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Background: An adequate diagnostic and therapeutic approach to Helicobacter pylori (H. pylori) infection is the cornerstone to avoid overdiagnosis, overuse of health resources, and increase in antibiotic resistances. The aim of the study was to evaluate the most common errors in clinical practice and the associated risk factors. Materials and Methods: This is a retrospective observational study including patients with H. pylori infection and no previous treatment belonging to two defined areas of the National Health System in Spain; some of them were enrolled in the European Registry on H. pylori management (Hp‐EuReg). Patients were attended by gastroenterologists between 2010 and 2019. According to current guidelines, we evaluated indications for H. pylori investigation, appropriateness of diagnostic test used in dyspeptic patients and discontinuation of surveillance after treatment. Results: A total of 1730 patients were included, receiving 2260 eradication regimens. H. pylori infection was investigated in 1.7% cases in absence of a formal indication. Oral endoscopy was incorrectly used in 56% of patients with dyspepsia under 55 years without alarm signs, and urea breath test (UBT) was incorrectly used in 22.4% of patients with dyspepsia ≥55 years or red flags. Levofloxacin containing regimens were used as first‐line therapy in 7.5% of non‐allergic to penicillin patients. After first‐line failure, clarithromycin was repeated in 2.6% of the patients who received second‐line therapy. Confirmatory test of H. pylori status was absent in 2.5% cases. Men, patients under 55 years, and patients diagnosed by UBT had a higher risk of not undergoing a confirmatory test. Conclusions: Investigation of H. pylori infection by gastroenterologists is rare in absence of a formal indication; however, endoscopy is commonly used for dyspeptic patients <55 years without red flags and non‐invasive tests are still used for dyspeptic patients ≥55 years or presenting alarm signs. Men, patients under 55 years, and patients diagnosed by UBT have an increased risk of being lost to follow‐up after eradication treatment. [ABSTRACT FROM AUTHOR]

Background: Data for Spain from the Rome Foundation Global Epidemiology Study on the disorders of gut–brain interaction (DGBI) were used to assess the national and regional prevalence of all 22 DGBI, the percentage of respondents meeting diagnostic criteria for at least one DGBI, and the impact on burden of disease in our country. Methods: Data were collected through an anonymous, nationwide, and secure Internet survey with multiple built‐in quality‐assurance techniques that included the Rome IV diagnostic questionnaire and an in‐depth supplemental questionnaire. Key Results: The survey was completed by 2072 adult Spanish participants (50.2% female) with a mean age of 45.67 ± 15.44 years with a good representative national distribution. 43.6% (41.5%–45.8%) met diagnostic criteria for at least one DGBI, with 8.2% for any esophageal disorder, 12.1% for any gastroduodenal disorder, 30.1% for any bowel disorder, and 11.5% for any anorectal disorder. Functional constipation was the most prevalent DGBI in Spain (12.8%). We found that proctalgia fugax (9.3%), unspecified bowel disorders (10.8%), and functional dysphagia (5.6%) showed unexplained high rates in our country. DGBI rates were higher for women. Having any DGBI was negatively associated with psychosocial variables (including quality of life, somatization, and concern about digestive problems), and associated with increased healthcare utilization. Conclusions & Inferences: We provide the first comprehensive data on the prevalence and burden of all DGBI in Spain using the Rome IV criteria. The enormous burden of DGBI in Spain highlights the need for specialized training and future research. [ABSTRACT FROM AUTHOR]

Background and Objectives: Empathy is considered a prerequisite for a successful physician-patient relationship. The Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE) is a regularly-used, patient-rated measure of physician empathy. The aim of this study is to translate and analyze the reliability and validity of the JSPPPE Spanish (Spain) version (Sp-JSPPPE) in primary care in order to use it with medical trainees.Methods: After translation and back translation of the JSPPPE, 369 patients from 21 primary care physicians in Pamplona (Navarre, Spain) completed the Sp-JSPPPE, a sociodemographic questionnaire, the Spanish (Spain) Consultation and Relational Empathy Measure (Sp-CARE), and a question about overall satisfaction. We studied internal reliability (Cronbach's α and ordinal α), homogeneity (corrected item-total correlations), construct validity (confirmatory factor analysis [CFA]) and concurrent validity (Spearman's correlation) of Sp-JSPPPE.Results: Cronbach's α and ordinal α were 0.870 and 0.919, respectively, for the Sp-JSPPPE, and all corrected item-total correlations exceeded the accepted cutoff of 0.30, demonstrating high internal reliability and homogeneity. CFA corroborated the one-factor structure proposed in the original version. The total score for the Sp-JSPPPE was significantly correlated with sp-CARE (Spearman's ϱ 0.651, P<.001) and with overall patient satisfaction (Spearman's ϱ 0.504, P<.001).Conclusions: The results support the reliability and validity of the Sp-JSPPPE in primary care. Sp-JSPPPE could be useful in empathy assessment of medical trainees, both graduate and postgraduate, in the Spanish context. [ABSTRACT FROM AUTHOR]

The management and effectiveness of the treatment of Helicobacter pylori infection are heterogeneous worldwide, despite the publication of international consensus conferences and guidelines, which have been widely available for years. The aim of the study was to describe the clinical management and the eradication rates in a region of Southern Europe (Spain). Between 2010 and 2019, we conducted a retrospective analysis of patients with H. pylori infection attended by gastroenterologists in two defined areas of the National Health System in Aragón. We compared the appropriateness of therapies according to guidelines, and described the effectiveness of each treatment. A total of 1644 penicillin non-allergic patients were included. The most prescribed therapy between 2010 and 2013 was the 'classic' triple therapy PCA (80%), whereas the 'concomitant' therapy PCAM was chosen by 90% of the gastroenterologists in 2015. After 2016, the use of the quadruple bismuth-containing therapy in a single capsule (Pylera®) quickly increased, representing almost half of the overall prescriptions in 2019. Throughout the decade, adherence to guidelines was 76.4% and global efficacy was 70.7% (ITT). Triple therapies' eradication rates were lower than 70% (ITT), whereas eradication rates with quadruple therapies achieved or were over 80% (ITT). In conclusion, despite the use of quadruple therapies and optimized treatments, the effectiveness of H. pylori management in daily clinical practice is far from the target of 90%. [ABSTRACT FROM AUTHOR]

