Pedro Almela

A Nationwide Study of Mortality Associated with Hospital Admission Due to Severe Gastrointestinal Events and Those Associated with Nonsteroidal Antiinflammatory Drug Use

BACKGROUND:The worst outcome of gastrointestinal complications is death. Data regarding those associated with nonsteroidal antiinflammatory drug (NSAID) or aspirin use are scarce.AIM:To determine mortality associated with hospital admission due to major gastrointestinal (GI) events and NSAID/aspirin use.METHODS:The study was based on actual count of deaths from two different data sets from 2001. Study 1 was carried out in 26 general hospitals serving 7,901,198 people. Study 2 used a database from 197 general hospitals, representative of the 269 hospitals in the Spanish National Health System. Information regarding gastrointestinal complications and deaths was obtained throughout the Minimum Basic Data Set (CIE-9-MC) provided by participating hospitals. Deaths attributed to NSAID/aspirin use were estimated on the basis of prospectively collected data from hospitals of study 1.RESULTS:The incidence of hospital admission due to major GI events of the entire (upper and lower) gastrointestinal tract was 121.9 events/100,000 persons/year, but those related to the upper GI tract were six times more frequent. Mortality rate was 5.57% (95% CI = 4.9–6.7), and 5.62% (95% CI = 4.8–6.8) in study 1 and study 2, respectively. Death rate attributed to NSAID/aspirin use was between 21.0 and 24.8 cases/million people, respectively, or 15.3 deaths/100,000 NSAID/aspirin users. Up to one-third of all NSAID/aspirin deaths can be attributed to low-dose aspirin use.CONCLUSION:Mortality rates associated with either major upper or lower GI events are similar but upper GI events were more frequent. Deaths attributed to NSAID/ASA use were high but previous reports may have provided an overestimate and one-third of them can be due to low-dose aspirin use.

Second-Line Rescue Therapy With Levofloxacin After H. pylori Treatment Failure: A Spanish Multicenter Study of 300 Patients

AIM:Quadruple therapy is generally recommended as second-line therapy after Helicobacter pylori (H. pylori) eradication failure. However, this regimen requires the administration of four drugs with a complex scheme, is associated with a relatively high incidence of adverse effects, and bismuth salts are not available worldwide anymore. Our aim was to evaluate the efficacy and tolerability of a triple second-line levofloxacin-based regimen in patients with H. pylori eradication failure.METHODS:Design: Prospective multicenter study. Patients: in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin had failed. Intervention: A second eradication regimen with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.) was prescribed for 10 days. Outcome: Eradication was confirmed with 13C-urea breath test 4–8 wk after therapy. Compliance with therapy was determined from the interview and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire.RESULTS:Three hundred consecutive patients were included. Mean age was 48 yr, 47% were male, 38% had peptic ulcer, and 62% functional dyspepsia. Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 81% (95% CI 77–86%) and 77% (73–82%). Adverse effects were reported in 22% of the patients, mainly including nausea (8%), metallic taste (5%), abdominal pain (3%), and myalgias (3%); none of them were severe.CONCLUSION:Ten-day levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous proton pump inhibitor-clarithromycin-amoxicillin failure, being simple and safe.

Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy.

