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Biomedical subjects

Javier P Gisbert

Publications and source records attributed to Javier P Gisbert.

At least 19 recordsLinked to original sources
PubMed2006

Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-term follow-up study of 394 patients.

AIM: To prospectively evaluate whether a relationship between thiopurine methyltransferase (TPMT) activity and incidence of adverse effects (especially myelotoxicity) exists, in a long-term follow-up study of a large group of patients with inflammatory bowel disease treated with azathioprine. METHODS: TPMT activity in red blood cells (RBC) was measured by a radiochemical method in 394 consecutive patients with Crohn's disease (238) or ulcerative colitis (156) starting treatment with azathioprine. The relationship among several variables and TPMT values was assessed, and the correlation between such levels and the incidence of adverse effects was evaluated. RESULTS: Mean TPMT value was 18.6 +/- 4 U/mL RBCs (range 9.4-33.7). No patient had low levels (<5), 7.1% had intermediate levels (5-13.7), and 92.9% had high levels (>13.8). Differences (P < 0.001) were demonstrated in TPMT activity depending on the type of inflammatory bowel disease, but not on the remaining variables (including treatment with 5-aminosalycilates). Adverse effects were reported in 74 patients (18.8%), the most frequent being gastrointestinal intolerance (9.1%) and myelotoxicity (4.3%). No patient having adverse effects had low TPMT levels. However, mean TPMT activity was lower in those with adverse effects (16.6 +/- 3 vs 19.1 +/- 4 U/mL, P < 0.001). Moreover, the probability of suffering myelotoxicity in the high TPMT group was only 3.5%, compared with 14.3% in the TPMT intermediate group (95% CI = 1.37-14.9; OR = 4.5). CONCLUSIONS: The strategy of determining TPMT activity in all patients prior to initiating treatment with azathioprine could help to minimize the risk of myelotoxicity, as patients with intermediate TPMT activity had fourfold more risk than high TPMT activity patients.

Adult↗
PubMed2006

Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori infection: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and a meta-analysis of accuracy of monoclonal stool antigen test (SAT) for the diagnosis of Helicobacter pylori infection. METHODS SELECTION OF STUDIES: assessing the accuracy of monoclonal SAT for the diagnosis of H. pylori infection. SEARCH STRATEGY: electronic and manual bibliographical searches. DATA EXTRACTION: independently done by two reviewers. DATA SYNTHESIS: meta-analyses combining the sensitivities, specificities, and likelihood ratios (LRs) of the individual studies. RESULTS: Twenty-two studies, including 2,499 patients, evaluated the monoclonal SAT before eradication therapy. Pooled sensitivity, specificity, LR+, and LR- were: 0.94 (95% CI 0.93-0.95), 0.97 (0.96-0.98), 24 (15-41), and 0.07 (0.04-0.12). The accuracy of both monoclonal and polyclonal SAT was evaluated together in 13 pretreatment studies, and higher pooled sensitivity was demonstrated with the monoclonal technique (0.95 vs 0.83). Twelve studies, including 957 patients, assessed the monoclonal SAT to confirm eradication after therapy. Pooled sensitivity, specificity, LR+, and LR- were 0.93 (0.89-0.96), 0.96 (0.94-0.97), 17 (12-23), and 0.1 (0.07-0.15). Both tests were evaluated together in eight post-treatment studies and, again, the monoclonal technique showed higher sensitivity (0.91 vs 0.76). Heterogeneity among studies disappeared when a single outlier study was excluded. Subanalysis depending on the reference method, the study population, or the study quality showed similar results. CONCLUSION: Monoclonal SAT is an accurate noninvasive method both for the initial diagnosis of H. pylori infection and for the confirmation of its eradication after treatment. The monoclonal technique has higher sensitivity than the polyclonal one, especially in the post-treatment setting.