The economic crisis caused by the Covid-19 pandemic has severely affected the advertising industry worldwide, but the Spanish case can be seen as a particularly privileged laboratory for such observations as a result of the collapse of investments and their redistribution to other time periods, economic sectors, or communication channels. The aim of this research is, firstly, to estimate the impact of the crisis on advertising investment, and secondly to analyze its consequences for the media system and new consumption dynamics. We carry out a comparative analysis of secondary data from national and international sources which enjoy broad business and social consensus, covering the period of the first wave of the pandemic in Spain (March-September 2020). The results enable the identification of the ongoing transformations and an outline of new scenarios for the advertising industry and media business. These scenarios are still under construction and feature a predominance of digital media and the Internet, but also a conjunction with television and its new formats and audiences. Among the most relevant findings of this research, we observed unexpected contradictions in advertising behavior. These include the first breakdown of advertising seasonality since measurement data exist in Spain, and a paradoxical, sharp rise in media use in conjunction with the collapse of advertising expenditure. [ABSTRACT FROM AUTHOR]

Background: First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer).Methods and Findings: This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer ("familial-risk group") and 3,038 as asymptomatic with average-risk for colorectal cancer ("average-risk group"). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36-2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83-1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90-1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts.Conclusions: Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population. [ABSTRACT FROM AUTHOR]

Background and Study Aim: Several factors have been shown to be related to colonoscopy quality; however, little is known about the effects of endoscopist factors. This study analyzed the influence of endoscopist-related characteristics on quality indicators for colonoscopy. Patients and Methods: The study included 48 endoscopists who each performed at least 20 colonoscopies in the colonoscopy arm of a randomized controlled trial comparing fecal immunochemical test vs. colonoscopy in colorectal cancer screening. These endoscopists performed a total of 3838 procedures in the trial. The following were calculated for each endoscopist: adenoma detection rate (ADR), advanced ADR, proximal ADR, distal ADR, and adenoma per colonoscopy rate (APCR). The characteristics of endoscopists were assessed with regard to colonoscopy quality using multivariate regression analysis. Endoscopist characteristics included age, sex, exclusive endoscopy practice, years as a physician, years as a specialist, specialty, total (life-long) number of colonoscopies performed, annual colonoscopy volume, number of hours/week dedicated to endoscopy and number of educational activities in the previous year. Results: Factors associated with ADR were age of the endoscopist (odds ratio [OR] 1.11, 95 % confidence interval [CI] 1.01 - 1.21; P = 0.01) and life-long number of colonoscopies (OR 1.06, 95 %CI 1.01 - 1.11; P = 0.01). Only exclusive dedication to endoscopy practice was found to be independently related to proximal ADR (OR 1.71, 95 %CI 1.15 - 2.74; P = 0.001). Life-long number of colonoscopies was independently related to detection of distal adenomas (OR 1.07, 95 %CI 1.01 - 1.13; P = 0.01). None of the analyzed endoscopist characteristics was associated with advanced ADR or APCR. Conclusions: This study found that the experience of the endoscopist and exclusive dedication to endoscopy practice, but not annual colonoscopy volume, were associated with better colonoscopy quality. [ABSTRACT FROM AUTHOR]

Objective. To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding. Materials and methods. Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose]). Results. Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively ( p < 0.001). Surgery to stop bleeding was required within 30 days in 3.5% and 0.8% of high- and low-risk patients, respectively ( p = 0.007). Mortality at 30 days was similar in both groups (3.3% in high-risk and 2.3% in low-risk patients). Conclusion. Among patients hospitalized owing to peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata. [ABSTRACT FROM AUTHOR]

Objective Patients undergoing percutaneous coronary intervention require dual antiplatelet therapy. Protonpump inhibitor (PPI) therapy is recommended for the prevention of upper GI complications. No study has determined the rate and type of GI bleeding events in such patients in routine clinical practice. Design Observational study with a prospective follow-up to confirm medication use and occurrence of events, which were validated. Patients and setting We have followed up a cohort of 1219 consecutive patients admitted for percutaneous coronary intervention in Zaragoza (Spain). Main outcome measures Major GI bleeding and cardiovascular events. Results At discharge, 96.7% of patients were on dual antiplatelet therapy and 76.6% on PPI therapy, which increased up to 87.9% during follow-up of 2107.6 patient (pt) s-years (1.72±1.07 years/patient). There were eight patients who developed GI bleeding during hospitalisation and 27 patients during follow-up, (1.52 bleeds per 100 pt-years). Most GI bleeding events (81.4%) occurred during the first year (mean time to bleeding event: 7.03±7.65 months) and 84.6% of patients were on long-term PPI at the time of the bleed. Lower GI bleeding occurred more frequently than upper GI bleeding (74% lower vs 26% upper). Peptic ulcer history and concomitant warfarin therapy were the only risk factors identified for upper or lower GI bleeding respectively. Conclusions Among patients on dual antiplatelet therapy and PPI co-therapy, gastrointestinal bleeding episodes are more frequent in the lower GI tract. This changing pattern of bleeding may reflect the success of gastroprotection and focuses attention on research to address lower GI bleeding in this population. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24.Methods: CRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24.Results: None of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk.Conclusions: TOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori ( H. pylori) infection and host genetic factors on GC susceptibility in a population of Spanish white GC patients. METHODS: DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- ( IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory ( IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology. RESULTS: Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77–3.66), smoking habit (OR 1.91, 95% CI 1.25–2.93), and positive family history of GC (OR 3.67, 95% CI 2.01–6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls. CONCLUSIONS: Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study ( IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported. [ABSTRACT FROM AUTHOR]