OBJECTIVES:To determine the prevalence of recurrence of gallstone pancreatitis, its clinical features, and the presence of prognostic factors of recurrence.METHODS:From January 1, 2000 to August 31, 2003, 233 patients admitted with acute gallstone pancreatitis (AGP) were prospectively studied. Patients were divided into two groups: recurrent and nonrecurrent group. Clinical, analytical, radiological, prognostic parameters, and severity (Atlanta criteria) were assessed, along with the performance of cholecystectomy or endoscopic sphincterotomy (ES). Clinical features of recurrence were analyzed. Univariate (χ2, Students t-test) and multivariate tests were performed. Statistical significance was assumed if p < 0.05.RESULTS:Two hundred and eighty-six attacks were identified. Forty-two patients (18.2%) recurred, suffering 53 recurrent attacks, which took place within 30 days in 23.3%. Patients who did not undergo surgery after the first attack had 31-fold risk of recurrence (OR = 31.5%, CI = 95%[7.22–137.84], p < 0.001). In patients not operated, recurrence was more frequent if ES was not performed (37.04%vs 0%, p= 0.019). Among patients with surgical risk, none who recurred underwent ES, compared with 27.9% of those who did not recur. Patients in the nonrecurrent group underwent cholecystectomy within the first 30 days or ES more frequently (31.2%vs 7.3%, p= 0.001).CONCLUSIONS:Recurrence of gallstone pancreatitis is a frequent event. Delay of cholecystectomy implies an increased risk of recurrence. ES could be an acceptable option to prevent recurrence in patients who are not candidates for surgery or who do not desire to undergo cholecystectomy.

Elevated serum eotaxin levels in patients with inflammatory bowel disease

OBJECTIVE:Eotaxin is a recently characterized chemokine with potent and selective chemotactic activity for eosinophils. Previous studies indicating that eosinophils accumulate and become activated in inflammatory bowel disease (IBD) led us to hypothesize that eotaxin is potentially involved in the pathophysiology of IBD and, therefore, that eotaxin would be increased in the serum of patients with IBD. The objective of this study was to test those assumptions.METHODS:We investigated 72 patients with IBD, 35 with ulcerative colitis, and 37 with Crohns disease. A total of 27 patients had active and 45 inactive disease; 26 were receiving corticosteroids. Eotaxin serum levels were determined by solid phase sandwich ELISA. Lymphocytes, monocytes, and granulocyte subpopulations were determined in fresh blood samples with an automated autoanalyzer.RESULTS:Serum eotaxin levels were significantly higher in patients with Crohns disease and in those with ulcerative colitis than in the control subjects (p < 0.0001). Patients with inactive Crohns disease had significantly higher levels of eotaxin than patients with inactive ulcerative colitis (p < 0.05). We did not find significant differences for activity or inactivity of disease, nor for treatment with prednisone. A negative correlation (p < 0.05) was found between eotaxin serum level and eosinophil counts in peripheral blood in patients with Crohns disease.CONCLUSIONS:There is an increased expression of eotaxin in IBD patients, suggesting that eotaxin may be involved in the pathogenesis of IBD. This increase is more accentuated in Crohns disease and negatively correlates with the eosinophil number in peripheral blood. Our data support the increasing evidence that eosinophil are functionally involved in the pathophysiology of IBD.

Long-Term Follow-Up of 1,000 Patients Cured of Helicobacter pylori Infection Following an Episode of Peptic Ulcer Bleeding

OBJECTIVES:To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients.METHODS:Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or 13C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by 13C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up.RESULTS:Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16–1.16%), and the incidence rate of rebleeding was 0.15% (0.05–0.36%) per patient-year of follow up.CONCLUSION:Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

Background: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. Aim: To evaluate the efficacy and tolerability of a second-line triple-regimen–containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Methods: Design: Prospective multicenter study. Patients: In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Intervention: Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Outcome: Eradication was confirmed using the 13C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. Results: The study sample comprised 1000 consecutive patients (mean age, 49±15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Conclusions: Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

A risk score system for identification of patients with upper-GI bleeding suitable for outpatient management

