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Background: Environmental determinants of appendicitis are poorly understood. Past work suggests that air pollution may increase the risk of appendicitis. Objectives: We investigated whether ambient ground-level ozone (O3) concentrations were associated with appendicitis and whether these associations varied between perforated and nonperforated appendicitis. Methods: We based this time-stratified case-crossover study on 35,811 patients hospitalized with appendicitis from 2004 to 2008 in 12 Canadian cities. Data from a national network of fixed-site monitors were used to calculate daily maximum O3 concentrations for each city. Conditional logistic regression was used to estimate city-specific odds ratios (ORs) relative to an interquartile range (IQR) increase in O3 adjusted for temperature and relative humidity. A random-effects meta-analysis was used to derive a pooled risk estimate. Stratified analyses were used to estimate associations separately for perforated and nonperforated appendicitis. Results: Overall, a 16-ppb increase in the 7-day cumulative average daily maximum O3 concentration was associated with all appendicitis cases across the 12 cities (pooled OR = 1.07; 95% CI: 1.02, 1.13). The association was stronger among patients presenting with perforated appendicitis for the 7-day average (pooled OR = 1.22; 95% CI: 1.09, 1.36) when compared with the corresponding estimate for nonperforated appendicitis [7-day average (pooled OR = 1.02, 95% CI: 0.95, 1.09)]. Heterogeneity was not statistically significant across cities for either perforated or nonperforated appendicitis (p > 0.20). Conclusions: Higher levels of ambient O3 exposure may increase the risk of perforated appendicitis. [ABSTRACT FROM AUTHOR]

Introduction: Recently, many surgical procedures have become regionalized in the United States, likely owing to research demonstrating a relationship between volume and outcome. We sought to describe patient characteristics and outcomes according to hospital volume along with patterns of regionalization for hepatic resection in Canada from 1995 to 2004.Methods: Discharge data from all hospitals across Canada except Quebec were obtained from the Canadian Institute for Health Information for 1995-2004. All patients undergoing a hepatic resection were identified using ICD-9 and ICD-10 codes. High-volume hospitals were defined as those performing ten or more procedures per year.Results: A total of 9,912 patients (mean age 59 years) underwent hepatic resection. The proportion of procedures performed at high-volume hospitals increased from 42% in 1995 to 84% in 2004. Overall mortality rate for the study period was 5.0% which decreased over time. Mortality rates were higher at low-volume (6.1%) compared to high-volume centers (4.6%), but this finding was not statistically significant (p = 0.7451). Those factors predictive of mortality in a multivariate analysis included age, gender, year of operation, operative indication, comorbidity score, and admission status.Discussion: Mortality rates have significantly improved. Hospital volume is not a significant predictor of mortality following liver resection in Canada. [ABSTRACT FROM AUTHOR]

Objective: We describe the epidemiology of emergency department (ED) visits for acetaminophen overdose in a large Canadian health region, with a focus on sociodemographic risk factors and temporal trends. Methods: Patients presenting to an ED in the Calgary Health Region (population ∼1.1 million) for acetaminophen overdose between 1997 and 2002 were identified using regional administrative data. Results: A total of 2699 patients made 3015 ED visits for acetaminophen overdose between 1997 and 2002, corresponding to an age- and sex-adjusted incidence of 45.7 per 100 000 population. Alcohol-related disorders were common (19%) and overdose rates were higher in females, younger patients, Aboriginals and social assistance recipients. The incidence decreased from 52.6 per 100 000 in 1997 to 35.1 per 100 000 in 2002 (34% relative reduction; p < 0.0005). When classified according to suicidal intent, the rates of intentional and unintentional overdose (69% and 25% of all overdoses, respectively) showed similar temporal trends. A marked seasoriality was observed, with a peak in spring and early summer. Conclusions: ED visit rates for acetaminophen overdose fell between 1997 and 2002. High-risk groups, including young females and marginalized populations, may benefit from preventive and educational initiatives. [ABSTRACT FROM AUTHOR]

