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Biomedical subjects

Carol A Keohane

Publications and source records attributed to Carol A Keohane.

9 recordsLinked to original sources
PubMed2006

SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties.

Structure-activity relationship (SAR) studies of 3-arylpropionic acids-a class of novel S1P(1) selective agonists-by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent.

Animals↗
PubMed2006

Medication dispensing errors and potential adverse drug events before and after implementing bar code technology in the pharmacy.

BACKGROUND: Many dispensing errors made in hospital pharmacies can harm patients. Some hospitals are investing in bar code technology to reduce these errors, but data about its efficacy are limited. OBJECTIVE: To evaluate whether implementation of bar code technology reduced dispensing errors and potential adverse drug events (ADEs). DESIGN: Before-and-after study using direct observations. SETTING: Hospital pharmacy at a 735-bed tertiary care academic medical center. INTERVENTION: A bar code-assisted dispensing system was implemented in 3 configurations. In 2 configurations, all doses were scanned once during the dispensing process. In the third configuration, only 1 dose was scanned if several doses of the same medication were being dispensed. MEASUREMENTS: Target dispensing errors, defined as dispensing errors that bar code technology was designed to address, and target potential ADEs, defined as target dispensing errors that can harm patients. RESULTS: In the pre- and post-bar code implementation periods, the authors observed 115,164 and 253,984 dispensed medication doses, respectively. Overall, the rates of target potential ADEs and all potential ADEs decreased by 74% and 63%, respectively. Of the 3 configurations of bar code technology studied, the 2 configurations that required staff to scan all doses had a 93% to 96% relative reduction in the incidence of target dispensing errors (P < 0.001) and 86% to 97% relative reduction in the incidence of potential ADEs (P < 0.001). However, the configuration that did not require scanning of every dose had only a 60% relative reduction in the incidence of target dispensing errors (P < 0.001) and an increased (by 2.4-fold) incidence of target potential ADEs (P = 0.014). There were several potentially life-threatening ADEs involving intravenous dopamine and intravenous heparin in that configuration. LIMITATIONS: The authors used surrogate outcomes; did not mask assessors to the purpose of study; and excluded the controlled substance fill process (a process with low error rates at baseline) from the study, which may bias the combined decrease in error rates toward a larger magnitude. CONCLUSIONS: 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.

Drug Labeling↗
PubMed2006

Discovery of 3-arylpropionic acids as potent agonists of sphingosine-1-phosphate receptor-1 (S1P1) with high selectivity against all other known S1P receptor subtypes.

A series of 3-arylpropionic acids were synthesized as S1P1 receptor agonists. Structure-activity relationship studies on the pendant phenyl ring revealed several structural features offering selectivity of S1P1 binding against S1P2-5. These highly selective S1P1 agonists induced peripheral blood lymphocyte lowering in mice and one of them was found to be efficacious in a rat skin transplantation model, supporting that S1P1 agonism is primarily responsible for the immunosuppressive efficacy observed in preclinical animal models.

Animals↗
PubMed2005

A controlled trial of smart infusion pumps to improve medication safety in critically ill patients.

OBJECTIVE: Intravenous medications are vital during inpatient management. Errors associated with the administration of medications through intravenous infusion pumps to critically ill patients can result in adverse drug events. We sought to assess the impact of smart pumps with integrated decision support software on the incidence and nature of medication errors and adverse drug events. DESIGN: We performed a prospective, randomized time-series trial and compared the serious medication error rate between intervention (decision support on) and control (decision support off) periods. Serious medication errors included both near-misses and preventable adverse drug events. Pump software produced log reports to help identify potential events. Events were presented to physicians for rating of event type, preventability, and severity. SETTING: Cardiac surgical intensive care and step-down units between February and December 2002. PATIENTS: Pump data were available for 744 cardiac surgery admissions. INTERVENTIONS: Decision support during medication administration provided feedback including alerts, reminders, and unit-specific drug rate limits. MEASUREMENTS AND MAIN RESULTS: We found a total of 180 serious medication errors, including 14 and 11 preventable adverse drug events and 73 and 82 nonintercepted potential adverse drug events in the control and intervention periods, respectively. The serious medication error rates in the control and intervention periods were 2.03 and 2.41 per 100 patient-pump-days, respectively (p = .124). We also found numerous opportunities for safety improvement. Violations of infusion practice during the intervention periods included 571 (25%) bypasses of the drug library. Medications were also frequently administered without documentation of physician orders in both periods (n = 823; 7.7%). CONCLUSION: 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.

