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Variceal bleeding and portal hypertensive gastropathy.

Cirrhosis can be the end stage of any chronic liver disease. At the time of diagnosis of cirrhosis varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, large size of varices and the presence of endoscopic red colour signs but only one-third of patients who have variceal haemorrhage have the above risk factors. Recent interest has been directed at identifying haemodynamic factors that may reflect the pathophysiological changes which lead to variceal bleeding, e.g. it has been confirmed that no bleeding occurs if HVPG falls below 12 mmHg and also a hypothesis has been put forward in which bacterial infection is considered a trigger for bleeding. Pharmacological treatment with beta-blockers is safe, effective and is the standard long-term treatment for the prevention of recurrence of variceal bleeding. Combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for reduction in HVPG response needs further study, and surrogate markers of pressure response need evaluation. If endoscopic treatment is chosen, variceal ligation is the modality of choice. The combination of simultaneous variceal ligation and sclerotherapy does not offer any benefit. However, the use of additional sclerotherapy for the complete eradication of small varices after variceal ligation needs to be evaluated. The results of current prospective randomized controlled trials comparing variceal ligation with pharmacological treatment are awaited with great interest. Finally, the use of transjugular intrahepatic portosystemic shunt (TIPS) for the secondary prevention of variceal bleeding is not substantiated by current data, as survival is not improved and because of its worse cost-benefit profile compared to other treatments. In contrast, there still is a role for the selective surgical shunts in the modern management of portal hypertension. The ideal patients should be well compensated cirrhotics, who have had troublesome bleeding - either who have failed at least one other modality of therapy (drugs or ligation), have bled from gastric varices despite medical or endoscopic therapy, or live far from suitable medical services. Recently, ligation has been compared to beta-blockers for primary prophylaxis but so far there is no good evidence to recommend banding for primary prophylaxis, if beta-blockers can be given.

Adrenergic beta-Antagonists↗

Primary prophylaxis of variceal bleeding in cirrhosis.

Variceal bleeding is the result of portal hypertension, which is a major complication of liver cirrhosis and carries a high mortality rate. Because of the mortality associated with variceal bleeding, strategies for prevention of the first bleed is important. Risk stratification is important in determining those at risk of bleeding from varices and current data suggest that patients with large varices with red signs, severe underlying liver disease and those who have a hepatic venous pressure gradient of greater than 12 mmHg are at high risk of bleeding. Surveillance for varices in patients with cirrhosis is therefore important. The current review evaluates the role of various treatments in the primary prophylaxis of variceal bleeding. The current first choice treatment is non-selective beta-blockers; which is cheap, easy to administer, and reduces the risk of first variceal haemorrhage significantly. Combination of beta-blockers and nitrates looks promising but needs further evaluation. Endoscopic variceal band ligation compares favourably with non-selective beta-blockers in preventing the first bleeding episode in cirrhotic patients and may be an alternative for patients who cannot tolerate, or have contraindications to beta-blockers. The role of monitoring the hepatic venous pressure gradient in those being treated with pharmacological agents, the role of newer drugs such as non-selective beta-blockers with intrinsic alpha-adrenergic activity and angiotensin receptor blockers require further evaluation.

Adrenergic beta-Antagonists↗

Transjugular intra-hepatic portosystemic shunt for refractory variceal bleeding.

BACKGROUND: The most dramatic complication of portal hypertension in cirrhotic patients is oesophageal variceal bleeding. Moreover, patients with bleeding unresponsive to medical and endoscopic treatment have a poor prognosis. OBJECTIVE: The aim of this study was to evaluate the efficacy of early transjugular intra-hepatic portosystemic shunt (TIPS) in patients with refractory variceal bleeding. PATIENTS AND METHODS: TIPS was performed for 28 patients (17 were stage Child C), successfully in 26. Variceal bleeding was controlled in all but one successfully stented patient. RESULTS: There was no mortality associated with the procedure. The two patients with a failure of TIPS insertion died of persistent bleeding in the first 48 h after failed TIPS. The 40-day mortality rate was 25%. Five patients died (one from persistent bleeding from gastric varices and four from multi-organ failure). Using multivariate analysis, the only independent factor associated with early mortality was the total bilirubin value. Fifteen surviving patients were listed for liver transplantation: four deaths occurred, eight patients were transplanted in the 6 months after TIPS and three are still waiting. Among the six patients who survived but were ineligible for transplantation, two died and four are still alive. Two episodes of early rebleeding and eight of late rebleeding occurred. Actuarial survival was 75% at one year and 52% at two years. CONCLUSIONS: Early TIPS is an effective rescue therapy for controlling refractory variceal bleeding.

