BACKGROUND There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522.)

Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department (ED) visit rates. OBJECTIVE:To assess the impact of a supplemental care bundle targeting high-risk elderly inpatients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and/or ED visitation at 30 and 60 days following discharge. PATIENTS/METHODS:Randomized controlled pilot study in 41 medical inpatients predisposed to unplanned readmission or postdischarge ED visitation, conducted at Baylor University Medical Center. The intervention group care bundle consisted of medication counseling/reconciliation by a clinical pharmacist (CP), condition specific education/enhanced discharge planning by a care coordinator (CC), and phone follow-up. RESULTS:Groups had similar baseline characteristics. Intervention group readmission/ED visit rates were reduced at 30 days compared to the control group (10.0% versus 38.1%, P ¼ 0.04), but not at 60 days (30.0% versus 42.9%, P ¼ 0.52). For those patients who had a readmission/postdischarge ED visit, the time interval to this event was longer in the intervention group compared to usual care (36.2 versus 15.7 days, P ¼ 0.05). Study power was insufficient to reliably compare the effects of the intervention on lengths of index hospital stay between groups. KEYWORDS: care coordination, discharge planning, elderly care, hospital readmission, transitional care. CONCLUSIONS:Elderly patients (aged 65 years and older) consume a disproportionate amount of acute health care resources, composing up to 20% of emergency department (ED) visits, 1,2 having a 2-fold to 5-fold increase in likelihood of hospital admission, 1 and frequently incurring lengths of hospital stay (LOS) approximately 15% higher than the national averages. 3 In addition, they are at increased risk for hospital readmission in the 90-day interval following hospital discharge. 1,4,5 Specific risk factors for readmission include age above 80 years, discharge within the previous 30 days, the presence of 3 or more comorbid diagnoses, use of 5 or more prescription medications, difficulty with at least 1 activity of daily living (ADL), and lack of discharge education. 6 These risk factors can translate into adverse drug events, 7-9 exacerbations of chronic diseases, 10 or functional decline 4,5 that can trigger ED visits or hospital readmission.Hospital-based care coordination-defined as a multidisciplinary interaction between inpatients and providers that focuses on education, communication, and discharge planning with the primary aim of improving outcomes-has demonstrated inconsistent results as a mechanism to reduce LOS, postdischarge ED visits, or hospital readmission rates. While disease-specific care coordination programs for congestive heart failure and chronic obstructive pulmonary disease have been effective in reducing rehospitalization rates, 10-15 the benefits of comprehensive care coordination for elderly general medical inpatients wit...

CYP3A activity in adults varies between individuals and it has been suggested that this has a genetic basis, possibly related to variant alleles in CYP3A4 and CYP3A5 genes. Accordingly, genotype-phenotype associations were investigated under constitutive and induced conditions. Midazolam's systemic and oral clearances, and the erythromycin breath test (ERBT) were determined in 57 healthy subjects: 23 (11 men, 12 women) European- and 34 (14 men, 20 women) African-Americans. Studies were undertaken in the basal state and after 14-15 days pretreatment with rifampin. DNA was characterized for the common polymorphisms CYP3A4*1B, CYP3A5*3, CYP3A5*6 and CYP3A5*7 by direct sequencing, and for exon 21 and exon 26 variants of MDR1 by allele-specific, real-time polymerase chain reaction. In 95% of subjects, the basal systemic clearance of midazolam was unimodally distributed and variability was less than four-fold whereas, in 98% of the study population, oral clearance varied five-fold. No population or sex-related differences were apparent. Similar findings were observed with the ERBT. Rifampin pretreatment markedly increased the systemic (two-fold) and oral clearance (16-fold) of midazolam, and the ERBT (two-fold) but the variabilities were unchanged. No associations were noted between these phenotypic measures and any of the studied genotypes, except for oral clearance and its fold-increase after rifampin. These were related to the presence of CYP3A4*1B and the inversely linked CYP3A5*3 polymorphism, with the extent of induction being approximately 50% greater in CYP3A5*3 homozygotes compared to wild-type subjects. In most healthy subjects, variability in intestinal and hepatic CYP3A activity, using midazolam as an in-vivo probe, is modest and common polymorphisms in CYP3A4 and CYP3A5 do not appear to have important functional significance.

Opioid-related adverse drug events were common among patients undergoing hospital-based invasive procedures and were associated with significantly worse clinical and cost outcomes. Hospital-acquired harm from ORADEs in the surgical patient population is an important opportunity for health systems to improve patient safety and reduce cost.