Antigens, Bacterial↗
PubMed2006

Accuracy of Helicobacter pylori diagnostic tests in patients with bleeding peptic ulcer: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and a meta-analysis of diagnostic accuracy of the different tests aimed to detect Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). METHODS SELECTION OF STUDIES: assessing the accuracy of H. pylori diagnostic methods in patients with UGIB. SEARCH STRATEGY: electronic bibliographical searches. DATA EXTRACTION: independently done by two reviewers. DATA SYNTHESIS: meta-analyses of the different tests were performed combining the sensitivities, specificities, and likelihood ratios (LRs) of the individual studies. RESULTS: Studies showed a high degree of heterogeneity. Pooled sensitivity, specificity, LR+ and LR- (95% confidence interval (CI)) for the different methods were: Rapid urease test (16 studies/1,417 patients): 0.67 (0.64-0.70), 0.93 (0.90-0.96), 9.6 (5.1-18.1), and 0.31 (0.22-0.44). Histology (10 studies/827 patients): 0.70 (0.66-0.74), 0.90 (0.85-0.94), 6.7 (2.5-18.4), and 0.23 (0.12-0.46). Culture (3 studies/314 patients): 0.45 (0.39-0.51), 0.98 (0.92-1.00), 19.6 (4-96), and 0.31 (0.05-1.9). Urea breath test (8 studies/520 patients): 0.93 (0.90-0.95), 0.92 (0.87-0.96), 9.5 (3.9-23.3), and 0.11 (0.07-0.16). Stool antigen test (6 studies/377 patients): 0.87 (0.82-0.91), 0.70 (0.62-0.78), 2.3 (1.4-4), and 0.2 (0.13-0.3). Serology (9 studies/803 patients): 0.88 (0.85-0.90), 0.69 (0.62-0.75), 2.5 (1.6-4.1), and 0.25 (0.19-0.33). CONCLUSION: Biopsy-based methods, such as rapid urease test, histology, and culture, have a low sensitivity, but a high specificity, in patients with UGIB. The accuracy of 13C-urea breath test remains very high in these patients. Stool antigen test is less accurate in UGIB. Although serology seems not to be influenced by UGIB, it cannot be recommended as the first diagnostic test for H. pylori infection in this setting.

Antigens, Bacterial↗
PubMed2006

The role of tacrolimus in inflammatory bowel disease: a systematic review.

Therapeutic management of inflammatory bowel disease remains beyond the limits of conventional therapy in many cases. Novel therapies used include tacrolimus, a new powerful immunosuppressive drug, employed in some case reports and a few studies that have tried to evaluate its effectiveness in Crohn's disease and ulcerative colitis with promising results, but its role in the management of inflammatory bowel disease remains controversial. We performed a systematic review that analyzed a total of 23 reported experiences in 286 patients with inflammatory bowel disease treated with tacrolimus. Although most of the published studies are uncontrolled, short, and heterogeneous, promising results have been obtained in fistulizing disease, unresponsive cases of both ulcerative colitis and Crohn's disease, and even extraintestinal manifestations. The overall outcome was good enough to consider tacrolimus as a rationale therapeutic option. However, comparative studies with standard therapeutic options like infliximab are needed to assess the correct role that tacrolimus may play in these patients.

Humans↗
PubMed2006

Clinical trial evaluating amoxicillin and clarithromycin hydrogels (Chitosan-polyacrylic acid polyionic complex) for H. pylori eradication.

