIR, but not with ADR or PCCRC. Trends toward fewer AEs were associated with higher annual colonoscopy volumes. There are few data available from endoscopists who perform fewer than 100 annual colonoscopies. Studies are needed on extremes in performance volumes to more clearly elucidate associations between colonoscopy volumes and outcomes.

The risk of suicide is higher for patients with colorectal cancer (crc) than for the general population. Given known differences in morbidity and sites of recurrence, we sought to compare the predictors of suicide for patients with colon cancer and with rectal cancer. Using the U.S. Surveillance, Epidemiology, and End Results database, adult patients with confirmed adenocarcinoma of the colon or rectum during 1973&ndash, 2009 were identified. Parametric and nonparametric tests were used to assess selected variables, and Cox proportional hazards regression models were used to determine predictors of suicide. The database identified 187,996 patients with rectal cancer and 443,368 with colon cancer. Compared with the rectal cancer group, the colon cancer group was older (median age: 70 years vs. 67 years, p < 0.001) and included more women (51% vs. 43%, p < 0.001). Suicide rates were similar in the colon and rectal cancer groups [611 (0.14%) vs. 337 (0.18%), p < 0.001]. On univariate analysis, rectal cancer was a predictor of suicide [hazard ratio (hr): 1.26, 95% confidence interval (ci): 1.10 to 1.43]. However, after adjusting for clinical and pathology factors, rectal cancer was not a predictor of suicide (hr: 1.05, 95% ci: 0.83 to 1.33). In the colon cancer cohort, independent predictors of suicide included older age, male sex, white race, and lack of primary resection. The aforementioned predictors, plus metastatic disease, similarly predicted suicide in the rectal cancer cohort. The suicide risk in crc patients is low (

An enantioselective high performance liquid chromatographic method with diode array detection (HPLC-DAD) was developed and validated for the determination of etodolac enantiomers in tablets and human plasma. Enantiomeric separation was achieved on a Kromasil Cellucoat chiral column (250 mm × 4.6mm i.d., 5 µm particle size) using a mobile phase consisting of hexane: isopropanol: triflouroacetic acid (90:10:0.1 v/v/v) at a flow rate of 1.0 mL min(-1). The chromatographic system enables the separation of the two enantiomers and the internal standard within a cycle time of 8 min. The resolution between the two enantiomers was 4.25 and the resolution between each enantiomer and the internal standard was more than 2.0. Detection was carried out at 274 nm, and the purity assessment was performed using a photodiode array detector. Solid phase extraction technique using C-18 cartridge was applied to extract the analytes from the plasma samples, and the percentage recovery was more than 95% for the lower quantification limit. The method has been validated with respect to selectivity, linearity, accuracy and precision, robustness, limit of detection and limit of quantification. The validation acceptance criteria were met in all cases. The linearity range for the determination of each enantiomer in human plasma was 0.4-30.0 µg mL(-1) and the limits of quantification of R-etodolac and S-etodolac were 0.20 and 0.19 µg mL(-1), respectively. The validated method was successfully applied to the determination of etodolac enantiomers in tablets and to a comparative pharmacokinetic study of the two enantiomers after the administration of 300 mg single oral dose etodolac racemate tablets to twelve healthy volunteers.

