My Yung

Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers

BACKGROUND Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers. METHODS We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers. FINDINGS 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002). INTERPRETATION Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.

Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial.

BACKGROUND Whether Helicobacter pylori increases the risk of ulcers in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) is controversial. We hypothesised that eradication of H pylori infection would reduce the risk of ulcers for patients starting long-term NSAID treatment. METHODS Patients were enrolled if they were NSAID naïve, had a positive urea breath test, had dyspepsia or an ulcer history, and required long-term NSAID treatment. They were randomly assigned omeprazole triple therapy (eradication group) or omeprazole with placebo antibiotics (placebo group) for 1 week. All patients were given diclofenac slow release 100 mg daily for 6 months from randomisation. Endoscopy was done at 6 months or if severe dyspepsia or gastrointestinal bleeding occurred. The primary endpoint was the probability of ulcers within 6 months. Analyses were by intention to treat. FINDINGS Of 210 arthritis patients screened, 128 (61%) were positive for H pylori. 102 patients were enrolled, and 100 were included in the intention-to-treat analysis. H pylori was eradicated in 90% of the eradication group and 6% of the placebo group. Five of 51 eradication-group patients and 15 of 49 placebo-group patients had ulcers. The 6-month probability of ulcers was 12.1% (95% CI 3.1-21.1) in the eradication group and 34.4% (21.1-47.7) in the placebo group (p=0.0085). The corresponding 6-month probabilities of complicated ulcers were 4.2% (1.3-9.7) and 27.1% (14.7-39.5; p=0.0026). INTERPRETATION Screening and treatment for H pylori infection significantly reduces the risk of ulcers for patients starting long-term NSAID treatment.

Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers

Abstract Objective: To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers. Design: Randomised prospective study of patients admitted with actively bleeding peptic ulcers. Setting: One university hospital. Subjects: 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment. Main outcome measures: Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital. Results: Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01). Conclusion: The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage. Key messages Endoscopic injection of adrenaline alone is effective in stopping bleeding peptic ulcers Further bleeding after adrenaline injection alone, however, occurs in 15-20% of patients, and the addition of heat probe thermocoagulation may improve permanent haemostasis and therefore patient outcome When compared with adrenaline injection alone the dual treatment significantly reduced the requirement for operative intervention and the length of hospital stay in the subgroup of patients with spurting ulcer haemorrhage In the endoscopic treatment of spurting ulcer haemorrhage heat probe thermocoagulation should be added after adrenaline injection

Prospective randomised study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation

Up to a third of patients have early rebleeding from oesophageal varices after endoscopic variceal ligation. Octreotide infusion is effective for control of variceal bleeding. We investigated the efficacy of octreotide infusion as an adjunct to endoscopic variceal ligation to prevent early rebleeding from varices. 100 consecutive patients admitted with endoscopically confirmed oesophageal varices and active bleeding or signs of recent haemorrhage were randomly assigned endoscopic variceal ligation alone or octreotide (50 micrograms intravenous bolus injection followed by intravenous infusion at 50 micrograms per h for 5 days) plus endoscopic variceal ligation. Three patients in each group were excluded. Bleeding was controlled in 44 of 47 patients who received variceal ligation alone and in 45 of 47 who received combined treatment (p = 1.0). Recurrent bleeding was documented in 18 (38% [24-52]) patients who received variceal ligation alone and in four (9% [3-21] who received combined treatment (p = 0.0007). The relative risk of rebleeding was lower (0.22 [0.08-0.60]) in the combined therapy group. Ten patients in the variceal ligation group and one in the combined therapy group required balloon tamponade for massive haematesis and haemodynamic instability (p = 0.0039). The in-hospital and 30-day mortality rates were higher in the variceal ligation group than in the combined therapy group (19 vs 9% and 23 vs 11%), but the differences did not reach significance. The relative risks of in-hospital (0.5 [0.04=5.3]) and 30-day (0.45 [0.17-1.2]) mortality were lower in the combined therapy group. Octreotide significantly reduces recurrent bleeding and the need for balloon tamponade in patients with variceal haemorrhage treated by endoscopic variceal ligation.

