Vision 2020 measures University of New Mexico's success by health of its state.

The University of New Mexico Health Sciences Center (UNMHSC) adopted a new Vision to work with community partners to help New Mexico make more progress in health and health equity than any other state by 2020. UNMHSC recognized it would be more successful in meeting communities' health priorities if it better aligned its own educational, research, and clinical missions with their needs. National measures that compare states on the basis of health determinants and outcomes were adopted in 2013 as part of Vision 2020 target measures for gauging progress toward improved health and health care in New Mexico. The Vision focused the institution's resources on strengthening community capacity and responding to community priorities via pipeline education, workforce development programs, community-driven and community-focused research, and community-based clinical service innovations, such as telehealth and "health extension." Initiatives with the greatest impact often cut across institutional silos in colleges, departments, and programs, yielding measurable community health benefits. Community leaders also facilitated collaboration by enlisting University of New Mexico educational and clinical resources to better respond to their local priorities. Early progress in New Mexico's health outcomes measures and state health ranking is a promising sign of movement toward Vision 2020.

Preparing clinical pharmacy scientists for careers in clinical/translational research: can we meet the challenge?: ACCP Research Affairs Committee Commentary.

Developing clinical pharmacists' research skills and their ability to compete for extramural funding is an important component of the American College of Clinical Pharmacy's (ACCP) vision for pharmacists to play a prominent role in generating the new knowledge used to guide patient pharmacotherapy. Given the recent emphasis on clinical/translational research at the National Institutes of Health (NIH) and the key role of drug therapy in the management of many diseases, there is an unprecedented opportunity for the profession to contribute to this enterprise. A crucial question facing the profession is whether we can generate enough appropriately trained scientists to take advantage of these opportunities to generate the new knowledge to advance drug therapy. Since the 2009 publication of the ACCP Research Affairs Committee editorial recommending the Ph.D. degree (as opposed to fellowship training) as the optimal method for preparing pharmacists as clinical/translational scientists, significant changes have occurred in the economic, professional, political, and research environments. As a result, the 2012 ACCP Research Affairs Committee was charged with reexamining the college's position on training clinical pharmacy scientists in the context of these substantial environmental changes. In this commentary, the potential impact of these changes on opportunities for pharmacists in clinical/translational research are discussed as are strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. Failure of our profession to take advantage of these opportunities risks our ability to contribute substantively to the biomedical research enterprise and ultimately improve the pharmacotherapy of our patients.

Building a multi-institutional community of practice to foster assessment.

This paper discusses the development of a multi-institutional community of practice that formed over 5 years. This community of practice was intentionally designed to support the evolution of student learning and programmatic assessment within member colleges and schools. Critical phases to the community's development are outlined, as well as its mission and goals. In addition, the community's contributions to faculty development and the scholarship of assessment are detailed. Success factors are discussed to assist others who may wish to initiate assessment-related collaborations across institutional borders. The community's vision for the future is also outlined.

Does body weight impact the efficacy of vasopressin therapy in the management of septic shock?

BACKGROUND: Vasopressors used for the management of septic shock are often dosed according to body weight. Use of vasopressin for physiologic replacement in patients with septic shock is usually administered as a standard non-weight-based dose. We hypothesized that the efficacy of vasopressin may be influenced by body weight. PURPOSE: The primary objective was to determine if the effects of vasopressin on other vasopressor dosing requirements is related to body weight. Secondary objectives included evaluation of blood pressure and heart rate after the start of vasopressin infusion. METHODS: A retrospective, cohort study in a large academic health center was conducted. Sixty-four adult inpatients with septic shock (26 medical intensive care unit and 38 surgical intensive care unit) who required vasopressor administration including vasopressin therapy were included. Dosing requirements of vasopressors were captured 1 hour before and during the hour of vasopressin initiation and 2 and 4 hours later. Other information collected during the study period included blood pressure, mean arterial pressure, and heart rate. RESULTS: Most of the patients (n = 61) received vasopressin at a dose of 0.04 U/min. Changes in vasopressor dosing were significantly correlated with weight-adjusted vasopressin at 2 hours (correlation coefficient = -0.36, P = .03) and 4 hours (correlation coefficient = -0.46, P < .001). Use of vasopressin was associated with significant increases in systolic blood pressure, diastolic blood pressure, and mean arterial pressure at each time point compared with baseline. CONCLUSIONS: Effects of vasopressin on catecholamine dosing requirements in the setting of septic shock may be influenced by body weight. Prospective studies are needed to examine weight-based dosing of vasopressin in this setting.

Cardiovascular risk among university students from developed and developing nations.

