Kimmel S.E.,University of Pennsylvania |
French B.,University of Pennsylvania |
Kasner S.E.,University of Pennsylvania |
Johnson J.A.,University of Florida |
And 27 more authors.
New England Journal of Medicine | Year: 2013
BACKGROUND: The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results. METHODS: We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy. RESULTS: At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy. CONCLUSIONS: Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. Copyright © 2013 Massachusetts Medical Society.
Anderegg S.V.,Georgia Regents Medical Center |
Anderegg S.V.,University of Kansas |
Wilkinson S.T.,Pharmacy |
Couldry R.J.,Pharmacy |
And 2 more authors.
American Journal of Health-System Pharmacy | Year: 2014
Purpose: The impact of an innovative medication reconciliation and discharge education program on 30-Day readmissions and emergency department (ED) visits was evaluated.Methods: An observational pre-post analysis was conducted at an academic medical center to compare rates of hospital readmissions and return to ED visits during three-Month periods before and after implementation of a restructured pharmacy practice model including (1) medication reconciliation at transitions of care for every patient and discharge education for a high-risk subgroup, (2) new or expanded services in the preanesthesia testing clinic and ED, (3) a medication reconciliation technician team, and (4) pharmacist-topatient ratios of 1:30 on acute care floors and 1:18 on critical care units. The primary outcome was the composite of rates of readmissions and return to ED visits within 30 days of discharge.Results: A total of 3,316 patients were included in the study. Pharmacy teams completed medication reconciliation in 95.8% of cases at admission and 69.7% of cases at discharge. Discharge education was provided to 73.5% of high-risk patients (defined as those receiving anticoagulation therapy or treatment for acute myocardial infarction, chronic obstructive pulmonary disease, congestive heart failure, or pneumonia). No significant difference was observed between the preimplementation and postimplementation groups with regard to the primary outcome. In the high-risk subgroup, there was a significant reduction in the 30-Day rate of hospital readmissions, which declined from 17.8% to 12.3% (p = 0.042); cost projections indicated that this reduction in readmissions could yield annual direct cost savings of more than $780,000.Conclusion: Implementation of a teambased pharmacy practice model resulted in a significant decrease in the rate of 30-Day readmissions for high-risk patients. © 2014, American Society of Health-System Pharmacists, Inc.
Campbell C.T.,Georgia Regents Medical Center |
Campbell C.T.,University of Georgia |
McCaleb R.,University of Arkansas for Medical Sciences |
Manasco K.B.,University of Georgia
Annals of Pharmacotherapy | Year: 2016
Objective: To review the current literature on inhaled antibiotic therapies currently in clinical trials for cystic fibrosis (CF) patients. Data Sources: A literature search was performed using PubMed (1975 to September 2015), International Pharmaceutical Abstracts (1970 to September 2015), and MEDLINE (1946 to September 2015) to identify studies for inclusion. The following search terms were used: cystic fibrosis, inhaled amikacin, inhaled liposomal amikacin, inhaled vancomycin, and/or inhaled levofloxacin. Study Selection and Data Extraction: All English-language phase II to III studies evaluating efficacy and/or safety, case reports, and retrospective studies of inhaled amikacin, inhaled vancomycin, and inhaled levofloxacin in CF patients were included. Data Synthesis: Currently available inhaled antibiotics, tobramycin and aztreonam, have demonstrated improvement in respiratory function of CF patients. Newer agents have shown potentially similar efficacy, with improvement in ease of use. Limited data suggest that inhaled liposomal amikacin and levofloxacin are both noninferior to tobramycin in terms of improvements in respiratory function. Inhaled levofloxacin has a lower rate of hospitalizations secondary to respiratory exacerbations and a reduction in the Pseudomonas aeruginosa sputum density compared with inhaled tobramycin. Inhaled vancomycin use has been documented in case reports and 2 small retrospective eradication trials, although data are limited to support its use. Conclusions: The horizon of inhaled antibiotic choices for CF patients is promising. The introduction of different drug classes and formulations to treat resistant Gram-negative and Gram-positive organisms increases the number of options for patients for both eradication and treatment of chronic colonization. © 2015, © The Author(s) 2015.