Background: Primary biliary cirrhosis is a chronic granulomatous cholangitis, characteristically associated with antimitochondrial antibodies. Twin and family aggregation data suggest that there is a significant genetic predisposition to primary biliary cirrhosis, but the susceptibility loci are unknown. Methods: To identify genetic loci conferring a risk for primary biliary cirrhosis, we carried out a genomewide association analysis in which DNA samples from 2072 Canadian and U.S. subjects (536 patients with primary biliary cirrhosis and 1536 controls) were genotyped for more than 300,000 single-nucleotide polymorphisms (SNPs). Sixteen of the SNPs most strongly associated with primary biliary cirrhosis were genotyped in two independent replication sets. We carried out fine-mapping studies across three loci associated with primary biliary cirrhosis. Results: We found significant associations between primary biliary cirrhosis and 13 loci across the HLA class II region; the HLA-DQB1 locus (encoding the major histocompatibility complex class II, DQ β chain 1) had the strongest association (P=1.78×10−19; odds ratio for patients vs. controls, 1.75). Primary biliary cirrhosis was also significantly and reproducibly associated with two SNPs at the IL12A locus (encoding interleukin-12α), rs6441286 (P=2.42×10−14; odds ratio, 1.54) and rs574808 (P=1.88×10−13; odds ratio, 1.54), and one SNP at the IL12RB2 locus (encoding interleukin-12 receptor β2), rs3790567 (P=2.76×10−11; odds ratio, 1.51). Fine-mapping analysis showed that a five-allele haplotype in the 3′ flank of IL12A was significantly associated with primary biliary cirrhosis (P=1.15×10−34). We found a modest genomewide association (P<5.0×10−5) with the risk of disease for SNPs at the STAT4 locus (encoding signal transducer and activator of transcription 4) and the CTLA4 locus (encoding cytotoxic T-lymphocyte–associated protein 4) and 10 other loci. Conclusions: Our data show significant associations between primary biliary cirrhosis and common genetic variants at the HLA class II, IL12A, and IL12RB2 loci and suggest that the interleukin-12 immunoregulatory signaling axis is relevant to the pathophysiology of primary biliary cirrhosis. (ClinicalTrials.gov number, NCT00242125.) N Engl J Med 2009;360:2544-55. [ABSTRACT FROM AUTHOR]

Background: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2., Methods: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day., Results: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation., Conclusions: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)., (Copyright © 2020 Massachusetts Medical Society.)

Cryptococcal disease, caused by Cryptococcus neoformans and Cryptococcus gattii, is associated with significant morbidity and mortality but limited data exist on its incidence and impact. A study utilizing the Nationwide Inpatient Sample from 2000 to 2007 to examine the epidemiology and impact of cryptococcal disease in the United States was undertaken. The International Classification of Diseases 9th Version code was used to identify hospital discharges with diagnosis of Cryptococcus (117.5). Our primary outcome was the incidence rate of cryptococcal admissions. The impact of AIDS, age, and sex on hospitalization rates, mortality, and costs was assessed. The results showed that a total of 10,077 hospitalizations for cryptococcosis occurred corresponding to a weighted estimate of 49,010 cases. The median age was 43 years (interquartile range 34-54), and 26% were female. Approximately 64% of cases occurred in persons with AIDS. Although rates declined overall, age-adjusted rates were significantly higher in males with AIDS than in uninfected persons (p < 0.001). The mortality rate decreased but was greater in HIV-uninfected versus infected cohorts (12% versus 10%, p < 0.001). Conversely, hospital costs were greater in persons with AIDS ($40,671 versus $40,096, p=0.02). Although cryptococcal disease rates are decreasing over time, the associated mortality and costs remain concerning.

