RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.

The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8(+) T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8(+)/HLA-A2/RHAMM R3 tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells in accordance with an increase of R3-specific CD8(+) T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37.

Effectiveness of a drug dosing service provided by community pharmacists in polymedicated elderly patients with renal impairment a comparative study

Background: Drug dosing errors are common in renal-impaired patients. Appropriate dosing adjustment and drug selection is important to ensure patients" safety and to avoid adverse drug effects and poor outcomes. There are few studies on this issue in community pharmacies. The aims of this study were, firstly, to determine the prevalence of dosing inadequacy as a consequence of renal impairment in patients over 65 taking 3 or more drug products who were being attended in community pharmacies and, secondly, to evaluate the effectiveness of the community pharmacist"s intervention in improving dosing inadequacy in these patients when compared with usual care. Methods: The study was carried out in 40 Spanish community pharmacies. The study had two phases: the first, with an observational, multicentre, cross sectional design, served to determine the dosing inadequacy, the drug-related problems per patient and to obtain the control group. The second phase, with a controlled study with historical control group, was the intervention phase. When dosing adjustments were needed, the pharmacists made recommendations to the physicians. A comparison was made between the control and the intervention group regarding the prevalence of drug dosing inadequacy and the mean number of drug-related problems per patient. Results: The mean of the prevalence of drug dosing inadequacy was 17.5% [95% CI 14.6-21.5] in phase 1 and 15.5% [95% CI 14.5-16.6] in phase 2. The mean number of drug-related problems per patient was 0.7 [95% CI 0.5-0.8] in phase 1 and 0.50 [95% CI 0.4-0.6] in phase 2. The difference in the prevalence of dosing inadequacy between the control and intervention group before the pharmacists" intervention was 0.73% [95% CI (−6.0) - 7.5] and after the pharmacists" intervention it was 13.5% [95% CI 8.0 - 19.5] (p < 0.001) while the difference in the mean of drug-related problems per patient before the pharmacists" intervention was 0.05 [95% CI( -0.2) - 0.3] and following the intervention it was 0.5 [95% CI 0.3 - 0.7] (p < 0.001). Conclusion: A drug dosing adjustment service for elderly patients with renal impairment in community pharmacies can increase the proportion of adequate drug dosing, and improve the drug-related problems per patient. Collaborative practice with physicians can improve these results.

Améliorer la prescription d'un traitement hypolipémiant lors d'un syndrome coronarien aigu: absence de benefice d'une alerte automatique.

Introduction: Seulement 25-30% des patients avec syndrome coronarien aigu (SCA) atteignent les valeurs cibles de LDL-cholestérol (LDL-C) dans leur suivi. L'objectif de cette étude pré/post est de tester une alerte automatique centralisée pour améliorer les pratiques. L'alerte apparaît sur les feuilles de laboratoire pour tous les patients ayant une troponine >= 0,1 microg/l; elle précise notamment les recommandations en matière de profil lipidique (LDL-C cible) à atteindre. Méthode: Tout patient admis au CHUV pour un SCA avec troponine >= 0,1 microg/l était éligible. Durant les 2 phases de l'étude (du 23.11.2008 au 15.08.201), un bilan lipidique complet a été dosé à l'admission et à 3 mois. La phase 1 (pré) était observationnelle et le message d'alerte a été introduit pour la phase 2 (post). Résultats: Phase 1: 157 patients dont 56 (35%) étaient déjà traités par une statine: 114 hommes (âge moyen 62 ans) et 43 femmes (73 ans). LDL-C moyen: 3,4 ± 1,0 mmol/l à l'admission et 2,4 ± 0,8 mmol/l à 3 mois (p <0,001). Phase 2: 140 patients dont 42 (30%) étaient déjà traités par une statine: 116 hommes (62 ans) et 24 femmes (67 ans). LDL-C moyen: 3,4 ± 1,1 mmol/l à l'admission et 2,2 ± 1,0 mmol/l à 3 mois (p <0,001). 66 % (104 patients) atteignent un LDL-C cible < = 2,6 mmol/l à 3 mois lors de la phase 1, versus 78% (110 patients) lors de la phase 2 (p = 0,2). Les patients déjà sous statine à l'admission ont une faible diminution du LDL-C à 3 mois (de 2,8 à 2,5 mmol/l phase 1, p <0,05; de 2,5 à 2,6 mmol/l phase 2, p = 0.2), alors que les patients chez qui une statine est introduite à l'admission ont une baisse significative et plus importante du LDL-C à 3 mois (de 3,8 à 2,3 mmol/l phase 1, p <0,001; de 3,7 à 2,1 mmol/l phase 2, p <0,001) que les patients déjà sous statine au préalable. Conclusion: La phase observationnelle montre un taux élevé de patients atteignant un LDL-C cible à 3 mois. L'introduction d'une alarme automatique centralisée n'a pas permis d'améliorer ces résultats. Par contre, les patients arrivant à l'hôpital avec un SCA et étant déjà sous statine devraient avoir une intensification de leur traitement.

