Dean S. Collier

From professional silos to interprofessional education: campuswide focus on quality of care.

Objectives The Institute of Medicine called for the integration of interprofessional education (IPE) into health professions curricula, in order to improve health care quality. In response, we developed, implemented, and evaluated a campus wide IPE program, shifting from traditional educational silos to greater collaboration. Methods Students (155) and faculty (30) from 6 academic programs (nursing, medicine, public health, allied health, dentistry, and pharmacy) engaged with a university hospital partner to deliver this program. The content addressed principles of IPE, teamwork development and 2 common quality care problems: hospital-acquired infections and communication errors. Pre-/post-surveys, the Readiness for Interprofessional Learning Scale, and the Interprofessional Education Perception Scale, were used for descriptive assessment of student learning. Results Students demonstrated increased understanding of health care quality and interprofessional teamwork principles and reported positive attitudes toward shared learning. While responses to the Readiness for Interprofessional Learning Scale grew more positive after the program, scores on the Interprofessional Education Perception Scale were more homogeneous. Both students and faculty highly evaluated the experience. Conclusion This program was a first step in preparing individuals for collaborative learning, fostering awareness and enthusiasm for IPE among students and faculty, and demonstrating the feasibility of overcoming common barriers to IPE such as schedule coordination and faculty buy-in.

Extracorporeal liver perfusion using human and pig livers for acute liver failure.

Background. Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation.Extracorporeal liver perfusion (ECLP) has been proposed as a method of “bridging” such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure. Methods. Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver. Findings. Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully “bridged” to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 &mgr;mol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 &mgr;mol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit. Interpretation. These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.

Omeprazole pharmacodynamics and gastric acid suppression in critically ill pediatric transplant patients.

Objective To characterize the pharmacodynamics and pharmacokinetics of omeprazole suspension in critically ill pediatric liver/intestinal transplant patients. Design Open-label pharmacodynamic and pharmacokinetic study. Setting Pediatric intensive care unit of an academic medical center. Patients Eleven pediatric liver and/or intestinal transplant patients. Interventions Extemporaneously prepared 0.5 mg/kg omeprazole suspension every 12 hrs via nasogastric tube before sequential measurements of omeprazole serum concentration and gastric pH monitoring. Gastric pH was monitored continuously for 48 hrs and plasma omeprazole concentrations were determined upon first and multiple dosing. Measurements and Main Results Mean onset of action of omeprazole in a sodium bicarbonate vehicle was 62 ± 82 mins (range, 2–226 mins). Subjects <4 yrs of age exhibited a more variable onset of omeprazole action (range, 3–226 mins) when compared with older subjects (onset of action, 2–40 min). Omeprazole maximum concentration and area under the concentration-time curve for the dosage interval were significantly greater upon multiple dosing when compared with the first dose. Mean baseline gastric pH in this study population was 1.0 ± 0.8. Gastric pH remained >4.0 for 78.8% ± 18.9% of the first dosage interval and 97.8% ± 5.4% of multiple dosage intervals regardless of age when administered twice daily as a suspension. Conclusion These results support the use of omeprazole administered twice daily as a suspension to maintain gastric pH of >4.0 and to achieve maximal pharmacodynamic effect in pediatric liver and/or intestinal transplant patients.

Rurality and other factors associated with adherence to immunosuppressant medications in community-dwelling solid-organ transplant recipients

BACKGROUND Data on immunosuppressant adherence of community-dwelling adult solid-organ transplant recipients (SOTRs) from rural populations in the United States are limited. Therefore, understanding the association of rurality and other factors of immunosuppressant adherence will help providers design and deliver patient-centered adherence enhancing interventions. OBJECTIVES The objective was to examine factors associated with a previously validated 4-item Immunosuppressant Therapy Adherence Scale (ITAS) score in community-dwelling adult SOTRs who received a transplant from an academic center in the Midwestern United States. METHODS For this observational study, cross-sectional survey data (patient demographic, medical condition, immunosuppressant therapy, and self-reported ITAS) received from adult SOTRs aged 19 years or older with other data from an academic transplant centers database were merged. Using multivariate logistic regression, significant SOTR characteristics associated with being adherent (ITAS score=12) versus nonadherent (ITAS score <12) were examined. RESULTS The survey response rate was 30% (n=556/1827). Those SOTRs responding (n=556) had a kidney (48%), liver (47%), or other (4.5%) transplant. They were more likely to be 50- to 64-year olds (52%), men (55%), white (90%), metroresident (59%), with an annual income less than