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 <3.5 g/dl). One-year mortality in patients with normal serum albumin and hypoalbuminaemia were 14% and 29% respectively (P = 0.004). For patients with serum albumin between 2.0 and 4.0 g/dl, an approximately linear, inverse relationship was observed between albumin and 1-year mortality [adjusted hazard ratio (HR) 1.45; 95% CI 1.03-2.03; P = 0.03]. For this outcome, the c-statistic of 5vMELD (0.778) was superior to those of MELD (0.754) and MELDNa (0.765) (both P ≤ 0.05)., Conclusions: Hypoalbuminaemia is an independent predictor of mortality on the LT waiting list. Compared with MELD and MELDNa, 5vMELD improves prediction of mortality suggesting that modification of these scores to include serum albumin should be considered as a means of prioritizing LT candidates., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation., Objective: To estimate the burden of HCV-related disease and costs from a Canadian perspective., Methods: Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, age- and sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals., Results: The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694., Conclusions: Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.

Objective: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases., Methods: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and⁄or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey., Results: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune⁄cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians' characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians' main concerns regarding noninvasive fibrosis assessment methods were access⁄availability (42.3%), lack of guidelines for clinical use (26.9%) and cost⁄lack of reimbursement (14.4%)., Conclusions: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better reimbursement policy to implement noninvasive tools to assess liver fibrosis.

Background & Aims: Hepatitis B virus (HBV) genotype and quantitative hepatitis B surface antigen (qHBsAg) have been related to clinical outcome. In this nationwide cross-sectional study, we aimed to investigate the epidemiology and clinical significance of HBV genotype and qHBsAg in patients with chronic hepatitis B (CHB)., Methods: Six hundred and thirty patients with CHB were seen in four urban tertiary referral centres in Canada. HBV genotype was determined by line probe assay (INNO-LIPA) and HBV DNA quantified by commercial PCR (Roche TaqMan, sensitivity <55 IU/ml or AMPLICOR, sensitivity <60 IU/ml). Titres of qHBsAg were determined by an in-house assay based on the WHO standard (calibration range 0.24-62.5 IU/ml)., Results: In 630 patients (57% male, 69% Asian, median age 42 years), 21% were hepatitis B e antigen positive and the median alanine aminotransferase was 29 U/L. The HBV genotype distribution was A (16%), B (29%), C (31%), D (16%), E (6%). HBV genotype was strongly associated with ethnicity, but neither genotype nor qHBsAg correlated with the degree of fibrosis. In the treatment-naïve patients, the baseline qHBsAg levels correlated with HBV DNA (r = 0.2517, P < 0.0008). The median qHBsAg levels were lowest in patients with genotype B (P < 0.0001), but no significant correlation was noted with all other HBV genotypes., Conclusions: In this large North American HBV epidemiological study, genotypes B and C were the most common; however, all genotypes (A-E) were observed with varied distribution nationwide. Baseline qHBsAg significantly correlated with HBV DNA and with HBV genotype B, but not with liver fibrosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic hepatitis C remains a significant medical and economic burden in Canada, affecting nearly 1% of the population. Since the last consensus conference on the management of chronic hepatitis C, major advances have warranted a review of recommended management approaches for these patients. Specifically, direct-acting antiviral agents with dramatically improved rates of virological clearance compared with standard therapy have been developed, and several single nucleotide polymorphisms associated with an increased probability of spontaneous and treatment-induced viral clearance have been identified. In light of this new evidence, a consensus development conference was held in November 2011; the present document highlights the results of the presentations and discussions surrounding these issues. It reviews the epidemiology of hepatitis C in Canada, preferred diagnostic testing approaches and recommendations for the treatment of chronically infected patients with the newly approved protease inhibitors (boceprevir and telaprevir), including those who have previously failed pegylated interferon and ribavirin therapy. In addition, recommendations are made regarding approaches to reducing the burden of hepatitis C in Canada.

