Vaughn L. Culbertson

Topical phenytoin treatment of stage II decubitus ulcers in the elderly.

OBJECTIVE: To compare the healing of stage II decubitus ulcers with topically applied phenytoin sodium with two other standard topical treatment procedures in a long-term care setting; and to assess the extent of systemic absorption after topical application in the phenytoin group. METHODS: Forty-seven nursing home patients with stage II decubitus ulcers were chosen for this study. The patients were matched for age, gender, and size and severity of wounds, and randomly assigned to each treatment group. Clinical assessment of decubitus ulcers was performed at the beginning of treatment and at each dressing change. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Two phenytoin sodium plasma concentrations were to be obtained on all patients in the phenytoin group. RESULTS: Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications (p ⩽ 0.05). The mean ± SD time to healing in the phenytoin group was 35.3 ± 14.3 days compared with 51.8 ± 19.6 and 53.8 ± 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within two to seven days in all subjects. Patients in the standard treatment groups required six to 21 days to produce new granulation tissue. Serum phenytoin sodium concentrations were nondetectable. No patient withdrew from the study secondary to adverse treatment effects. CONCLUSIONS: Both the phenytoin and standard treatment groups showed progress over the study period. However, the phenytoin group demonstrated more rapid results in all aspects of ulcer healing.

Consumer Preferences for Verbal and Written Medication Information

The extent of medication use and drug information preferences was surveyed randomly from patients at six different pharmacy health care systems. Following verbal consultation, each patient was given one or more modified United States Pharmacopeia drug information leaflets corresponding to the verbal information and a self-addressed, stamped questionnaire to complete. Chi-square analysis was performed on 317 responses with overwhelming acceptance (96 percent) of the medication information provided. Although a majority of respondents (62 percent) preferred a combination of both written and oral information, specific information preferences (oral, written, or both) were significantly related to educational level, pharmacy attended, and prescription status. Nearly 45 percent of the respondents indicated the information was responsible for changing their medication use. Subjects who were elderly, taking cardiovascular medications, or getting refill prescriptions were significantly less likely to change as a result of the information provided. Although 65 percent of the respondents were unwilling to pay an additional fee for the service, females and those who were 45–54 years and over 65 years old were significantly more willing to pay for the information. In addition, the willingness to pay tended to increase as the number of daily medications taken increased. Consideration of socioeconomic and prescription variables may help define subgroups with specific information preferences and counseling activities that may be directly reimbursable.

Retrospective Detection of Potential Medication Errors Involving Drugs with Similar Names

OBJECTIVE To estimate frequencies of potential errors involving similarly named drugs using a retrospective claims database and measure the association between frequencies of potential errors and two measures of drug name similarity, edit distance (minimum number of insertions, substitutions, or deletions of characters required to change a given word into another target word) and normalized edit distance (proportion of letters that must be changed to commute one word to another, and ranges from 0 to 1, with 0 indicating identical words, and 1 indicating a pair of words with no common letters). DESIGN Retrospective database analysis. SETTING Idaho Medicaid claims data from 1993 to 2000. PATIENTS Not applicable. INTERVENTION Potential errors were detected using adjacent claims generated by dispensing of one drug followed by dispensing of the other drug with a similar name. In all, four potential error criteria were developed: two for detecting potential refill errors and two for detecting potential initial errors. A total of 10 drug pairs were randomly selected from the Idaho Medicaid claims database for each value of edit distance, which ranged from 1 to 30 (n = 300). MAIN OUTCOME MEASURES Frequencies of potential medication errors in claims sequences for initial and refill claims, edit distance, and normalized edit distance. RESULTS Of 300 drug pairs studied, 106 (35.33%) were involved in at least one potential error. A total of 1,138 dispensing episodes satisfied the criteria for potential errors. Frequencies of potential errors per drug pair were negatively associated with edit distance (r = -0.133, P < .05) and normalized edit distance (r = -0.226, P < .01). Frequencies of potential initial errors also were negatively associated with edit distance (r = -0.126, P < .05) and normalized edit distance (r = -0.222, P < .01). Potential refill errors also had negative association with edit distance (r = -0.134, P < .05) and normalized edit distance (r = -0.226, P < .01). CONCLUSION Error criteria were successfully applied to a retrospective claims database to detect potential initial and refill errors that involved similarly named drugs.