Hartranft M.E.,Georgia Regents Medical Center |
Regal R.E.,University of Michigan
Annals of Pharmacotherapy | Year: 2014
Objective: To describe the treatment of a case of olmesartan-induced enteropathy in a patient with inflammatory areas widely distributed along the gastrointestinal tract. Case Summary: A 75-year-old patient presented with a 5-month history of recurrent severe diarrhea, diagnosed as olmesartan-induced enteropathy. A modified regimen of oral enteric-coated budesonide (EC-BUD), in combination with other antidiarrheal and anti-inflammatory therapies, was prescribed. The patient experienced rapid improvement in symptoms and was able to titrate off all enteropathy medications, including budesonide within 4 months after hospital discharge. Discussion: Olmesartan-induced enteropathy is a recently identified adverse effect of this angiotensin II receptor blocker. Oral budesonide is indicated for use in Crohn's disease to provide topical anti-inflammatory therapy without significant systemic steroid absorption. Budesonide, as enteric-coated oral 3-mg capsules, was chosen as therapy in this patient because of its localized effect and proven efficacy in gastrointestinal inflammatory disorders. The administration technique was modified to target areas of inflammation throughout the gastrointestinal tract. Conclusions: We postulate that this modified administration of EC-BUD may be an effective therapeutic modality for olmesartan-induced enteropathy. It may likewise be an appropriate adjunct to other conditions involving widespread gastrointestinal inflammation, including eosinophilic gastroenteritis and gastrointestinal graft versus host disease. © The Author(s) 2014.
Ploessl C.,Georgia Regents Medical Center |
Ploessl C.,University of Georgia |
White C.,Georgia Regents University |
Manasco K.,Georgia Regents Medical Center |
Manasco K.,University of Georgia
Pediatric Infectious Disease Journal | Year: 2015
Background: Vancomycin trough concentrations specific to pediatric patients have yet to be validated that achieve an area under the curve (AUC) over 24 hours to minimum inhibitory concentration (MIC) ratio ≥400. The primary objective of this study was to validate a pharmacokinetic model in a pediatric hospital and determine the correlation between a calculated AUC/MIC ratio and measured trough vancomycin concentration. Methods: A retrospective evaluation of patients aged 3 months to 18 years prescribed vancomycin at a pediatric hospital between January 2012 and June 2013. The correlation between patient-specific AUC/MIC and measured vancomycin trough concentration was assessed. Results: Forty pediatric patients with 40 vancomycin trough concentrations and documented Staphylococcus aureus cultures were included in the study. Median age was 8.5 (interquartile range, 2.14.3) years, median weight 28.7 (range, 14.50.2) kg, and mean baseline serum creatinine 0.51 ± 0.3 mg/dL. The mean daily dose of vancomycin prescribed was 58 ± 13.8 mg/kg/d. The mean vancomycin trough concentration was 11 ± 5.5 mcg/mL, and the mean AUC/MIC was 534 ± 373. No correlation was found between trough concentration and AUC/MIC (r2 = 0.082, p = 0.07). Conclusions: This study validates the clinical applicability of a pharmacokinetic model for calculating vancomycin clearance to determine patientspecific AUC over 24 hours in pediatrics. Trough concentrations associated with proposed therapeutic AUC/MIC ratios were lower than reported in the adult population. Further research is needed to determine if AUC/MIC, trough concentration, or both is best for monitoring therapeutic efficacy of vancomycin in pediatrics. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Shah A.,Georgia Regents Medical Center |
Mangaonkar A.,Georgia Regents Medical Center
The Annals of pharmacotherapy | Year: 2015
OBJECTIVE: To review and summarize data on idelalisib, which was approved by the Food and Drug Administration (FDA) in July 2014 for use in combination with rituximab for relapsed chronic lymphocytic leukemia (CLL).DATA SOURCES: A literature search using PubMed was conducted from January 2011 through May 2015 using the terms idelalisib, GS-101, CAL-101, PI3Kδ, and CLL. Data were also obtained through the FDA briefing documents, American Society of Clinical Oncology, and American Society of Hematology abstracts.STUDY SELECTION AND DATA EXTRACTION: The literature search was limited to human studies published in English. Priority was placed on trials of idelalisib in CLL.DATA SYNTHESIS: Idelalisib is a