Development of Professional Attributes through Integration of Science and Practice at First-Year Pharmacy Level.

The design, implementation and evaluation of a year 1 pharmacy-integrated learning component, using the World Health Organisation's (WHO) analgesic ladder as a scaffold for case-based learning, is described. A novel aspect of the integrated component is the mapping of the cases to the national Core Competency Framework (CCF) for Pharmacists in Ireland and to the school's own cross-cutting curricular integration themes. The integrated cases were student led and delivered through peer-to-peer teaching for 68 first-year pharmacy students. The integrated cases mapped strongly to three of the CCF's domains, namely, personal skills, organisation and management skills and supply of medicines. With regard to the school's curricular integrative themes, the cases mapped strongly to the curricular integration themes of professionalism and communications; medicines sourcing, production and use; and safe and rational use of medicines. Highlights from an anonymous online student survey were the recognition by students of the importance of core science knowledge for practice, the enabling of integrated learning and the suitability of the integrated component for entry-level. While a majority of students were found to favour individual work over group work, future iterations will need to consider a greater degree of group work with a view to reducing the volume of content and time required to complete the cases.

Analyzing repeated measures semi-continuous data, with application to an alcohol dependence study.

Two-part random effects models (Olsen and Schafer,(1) Tooze et al.(2)) have been applied to repeated measures of semi-continuous data, characterized by a mixture of a substantial proportion of zero values and a skewed distribution of positive values. In the original formulation of this model, the natural logarithm of the positive values is assumed to follow a normal distribution with a constant variance parameter. In this article, we review and consider three extensions of this model, allowing the positive values to follow (a) a generalized gamma distribution, (b) a log-skew-normal distribution, and (c) a normal distribution after the Box-Cox transformation. We allow for the possibility of heteroscedasticity. Maximum likelihood estimation is shown to be conveniently implemented in SAS Proc NLMIXED. The performance of the methods is compared through applications to daily drinking records in a secondary data analysis from a randomized controlled trial of topiramate for alcohol dependence treatment. We find that all three models provide a significantly better fit than the log-normal model, and there exists strong evidence for heteroscedasticity. We also compare the three models by the likelihood ratio tests for non-nested hypotheses (Vuong(3)). The results suggest that the generalized gamma distribution provides the best fit, though no statistically significant differences are found in pairwise model comparisons.

A topological study of prodrugs of 5-fluorouracil.

Various physicochemical properties are correlated with the first-order connectivity index for a series of prodrug derivatives of 5-fluorouracil. Partition coefficient data available in the literature were complemented by calculated logP values using the CLOGP program. The first-order connectivity index correlated quite well with the experimental logP values (n=16) while the correlation with ClogP improved with the removal of compounds VI, VII and XVII. A molecular modelling study provided data for the molecular area and volume of all prodrugs studied. The regression equations obtained showed that there was good correlation between the topological index and the molecular area and volume. The connectivity index is an adequate topological descriptor. The first-order valence index was preferred over that of order two. Comparison of ClogP values provides group contribution values while the comparison of molecular volume data provides information on the volumes of individual substituents relative to that of hydrogen.

Gamma knife radiosurgery for brain metastasis of nonsmall cell lung cancer: is there a difference in outcome between morning and afternoon treatment?

BACKGROUND: Circadian cell-cycle progression causes fluctuating radiosensitivity in many tissues, which could affect clinical outcomes. The purpose of this study was to determine whether outcomes of single-session gamma knife radiosurgery (GKRS) for metastatic nonsmall cell lung cancer (NSCLC) differ based on treatment time. METHODS: Fifty-eight patients received GKRS between 10:00 am and 12:30 pm and 39 patients received GKRS between 12:30 pm and 3:00 pm. The mean peripheral dose was 18.6 Gy. The mean tumor size was 7.3 cm³. Magnetic resonance imaging was used to score local control at 3 months. Cause of death (COD) was categorized as central nervous system (CNS)-related or systemic. RESULTS: Demographic and disease characteristics of the 2 groups were similar. Local control at 3 months was achieved in 97% (35/36) of patients who underwent GKRS early in the day versus 67% (8/12) of patients who underwent GKRS later in the day (chi-square, P = .014). Early GKRS was associated with better survival (median 9.5 months) than late GKRS (median 5 months) (Kaplan-Meier log-rank test, P = .025). Factors contributing to better survival in a Cox regression model included early treatment time (P = .004) and recursive partition analysis class (P < .001). Cause of death in the early treatment group was CNS-related in 6% (3/47) of patients versus 24% (8/34) of patients in the late treatment group (chi-square test, P = .026). CONCLUSIONS: GKRS for metastatic NSCLC had better local control, better survival, and a lower rate of CNS-related cause of death when given earlier in the day versus later in the day. These retrospective data should encourage future study in brain radiosurgery and non-CNS stereotactic body radiotherapy series.

The interrelation of physicochemical parameters and topological descriptors for a series of beta-blocking agents.

The intercorrelation between a series of physicochemical parameters and topological indices for a set of beta-blockers is investigated. Partition coefficients are calculated using the ClogP program, and the results are compared with previous data, both experimental and theoretical. These data are complemented by hydrophilicity and solubility calculations, together with the determination of molecular area and volume. Connectivity indices, of order 1 and 2, including simple, valence, and differential terms, are evaluated. The derivation of a recently proposed topological descriptor, the eccentric adjacency index, from the adjacency and distance matrices, is presented. The corresponding valence term, a novel descriptor, is developed, and other indices related to the distance matrix, the Wiener and Hyper-Wiener terms, are included. A high degree of linear correlation between the connectivity indices is noted. The correlations for first-order terms are slightly superior to the corresponding second-order values. This is particularly true when considering the valence terms compared with the nonvalence terms. The relationship between these terms and reported pharmacological properties are investigated. A decrease in the eccentric adjacency index resulted in an increase in the pharmacological property.