The management of Helicobacter pylori infection has to rely on previous local effectiveness due to the geographical variability of antibiotic resistance. The aim of this study was to evaluate the effectiveness of first and second-line H. pylori treatment in Spain, where the empirical prescription is recommended. A multicentre prospective non-interventional registry of the clinical practice of European gastroenterologists concerning H. pylori infection (Hp-EuReg) was developed, including patients from 2013 until June 2019. Effectiveness was evaluated descriptively and through a multivariate analysis concerning age, gender, presence of ulcer, proton-pump inhibitor (PPI) dose, therapy duration and compliance. Overall, 53 Spanish hospitals were included, and 10,267 patients received a first-line therapy. The best results were obtained with the 10-day bismuth single-capsule therapy (95% cure rate by intention-to-treat) and with both the 14-day bismuth-clarithromycin quadruple (PPI-bismuth-clarithromycin-amoxicillin, 91%) and the 14-day non-bismuth quadruple concomitant (PPI-clarithromycin-amoxicillin-metronidazole, 92%) therapies. Second-line therapies were prescribed to 2448 patients, with most-effective therapies being the triple quinolone (PPI-amoxicillin-levofloxacin/moxifloxacin) and the bismuth-levofloxacin quadruple schemes (PPI-bismuth-levofloxacin-amoxicillin) prescribed for 14 days (92%, 89% and 90% effectiveness, respectively), and the bismuth single-capsule (10 days, 88.5%). Compliance, longer duration and higher acid inhibition were associated with higher effectiveness. "Optimized" H. pylori therapies achieve over 90% success in Spain. [ABSTRACT FROM AUTHOR]

The Ministry of Industry announced in February 2010 [1] a plan to collect between ϵ1500 and ϵ2000 million with the auction of new frequency bands for mobile telephony. The bid for a total of 310 MHz in different frequency bands will be done by a mixed formula: 90 percent through auctions and 10 percent by competition. [ABSTRACT FROM PUBLISHER]

Comparing pandemic waves could aid in understanding the evolution of COVID-19. The objective of the present study was to compare the characteristics and outcomes of patients hospitalized for COVID-19 in different pandemic waves in terms of severity and mortality. We performed an observational retrospective cohort study of 5,220 patients hospitalized with SARS-CoV-2 infection from February to September 2020 in Aragon, Spain. We compared ICU admissions and 30-day mortality, clinical characteristics, and risk factors of the first and second waves of COVID-19. The SARS-CoV-2 genome was also analyzed in 236 samples. Patients in the first wave (n = 2,547) were older (median age 74 years [IQR 60-86] vs. 70 years [53-85]; p < 0.001) and had worse clinical and analytical parameters related to severe COVID-19 than patients in the second wave (n = 2,673). The probability of ICU admission at 30 days was 16% and 10% (p < 0.001) and the cumulative 30-day mortality rates 38% and 32% in the first and second wave, respectively (p = 0.007). Survival differences were observed among patients aged 60 to 80 years. We also found some variability among death risk factors and the viral genome between waves. Therefore, the two analyzed COVID-19 pandemic waves were different in terms of disease severity and mortality., (© 2021. The Author(s).)

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians., (© 2015 UICC.)

Recently, differential scanning calorimetry (DSC) has been acknowledged as a novel tool for diagnosing and monitoring several diseases. This highly sensitive technique has been traditionally used to study thermally induced protein folding/unfolding transitions. In previous research papers, DSC profiles from blood samples of patients were analyzed and they exhibited marked differences in the thermal denaturation profile. Thus, we investigated the use of this novel technology in blood serum samples from 25 healthy subjects and 30 patients with gastric adenocarcinoma (GAC) at different stages of tumor development with a new multiparametric approach. The analysis of the calorimetric profiles of blood serum from GAC patients allowed us to discriminate three stages of cancer development (I to III) from those of healthy individuals. After a multiparametric analysis, a classification of blood serum DSC parameters from patients with GAC is proposed. Certain parameters exhibited significant differences (P < 0.05) and allowed the discrimination of healthy subjects/patients from patients at different tumor stages. The results of this work validate DSC as a novel technique for GAC patient classification and staging, and offer new graphical tools and value ranges for the acquired parameters in order to discriminate healthy from diseased subjects with increased disease burden.

Objective: To assess, from the perspective of the National Healthcare System, the efficiency of a fixed-dose combination of naproxen and esomeprazole (naproxen/esomeprazole) in the treatment of osteoarthritis (OA) compared to other NSAID, alone or in combination with a proton pump inhibitor (PPI)., Methods: A Markov model was used; it included different health states defined by gastrointestinal (GI) events: dyspepsia, symptomatic or complicated ulcer; or cardiovascular (CV) events: myocardial infarction, stroke or heart failure. The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008. The total costs (€, 2012), including drug and event-related costs, and the health outcomes expressed in quality-adjusted life years (QALY) were estimated in patients with increased GI risk, aged 65 or over, for a 1-year time horizon and a 6-month treatment with celecoxib (200mg/day), celecoxib+PPI, diclofenac (150mg/day)+PPI, etoricoxib (60mg/day), etoricoxib+PPI, ibuprofen (1,800mg/day)+PPI, naproxen (1,000mg/day)+PPI or naproxen/esomeprazole (naproxen 1,000mg/esomeprazole 40mg/day). The selected PPI was omeprazole (20mg/day)., Results: Naproxen/esomeprazole was a dominant strategy (more effective and less costly) compared to celecoxib, etoricoxib and diclofenac+PPI. Celecoxib+PPI and etoricoxib+PPI were more effective. Considering a cost-effectiveness threshold of €30,000 per additional QALY, naproxen/esomeprazole was cost-effective compared to ibuprofen+PPI and naproxen+PPI with incremental cost-effectiveness ratios (ICER) of €15,154 and €5,202 per additional QALY, respectively., Conclusions: A fixed-dose combination of naproxen and esomeprazole is a cost-effective, and even dominant, alternative compared to other options in OA patients with increased GI risk., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Background: Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed., Methods: Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided., Results: APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN., Conclusions: Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Introduction: Despite recent advances in endoscopic and pharmacological management, nonvariceal upper gastrointestinal bleeding (NVUGIB) is still associated with considerable mortality and morbidity that vary between countries. The European Survey of Nonvariceal Upper Gastrointestinal Bleeding (ENERGiB) reported clinical outcomes across Europe (Belgium, Greece, Italy, Norway, Portugal, Spain, and Turkey) and evaluated management strategies in a "real-world" European setting. This article presents the differences in clinical management strategies among countries participating in ENERGiB., Methods: Adult patients consecutively presenting with overt NVUGIB at 123 participating hospitals over a 2-month period were included. Data relevant to the initial NVUGIB episode and for up to 30 days afterwards were collected retrospectively from patient medical records., Results: The number of evaluable patients was 2,660; patient demographics and clinical characteristics were similar across countries. There was wide between-country variability in the area and speciality of the NVUGIB management team and unit transfer rates after the initial hospital assessment. The mean time from admission to endoscopy was <1 day only in Italy and Spain. Wide variation in the use of preendoscopy (35.0-88.7%) and relatively consistent (86.5-96.0%) postendoscopic pharmacological therapy rates were observed. There was substantial by-country variability in the rate of therapeutic procedures performed during endoscopy (24.9-47.6%). NVUGIB-related healthcare resource consumption was high and variable (days hospitalized, mean 5.4-8.7 days; number of endoscopies during hospitalization, mean 1.1-1.7)., Conclusions: ENERGiB demonstrates that there are substantial differences in the management of patients with acute NVUGIB episodes across Europe, and that in many cases the guideline recommendations for the management of NVUGIB are not being followed.

Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups. Our goal was to perform a nationwide, case-control study in Spain to evaluate the relevance of several functional GST gene polymorphisms and environmental factors to GC risk and phenotype. DNA from 557 GC patients and 557 sex- and age-matched healthy controls (HC) was typed for two deletions in the GSTM1 and GSTT1 genes and two SNPs in the GSTP1 gene (rs1695 and rs1138272) using polymerase chain reaction-restriction fragment length polymorphism methods. Logistic regression analysis identified Helicobacter pylori infection with CagA strains [odds ratio (OR): 2.36; 95% confidence interval (CI): 1.78-3.15], smoking habit (OR: 2.10; 95% CI: 1.48-2.97) and family history of GC (OR: 3.2; 95% CI: 2.02-5.16) as independent risk factors for GC. No differences in the frequencies of GSTM1 or GSTT1 null genotypes were observed between cases and controls (GSTM1: 50.8% vs. 48%; GSTT1: 21.5% vs. 21%). Moreover, simultaneous carriage of both, the GSTM1 and the GSTT1 null genotypes, was almost identical in both groups (10.7% in GC vs. 10.6% in HC). In addition, no significant differences in GSTP1 Ile105Val (rs1695) and GSTP1 Val114Ala (rs1138272) genotype distribution were observed between GC patients and controls. Subgroup analysis for age, gender, Helicobacter pylori status, smoking habits, family history of GC, anatomic location and histological subtype revealed no significant association between GST variants and GC risk. Our results show that the GST polymorphisms evaluated in this study are not relevant when determining the individual susceptibility to GC or phenotype in a South-European population.

Background: Mortality related to nonvariceal upper gastrointestinal bleeding (NVUGIB) has not changed. More information is needed to improve the management of this entity. The aims of this study were: a) to determine the characteristics of bleeding episodes, b) to describe the clinical approaches routinely used in NVUGIB, and c) to identify adverse outcomes related to endoscopic or medical treatments in Spain., Methods: The European survey of nonvariceal upper GI bleeding (ENERGiB) was an observational, retrospective cohort study on NVUGIB with endoscopic evaluation carried out across Europe. The present study focused on Spanish patients in the ENERGiB study. The patients were managed according to routine care. The mean and standard deviation were calculated for quantitative variables and absolute and relative frequencies were calculated for categorical variables., Results: Patients (n=403) were mostly men (71%), with a mean age of 65 years, and co-morbidities (62.5%). Most of the patients were managed by gastroenterologists (57.1%) or internal medicine teams (25.1%). A proton pump inhibitor was used empirically in 80% before endoscopy. Bleeding persistence occurred in 6.4% and recurrence in 6.7%. The mortality rate at 30 days was 3.5%., Conclusions: This study contributes to the characterization of Spanish patients and NVUGIB episodes in a real clinical setting and identifies the routine management of this entity, which is in line with the standards proposed by recent clinical practice guidelines. A notable finding was that age and the number of comorbidities in NVUGIB patients were increasing. These factors could explain the persistent mortality rate, despite the evident advances in the management of this entity., (Copyright © 2011 Elsevier España, S.L. y AEEH y AEG. All rights reserved.)

Objective: Patients undergoing percutaneous coronary intervention require dual antiplatelet therapy. Proton-pump inhibitor (PPI) therapy is recommended for the prevention of upper GI complications. No study has determined the rate and type of GI bleeding events in such patients in routine clinical practice., Design: Observational study with a prospective follow-up to confirm medication use and occurrence of events, which were validated., Patients and Setting: We have followed up a cohort of 1219 consecutive patients admitted for percutaneous coronary intervention in Zaragoza (Spain)., Main Outcome Measures: Major GI bleeding and cardiovascular events., Results: At discharge, 96.7% of patients were on dual antiplatelet therapy and 76.6% on PPI therapy, which increased up to 87.9% during follow-up of 2107.6 patient (pt) s-years (1.72±1.07 years/patient). There were eight patients who developed GI bleeding during hospitalisation and 27 patients during follow-up, (1.52 bleeds per 100 pt-years). Most GI bleeding events (81.4%) occurred during the first year (mean time to bleeding event: 7.03±7.65 months) and 84.6% of patients were on long-term PPI at the time of the bleed. Lower GI bleeding occurred more frequently than upper GI bleeding (74% lower vs. 26% upper). Peptic ulcer history and concomitant warfarin therapy were the only risk factors identified for upper or lower GI bleeding respectively., Conclusions: Among patients on dual antiplatelet therapy and PPI co-therapy, gastrointestinal bleeding episodes are more frequent in the lower GI tract. This changing pattern of bleeding may reflect the success of gastroprotection and focuses attention on research to address lower GI bleeding in this population.

