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Background: Non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose acetylsalicylic acid (ASA) have several adverse gastrointestinal (GI) effects, including upper GI bleeding. We aimed to develop a simple risk score to identify high risk NSAID and ASA users for primary upper GI bleeding., Methods: Using data from two large anonymized health insurance databases, we defined a development and validation cohort with NSAID and ASA users which were followed-up for the occurrence of a primary upper GI bleeding. Cox regression analyses identified risk factors which were combined into simple risk scores. C-statistics were used to evaluate the discriminative ability of these scores in a validation cohort., Results: In total, 421 cases of upper GI bleeding were identified in the initial cohort of 784,263 NSAID users (incidence rate 54.2 per 10,000 person-years), while 1,295 cases of upper GI bleeding were identified in 235,531 ASA users (incidence rate 37.9 per 10,000 person-years). The risk of upper GI bleeding increased with a higher risk score, which for NSAID users included age, male gender, anemia and concomitant use of ASA or anticoagulants. For ASA users, age, anemia, diabetes and concomitant use of other antiplatelet drugs or anticoagulants were included in the risk score. The C-statistics in the validation cohort were 0.68 and 0.63 or NSAID and ASA users, respectively., Conclusion: Risk factors for primary upper GI bleeding are to a large extent similar for NSAID and ASA users. Using a risk score based on these risk factors, patients at the highest risk can be identified with moderate accuracy.

Background and Study Aims: This study aimed to reassess whether the Forrest classification is still useful for the prediction of rebleeding and mortality in peptic ulcer bleedings and, based on this, whether the classification could be simplified., Patients and Methods: Prospective registry data on peptic ulcer bleedings were collected and categorized according to the Forrest classification. The primary outcomes were 30-day rebleeding and all-cause mortality rates. Receiver operating characteristic curves were used to test whether simplification of the Forrest classification into high risk (Forrest Ia), increased risk (Forrest Ib-IIc), and low risk (Forrest III) classes could be an alternative to the original classification., Results: In total, 397 patients were included, with 18 bleedings (4.5%) being classified as Forrest Ia, 73 (18.4%) as Forrest Ib, 86 (21.7%) as Forrest IIa, 32 (8.1%) as Forrest IIb, 59 (14.9%) as Forrest IIc, and 129 (32.5%) as Forrest III. Rebleeding occurred in 74 patients (18.6%). Rebleeding rates were highest in Forrest Ia peptic ulcers (59%). The odds ratios for rebleeding among Forrest Ib-IIc ulcers were similar. In subgroup analysis, predicting rebleeding using the Forrest classification was more reliable for gastric ulcers than for duodenal ulcers. The simplified Forrest classification had similar test characteristics to the original Forrest classification., Conclusion: The Forrest classification still has predictive value for rebleeding of peptic ulcers, especially for gastric ulcers; however, it does not predict mortality. Based on these results, a simplified Forrest classification is proposed. However, further studies are needed to validate these findings., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Low-dose aspirin (ASA) increases the risk of upper gastrointestinal (GI) complications. Proton pump inhibitors (PPIs) reduce these upper GI side effects, yet patient compliance to PPIs is low. We determined the cost-effectiveness of gastroprotective strategies in low-dose ASA users considering ASA and PPI compliance., Methods: Using a Markov model we compared four strategies: no medication, ASA monotherapy, ASA+PPI co-therapy and a fixed combination of ASA and PPI for primary and secondary prevention of ACS. The risk of acute coronary syndrome (ACS), upper GI bleeding and dyspepsia was modeled as a function of compliance and the relative risk of developing these events while using medication. Costs, quality adjusted life years and number of ACS events were evaluated, applying a variable risk of upper GI bleeding. Probabilistic sensitivity analyses were performed., Results: For our base case patients using ASA for primary prevention of ACS no medication was superior to ASA monotherapy. PPI co-therapy was cost-effective (incremental cost-effectiveness ratio [ICER] €10,314) compared to no medication. In secondary prevention, PPI co-therapy was cost-effective (ICER €563) while the fixed combination yielded an ICER < €20,000 only in a population with elevated risk for upper GI bleeding or moderate PPI compliance. PPI co-therapy had the highest probability to be cost-effective in all scenarios. PPI use lowered the overall number of ACS., Conclusions: Considering compliance, PPI co-therapy is likely to be cost-effective in patients taking low dose ASA for primary and secondary prevention of ACS, given low PPI prices. In secondary prevention, a fixed combination seems cost-effective in patients with elevated risk for upper GI bleeding or in those with moderate PPI compliance. Both strategies reduced the number of ACS compared to ASA monotherapy.

