Caroline McCloskey

Clinical trial: the incidence and early mortality after peptic ulcer perforation, and the use of low-dose aspirin and nonsteroidal anti-inflammatory drugs

Backgroundu2002 It is not clear whether the incidence or early mortality related to peptic ulcer perforation has changed.

Upper gastrointestinal bleeding and the changing use of COX-2 non-steroidal anti-inflammatory drugs and low-dose aspirin

Backgroundu2002 Rofecoxib was withdrawn in 2004.

Mortality following blood transfusion for non-variceal upper gastrointestinal bleeding

Objective Blood transfusion remains an integral step in the management of acute non-variceal upper gastrointestinal bleeding (NV-UGIB), but its safety is being increasingly questioned in less severe cases. The authors aimed to measure 30-day and 2-year mortalities after blood transfusion for NV-UGIB. Methods Cox proportional hazards models were used to estimate the association of blood transfusion with mortality while adjusting for age, Charlson comorbidity score, the complete Rockall score for acute UGIB, admission status and medication intake prior to bleeding. Main outcome measures Death from any cause at 30 days and 2 years after NV-UGIB. Results 1340 patients presented with NV-UGIB< (808 men (60.3%), median age 67 years) of whom 564 (42.1%) were transfused. The overall mortality was 5.3% at 30 days and 26.0% at 2 years in all patients. Comparing subjects with a haemoglobin concentration greater than 10.0 g/dl who were transfused with those who were not, 30-day mortalities (95% CIs) were 11.5% (6.7 to 18.0) versus 3.6% (2.3 to 5.3), respectively, p<0.001, and 2-year mortalities (95% CIs) were 40% (32 to 49) versus 20% (17 to 23), p<0.001. After adjusting for age, Charlson score, Rockall score and haemoglobin, the HRs (95% CIs) for death after transfusion were 1.88 (1.00 to 3.55) (p=0.051) at 30 days and 1.71 (1.28 to 2.28), (p<0.001) at 2 years. Conclusion In patients with moderately severe NV-UGIB, mortality is higher following blood transfusion. Whether this reflects selection bias, an effect of comorbidity or an effect of transfusion requires urgent prospective study.

Gastro-protective policy and the incidence of upper gastrointestinal bleeding

Objectives In recent years, policies have been proposed in order to guide the safer use of non-steroidal anti-inflammatory drugs (NSAIDs) and antiulcer therapy. We aimed to investigate the incidence of upper gastrointestinal bleeding (UGIB) before and after the introduction of these policies, 2007–2009, in a well-defined population in southwest Scotland. Methods All patients with non-variceal upper gastrointestinal bleeding (NV-UGIB), diagnosed at a single regional unit, were included. Total drugs prescribed in our population were noted, including antiulcer drugs, antithrombotic drugs and both cyclo-oxygenase-2 enzyme-selective and non-selective inhibiting NSAIDs. Results The incidence, the number of cases per 100u2005000 population per annum, of NV-UGIB fell from 134.7 in 2007 to 125.1 in 2008, and to 90.3 cases in 2009 (p<0.001). There was also a significant rise in the use of non-selective NSAIDs, proton pump inhibitors and antithrombotic drugs. Conclusions Although a cause-and-effect relationship cannot be fully proven, physician education through drug-use policies is associated with a drop in the incidence of NV-UGIB. This is relevant to the prevention of this common condition.

Falling mortality when adjusted for comorbidity in upper gastrointestinal bleeding: relevance of multi-disciplinary care

Objectives The understanding of changes in comorbidity might improve the management of upper gastrointestinal bleeding (UGIB); such changes might not be detectable in short-term studies. We aimed to study UGIB mortality as adjusted for comorbidity and the trends in risk scores over a 14-year period. Methods Patients presenting with UGIB to a single institution, 1996–2010, were assessed. Those with multiple comorbidities were managed in a multi-disciplinary care unit since 2000. Trends with time were assessed using logistic regression, including those for Charlson comorbidity score, the complete Rockall score and 30-day mortality. Results 2669 patients were included. The Charlson comorbidity score increased significantly with time: the odds of a high (3+) score increasing at a relative rate of 4.4% a year (OR 1.044; p<0.001). The overall 30-day mortality was 4.9% and inpatient mortality was 7.1%; these showed no relationship with time. When adjusted for the increasing comorbidity, the odds of death decreased significantly at a relative rate of 4.5% per year (p=0.038). After the introduction of multi-disciplinary care, the raw mortality OR was 0.680 (p=0.08), and adjusted for comorbidity it was 0.566 (p=0.013). Conclusions 30-day mortality decreased when adjusted for the rising comorbidity in UGIB; whether this is related to the introduction of multi-disciplinary care needs to be considered.