Colorectal cancer (CRC) is the most common malignant tumor in Spain, when men and women are considered together, and the second leading cause of cancer death. Every week in Spain over 500 cases of CRC are diagnosed, and nearly 260 people die from the disease. Epidemiologic estimations for the coming years show a significant increase in the number of annual cases. CRC is a perfectly preventable tumor and can be cured in 90% of cases if detected in the early stages. Population-based screening programs have been shown to reduce the incidence of CRC and mortality from the disease. Unless early detection programs are established in Spain, it is estimated that in the coming years, 1 out of 20 men and 1 out of 30 women will develop CRC before the age of 75. The Alliance for the Prevention of Colorectal Cancer in Spain is an independent and non-profit organization created in 2008 that integrates patients' associations, altruistic non-governmental organizations and scientific societies. Its main objective is to raise awareness and disseminate information on the social and healthcare importance of CRC in Spain and to promote screening measures, early detection and prevention programs. Health professionals, scientific societies, healthcare institutions and civil society should be sensitized to this highly important health problem that requires the participation of all sectors of society. The early detection of CRC is an issue that affects the whole of society and therefore it is imperative for all sectors to work together., (Copyright © 2012 Elsevier España, S.L. y AEEH y AEG. All rights reserved.)

Background: Prescription of non-steroidal anti-inflammatory drugs (NSAIDs) should be based on the assessment of both gastrointestinal (GI) and cardiovascular (CV) risk for the individual patient. We aimed to assess the GI/CV risk profile and the pharmacological management of patients with osteoarthritis (OA) in clinical practice., Methods: We conducted a cross-sectional, multicentre, observational study of consecutive OA patients that visited 1,760 doctors throughout the Spanish National Health System (NHS) in a single day. The presence of GI risk factors, CV histories, hypertension and current pharmacological treatments was recorded., Results: Of the 60,868 patients, 17,105 had a diagnosis of OA and were evaluable. The majority (93.4%) had more than one GI risk factor and 60.3% were defined to be at high-GI risk. Thirty-two percent had a history of CV events, 57.6% were treated with anti-hypertensive therapy and 22.6% had uncontrolled hypertension. One-fifth of patients were treated with non-NSAID therapies, whereas the remaining patients received NSAIDs. Non-selective NSAIDs (nsNSAID) plus proton pump inhibitor (PPI) or cyclooxigenase-2 (COX-2)-selective NSAIDs alone were more frequently prescribed in patients at increased GI risk. Patients with a positive CV history received nsNSAIDs or COX-2-selective NSAIDs in 41.3% and 31.7% of cases, respectively. When both the GI and CV histories were combined, 51% of the overall population was being prescribed drugs that were either not recommended or contraindicated., Conclusions: Over 90% of patients with OA are at increased GI and/or CV risk. In over half of these patients, the prescription of NSAIDs was not in accordance with current guidelines or recommendations made by regulatory agencies.

Background: Temporal changes in the incidence of cause-specific gastrointestinal (GI) complications may be one of the factors underlying changing medical practice patterns., Aim: To report temporal changes in the incidence of five major causes of specific gastrointestinal (GI) complication events., Methodology: Population-based study of patients hospitalised due to GI bleeding and perforation from 1996 to 2005 in Spain. We report crude rates, and estimate regression coefficients of temporal trends, severity and recorded drug use for five frequent GI events. GI hospitalisation charts were validated by independent review of large random samples., Results: The incidence per 100 000 person-years of hospitalisations due to upper GI ulcer bleeding and perforation decreased over time [from 54.6 and 3.9 in 1996 (R² = 0.944) to 25.8 and 2.9 in 2005 (R² = 0.410) respectively]. On the contrary, the incidence per 100 000 person-years of colonic diverticular and angiodysplasia bleeding increased over time [3.3 and 0.9 in 1996 (R² = 0.443) and 8.0 and 2.6 in 2005 (R² = 0.715) respectively]. A small increasing trend was observed for the incidence per 100 000 person-years of intestinal perforations (from 1.5 to 2.3 events). Based on data extracted from the validation process, recent recorded drug intake showed an increased frequency of anticoagulants with colonic diverticular and angiodysplasia bleeding, whereas NSAID and low-dose aspirin use were more prevalent in peptic ulcer bleeding and colonic diverticular bleeding respectively., Conclusions: From 1996 to 2005, hospitalisations due to peptic ulcer bleeding and perforation have decreased significantly, whereas the number of cases of colonic diverticular and angiodysplasia bleeding have increased., (© 2011 Blackwell Publishing Ltd.)

Background: The European Community has made a commitment to colorectal cancer (CRC) screening, but regional considerations may affect the design of national screening programs. We developed a decision analytic model tailored to a pilot screening program for high-risk persons in Spain with the aim of informing public policy decisions., Materials and Methods: We constructed a decision analytic Markov model based on our validated model of CRC screening that reflected CRC epidemiology and costs in persons with first-degree relatives with CRC in Aragón, Spain, and superimposed colonoscopy every 5 or 10 years from ages 40 to 80 years. The pilot program's preliminary clinical results and our modeling results were presented to regional health authorities., Results: In the model, without screening, 88 CRC cases occurred per 1,000 persons from age 40 to 85 years. In the base case, screening reduced this by 72% to 77% and gained 0.12 discounted life years per person. Screening every 10 years was cost saving, and screening every 5 years versus every 10 years cost 7,250 euros per life year gained. Based on these savings, 36 to 39 euros per person per year could go toward operating costs while maintaining a neutral budget. If screening costs doubled, screening remained highly cost-effective but no longer cost saving. These results contributed to the health authorities' decision to expand the pilot program to the entire region in 2009., Conclusions: Colonoscopic screening of first-degree relatives of persons with CRC may be cost saving in public systems like that of Spain. Decision analytic modeling tailored to regional considerations can inform public policy decisions., Impact: Tailored decision analytic modeling can inform regional policy decisions on cancer screening., (©2010 AACR.)

