Ulcer Bleeding in the United States: Epidemiology, Treatment Success, and Resource Utilization.

BACKGROUND AND GOALS: Peptic ulcer disease is the most frequent cause of upper gastrointestinal bleeding. We sought to establish the epidemiology and hemostasis success rate of the different treatment modalities in this setting. METHODS: Retrospective cohort study using the National Inpatient Sample. Non-elective adult admissions with a principal diagnosis of ulcer bleeding were included. The primary outcome was endoscopic, radiologic and surgical hemostasis success rate. Secondary outcomes were patients' demographics, in-hospital mortality and resource utilization. On subgroup analysis, gastric and duodenal ulcers were studied separately. Confounders were adjusted for using multivariate regression analysis. RESULTS: A total of 136,425 admissions (55% gastric and 45% duodenal ulcers) were included. The mean patient age was 67 years. The majority of patients were males, Caucasians, of lower income and high comorbidity burden. The endoscopic, radiological and surgical therapy and hemostasis success rates were 33.6, 1.4, 0.1, and 95.1%, 89.1 and 66.7%, respectively. The in-hospital mortality rate was 1.9% overall, but 2.4% after successful and 11.1% after failed endoscopic hemostasis, respectively. Duodenal ulcers were associated with lower adjusted odds of successful endoscopic hemostasis, but higher odds of early and multiple endoscopies, endoscopic therapy, overall and successful radiological therapy, in-hospital mortality, longer length of stay and higher total hospitalization charges and costs. CONCLUSIONS: The ulcer bleeding endoscopic hemostasis success rate is 95.1%. Rescue therapy is associated with lower hemostasis success and more than a ten-fold increase in mortality rate. Duodenal ulcers are associated with worse treatment outcomes and higher resource utilization compared with gastric ulcers.

Decision-Utility Analysis of Empiric Treatment Versus Test and Treat Strategies for Helicobacter pylori in Patients With Duodenal Ulcer.

OBJECTIVES: The optimal strategy of Helicobacter pylori eradication in patients with duodenal ulcer is unclear. In this study, we aimed to compare the utility and the ulcer recurrence rate using the empiric treatment versus the test and treat strategies in patients with uncomplicated duodenal ulcer. METHODS: A decision-utility analysis was performed using a decision tree. The empiric treatment strategy was compared with the test and treat strategy. The probabilities of recurrent ulcers were determined and utilities of the 2 strategies were compared using the quality-adjusted life-year (QALY). Sensitivity analysis was performed to evaluate for model robustness. RESULTS: The probability of recurrent ulcer with the empiric strategy was 10.5%. The probabilities of recurrent ulcer with the test and treat strategy were 12.6%, 14.7%, 16.8%, and 17.9% based on 95%, 90%, 85%, and 80% sensitivity for histopathology, respectively. At the 95% estimate for the sensitivity of histopathology, the empiric strategy was associated with greater QALY compared with the test and treat strategy, 0.9875 versus 0.9853. The empiric treatment strategy was associated with greater QALY at extreme values for the estimates in our model. CONCLUSIONS: The empiric treatment strategy is associated with 2.1% to 7.4% lower recurrence rate for a range of test sensitivity between 95% and 80%, and results in greater QALY compared with the test and treat strategy.

[Peritonitis aggressiveness assessment]. / Opredelenie agressivnosti techeniia peritonita (pilotnoe issledovanie).

Peritonitis due to perforated duodenal ulcer was taken as a model. Patients were conditionally divided into three groups depending on the time after perforation: 6-12, 13-24 and over 24 hours. Analysis of microflora and pH of abdominal exudate was performed immediately after laparotomy. AIM: simple and reproducible method for determining the aggressiveness of peritonitis was developed. The authors believe that the diagnostic test is useful to individualize surgical approach in patient with advanced. peritonitis regardless time after perforation.

Upper gastrointestinal haemorrhage and deprivation: a nationwide cohort study of health inequality in hospital admissions.

