Primary non-variceal upper gastrointestinal bleeding in NSAID and low-dose aspirin users: development and validation of risk scores for either medication in two large Dutch cohorts.

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.

Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified?

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.

Adherence to microsatellite instability testing in young-onset colorectal cancer patients.

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.

Recording of family history is associated with colorectal cancer stage.

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.