Background: Proton pump inhibitors (PPIs) are the preferred agents for the prevention of aspirin-associated upper gastrointestinal bleeding (UGIB). Data are limited to determine whether PPIs are being used to reduce UGIB risk., Aim: To evaluate the implementation of PPI treatment to reduce the GI risk in two cardiology centres from Europe and the United States., Methods: A retrospective cross-sectional study was carried out at the University of Michigan and University Hospital-Zaragoza in 429 consecutive patients hospitalized for percutaneous coronary intervention (PCI) on dual antiplatelet therapy., Results: Admission for PPI co-therapy was similar (34% vs. 30%) in both centres. At discharge, the proportion of high-risk patients receiving PPI therapy in the Spanish centre (75.4%) was higher than their American peers (55.6%) (OR: 2.5; 95% CI; 1.3-4.7). No differences in PPI prescription rates were found among Spanish patients with/without GI risk factors. The opportunity to initiate PPI co-therapy in high-risk patients was missed in 81.8% (36/44) of those not on PPI at admission in US patients vs. 24.1% (19/79) (P < 0.0001) in Spanish patients., Conclusions: There are important differences concerning PPI prescription and risk stratification in the two centres when managing PCI patients. Efforts to stratify risks and utilize appropriate strategies for UGIB prophylaxis in high-risk patients are warranted., (2010 Blackwell Publishing Ltd.)

Background & Aims: Ten common low-penetrant genetic variants have been consistently associated with colorectal cancer (CRC) risk; little is known about the correlation between these variants and CRC phenotype. Characterization of such a correlation would improve CRC management and prevention programs. We assessed the association between these genetic variants and CRC phenotype in patients and modeled pairwise combinations to detect epistasis., Methods: The validation population corresponded to a prospective, multicenter, population-based cohort (EPICOLON I) of 1096 patients with newly diagnosed CRC. The replication set was an independent, prospective, multicenter Spanish cohort (EPICOLON II) of 895 patients with newly diagnosed CRC. For individual single nucleotide polymorphism (SNP) association analyses, a multivariate method using logistic regression was applied in EPICOLON I and subsequently prospectively validated in EPICOLON II. Interactions between SNPs were assessed using the likelihood ratio test., Results: Validated results confirmed that the C allele on 8q23.3 (rs16892766) was significantly associated with advanced-stage tumors (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.15-1.90; P value = 4.9 x 10(-3)). The G allele on 8q24.21 (rs6983267) was more common in patients with a familial history of CRC (OR, 2.02; 95% CI, 1.35-3.03; P value = 3.9 x 10(-4)). The combination of rs6983267 on 8q24.21 and rs9929218 on 16q22.2 was associated with a history of colorectal adenoma (carriers of GG and AA, respectively; OR, 2.28; 95% CI, 1.32-3.93; P = 5.0 x 10(-4))., Conclusions: CRC susceptibility variants at 8q23.3, 8q24.21, and 16q22.2 appear to be associated with cancer phenotype. These findings might be used to develop screening and surveillance strategies., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Medical management of adults with osteoarthritis (OA) who require non-steroidal anti-inflammatory drugs (NSAIDs) must be decided after assessing prevalent gastrointestinal (GI) and cardiovascular (CV) risks in the individual patient., Objective: To evaluate the GI and CV risk profile of patients with OA who require NSAIDs., Methods: A transversal, multicentre and observational study was conducted in consecutive patients with OA who were considered candidates for NSAID treatment and were visited by 374 unselected rheumatologists throughout the National Health System. Patients were classified into three risk groups (low, moderate and high) for their GI and CV characteristics. These were defined by considering the presence of a number of well-established GI risk factors or by application of the Systematic Coronary Risk Evaluation model for assessing the overall risk for CV disease, respectively., Results: Of 3293 consecutive patients, most (86.6%) were at increased GI risk and a considerable number, 22.3%, were at high GI risk. The CV risk was high in 44.2% of patients, moderate in 28.5% and low in 27.3%. Overall, 15.5% of patients presented a very high-risk profile, having high GI and CV risks. The type of NSAID prescription was similar regardless of the associated GI and CV risk profile., Conclusion: Most patients with OA requiring NSAIDs for pain control showed a high prevalence of GI and CV risk factors. Over half of the patients were at either high GI or CV risk, or both, such that the prescription of OA treatments should be very carefully considered.

Unlabelled: Preventive measures in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDS) have been reported to be underused. The aim of the present study was to analyze differences between the indication and prescription of gastroprotection with proton pump inhibitors (PPI) in patients treated with NSAIDS and with risk factors for gastrointestinal complications., Methods: We performed an observational, cross-sectional, multicenter study. Data were gathered retrospectively from medical records and from a questionnaire on risk factors and indication for gastroprotection., Results: A total of 432 physicians gathered data from 2,160 patients treated with NSAIDs. Nearly all (90.4%) of the patients were prescribed gastroprotection with a PPI. Long-term versus short-term (<1 month) NSAID treatment was associated with gastroprotection (OR=2.37; 95% CI 1.779-3.171). The mean number of risk factors per patient was 2+/-0.16 (range 0-7), and a significant association was found between the number of risk factors and the percentage of patients receiving gastroprotection. Nevertheless, the proportion of patients with risk factors not receiving gastroprotection was 3% for those with a prior history of ulcer and/or gastrointestinal bleeding due to NSAIDS and 7-10% for the remaining factors. Differences were found between the indication for gastroprotection and the gastroprotection prescribed among the various specialties. The specialists prescribing gastroprotection the least were radiotherapy specialists., Conclusions: These results demonstrate that, in daily clinical practice, differences between the indication and prescription of gastroprotection in patients treated with NSAIDS and with risk factors are small in Spain., (Copyright 2009 Elsevier España, S.L. All rights reserved.)