Adult↗

Changes in aetiology and clinical outcome of acute upper gastrointestinal bleeding during the last 15 years.

OBJECTIVES: The diagnostic and therapeutic approaches to patients with acute upper gastrointestinal bleeding have been improved during the last decades. The aim of this study was to compare the aetiology and clinical outcome of acute upper gastrointestinal bleeding (AUGIB) between two distinct periods during the last 15 years. METHODS: The causes of AUGIB and clinical outcome of 668 patients hospitalised with the problem in 1986-1987 were compared to 636 patients with AUGIB in 2000-2001. Patients were admitted to our hospital or they bled while they were inpatients for other reasons. No patient was excluded because of age or concurrent diseases. Endoscopic haemostasis with adrenaline injection for bleeding peptic ulcers was performed in the second period while no endoscopic method of haemostasis was performed in the first period. RESULTS: We observed an increase in the age of patients (56.5 +/- 16.9 vs 62.9 +/- 17.5 years, P < 0.0001) and the percentage of patients who received non-steroidal anti-inflammatory drugs (NSAIDs) before bleeding (from 44% to 63.5%, P < 0.0001). An increase in the diagnosis rate of gastric ulcer (12% vs 19.2%, P = 0.005) and varices (13.2% vs 3.3%, P < 0.001) with a simultaneous decrease in that of erosive gastroduodenitis (18.4% vs 7.2%, P < 0.0001) and duodenal ulcer (48.7% vs 33.3%, P < 0.0001) as a cause of bleeding was also observed. In peptic ulcer bleeding, emergency surgical haemostasis was reduced from 14% to 5.3%, P < 0.001. Overall mortality was also reduced from 5.2% to 3.1% and in peptic ulcer bleeding patients from 3.3% to 2.4%, respectively, but the differences are not statistically significant. CONCLUSION: The aetiology of AUGIB has changed during the last 15 years probably due to the better therapeutic approach to chronic duodenal ulcers and increasing use of NSAIDs in the elderly. Emergency surgical haemostasis has been reduced but the reduction of mortality was not significant.

Acute Disease↗

The role of capsule endoscopy in the work-up of obscure gastrointestinal bleeding.

OBJECTIVE: To evaluate the role of capsule endoscopy in the detection of causes of obscure gastrointestinal bleeding. METHODS: Fifteen patients, nine males and six females, mean age 46 years (range 20-75 years), were investigated. All patients had undergone upper and lower gastrointestinal endoscopy with no evidence of causes of bleeding. Indication for capsule endoscopy was overt bleeding in 10 patients (eight with melaena and two with rectal bleeding) and anaemia in five patients. RESULTS: Diagnosis was made in four out of 10 patients with overt bleeding (40%) and in four out of five (80%) in the group with anaemia. The overall detection rate was 53%. Of the eight patients with melaena, two had angiodysplasia, one showed a diffuse inflammation of the jejunum and ileum probably related to associated portal hypertension, and five had a normal examination. Of the two patients with rectal bleeding, one had a polyp in the terminal ileum and the other a normal examination. Of the five patients with anaemia, one had jejunal carcinoma, three had Crohn's disease and one had a normal endoscopy. CONCLUSION: Wireless capsule endoscopy is safe, effective, non-invasive, and provides definitive diagnosis in about one-half of patients presenting with obscure gastrointestinal bleeding and previous negative endoscopic examinations.

Adenocarcinoma↗

The use of recombinant factor VIIa for severe intractable bleeding during spine surgery.