Adeno-associated virus (AAV) vectors achieve prolonged transgene expression in mouse myocardium and arteries in vivo: a comparative study with adenovirus vectors.

Plasmid DNA and adenovirus vectors currently used in cardiovascular gene therapy trials are limited by low efficiency and short-lived transgene expression, respectively. Recombinant adeno-associated virus (AAV) has recently emerged as an attractive vector for cardiovascular gene therapy. In the present study, we have compared AAV and adenovirus vectors with respect to gene transfer efficiency and the duration of transgene expression in mouse hearts and arteries in vivo. AAV vectors (titer: 5 x 10(8) transducing units (TU)/ml) and adenovirus vectors (1.2 x 10(10) TU/ml) expressing a green fluorescent protein (EGFP) gene were injected either intramyocardially (n=32) or intrapericardially (n=3) in CD-1 mice. Hearts were harvested at varying time intervals (3 days to 1 year) after gene delivery. After intramyocardial injection of 5 microl virus stock solution, cardiomyocyte transduction rates with AAV vectors were 4-fold lower than with adenovirus vectors (1.5% (range: 0.5-2.6%) vs. 6.2% (range: 2.7-13.7%); P<0.05), but similar to titer-matched adenovirus vectors (0.7%; range: 0.2-1.2%). AAV-mediated EGFP expression lasted for at least 1 year. AAV vectors instilled into the pericardial space transduced epicardial myocytes. Arterial gene transfer was studied in mouse carotids (n=26). Both vectors selectively transduced endothelial cells after luminal instillation. Transduction rates with AAV vectors were 8-fold lower than with adenovirus vectors (2.0% (range: 0-3.2%) vs. 16.2% (range: 8.5-20.2%); P<0.05). Prolonged EGFP expression was observed after AAV but not adenovirus-mediated gene transfer. In conclusion, AAV vectors deliver and express genes for extended periods of time in the myocardium and arterial endothelium in vivo. AAV vectors may be useful for gene therapy approaches to chronic cardiovascular diseases.

A new technique for simultaneous validation of two manual nonmercury auscultatory sphygmomanometers (A&D UM-101 and Accoson Greenlight 300) based on the International protocol.

INTRODUCTION: Auscultatory nonmercury manual devices seem good alternatives for the mercury sphygmomanometers in the clinic and for research settings, but individual internal validation of each device is time-consuming. The aim of this study was to validate a new technique capable of testing two devices simultaneously, based on the International protocol of the European Society of Hypertension. METHODS: The concept of the new technique is to measure blood pressure alternatively by two observers using a mercury sphygmomanometer and by two observers using the A&D UM-101 and Accoson Greenlight 300 devices, connected by Y-tube to obtain simultaneous readings with both nonmercury devices. Thirty-three participants were enrolled (mean age 47.2±14.0 years). Nine sequential blood pressure measurements were performed for each participant. RESULTS: Both devices passed phase 1 using 15 participants. In phase 2.1 (n=33), on a maximum of 99 measurements, the Accoson device produced 81/95/99 measurements within 5/10/15 mmHg for systolic blood pressure (SBP) and 87/98/99 for diastolic blood pressure (DBP). The A&D device produced 86/96/99 for SBP and 94/99/99 for DBP. In phase 2.2 (n=33), 30 participants had at least 2 out of 3 SBP obtained with Accoson device within 5 mmHg of the mercury device, as compared with 29 of 33 participants with the A&D device. For DBP, this was 33 of 33 participants for both devices. CONCLUSION: Both the nonmercury devices passed the International protocol. The new technique of simultaneous device testing using a Y-tube represents a time saving application of the International protocol.

CSF1R mutations link POLD and HDLS as a single disease entity.

