MAP(ASH): A new scoring system for the prediction of intervention and mortality in upper gastrointestinal bleeding.

BACKGROUND AND AIM: Risk stratification for upper gastrointestinal bleeding (UGIB) is recommended. However, scoring system accuracy is suboptimal, and score calculation can be complex. Our aim was to develop a new score, the MAP(ASH) score, with information available in the emergency room and to validate it. METHODS: The score was built from a prospective database of patients with UGIB and validated in an international database of 3012 patients from six hospitals. Outcomes were 30-day mortality, endoscopic intervention, any intervention (red blood transfusion, endoscopic treatment, interventional radiology, surgery, or death), and rebleeding. Accuracy to predict outcomes was assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Five hundred forty-seven patients were included in the development cohort. Impaired mental status, albumin < 2.5 g/dL, pulse > 100, American Society of Anesthesiologists score > 2, systolic blood pressure < 90 mmHg, and hemoglobin < 10 g/dL were included in the score. The model had a good predictive accuracy for intervention (AUROC = 0.83; 95% confidence interval [CI]: 0.79-0.88) and fair for mortality (AUROC = 0.74; 95% CI: 0.68-0.81). Regarding endoscopic intervention, AUROC was 0.61 (95% CI: 0.56-0.66) in the original cohort and 0.69 (95% CI: 0.66-0.71) in the validation cohort, showing a poor performance, similar to other scores. For rebleeding, the MAP(ASH) (AUROC 0.73; 95% CI: 0.69-0.77) was similar to Glasgow Blatchford score (AUROC = 0.72; 95% CI: 0.67-0.76) but superior to AIMS65 (AUROC = 0.64; 95% CI: 0.59-0.68). CONCLUSION: MAP(ASH) is a simple pre-endoscopy risk score to predict intervention after UGIB, with fair discrimination at predicting mortality. Because of its applicability, it could be an option in clinical practice.

Previous Use of Antithrombotic Agents Reduces Mortality and Length of Hospital Stay in Patients With High-risk Upper Gastrointestinal Bleeding.

BACKGROUND & AIMS: Anti-thrombotic agents are risk factors for upper gastrointestinal bleeding (UGIB). However, few studies have evaluated their effects on patient outcomes. We assessed the effects of anti-thrombotic agents on outcomes of patients with high-risk UGIB. METHODS: We performed a prospective study of 619 patients with acute UGIB (defined by hematemesis, coffee-ground vomit or melena) who required intervention and underwent endoscopy at 8 centers in North America, Asia, and Europe, from March 2014 through March 2015. We collected data recorded on use of anti-thrombotic agents, clinical features, and laboratory test results to calculate AIMS65, Glasgow-Blatchford Score, and full Rockall scores. We also collected and analyzed data on co-morbidities, endoscopic findings, blood transfusion, interventional radiology results, surgeries, length of hospital stay, rebleeding, and mortality. RESULTS: Of the 619 patients who required endoscopic therapy, data on use of anti-thrombotic agents was available for 568; 253 of these patients (44%) used anti-thrombotic agents. Compared to patients not taking anti-thrombotic agents, patients treated with anti-thrombotics were older (P < .001), had a higher mean American Society of Anesthesiologists classification score (P < .0001), had a higher mean Rockall score (P < .0001), a higher mean AIMS65 score (P < .0001), and more frequently bled from ulcers (P < .001). There were no differences between groups in sex, systolic blood pressure, level of hemoglobin at hospital admission, frequency of malignancies, Glasgow-Blatchford Score, need for surgery or interventional radiology, number of rebleeding events, or requirement for transfusion. All-cause mortality was lower in patients who took anti-thrombotic drugs (11 deaths, 4%) than in patients who did not (37 deaths, 12%) (P = .002); this was due to lower bleeding-related mortality in patients taking anti-thrombotic drugs (3 deaths, 1%) than in patients who were not (19 deaths, 6%) (P = .003). Patients taking anti-thrombotic drugs had mean hospital stays of 6.9 days (95% CI, 2-23 days) compared to 7.9 days for non-users of anti-thrombotic agents (95% CI, 2-26 days) (P = .04). CONCLUSIONS: Despite being older, with higher American Society of Anesthesiologists classification, AIMS65, and Rockall scores, patients who have UGIB that requires endoscopic therapy and take anti-thrombotic drugs have lower mortality due to GI bleeding and shorter hospital stays, with similar rates of rebleeding, surgery, and transfusions, compared with those not taking anti-thrombotic drugs.