STUDY DESIGN: A report on the use of recombinant activated factor VII in 4 patients who developed severe intractable bleeding and coagulopathy during spine surgery. OBJECTIVE: To describe the role of recombinant activated factor VII for hemostasis during spine surgery. SUMMARY OF BACKGROUND DATA: Recombinant activated factor VII is indicated for the treatment of bleeding episodes and the prevention of bleeding during surgery in patients with hemophilia with inhibitors. However, its use in adults undergoing spine surgery has not yet been reported. METHODS: Four patients who underwent multilevel spine surgery through an anterior approach incurred massive bleeding and subsequently became coagulopathic. Standard hemostatic techniques were performed and blood products were transfused. Persistence of the bleeding prompted the use of recombinant activated factor VII. RESULTS: Treatment with recombinant activated factor VII led to an improvement in prothrombin time and partial thromboplastin time and brought about cessation in gross, nonsurgical bleeding intraoperatively. No clinically relevant thrombotic complications related to the drug were noted. CONCLUSIONS: Recombinant activated factor VII is promising as an adjunctive hemostatic agent for patients with perioperative bleeding problems during spine surgery. Efficacy is seen even at low doses.

Adult↗

Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients.

OBJECTIVE: To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients. DESIGN: A noninferiority analysis was used to compare rates of clinically significant upper gastrointestinal bleeding in a prospective, phase 3, double-blind trial with parallel omeprazole suspension and cimetidine treatment groups. SETTING: A total of 47 intensive care units in the United States. PATIENTS: A total of 359 critically ill patients who required mechanical ventilation for > or =48 hrs, had an Acute Physiology and Chronic Health Evaluation score of > or =11 at baseline, had an intact stomach with a nasogastric or orogastric tube in place, and had at least one additional risk factor for upper gastrointestinal bleeding. INTERVENTIONS: Patients were randomized to treatment with omeprazole suspension (two 40-mg doses on day 1, via orogastric or nasogastric tube, and 40 mg each day thereafter) or intravenous cimetidine (300-mg bolus and 50 mg/hr thereafter) for up to 14 days. Gastric aspirates were sampled for bleeding and pH. Medication doses were doubled for failure of pH control (two successive aspirates with pH < or = 4). MEASUREMENTS AND MAIN RESULTS: Clinically significant upper gastrointestinal bleeding (bright red blood not clearing after 5-10 mins of lavage or persistent Gastroccult-positive "coffee-grounds" material for 8 hrs on days 1-2 or for 2-4 hrs on days 3-14 and not clearing with > or =100 mL of lavage) was the primary end point of the trial. The rate of clinically significant bleeding in the per-protocol population was 4.5% with omeprazole suspension and 6.8% with cimetidine, meeting the criteria for the noninferiority of omeprazole suspension. Median gastric pH was > or =6 on all trial days with omeprazole suspension treatment and on 50% of days with cimetidine treatment (p < .001, all trial days). In the omeprazole suspension group, median gastric pH was >4 on each trial day in 95% of patients. CONCLUSIONS: Immediate-release omeprazole suspension is effective in preventing upper gastrointestinal bleeding and more effective than intravenous cimetidine in maintaining gastric pH of >4 in critically ill patients.

Administration, Oral↗

Reliability and reproducibility of classification of children as "bleeders" versus "non-bleeders" using a questionnaire for significant mucocutaneous bleeding.

The diagnosis of type 1 von Willebrand disease (VWD), the most common inherited bleeding disorder in humans, is greatly dependent on an accurate diagnosis of significant mucocutaneous bleeding. In a previous study, the authors modified the criteria of the International Society on Thrombosis and Haemostasis for significant mucocutaneous bleeding to a format, the Hospital for Sick Children (HSC) criteria, that was more applicable to diagnose significant mucocutaneous bleeding in children. To assess the reliability and reproducibility of classification of subjects as "bleeders" versus "non-bleeders" using a questionnaire for significant mucocutaneous bleeding targeted to children, 39 subjects interviewed for a previous HSC VWD study were reinterviewed for the current study. The original bleeding classification was confirmed in 80% of subjects interviewed for a second time, indicating that this method of classification is reproducible (kappa = 0.65), with a "substantial" agreement among the investigators who reviewed the questionnaire responses (kappa = 0.71). The validity and utility of the HSC questionnaire for primary screening of children with suspected mucocutaneous bleeding disorders merits assessment in further clinical studies.