OBJECTIVE: Pigmented orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) are rare neurodegenerative disorders characterized by cerebral white matter abnormalities, myelin loss, and axonal swellings. The striking overlap of clinical and pathologic features of these disorders suggested a common pathogenesis; however, no genetic or mechanistic link between POLD and HDLS has been established. Recently, we reported that mutations in the colony-stimulating factor 1 receptor (CSF1R) gene cause HDLS. In this study, we determined whether CSF1R mutations are also a cause of POLD. METHODS: We performed sequencing of CSF1R in 2 pathologically confirmed POLD families. For the largest family (FTD368), a detailed case report was provided and brain samples from 2 affected family members previously diagnosed with POLD were re-evaluated to determine whether they had HDLS features. In vitro functional characterization of wild-type and mutant CSF1R was also performed. RESULTS: We identified CSF1R mutations in both POLD families: in family 5901, we found c.2297T>C (p.M766T), previously reported by us in HDLS family CA1, and in family FTD368, we identified c.2345G>A (p.R782H), recently reported in a biopsy-proven HDLS case. Immunohistochemical examination in family FTD368 showed the typical neuronal and glial findings of HDLS. Functional analyses of CSF1R mutant p.R782H (identified in this study) and p.M875T (previously observed in HDLS), showed a similar loss of CSF1R autophosphorylation of selected tyrosine residues in the kinase domain for both mutations when compared with wild-type CSF1R. CONCLUSIONS: We provide the first genetic and mechanistic evidence that POLD and HDLS are a single clinicopathologic entity.

Identification and potential origin of invasive clawed frogs Xenopus (Anura: Pipidae) in Sicily based on mitochondrial and nuclear DNA

African clawed frogs of the widespread polytypic species Xenopus laevis Daudin, 1802 (ranging large parts of sub-Saharan Africa) have been spreading since the 1940s, and have established reproductive populations in Europe, Asia and the Americas, where they can have negative impact as competitors of native amphibians and as disease vectors for chytridomycosis or ranaviruses. Here we use two mitochondrial (cytochrome b, 16S rDNA) and one nuclear (RAG 1: Recombination Associated Gene 1) DNA markers to infer the potential origin of invasive clawed frogs from Sicily that represent the largest invasive population in Europe. Identical mtDNA haplotypes match with those of Xenopus laevis, and Sicilian clawed frogs very probably belong to a lineage from the Cape Region of South Africa, most likely originating from a laboratory stock. Nuclear data support this conclusion. Identical mtDNA sequences (cyt b, 16S) of frogs sampled across their range in Sicily suggest the occurrence of a single source population and a potential bottleneck at their release, but faster evolving multilocus nuclear data (microsatellites, SNPs) on the population genetics would be important in the future to better support this hypothesis

Development of a pediatric eosinophilic esophagitis activity index (ped-EEsAI): International experts propose dysphagia, whitish exudates on endoscopy , and intraepithelial eosinophili count as major items related to EoE activity

Background and Aims: The international EEsAI study group aims to develop, validate and evaluate the first pediatric EoE activity index (ped-EEsAI). We report on results of phase 1, which aims to generate candidate items. Methods: This study involves 3 phases: (1) item generation, (2) index derivation and testing on a first patient cohort, and (3) validation in a second cohort. In phase 1, item generation, weighting and reduction are achieved through a Delphi process with an international EoE expert group. The experts proposed and ranked candidate items on a 7-point Likert scale (0 = no, 6 = perfect relationship with EoE activity). Results: 23 international EoE experts proposed and ranked 39 items (20 clinical, 6 endoscopic, 8 histologic, 5 laboratory items). Rank order for clinical items: dysphagia related to food consistencies (median 5, range 2-6), severity of dysphagia (5, 3-6), frequency of dysphagia episodes (5, 3-6), regurgitation and vomiting (4, 2-5), response to dietary restrictions (4, 1-6); endoscopic items: whitish exudates (5, 3-6), furrowing (4, 3-6), corrugated rings (4, 2-6), linear shearing (4, 2-6), strictures (3, 2-6); histologic items: intraepithelial eosinophil count (5, 4-6), lamina propria fibrosis (3, 2-6), basal layer enlargement (3, 1-5); laboratory items: % blood eosinophils (3, 0-5). Conclusions: These items will now be reduced in further Delphi rounds, tested on a cohort of 100 pediatric EoE patients and validated in a second independent cohort, resulting in a robust, broadly accepted disease activity index for use in clinical trials and daily care.