Background Despite universal vaccination, chronic hepatitis B virus (HBV) infection remains a public health concern in North America owing to immigration. We aimed to characterize the number of people with a positive result of testing for HBV surface antigen (HBsAg) in Calgary, a large urban Canadian health care region, and to assess whether recommended laboratory tests and specialist consultation were done for those identified as HBsAg-positive. Methods Based on laboratory and Alberta Health Services administrative data, we identified all adults (age > 18 yr) with a positive HBsAg test result from Jan. 1 to Dec. 31, 2014 within the Calgary Zone. Demographic and relevant laboratory data were extracted within 6 months of a positive HBsAg test result, and referral to hepatology (2011-2014) was identified from data on referral to a centralized clinic. Parametric and nonparametric statistical methods were used for analyses. Results We identified 1214 HBsAg-positive people (584 women [48.1%]; median age 44 [interquartile range (IQR) 36-55] yr). A total of 1192 people (98.2%) had alanine aminotransferase testing (median level 23 [IQR 16-34] U/L; 117 [9.8%] with elevated levels), 682 (56.2%) had testing for HBV DNA (median level 2.8 [IQR 2.1-3.8] logIU/mL), 630 (51.9%) had HBV e antigen testing (negative result in 548 [87.0%]), and 145 (11.9%) had HBV e antibody testing (positive result in 111 [76.6%]). Overall, 144 people (11.9%) received anti-HBV treatment, and 390 (32.1%) were referred to a hepatologist. Interpretation Many HBsAg-positive people in Calgary did not receive the recommended laboratory assessments. The results highlight the necessity of continual public health efforts to screen for chronic HBV infection in Canada and to ensure adequate follow-up in order to reach the World Health Organization's goal of viral hepatitis elimination by 2030.

Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme that is responsible for the oxidation of intracellular aldehydes. Elevated levels of ALDH have been demonstrated in murine and human progenitor cells compared with other hematopoietic cells, and this is thought to be important in chemoresistance and purification techniques and an indication of the proper function of the cell. A Flowcytometric method for the assessment of ALDH activity in viable cells recently has been developed. Forty six cord blood samples from mothers which underwent normal delivery of full term infants were obtained, after informed consent. Mononuclear cells were obtained by Ficoll-Paque density centrifugation and ammonium chloride red cell lysis. Percentage of viable cells was determined by trypan blue exclusion dye. Cells were labeled with Aldefluor reagent (Vancouver Canada) as described by the manufacturer. Cells were then stained with phycoerythrin (PE)–conjugated anti-CD34 (Miltenyi Biotec, Cologne, Germany) antibodies for 30 min at 4°C. Cells were washed and re-suspended in phosphate-buffered saline (PBS) with 2% fetal calf serum. Cells were then analyzed on coulter epics flow cytometer. The mean percentage of ALDH enzyme expression among the CD34+ cells in the cord blood samples was 61.3% with a minimum of 28% and a maximum of 94.6%. Significant correlations were found between the white blood cell (WBCS) count in the cord blood samples and both the CD34+ cell count and the count of ALDH expressing cells, while no correlation was found between the CD34+ cells count or the ALDH expressing cells count in the cord blood samples and either the sex or the weight of the newborn. Identification and isolation of cells on the basis of ALDH activity provides a tool for their isolation and further analysis. In summary, a high ALDH-1 activity identifies CD34+ cells in cord blood. Key words: Umbilical cord blood, stem cells, aldehyde dehydrogenase (ALDH), CD34.

Background Modifications to the Model for End-Stage Liver Disease (MELD) have been proposed to improve prioritization of liver transplant (LT) candidates. Using a U.S. database, we derived a revised MELD including sodium and albumin [5-variable MELD (5vMELD)] that improved prediction of waiting list mortality. Our objectives were to confirm the association between hypoalbuminaemia and mortality and to externally validate 5vMELD in Canadian LT candidates. Methods Among adults registered on the LT waiting list at the University of Alberta (01/2000-10/2009), Cox regression determined the association between albumin and 1-year waiting list mortality. The discrimination of MELD, MELDNa and 5vMELD for predicting 1-year mortality were compared using c-statistics. Results Among 677 patients, 17% died and 51% underwent LT within 1 year of listing. Median serum albumin was 3.1 g/dl (IQR 2.6–3.6) and 70% of patients were hypoalbuminaemic (albumin