BACKGROUND: A key aspect in halting global increase in cardiovascular events is prevention and especially prevention at an early age. Unfortunately, global data regarding cardiovascular risk factors in the young are limited. Therefore the objectives of this study were to identify the most common cardiovascular risk factors among young adults in a university setting in both developed and developing countries. METHODS: Lifestyle and cardiovascular risk factors (smoking status, rates of physical activity, alcohol use, family history, blood pressure, fasting lipid panel, fasting blood glucose) were prospectively evaluated in young adults at three different university settings [University of Michigan (Ann Arbor, USA), University of Kalamoon (Deratiah, Syria), and Kakatiya University (Warangal, India)]. RESULTS: A total of 296 subjects (mean age and standard deviation 22 ± 3 years) were evaluated. Rates of current smoking were markedly higher (p < 0.001) in Syria (43%) compared with the USA (6.2%) and India (1.7%). Subjects in India were significantly (p < 0.001) less likely to engage in physical activity (20.2%) compared with the USA (90.7%) and Syria (68.8%). Fasting blood glucose levels and body mass index were significantly higher (p < 0.001) in Syria as compared to other countries. Significant differences were also noted in LDL, HDL, and triglycerides among the three sites. CONCLUSIONS: Cardiovascular risk factors among young adults in a university setting vary depending on global setting. Based upon the results of this study, targeted interventional programs based on risk findings from individual countries may be a reasonable future strategy to help reduce long term cardiovascular morbidity and mortality.

Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine.

Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used beta-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4-phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate-release (IR) tartrate and extended-release (ER) succinate metoprolol formulations. Ten healthy participants received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol area under the plasma concentration-time curve from time 0 to the 24-hour blood draw (AUC(0-24h)) by 4- and 5-fold, respectively for IR, and 3- and 4-fold, respectively, for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol, and stereoselective metabolism is lost. This could theoretically result in greater beta-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses/drug input rates employed.

The impact of paroxetine coadministration on stereospecific carvedilol pharmacokinetics.

STUDY OBJECTIVE: to assess the impact of paroxetine coadministration on the stereoselective pharmacokinetic (PK) properties of carvedilol. DESIGN: prospective, randomized, 2-phase crossover. SETTING: the University of Michigan General Clinical Research Unit and Michigan Clinical Research Unit. PARTICIPANTS: twelve healthy volunteers aged 18 to 45 years, male and female, receiving no treatment with prescription or nonprescription medications. INTERVENTIONS: participants received single dose oral carvedilol (12.5 mg) with and without coadministration of immediate-release paroxetine (10 mg orally twice daily), in random order. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 hours post-carvedilol dose for determination of R and S carvedilol plasma enantiomer concentrations by high pressure liquid chromatography. MEASUREMENTS AND MAIN RESULTS: pharmacokinetic (PK) parameters were calculated for each enantiomer by noncompartmental methods and compared between study phases by analysis of variance (ANOVA) controlling for study phase order and subject, with Tukey's studentized range test post hoc. Area under the concentration-time curve (AUC) increased significantly with paroxetine coadministration, approximately 2.5-fold and 1.9-fold for the R and S enantiomers, respectively. R/S AUC ratio increased significantly, from approximately 2.3 to 3.0. Individual increases in enantiomeric AUCs with paroxetine coadministration ranged from 0% to 571% and changes in R/S ratio ranged from -8% to 108%. Heart rate, P-R interval, and blood pressure were monitored and no clinically significant changes in carvedilol effects were noted. CONCLUSION: this study demonstrated a PK drug-drug interaction between paroxetine and carvedilol, with considerable interparticipant variability in carvedilol PK parameters and magnitude of drug interaction. Stereoselectivity of carvedilol metabolism is preserved with paroxetine coadministration, and R/S AUC ratio generally widens. Although this drug interaction could potentially increase adrenergic antagonism and have significant clinical effects in patients, these effects were not seen in our healthy volunteer participants.

Key articles and guidelines relative to intensive care unit pharmacotherapy: 2009 update.

Compilations of key articles and guidelines in a particular clinical practice area are useful not only to clinicians who practice in that area, but also to all clinicians. We compiled pertinent articles and guidelines pertaining to drug therapy in the intensive care setting from the perspective of experienced critical care pharmacists. A broad assembly of practitioners with expertise in various areas of intensive care unit pharmacology were involved in the compilation of this update.

Intestinal dipeptide absorption is preserved during thermal injury and cytokine treatment.