07043-017 North Fork Maquoketa Final Report

The North Fork Maquoketa River Headwaters (NFMRH) has been identified as impaired by nutrients, episodic slugs of ammonia and sediment. The NFMRH TMDL plan calls for a "phasing approach" to managing water quality when the origin is non-point source contaminants. This project will address phase 1 using a performance reward program for targeted cooperators to improve environmental index scores using cost-share, EQIP practices and flexible management alternatives. Pre-project assessments suggest that rewards should target refined management of erosion-prone fields and farms with livestock populations, which contribute to the P and N loads responsible for fertilizing filamentous algae blooms that depress dissolved oxygen concentrations in the NFMRH. The Phosphorus Index, Soil Conditioning Index and cornstalk nitrate test will be used by producers to determine effective alternatives, such as no-till planting, to reduce nutrient and sediment delivery. These evironmental indexes will be especially useful for livestock producers in the livestock dense watershed. This project will extend a NRCS-sponsored Conservation Innovation Grant currently offered to producers in the Coffee Creek sub-watershed to a three-year, watershed-wide effort that will be necessary to make significant improvements in environmental management.

Diagnostic algorithm for a validated displacement grading of pediatric supracondylar fractures.

Background: The first AO comprehensive pediatric long bone fracture classification system has been established following a structured path of development and validation with experienced pediatric surgeons. Methods: A follow-up series of agreement studies was applied to specify and evaluate a grading system for displacement of pediatric supracondylar fractures. An iterative process comprising an international group of 5 experienced pediatric surgeons (Phase 1) followed by a pragmatic multicenter agreement study involving 26 raters (Phase 2) was used. The last evaluations were conducted on a consecutive collection of 154 supracondylar fractures documented by standard anteroposterior and lateral radiographs. Results: Fractures were classified according to 1 of 4 grades: I = incomplete fracture with no or minimal displacement; II = Incomplete fracture with continuity of the posterior (extension fracture) or anterior cortex (flexion fracture); III = lack of bone continuity (broken cortex), but still some contact between the fracture planes; IV = complete fracture with no bone continuity (broken cortex), and no contact between the fracture planes. A diagnostic algorithm to support the practical application of the grading system in a clinical setting, as well as an aid using a circle placed over the capitellum was proposed. The overall kappa coefficients were 0.68 and 0.61 in the Phase 1 and Phase 2 studies, respectively. In the Phase 1 study, fracture grades I, II, III, and IV were classified with median accuracies of 91%, 82%, 83%, and 99.5%, respectively. Similar median accuracies of 86% (Grade I), 73% (Grade II), 83%(Grade III), and 92% were reported for the Phase 2 study. Reliability was high in distinguishing complete, unstable fractures from stable injuries [ie, kappa coefficients of 0.84 (Phase 1) and 0.83 (Phase 2) were calculated]; in Phase 2, surgeons' accuracies in classifying complete fractures were all above 85%. Conclusions: With clear and unambiguous definition, this new grading system for supracondylar fracture displacement has proved to be sufficiently reliable and accurate when applied by pediatric surgeons in the framework of clinical routine as well as research.

Precast Concrete Panel Thickness for Epoxy-Coated Prestressing Strands, Volume 2, HR-353, 1994

This final report for Phase 1 of the research on epoxy-coated, prestressing strands in precast prestressed concrete (PC) panels has been published in two volumes. Volume 1--Technical Report contains the problem description, literature review, and survey results; descriptions of the test specimens, experimental tests, and analytical models; discussions of the analytical and experimental results; summary, conclusions, and recommendations; list of references; and acknowledgments. Volume 2--Supplemental Report contains additional information in the form of appendix material for Volume 1 on the questionnaires, strand forces, geometry of the specimens, concrete crack patterns that formed in the strand transfer length and strand development length specimens, concrete strains in the strand transfer length specimens, and load-point deflections and strand-slip measurements for the strand development length specimens. Appendix A contains the questionnaires that were sent to the design agencies and precast concrete producers. A summary of the results to the questions on the surveys are given as the number of respondents who provided the same answers and as paraphrased comments from the respondents. Appendix B contains graphs of strand force versus time, strand force versus temperature, and strand force versus strand cutting sequence for the concrete castings. Appendix C contains figures that show the location of each specimen in the prestress bed, the geometrical configurations for the strand transfer length (T-type) specimens and strand development length (D-type) specimens, and the concrete cracks that developed in some of the T-type specimens when they were prestressed. Appendix D contains figures that show the concrete cracks that developed in the D-type specimens during the strand development length tests. For each of these tests, the sequence of the failure for the specimen is specified. Appendix E contains graphs of concrete strain versus distance from the end of the T-type specimens that were instrumented with internal embedment strain gages. Appendix F contains graphs of load versus load-point deflection and load versus strand-slip for the strand development length tests of the D-type specimens.