Mortality for liver resection has remarkably improved owing to multiple factors. We sought to determine the impact of the various types of fellowship training on patient survival after liver resection.Patients who underwent hepatic resection between 1995 and 2004 in either the Calgary or Capital health regions (Edmonton) of Alberta, Canada, were identified using ICD-9 and -10 codes. Primary outcomes included in-hospital mortality and patient survival according to surgeon volume and training type (surgical oncology v. hepatobiliary v. others).A total of 1033 patients underwent hepatic resection. Surgeon volume was not predictive of either in-hospital mortality (adjusted odds ratio 0.63, 95% confidence interval [CI] 0.32-1.20) or patient survival (unadjusted hazard ratio 1.11, 95% CI 0.82-1.51). Nonsignificance was also demonstrated for a surgeon's type of fellowship training.The various modes of fellowship training do not appear to influence inhospital mortality or patient survival after hepatic resection.Le taux de mortalité dans les cas de résection du foie a diminué considérablement à cause de multiples facteurs. Nous avons cherché à déterminer l'effet des divers types de formation au niveau du fellowship sur la survie des patients après une résection du foie.Les patients qui ont subi une résection hépatique entre 1995 et 2004 dans les régions sanitaires de Calgary ou de la Capitale (Edmonton) de l'Alberta, au Canada, ont été identifiés au moyen des codes CIM-9 et 10. La mortalité à l'hôpital et la survie des patients selon le volume de patients traités par le chirurgien et le type de la formation (oncologie chirurgicale c. hépatobiliaire c. autres) ont constitué les principales mesures de résultats.Au total, 1033 patients ont subi une résection hépatique. Le volume de patients traités par le chirurgien n'était pas un prédicteur de mortalité à l'hôpital (rapport de cotes rajusté, 0,63, intervalle de confiance [IC] à 95 % 0,32–1,20) ni de survie du patient (rapport de risque non rajusté, 1,11, IC à 95 % 0,82–1,51). On a aussi démontré la non importance de la formation au niveau du fellowship selon le type de chirurgien.Les divers modes de formation au niveau du fellowship ne semblent pas avoir d'effet sur la mortalité à l'hôpital ou la survie des patients après une résection hépatique.

Rituximab, an anti-CD20 monoclonal antibody that selectively depletes B cells, has shown promise in autoantibody-associated, immune-mediated disorders. As ursodeoxycholic acid (UDCA) is not successful in all patients with primary biliary cirrhosis (PBC), additional treatment options are necessary. The objective of this study was to assess the safety and efficacy of rituximab in patients with PBC refractory to UDCA.Fourteen PBC patients refractory to UDCA received two rituximab infusions (1,000 mg) 2 weeks apart. The primary efficacy outcome was normalization and/or 25% improvement in serum alkaline phosphatase (ALP) concentration at 6 months.The median age was 53 years, and 92% were female and antimitochondrial antibody (AMA) positive. The median UDCA dosage was 15.3 mg/kg/day (interquartile range 14.5-17.8). Although rituximab was well tolerated, one patient withdrew due to an asthma exacerbation during the first infusion. Effective B-cell depletion was observed in the remaining 13 patients, including three that developed human anti-chimeric antibodies. ALP normalization and/or ≥ 25% improvement was observed in three patients (23%) at 6, 12, and 18 months. Significant reductions in median ALP (from 259 U/l at baseline to 213 U/l at 6 months; median decrease 16%), and serum IgM and AMA levels were observed at 6 months. Although fatigue was stable, pruritus improved in 60% of patients at 12 months (vs. 8% with worsening pruritus).Selective B-cell depletion with rituximab was safe and associated with a significant decrease in autoantibody production, but had limited biochemical efficacy in PBC patients with an incomplete response to UDCA.

Background High-throughput technologies have the potential to identify non-invasive biomarkers of liver pathology and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic hepatitis C virus (HCV) infection. Methods Sera from 45 non-diabetic patients with chronic HCV were quantitatively analyzed using 1H-NMR spectroscopy. A metabolite profile of advanced fibrosis (METAVIR F3-4) was established using orthogonal partial least squares discriminant analysis modeling and validated using seven-fold cross-validation and permutation testing. Bioprofiles of moderate to severe steatosis (≥33 %) and necroinflammation (METAVIR A2-3) were also derived. The classification accuracy of these profiles was determined using areas under the receiver operator curves (AUROCSs) measuring against liver biopsy as the gold standard. Results In total 63 spectral features were profiled, of which a highly significant subset of 21 metabolites were associated with advanced fibrosis (variable importance score >1 in multivariate modeling; R2 = 0.673 and Q2 = 0.285). For the identification of F3–4 fibrosis, the metabolite bioprofile had an AUROC of 0.86 (95 % CI 0.74–0.97). The AUROCs for the bioprofiles for moderate to severe steatosis were 0.87 (95 % CI 0.76–0.97) and for grade A2–3 inflammation were 0.73 (0.57–0.89). Conclusion This proof-of-principle study demonstrates the utility of a metabolomics profiling approach to non-invasively identify biomarkers of liver fibrosis, steatosis and inflammation in patients with chronic HCV. Future cohorts are necessary to validate these findings. Electronic supplementary material The online version of this article (doi:10.1186/s40169-016-0109-2) contains supplementary material, which is available to authorized users.