Eradication of Helicobacter pylori prevents recurrence of ulcer after simple closure of duodenal ulcer perforation: randomized controlled trial.

OBJECTIVE In this randomized trial, the authors sought to determine whether eradication of Helicobacter pylori could reduce the risk of ulcer recurrence after simple closure of perforated duodenal ulcer. BACKGROUND DATA Immediate acid-reduction surgery has been strongly advocated for perforated duodenal ulcers because of the high incidence of ulcer relapse after simple patch repair. Although H. pylori eradication is now the standard treatment of uncomplicated and bleeding peptic ulcers, its role in perforation remains controversial. Recently a high prevalence of H. pylori infection has been reported in patients with perforations of duodenal ulcer. It is unclear whether eradication of the bacterium confers prolonged ulcer remission after simple repair and hence obviates the need for an immediate definitive operation. METHODS Of 129 patients with perforated duodenal ulcers, 104 (81%) were shown to be infected by H. pylori. Ninety-nine H. pylori-positive patients were randomized to receive either a course of quadruple anti-helicobacter therapy or a 4-week course of omeprazole alone. Follow-up endoscopy was performed 8 weeks, 16 weeks (if the ulcer did not heal at 8 weeks), and 1 year after hospital discharge for surveillance of ulcer healing and determination of H. pylori status. The endpoints were initial ulcer healing and ulcer relapse rate after 1 year. RESULTS Fifty-one patients were assigned to the anti-Helicobacter therapy and 48 to omeprazole alone. Nine patients did not undergo the first follow-up endoscopy. Of the 90 patients who did undergo follow-up endoscopy, 43 of the 44 patients in the anti-Helicobacter group and 8 of the 46 in the omeprazole alone group had H. pylori eradicated; initial ulcer healing rates were similar in the two groups (82% vs. 87%). After 1 year, ulcer relapse was significantly less common in patients treated with anti-Helicobacter therapy than in those who received omeprazole alone (4.8% vs. 38.1%). CONCLUSIONS Eradication of H. pylori prevents ulcer recurrence in patients with H. pylori-associated perforated duodenal ulcers. Immediate acid-reduction surgery in the presence of generalized peritonitis is unnecessary.

Predicting Mortality in Patients With Bleeding Peptic Ulcers After Therapeutic Endoscopy

BACKGROUND & AIMS Despite advances in management of patients with bleeding peptic ulcers, mortality is still 10%. This study aimed to identify predictive factors and to develop a prediction model for mortality among patients with bleeding peptic ulcers. METHODS Consecutive patients with endoscopic stigmata of active bleeding, visible vessels, or adherent clots were recruited, and risk factors for mortality were identified in this deprivation cohort by using multiple stepwise logistic regression. A prediction model was then built on the basis of these factors and validated in the evaluation cohort. RESULTS From 1993 to 2003, 3220 patients with bleeding peptic ulcers were treated. Two hundred eighty-four of the patients developed rebleeding (8.8%); emergency surgery was performed on 47 of these patients, whereas others were managed with endoscopic retreatment. Two hundred twenty-nine of these sustained in-hospital death (7.1%). In patients older than 70 years, presence of comorbidity, more than 1 listed comorbidity, hematemesis on presentation, systolic blood pressure below 100 mm Hg, in-hospital bleeding, rebleeding, and need for surgery were significant predictors for mortality. Helicobacter pylori-related ulcers had lower risk of mortality. The receiver operating characteristic curve comparing the prediction of mortality with actual mortality showed an area under the curve of 0.842. From 2004 to 2006, data were collected prospectively from a second cohort of patients with bleeding peptic ulcers, and mortality was predicted by using the model developed. The receiver operating characteristic curve showed an area under the curve of 0.729. CONCLUSIONS Among patients with bleeding peptic ulcers after endoscopic hemostasis, advanced age, presence of listed comorbidity, multiple comorbidities, hypovolemic shock, in-hospital bleeding, rebleeding, and need for surgery successfully predicted in-hospital mortality.

