To develop a pharmacokinetic model describing total and unbound teicoplanin concentrations in patients with haematological malignancy and to perform Monte Carlo simulations to evaluate target attainment of unbound trough concentrations with various dose regimens. This was a hospital-based clinical trial (EudraCT 2013-004535-72). The dosing regimen was 600/800 mg q12h for three doses then 600/800 mg daily. Serial total and unbound teicoplanin concentrations were collected. Maximum protein binding was estimated from serum albumin concentration. Population pharmacokinetic analyses and Monte Carlo simulations were conducted using Pmetrics^®. Target total and unbound trough concentrations were ≥20 and ≥1.5 mg/L, respectively. Thirty adult patients were recruited with a mean (SD) bodyweight of 69.1 (15.8) kg, a mean (SD) CL_CR of 72 (41) mL/min and a median (IQR) serum albumin concentration of 29 (4) g/L. A three-compartment complex binding pharmacokinetic model best described the concentration–time data. Total and unbound teicoplanin concentrations were related by serum albumin concentration and a dissociation constant. CL_CR and bodyweight were supported as covariates for CL and volume of the central compartment, respectively. Dosing simulations showed that high CL_CR was associated with reduced probability of achieving target total and unbound trough concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound trough concentrations. A method to estimate the unbound teicoplanin concentration from the measured total concentration at different serum albumin concentration was demonstrated. Standard teicoplanin dosing regimens should be used with caution in patients with haematological malignancy. Bodyweight, CL_CR and serum albumin concentration are important considerations for appropriate dosing.

To assess the safety culture in an acute medical admissions unit (AMAU) of a teaching hospital in order to benchmark results against international data and guide a unit-based, integrated, risk management strategy. The safety attitudes questionnaire (SAQ), a validated instrument for the measurement of safety culture was applied to an AMAU. All AMAU healthcare staff (n = 92) were surveyed: doctors, nurses, healthcare assistants (HCAs) and allied healthcare professionals (AHPs). Safety attitude scores for the overall unit and individual caregiver types were assessed across six domains of safety culture. When compared against an international benchmark, the AMAU scored significantly higher for four of the six safety domains: p < 0.01 for ‘teamwork climate’, ‘safety climate’ and ‘stress recognition’ and p < 0.05 for ‘job satisfaction’. The difference between nurse manager scores and the overall mean for the study group was statistically significant for the domains of ‘teamwork climate’ (p < 0.05) and ‘safety climate’ (p < 0.01). HCAs scored significantly lower relative to staff overall with regard to ‘working conditions’ (p < 0.05) and ‘perceptions of management’ (p < 0.01). The SAQ was successfully applied to an AMAU setting giving a valuable insight into staff issues of concern across the safety spectrum: employee and environmental safety, clinical risk management and medication safety.

Rationale: Currently, studies on adherence to inhaled medications report average adherence over time. This measure does not account for variations in the interval between doses, nor for errors in inhaler use. Objectives: To investigate whether adherence calculated as a single area under the (concentration-time) curve (AUC) measure, incorporating the interval between doses and inhaler technique, was more reflective of patient outcomes than were current methods of assessing adherence. Methods: We attached a digital audio device (INhaler Compliance Assessment) to a dry powder inhaler. This recorded when the inhaler was used, and analysis of the audio data indicated if the inhaler had been used correctly. These aspects of inhaler use were combined to calculate adherence over time, as an AUC measure. Over a 3-month period, a cohort of patients with asthma was studied. Adherence to a twice-daily inhaler preventer therapy using this device and clinical measures were assessed. Measurements and Main Results: Recordings from 239 patients with severe asthma were analyzed. Average adherence that was based on the dose counter was 84.4%, whereas the ratio of expected to observed accumulated AUC, actual adherence, was 61.8% (P < 0.01). Of all the adherence measures, only adherence calculated as AUC reflected changes in asthma quality of life, β-agonist reliever use, and peak expiratory flow over the 3 months (P < 0.05 compared with other measures of adherence). Conclusions: Adherence that incorporates the interval between doses and inhaler technique, and calculated as AUC, is more reflective of changes in quality of life and lung function than are the currently used measures of adherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01529697).