Occult vs. overt upper gastrointestinal bleeding – inverse relationship and the use of mucosal damaging and protective drugs

While efforts have focused on the prevention of overt upper gastrointestinal bleeding (UGIB), little is known about occult GIB, which might also originate from sites not protected by acid inhibition.

Upper gastrointestinal bleeding in hospital inpatients: the role of antithrombotic drugs

Background Critically ill patients are considered to be most at risk from developing non-variceal upper gastrointestinal bleeding (NVGIB) while in hospital. The increasing prescription of low-dose aspirin and other antithrombotic drugs for protection against thromboembolism to many patients admitted to hospital may increase the vulnerability of a wider group to NVGIB. Objective This study compares two groups of patients with NVGIB: group I, inpatients cared for outside the intensive care unit; and group II, patients admitted with this condition, while considering the use of antithrombotic drugs. Methods We identified all patients who developed NVGIB in the two calendar years between 2008 and 2009 and compared group I with group II while taking into account their clinical details including Rockall scores and drug usage. Results Compared with group II (n=274), group I (n=96) were older (median age of 77u2005years vs 68; p<0.001), had fewer males (45.8% vs 60.6%; p=0.016), higher prevalence of cardiovascular disease (52.1% vs 29.2%; p<0.001), more patients with complete Rockall score ≥3 (84.4% vs 66.7%; p=0.001) and more patients treated with aspirin or other antithrombotic drugs (64.6% vs 44.5%; p=0.001). After adjustment for age and sex, group I were still significantly more likely to be taking antithrombotic drugs than group II (OR (95% CIs), 2.15 (1.25 to 3.68); p=0.006). The endoscopic abnormalities in more than 80% of patients included erosive oesophagitis, gastric or duodenal ulcers or erosions. Conclusions Subjects who develop NVGIB as inpatients have higher Rockall scores are mainly older females with cardiovascular disease and using antithrombotic drugs. Secondary care clinicians should be mindful of this at-risk group of patients and consider giving them prophylactic antiulcer therapy.

Misoprostol for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs (MASTERS): a randomised, double-blind, placebo-controlled, phase 3 trial

BACKGROUNDnThe incidence of obscure gastrointestinal bleeding, which originates from the small bowel and is mainly associated with the use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), is rising. We assessed the efficacy and safety of misoprostol for the treatment of small bowel ulcers and erosions in patients taking low-dose aspirin or NSAIDs with obscure gastrointestinal bleeding.nnnMETHODSnIn this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients (aged ≥18 years) with small bowel ulcers who were taking low-dose aspirin, NSAIDs, or both for a minimum of 4 weeks, at University Hospital Crosshouse (Kilmarnock, UK). Eligible patients had evidence of obscure gastrointestinal bleeding (iron deficiency anaemia, a decrease in haemoglobin concentration of ≥20u2008×u2008103 mg/L, or positive faecal occult blood test) and normal upper endoscopy and colonoscopy. Patients were randomly assigned (1:1) using an interactive voice response system to receive 200 μg oral misoprostol or placebo four times daily for 8 weeks. Patients, investigators, and assessors were masked to treatment allocation. The primary endpoint was the complete healing of small bowel ulcers and erosions, assessed by video capsule endoscopy after 8 weeks of treatment. Primary analysis was by modified intention to treat, which included all randomised patients who received at least one dose of study treatment. Safety was assessed in the same population. The trial is registered with ClinicalTrials.gov, number NCT02202967.nnnFINDINGSnBetween Jan 7, 2016, and Oct 11, 2017, we randomly allocated 104 eligible patients: 52 to receive misoprostol and 52 to receive placebo. Two patients allocated to misoprostol were later found to meet one of the exclusion criteria, thus 50 randomly assigned patients in the misoprostol group and 52 patients in the placebo group received at least one dose of study treatment. Complete healing of small bowel ulcers and erosions was noted at week 8 in 27 (54%) of 50 patients in the misoprostol group and nine (17%) of 52 patients in the placebo group (percentage difference 36·7%, 95% CI 19·5-53·9; p=0·0002). Adverse events occurred in 23 (46%) of 50 patients in the misoprostol group and 22 (42%) of 52 patients in the placebo group. The most common adverse events were abdominal pain (ten [20%] in the misoprostol group vs 13 [25%] in the placebo group), nausea or vomiting (nine [18%] vs seven [13%]), and diarrhoea (11 [22%] vs six [12%]). Four (8%) of 50 patients in the misoprostol group had severe adverse events, compared with none in the placebo group. No serious adverse events were reported.nnnINTERPRETATIONnMisoprostol is effective for the treatment of small bowel ulcers and erosions in patients using low-dose aspirin and NSAIDs. Misoprostol might represent a pharmacological treatment option for lesions causing obscure gastrointestinal bleeding that is associated with aspirin and NSAIDs, but its use should be balanced against the risk of side-effects.nnnFUNDINGnNational Health Service (NHS) Greater Glasgow and Clyde and NHS Ayrshire and Arran.