Background: Liver stiffness measurement (LSM) using transient elastography (TE) is a promising tool for the noninvasive assessment of hepatic fibrosis., Objectives: To determine the feasibility and performance of TE in a North American cohort of patients with chronic liver disease., Methods: LSMs were obtained using TE in 260 patients with chronic hepatitis B or C, or nonalcoholic fatty liver disease from four Canadian hepatology centres. The accuracy of TE compared with liver biopsy for the prediction of significant fibrosis (Metavir fibrosis score of F2 or greater), bridging fibrosis (Metavir fibrosis score of F3 or greater) and cirrhosis (Metavir fibrosis score of F4 ) was assessed using area under ROC curves (AUROCs), and compared with the aspartate aminotransferase-to-platelet ratio index. The influence of alanine aminotransferase (ALT) levels and other factors on liver stiffness was determined using linear regression analyses., Results: failure of TE occurred in 2.7% of patients, while liver biopsies were inadequate for staging in 0.8%. Among the remaining 251 patients, the AUROCs of TE for Metavir fibrosis scores of F2 and F3 or greater, and F4 were 0.74 (95% CI 0.68 to 0.80), 0.89 (95% CI 0.84 to 0.94), and 0.94 (95% CI 0.90 to 0.97), respectively. LSM was more accurate than the aminotransferase-to-platelet ratio index for bridging fibrosis (AUROC 0.78) and cirrhosis (AUROC 0.88), but not significant fibrosis (AUROC 0.76). At a cut-off of 11.1 kPa, the sensitivity, specificity, and positive and negative predictive values for cirrhosis (prevalence 11%) were 96%, 81%, 39% and 99%, respectively. For significant fibrosis (prevalence 53%), a cut-off of 7.7 kPa was 68% sensitive and 69% specific, and had a positive predictive value of 70% and a negative predictive value of 65%. Liver stiffness was independently associated with ALT, body mass index and steatosis. The optimal LSM cut-offs for cirrhosis were 11.1 kPa and 11.5 kPa in patients with ALT levels lower than 100 U⁄L and 100 U⁄L or greater, respectively. For fibrosis scores of F2 or greater, these figures were 7.0 kPa and 8.6 kPa, respectively., Conclusions: the major role of TE is the exclusion of bridging fibrosis and cirrhosis. However, TE cannot replace biopsy for the diagnosis of significant fibrosis. Because liver stiffness may be influenced by significant ALT elevation, body mass index and⁄or steatosis, tailored liver stiffness cut-offs may be necessary to account for these factors.

Purpose: The risk of abdominal surgery in patients with end-stage renal failure is poorly defined. Our objective was to describe outcomes of colorectal surgery in dialysis patients from a population-based perspective., Methods: We analyzed the 1993 to 2007 Nationwide Inpatient Sample to identify patients hospitalized for colorectal surgery. The effect of renal failure on mortality, complications, length of stay, and charges was evaluated using logistic regression models., Results: Between 1993 and 2007, there were 755,343 admissions for colorectal surgery in the Nationwide Inpatient Sample database; 5806 patients (0.77%) were receiving dialysis treatment (87.4% hemodialysis, 4.9% peritoneal dialysis, 7.7% method not specified). Patients undergoing dialysis had an increased risk of mortality (22.1% vs 2.8%; adjusted OR 4.83; 95% CI 4.58-5.31) and complications (52.1% vs 34.0%; adjusted OR 2.04; 95% CI 1.90-2.17). Dialysis patients undergoing nonelective procedures had a 2-fold higher mortality rate than patients having had elective surgery (25.5% vs 10.3%; adjusted OR 2.01; 95% CI 1.65-2.43). In nonelective surgery, independent predictors of mortality included procedures with an end-stoma (adjusted OR 1.86; 95% CI 1.58-2.18), age over 60 (adjusted OR 1.73; 95% CI 1.43-2.08), total colectomy (adjusted OR 1.68; 95% CI 1.27-2.22), vascular insufficiency as surgical indication (adjusted OR 1.58; 95% CI 1.32-1.90), nonprivate insurance coverage (adjusted OR 1.38; 95% CI 1.07-1.77) and malnutrition (adjusted OR 1.26; 95% CI 1.01-1.59)., Conclusions: Patients receiving dialysis treatment have an increased risk of morbidity and mortality following colorectal surgery. Elective procedures are associated with a 10% rate of mortality in this population. Dialysis patients are especially susceptible to infectious and pulmonary complications after colorectal resection. Additional studies are necessary to refine risk stratification in this high-risk patient population.

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38).