Objectives: Changing patterns in medical practice may contribute to temporal changes in the incidence of upper and lower gastrointestinal (GI) complications. There are limited data on the incidence of lower GI complications in clinical practice and most studies that have been done have serious methodological limitations to inferring the actual burden of this problem. The aims of this study were to analyze time trends of hospitalizations resulting from GI complications originating both from the upper and lower GI tract in the general population, and to determine the risk factors, severity, and clinical impact of these GI events., Methods: This was a population-based study of patients hospitalized because of GI complications in 10 general hospitals between 1996 and 2005 in Spain. We report the age- and gender-specific rates, estimate the regression coefficients of the upper and lower GI event trends, and evaluate the severity and associated risk factors. GI hospitalization charts were validated by an independent review of large random samples of unspecific and specific codes distributed among all hospitals and study years., Results: Upper GI complications fell from 87/100,000 persons in 1996 to 47/100,000 persons in 2005, whereas lower GI complications increased from 20/100,000 to 33/100,000. Overall, mortality rates decreased, but the case fatality remained constant over time. Lower GI events had a higher mortality rate (8.8 vs. 5.5%), a longer hospitalization (11.6+/-13.9 vs. 7.9+/-8.8 days), and higher resource utilization than did upper GI events. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) without concomitant proton pump inhibitor was more frequently recorded among upper GI complications than among lower GI complications. When comparing upper GI events with lower GI events, we found that male gender (adjusted odds ratio (OR): 1.94; 95% confidence interval (CI): 1.70-2.21), and recorded NSAID use (OR: 1.92; 95% CI: 1.60-2.30) were associated to a greater extent with upper GI events, whereas older age (OR: 0.83; 95% CI: 0.77-0.89), number of comorbidities (OR: 0.91; 95% CI: 0.86-0.96), and having a diagnosis in recent years (OR: 0.92; 95% CI: 0.90-0.94) were all associated to a greater extent with lower GI events than with upper GI events after adjusting for age, sex, hospitalization, and discharge year., Conclusions: Over the past decade, there has been a progressive change in the overall picture of GI events leading to hospitalization, with a clear decreasing trend in upper GI events and a significant increase in lower GI events, causing the rates of these two GI complications to converge. Overall, mortality has also decreased, but the in-hospital case fatality of upper or lower GI complication events has remained constant. It will be a challenge to improve future care in this area unless we develop new strategies to reduce the number of events originating in the lower GI tract, as well as reducing their associated mortality.

The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma has increased in Western countries in recent decades. The aim of this study is to describe the changes in incidence and prevalence of BE diagnosis, dysplasia, and adenocarcinoma development in BE patients in a South-European Mediterranean area. Retrospective population-based analyses of endoscopy and pathology reports from 1976 to 2001 was performed. Data from patients with diagnosis of BE and/or esophageal carcinoma were collected. The study period was divided in four quartiles for statistical calculations; parametric and nonparametric tests were used. A 6.9-fold increase was found in the diagnosis of long-segment BE from the first to the fourth quartile, and a 9.3-fold increase in short-segment BE from 1995 to 2000, in contrast to a much smaller increase of 1.9-fold increase in the number of upper gastrointestinal endoscopies. The adjusted incidence of BE diagnosis increased from 0.73 to 9.73 cases/100,000 (first to fourth quartile, respectively) and the adjusted prevalence from 6.51 to 76.04 cases/100,000 (1985-2001). The incidence of dysplasia was 2.13% per year (95% confidence interval: 0.05-11.3%) - 1.78% for low-grade dysplasia and 0.36% for high-grade dysplasia - giving a total incidence of 1 per 47 patient-years. The incidence of adenocarcinoma during follow-up was 0.48% per year (95% confidence interval: 0.006-2.62%), for an incidence of 1 per 210 patient-years. Nineteen patients with BE (14 long-segment BE, 5 short-segment BE) were diagnosed with esophageal adenocarcinoma, with eight being diagnosed during endoscopic surveillance. Only 14 (8%) adenocarcinoma patients diagnosed during the study period had a history of BE. BE diagnosis has dramatically increased over recent decades in our population, unrelated to an increase in endoscopies. Progression to low-grade dysplasia and adenocarcinoma is rare. Surveillance may have a low impact on the survival of adenocarcinoma patients in Southern Europe.

Background: There is an overexpression of cyclo-oxygenase 2 (COX-2) in Barrett's oesophagus (BO)., Aim: To determine the long-term effect of a COX-2 inhibitor on cellular mechanisms involved in BO., Methods: A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX-2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student-t test and the U-Mann-Whitney test were used for quantitative and ordinal variables., Results: Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX-2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low-grade dysplasia or cyclin D1 was observed., Conclusions: The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX-2 and VEGF expression and increases cell apoptosis.

Objectives: After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants., Methods: This case-control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported., Results: Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27-0.39), H2-receptor antagonists (H2-RAs) (RR 0.65, 95% CI 0.50-0.85), and nitrates (RR 0.52, 95% CI 0.38-0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09-0.19 vs RR 0.30, 95% CI 0.17-0.53 with H2-RAs; RR 0.48, 95% CI 0.19-1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22-0.51 vs RR 0.40, 95% CI 0.19-0.73 with H2-RA; RR 0.69, 95% CI 0.36-1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07-0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk., Conclusion: Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants.

Recent studies have revealed elevated expression of transforming growth factor beta1 (TGF-beta1) in gastric mucosa of patients with gastric cancer (GC) and those undergoing ulcer repair. As production of TGF-beta1 is genetically regulated, we aimed to assess whether functional polymorphisms of the TGFB1 gene are involved in susceptibility to and clinical characteristics of Helicobacter pylori-related diseases. DNA from 142 unrelated Spanish patients with GC, 200 with peptic ulcer and 342 healthy controls was typed for the MspA1I T+869C, and the Sau96I G+915C polymorphisms of the TGFB1 gene using polymerase chain reaction and RFLP analysis. H. pylori infection and CagA/VacA antibody status were determined by Western blot in patients and controls. H. pylori infection (odds ratio (OR): 11.44; 95% confidence interval (CI): 4.45-29.42; P<0.001) and non-steroidal anti-inflammatory drugs (OR: 5.07; 95% CI: 2.53-10.16; P<0.001) were identified as independent risks factors for duodenal ulcer (DU), whereas the TGFB1+869(*)C/C genotype was associated with reduced risk of developing the disease (OR: 0.32; 95% CI=0.15-0.68; P=0.003). Our results show that the TGFB1 T+869C gene polymorphism is involved in the susceptibility to DU and provide further evidence that host genetic factors play a key role in the pathogenesis of H. pylori-related diseases.