Parkinsonism Treatment: Part III—Update

55,000. The SOTRs were living with a transplant for 6.3 years (median), reported excellent-to-good health status (77%), and received different immunosuppressant regimens. More than half of the SOTRs (58%) were adherent. In multivariate analyses, compared with patients aged 65 years or older, younger patients, nonmetro rural- versus metroresident, and those having more (≥6) versus less (<6) comorbidities were significantly less likely to report adherence. SOTRs receiving tacrolimus-based combination immunosuppressant versus tacrolimus alone were more likely to report adherence. CONCLUSIONS When designing and delivering patient care-centered interventions including those that use technology to increase immunosuppressant adherence, providers need to consider rural residence besides other well-established patient factors (younger age, immunosuppressant drug, and comorbidities) of nonadherence.

Effect of omeprazole, lansoprazole, and ranitidine on the dna synthesis of mononuclear cells

OBJECTIVE: The purpose of this review is to update clinicians with recent advances in the management of parkinsonism, including drug therapy, transplantation, and diet. DATA SOURCES: Pertinent articles were obtained from an English-language literature search using MEDLINE (1970–1991), Index Medicus (1987–1991), Current Contents (1990), and bibliographic reviews of review articles. Index terms included parkinsonism, selegiline, pergolide, vitamin E, and transplantation. Fifty-five articles (representing 85 percent of the complete literature search) were selected by multiple reviewers for their contribution to the stated purpose. Emphasis was placed on double-blind, placebo-controlled, and randomized studies. Data from cited articles were examined by multiple reviewers for support of their stated hypothesis and were included as background for justification of major points in this article; critical studies were abstracted in more detail. RESULTS: New therapeutic measures have been added to the treatment of parkinsonism. Selegiline, a monoamine oxidase inhibitor type B, has shown beneficial results, especially in early stages. Pergolide, a dopamine agonist, may be an efficacious alternative to bromocriptine resistance or intolerable adverse effects. Vitamin E may have protective antioxidant properties, but very few clinical data are available. Fetal tissue transplantation needs continued research and remains very controversial. Diet modification may maximize the results of therapy with exogenous dopamine therapy. CONCLUSIONS: Clinicians should familiarize themselves with new alternatives for the management of parkinsonism in order to be reliable consultants for both professional and lay persons.

Evaluation of the pharmacokinetic interaction between cimetidine or famotidine and cyclosporine in healthy men.

OBJECTIVE To examine and compare the effects of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of peripheral blood mononuclear cells. DESIGN Ex vivo laboratory study. SETTING Clinical research laboratory of an academic medical center. SUBJECTS Healthy volunteers. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Venous blood was collected from normal subjects and peripheral blood mononuclear cells (PBMCs) were isolated using centrifugation techniques over a Ficoll-Hypaque density gradient. PBMCs were added to 12-well culture plates in four groups of media: a) control; b) control plus lansoprazole (25 microg/mL); c) control plus omeprazole (0.35 microg/mL); and d) control plus ranitidine (50 microg/mL). PBMCs were exposed to the drug for 96 hrs, with addition of phytohemagglutinin (2.5 microg/ mL) for the last 48 hrs, and 3H-thymidine (1 microCi) during the final 6 hrs. PBMCs were filtered onto glass-fiber filter paper and the radioactivity was determined by scintillation counting. Since radioactivity is measured only in those cells undergoing DNA synthesis or cell division, results are expressed as quantification of 3H-thymidine uptake. Median disintegrations per min (DPM)/number of PBMCs per well+/-SEM are reported: control 68.3+/-37.8; ranitidine 38.4 +/-94.2; lansoprazole 14.6+/-84.4; and omeprazole 15.1+/-48.9. There was a significant difference between lansoprazole vs. ranitidine (p< .01), and omeprazole vs. ranitidine (p< .05), and no significant difference between lansoprazole and omeprazole. CONCLUSIONS This is the first study to compare the potential immunomodulating effects of these commonly used agents. Ranitidine caused increased DNA synthesis in PBMCs when compared with lansoprazole and omeprazole. This phenomenon may be an important, often disregarded, effect of histamine-2-receptor antagonists when used in postsurgical or trauma patients who have T-lymphocyte-mediated immune suppression.