Field Instrumentation, Testing, and Long-Term Monitoring of High-Mast Lighting Towers in the State of Iowa, TR-518, 2006

As a result of the collapse of a 140 foot high-mast lighting tower in Sioux City, Iowa in November of 2003, a thorough investigation into the behavior and design of these tall, yet relatively flexible structures was undertaken. Extensive work regarding the root cause of this failure was carried out by Robert Dexter of The University of Minnesota. Furthermore, a statewide inspection of all the high-mast towers in Iowa revealed fatigue cracks and loose anchor bolts on other existing structures. The current study was proposed to examine the static and dynamic behavior of a variety of towers in the State of Iowa utilizing field testing, specifically long-term monitoring and load testing. This report presents the results and conclusions from this project. The field work for this project was divided into two phases. Phase 1 of the project was conducted in October 2004 and focused on the dynamic properties of ten different towers in Clear Lake, Ames, and Des Moines, Iowa. Of those ten, two were also instrumented to obtain stress distributions at various details and were included in a 12 month long-term monitoring study. Phase 2 of this investigation was conducted in May of 2005, in Sioux City, Iowa, and focused on determining the static and dynamic behavior of a tower similar to the one that collapsed in November 2003. Identical tests were performed on a similar tower which was retrofitted with a more substantial replacement bottom section in order to assess the effect of the retrofit. A third tower with different details was dynamically load tested to determine its dynamic characteristics, similar to the Phase 1 testing. Based on the dynamic load tests, the modal frequencies of the towers fall within the same range. Also, the damping ratios are significantly lower in the higher modes than the values suggested in the AASHTO and CAN/CSA specifications. The comparatively higher damping ratios in the first mode may be due to aerodynamic damping. These low damping ratios in combination with poor fatigue details contribute to the accumulation of a large number of damage-causing cycles. As predicted, the stresses in the original Sioux City tower are much greater than the stresses in the retrofitted towers at Sioux City. Additionally, it was found that poor installation practices which often lead to loose anchor bolts and out-of-level leveling nuts can cause high localized stresses in the towers, which can accelerate fatigue damage.

Promotion of learning skills in the study of economics. pilot project in the subject area of

This communication is part of a larger teaching innovation project financed by the University ofBarcelona, whose objective is to develop and evaluate transversal competences of the UB, learningability and responsibility. The competence is divided into several sub-competencies being the ability toanalyze and synthesis the most intensely worked in the first year. The work presented here part fromthe results obtained in phase 1 and 2 previously implemented in other subjects (Mathematics andHistory) in the first year of the degree of Business Administration Degree. In these subjects’ previousexperiences there were deficiencies in the acquisition of learning skills by the students. The work inthe subject of Mathematics facilitated that students become aware of the deficit. The work on thesubject of History insisted on developing readings schemes and with the practical exercises wassought to go deeply in the development of this competence.The third phase presented here is developed in the framework of the second year degree, in the WorldEconomy subject. The objective of this phase is the development and evaluation of the same crosscompetence of the previous phases, from a practice that includes both, quantitative analysis andcritical reflection. Specifically the practice focuses on the study of the dynamic relationship betweeneconomic growth and the dynamics in the distribution of wealth. The activity design as well as theselection of materials to make it, has been directed to address gaps in the ability to analyze andsynthesize detected in the subjects of the first year in the previous phases of the project.The realization of the practical case is considered adequate methodology to improve the acquisition ofcompetence of the students, then it is also proposed how to evaluate the acquisition of suchcompetence. The practice is evaluated based on a rubric developed in the framework of the projectobjectives. Thus at the end of phase 3 we can analyze the process that have followed the students,detect where they have had major difficulties and identify those aspects of teaching that can help toimprove the acquisition of skills by the students. The interest of this phase resides in the possibility tovalue whether tracing of learning through competences, organized in a collaborative way, is a goodtool to develop the acquisition of these skills and facilitate their evaluation.

