Previously our laboratory has shown that ketamine exposure (24 hours of clinically relevant anesthesia) causes significant increases in neuronal cell death in perinatal rhesus monkeys. Sensitivity to this ketamine-induced neurotoxicity was observed on gestational days 120-123 (in utero exposure via maternal anesthesia) and on postnatal days (PNDs) 5-6, but not on PNDs 35-37. In the present study, six monkeys were exposed on PND 5 or 6 to intravenous ketamine anesthesia to maintain a light surgical plane for 24 hrs and six control animals were unexposed. At 7 months of age all animals were weaned and began training to perform a series of cognitive function tasks as part of the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB). The OTB tasks used here included those for assessing aspects of learning, motivation, color discrimination, and short-term memory. Subjects responded for banana-flavored food pellets by pressing response levers and press-plates during daily (M-F) test sessions (50 min) and were assigned training scores based upon their individual performance. As reported earlier [47] beginning around 10 months of age, control animals significantly outperformed (had higher training scores than) ketamine-exposed animals for approximately the next 10 months. For animals now over 3 and one-half years of age, the cognitive impairments continue to manifest in the ketamine-exposed group as poorer performance in the OTB learning and color and position discrimination tasks, as deficits in accuracy of task performance, but also in response speed. There are also apparent differences in the motivation of these animals which may be impacting OTB performance. These observations demonstrate that a single 24-hr episode of ketamine anesthesia, occurring during a sensitive period of brain development, results in very long-lasting deficits in brain function in primates and provide proof-of-concept that general anesthesia during critical periods of brain development can result in subsequent functional deficits.
IMPORTANCE Histamine-2 receptor antagonists (H 2 RAs) 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 H 2 RA 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 H 2 RAs 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 H 2 RA 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 H 2 RAs in mechanically ventilated patients. Numerous other risk factors are apparent. These data warrant confirmation in comparative prospective studies.
In a Medicaid-receiving population, baseline glucose and lipid testing for SGA-treated patients was infrequent and showed little change following the diabetes warning and monitoring recommendations. A change in SGA drug selection consistent with intentions to reduce metabolic risk was observed.
MS prevalence rates from a representative commercially insured database were higher than or consistent with prior US estimates. For further accuracy improvement of US prevalence estimates, results should be confirmed after validation of MS identification algorithms, and should be expanded to other US populations, including the government-insured and the uninsured.
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