potent, first-in-class selective inhibitor of phosphatidylinositol-3-kinaseδ (PI3Kδ) approved by the FDA in July 2014 for the treatment of relapsed CLL, in combination with rituximab, in patients for whom rituximab monotherapy would be considered appropriate due to other comorbidities. PI3Kδ is hyperactivated in B-cell malignancies and plays a vital role in the B-cell receptor pathway, a key oncogenic driver in various B-cell malignancies, including CLL. Several phase I/II studies have demonstrated clinical activity of idelalisib in CLL, particularly in the setting of relapsed/refractory disease, with overall response rate ranging from 70% to 82%. The FDA approval was based on a phase III, randomized trial of rituximab monotherapy (n = 110) or idelalisib in combination with rituximab (n = 110) in heavily, pre-treated patients (median of 3 prior therapies) with relapsed CLL. Idelalisib was administered as 150 mg orally twice daily. Idelalisib plus rituximab was associated with an overall response rate of 81% and overall survival of 91% at 12 months. The median progression-free survival was not reached in the idelalisib arm at the time of the first interim analysis. The incidence of grade 3 or higher adverse events in the idelalisib plus rituximab arm was as follows: neutropenia (34%), thrombocytopenia (10%), anemia (5%), elevation in transaminases (5%), and diarrhea (4%).CONCLUSION: Idelalisib in combination with rituximab is a safe and effective new treatment option for patients with relapsed CLL, including those with poor prognostic factors. As the results from various ongoing studies become available, the role of idelalisib will likely continue to expand. © The Author(s) 2015.
Shumiloff N.A.,University of Georgia |
Lam W.M.,Georgia Regents Medical Center |
Manasco K.B.,University of Georgia
Annals of Pharmacotherapy | Year: 2013
Objective: To review the current literature on the efficacy and safety of low- versus high-dose adrenocorticotropic hormone (ACTH) regimens, low-dose ACTH regimens, and comparison of ACTH with oral corticosteroids or vigabatrin for the treatment of West syndrome. Data Sources: A literature search was performed using MEDLINE, PubMed, and Inter national Pharmaceutical Abstracts (1975-November 2012) to identify studies for inclusion. In addition, reference citations from identified publications were reviewed. The following search terms were used: infantile spasms, West syndrome, adrenocorticotropic hormone, corticotropin, symptomatic West syndrome, cryptogenic West syndrome, pediatric, children, infant, adolescent, and neonate. Study Selection and Data Extraction: Studies included in this article evaluated low-dose versus high-dose ACTH, low-dose ACTH, and ACTH compared with vigabatrin and oral corticosteroids. Data reporting the efficacy and adverse effects of ACTH, vigabatrin, and oral corticosteroids were extracted from each publication. Only English-language publications were included. We initially reviewed 20 studies, and 14 were included: 5 prospective randomized clinical trials and 9 chart reviews. Data Synthesis: West syndrome is an age-specific epileptic disorder that occurs in infancy and early childhood. It is characterized by the triad of infantile spasms, neurodevelopmental regression or delay, and hypsarrhythmia on electroencephalogram (EEG). The efficacy and adverse events of ACTH with different dosage regimens were reviewed and analyzed. ACTH compared with vigabatrin and oral corticosteroids was also evaluated. Based on this review, low-dose ACTH is probably as effective as high-dose ACTH. Compared with other agents, ACTH is suggested to be more effective than oral corticosteroids, and compared with vigabatrin, it has improved outcomes in the cessation of spasms. However, studies evaluating the efficacy of ACTH are limited by small sample size, inconsistent dosage regimens, and the use of synthetic or natural ACTH products. Serious adverse events, including intracranial hemorrhage, brain atrophy, Cushing syndrome, infection, weight gain, and hypertension, may deter the use of ACTH. Short-term therapy is recommended to reduce the risk of adverse effects. Conclusions: The current literature suggests that short-term, low-dose ACTH should be considered first-line treatment of infantile spasms. © 1967-2013 Harvey Whitney Books Co. All rights reserved.
Clemmons A.B.,University of Georgia |
Clemmons A.B.,Georgia Regents Medical Center |
Ensley E.,University of Georgia |
Ensley E.,Georgia Regents Medical Center |
And 2 more authors.