Perceptions of Practicing Pharmacists in Idaho about a Potential Behind-the-Counter Drug Program:

Background: In late 2007, the Food and Drug Administration (FDA) held public hearings exploring the establishment of a new behind-the-counter (BTC) drug program. However, little is known about the views ol pharmacists regarding such a program. Objective: To assess the overall perceptions of Idahos practicing pharmacists about the creation of a formal BTC drug program, the appropriateness of including certain drug categories, specific barriers to its adoption, and the impact of the new program on access to medicines. Methods: A survey of practicing pharmacists in Idaho was conducted by mail, utilizing anonymous responses. Key questions exploring the views of pharmacists about the new BTC drug program utilized 5-point Likert scales. Data were also collected on respondent characteristics. Results: A total of 357 practicing pharmacists in Idaho (31% response rate) returned the mail survey; 84% of pharmacists agreed that the FDA should be exploring an expanded BTC program, and 88% of pharmacists agreed that this program would improve access to some prescription-only products and convenience (or patients. Almost 71% of pharmacists reported a personal willingness to both initiate and monitor certain BTC drug therapies. When focusing on specific drug categories for BTC status, the highest support was (or selected agents within smoking cessation therapies (85%). nasal corticosteroids for allergies (81%). and vaccines (75%). Pharmacists who reported low barriers to the adoption of a new BTC program were significantly more likely to support this program than were those reporting high barriers. Only 39% of pharmacists agreed that adequate facilities were currently available for private evaluation and counseling of BTC patients. Conclusions: Pharmacists in a statewide survey of perceptions regarding a new BTC drug program overwhelmingly believe that patients would benefit. Pharmacists strongly support the development of the new program, and more than two thirds indicate that they would likely participate, given the necessary supporting institutional framework. Perceived barriers are related to willingness to participate and likely can be minimized through education and provision of private consulting areas.

Assessing and predicting drug-induced anticholinergic risks: an integrated computational approach

Background: Anticholinergic (AC) adverse drug events (ADEs) are caused by inhibition of muscarinic receptors as a result of designated or off-target drug–receptor interactions. In practice, AC toxicity is assessed primarily based on clinician experience. The goal of this study was to evaluate a novel concept of integrating big pharmacological and healthcare data to assess clinical AC toxicity risks. Methods: AC toxicity scores (ATSs) were computed using drug–receptor inhibitions identified through pharmacological data screening. A longitudinal retrospective cohort study using medical claims data was performed to quantify AC clinical risks. ATS was compared with two previously reported toxicity measures. A quantitative structure–activity relationship (QSAR) model was established for rapid assessment and prediction of AC clinical risks. Results: A total of 25 common medications, and 575,228 exposed and unexposed patients were analyzed. Our data indicated that ATS is more consistent with the trend of AC outcomes than other toxicity methods. Incorporating drug pharmacokinetic parameters to ATS yielded a QSAR model with excellent correlation to AC incident rate (R2 = 0.83) and predictive performance (cross validation Q2 = 0.64). Good correlation and predictive performance (R2 = 0.68/Q2 = 0.29) were also obtained for an M2 receptor-specific QSAR model and tachycardia, an M2 receptor-specific ADE. Conclusions: Albeit using a small medication sample size, our pilot data demonstrated the potential and feasibility of a new computational AC toxicity scoring approach driven by underlying pharmacology and big data analytics. Follow-up work is under way to further develop the ATS scoring approach and clinical toxicity predictive model using a large number of medications and clinical parameters.

MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia

In 2009 the U.S. Food and Drug Administration (FDA) placed a black box warning on metoclopramide (MCP) due to the increased risks and prevalence of tardive dyskinesia (TD). In this study, we developed a multi-step biomedical informatics screening (MSBIS) approach leveraging publicly available bioactivity and drug safety data to identify concomitant drugs that mitigate the risks of MCP-induced TD. MSBIS includes (1) TargetSearch (http://dxulab.org/software) bioinformatics scoring for drug anticholinergic activity using CHEMBL bioactivity data; (2) unadjusted odds ratio (UOR) scoring for indications of TD-mitigating effects using the FDA Adverse Event Reporting System (FAERS); (3) adjusted odds ratio (AOR) re-scoring by removing the effect of cofounding factors (age, gender, reporting year); (4) logistic regression (LR) coefficient scoring for confirming the best TD-mitigating drug candidates. Drugs with increasing TD protective potential and statistical significance were obtained at each screening step. Fentanyl is identified as the most promising drug against MCP-induced TD (coefficient: −2.68; p-value < 0.01). The discovery is supported by clinical reports that patients fully recovered from MCP-induced TD after fentanyl-induced general anesthesia. Loperamide is identified as a potent mitigating drug against a broader range of drug-induced movement disorders through pharmacokinetic modifications. Using drug-induced TD as an example, we demonstrated that MSBIS is an efficient in silico tool for unknown drug-drug interaction detection, drug repurposing, and combination therapy design.

Implications of Off-Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

Serotonergic adverse drug events (ADEs) are caused by enhanced intrasynaptic concentrations of 5‐hydroxytryptamine (5‐HT). No systematic process currently exists for evaluating cumulative 5‐HT and off‐target toxicity of serotonergic drugs. The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) by using a molecular bioinformatics, polypharmacologic approach for assessment of the participation of individual 5‐HT drugs in serotonin syndrome (SS) reports.