Adolescent↗

Endoscopic marking with a metallic clip facilitates transcatheter arterial embolization in upper peptic ulcer bleeding.

PURPOSE: To enable accurate transcatheter arterial embolization (TAE) of the target vessel, a new technique to localize the exact position of a bleeding ulcer was tested that involves endoscopic marking of the ulcer with a metallic clip. MATERIALS AND METHODS: In 13 patients (mean age, 75 years) with acute bleeding ulcers (11 duodenal ulcers, two malignant ulcers), a metallic clip was placed at gastroscopy followed or preceded by routine endoscopic treatment. The metallic clip was placed in the fibrous edge of the ulcer adjacent to the bleeding point. In 10 patients, TAE was indicated as a result of continued or recurrent bleeding. The artery was embolized with microcoils as close as possible to the clip. In three patients, there was no indication for TAE, so plain abdominal radiography was performed to determine whether the marking clip was still in place. RESULTS: In 11 patients, the clip was still in place on radiography; in two, it had disappeared. Hemostasis was achieved in eight of 10 patients after TAE. In six patients, the clip was essential to identify the bleeding vessel. CONCLUSION: Marking of the bleeding ulcer with a clip before TAE enhances the possibility that the correct vessel is embolized. This will most likely minimize the risk of recurrent bleeding after embolization, especially in patients who do not show contrast medium extravasation.

Adult↗

Variceal recurrence, rebleeding, and survival after endoscopic injection sclerotherapy in 287 alcoholic cirrhotic patients with bleeding esophageal varices.

OBJECTIVE: This study tested the validity of the hypothesis that eradication of esophageal varices by repeated injection sclerotherapy would reduce recurrent variceal bleeding and death from bleeding varices in a high-risk cohort of alcoholic patients with cirrhosis. SUMMARY BACKGROUND DATA: Although banding of esophageal varices is now regarded as the most effective method of endoscopic intervention, injection sclerotherapy is still widely used to control acute esophageal variceal bleeding as well as to eradicate varices to prevent recurrent bleeding. This large single-center prospective study provides data on the natural history of alcoholic cirrhotic patients with bleeding varices who underwent injection sclerotherapy. METHODS: Between 1984 and 2001, 287 alcoholic cirrhotic patients (225 men, 62 women; mean age, 51.9 years; range, 24-87 years; Child-Pugh grades A, 39; B, 116; C, 132) underwent a total of 2565 upper gastrointestinal endoscopic sessions, which included 353 emergency and 1015 elective variceal injection treatments. Variceal rebleeding, eradication, recurrence, and survival were recorded. RESULTS: Before eradication of varices was achieved, 104 (36.2%) of the 287 patients had a total of 170 further bleeding episodes after the first endoscopic intervention during the index hospital admission. Rebleeding was markedly reduced after eradication of varices. In 147 (80.7%) of 182 patients who survived more than 3 months, varices were eradicated after a mean of 5 injection sessions and remained eradicated in 69 patients (mean follow-up, 34.6 months; range, 1-174 months). Varices recurred in 78 patients and rebled in 45 of these patients. Median follow-up was 32.3 months (mean, 42.1 months; range, 3-198.9 months). Cumulative overall survival by life-table analysis was 67%, 42%, and 26% at 1, 3, and 5 years, respectively. A total of 201 (70%) patients died during follow-up. Liver failure was the most common cause of death. CONCLUSION: Repeated sclerotherapy eradicates esophageal varices in most alcoholic cirrhotic patients with a reduction in rebleeding. Despite control of variceal bleeding, survival at 5 years was only 26% because of death due to liver failure in most patients.

Adult↗

Successful treatment of depot medroxyprogesterone acetate-related vaginal bleeding improves continuation rates in adolescents.