Objective: The present study examined the effects of aqueous and methanolic extracts of palm dates (fruits and seeds) on diabetic nephropathy in a rat model of type 2 DM. Methods: Sixty male albino rats subdivided into a) normal control (NC) group, b) diabetic control (DM) group, c) aqueous fruit extract (AFE) group, d) methanolic fruit extract (MFE) group, e) aqueous seed extract (ASE) group and f) methanolic seed extract (ASE) group. Treatment with both extracts done for 15 weeks after induction of type 2 DM. by the end of experiment fasting blood glucose, serum lipid profile, creatinine, urea, uric acid, urinary albumin excretion, kidney tissue MDA, catalase, SOD, GSH were measured and kidney histopathological examination was done. Results: Diabetic untreated rats showed significant hyperglycemia and hyperlipidemia and deterioration in kidney functions and morphology with enhanced oxidative stress in kidney tissues. On other hand, rats treated with either aqueous or methanolic fruit or seed extracts showed significant improvement in all studied parameters compared to DM group (p

Background. Hospital outcome report cards are used to judge provider performance, including for liver transplantation. We aimed to determine the impact of the choice of risk adjustment method on hospital rankings based on mortality rates in cirrhotic patients. Material and methods. We identified 68,426 cirrhotic patients hospitalized in the Nationwide Inpatient Sample database. Four risk adjustment methods (the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups) were used in logistic regression models for mortality. Observed to expected (O/E) death rates were calculated for each method and hospital. Statistical outliers with higher or lower than expected mortality were identified and rankings compared across methods. Results. Unadjusted mortality rates for the 553 hospitals ranged from 1.4 to 30% (overall, 10.6%). For 163 hospitals (29.5%), observed mortality differed significantly from expected when judged by one or more, but not all four, risk adjustment methods (25.9% higher than expected mortality and 3.6% lower than expected mortality). Only 28% of poor performers and 10% of superior performers were consistently ranked as such by all methods. Agreement between methods as to whether hospitals were flagged as outliers was moderate (kappa 0.51-0.59), except the Charlson/Deyo and Elixhauser algorithms which demonstrated excellent agreement (kappa 0.75). Conclusions. Hospital performance reports for patients with cirrhosis require sensitivity to the method of risk adjustment. Depending upon the method, up to 30% of hospitals may be flagged as outliers by one, but not all methods. These discrepancies could have important implications for centers erroneously labeled as high mortality outliers.