Severity and Outcomes of Upper Gastrointestinal Bleeding With Bloody Vs. Coffee-Grounds Hematemesis.

OBJECTIVES: Numerous reviews indicate bloody hematemesis signifies more severe bleeding than coffee-grounds hematemesis. We assessed severity and outcomes related to bleeding symptoms in a prospective study. METHODS: Consecutive patients presenting with hematemesis or melena were categorized as bloody emesis (N=1209), coffee-grounds emesis without bloody emesis (N=701), or melena without hematemesis (N=1069). We assessed bleeding severity (pulse, blood pressure) and predictors of outcome (hemoglobin, risk stratification scores) at presentation, and outcomes of bleeding episodes. The primary outcome was a composite of transfusion, intervention, or mortality. RESULTS: Bloody and coffee-grounds emesis were similar in pulse ≥100 beats/min (35 vs. 37%), systolic blood pressure ≤100 mm Hg (12 vs. 12%), and hemoglobin ≤100 g/l (25 vs. 27%). Risk stratification scores were lower with bloody emesis. The composite end point was 34.7 vs. 38.2% for bloody vs. coffee-grounds emesis; mortality was 6.6 vs. 9.3%. Hemostatic intervention was more common (19.4 vs. 14.4%) with bloody emesis (due to a higher frequency of varices necessitating endoscopic therapy), as was rebleeding (7.8 vs. 4.5%). Outcomes were worse with hematemesis plus melena vs. isolated hematemesis for bloody (composite: 62.4 vs. 25.6%; hemostatic intervention: 36.5 vs. 13.8%) and coffee-grounds emesis (composite: 59.1 vs. 27.1%; hemostatic intervention: 26.4 vs. 8.1%). CONCLUSIONS: Bloody emesis is not associated with more severe bleeding episodes at presentation or higher mortality than coffee-grounds emesis, but is associated with modestly higher rates of hemostatic intervention and rebleeding. Outcomes with hematemesis are worsened with concurrent melena. The presence of bloody emesis plus melena potentially could be considered in decisions regarding timing of endoscopy.

Relationship of time to presentation after onset of upper GI bleeding with patient characteristics and outcomes: a prospective study.

BACKGROUND AND AIMS: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. METHODS: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. RESULTS: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). CONCLUSIONS: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation.

Population-based epidemiology study of autoimmune hepatitis: a disease of older women?

BACKGROUND AND AIM: The etiology of autoimmune hepatitis (AIH) is unknown, and limited epidemiological data are available. Our aim was to perform a population based epidemiological study of AIH in Canterbury, New Zealand. METHODS: To calculate point prevalence, all adult and pediatric outpatient clinics and hospital discharge summaries were searched to identify all cases of AIH in the Canterbury region. Incident cases were recruited prospectively in 2008. Demographic and clinical data were extracted from case notes. Both the original revised AIH criteria and the simplified criteria were applied and cases were included in the study if they had definite or probable AIH. RESULTS: When the original revised criteria were used, 138 cases (123 definite and 14 probable AIH), were identified. Prospective incidence in 2008 was 2.0/100,000 (95% confidence interval [CI] 0.8-3.3/100,000). Point prevalence on 31 December 2008 was 24.5/100,000 (95% CI 20.1-28.9). Age-standardized (World Health Organization standard population) incidence and prevalence were 1.7 and 18.9 per 100,000, respectively. Gender-specific prevalence confirmed a female predominance, while ethnicity-specific prevalence showed higher prevalence in Caucasians. 72% of cases presented after 40 years of age and the peak age of presentation was in the sixth decade of life. CONCLUSIONS: This is the first and largest population-based epidemiology study of AIH in a geographically defined region using standardized inclusion criteria. The observed incidence and prevalence rates are among the highest reported. The present study confirms that AIH presents predominantly in older women, with a peak in the sixth decade, contrary to the classical description of the disease.

Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study.

OBJECTIVE:  To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. DESIGN:  International multicentre prospective study. SETTING:  Six large hospitals in Europe, North America, Asia, and Oceania. PARTICIPANTS:  3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. MAIN OUTCOME MEASURES:  Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. RESULTS:  The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay. CONCLUSIONS:  The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited.Trial registration Current Controlled Trials ISRCTN16235737.

International prospective observational study of upper gastrointestinal haemorrhage: Does weekend admission affect outcome?

INTRODUCTION: Out of hours admissions have higher mortality for many conditions but upper gastrointestinal haemorrhage studies have produced variable outcomes. METHODS: Prospective study of 12 months consecutive admissions of upper gastrointestinal haemorrhage from four international high volume centres. Admission period (weekdays, weeknights or weekends), demographics, haemodynamic parameters, laboratory results, endoscopy findings, further procedures and 30-day mortality were recorded. Five upper gastrointestinal haemorrhage risk scores were calculated. RESULTS: 2118 patients, 60% male, median age 66 years were studied. Compared with patients presenting on weekdays, patients presenting at weekends had no significant differences in comorbidity, pulse, systolic BP, risk scores, frequency of peptic ulcers or varices. Those presenting on weekdays had lower haemoglobin (p = 0.007) and were more likely to have a normal endoscopy (p < 0.01). Time to endoscopy was less for weeknight presentation (p = 0.001). Sixty-seven per cent of those presenting on weekdays, 75% on weeknights and 60% at weekends had endoscopy within 24 h. Transfusion requirements, need for endoscopic therapy or surgery/embolization, rebleeding rates (6.1%) and mortality (7.2%) did not differ with presentation time. CONCLUSION: This multi-centre international study in large centres found no difference in demographics, comorbidity or haemodynamic stability and no increase in mortality for patients presenting with upper gastrointestinal haemorrhage out of hours.

Autoimmune hepatitis: the role of environmental risk factors: a population-based study.

PURPOSE: The etiology of autoimmune hepatitis (AIH) likely involves a complex interaction of genetic and environmental factors. We aim to investigate the associations between exposure to putative environmental factors and AIH and to quantify AIH risk in a first-degree relative. METHODS: We conducted a population-based case-control study. Cases were AIH patients who were alive and resided in Canterbury, New Zealand, between 1 July 2011 and 30 June 2012. Controls were randomly selected from the Electoral Roll and were matched 2:1 to each case by age and gender. Self-reporting questionnaires that cover lifestyle factors, childhood factors and family history were used. RESULTS: 72 AIH cases and 144 controls were included. We found that exposure to antibiotics within 12 months prior to AIH diagnosis (OR 12.98, 95 % CI 2.49-67.67, p < 0.01) was an independent risk factor for the development of AIH. Alcohol consumption (OR 0.43, 95 % CI 0.28-0.68, p < 0.01) and childhood home with wood heating (OR 0.30, 95 % CI 0.14-0.63, p < 0.01) were independently associated with reduced risks of later development of AIH. The crude risk of AIH in first-degree relatives of a patient with AIH was 0.2 % (95 % CI <0.1-2.0). CONCLUSIONS: We found that antibiotics are an independent risk factor for the development of AIH, whereas alcohol consumption and living in a childhood home with wood heating are independent protective factors against the later development of AIH.

Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians.

PURPOSE: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians. METHODS: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays. Chi square analysis was used to test for association of allele and genotype with overall AIH, and with severe fibrosis and ALT levels at 6 months. RESULTS: Significant risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI 1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed that rs2187668 was independently associated with type 1 AIH susceptibility (OR = 2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of FAS SNP rs1800682 was associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI 1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015). CONCLUSIONS: This is the first population-based study to investigate genetic risk loci for type 1 AIH in New Zealand Caucasians. We report significant independent association of HLA-DRB1*03:01 with overall susceptibility to type 1 AIH, as well as FAS with a more aggressive disease phenotype.