Background: The outcomes of pregnancy in patients with cirrhosis are poorly described. Our objective was to assess obstetric outcomes in cirrhotic women and their infants from a population-based perspective., Methods: We analysed the 1993-2005 US Nationwide Inpatient Sample database to identify obstetric hospitalizations among patients with cirrhosis (n=339) and controls matched on age, hospital and year (n=6625). The effect of cirrhosis on maternal and fetal outcomes was evaluated using regression models with adjustment for patient and hospital factors., Results: Between 1993 and 2005, 114 antepartum and 225 delivery admissions in cirrhotic patients were identified. The estimated mean number of deliveries nationwide increased from 68 to 106 annually between 1993 and 1999 and 2000 and 2005 (P=0.0004). Patients with cirrhosis were more likely to deliver by caesarean [42 vs. 28%; adjusted odds ratio (OR) 1.41; 95% confidence interval (CI) 1.06-1.88]. Maternal (1.8 vs. 0%; P<0.0001) and fetal mortality (5.2 vs. 2.1%; P<0.0001), antepartum admission (OR 2.97; 95% CI 2.24-3.96), and maternal (OR 2.03; 95% CI 1.60-2.57) and fetal complications (OR 3.66; 95% CI 2.74-4.88) were greater among cirrhotic patients than controls. Gestational hypertension, placental abruption and uterovaginal haemorrhage were more common in patients with cirrhosis; their infants had higher rates of prematurity and growth restriction. Hepatic decompensation occurred in 15%, including ascites in 11% and variceal haemorrhage in 5%. In women with decompensation, maternal and fetal mortality were 6 and 12% respectively., Conclusions: Although rare, pregnancies among women with cirrhosis are increasing. Cirrhotic patients and their infants have an increased risk of obstetric complications, emphasizing the importance of close maternal-fetal monitoring during pregnancy.

Unlabelled: The recent epidemiology and outcomes of primary biliary cirrhosis (PBC) in North America are incompletely described, partly due to difficulties in case ascertainment. In light of their availability, broad coverage, and limited expense, administrative databases may facilitate such investigations. We used population-based administrative data (inpatient, ambulatory care, and physician billing databases) and a validated International Classification of Diseases coding algorithm to describe the epidemiology and natural history of PBC in the Calgary Health Region (population approximately 1.1 million). Between 1996 and 2002, the overall age/sex-adjusted annual incidence of PBC was 30.3 cases per million (48.4 per million in women, 10.4 per million in men). Although the incidence remained stable, the prevalence increased from 100 per million in 1996 to 227 per million in 2002 (P < 0.0005). Among 137 incident cases with a total follow-up of 801 person-years from diagnosis (median 5.8 years), 27 patients (20%) died and six (4.4%) underwent liver transplantation. The estimated 10-year probabilities of survival, liver transplantation, and transplant-free survival were 73% (95% confidence interval [CI] 60%-83%), 6% (95% CI 2.5%-12.6%), and 68% (95% CI 55%-78%), respectively. Survival in PBC patients was significantly lower than that of the age/sex-matched Canadian population (standardized mortality ratio 2.87; 95% CI 1.89-4.17); male sex (hazard ratio [HR] 3.80; 95% CI 1.85-7.82) and an older age at diagnosis (HR per additional year, 1.06; 95% CI 1.03-1.10) were independent predictors of mortality., Conclusion: This population-based study demonstrates that the burden of PBC in Canada is high and growing. Survival of PBC patients is significantly lower than that of the general population, emphasizing the importance of developing new therapies for this condition.