AIM: It has been suggested that enhancement of amoxicillin or clarithromycin concentration at the gastric tissue may improve the anti-Helicobacter pylori effect of these drugs. This could be achieved by allowing the drug to remain longer in the stomach using dried hydrogels. Our aim was to evaluate the efficacy of an H. pylori eradication regimen including both amoxicillin and clarithromycin hydrogels. METHODS DESIGN: prospective clinical trial. PATIENTS: with peptic ulcer or functional dyspepsia. INTERVENTION: 7-day rabeprazole-amoxicillin-clarithromycin regimen. In addition, amoxicillin and clarithromycin hydrogels were administered twice daily during the 7 days. The polyionic complex hydrogel was prepared with Chitosan and polyacrylic acid. OUTCOME: H. pylori eradication was defined as a negative C-urea breath test 8 weeks after completing therapy. RESULTS: Forty patients were included. One patient did not return for follow-up. Ninety percent of the patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 74% (95% CI=58%-86%) and 70% (55%-82%). Mild adverse effects were reported in 4 (10%) patients (diarrhea in 3, and nausea/heartburn in 1). CONCLUSIONS: Although dried polyionic complexes could serve as suitable candidates for amoxicillin and clarithromycin site-specific delivery in the stomach, its addition does not increase the eradication efficacy of the generally prescribed proton pump inhibitor plus amoxicillin and clarithromycin regimen.

Acrylic Resins↗
PubMed2006

Risk assessment and outpatient management in bleeding peptic ulcer.

AIMS: 1) To review clinical and endoscopic variables in patients hospitalized for upper gastrointestinal bleeding (UGIB) due to peptic gastroduodenal lesions over a period of 3 years; 2) to identify factors associated with unfavorable evolution; and 3) to evaluate characteristics of patients discharged immediately after endoscopy. METHODS: A 3-year retrospective analysis of all UGIB episodes was performed. Patients with gastroduodenal ulcer or erosive gastritis/duodenitis at endoscopy were included. The prognostic value of several clinical, endoscopic, and analytical variables was assessed. Persistence or recurrence of bleeding, surgery, and mortality were considered as outcome variables (evolution was classified as "unfavorable" when any of these was observed). RESULTS: A total of 341 patients were identified, with a mean age of 62 years. Melena was the most frequent UGIB presentation (70%). Forty-five percent had associated diseases, and 45% were taking gastroerosive drugs. Duodenal ulcer was the most frequent cause of UGIB (48%), followed by gastric ulcer (32%). The evolution of UGIB was unfavorable in 7% of cases. Variables associated with unfavorable evolution in the multivariate analysis were: systolic blood pressure < or = 100 mm Hg, heart rate > or = 100 bpm, and a Forrest endoscopic classification of severe. Only 10% of patients were immediately discharged, with no subsequent complications. However, if predictive variables obtained in the multivariate analysis had been used, hospitalization could have been prevented in 115 patients (34%) without subsequent complications. CONCLUSIONS: A number of clinical and endoscopic variables (blood pressure, heart rate, and endoscopic stigmata of bleeding) with prognostic value have been identified. These are easy to obtain and apply in clinical practice and allow an accurate estimation of the evolution of UGIB. This diagnostic strategy identifies a relatively high proportion of UGIB patients who can be managed on an outpatient basis.

Ambulatory Care↗
PubMed2006

Third-line rescue therapy with levofloxacin after two H. pylori treatment failures.

AIM: Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin fails in a considerable number of cases. A rescue therapy still fails in more than 20% of the cases. Our aim was to evaluate the efficacy and tolerability of a third-line levofloxacin-based regimen in patients with two consecutive Helicobacter pylori eradication failures. METHODS DESIGN: Prospective multicenter study. PATIENTS: In whom a first treatment with omeprazole-clarithromycin-amoxicillin and a second with omeprazole-bismuth-tetracycline-metronidazole (or ranitidine bismuth citrate with these antibiotics) had failed. INTERVENTION: A third 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. RESULTS: One-hundred patients were initially included, and nine were lost for follow-up. All patients but five took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 66% (95% CI = 56-75%) and 60% (50-70%). Adverse effects were reported in 25% of the patients, mainly including metallic taste (8%), nausea (8%), myalgia/arthralgia (5%), and diarrhea (4%); none of them were severe. CONCLUSION: Levofloxacin-based rescue therapy constitutes an encouraging empirical third-line strategy after multiple previous H. pylori eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, and tetracycline.

