Development of clinical pharmacy services in Australia, Austria, Belgium, Bosnia-Herzegovina, Canada, Germany, Japan, Kosovo, Switzerland, the Netherlands, Thailand, USA and correlation with educational standards, level of research, and implemen.

OBJECTIVE: This study aimed to compare determinants of professional development between different countries to identify barriers and facilitators of development towards clinical pharmacy services and stimulate discussion of under-used potential and opportunities. MATERIALS: The study was conceived as a survey. The questionnaire was administered to a group of experts. METHODS: The survey was conducted as a cross-sectional study with descriptive and correlation analysis. A questionnaire was developed and adjusted to the study focus, covering aspects on general regulations for community pharmacies, professional education, implementation of clinical pharmacy services, and research in patient care. Results were compared for analyses. RESULTS: A total of twelve countries were included in this survey. Pharmacy studies took between 4 and 6 years plus residency in most countries. Curricula remained drug-oriented only in Austria, Bosnia-Herzegovina, and Germany; these three countries had the least pharmacotherapy content in their curricula. Canada, the USA, and Australia have established clinical pharmacy services in almost all fields of practice. Most other countries have implemented at least some clinical services, with the exception of Bosnia-Herzegovina, Germany, and Kosovo. The correlation coefficient between education, research, and implementation was 0.91. CONCLUSION: The results of the survey show that clinical pharmacy services are established to very different extents among the participating countries. The strong correlation suggests that achieving a successful transition in professional practice needs to address several aspects of education and research to reach progress. The collected data might help to identify potential areas of improvement to foster implementation of clinical pharmacy services.
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In Vitro Comparison of Raypex 6 and Endopilot Using a Novel, Computer-Aided Measurement System, for Determining the Working Length.

INTRODUCTION: Experimental evaluation of endometric devices usually relies on visual, subjective detection of the apical constriction to determine the accuracy of measurements. The aim of the present study was to analyze the accuracy of measurements of Raypex 6 and EndoPilot using a novel, objective image-analysis system. METHODS: Onehundred and twenty teeth were randomized and allocated to three groups: After coronal flaring, either Raypex 6 or EndoPilot were used to determine the endodontic working length during instrumentation using manual files (RPM and EPM group respectively). In addition, EndoPilot was used for continuous, automatic measurement during rotating instrumentation (EPA group). If the working length had been reached according to endometric results, the files were fixed in place. Tooth and file were then embedded and prepared for analysis. Subsequently, the distance between the tip of the file and the apical constriction (DAC) or the apical foramen (DAF) was calculated using trigonometric analysis and the position of the file relative to AC and AF was analyzed. RESULTS: Both inter- and intra-examiner-reliability of the trigonometric analysis were nearly perfect (ICC = 0.999, p<0.001). DAC was not significantly different between groups (p>0.05, t-test). DAF was significantly decreased when EPA had been used compared to EPM (p<0.05, Exact-test). EPA resulted in files being positioned beyond AF significantly more often than the other two methods (p<0.01). CONCLUSIONS: All methods allowed reliable detection of AC. However, EPA significantly increased the risk of overpreparation. Objective, digital assessment based on image analysis was suitable to compare the accuracy of different endometric devices.

Detection models for freehand SPECT reconstruction.

Nuclear imaging modalities are commonly used tools in today's diagnostics and therapy planning. However for interventional use they suffer from drawbacks which limit their application. Freehand SPECT was developed to provide 3D functional imaging during interventions. It combines a nuclear detector with an optical tracking system to obtain its position and orientation in space and synchronizes this with the detector readings. This information can be used to compute a 3D tomographic reconstruction of an activity distribution of a nuclear tracer. As there is no fixed geometry, the system matrix has to be computed on the fly. This is done with models of the detection process for completely arbitrary freehand acquisitions. The accuracy of the reconstructions is highly dependent on the used models of the detection process. Different models of the detection process were developed and evaluated in this work, in particular two analytical models as well as lookup tables generated from either real measurements or Monte Carlo simulations. We showed that it is possible to perform acceptable reconstructions with a simple but efficient analytical model. The use of lookup tables to generate the system matrix in Freehand SPECT is a fast solution with good accuracy.

Cytochrome P450 3A-mediated metabolism of the topoisomerase I inhibitor 9-aminocamptothecin: impact on cancer therapy.