Background: In 1997, the Bethesda guidelines recommended microsatellite instability testing for colorectal cancer in patients younger than 45 years to screen for Lynch syndrome. In 2004, these guidelines were revised to set the screening age at younger than 50 years., Objective: The aim of this study was to investigate to what extent these guidelines were followed in young patients with colorectal cancer in the Mid-Netherlands and to identify the predictors of nonadherence., Design: This is a retrospective cohort study., Settings: This study was conducted in 1 academic and 5 nonacademic hospitals., Patients: All patients diagnosed with colorectal cancer younger than 45 years in the period 1999 to 2004 and younger than 50 years in the period 2005 to 2008 were included. Patients known to be affected by or at risk for Lynch syndrome before diagnosis were excluded., Main Outcome Measures: Patient and tumor characteristics, including microsatellite instability testing results, were collected from the database of the Comprehensive Cancer Center, the National Pathological Archive, participating hospitals, and the regional institute of clinical genetics. Logistic regression analysis was performed to detect a trend in adherence over the years and to identify the predictors of nonadherence., Results: A total of 335 patients were identified. Microsatellite instability testing was performed in 130/335 (39%) patients. Adherence did not improve in the period 1999 to 2008. We found that older age at diagnosis (OR 0.96, 95% CI 0.92-1.00), male sex (OR 0.60, 95% CI 0.38-0.95), and stage IV colorectal cancer (OR 0.45, 95% CI 0.24-0.84) were independent predictors of nonadherence, whereas proximal tumor localization, poor differentiation, and mucinous histology were not., Limitations: This study was limited by its retrospective design., Conclusions: Adherence to the Bethesda guidelines in young-onset colorectal cancer is low, particularly in older and male patients and in patients with metastatic disease, which suggests that efforts to improve adherence are needed.

Objectives: To evaluate the cost-effectiveness of competing gastroprotective strategies, including single-tablet formulations, in the prevention of gastrointestinal (GI) complications in patients with chronic arthritis taking nonsteroidal anti-inflammatory drugs (NSAIDs)., Methods: We performed a cost-utility analysis to compare eight gastroprotective strategies including NSAIDs, cyclooxygenase-2 inhibitors, proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol, and single-tablet formulations. We derived estimates for outcomes and costs from medical literature. The primary outcome was incremental cost per quality-adjusted life-year gained. We performed sensitivity analyses to assess the effect of GI complications, compliance rates, and drug costs., Results: For average-risk patients, NSAID + PPI cotherapy was most cost-effective. The NSAID/PPI single-tablet formulation became cost-effective only when its price decreased from €0.78 to €0.56 per tablet, or when PPI compliance fell below 51% in the NSAID + PPI strategy. All other strategies were more costly and less effective. The model was highly sensitive to the GI complication risk, costs of PPI and NSAID/PPI single-tablet formulation, and compliance to PPI. In patients with a threefold higher risk of GI complications, both NSAID + PPI cotherapy and single-tablet formulation were cost-effective., Conclusions: NSAID + PPI cotherapy is the most cost-effective strategy in all patients with chronic arthritis irrespective of their risk for GI complications. For patients with increased GI risk, the NSAID/PPI single-tablet formulation is also cost-effective., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) associated with Lynch syndrome usually presents at a relatively young age. The Revised Bethesda Guidelines advise screening for Lynch syndrome in patients diagnosed with CRC and a positive family history (FH) of CRC and other Lynch-related cancers., Objective: To evaluate recording of the FH and identify factors associated with recording in young patients with CRC., Patients and Methods: In one academic and two nonacademic hospitals, of all patients diagnosed with CRC at the age of 60 years or younger between 1999 and 2007, electronic medical records were evaluated for a recorded FH of CRC and other Lynch-related cancers. Patient and tumor characteristics were retrieved from the Dutch Comprehensive Cancer Centre and the Dutch Pathological Archive., Results: A total of 676 patients were identified. FH was recorded in 395/676 (58%) patients. From 1999 to 2007, recording improved with an odds ratio (OR) of 1.10 [95% confidence interval (CI) 1.03-1.17] per year. Stage III CRC (OR 1.71, 95% CI 1.07-2.75) and administration of chemotherapy (OR 1.84, 95% CI 1.17-2.89) were associated with recording in multivariate analysis. Other factors, including age at diagnosis, sex, surgery, radiotherapy, proximal tumor localization, poor differentiation, and mucinous histology, were not associated with recording., Conclusion: A FH of CRC and other Lynch-related cancers was not recorded in ∼40% of young CRC patients and recording improved only slightly over the years. As a first step in the identification of Lynch-related cancer families, physicians should be trained to record a detailed FH in the work-up of all newly diagnosed CRC patients.