One-week use of ranitidine bismuth citrate, amoxycillin and clarithromycin for the treatment of Helicobacter pylori-related duodenal ulcer

Proton pump inhibitors have been widely used in combination with amoxycillin, clarithromycin or metronidazole for the treatment of Helicobacter pylori infection.

The antimicrobial susceptibility of Helicobacter pylori in Hong Kong (1997-2001).

Treatment failure due to antimicrobial resistance has become a major clinical problem in dealing with patients infected with Helicobacter pylori , so we studied the susceptibility of H. pylori at the Prince of Wales Hospital, Hong Kong. A total of 1118 nonduplicate H. pylori strains were isolated from gastric biopsies from patients between 1997 and 2001. These were tested against clarithromycin and metronidazole by disk diffusion method [1]. Twenty-three clarithromycin-resistant H. pylori strains (CLR-R) were selected randomly for mutation site detection by a PCR method and restriction enzymes ( Bbs I and Bsa I) digestion method [2]. To further investigate the genomic DNA of a pair of clarithromycin-resistant and clarithromycin-sensitive (CLR-S) strains, Hin dIII digestion was undertaken [3]. The prevalence of metronidazole-resistant of H. pylori varied in different countries: 12.4% in Japan [4], 78.5% in Saudi Arabia [5], 77.8% in Shanghai [6] and 57% in Hong Kong was reported by another center [7]. In our study, the percentage of metronidazole-resistant of H. pylori was 71.4% in 2000. There was an increasing prevalence of resistance to metronidazole, rising from 25.2% in 1997 to 71.4% in 2000. However, the percentage of metronidazole-resistance of H. pylori reduced to 58.3% in 2001 (Table 1). This may be because we used less metronidazole to treat our patients. The percentage of CLR-R of H. pylori was 3.3% in Germany [8] and 12.7% in Nigeria [9]. A figure of 10.8% was reported by another center in Hong Kong [10]. In our study, there was an increasing percentage of clarithromycin, rising from 4.7% in 1997 to 10.3% in 2000. It reduced to 8.3% in 2001 (Table 1). Among 23 CLR-R isolates tested, we confirmed that 22 isolates were due to A2144G point mutation. Only one isolate was due to A2143G point mutation (Figure 1). In our center, a CLR-S strain was isolated from an adult patient in January 1998. Ten months later (October 1998), a CLR-R strain was isolated from the same patient. To investigate whether Clarithromycin resistance developed as a result of a point mutation in strain CLR-S after drug treatment, overall genotypic characteristics of both strains were analyzed. Both strains had a different Hin dIII DNA fingerprint, suggesting that they were genetically unrelated (Figure 2). Therefore, we proposed that the CLR-R strain was not developed from the CLR-S strain. To explain the occurrence of the CLR-R strain, the following two possibilities could be considered. Firstly, the CLR-R strain may have coexisted with CLR-S strain at the time of the first isolation in January 1998, but we were unable to pick it up. That Reprint requests to : Thomas K. W. Ling, Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, SAR, PR China. Figure 1 Restriction profiles of clarithromycin resistant strains with BsaI and BbsI; Lanes 1–8 were digested by BsaI. Lanes 9–16 were digested by BbsI. M1: 100bp DNA ladder Plus. M2:φX174 HaeIII. Lanes 4, 6, 7 and 8 had A2144G point mutation. Lane 9 had A2143G point mutation.

Economic analysis of celecoxib versus diclofenac plus omeprazole for the treatment of arthritis in patients at risk of ulcer disease

Aim : To evaluate the economic impact of celecoxib therapy vs. diclofenac plus omeprazole therapy for the treatment of arthritis in Chinese patients with a high risk of bleeding, from the perspective of a public health organization in Hong Kong.

Economic analysis of four triple regimens for the treatment of Helicobacter pylori-related peptic ulcer disease in in-patient and out-patient settings in Hong Kong.

One‐week triple regimens have been shown to be effective for the treatment of Helicobacter pylori‐related peptic ulcer disease.