The metabolism of 9-aminocamptothecin (9-AC) was investigated in human and rat liver microsomes. In both species 9-AC was almost exclusively biotransformed to dihydroxy-9-AC (M1) and monohydroxy-9-AC (M2). The enzymatic efficiencies of the formation of M1 and M2 (V(max)/K(m)) were 1.7- and 2.7­fold higher in rat than in human liver microsomes indicating species-related differences in 9-AC hydroxylation. Incubation in the presence of human recombinant cytochrome P450 (CYP) enzymes demonstrated that the formation of M1 and M2 is mainly catalyzed by CYP3A4 and only to a minor extent by extrahepatic CYP1A1. The predominant role of CYP3A4 was further supported by a dramatic inhibition of metabolite formation in the presence of the CYP3A4 substrates troleandomycin and ketoconazole. Experiments conducted in isolated perfused rat livers further demonstrated that biliary excretion of 9-AC, M1 and M2 during 60 min of perfusion was pronounced and accounted for 17.7±2.59, 0.05±0.01 and 2.75±0.14% of total 9-AC applied to the liver, respectively. In summary, this study established that CYP3A-dependent hydroxylation is the main metabolic pathway for 9-AC in rat and human liver, which have to be taken into consideration during cancer therapy of patients.

Evaluation of a 4D cone-beam CT reconstruction approach using a simulation framework.

Current image-guided navigation systems for thoracic abdominal interventions utilize three dimensional (3D) images acquired at breath-hold. As a result they can only provide guidance at a specific point in the respiratory cycle. The intervention is thus performed in a gated manner, with the physician advancing only when the patient is at the same respiratory cycle in which the 3D image was acquired. To enable a more continuous workflow we propose to use 4D image data. We describe an approach to constructing a set of 4D images from a diagnostic CT acquired at breath-hold and a set of intraoperative cone-beam CT (CBCT) projection images acquired while the patient is freely breathing. Our approach is based on an initial reconstruction of a gated 4D CBCT data set. The 3D CBCT images for each respiratory phase are then non-rigidly registered to the diagnostic CT data. Finally the diagnostic CT is deformed based on the registration results, providing a 4D data set with sufficient quality for navigation purposes. In this work we evaluate the proposed reconstruction approach using a simulation framework. A 3D CBCT dataset of an anthropomorphic phantom is deformed using internal motion data acquired from an animal model to create a ground truth 4D CBCT image. Simulated projection images are then created from the 4D image and the known CBCT scan parameters. Finally, the original 3D CBCT and the simulated X-ray images are used as input to our reconstruction method. The resulting 4D data set is then compared to the known ground truth by normalized cross correlation(NCC). We show that the deformed diagnostic CTs are of better quality than the gated reconstructions with a mean NCC value of 0.94 versus a mean 0.81 for the reconstructions.

Towards intra-operative 3D nuclear imaging: reconstruction of 3D radioactive distributions using tracked gamma probes.

Nuclear medicine imaging modalities assist commonly in surgical guidance given their functional nature. However, when used in the operating room they present limitations. Pre-operative tomographic 3D imaging can only serve as a vague guidance intra-operatively, due to movement, deformation and changes in anatomy since the time of imaging, while standard intra-operative nuclear measurements are limited to 1D or (in some cases) 2D images with no depth information. To resolve this problem we propose the synchronized acquisition of position, orientation and readings of gamma probes intra-operatively to reconstruct a 3D activity volume. In contrast to conventional emission tomography, here, in a first proof-of-concept, the reconstruction succeeds without requiring symmetry in the positions and angles of acquisition, which allows greater flexibility. We present our results in phantom experiments for sentinel node lymph node localization. The results indicate that 3D intra-operative nuclear images can be generated in such a setup up to an accuracy equivalent to conventional SPECT systems. This technology has the potential to advance standard procedures towards intra-operative 3D nuclear imaging and offers a novel approach for robust and precise localization of functional information to facilitate less invasive, image-guided surgery.

Faster integration of human allograft bone than of the bovine substitute Lubboc: non-randomized evaluation of 20 cases with benign tumors or tumor-like conditions.

In 20 patients, we studied healing and time for complete integration of human cancellous bone allografts and the bovine substitute Lubboc on plain radiographs. They were all operated on because of benign tumors or tumor-like conditions, and followed until integration of the graft or for at least 1 year after operation. The median follow-up was 10 (2-40) months. Allografts showed a better integration than the bovine substitute. We conclude that allografts are to be preferred for these indications.