William R. Wolowich

Incidence and Predictors of Nephrotoxicity Associated with Intravenous Colistin in Overweight and Obese Patients

ABSTRACT Intravenous colistin is used to treat resistant Gram-negative infections and is associated with nephrotoxicity. In overweight and obese adults, a paucity of data exists regarding the incidence and predictors of such toxicity. A retrospective nested case-control study was performed over 35 months for patients receiving intravenous colistin for ≥72 h with a body mass index (BMI) of ≥25 kg/m2. The objective was to investigate the incidence and predictors of nephrotoxicity. Severity of acute kidney injury was defined by RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Dosing and mortality were secondarily investigated. Forty-two patients met the inclusion criteria, and 20 (48%) developed nephrotoxicity. Patients with toxicity were in the risk (15%), injury (5%), and failure (80%) categories based on RIFLE criteria. A logistic regression model identified four predictors of colistin-associated nephrotoxicity: a BMI of ≥31.5 kg/m2 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.15 to 8.35), diabetes (OR, 2.11; 95% CI, 0.84 to 5.29), the length of hospitalization in days prior to receipt of colistin (OR, 1.04; 95% CI, 0.99 to 1.08), and age (OR, 1.08; 95% CI, 1.00 to 1.17). Among all of the patients, dosing based on the actual body weight and excessive dosing due to the use of the actual body weight were frequent at 64% and 92%, respectively. The 30-day all-cause in-hospital mortality rate was 40% in the toxicity group and 14% in the nontoxicity group (P = 0.14). Patients receiving intravenous colistin should be monitored for nephrotoxicity, especially when the BMI exceeds 31.5 kg/m2. Prospective, randomized, controlled trials are warranted to further examine nephrotoxicity incidence and predictors and appropriate dosing strategies in this population.

Analysis of the psychoactive terpenoid salvinorin A content in five Salvia divinorum herbal products.

Study Objective. To determine the content of the hallucinogen salvinorin A in a variety of Salvia divinorum herbal products and to compare the content with the label claims of potency and purity.

Simvastatin-Ezetimibe-Induced Hepatic Failure Necessitating Liver Transplantation

Serum aminotransferase elevations are a commonly known adverse effect of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin‐ezetimibe. We describe a 70‐year‐old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg‐ezetimibe 40 mg/day. The patients lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work‐up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatin‐ezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work‐up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate‐to‐severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2‐year follow‐up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin‐ezetimibe‐induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatin‐ezetimibe‐induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin‐ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.

The Impact of Student-Faculty Ratio on Pharmacy Faculty Scholarship

Objective. To determine the relationship and impact of student-faculty ratio on scholarship of pharmacy faculty members. Methods. The number and rank of faculty members, pharmacy program characteristics, and faculty productivity data were collected to determine the impact of student-faculty ratio on faculty scholarship. Results. Faculty scholarship was not predicted by student-faculty ratio. Factors impacting positively on faculty productivity included National Institutes of Health funding; presence of clinical associate professors, instructors, and lecturers; and programs located in public universities. Conclusions. Faculty productivity is not related to the student-faculty ratio, wherein more faculty members and fewer students equates to increased scholarship. However, public universities may have different infrastructures which are associated with greater academic productivity compared to private institutions. Additionally, utilizing instructors and clinical or nontenure-track faculty members can significantly increase scholarship among faculty members.

Variability Within Investigations of Intravenous Colistin: The Scope of the Problem

An accurate understanding of this lastline antibacterial drug is essential as clinicians worldwide care for patients infected by drug-resistant organisms. Unfortunately, although concerns exist, the full magnitude and range of discrepancies within this area of research have not been well described. The purpose of this letter is to provide objective data detailing the extensive variability in current colistin literature as it relates to study populations, endpoint selection, and other reporting practices. We searched Scopus (www.scopus. com/home/url) and PubMed (www. ncbi.nlm.nih.gov/pubmed) using the Medical Subject Heading terms “colistin” and “colistimethate” along with the operator “OR” to identify human research published in English between January 1990 and July 2013 with an abstract available. Publications reporting original research or outcomes data for a cohort of adult (age>18years)patientswhoreceived intravenous colistin were included. Of the 1695 identified studies, 51 (3%) articles met inclusion criteria and were evaluated for this descriptive report. Included studies ranged from 1999 to 2013, with two-thirds published after 2008. Prospective studies composed 35% of the sample. Studies originated from 21 unique countries, with the United States and Greece being most frequent at 22% and 20% of publications, respectively. Of the articles reporting doses in milligrams of CBA, two-thirds were from North America, whereas none of the articles reporting in international units of CMS originated from this region.

Improvement in Surrogate Endpoints by a Multidisciplinary Team in a Mobile Clinic Serving a Low-income, Immigrant Minority Population in South Florida

To determine effect on surrogate endpoints for cardiovascular disease (CVD), we performed a retrospective chart review of 114 patients seen by a multidisciplinary team that provided primary care services in a mobile clinic over 12 months. Eligible patients had outcomes available for at least six months. Mixed effect modeling examined variation in surrogate markers for CVD: blood pressure (BP), heart rate, and body mass index. Repeated measures ANOVA compared lipids, hemoglobin A1c, and medication use from baseline and throughout study. Most patients were female (75%), Haitian (76%), and low-income (

Difficulty and discrimination indices of multiple-choice examination items in a college of pharmacy therapeutics and pathophysiology course sequence

747/month) with average age 63 years. Common diagnoses were hypertension (82%) and hyperlipidemia (63%). Significant reduction in systolic BP, total- and LDL-cholesterol, and hemoglobin A1c were found (p<.05). Use of ACE-inhibitors, beta-blockers, diuretics, aspirin, metformin, and statins increased significantly (p<.05). Mobile clinic with a multidisciplinary team improved surrogate endpoints over 12 months in underserved, low-income, mostly foreign-born, Haitian population in U.S.

Solifenacin succinate for the treatment of symptoms of overactive bladder

The purpose of this study was to identify differences in difficulty and discrimination among multiple‐choice examination items with regard to format and content in pharmacy therapeutics and pathophysiology (TP) courses.