Annals of Pharmacotherapy | Year: 2014
Background: Fixed-dose rasburicase (FDR) is common practice in treating hyperuricemia associated with tumor lysis syndrome in adults; however, there is a lack of data regarding the effectiveness of this dosing strategy specifically in the overweight and obese patient populations. Objective: To determine if patient weight per body mass index (BMI) category is associated with failure of initial FDR as defined by the need for additional dose(s) based on a uric acid level (UAL) ≥7.5 mg/dL within 10 days of previous rasburicase administration. Method: Adults who received FDR per institutional guidelines from October 2008 to August 2013 were reviewed. Patients had either a baseline UAL ≥7.5 mg/dL or were considered high risk (leukemia or lymphoma diagnosis with white blood cell count >50 000/mm3 or lactate dehydrogenase level greater than 2 times the upper limit of normal). Patients were stratified by BMI as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), or obese (30+). Result: Overall, 12 out of 151 patients who received FDR required a repeat dose of rasburicase. The percentage of patients requiring a repeat rasburicase dose was not different between obese/overweight versus normal/underweight patients (8.7% vs 6.4%, P = 0.75). Similarly, there was no difference between obese alone versus normal/underweight patients (12.3% vs 6.4%; P = 0.51). Conclusion: In this retrospective analysis, patient BMI did not correlate with failure of FDR in adults, suggesting that this dosing strategy is efficacious in the adult population. © The Author(s) 2014.
PubMed | Georgia Regents Medical Center and University of Georgia
Type: Journal Article | Journal: The Annals of pharmacotherapy | Year: 2016
Acid suppressive therapy (AST)-namely, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs)-is routinely prescribed to hospitalized patients for stress ulcer prophylaxis (SUP).To identify the incidence of and indications for AST use in the hematology/oncology population as well as to identify the occurrence of the following PPI-associated adverse events: pneumonia and Clostridium difficile-associated diarrhea (CDAD).A retrospective chart review was conducted on adult hematology/oncology patients admitted to any oncology service for 48 hours from October 1, 2014, to December 31, 2014.Of the 298 patients who met the inclusion criteria, 73% (n = 218) received an AST during admission. The most common indication for an AST was SUP (63%). The incidence of hospital-acquired pneumonia (HAP) was 10%, 0%, and 4% in patients who received a PPI, H2RA, and no AST, respectively (14/142 vs 0/70 vs 3/80; odds ratio [OR] for PPI vs no AST = 2.68; 95% CI = 0.75-9.63). The incidence of CDAD was 3%, 1.3%, and 1.2% in patients who received a PPI, H2RA, and no AST, respectively (4/142 vs 1/70 vs 1/80; OR for PPI vs H2RA = 1.92; 95% CI = 0.21-17.47).This is the first study to describe the incidence of and indications for AST use in the hospitalized hematology/oncology population. There was a high occurrence of AST use, particularly PPIs, in these patients at our institution. Additionally, there was a trend toward an increased risk of HAP and CDAD in patients who received AST during admission.
PubMed | Georgia Regents Medical Center, Alexandria University, Ohio State University, Ohio University and Alexandria Medical School
Type: Journal Article | Journal: Journal of neurological surgery. Part B, Skull base | Year: 2015
IntroductionVarious lateral and anterior approaches to access the infratemporal fossa (ITF) have been described. We provide our observations regarding the endoscopic transpterygoid and preauricular subtemporal approaches, listing their respective advantages and limitations through cadaveric dissection. MethodsA cadaver study was performed on five adult specimens. An endoscopic transpterygoid approach to the ITF was completed bilaterally in three specimens, and an open preauricular ITF approach was performed bilaterally in two specimens. ResultsAfter completing the cadaveric dissections, we studied differences between the endoscopic transpterygoid approach and open preauricular subtemporal approaches in regard to exposure and ease of dissection of different structures in the ITF. ConclusionsIn comparison with a lateral approach, the endonasal endoscopic transpterygoid approach provides better visualization and more direct exposure of median structures such as the nasopharynx, eustachian tube, sella, and clivus. We concluded that the endoscopic transpterygoid approach can be utilized to resect benign lesions and some select group of malignancies involving the infratemporal and middle cranial fossae. Open approaches continue to play an important role, especially in the resection of extensive malignant tumors extending to these regions.