Small Bowel and Other GI Lesions in Obscure Gastrointestinal Bleeding and Low Dose Aspirin vs. Nsaids. Screening Phase of the Masters Trial

Introduction While NSAIDs can affect any part of the GI tract, little is known about the effect of aspirin in the small bowel or colon. In this prospective analysis, we compared upper GI, small bowel, and colonic findings in patients taking aspirin vs. those taking NSAIDs while being considered in the screening phase of the MASTERS Trial (Misoprostol for the Healing of Small Bowel Ulceration in Patients with Obscure Blood Loss while Taking Low-Dose Aspirin or Non-Steroidal Anti-inflammatory Drugs). Method For MASTERS, obscure occult bleeding was defined as having absence of potentially bleeding lesions on colonoscopy and endoscopy, and in the presence of one or more of the following: positive faecal occult blood test; iron deficiency anaemia; or drop in Hb, > 2u2009gm/dl from baseline. Suitable patients underwent small bowel video capsule endoscopy (Omom systems, China). Results DEMOGRAPHY: 127 patients were assessed: 80 taking aspirin alone without NSAIDs and 47 taking NSAIDs alone without aspirin; they all had colonoscopy while smaller numbers underwent upper GI or capsule endoscopy. The aspirin group had older patients (median 69 vs. 61 years, p Conclusion (1) In this prospective analysis, patients with obscure occult bleeding and using aspirin have similar prevalence and range of lesions in the small bowel and upper GI tract as those using NSAIDs. (2) The use of NSAIDs was associated with fewer patients with colonic polyps. These results might help in planning and interpreting the investigations of obscure bleeding. They might also be relevant to colon cancer chemoprevention. Disclosure of Interest None Declared

Antithrombotic drugs and non-variceal bleeding outcomes and risk scoring systems: comparison of Glasgow Blatchford, Rockall and Charlson scores

Objectives Antithrombotic drugs (ATDs) cause non-variceal upper gastrointestinal bleeding (NVUGIB). Risk scoring systems have not been validated in ATD users. We compared Blatchford, Rockall and Charlson scores in predicting outcomes of NVUGIB in ATD users and controls. Methods A total of 2071 patients with NVUGIB were grouped into ATD users (n=851) and controls (n=1220) in a single-centre retrospective analysis. Outcomes included duration of hospital admission, the need for blood transfusion, rebleeding requiring surgery and 30-day mortality. Results Duration of admission correlated with all scores in controls, but correlations were significantly weaker in ATD users. Rank correlation coefficients in control versus ATD: 0.45 vs 0.20 for Blatchford; 0.48 vs 0.32 for Rockall and 0.42 vs 0.26 for Charlson (all p<0.001). The need for transfusion was best predicted by Blatchford (p<0.001 vs Rockall and Charlson in both ATD users and controls), but all scores performed less well in ATD users. Area under the receiver operation characteristic curve (AUC) in control versus ATD: 0.90 vs 0.85 for Blatchford; 0.77 vs 0.61 for Rockall and 0.69 vs 0.56 for Charlson (all p<0.005). In predicting surgery, Rockall performed best; while mortality was best predicted by Charlson with lower AUCs in ATD patients than controls (p<0.05). Stratification showed the scores performance to be age-dependent. Conclusions Blatchford score was the strongest predictor of transfusion, Rockalls had the strongest correlation with duration of admission and with rebleeding requiring surgery and Charlson was best in predicting 30-day mortality. Modifications of these systems should be explored to improve their efficiency in ATD users.