Clinical Pharmacokinetic and Pharmacodynamic Monitoring for Mycophenolate Mofetil

Objective: To investigate the potential interaction between cimetidine or famotidine and cyclosporine in healthy men. Design: All subjects received oral cyclosporine at baseline, after the first week of 1 histamine2 (H2)-blocker, and a third time after a 1-week washout plus 1 week of the second H2-blocker. Blood samples were collected just before each dose of cyclosporine and for up to 36 hours afterward for pharmacokinetic analysis. Setting: A college of pharmacy in a university teaching hospital. Participants: The study population consisted of 8 healthy men at least 19 years of age. Main Outcome Measures: Cyclosporine concentrations in whole blood were measured using a polyclonal fluorescence polarization immunoassay. Cyclosporine pharmacokinetic parameters during each of the 3 treatment periods were compared. Results: The average times to maximum cyclosporine concentrations were similar between baseline (3.2 h), cimetidine (2.9 h), and famotidine (3.6 h) dosing periods. There were no significant differences in area under the curve, half-life, or maximum concentration during the 3 dosing periods. Conclusions: Neither cimetidine or famotidine produced a significant change in the pharmacokinetics of single-dose oral cyclosporine in healthy men.

Advancing Interprofessional Education: A Qualitative Analysis of Student and Faculty Reflections

The use of mycophenolate mofetil (MMF), in combination with cyclosporine (CsA) or tacrolimus (FK) and corticosteroids, has been shown to improve clinical outcomes through significant reduction in the incidence of acute rejection in solid organ transplant patients. A fixed oral dosing regimen of 1 or 1.5 g MMF twice daily received Food and Drug Administration approval in 1995 with no recommendations for concentration monitoring at that time. Subsequent evidence has generated substantial debate on the need of clinical monitoring for MMF. This article summarizes the rationale, evidence, and approaches of clinical monitoring for MMF. Mycophenolic acid (MPA), the active moiety of MMF, noncompetitively inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH), which is the target enzyme for MPA. Pharmacokinetic monitoring, by use of MPA predose or MPA area under the concentration-time curve (AUC) values, and pharmacodynamic monitoring by analysis of inhibition of IMPDH have been evaluated in organ transplant patients. The possibility of drug interactions between other immunosuppressive agents has also received attention recently. The clinical implications of drug interactions are discussed in this article.

Proton pump inhibitors and acute kidney injury: a nested case–control study

Interprofessional education (IPE) is imperative when training health professions students to practice in an environment requiring a team based approach. IPE has not been widely practiced in the United States (US) since its immergence in the 1970’s and waning in the 1980’s.Contemporary curricula, instruction, and IPE activities still need to be tested. This report focuses on the analysis of qualitative feedback collected from faculty and students participating in IPE activities, designed for first year health professions students in the Fall 2010 (n=542), and Fall 2011 (n=555). An interprofessional research team conducted analysis using an immersion/crystallization framework. Eight major themes emerged from comments provided through evaluations of the IPE activities. Students expressed a desire to learn more about roles, skills, and responsibilities of other professions and wanted additional IPE opportunities integrated throughout their education. Skill level of small IPE group facilitators emerged as an important component for successful IPE activities. Lessons learned through this analysis will guide future augmentation of interprofessional activities locally and can be applied at other medical campuses.