OBJECTIVE: Inequalities in health are well recognized in cardiovascular disease and cancer, but in comparison, we have minimal understanding for upper gastrointestinal bleeding. Since furthering our understanding of such inequality signposts preventable disease, we investigated in detail the association between upper gastrointestinal bleeding and socioeconomic status. DESIGN: Population-based cohort study. SETTING: All English National Health Service hospitals. POPULATION: English adult population, 1 January 2001 to 31 December 2007. EXPOSURE MEASURES: Deprivation scores defined according to quintiles of neighbourhood areas ranked by the Indices of Multiple Deprivation for England 2007. OUTCOME MEASURES: Rates of all adult admissions coded with a primary diagnosis of upper gastrointestinal bleed were analysed by deprivation quintile and adjusted for age, sex, region and year using Poisson regression. RESULTS: The annual hospitalization rate for non-variceal haemorrhage was 84.6 per 100,000 population (95% CI 83.5 to 84.1; n=237,145), and for variceal haemorrhage, it was 2.83 per 100,000 population (95% CI 2.87 to 2.99; n=8291). There was a twofold increase in the hospitalization rate ratio for non-variceal haemorrhage from the most deprived areas compared to the least deprived (2.00, 95% CI 1.98 to 2.03). The ratio for variceal haemorrhage was even more pronounced (2.49, 95% CI 2.32 to 2.67). Inequality increased over the study period (non-variceal p<0.0001, variceal p=0.0068), and adjusting for age and sex increased the disparity between deprived and affluent areas. Case fatality did not have a similar socioeconomic gradient. CONCLUSION: Both variceal and non-variceal haemorrhage hospitalization rates increased with deprivation, and there was a similar gradient in all areas of the country and in all age bands. The existence of such a steep gradient suggests that there are opportunities to reduce hospitalizations down to the low rates seen in the most affluent, and thus, there is the potential to prevent almost 10,000 admissions and over 1000 deaths a year.

Sequential therapy versus standard triple drug therapy for eradication of Helicobacter pylori in patients with perforated duodenal ulcer following simple closure.

BACKGROUND: Resistance to clarithromycin, a component of standard triple therapy, leads to inconsistent eradication rates of Helicobacter pylori infection. Some studies have shown higher eradication rates for H. pylori using sequential regimen. This study was done to compare the eradication rates for H. pylori infection between the standard triple drug therapy and the sequential therapy. METHODS: Seventy-three patients with perforated duodenal ulcer following simple closure with H. pylori infection were randomized to receive either standard triple drug therapy or the sequential therapy. Standard triple drug therapy comprised of omeprazole, clarithromycin, and amoxicillin for 10 days. Sequential therapy comprised of omeprazole and amoxicillin or the first 5 days followed by omeprazole, clarithromycin, and amoxicillin for the next 5 days. Follow-up endoscopy was done at 2 months to assess the eradication rates, compliance, and side effects with each regimen. RESULTS: Eradication rates for standard triple therapy and sequential regimen were 81.25% and 87.09%, respectively (p = 0.732). The cost of sequential therapy was cheaper and incidence of side effects and compliance were similar in each group. CONCLUSION: Standard triple therapy and sequential therapy have similar efficacy for eradication of H. pylori and sequential therapy is an economical alternative to standard triple therapy.

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres.

BACKGROUND AND AIM: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. METHODS: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 +/- 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. RESULTS: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. CONCLUSIONS: The FSSG score reflects the severity of the endoscopic findings of GERD.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Clinical practice and evidence in endoscopic treatment of bleeding peptic gastroduodenal ulcer.

OBJECTIVE: To investigate treatment practice in non-variceal upper gastrointestinal bleeding (NVUGIB) caused by gastroduodenal ulcer and how it adheres to the best evidence as documented in randomized studies and meta-analyses. MATERIAL AND METHODS: The literature was surveyed to identify appropriate practices, and a structured multiple choice questionnaire developed and mailed to all departments in Denmark treating UGIB. RESULTS: All 42 departments responded. All had therapeutic gastroscopes and equipment necessary for endoscopic haemostasis; 90% of departments had written guidelines. Adjuvant pharmacologic treatment included tranexamic acid in 38%. Proton-pump inhibitors (PPIs) were used by all departments, with 29% starting prior to endoscopic treatment. Eight departments (19%) used continuous PPI infusion, three of them starting with a bolus dose. In 50% of departments an anaesthesiologist was always present regardless of whether endotracheal intubation (routinely used by 10%) was used or not. Ten percent did not treat Forrest IIa and IIb ulcers, while IIc ulcers were treated by 36%. In 10% of departments clots were never removed, while in 2/3 attempts were made to remove resistant clots by mechanic means. Seven departments (17%) used monotherapy with epinephrine, while 59% always used dual therapy; 19% injected less than 10 ml. In rebleeding, 92% attempted endoscopic treatment before surgery, and used epinephrine in 79% of cases, while the remainder used epinephrine or polidocanol at the discretion of the endoscopist. Two out of three departments used high-dependency or intensive-care units for surveillance. Seventeen percent applied scheduled second-look gastroscopy. CONCLUSIONS: Practice is variable, even in areas with established evidence based on randomized controlled studies, such as dosage and way of administration and duration of PPI treatment, injection treatment used as monotherapy and the volume used, including ulcers with clots for treatment, and the use of scheduled second-look endoscopy. Since the rebleeding rate has remained unchanged for decades, and rebleeding implies increased surgery and mortality rates, appropriate practices must be promoted in order to improve results. Development and implementation of national guidelines may facilitate the process.