Aged↗
PubMed2005

Effect of bar-code technology on the incidence of medication dispensing errors and potential adverse drug events in a hospital pharmacy.

We performed a direct observation prepost study to evaluate the impact of barcode technology on medication dispensing errors and potential adverse drug events in the pharmacy of a tertiary-academic medical center. We found that barcode technology significantly reduced the rate of target dispensing errors leaving the pharmacy by 85%, from 0.37% to 0.06%. The rate of potential adverse drug events (ADEs) due to dispensing errors was also significantly reduced by 63%, from 0.19%to 0.069%. In a 735-bed hospital where 6 million doses of medications are dispensed per year, this technology is expected to prevent about 13,000 dispensing errors and 6,000 potential ADEs per year.

Clinical Pharmacy Information Systems↗
PubMed2003

Intelligent intravenous infusion pumps to improve medication administration safety.

Intravenous (IV) medications are vital in the management of hospitalized patients. Inpatients frequently receive several IV medications concurrently, and these are commonly delivered with infusion pump systems. In particular, critically ill patients receive potent "high-alert" IV drugs, many with narrow safety margins requiring careful nursing titration. However, while intravenous medications have important benefits, errors associated with IV medication administration can result in severe or life-threatening adverse drug events (ADEs). Although errors in prescribing are often intercepted, administration errors do not get caught with most current systems While several safety improvements in IV infusion pump design have reduced mechanical complications, errors with IV drug administration such as incorrect programming persist. Intelligent IV infusion pumps have integrated software to provide point of care decision support (DS). This software includes drug library profiles configured for specific patient care units and includes programming of safety limits for drug/dose calculations.

Decision Making, Computer-Assisted↗
PubMed2002

Metabolism of a thiazole benzenesulfonamide derivative, a potent and elective agonist of the human beta3-adrenergic receptor, in rats: identification of a novel isethionic acid conjugate.

(R)-N-[4-[2-[[2-Hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]- 4-[4-(4-trifluoro-methylphenyl)thiazol-2-yl]benzenesulfonamide (1) is a potent and selective agonist of the human beta3-adrenergic receptor. We report herein the data from studies of the metabolism and excretion of 1 in rats. Five metabolites were identified in the bile of male Sprague-Dawley rats administered 3H-labeled 1 by either oral gavage (10 mg/kg) or intravenous injection (3 mg/kg). These included a pyridine N-oxide derivative (M2), a primary amine resulting from N-dealkylation and loss of the pyridinyl-2-hydroxyethyl group (M4), a carboxylic acid derived from N-dealkylation and loss of the pyridyl-2-hydroxyethyl amine (M5), and the corresponding taurine and isethionic acid conjugates (M1 and M3). Metabolites M1 and M3 also were identified in rats treated with M5 and were generated in incubations of M5 with rat liver subcellular fractions in the presence of ATP and coenzyme A with supplementary taurine or isethionic acid. These results suggest that M5 is the precursor of M1 and M3 and that the formation of these conjugated metabolites follows similar mechanisms of amino acid conjugation. On the other hand, M2, M4, and M5 were produced from 1 in an NADPH-dependent manner in incubations with liver microsomes from rats, dogs, monkeys, and humans. In human liver preparations, these routes of biotransformation were shown to be catalyzed by cytochrome P450 3A4. In a bidirectional transport assay, transport of 1 across a monolayer of cells expressing P-glycoprotein (Pgp) was observed to be similar to that of vinblastine, which is an established substrate of the transporter protein. This finding, together with the observation that the parent compound was excreted in the feces of bile duct-cannulated animals following intravenous dosing, suggests that 1 is subject to Pgp-mediated excretion from intestine of rats.

Adrenergic beta-3 Receptor Agonists↗
PubMedDate not supplied

Intravenous medication safety and smart infusion systems: lessons learned and future opportunities.

The Institute of Medicine report To Err Is Human: Building a Safe Health System greatly increased national awareness of the need to improve patient safety in general and medication safety in particular. Infusion-related errors are associated with the greatest risk of harm, and "smart" (computerized) infusion systems are currently available that can avert high-risk errors and provide previously unavailable data for continuous quality improvement (CQI) efforts. As healthcare organizations consider how to invest scarce dollars, infusion nurses have a key role to play in assessing need, evaluating technology, and selecting and implementing specific products. This article reviews the need to improve intravenous medication safety. It describes smart infusion systems and the results they have achieved. Finally, it details the lessons learned and the opportunities identified through the use of smart infusion technology at Brigham and Women's Hospital in Boston, Massachusetts.

Humans↗