Background: The risk of cardiac surgery in patients with cirrhosis is poorly defined. Our objective was to describe outcomes of coronary artery bypass graft (CABG) surgery in cirrhotic patients from a population-based perspective., Methods: We analysed the 1998-2004 Nationwide In-patient Sample to identify patients hospitalized for CABG surgery. The effect of cirrhosis on mortality, complications, length of stay (LOS) and charges was evaluated using logistic regression models., Results: Between 1998 and 2004, there were 403 094 CABG admissions; 711 patients (0.2%) had cirrhosis. The average annual number of surgeries increased 4.2% [95% confidence interval (CI) 0.7-7.8] in cirrhotic patients, but decreased 5.5% (3.4-7.5) in non-cirrhotic patients. Patients with cirrhosis had an increased risk of mortality [17 vs. 3%; adjusted odds ratio (OR) 6.67; 95% CI 5.31-8.31], complications [43 vs. 28%; OR 1.99 (95% CI 1.72-2.30)] and greater LOS and charges (P<0.0001). Predictors of mortality included age over 60 (OR 2.21; 95% CI 1.31-3.73), female gender (OR 1.92; 95% CI 1.08-3.41), ascites (OR 3.80; 95% CI 1.95-7.39) and congestive heart failure (OR 1.75; 95% CI 1.08-2.84). Hospital volume and off-pump CABG did not affect mortality., Conclusions: Patients with cirrhosis have an increased risk of morbidity and mortality following CABG surgery. Additional studies are necessary to refine risk stratification in this high-risk patient population.

Background: Leaving hospital against medical advice (AMA) may have consequences with respect to health-related outcomes; however, inflammatory bowel disease (IBD) patients have been inadequately studied. Thus, we determined the prevalence of self-discharge, assessed predictors of AMA status, and evaluated time trends., Methods: We analyzed the 1995-2005 Nationwide Inpatient Sample (NIS) to identify 93,678 discharges with a primary diagnosis of IBD admitted to the hospital emergently and did not undergo surgery. We described the proportion of IBD patients who left AMA. Predictors of AMA status were evaluated using a multivariate logistic regression model and temporal trend analyses were performed with Poisson regression models., Results: Between 1995 and 2005, 1.31% of IBD patients left hospitals AMA. Crohn's disease (CD) patients were more likely to leave AMA (adjusted odds ratio [aOR], 1.53; 95% confidence intervals [CI]: 1.30-1.79). Characteristics associated with leaving AMA included: ages 18-34 (aOR, 7.77, 95% CI: 4.34-13.89); male (aOR, 1.75; 95% CI: 1.55-1.99); Medicaid (aOR, 4.55; 95% CI: 3.81-5.43) compared to private insurance; African Americans (aOR, 1.34; 95% CI: 1.09-1.64) compared to white; substance abuse (aOR, 2.75; 95% CI: 2.14-3.54); and psychosis (aOR, 1.55; 95% CI: 1.13-2.14). The incidence rates of self-discharge for CD patients were stable (P > 0.05) between 1995 and 1999, while they significantly (P < 0.0001) increased after 1999. In contrast, AMA rates for UC patients remained stable during the study period., Conclusions: Approximately 1 in 76 IBD patients admitted emergently for medical management leave the hospital AMA. These were primarily disenfranchised patients who may lack adequate outpatient follow-up.

Unlabelled: Risk-adjusted health outcomes are often used to measure the quality of hospital care, yet the optimal approach in patients with liver disease is unclear. We sought to determine whether assessments of illness severity, defined as risk for in-hospital mortality, vary across methods in patients with cirrhosis. We identified 258,731 patients with cirrhosis hospitalized in the Nationwide Inpatient Sample between 2002 and 2005. The performance of four common risk adjustment methods (the Charlson/Deyo and Elixhauser comorbidity algorithms, Disease Staging, and All Patient Refined Diagnosis Related Groups [APR-DRGs]) for predicting in-hospital mortality was determined using the c-statistic. Subgroup analyses were conducted according to a primary versus secondary diagnosis of cirrhosis and in homogeneous patient subgroups (hepatic encephalopathy, hepatocellular carcinoma, congestive heart failure, pneumonia, hip fracture, and cholelithiasis). Patients were also ranked according to the probability of death as predicted by each method, and rankings were compared across methods. Predicted mortality according to the risk adjustment methods agreed for only 55%-67% of patients. Similarly, performance of the methods for predicting in-hospital mortality varied significantly. Overall, the c-statistics (95% confidence interval) for the Charlson/Deyo and Elixhauser algorithms, Disease Staging, and APR-DRGs were 0.683 (0.680-0.687), 0.749 (0.746-0.752), 0.832 (0.829-0.834), and 0.875 (0.873-0.878), respectively. Results were robust across diagnostic subgroups, but performance was lower in patients with a primary versus secondary diagnosis of cirrhosis., Conclusion: Mortality analyses in patients with cirrhosis require sensitivity to the method of risk adjustment. Because different methods often produce divergent severity rankings, analyses of provider-specific outcomes may be biased depending on the method used.