Amoxicillin↗
PubMed2006

[Monitoring of thiopurine methyltransferase and thiopurine metabolites to optimize azathioprine therapy in inflammatory bowel disease].

Determination of the activity of thiopurine methyltransferase (TPMT) and of thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine nucleotides) could be useful for individualized monitoring of azathioprine (AZA) and 6-mercaptopurine (6-MP) doses. TPMT activity in the general population follows a trimodal distribution, in which approximately 0.3% of the population is homozygotic for the low-activity allele. A notable correlation has been observed between the low TPMP activity genotype or phenotype and the risk of myelotoxicity. Patients with a high TPMT activity genotype or homozygous phenotype should receive immunosuppressive doses that have clearly been demonstrated to be effective. In contrast, in patients with a low TPMT activity genotype or homozygous phenotype, the use of AZA/6-MP should be contraindicated or only very small doses should be administered. Importantly, TPMP deficiency explains only some cases of myelotoxicity and consequently periodic laboratory testing should be performed in patients receiving AZA/6-MP, even though TPMP function may be normal. Currently, the utility of routine thiopurine metabolite determinations in patients undergoing AZA/6-MP therapy has not been established and this practice should be limited to specific situations such as lack of response to thiopurine therapy or the occurrence of thiopurine-related adverse effects. Randomized trials comparing the routine strategy of AZA/6-MP dosing (based exclusively on the patient's weight) versus individualized monitoring (based on quantification of TPMP activity and/or thiopurine metabolites) are required before definitive conclusions on the most effective alternative can be drawn.

Antimetabolites↗
PubMed2006

[Seven or ten days? Cost-effectiveness study on the duration of H. pylori treatment in primary care].

OBJECTIVE: To determine through an economic evaluation study whether it is cost-effective to extend treatment of dyspeptic patients from 7 to 10 days, distinguishing between functional dyspepsia, unexamined dyspepsia, and ulcer disease. DESIGN: Cost-effectiveness study by means of a decision 3 comparing direct costs per patient cured with 2 strategies: a) 7 days treatment versus b) 10 days. Two-year study in the National Health System. SETTING: Primary care. PARTICIPANTS: One-hundred patients with peptic ulcer, functional dyspepsia, or unexamined dyspepsia who received treatment for H pylori infection. INTERVENTIONS: H pylori eradication treatment with a proton pump inhibitor, clarithromycin, and amoxycillin for 7 or 10 days. Measurement variable: incremental cost per patient cured. RESULTS: In peptic ulcer patients, the incremental cost per patient cured on extending the eradication treatment from 7 to 10 days was euro147 (95% CI, 121.3-162.7), whereas in patients with functional or unexamined dyspepsia, it was -euro39.8 (95% CI, -28.5 to -60.7) and -euro27.3 (95% CI, -14.92 to -52.72), respectively. The sensitivity analysis showed that the efficacy of eradication treatment (7 vs 10) was the factor that most affected the stability of the results. CONCLUSIONS: Seven days is the most cost-effective duration of the triple therapy for eradicating H pylori in ulcer patients. However, 10 days is more cost-effective in functional dyspepsia patients or those with no prior endoscope diagnosis.

Cost-Benefit Analysis↗
PubMed2006

Chronic hepatitis C and Crohn's disease: nosocomial infection treatment with PEG-interferon plus ribavirin.

We describe the case of a patient with a diagnosis of Crohn's disease and accidental infection during abdominal surgery by hepatitis C virus (HCV) who received combination therapy with pegylated interferon-alpha2b (1.5 microg/kg weekly) plus ribavirin (10.6 mg/kg daily) for histologically demonstrated chronic hepatitis C. After 48 weeks treatment, serum transaminase levels were normal and viremia (HCV RNA) was negative (end-of-treatment response); 24 weeks later (follow-up period), a sustained virological response was demonstrated. The tolerance to combination antiviral therapy was good, without intestinal symptoms of inflammatory bowel disease recurrence. We conclude that current antiviral therapies with immunomodulatory effects may be helpful and safe for patients with inflammatory bowel disease infected by hepatitis C virus.