Background: It has been suggested that patients presenting with upper gastrointestinal bleeding (UGIB) during the weekend have a worse outcome compared with weekdays, with an increased risk of recurrent bleeding and mortality., Aim: To investigate the association between timing of admission and adverse outcome after UGIB., Methods: We prospectively collected data from patients presenting with symptoms suggestive of UGIB to the emergency room of eight participating hospitals. Using standard descriptive statistics and logistic regression analyses, differences in 30-day mortality, rebleeding rate, and need for angiography and surgical intervention were assessed for week- and weekend admissions and time of admission. Moreover, patient- and procedure-related factors were identified that could influence outcome., Results: In total, 571 patients were included with suspected UGIB. Patient admitted during the weekend had a higher mortality rate than patients admitted during the week [9% vs.3%; adjusted odds ratio 2.68 (95%CI 1.07-6.72)]. Weekend admissions were not associated with other adverse outcomes. Patients admitted during the weekend presented more often with bleeding and had a significantly lower systolic and diastolic blood pressure. No differences were found in procedure-related factors. Time of admission was not associated with an adverse outcome, although patients admitted during the evening had a significantly longer time to endoscopy (15, 22 and 16 h for day, evening and night admissions respectively, P < 0.01)., Conclusion: Although quality of care did not appear to differ between week/weekend admissions, patients with suspected upper gastrointestinal bleeding admitted during the weekend were at higher risk of an adverse outcome. This might be due to the fact that these patients have more severe haemorrhage., (© 2012 Blackwell Publishing Ltd.)

Background and Study Aims: Several algorithms predicting outcomes in acute gastrointestinal bleeding have been developed over the past three decades. These algorithms differ substantially and therefore the aim of the current study was to conduct a systematic review to compare their predictive performance and methodological quality in gastrointestinal bleeding., Methods: A PubMed literature search was performed up to 1 July 2011. All studies reporting prediction scores in gastrointestinal bleeding were included. Studies were analyzed for predictive performance, and a quality appraisal of these rules was performed for which a score range of 0 (lowest) to 29 (highest) was used., Results: A total of 372 studies were identified, of which 16 were eligible for inclusion. The studies evaluated different outcomes: mortality (n = 5), rebleeding (n = 2), intervention required (n = 2), or a combination (n = 7). The predictive performance of the identified prediction scores varied between an area under the curve of 0.71 - 0.92 (if given). The mean overall quality rating was 17 (SD 4.0, range 9 - 25). Major methodological shortcomings were the absence of validation and absence of impact analyses. Eight of 16 scores (50 %) were determined "easy to use," and five scores (31 %) reported some type of action based on the results., Conclusion: Substantial heterogeneity in outcomes and results was seen in the 16 identified prediction scores. Moreover, the methodological quality was suboptimal in most studies. However, we suggest that clinicians should use the "best available" scores according to performance and quality, which are the Blatchford score to assess the need for intervention, and the scores of Villanueva et al. for poor outcome, Guglielmi et al. for rebleeding, and Chiu et al. for mortality risk., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Incidence rates of both obesity and gastro-oesophageal reflux disease (GERD) are increasing, particularly in the Western world. It has been suggested that GERD symptoms may be improved by weight reduction., Aim: To review the literature on the effect of various weight reducing modalities on manifestations of GERD in obese patients., Methods: A literature search was performed using PubMed, EMBASE and the Cochrane Library, combining the words obesity and gastro-oesophageal reflux with bariatric surgery, diet, lifestyle intervention and weight loss., Results: With regard to diet/lifestyle intervention (conservative), four of seven studies reported an improvement of GERD. For Roux-en-Y gastric bypass, a positive effect on GERD was found in all studies, although this was mainly evaluated by questionnaires. In contrast, for vertical banded gastroplasty, no change or even an increase of GERD was noted, whereas the results for laparoscopic adjustable gastric banding were conflicting., Conclusions: Dietary and lifestyle intervention may improve GERD in obese patients; however, the most favourable effect is likely to be found after bariatric surgery, especially after Roux-en-Y gastric bypass. Future studies need to elucidate for which GERD patients laparoscopic adjustable gastric banding might have a beneficial effect and how they can be identified preoperatively.