A Simulation-Based Assessment of Levetiracetam Concentrations Following Fixed and Weight-Based Loading Doses: A Meta-Regression and Pharmacokinetic Modeling Analysis.

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight-based loading doses of LEV with respect to established therapeutic target concentrations. Meta-regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight-based dosing) to achieve maximum (Cpeak) and 12-h (C12h) plasma concentrations that exceed 12 mg/L. The meta-regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight-based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight-based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing.

Exploring the Professional Identity of Hospital Pharmacists in British Columbia.

Background: Pharmacists lack a cohesive professional identity, with only limited previous research on the formation of a professional identity for pharmacy. In particular, there is sparse information on the professional identity of pharmacists who practise in hospital settings. Objectives: To determine hospital pharmacists' professional identity and the characteristics of an ideal pharmacist and ideal practice setting. Methods: This qualitative study used key informant interviews with semistructured questions. A maximum variation sampling strategy was used to recruit a cross-section of pharmacists from different geographic areas of British Columbia who were practising in a variety of roles. The interviews were transcribed and then analyzed thematically. Results: Nineteen pharmacists participated in the study. Seven themes pertaining to hospital pharmacists' professional identity were generated, specifically medication expert, therapy optimizer, collaborator, educator, researcher, patient advocate, and unknown professional. Similarities were found with personas previously identified in a population of primarily community pharmacists. The ideal pharmacist was described as being a medication expert, a collaborator, and a leader. The ideal practice setting was characterized as being adequately funded and allowing pharmacists to practise to their full scope. Conclusions: Hospital pharmacists' professional identity is based on being a medication expert who is seen as an essential member of a collaborative team.

Contexte: Les pharmaciens manquent d'une identité professionnelle cohérente et les recherches antérieures portant sur la formation d'une identité professionnelle de la profession sont limitées. En particulier, les informations sur l'identité professionnelle des pharmaciens exerçant en milieu hospitalier sont rares. Objectif: Déterminer l'identité professionnelle des pharmaciens d'hôpitaux ainsi que les caractéristiques d'un pharmacien idéal et d'un milieu d'exercice idéal. Méthodes: Pour cette étude qualitative, des questions d'entretien semi-structurées ont été utilisées auprès d'informateurs clés. Une stratégie d'échantillonnage à variation maximale a été utilisée pour recruter un échantillon représentatif de pharmaciens de différentes régions géographiques de la Colombie-Britannique pratiquant divers rôles. Les entretiens ont ensuite été retranscrits puis analysés par thème. Résultats: Dix-neuf pharmaciens ont participé à l'étude. Sept thèmes relatifs à l'identité professionnelle des pharmaciens d'hôpitaux se sont dessinés: expert en médicaments, optimisateur thérapeutique, collaborateur, éducateur, chercheur, défenseur des patients et professionnel méconnu. Des similitudes se sont dégagées avec des identités précédemment cernées dans une population constituée principalement de pharmaciens communautaires. Le pharmacien idéal a été décrit comme étant un expert en médicaments, un collaborateur et un leader. Le milieu de pratique idéal a quant à lui été décrit comme un milieu adéquatement financé permettant aux pharmaciens d'exercer pleinement leurs compétences. Conclusions: L'identité professionnelle du pharmacien hospitalier repose sur le fait d'être un expert en médicaments. Cet expert est considéré comme membre essentiel d'une équipe collaborative.

Correlation of Calculated Vancomycin Trough Concentrations and Exposure: A Monte Carlo Simulation.

BACKGROUND: Current recommendations are to dose vancomycin to target 24-hour area under the curve (AUC) of 400-600 mg·h/L to optimize efficacy and safety. Limited data support AUC monitoring, and some centers continue to use trough concentrations. A target of 10-20 mg/L has been proposed to reduce nephrotoxicity risk. OBJECTIVE: To use previously published pharmacokinetic equations in a Monte Carlo simulation relating AUC exposure to trough concentrations when targeting an AUC between 400 and 600 mg·h/L. METHODS: Previously published pharmacokinetic data were used as input parameters for a Monte Carlo simulation using previously published formulae to correlate AUC to simulated trough concentrations. Pharmacokinetic parameters were assumed to occur in a normal distribution pattern. We excluded irrelevant simulated cases. Maintenance doses of 15 mg/kg were rounded to the nearest 250 mg. Calculated trough concentrations for AUCs of both 400 and 600 mg·h/L were evaluated in each simulation. RESULTS: A total of 10 000 Monte Carlo simulations were performed. Targeting an AUC of 400 mg·h/L resulted in a mean trough concentration of 10.3 ± 0.8 mg/L. Targeting an AUC of 600 mg·h/L resulted in a mean trough concentration of 15.4 ± 1.2 mg/L. CONCLUSION AND RELEVANCE: We demonstrate that a lower trough concentration range may be supported by an AUC of 400-600 mg·h/L, which may reduce risk and rates of nephrotoxicity without compromising previously established efficacious target trough concentrations.

How do patients with systemic autoimmune rheumatic disease perceive the use of their medications: a systematic review and thematic synthesis of qualitative research.

BACKGROUND: Pharmacotherapy is paramount to the management of systemic autoimmune rheumatic diseases (SARDs), yet there is sub-optimal adherence and limited adherence interventions. To understand how to better support patients' medication use, our two-fold objectives were: 1) to conduct a systematic review of qualitative research studies of medication taking among SARD patients; and 2) to thematically synthesize qualitative research studies to obtain SARD patients' perspectives and experiences with medication use. METHODS: We conducted a search of MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Social Sciences Citation Index databases to identify qualitative research studies exploring views on medication use among patients with SARDs, their healthcare providers, or caregivers. We used thematic synthesis to combine data from selected studies, and identify analytical themes on SARD patients' perspectives and experiences with medication use. RESULTS: Our systematic review identified 18 studies. Thematic synthesis identified seven analytical themes: 1) effects of medications on emotional and social well-being, 2) impacts of healthcare provider relationships on treatment, 3) gaining control over treatment, 4) fear and concern with side effects of treatment, 5) understanding the importance of treatment, 6) practical barriers to taking medication, and 7) motivation towards adherence to treatment. CONCLUSION: This systematic review and thematic synthesis contributes to better understanding of SARDs patients' perspectives on medication use. Given the paucity of existing adherence interventions targeting this patient population, our study has certain practical implications for care, namely the need to address emotional and social impacts of medication use and the necessity of establishing a meaningful and trusting professional relationship with patients.