Effectiveness of a drug dosing service provided by community pharmacists in polymedicated elderly patients with renal impairment a comparative study

Background: Drug dosing errors are common in renal-impaired patients. Appropriate dosing adjustment and drug selection is important to ensure patients" safety and to avoid adverse drug effects and poor outcomes. There are few studies on this issue in community pharmacies. The aims of this study were, firstly, to determine the prevalence of dosing inadequacy as a consequence of renal impairment in patients over 65 taking 3 or more drug products who were being attended in community pharmacies and, secondly, to evaluate the effectiveness of the community pharmacist"s intervention in improving dosing inadequacy in these patients when compared with usual care. Methods: The study was carried out in 40 Spanish community pharmacies. The study had two phases: the first, with an observational, multicentre, cross sectional design, served to determine the dosing inadequacy, the drug-related problems per patient and to obtain the control group. The second phase, with a controlled study with historical control group, was the intervention phase. When dosing adjustments were needed, the pharmacists made recommendations to the physicians. A comparison was made between the control and the intervention group regarding the prevalence of drug dosing inadequacy and the mean number of drug-related problems per patient. Results: The mean of the prevalence of drug dosing inadequacy was 17.5% [95% CI 14.6-21.5] in phase 1 and 15.5% [95% CI 14.5-16.6] in phase 2. The mean number of drug-related problems per patient was 0.7 [95% CI 0.5-0.8] in phase 1 and 0.50 [95% CI 0.4-0.6] in phase 2. The difference in the prevalence of dosing inadequacy between the control and intervention group before the pharmacists" intervention was 0.73% [95% CI (−6.0) - 7.5] and after the pharmacists" intervention it was 13.5% [95% CI 8.0 - 19.5] (p < 0.001) while the difference in the mean of drug-related problems per patient before the pharmacists" intervention was 0.05 [95% CI( -0.2) - 0.3] and following the intervention it was 0.5 [95% CI 0.3 - 0.7] (p < 0.001). Conclusion: A drug dosing adjustment service for elderly patients with renal impairment in community pharmacies can increase the proportion of adequate drug dosing, and improve the drug-related problems per patient. Collaborative practice with physicians can improve these results.

Effectiveness of a drug dosing service provided by community pharmacists in polymedicated elderly patients with renal impairment a comparative study

Background: Drug dosing errors are common in renal-impaired patients. Appropriate dosing adjustment and drug selection is important to ensure patients" safety and to avoid adverse drug effects and poor outcomes. There are few studies on this issue in community pharmacies. The aims of this study were, firstly, to determine the prevalence of dosing inadequacy as a consequence of renal impairment in patients over 65 taking 3 or more drug products who were being attended in community pharmacies and, secondly, to evaluate the effectiveness of the community pharmacist"s intervention in improving dosing inadequacy in these patients when compared with usual care. Methods: The study was carried out in 40 Spanish community pharmacies. The study had two phases: the first, with an observational, multicentre, cross sectional design, served to determine the dosing inadequacy, the drug-related problems per patient and to obtain the control group. The second phase, with a controlled study with historical control group, was the intervention phase. When dosing adjustments were needed, the pharmacists made recommendations to the physicians. A comparison was made between the control and the intervention group regarding the prevalence of drug dosing inadequacy and the mean number of drug-related problems per patient. Results: The mean of the prevalence of drug dosing inadequacy was 17.5% [95% CI 14.6-21.5] in phase 1 and 15.5% [95% CI 14.5-16.6] in phase 2. The mean number of drug-related problems per patient was 0.7 [95% CI 0.5-0.8] in phase 1 and 0.50 [95% CI 0.4-0.6] in phase 2. The difference in the prevalence of dosing inadequacy between the control and intervention group before the pharmacists" intervention was 0.73% [95% CI (−6.0) - 7.5] and after the pharmacists" intervention it was 13.5% [95% CI 8.0 - 19.5] (p < 0.001) while the difference in the mean of drug-related problems per patient before the pharmacists" intervention was 0.05 [95% CI( -0.2) - 0.3] and following the intervention it was 0.5 [95% CI 0.3 - 0.7] (p < 0.001). Conclusion: A drug dosing adjustment service for elderly patients with renal impairment in community pharmacies can increase the proportion of adequate drug dosing, and improve the drug-related problems per patient. Collaborative practice with physicians can improve these results.