Comparison of hospital course and outcome in hospital-acquired vs pre-existing delirium.

BACKGROUND: Delirium is a major source of morbidity in the inpatient hospital setting. This study examined differences between patients with delirium present prior to hospital admission and those with hospitalacquired delirium in several health outcomes. METHODS: A total of 12,529 patients on 2 inpatient units were included in this retrospective cohort study. Outcomes were assessed using chart review. Other variables were compared across groups and included in multivariate models predicting discharge location within the hospitalacquired delirium group. RESULTS: Of 709 patients with delirium, 83% had pre-admission prevalent and 17% had post-admission incident delirium. Compared with patients with preexisting delirium, patients with hospital-acquired delirium had greater hospital durations and mortality and were more likely to receive ICU care, more likely to receive multiple classes of medications, and less likely to be discharged home without home health services. Multivariate analysis in the hospital-acquired delirium group found that several variables independently predicted discharge location. CONCLUSIONS: Patients with hospital-acquired delirium had worse hospital outcomes and a more complicated hospital course than those with preexisting delirium. Administration of various medications, several demographic variables, and some hospital-related variables were independently associated with worse outcomes within the hospital-acquired delirium group. These results demonstrate that patients with hospitalacquired delirium are a vulnerable subgroup deserving special attention.

Altered methamphetamine place conditioning in mice vaccinated with a succinyl-methamphetamine-tetanus-toxoid vaccine.

BACKGROUND AND OBJECTIVES: We previously reported that an anti-methamphetamine (MA) vaccine attenuated drug-conditioned effects in mice, but it used a carrier protein and adjuvant not available for clinical use. Here we produced a vaccine with the same hapten (succinyl-methamphetamine, SMA) but attached to tetanus toxoid (SMA-TT) and adsorbed to aluminum hydroxide, components approved for use in humans. We then assessed the vaccine's ability to generate anti-MA antibodies, alter acquisition and reinstatement of MA place conditioning, and prevent MA brain penetration. METHODS: Mice were administered SMA-TT at weeks 0 and 3 and non-vaccinated mice received saline. Anti-MA antibody concentrations were determined at 8 and 12 weeks. Place conditioning began during week 9 in which vaccinated and non-vaccinated mice were divided into groups and conditioned with .5, or 2.0 mg/kg MA. Following acquisition training, mice were extinguished and then a reinstatement test was performed in which mice were administered their original training dose of MA. Separate groups of non-vaccinated and vaccinated mice were administered .5 and 2.0 mg/kg MA and brain MA levels determined. RESULTS AND CONCLUSIONS: Anti-MA antibody levels were elevated at week 8 and remained so through week 12. The SMA-TT vaccine attenuated acquisition and reinstatement of MA place conditioning. Significantly greater proportions of vaccinated mice during acquisition and reinstatement tests showed conditioned place aversion. Moreover, MA brain levels were decreased in vaccinated mice following administration of both doses of MA. SCIENTIFIC SIGNIFICANCE: Results support further development of anti-MA vaccines using components approved for use in humans.

A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats.

Vaccines for opioid dependence may provide a treatment that would reduce or slow the distribution of the drug to brain, thus reducing the drug's reinforcing effects. We tested whether a conjugate vaccine against morphine (keyhole limpet hemocyanin-6-succinylmorphine; KLH-6-SM) administered to rats would produce antibodies and show specificity for morphine or other heroin metabolites. The functional effects of the vaccine were tested with antinociceptive and conditioned place preference (CPP) tests. Rats were either vaccinated with KLH-6-SM and received two boosts 3 and 16 weeks later or served as controls and received KLH alone. Anti-morphine antibodies were produced in vaccinated rats; levels increased and were sustained at moderate levels through 24 weeks. Antibody binding was inhibited by free morphine and other heroin metabolites as demonstrated by competitive inhibition ELISA. Vaccinated rats showed reduced morphine CPP, tested during weeks 4 to 6, and decreased antinociceptive responses to morphine, tested at week 7. Brain morphine levels, assessed using gas-chromatography coupled to mass spectrometry (GC-MS) on samples obtained at 26 weeks, were significantly lower in vaccinated rats. This suggests that morphine entry into the brain was reduced or slowed. These results provide support for KLH-6-SM as a candidate vaccine for opioid dependence.

The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats.

Medications that target norepinephrine (NE) neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX), a longer-acting α1 antagonist blocked cocaine's subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6-8) were administered saline, cocaine (COC, 10 mg/kg) or DOX (0.3 or 1.0 mg/kg) alone or in combination for 5 consecutive days (development). Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression). COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg), but not the low dose (0.3 mg/kg) of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine's behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.