Adult↗
PubMed2006

Thymidylate synthase expression pattern, expression level and single nucleotide polymorphism are predictors for disease-free survival in patients of colorectal cancer treated with 5-fluorouracil.

Several variables associated to thymidylate synthase (TS), the biological target of 5-fluorouracil (5FU) have been studied for their possible role as predictors of the clinical outcome and response to chemotherapy in colorectal cancer (CRC) patients. The level of protein expression and the number of variable tandem-repeats of a 28-bp sequence within the gene promoter have been proposed as predictive and/or prognostic factors with variable agreement, while consensus seems to be achieved with respect to the value of a single nucleotide polymorphism (SNP) described within this same region. More recently, an association between TS expression pattern and survival has been disclosed. Paraffin-embedded sections from 140 CRC patients were analyzed by immuno-histochemistry (Mab TS106) for TS levels and expression pattern. Also, VNTR and SNP were determined by polymerase-chain reaction (PCR) and restriction-length-fragment polymorphism (RFLP) in 123 and 112 patients, respectively. Cytoplasmic expression pattern tended to be associated to C SNP (p=0.06). Low TS expression levels, cytoplasmic expression pattern and C SNP arose as variables associated to longer progression-free survival (PFS) in patients treated with 5FU. Accordingly, patients having at least two favourable or unfavourable variables were classified respectively as 'low risk' and 'high risk', the former showing significantly longer PFS (p=0.0299). The possibility for designing a selection method for subsequent therapies is suggested on the basis of a probable combined effect of the above mentioned parameters but further studies in larger populations are needed to confirm these results.

Aged↗
PubMed2005

[Thiopurine methyltransferase activity in inflammatory bowel disease. A study on 7046 Spanish patients].

BACKGROUND AND OBJECTIVE: Our objective was to assess the activity of thiopurine methyltransferase (TPMT) in a very large number of Spanish patients with inflammatory bowel disease (IBD), to evaluate the influence of several variables (including azathioprine or 6-mercaptopurine) on that activity, and to know the proportion of patients with low TPMT activity and therefore high risk of myelotoxicity when treated with these drugs. PATIENTS AND METHOD: TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several variables and TPMT values was assessed by multiple lineal regression. RESULTS: 7046 patients were included (mean age: 37 years; 53% males): 70% with Crohn's disease, 22% with ulcerative colitis, and 8% with indeterminate colitis. Mean TPMT value was 20 (6) U/ml RBCs (minimum 0 and maximum 46). TPMT activity distribution was as follows: low levels (< 5 U/ml), 0.5%; intermediate (5-13.7), 11.1%; and high (> or = 13.8), 88.4%. TPMT values did not follow a normal distribution (p < 0.001). In the univariate study, statistically significant differences (p < 0.001), yet of doubtly clinical significance because its minimal magnitude, were demonstrated in TPMT values depending on age, sex, type of disease, and treatment with azathioprine/6-mercaptopurine. In the multivariate study, the variables associated with TPMT activity were: sex, treatment with 5-aminosalicylates, steroids and azathioprine/6-mercaptopurine. CONCLUSIONS: This study shows that 0.5% of the Spanish patients with IBD have low TPMT activity (< 5 U/ml RBCs), a figure similar to that reported in other countries, these patients being at higher risk of myelotoxicity when treated with azathioprine or 6-mercaptopurine. The drugs usually prescribed for the treatment of IBD, including 5-aminosalicylates and azathioprine/6-mercaptopurine, do not seem to modify in a clinically relevant manner TPMT activity.

Adolescent↗
PubMed2005

[Indications and consequences of Helicobacter pylori eradication on gastroesophageal reflux disease].