To establish the efficacy of PPI therapy for ulcer bleeding in the United States, do we need more patients or more PPI [corrected].

Proton pump inhibitor (PPI) therapy is widely used in the management of patients with ulcer bleeding. However, most randomized controlled trials (RCTs) have been conducted outside of the United States. Jensen and colleagues have conducted the first United States-based RCT to compare a PPI with an H(2)-receptor antagonist following appropriate endoscopic hemostatic treatment for patients with ulcer bleeding. Unfortunately, the trial had to be discontinued prematurely because of problems with enrolment. There was a statistically nonsignificant difference in rebleeding rates between the two treatment arms. A type II statistical error probably explains this apparent lack of efficacy. However, U.S. patients may also require higher doses of PPI for adequate control of intragastric acidity.

[Quantitative-qualitative assessment of duodenogastric reflux at 24-h pH-metry].

AIM: To study characteristics (other than duration) of duodenogastric reflux (DGR), correlations of secretory function and DGR characteristics with gastroduodenal disorders (ulcer, chronic hyperacid gastritis). MATERIAL AND METHODS: A total of 110 patients were examined with 24-h pH-metry: 68 patients with duodenal ulcer (DU), 15 patients with gastric ulcer (GU), 27 patients with chronic hyperacid gastritis (CHG). Mean levels of pH and duration of hyperacidity in the body and an antral part of the stomach, duration of DGR, pH in the body and antral part of the stomach depending on DGR severity were studied. RESULTS: DGR was registered almost in all the patients with DU, GU and CHG. Groups of the patients differed by duration and height" of the DGR. CONCLUSION: Patients with DU are characterized by low refluxes which do not reach gastric body.

Cost-effectiveness of a 'score and scope' strategy for the management of dyspepsia.

OBJECTIVE: It is important to identify the best initial work-up in patients with uninvestigated dyspepsia because of its epidemiological and economical relevance. The objective of the study was to assess systematically the effectiveness and cost-effectiveness of invasive and non-invasive strategies for the management of dyspepsia. METHODS: A decision analysis was performed to compare prompt endoscopy, score and scope, test and scope, test and treat, and empirical antisecretory treatment. Published and local data on the prevalence of different diagnoses, rates of Helicobacter pylori infection, accuracy values of diagnostic tests, and effectiveness of drug treatments were used. The perspective of analysis was that of the public healthcare payer, and only direct costs were included, with a one-year post-therapy time horizon. The main outcome measure was cost per asymptomatic patient, valued in 2003 Euros. RESULTS: Endoscopy was found to be the most effective strategy for the management of dyspepsia (38.4% asymptomatic patients), followed by test and scope (35.5%), test and treat (35.3%), score and scope (34.7%), and empirical treatment (28.5%). Incremental cost-effectiveness ratios showed that score and scope was the most cost-effective alternative (483.17 Euros per asymptomatic patient), followed by prompt endoscopy (1396.85 Euros). Sensitivity analyses showed variations when varying the values of prevalence of duodenal ulcer, and the values of healing of functional dyspepsia with antisecretory and eradication drugs. There were no changes when varying the prevalence of H. pylori in dyspepsia. CONCLUSIONS: We would recommend stratifying patients by a score system, referring first to endoscopy those patients at higher risk of organic dyspepsia.

Polymorphisms and the pocketbook: the cost-effectiveness of cytochrome P450 2C19 genotyping in the eradication of Helicobacter pylori infection associated with duodenal ulcer.

The clinical outcome of duodenal ulcer treated with proton pump inhibitor (PPI)-based, anti-Helicobacter pylori (H.p.) regimens varies according to cytochrome P450 2C19 (CYP2C19) genotype. CYP2C19 genotypes differ markedly in peoples of Pacific Rim descent compared with another ethnicity. The authors sought to determine the specific impact that these factors have on the cost-effectiveness of duodenal ulcer management. Their model consisted of two patient cohorts with Helicobacter pylori and duodenal ulcer, trichotomized into CYP2C19 homozygous extensive metabolizers (EMs), heterozygous EMs, and poor metabolizers (PMs), altering the anti-H.p. regimen in the genotyped cohort only. The authors took the perspective of a third-party payer, and the denominator was ulcer episode prevented. In the reference case, the use of CYP2C19 genotyping prior to initiating anti-H.p. therapy was dominant (costs were saved with each ulcer episode prevented) in all geographic regions of the United States. The subsequent break-even analysis showed a range of 89.20 dollars to 118.96 dollars--from Hawaii to the Midwest, respectively--required to eliminate the cost-savings from each genotype test performed. Using probabilities most unfavorable to genotyping, the variation of peoples with Pacific Rim origins from 0% to 100% altered the cost-effectiveness from 495 dollars to 2125 dollars per ulcer event prevented, respectively. The results suggest that treatment decisions for H.p. infection that are based on a patient's CYP2C19 genotype decreases expenses for health plans implementing testing. This analysis provides an economic basis to support recent calls to expand this technology into routine clinical care to prevent toxicity of narrow therapeutic index drugs.