High discontinuation rates for depot medroxyprogesterone acetate (DMPA) in adolescents may contribute to the number of unintended pregnancies. Many cite vaginal bleeding as a reason for discontinuing DMPA use. In this study, we attempted to determine if treating DMPA-associated vaginal bleeding with monophasic oral contraceptive pills (OCP) raised continuation rates. A total of 131 patients who reported vaginal bleeding while on DMPA were included in this study and 83 were treated with monophasic OCP. Of those who received OCP, 38.7% reported that vaginal bleeding stopped completely, 51.8% reported that vaginal bleeding stopped temporarily, and 6.0% reported no change. Overall, 94% of enrolled patients who received OCP as a treatment for DMPA-associated vaginal bleeding continued DMPA use. Our findings indicate that vaginal bleeding due to DMPA can be successfully treated, leading to improvement in continuation rates.

Adolescent↗

Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer.

AIM: To perform a meta-analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer. METHODS: A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of peptic ulcer re-bleeding. Studies with all patients taking non-steroidal anti-inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers. RESULTS: In the first meta-analysis, the mean percentage of re-bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non-eradication therapy group without long-term antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09-0.37; 'number needed to treat' (NNT), 5; 95% CI, 4-8]. In the second meta-analysis, the re-bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non-eradication therapy group with maintenance antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08-0.76; NNT, 20; 95% CI, 12-100). When only patients with successful H. pylori eradication were included, the re-bleeding rate was 1%. CONCLUSIONS: The treatment of H. pylori infection is more effective than antisecretory non-eradication therapy (with or without long-term maintenance antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.

Antacids↗

COX-2-selective inhibitors and the risk of upper gastrointestinal bleeding in high-risk patients with previous gastrointestinal diseases: a population-based case-control study.

BACKGROUND: Clinical trials have suggested that cyclo-oxygenase-2-selective inhibitors are associated with a lower risk of upper gastrointestinal bleeding than are non-selective, non-aspirin, non-steroidal anti-inflammatory drugs. This has not yet been confirmed in studies of patients with an increased susceptibility to upper gastrointestinal bleeding. AIM: To examine the risk of upper gastrointestinal bleeding in high-risk patients who filled prescriptions for cyclo-oxygenase-2 inhibitors or other non-steroidal anti-inflammatory drugs. METHODS: A population-based case-control study was performed in the Danish county of North Jutland from 1 January 2000 to 31 December 2002. From the County Hospital Discharge Registry and the Civil Registration System, we identified incident cases with upper gastrointestinal bleeding (n = 780) and randomly selected controls (n = 2906), respectively. All cases and controls had previous gastrointestinal diseases. Data on drug exposure were obtained from the countywide Prescription Database. RESULTS: Thirty-five cases (4.5%) filled prescriptions for cyclo-oxygenase-2 inhibitors within 30 days of the date of upper gastrointestinal bleeding, compared with 79 controls (2.7%). Adjusted odds ratios for upper gastrointestinal bleeding according to prescription for celecoxib, rofecoxib and non-steroidal anti-inflammatory drugs were 1.3 [95% confidence interval (CI), 0.7-2.8], 2.1 (95% CI, 1.2-3.5) and 3.3 (95% CI, 2.4-4.4), respectively. CONCLUSIONS: In patients with increased susceptibility to gastrointestinal adverse events, a lower risk of upper gastrointestinal bleeding was observed in users of cyclo-oxygenase-2 inhibitors compared with users of other non-aspirin, non-steroidal anti-inflammatory drugs.

Adolescent↗

Systematic review and meta-analysis: enhanced efficacy of proton-pump inhibitor therapy for peptic ulcer bleeding in Asia--a post hoc analysis from the Cochrane Collaboration.