Several epidemiological data indicate that H. pylori infection prevalence in patients with gastroesophageal reflux disease (GERD) is lower than that reported in respective controls, which would suggest that the organism plays a protective role against this disease. On the other hand, most studies demonstrate that the presence of the infection in patients with GERD does not negatively affect the therapeutic efficacy of proton pump inhibitors (PPIs), and, in case of negatively influencing it, the effects are not clinically relevant and are easily controllable with standard antisecretory treatment. Therefore, the decision to administer H. pylori eradication treatment to a patient should not be influenced by the concomitant presence of GERD. In most cases, H. pylori eradication does not seem to induce GERD development, and it does not seem to worsen GERD when it was already present. Nevertheless, when the gastritis pattern is unknown before the antibiotic administration, the effect of H. pylori eradication on gastric acid secretion and the incidence of GERD is unpredictable. In the exceptional cases in which H. pylori eradication could have negative effects on GERD, its clinical relevance will be limited, and reflux symptoms or endoscopic esophagitis will favourably respond to the standard PPI antisecretory treatment. Therefore, again, when H. pylori eradication is indicated in a particular patient, the concomitant diagnosis of GERD should not change our attitude. Finally, is has recently been recommended to eradicate H. pylori infection in those patients with GERD needing long-term treatment with PPI, as some studies have reported that these drugs induce, in presence of the organism, an atrophic gastritis, with the consequent risk of gastric cancer. However, most of these studies have important methodological defects, and several authors have reported contrary results. In any case, the appearance in the gastric mucosa of clinically relevant lesions, such as intestinal metaplasia, dysplasia or adenocarcinoma, in patients treated with PPI for several years, has not yet been demonstrated, although this could simply be a problem of time. This question seems to be too controversial to be answered with the available data, and we should wait until new studies clarify this topic. In the meantime, as it occurs with any controversial indication, the decision of the doctor facing a patient infected by H. pylori and needing maintenance therapy with PPIs should be assessed on a case by case basis.

Anti-Bacterial Agents↗
PubMed2005

Systematic review and meta-analysis: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics in Helicobacter pylori eradication.

OBJECTIVE: To systematically review the Helicobacter pylori eradication efficacy with ranitidine bismuth citrate (RBC) and two antibiotics, and to conduct a meta-analysis of randomized clinical trials comparing the efficacy of proton pump inhibitor (PPI) vs. RBC with two antibiotics for 1 week. METHODS SELECTION OF STUDIES: Studies evaluating RBC plus two antibiotics were considered. For the meta-analysis, randomized controlled trials comparing PPI vs. RBC plus two antibiotics for 1 week were included. SEARCH STRATEGY: Electronic and manual bibliographical searches. Assessment of study quality and data extraction: Independently done by two reviewers. DATA SYNTHESIS: 'Intention-to-treat' eradication rate. Meta-analysis was performed, combining the odds ratios (OR) of the individual studies. Subanalysis: Depending on the type of antibiotics and the quality of the studies. RESULTS: Mean H. pylori eradication with 7-day RBC-clarithromycin-amoxicillin, RBC-clarithromycin-nitroimidazole, and RBC-amoxicillin-nitroimidazole was 83%, 86%, and 71%, respectively. The meta-analysis showed comparable efficacy with RBC and PPI when they were combined with clarithromycin and amoxicillin (OR = 1.11; 95% CI = 0.88-1.40), or with amoxicillin and metronidazole (OR = 0.92; 95%CI = 0.60-1.41). However, when comparing PPI vs. RBC plus clarithromycin and a nitroimidazole, higher cure rates with RBC than with PPI were demonstrated (OR = 1.65; 95% CI = 1.15-2.37). CONCLUSION: The efficacy of RBC and PPI-based triple regimens were comparable when using the clarithromycin-amoxicillin or the amoxicillin-metronidazole combination. However, RBC seems to have a higher efficacy than PPI when clarithromycin and a nitroimidazole are the antibiotics prescribed. Therefore, if one prefers to use the clarithromycin-nitroimidazole regimen, RBC should be used instead of a PPI.

Amoxicillin↗