Implementation of the handoff program was associated with reductions in medical errors and in preventable adverse events and with improvements in communication, without a negative effect on workflow. (Funded by the Office of the Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services, and others.).

associated infections (HAIs) account for a large proportion of the harms caused by health care and are associated with high costs. Better evaluation of the costs of these infections could help providers and payers to justify investing in prevention. OBJECTIVE To estimate costs associated with the most significant and targetable HAIs. DATA SOURCES For estimation of attributable costs, we conducted a systematic review of the literature using PubMed for the years 1986 through April 2013. For HAI incidence estimates, we used the National Healthcare Safety Network of the Centers for Disease Control and Prevention (CDC). STUDY SELECTION Studies performed outside the United States were excluded. Inclusion criteria included a robust method of comparison using a matched control group or an appropriate regression strategy, generalizable populations typical of inpatient wards and critical care units, methodologic consistency with CDC definitions, and soundness of handling economic outcomes. DATA EXTRACTION AND SYNTHESIS Three review cycles were completed, with the final iteration carried out from July 2011 to April 2013. Selected publications underwent a secondary review by the research team. MAIN OUTCOMES AND MEASURES Costs, inflated to 2012 US dollars. RESULTS Using Monte Carlo simulation, we generated point estimates and 95% CIs for attributable costs and length of hospital stay. On a per-case basis, central line-associated bloodstream infections were found to be the most costly HAIs at $45

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1. Sphk1 null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in most Sphk1؊/؊ tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from the Sphk1؊/؊ mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs of Sphk1؊/؊ mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in the Sphk1 null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with these Sphk1 null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.Sphingosine-1-phosphate (S1P) 1 is a signaling molecule that influences cellular functions including proliferation, survival, migration, adhesion molecule expression, and morphogenesis (1-4). S1P binds to members of the S1P receptor family (also known as EDG receptors) and, via G proteins, triggers multiple signaling pathways (5, 6). S1P has also been shown to function intracellularly mediating calcium homeostasis, cell growth, and suppression of apoptosis (7,8). In mammals, vascular development and lymphocyte trafficking are dependent on S1P receptor signaling (9 -13).Sphingosine kinase (SPHK) catalyzes the synthesis of S1P via the phosphorylation of sphingosine. SPHK activity is elevated by several stimuli, including platelet-derived growth factor, vascular endothelial growth factor, tumor necrosis factor-␣, and phorbol ester, which trigger an increase in cellular S1P levels (14). Sphk genes have been identified in mammals (15-18), insects (19), plants (20), yeast (21), worm (22), and slime mold (23, 24). Mammals carry two known SphK genes, which in mice are encoded by Sphk1 and Sphk2. The two enzymes contain five highly conserved regions (C1-C5) and an ATP binding site within a conserved lipid kinase catalytic domain (15, 16). SPHK1 has a predominantly cytoplasm localization but can be induced to localize to the inner leaflet of the plasma membrane. Interestingly in endothelial cells SPHK1 is secreted and is capable of producing S1P extracellularly (25). Sphk1 shows a tissue distribution and developmental expression pattern different from Sphk2, although both enzymes are widely expressed (16,26).The importance of S1P receptor signaling in lymphocyte trafficking was first illuminated by the activities of FTY720, a potent immunosuppressive agent. FT...