Recurrent duodenal ulcer haemorrhage: a pharmacoeconomic comparison of various management strategies.

BACKGROUND: Duodenal ulcer (DU) bleeding has a 7 - 13% mortality rate and bleeding often recurs. Prevention of recurrence is, therefore, an important goal. Eradication of Helicobacter pylori or maintenance treatment with a proton pump inhibitor (PPI) may reduce recurrent DU bleeding. Economic comparison of these options is sparse. METHODS: After the control of index bleeding with endotherapy and drugs, three strategies were evaluated: empirical treatment for possible H. pylori infection followed by a PPI for 2 months; test for H. pylori, eradication if positive, maintenance PPI if negative; maintenance PPI alone. Probability and direct cost data were obtained from a Medline search and Indian hospitals, respectively. Cost-minimisation, cost-utility, one- and two-way sensitivity analyses and threshold values were evaluated. RESULTS: Treatment of H. pylori, particularly empirical, was the preferred strategy and dominated maintenance treatment with PPI. The test-and-treat strategy was better than the empirical treatment strategy only when the probabilities of H. pylori eradication, ulcer healing following eradication and of frequency of H. pylori infection in bleeding DU were less than 58, 73 and 58%, respectively. CONCLUSIONS: Eradication of H. pylori is preferred in preventing recurrent bleeding from DU.

[Medico-economic efficacy of eradication schemes in helicobacter infections in patients with duodenal ulcers]. / Mediko-ékonimicheskaia éffektivnos' éradikatsionnykh skhem pri khelikobakternoi infektsii u bol'nykh s iazvennoi bolezn'iu dvenadtsatiperstnoi kishki.

The purpose of the study was to make a comparative medical and economic analysis of the application of Rabeprazole (Pariet) and Omeprazole generic in a seven-day eradication therapy.

A simplified prognostic scoring system for peptic ulcer perforation in developing countries.

BACKGROUND: Several complex prognostic scoring systems are available for abdominal sepsis. We constructed and assessed a simplified scoring system for peptic perforation, which can be easily used in developing countries. METHODS: One hundred and forty consecutive patients with perforated pre-pyloric or duodenal ulcer undergoing Graham's patch omentopexy closure were studied prospectively. Each factor was given a score based on its severity in accordance with the APACHE-II scoring system to construct the simplified prognostic (Jabalpur) scoring system, and multiple regression analysis was used to identify risk factors. This system was prospectively validated in the next 50 consecutive patients and compared to existing systems. RESULTS: The factors associated with mortality were age, presence of co-morbid illness, perforation-to-operation interval, preoperative shock, heart rate, and serum creatinine. The mean score in survivors (4.9) was less than that in those who died (12.5; p<0.0001). This scoring system compared favorably with other scoring systems. CONCLUSIONS: The Jabalpur scoring system is effective for prognostication in cases of peptic perforation. It is simple and user-friendly as it uses only six routinely documented clinical risk factors.

Evidence-based analysis: postoperative gastric bleeding: etiology and prevention.

Although the incidence of stomach hemorrhage is declining, stress-related gastric bleeding remains an important source of morbidity and mortality in cancer patients undergoing major surgical procedures to remove tumor. Prevention of stress-related bleeding is desirable; however, the optimal use of drugs to prevent gastric bleeding is unclear. Prophylaxis is recommended for surgical patients who require prolonged mechanical ventilation or have a coaguloathy. Histamine-2 receptor antagonists and sucralfate will reduce the likelihood of clinically important gastric-bleeding. Sucralfate appears to be less effective than H-2 blockers, but it is associated with fewer side effects such as nosocomial pneumonia. Preliminary studies show that proton pump inhibitors are most effective, have few side effects, but are most expensive. Intravenous proton pump inhibitors may be the drugs of choice for stress ulcer prophylaxis (SUP) in high-risk patients.

[The significance of the ulcer defect condition for the rehabilitation of patients with duodenal peptic ulcer complicated by chronic pancreatitis]. / Znachenie sostoianiia iazvennogo defekta v reabilitatsii bol'nykh iazvennoi bolezn'iu dvenadtsatiperstnoi kishki, oslozhnennoi khronicheskim pankreatitom.

Radical duodenoplasty is the optimum operation in the patients with duodenal peptic ulcers that are complicated with stenosis. Radical duodenoplasty in the patients with ulcer that is cicatrized reduces their stay in the resuscitation's department, reduces the reactive pancreatitis development, makes easier the early postoperative period and decreases of treatment expenses. So, preoperative rehabilitation is necessary in the patients with duodenal peptic ulcers.