BACKGROUND: Intestinal barrier function is impaired during thermal injury; however, the effects of thermal injury on the absorption of dietary peptides are not well characterized. The purpose of this study was to determine the impact of thermal injury on dipeptide absorption in rats and to describe the influence of inflammatory cytokines on the expression of the oligopeptide transporter PEPT1 and dipeptide permeability in cultured intestinal cells (Caco-2 cells). METHODS: Sprague Dawley rats were assigned to 30% body surface area burn (n = 7) or sham (n = 8) groups. Twenty-four hours following burn/sham, the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing the dipeptide glycylsarcosine (Gly-Sar), and intestinal permeability (P(eff)) was calculated. For in vitro experiments, Caco-2 cells were grown on permeable supports and treated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 (10 ng/mL) alone and in combination for 48 hours. The effective apical-to-basolateral permeabilities (P(eff)) of Gly-Sar were measured, and PEPT1 expression was determined using reverse transcription-polymerase chain reaction. RESULTS: Gly-Sar P(eff) was similar in burn and sham rats (6.67 +/- 2.27 x 10(-5) vs 7.58 +/- 2.20 x 10(-5) cm/s, respectively, P = .45). In Caco-2 cells, cytokine treatment did not alter PEPT1 expression (P = .954) or the P(eff) of Gly-Sar (P = .806). CONCLUSIONS: Intestinal absorption of the dipeptide Gly-Sar is preserved 24 hours following thermal injury in rats. Likewise, PEPT1 expression and peptide absorption are preserved following treatment with TNF-alpha, IL-6, and IL-10 in Caco-2 monolayers. These findings imply that intestinal dipeptide absorption may be preserved during burn injury. This may lead to new strategies to optimize enteral protein delivery in burn patients.

Continuous infusion of pantoprazole with octreotide does not improve management of variceal hemorrhage.

STUDY OBJECTIVE: To assess the effect of a prolonged continuous infusion of pantoprazole on patient outcomes when the drug was combined with standard octreotide therapy in patients with variceal hemorrhage. DESIGN: Retrospective cohort study. SETTING: Large academic hospital. Patients. One hundred thirty adults who received treatment for a documented variceal hemorrhage; 53 patients received standard octreotide therapy plus a prolonged continuous infusion of pantoprazole (continuous-infusion group) and 77 patients received either octreotide alone, octreotide with a short-term (<24 hrs) infusion of pantoprazole, or octreotide with intermittent acid suppression (control group). MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the number of units of packed red blood cells transfused during hospitalization. Baseline characteristics between the treatment groups were similar. The duration of therapy for variceal hemorrhage was significantly longer in the continuous-infusion group than in the control group. Transfusion requirements for packed red blood cells (mean+/-SD 6.4+/-6.5 vs 5.8+/-6.6 units, p=0.66) and platelets (8.8+/-15.1 vs 5.1+/-11.9 units, p=0.13) were similar for the continuous-infusion group versus the control group. The continuous-infusion group, however, received significantly more units of fresh-frozen plasma than the control group (6.1+/-10.6 vs 2.9+/-6.2 units, p=0.05). There was no significant difference in mortality rate between groups. CONCLUSION: Prolonged continuous infusions of pantoprazole with octreotide seemed to offer no additional benefit compared with octreotide plus short-term infusions of pantoprazole or intermittent acid suppression in the management of acute variceal hemorrhage. Prospective studies should be conducted to evaluate the role of continuously infused proton pump inhibitors in this setting before their use can be advocated.

Lack of interaction between the peptidomimetic substrates captopril and cephradine.

Intestinal peptide transporters, including hPEPT1, facilitate the absorption of cephalosporins and angiotensin-converting enzyme inhibitors, and have been investigated as a means to improve oral drug absorption. Renal peptide transporters including hPEPT2, may also facilitate renal reabsorption of such compounds. In vitro and animal studies suggest that co-administration of peptidomimetic compounds may alter oral pharmacokinetics, although this has not been well studied in humans. The purpose of this study was to determine whether co-administration of the hPEPT substrates captopril and cephradine alters the oral pharmacokinetics of either agent. Nine healthy male volunteers received a single oral 25-mg dose of captopril, a single oral 500-mg dose of cephradine, or concurrent ingestion of captopril and cephradine in a cross-over manner. Venous blood samples were taken and captopril and cephradine pharmacokinetics were determined using noncompartmental analyses. No significant differences were observed in captopril or cephradine pharmacokinetics when administered together as compared to each agent alone (a marginal decrease in C(max) was observed for both captopril and cephradine during co-administration [5-15%]; however, differences were not statistically significant). The results of our study suggest that hPEPT1 and hPEPT2 are unlikely to contribute to clinically important drug interactions in humans.

Interferon-gamma increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers.

