Delirium in hospitalized patients: implications of current evidence on clinical practice and future avenues for research--a systematic evidence review.

BACKGROUND: Despite the significant burden of delirium among hospitalized adults, critical appraisal of systematic data on delirium diagnosis, pathophysiology, treatment, prevention, and outcomes is lacking. PURPOSE: To provide evidence-based recommendations for delirium care to practitioners, and identify gaps in delirium research. DATA SOURCES: Medline, PubMed, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) information systems from January 1966 to April 2011. STUDY SELECTION: All published systematic evidence reviews (SERs) on delirium were evaluated. DATA EXTRACTION: Three reviewers independently extracted the data regarding delirium risk factors, diagnosis, prevention, treatment, and outcomes, and critically appraised each SER as good, fair, or poor using the United States Preventive Services Task Force criteria. DATA SYNTHESIS: Twenty-two SERs graded as good or fair provided the data. Age, cognitive impairment, depression, anticholinergic drugs, and lorazepam use were associated with an increased risk for developing delirium. The Confusion Assessment Method (CAM) is reliable for delirium diagnosis outside of the intensive care unit. Multicomponent nonpharmacological interventions are effective in reducing delirium incidence in elderly medical patients. Low-dose haloperidol has similar efficacy as atypical antipsychotics for treating delirium. Delirium is associated with poor outcomes independent of age, severity of illness, or dementia. CONCLUSION: Delirium is an acute, preventable medical condition with short- and long-term negative effects on a patient's cognitive and functional states.

Pharmacological management of delirium in hospitalized adults--a systematic evidence review.

BACKGROUND AND OBJECTIVES: Despite the significant burden of delirium among hospitalized adults, there is no approved pharmacologic intervention for delirium. This systematic review evaluates the efficacy and safety of pharmacologic interventions targeting either prevention or management of delirium. DATA SOURCES: We searched Medline, PubMed, the Cochrane Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) information systems from January 1966 to October 2008. We included randomized, controlled trials comparing pharmacologic compounds either to each other or placebo. We excluded non-comparison trials, studies with patients aged < 18 years, a history of an Axis I psychiatric disorder, and patients with alcohol-related delirium. REVIEW METHODS: Three reviewers independently extracted the data for participants, interventions and outcome measures, and critically appraised each study using the JADAD scale. RESULTS: We identified 13 studies that met our inclusion criteria and evaluated 15 compounds: second-generation antipsychotics, first-generation antipsychotics, cholinergic enhancers, an antiepileptic agent, an inhaled anesthetic, injectable sedatives, and a benzodiazepine. Four trials evaluated delirium treatment and suggested no differences in efficacy or safety among the evaluated treatment methods (first and second generation antipsychotics). Neither cholinesterase inhibitors nor procholinergic drugs were effective in preventing delirium. Multiple studies, however, suggest either shorter severity and duration, or prevention of delirium with the use of haloperidol, risperidone, gabapentin, or a mixture of sedatives in patients undergoing elective or emergent surgical procedures. CONCLUSION: The existing limited data indicates no superiority for second-generation antipsychotics over haloperidol in managing delirium. Although preliminary results suggest delirium prevention may be accomplished through various mechanisms, further studies are necessary to prove effectiveness.

Intein-mediated assembly of a functional beta-glucuronidase in transgenic plants.

The DnaE intein in Synechocystis sp. strain PCC6803 is the first and only naturally split intein that has been identified so far. It is capable of catalyzing a protein trans-splicing mechanism to assemble a mature protein from two separate precursors. Therefore, it is a powerful tool for protein modification and engineering. Inteins have not been identified, nor have intein-mediated protein splicing reactions been demonstrated, in plant cells. In this paper, we describe the use of the Ssp DnaE split intein in transgenic plants for reconstitution of a protein trans-splicing reaction. We have synthesized artificial genes that encode for N-terminal half (Int-n) and C-terminal half (Int-c) fragments of Ssp DnaE split intein and divided beta-glucuronidase (GUS) gene to encode GUS-n and GUS-c parts of the enzyme as reporter. The in-frame fusions of GUSn/Intn and Intc/GUSc were constructed and transfected into Arabidopsis. We have observed in vivo reassembly of functional beta-glucuronidase when both GUSn/Intn and Intc/GUSc constructs were introduced into the same Arabidopsis genome either by cotransformation or through genetic crossing, hereby signifying an intein-mediated protein trans-splicing mechanism reconstituted in plant cells.