Background & Aim: The role that H. pylori infection plays in the development of and Barrett's esophagus (BE) is uncertain. We tested the hypothesis that infection with cagA+ Helicobacter pylori strains protects against the development of BE., Methods: We studied 104 consecutive patients, residents in an area with a high prevalence of H. pylori infection, with BE and 213 sex- and age-matched controls. H. pylori infection and CagA antibody status were determined by western blot serology., Results: H. pylori prevalence was higher in patients with BE than in controls (87.5% vs. 74.6%; OR. 2.3; 95% CI: 1.23-4.59). Increasing age was associated with a higher prevalence of H. pylori (p < 0.05). The prevalence of CagA+ H. pylori serology was similar in patients with BE and controls (64.4% vs. 54.5%; NS). Type I H. pylori infection (CagA+ and VacA+) was similar in patients with BE and controls (44.2% vs. 41.3%; NS). Logistic regression analysis identified alcohol (O.R. 7.09; 95% CI 2.23-22.51), and H. pylori infection (OR: 2.41; 95%CI: 1.20-4.84) but not CagA+ serology as independent factors., Conclusion: Neither H. pylori infection nor H. pylori infection by CagA+ strains reduce the risk of BE in a population with high prevalence of H. pylori infection.

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.

Background: It is unknown whether the incidence of peptic ulcer changes in areas with a high prevalence of Helicobacter pylori infection., Aim: To determine trends in peptic ulcer complications in a community with a high prevalence of H. pylori infection., Methods: New endoscopic diagnoses of peptic ulcers and their complications from 1985 to 2000 were obtained. H. pylori infection in the adult population, the number of prescriptions for anti-secretory drugs and non-steroidal anti-inflammatory drugs were also evaluated., Results: Although the global prevalence of H. pylori infection remains high in this population (>60%), a 41.4 to 25.4% decrease in the incidence of peptic ulcers and ulcer complications was observed. This was associated with a decrease in the prevalence of H. pylori infection in people under 65 years of age, a 3.5-fold increase in the number of prescriptions of proton-pump inhibitors and an increase in the number of prescriptions of non-steroidal anti-inflammatory drugs, especially coxibs., Conclusions: In an area with a high prevalence of H. pylori infection, the incidence of peptic ulcer and associated complications is declining rapidly. This was associated with a reduction of the prevalence of H. pylori infection in the young and a widespread use of proton-pump inhibitors. The increase in the use of non-steroidal anti-inflammatory drugs, especially coxibs, has not changed the tendency.

Background and Aim: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country., Materials and Methods: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection., Results: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8)., Conclusion: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.

Background: Nonsteroidal anti-inflammatory drugs induce gastrointestinal side effects. In this study we have analyzed the economic impact of these side effects on the National Health System., Material and Methods: Costs were calculated based on actual data obtained from a General Hospital attending a population of 256,000 people with similar demographic distribution to the country 39 million people. The number of prescriptions of NSAID issued in the area during a 12 month period (1998), the attributable risks obtained from different epidemiological studies of this area and the rate and type of co-prescribing of gastroprotective agents were obtained from different local and national surveys and specialized agencies. Costs of complication and dyspepsia treatments were obtained from actual cost charged by the Spanish National Institute of Health. Sensitivity analyses were also performed to estimate maximal and minimum costs., Results: Costs per 100,000 people/year were: a) hospitalization = 24,100,983 pesetas; b) gastroprotective agents = 81,759,255 pesetas; c) management of dyspepsia = 31,527,895 pesetas. Estimates showed that global costs per 100,000 people/year were nor higher than 31,353 million and nor lower than 71,312 million pesetas. It was also estimated that gastroprotective therapy was inadequately prescribed in 80% of cases (25,720 million pesetas), and that 8,312 million pesetas per 100,000 patient/year of the global cost was due to OTC NSAID use. Globally, GI side effects increased 86% the actual cost of NSAID in 1998. Almost half of that increase was due to inadequate prescription of gastroprotective therapy and only 5.4% of that was due to OTC NSAID use., Conclusions: Gastrointestinal side effects due to NSAID use have an enormous economic impact on the National Health System. Any new therapeutic strategy in the management of rheumatic conditions which decrease the rate of complications and the need of coprescription of gastroprotective agents will decrease these costs.

50 cases of PBC registered in Navarra during 1974-1987 were studied retrospectively. 38% of the diagnosis were carried out in the non-symptomatic period. There were no histological differences between symptomatic (2.24 +/- 1.16) periods. In the first group the delay in diagnosis was very high: 28.21 months, the jaundice being followed by itching of 11.65 months duration. The rate of PBC has increased progressively, rising to a global incidence of 25.15/million and 78.03/million for women over 25 years old. There figures are 3 and 9 times higher than those published in spanish and most foreign literature. We did not find any significant differences between the several health service areas in Navarra, nor between rural or urban areas. Our paper brings to the fore this question: is Navarra an area of especial prevalence of PBC or does it simply offer better diagnosis conditions?

The present study has attempted to determine the prevalence of peptic ulcer (UP) in smokers and nonsmokers in the geographic region of Aragon (Spain) using a sample of 10,000 subjects, 1,897 with ulcer, 1,708 of them diagnosed by endoscopy. The prevalence of smokers is 42.4% (63% of males and 14% of females). The prevalence of peptic ulcer in smokers (26.87%) is double that of nonsmokers (13.38%) (p less than 0.05). In males, all of the locations (duodenal, duodenal + gastric and gastric) are more common among smokers than among nonsmokers. These differences do not exist in women, gastric ulcer being more common among nonsmokers. Complications were more frequent among smokers with ulcer (60%) than among nonsmokers with ulcer (40%).