Sphingosine 1-phosphate (S1P) is a bioactive lysolipid with pleiotropic functions mediated through a family of G proteincoupled receptors, S1P 1,2,3,4,5 . Physiological effects of S1P receptor agonists include regulation of cardiovascular function and immunosuppression via redistribution of lymphocytes from blood to secondary lymphoid organs. The phosphorylated metabolite of the immunosuppressant agent FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol) and other phosphonate analogs with differential receptor selectivity were investigated. No significant species differences in compound potency or rank order of activity on receptors cloned from human, murine, and rat sources were observed. All synthetic analogs were high-affinity agonists on S1P 1 , with IC 50 values for ligand binding between 0.3 and 14 nM. The correlation between S1P 1 receptor activation and the ED 50 for lymphocyte reduction was highly significant (p Ͻ 0.001) and lower for the other receptors. In contrast to S1P 1 -mediated effects on lymphocyte recirculation, three lines of evidence link S1P 3 receptor activity with acute toxicity and cardiovascular regulation: compound potency on S1P 3 correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus bradycardia and hypertension was consistent with affinity for S1P 1 relative to S1P 3 ; and toxicity, bradycardia, and hypertension were absent in S1P 3 Ϫ/Ϫ mice. Blood pressure effects of agonists in anesthetized rats were complex, whereas hypertension was the predominant effect in conscious rats and mice. Immunolocalization of S1P 3 in rodent heart revealed abundant expression on myocytes and perivascular smooth muscle cells consistent with regulation of bradycardia and hypertension, whereas S1P 1 expression was restricted to the vascular endothelium.

Use of the bar-code eMAR substantially reduced the rate of errors in order transcription and in medication administration as well as potential adverse drug events, although it did not eliminate such errors. Our data show that the bar-code eMAR is an important intervention to improve medication safety. (ClinicalTrials.gov number, NCT00243373.)

IMPORTANCE Handoff miscommunications are a leading cause of medical errors. Studies comprehensively assessing handoff improvement programs are lacking. OBJECTIVE To determine whether introduction of a multifaceted handoff program was associated with reduced rates of medical errors and preventable adverse events, fewer omissions of key data in written handoffs, improved verbal handoffs, and changes in resident-physician workflow. DESIGN, SETTING, AND PARTICIPANTS Prospective intervention study of 1255 patient admissions (642 before and 613 after the intervention) involving 84 resident physicians (42 before and 42 after the intervention) INTERVENTIONS Resident handoff bundle, consisting of standardized communication and handoff training, a verbal mnemonic, and a new team handoff structure. On one unit, a computerized handoff tool linked to the electronic medical record was introduced. MAIN OUTCOMES AND MEASURESThe primary outcomes were the rates of medical errors and preventable adverse events measured by daily systematic surveillance. The secondary outcomes were omissions in the printed handoff document and resident time-motion activity.RESULTS Medical errors decreased from 33.8 per 100 admissions (95% CI, 27.3-40.3) to 18.3 per 100 admissions (95% CI, 14.7-21.9; P < .001), and preventable adverse events decreased from 3.3 per 100 admissions (95% CI, 1.7-4.8) to 1.5 (95% CI, 0.51-2.4) per 100 admissions (P = .04) following the intervention. There were fewer omissions of key handoff elements on printed handoff documents, especially on the unit that received the computerized handoff tool (significant reductions of omissions in 11 of 14 categories with computerized tool; significant reductions in 2 of 14 categories without computerized tool). Physicians spent a greater percentage of time in a 24-hour period at the patient bedside after the intervention (8.3%; 95% CI 7.1%-9.8%) vs 10.6% (95% CI, 9.2%-12.2%; P = .03). The average duration of verbal handoffs per patient did not change. Verbal handoffs were more likely to occur in a quiet location (33.3%; 95% CI, 14.5%-52.2% vs 67.9%; 95% CI, 50.6%-85.2%; P = .03) and private location (50.0%; 95% CI, 30%-70% vs 85.7%; 95% CI, 72.8%-98.7%; P = .007) after the intervention.CONCLUSIONS AND RELEVANCE Implementation of a handoff bundle was associated with a significant reduction in medical errors and preventable adverse events among hospitalized children. Improvements in verbal and written handoff processes occurred, and resident workflow did not change adversely.

Intravenous medication errors and adverse drug events were frequent and could be detected using smart pumps. We found no measurable impact on the serious medication error rate, likely in part due to poor compliance. Although smart pumps have great promise, technological and nursing behavioral factors must be addressed if these pumps are to achieve their potential for improving medication safety.

The overall rates of dispensing errors and potential ADEs substantially decreased after implementing bar code technology. However, the technology should be configured to scan every dose during the dispensing process.