The di/tri-peptide transporter h-PEPT1 plays an important role in the oral absorption of di/tri-peptides and numerous drugs. Inflammatory conditions may influence intestinal xenobiotic transporter function; however, the effects of inflammation on h-PEPT1 have not been well described. This study was conducted to determine the effects of the inflammatory cytokine interferon-gamma (IFN-gamma) on h-PEPT1 mediated dipeptide absorption. Caco-2 monolayers were grown on permeable supports. The effective apical-to-basolateral permeability (P(eff)) of glycylsarcosine (Gly-Sar) was measured following incubation with IFN-gamma or control media. Additional experiments were conducted at 4 degrees C, and with escalating concentrations of Gly-Sar. h-PEPT1 expression was determined using semiquantitative RT-PCR. IFN-gamma 50 ng/ml increased Gly-Sar P(eff) 28.6% compared to controls (p=0.03). In experiments conducted at 4 degrees C, Gly-Sar P(eff) decreased 39.6% in IFN-gamma treated cells (p=0.003) and 28.4% in controls (p=0.006). In controls and IFN-gamma treated cells, concentration dependent transport was seen with escalating concentrations of Gly-Sar. Compared to controls, IFN-gamma 50 and 100 ng/ml increased h-PEPT1 mRNA expression by 14.2% and 11.5%, respectively (p=0.019). In summary, IFN-gamma increases h-PEPT1 expression and permeation of the dipeptide Gly-Sar in Caco-2 monolayers. These findings imply that intestinal absorption of peptides and peptidomimetic drugs may be increased in certain inflammatory conditions.

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

Proton pump inhibitor formulary considerations in the acutely ill. Part 2: Clinical efficacy, safety, and economics.

OBJECTIVE: To review, using an evidence-based approach, the clinical efficacy, safety, and cost-effectiveness of proton pump inhibitors (PPIs) for treatment of common acid peptic disorders in the acutely ill and provide clinicians with guidance when making hospital formulary decisions with this class of agents. DATA SOURCES: MEDLINE (1966-May 2005) and the Cochrane Library databases were searched using the key words proton pump inhibitor, acid suppression, peptic ulcer disease, gastrointestinal bleeding, stress ulcer prophylaxis, critical care, safety, and cost-effectiveness. Bibliographies of cited references were reviewed, and a manual search of abstracts from recent gastroenterology, critical care, and surgery scientific meetings was completed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review. DATA SYNTHESIS: PPIs have become a mainstay for acute acid suppression in hospitalized patients. Various commercially available PPI products are available either enterally or parenterally for administration to patients unable to swallow a tablet or capsule. The results of studies comparing the clinical efficacy of different PPI dosage forms and routes of administration, safety considerations, and cost-effectiveness analyses are among the factors to consider when making formulary decisions for this class of drugs. CONCLUSIONS: While the introduction of new PPI products has expanded the therapeutic options for acid suppression in acutely ill patients, a number of unresolved questions remain surrounding the interchangeability of these products, the clinical significance of one PPI formulation over the other, and how oral/enteral therapy should be used as step-down therapy after parenteral therapy.

Proton pump inhibitor formulary considerations in the acutely ill. Part 1: Pharmacology, pharmacodynamics, and available formulations.

OBJECTIVE: To review important proton pump inhibitor (PPI) pharmacologic, pharmacokinetic, and pharmacodynamic principles in acutely ill patients, compare PPI formulation options for patients unable to swallow a tablet or capsule, and provide clinicians with guidance when making hospital formulary decisions with this class of agents. DATA SOURCES: MEDLINE (1966-May 2005) and the Cochrane Library databases were searched using the key words proton pump inhibitor, acid suppression, peptic ulcer disease, gastrointestinal bleeding, stress ulcer prophylaxis, and critical illness. Bibliographies of cited references were reviewed, and a manual search of abstracts from recent gastroenterology, critical care, and surgery scientific meetings was completed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review. DATA SYNTHESIS: PPIs have become a mainstay for acute acid suppression in hospitalized patients over other therapeutic options. Various commercially available PPI products are available for administration, either enterally or parenterally, to patients unable to swallow a tablet or capsule. Newer oral PPI formulations offer numerous advantages over older products. The results of studies comparing the pharmacokinetics and pharmacodynamics of different PPI dosage forms and routes of administration are among the factors to consider when making formulary decisions. CONCLUSIONS: While the introduction of new PPI products has expanded the therapeutic options for acid suppression in acutely ill patients, a number of unresolved questions remain surrounding the interchangeability of these products, the clinical significance of one PPI formulation over the other, and how oral/enteral PPI therapy should be used as step-down therapy after parenteral PPI therapy.

Key articles and guidelines relative to intensive care unit pharmacology--2004.

Compilations of key articles and guidelines in a particular clinical practice area are useful not only to clinicians who practice in that area, but to all clinicians. We compiled pertinent articles and guidelines pertaining to drug therapy in the intensive care setting from the perspective of actively practicing critical care pharmacists. This document differs from the original 2002 version in that a broader assembly of intensive care practitioners was involved in the compilation.