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IMPORTANCE Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are commonly used to prevent gastrointestinal tract (GI) hemorrhage in critically ill patients. The stronger acid suppression of PPIs may reduce the rate of bleeding but enhance infectious complications, specifically pneumonia and Clostridium difficile infection (CDI). OBJECTIVE To evaluate the occurrence and risk factors for GI hemorrhage, pneumonia, and CDI in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS A pharmacoepidemiological cohort study was conducted of adult patients requiring mechanical ventilation for 24 hours or more and administered either an H2RA or PPI for 48 hours or more while intubated across 71 hospitals between January 1, 2003, and December 31, 2008. Propensity score–adjusted and propensity-matched multivariate regression models were used to control for confounders. MAIN OUTCOMES AND MEASURES Primary outcomes were secondary diagnoses of International Classification of Diseases, Ninth Revision (ICD-9)–coded GI hemorrhage, pneumonia, and CDI occurring 48 hours or more after initiating invasive ventilation. RESULTS Of 35 312 patients, 13 439 (38.1%) received H2RAs and 21 873 (61.9%) received PPIs. Gastrointestinal hemorrhage (2.1% vs 5.9%; P < .001), pneumonia (27% vs 38.6%; P < .001), and CDI (2.2% vs 3.8%; P < .001) occurred less frequently in the H2RA group. After adjusting for propensity score and covariates, odds ratios of GI hemorrhage (2.24; 95% CI, 1.81-2.76), pneumonia (1.2; 95% CI, 1.03-1.41), and CDI (1.29; 95% CI, 1.04-1.64) were greater with PPIs. Similar results were obtained in the propensity-matched models of 8799 patients in each cohort. CONCLUSIONS AND RELEVANCE Proton pump inhibitors are associated with greater risks of GI hemorrhage, pneumonia, and CDI than H2RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies.

Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as a salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed.

Background: Patients with chronic diseases are particularly affected by prescription copayment increases, as they are faced with the decision to switch to formulary alternatives or pay more to stay on their current medication.Objective: To evaluate the impact of increased copayments as a result of a change in formulary status on the continuation rates of nonformulary medications in multitiered pharmacy benefit plans.Methods: A retrospective cohort study was conducted on patients with chronic diseases who were part of a health plan in the western US. Individuals were selected if they were taking a medication that was being removed from the health plan's formulary and, thus, experienced increases in their copayments for nonformulary medications (n = 1,244). The time periods before and after the increase in copayments were studied. Adjusting for demographics, chronic comorbidities, medication use, Medicare + Choice status, and percentage increase in copayment for nonformulary medications, Cox regressions were used to assess continuation rates for these drugs.Results: A clear relationship between increasing copayment differentials and continuation rates for nonformulary medications in the period after the copayment increases could not be established. In general, those who experienced higher copayment differentials (50–100%, 100–200%, >200%) were more likely to continue their nonformulary medication than were those who experienced copayment increases of 25–50% and >25%.Conclusions: Individuals confronted with increased copayments often switched their drugs to formulary alternatives. However, a clear relationship could not be established between increasing copayments and continuation behavior. Further research is needed to determine whether these switching behaviors result in inappropriate medication behaviors, such as complete discontinuation of drug therapy due to the increased costs.

The effects of chronic administration of MK-801 (NMDA-receptor antagonist) and remacemide (sodium channel blocker) on monkey learning of several brain function tasks was assessed in juveniles (nine months old). Low (LO) and high (HI) doses of both drugs were given orally each day for 18 months. There were no adverse effects of any treatment on tests of short-term memory or motivation. HI doses of both MK-801 and remacemide delayed acquisition of a visual discrimination task (the remacemide effect was much greater). HI doses of remacemide alone severely disrupted learning task acquisition and this effect lasted for several months after dosing. Thus, in monkeys, chronic blockade of NMDA receptors is relatively well tolerated, whereas blockade of sodium channels (perhaps in conjunction with NMDA receptor blockade) has long-term-perhaps permanent-consequences. To further explore the roles of NMDA receptors and sodium channels in these effects, MK-801, phenytoin (sodium channel blocker), or both were administered to rats and the acquisition of tasks similar to those used in the monkey study were assessed. Dosing began at weaning and continued for nine months. Throughout the study, HI MK-801 subjects exhibited impaired performance in all tasks. Some effects of MK-801 were blocked completely by phenytoin. In the rat, blockade of sodium channels was well tolerated but blockade of NMDA receptors had significant and long-term (permanent) adverse consequences. These data contrast markedly with those obtained for the monkey and suggest, at least for some drug classes, that the rat might not be a good predictor of effects in primates.

Introduction:Real-world comparative studies evaluating traditional with newer antianginal medications in chronic stable angina (CSA) on cardiovascular (CV) outcomes and healthcare utilization are limited.

Introduction:Though, deep vein thrombosis (DVT) and pulmonary embolism (PE) impose a major burden on US healthcare system, limited data exists on the economic impact of DVT and PE on younger working population. DVT, which occurs in approximately 1 in every 1,000 adults every year, is estimated to cost between 5-8 billion annually or on average 20,000 per treated patient per year. PE occurs in 0.6 million patients annually and results in 50,000 to 200,000 deaths every year. This study examined the total burden of illness, including the direct and indirect healthcare costs to employers and employees with DVT and PE.