Background & Aims The severe depletion of muscle mass at the third lumbar vertebral level (sarcopenia) is a marker of malnutrition and is independently associated with mortality in patients with cirrhosis. Instead of monitoring sarcopenia by cross-sectional imaging, we investigated whether ultrasound-based measurements of peripheral muscle mass, measures of muscle function, along with nutritional factors, are associated with severe loss of muscle mass. Methods We performed a prospective study of 159 outpatients with cirrhosis (56% male; mean age, 58 ± 10 years; mean model for end-stage liver disease score, 10 ± 3; 60% Child-Pugh class A) evaluated at the Cirrhosis Care Clinic at the University of Alberta Hospital from March 2011 through September 2012. Lumbar skeletal muscle indices were determined by computed tomography or magnetic resonance imaging. We collected clinical data and data on patients' body composition, nutrition, and thigh muscle thickness (using ultrasound analysis). We also measured mid-arm muscle circumference, mid-arm circumference, hand grip, body mass index, and serum level of albumin; patients were evaluated using the subjective global assessment scale. Findings from these analyses were compared with those from cross-sectional imaging, for each sex, using logistic regression analysis. Results Based on cross-sectional imaging analysis, 43% of patients had sarcopenia (57% of men and 25% of women). Results from the subjective global assessment, serum level of albumin, and most nutritional factors were significantly associated with sarcopenia. We used multivariate analysis to develop a model to identify patients with sarcopenia, and developed a nomogram based on body mass index and thigh muscle thickness for patients of each sex. Our model identified men with sarcopenia with an area under the receiver operating characteristic curve value of 0.78 and women with sarcopenia with an area under the receiver operating characteristic curve value of 0.89. Conclusions In a prospective study of patients with cirrhosis, we found that the combination of body mass index and thigh muscle thickness (measured by ultrasound) can identify male and female patients with sarcopenia almost as well as cross-sectional imaging (area under the receiver operating characteristic curve values of 0.78 and 0.89, respectively). These factors might be used in screening and routine nutritional monitoring of patients with cirrhosis.

Background: Amoebic liver abscess (ALA) may be associated with significant morbidity and mortality, but nationwide American data is unavailable. Our objective was to describe ALA epidemiology and outcomes in USA from a population-based perspective. Methods: Patients hospitalized with ALA between 1993 and 2007 were identified using the Nationwide Inpatient Sample. Patient characteristics, interventions and outcomes including mortality were determined. The annual incidence of ALA and temporal trends were determined using the negative binomial regression models. Results: Between 1993 and 2007, 848 hospitalizations for ALA, corresponding to ∼4100 hospitalizations nationwide, were identified. The annual incidence was 1.38 per million population with a 2.4% [95% confidence interval (CI) 0–4.8%; P=0.06] average annual decline during this study. Most patients were hospitalized in western (54%) and southern states (27%), and 48% were Hispanic. Males (incidence rate ratio vs. females: 4.53; 95% CI 4.19–4.90) had the highest incidence rates. Percutaneous and surgical drainage was required in 48 and 7% of patients respectively. Although length of stay [median, 6 days; interquartile range (IQR) 4–10] and hospital charges (US$25 345; IQR US$15 030–42 275) were substantial, in-hospital mortality was rare (0.8%). Females [odds ratio (OR) 6.12; CI 1.39–26.8], patients ≥60 years (OR 13.3; 95% CI 2.5–71.5), and those with ≥3 comorbidities (OR 5.80; 95% CI 1.30–25.8), particularly malnutrition, had an increased risk of death. Conclusions: ALA is rare and the incidence has decreased in USA. Young, Hispanic males in southwestern states are most frequently affected. Mortality caused by ALA is lower than what was reported previously.

The purpose of this study was to determine whether morbidity and mortality in patients undergoing elective resection of colon cancer are associated with surgeon or hospital volume. Using the Nationwide Inpatient Sample database, we identified all adult patients who underwent elective resection for colon cancer as their primary procedure between 2003 and 2007. Cases were divided into three groups according to the mean number of resections performed annually by each surgeon: low volume (≤4/year), intermediate volume (5–9/year), or high volume (≥10/year). Annual hospital case-load was also categorized as low volume (≤30/year), intermediate volume (31–60/year), and high volume (≥61/year). Multiple logistic regression models were used to identify differences in morbidity and mortality. A total of 54,000 patients underwent resection of colon cancer by 7,313 surgeons in 1,398 hospitals. After adjusting for important covariates including hospital volume, colon cancer resection by high-volume surgeons was an independent predictor of decreased morbidity (odds ratio [OR], 0.91; 95% CI, 0.85–0.97) and mortality (OR, 0.75; 95% CI, 0.65–0.86). Mortality was lowest among patients operated on by high-volume surgeons in high-volume hospitals (2.2% vs. 3.9%; OR, 0.56; 95% CI, 0.46–0.68). In patients undergoing elective resection of colon cancer, procedures done by high-volume surgeons are associated with decreased morbidity and mortality.

Background Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients. Methods We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA). Results We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07–0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05–0.83). Conclusions In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients.