Dave Barlow

Incidence, type and causes of dispensing errors: A review of the literature

Objectives To identify, review and evaluate the published literature on the incidence, type and causes of dispensing errors in community and hospital pharmacy.

Prediction of 3-hydroxypyridin-4-one (HPO) hydroxyl pKa values

As an aid in optimising the design of 3-hydroxypyridin-4-ones (HPOs) intended for use as therapeutic Fe(3+) chelating agents, various quantum mechanical (QM) and semi-empirical (QSAR) methods have been explored for predicting the pK(a) values of the hydroxyl groups in these compounds. Using a training set of 15 HPOs with known hydroxyl pK(a) values, reliable predictions are shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Pauling radii, and water as solvent). With this methodology, the observed hydroxyl pK(a) values for the training set compound are closely matched by the predicted pK(a) values, with the correlation between the observed and predicted values giving r(2) = 0.98. Predictions subsequently made by this method for a test set of 48 HPOs of known hydroxyl pK(a) values (11 of which were determined experimentally in this study), gave predicted pK(a) values accurate to within ±0.2 log units. In order to further investigate the predictive power of the method, two novel HPOs were synthesised and their hydroxyl pK(a) values were determined experimentally. Comparison of these predicted pK(a) values against the measured values gave absolute deviations of 0.13 (10.18 vs. 10.31) and 0.43 (5.58 vs. 5.15).

A study of unprevented dispensing incidents in Welsh NHS hospitals

Objective To monitor unprevented dispensing incidents in NHS hospitals by identifying incident types, drugs involved and factors that may have contributed to the occurrence of incidents.

Prediction of Absolute Hydroxyl pKa Values for 3-Hydroxypyridin-4-ones

pKa values have been calculated for a series of 3-hydroxypyridin-4-one (HPO) chelators in aqueous solution using coordination constrained ab initio molecular dynamics (AIMD) in combination with thermodynamic integration. This dynamics-based methodology in which the solvent is treated explicitly at the ab initio level has been compared with more commonly used simple, static, approaches. Comparison with experimental numbers has confirmed that the AIMD-based approach predicts the correct trend in the pKa values and produces the lowest average error (∼0.3 pKa units). The corresponding pKa predictions made via static quantum mechanical calculations overestimate the pKa values by 0.3-7 pKa units, with the extent of error dependent on the choice of thermodynamic cycle employed. The use of simple quantitative structure property relationship methods gives prediction errors of 0.3-1 pKa units, with some values overestimated and some underestimated. Beyond merely calculating pKa values, the AIMD simulations provide valuable additional insight into the atomistic details of the proton transfer mechanism and the solvation structure and dynamics at all stages of the reaction. For all HPOs studied, it is seen that proton transfer takes place along a chain of three H2O molecules, although direct hydrogen bonds are seen to form transiently. Analysis of the solvation structure before and after the proton transfer event using radial pair distribution functions and integrated number densities suggests that the trends in the pKa values correlate with the strength of the hydrogen bond and the average number of solvent molecules in the vicinity of the donor oxygen.

Unprevented or prevented dispensing incidents: which outcome to use in dispensing error research?

Objectives  To compare the rate, error type, causes and clinical significance of unprevented and prevented dispensing incidents reported by Welsh National Health Service (NHS) hospital pharmacies.

Measuring dispensary workload: a comparison of the event recording and direct time techniques

Objectives  To compare dispensary workload, determined using the Welsh benchmarking event recording technique and the direct time technique, at two district general UK National Health Service hospitals within different university local health Boards (hospital A – manual dispensing system; hospital B – automated dispensing system).

Exploratory study to identify the process used by pharmacy staff to verify the accuracy of dispensed medicines

To determine the common stages and strategies involved in the dispensing accuracy‐checking process used by pharmacy staff and to determine the training activities used by these staff to gain the knowledge and skills for accuracy checking.