Background: Nearly 1% of Canadians are infected with the hepatitis C virus (HCV). Simulation analyses have suggested that HCV will place an increasing burden on the health care system as the infected population ages, but supportive clinical data are limited., Objectives: To study temporal trends in HCV-related hospitalizations and predictors of increased health care utilization from a Canadian population-based perspective., Methods: An administrative hospitalization database from the Calgary Health Region was used to identify patients who were admitted for HCV between 1994 and 2004. The primary outcomes were liver-related HCV hospitalizations, length of stay, hospital costs and in-hospital mortality. Average annual growth rates in outcomes were calculated and subgroup analyses were conducted according to age, sex and HIV/HCV coinfection status., Results: Between 1994 and 2004, there were 4002 HCV-related hospitalizations; 22% were liver-related. Liver-related hospitalizations, lengths of stay and in-hospital mortality increased approximately fourfold or an average of 15% to 18% annually (P<0.0005). Patients aged 40 to 59 years and HIV/HCV coinfected patients experienced the largest average annual growth rates (19% to 27% and 30% to 40%, respectively; P<0.0005), reflecting the accelerated natural history of HCV in these subgroups. Hospital costs for liver-related HCV hospitalizations increased by an average of 41% annually (P=0.001) between 2000 and 2004. The average annual increase in liver-related hospitalizations remained significant in a sensitivity analysis, even when 75% of HCV cases were under-reported in 1994., Conclusions: The present studies' findings confirm the growing burden of HCV on the Canadian health care system. Strategies to prevent HCV infection and maximize the dissemination and most effective use of potentially curative antiviral therapies are necessary to reduce these trends.

Background: Surveys originating from universities appear to have higher response rates than those from commercial sources. In light of the growing scrutiny placed on physician-industry relations, the present study aimed to determine the impact of the pharmaceutical industry versus university sponsorship on response to a postal survey completed by Canadian hepatitis C virus (HCV) care providers., Patients and Methods: In the present controlled trial, 229 physicians and nurses involved in HCV treatment were randomly assigned to receive a survey with sponsorship from a pharmaceutical company or university. The primary outcome was the proportion of completed surveys returned. The secondary outcomes included the response rate after the first mailing and the number of days taken to respond., Results: One hundred fifteen participants were randomly assigned to receive the pharmaceutical industry survey and 114 were assigned to receive the university survey. The final response rate was 72.9% (167 of 229), which did not differ between the industry and university groups (RR=0.91; 95% CI 0.78 to 1.07). Nurses (OR=2.20; 95% CI 1.08 to 4.48) and participants from an academic centre (OR=3.14; 95% CI 1.64 to 6.00) were more likely to respond. The response rate after the first mailing (RR=0.85; 95% CI 0.68 to 1.07) and the median number of days taken to respond (21 days in both groups; P=0.20) did not differ between the industry and university groups., Conclusions: Pharmaceutical industry sponsorship does not appear to negatively impact response rates to a postal survey completed by Canadian HCV care providers.

Several government and nongovernment organizations held a consensus conference on the management of acute and chronic viral hepatitis to update previous management recommendations. The conference became necessary because of the introduction of new forms of therapy for both hepatitis B and hepatitis C. The conference issued recommendations on the investigation and management of chronic hepatitis B, including the use of lamivudine, adefovir and interferon. The treatment of hepatitis B in several special situations was also discussed. There were also recommendations on the investigation and treatment of chronic hepatitis C and hepatitis C-HIV coinfection. In addition, the document makes some recommendations about the provision of services by provincial governments to facilitate the delivery of care to patients with hepatitis virus infection. The present document is meant to be used by practitioners and other health care providers, including public health staff and others not directly involved in patient care.