BACKGROUND: Proton-pump inhibitors reduce re-bleeding rates after ulcer bleeding. However, there is significant heterogeneity among different randomized-controlled trials. AIM: To see whether proton-pump inhibitors for ulcer bleeding produced different clinical outcomes in different geographical locations. METHODS: This was a post hoc analysis of our Cochrane Collaboration systematic review and meta-analysis of proton-pump inhibitor therapy for ulcer bleeding. Sixteen randomized-controlled trials conducted in Europe and North America were pooled and re-analysed separately from seven conducted in Asia. We calculated pooled rates for 30-day all-cause mortality, re-bleeding and surgical intervention and derived odds ratios and numbers needed to treat with 95% confidence intervals. RESULTS: There was no significant heterogeneity for any outcome. Reduced all-cause mortality was seen in the Asian randomized-controlled trials (odds ratios = 0.35; 95% confidence interval: 0.16-0.74; number needed to treat = 33), but not in the others (odds ratios = 1.36; 95% confidence interval: 0.94-1.96; number needed to treat--incalculable). There were significant reductions in re-bleeding and surgery in both sets of randomized-controlled trials, but the effects were quantitatively greater in Asia. CONCLUSIONS: Proton-pump inhibitor therapy for ulcer bleeding has been more efficacious in Asia than elsewhere. This may be because of an enhanced pharmacodynamic effect of proton-pump inhibitors in Asian patients.

Anti-Inflammatory Agents, Non-Steroidal↗

Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?

BACKGROUND: A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. AIM: To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. METHODS: We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis. RESULTS: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants. CONCLUSIONS: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.

Adult↗

Review article: gastrointestinal bleeding with low-dose aspirin - what's the risk?

This review examines ulcers and gastrointestinal bleeding with low-dose aspirin, focusing on randomized placebo-controlled trials. The single endoscopic trial assessing ulcers showed no significant difference in 12-week ulcer incidence: 6% of 381 given placebo vs. 7% of 387 given 81 mg enteric-coated aspirin. The relative risk of major gastrointestinal bleeding with low-dose aspirin in a meta-analysis of placebo-controlled trials of vascular protection was 2.07 (95% CI: 1.61-2.66). The absolute rate increase with aspirin above placebo was 0.12% per year (95% CI: 0.07-0.19%) with a number-needed-to-harm of 833 patients (95% CI: 526-1429). A meta-analysis of aspirin 50-1500 mg daily reported an odds ratio for any gastrointestinal bleeding of 1.68 (95% CI: 1.51-1.88) with an number-needed-to-harm at 1 year of 247. The relative risk of hospitalization for upper gastrointestinal bleeding with low-dose aspirin in a large Danish cohort study was 2.6 (95% CI: 2.2-2.9) with an absolute annual incidence of 0.6%. Factors that may increase the risk of gastrointestinal bleeding include prior history of ulcers or gastrointestinal bleeding, corticosteroid use, anticoagulant therapy and addition of a non-aspirin non-steroidal anti-inflammatory drug. When determining whether low-dose aspirin is appropriate for an individual patient, the cardiovascular benefit must be weighed against the potential for clinical events such as gastrointestinal bleeding.

Adrenal Cortex Hormones↗

Pre-endoscopic proton pump inhibitor therapy reduces recurrent adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding.

BACKGROUND: Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce rebleeding rates in patients with high-risk acute non-variceal upper gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy, although its incremental benefit is unproven. AIM: To determine if providing PPIs before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal upper gastrointestinal bleeding patients. METHODS: We performed a retrospective review to identify patients presenting to two tertiary care centres with acute non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects receiving PPI therapy before endoscopy were compared with those not receiving pre-endoscopic PPI therapy. The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality, readmission within 30 days for acute non-variceal upper gastrointestinal bleeding). RESULTS: 385 patients were included in our study [132 (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI]. Patients receiving pre-endoscopic PPI therapy were significantly less likely to develop adverse outcomes compared with those not given pre-endoscopic PPIs (25% vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and length of hospital stay were also significantly lower in patients receiving pre-endoscopic PPI. CONCLUSIONS: The use of PPIs before endoscopy significantly reduces the risk of developing adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding. Future studies are required to better characterize this relationship.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Multiple bleeds in haemophilia A.

One hundred and eighty-one bleeding episodes involving two sites simultaneously were noted during a survey of 4935 bleeding episodes, an incidence of 3.7%. Elbows, knees and ankles were the commonest sites involved in double bleeds, while the thigh, upper arm and elbow were the commonest sites involved in the double bleeds needing most transfusions. The overall transfusion requirements were less than for single bleeds. The frequency of multiple bleeds correlated significantly with the overall bleeding frequency, but not with the number of days under observation.

Ankle↗