In contrast, for nonulcer bleeds, the PAF was slightly increased for gastrointestinal cancer, alcohol, anticoagulants, and selective serotonin reuptake inhibitors. The crude ORs were re-estimated for medications after excluding cases with nonmedication risk factors and these are

shown in Supplementary Table 2. NSAID use was strongly associated with bleeding, with an OR of 1.67, and this increased to 2.80 with the exclusion of nonmedication risk factors. The corresponding adjusted ORs associated with NSAIDs were selleck chemical 1.59 with nonmedication risk factors included and 1.73 without. Altering the exposure exclusion window for NSAIDs to 30 days rather than 60 days before the bleed slightly increased the effect of NSAIDS, but had only a minimal effect on the other results, including comorbidity (see Supplementary Table 3). Restricting the analysis to those older than 65 years old increased the proportion of cases attributable to the combined effect of all exposures from 48% to 63%, and reduced the additional proportion of cases attributable to nongastrointestinal comorbidity from 19.8% to 16.1%. Re-estimating the model using multiple imputation for missing alcohol and smoking status (modeled as binary exposures) slightly reduced the PAF associated with comorbidity from 22.9% to 22.4%, but when alcohol and smoking Doxorubicin molecular weight status

were omitted from the model, the PAF was almost unaltered at 22.2%. Finally, the full model was re-estimated for each component of the Charlson Index (Table 6). The contribution of these individual comorbidities was minimal in comparison with their combined weighted effect in the Charlson Index in the main analysis. This

study has demonstrated that a combined measure of nongastrointestinal comorbidity is a significant independent predictor of upper GIB, even after accounting for all other recognized and measured risk factors. In addition, dipyridamole it explained a greater proportion of the burden of bleeding than any other risk factor in the population. The effect of this combined measure of nongastrointestinal comorbidity was far in excess of that which would be expected from its constituent diseases. The association of comorbidities with upper GIB has been studied previously, but only in smaller secondary care surveys with comorbidity as a confounder and not as the primary exposure. We searched PubMed using variants of comorbidity, etiology, causality, risk factors, and gastrointestinal hemorrhage; however, no studies were identified that set out to address the question of our article. Studies were most frequently designed to measure the association of a single medication while adjusting for any confounding by comorbidity.21 and 22 Two studies assessed a larger range of medications in cross-sectional hospital-based surveys.