BACKGROUND The aim of this study was to develop a risk score system for identification of patients with upper-GI hemorrhage who are suitable for outpatient management. METHODS From a prospective cohort of 983 consecutive patients with upper-GI hemorrhage not associated with portal hypertension, 581 cases that did not meet pre-established criteria for admission were selected, and a logistic regression analysis was performed to identify factors associated with two adverse outcomes: recurrent bleeding and/or the need for emergency surgery. The risk score system was developed by using the beta coefficients of the logistic model, and its performance was evaluated. The results of this model were combined with pre-established criteria for admission to build a simplified scoring system for identification of patients who can be managed safely on an outpatient basis. RESULTS Chronic alcoholism, active malignancy, prior upper digestive tract surgery, wasting syndrome, hemodynamic compromise, duodenal ulcer as the cause of upper-GI hemorrhage, and hemorrhage of unknown cause were independently associated with a greater risk of unfavorable outcomes in the group that did not meet pre-established criteria for admission. The logistic model showed a high capacity for discrimination (C statistic: 0.87) and good calibration (p value for Hosmer-Lemeshow goodness-of-fit test, 0.62), with a sensitivity of 100% and specificity of 64%. The simplified score had a sensitivity of 100% and specificity of 29% for adverse outcomes, and sensitivity of 78% and specificity of 38% for mortality. CONCLUSIONS The score system developed in this study may be helpful in deciding between hospitalization and outpatient management for patients with upper-GI hemorrhage, but it remains to be validated in patient groups other than those used for its development.

Eradication of Helicobacter pylori for the Prevention of Peptic Ulcer Rebleeding

Aim:  To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long‐term study including more than 400 patients.

Usefulness of alanine and aspartate aminotransferases in the diagnosis of microlithiasis in idiopathic acute pancreatitis

SummaryBackground. It has been shown that biochemical laboratory values only are useful parameters in distinguishing gallstone from nongallstone acute pancreatitis. We assessed the diagnostic usefulness of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for identification of occult microlithiasis in idiopathic acute pancreatitis.Methods. Ninety-one patients with idiopathic acute pancreatitis who underwent microscopic examination of stimulated duodenal bile sediments were retrospectively studied. According to earliness of ALT and AST assay after the onset of abdominal pain, patients were divided into two groups: group A, within the first 24 h (n=56) and group B, between 24 and 72 h (n=35).Results: ALT and AST values expressed as number of elevations of the upper limits of normal were higher in group A patients with positive biliary drainage than in group B. Median (range) ALT and AST values were 2.5 (0.1–18.1) vs 0.4 (0.1–8.6) and 3 (0.3–17.4) vs 0.5 (0.3—11.9), respectively. In the univariate analysis and receiver operating characteristic (ROC) curves, ALT within the first 24 h showed a sensitivity of 73%, specificity of 86%, and positive predictive value of 92% for a cutoff of 1.2 elevations of the upper limit of normal. These values were slightly higher, although without statistically significant differences, than those of AST (73, 80, and 89%, respectively).Conclusion. Serum increases of aminotransferases, especially alanine aminotransferase (ALT), were suggestive of microlithiasis in idiopathic acute pancreatitis, particularly when assessed early after the onset of abdominal pain.

Outpatient Management of Upper Digestive Hemorrhage Not Associated With Portal Hypertension: A Large Prospective Cohort

OBJECTIVES:To evaluate the safety of outpatient management of upper GI hemorrhage (UGIH) not associated with portal hypertension.METHODS:A prospective cohort of 983 subjects who went to the Accident & Emergency Department (A&ED) of a University hospital in Valencia (Spain), for UGIH not associated with portal hypertension during 1994 to 1997 were evaluated. After evaluation in the A&ED, 216 patients (22%) were discharged and referred for outpatient follow-up, but 15 patients could not be located thus, reducing the follow-up to 201 subjects. The main outcome measures were rebleeding within 10 days, emergency surgery within 15 days, and mortality for any cause during the 30 days after the initial hemorrhaging episode.RESULTS:UGIH in subjects under outpatient care were less severe than those subjects in the hospitalized group. Hemorrhaging recurred in 7.3% of inpatients versus 0.5% of outpatients (p < 0.01); emergency surgery was required in 5.6% of the hospitalized patients and 0.5% of the outpatients (p < 0.01); a total of 20 deaths occurred in the hospitalized group (2.6%), while three (1.5%) occurred in outpatients (p = 0.26). After adjusting for several significant risk factors, outpatient management was not associated with outcomes that were worse.CONCLUSIONS:Treatment under an outpatient regime is a safe alternative for a large percentage of selected patients with UGIH not associated with portal hypertension.