Previously it was shown that the Arabidopsis apyrase genes AtAPY1 and AtAPY2 are crucial for male fertility because mutant pollen (apy1-1; apy2-1) with T-DNA insertions in both genes could not germinate (Steinebrunner et al. (2003) Plant Physiol. 131: 1638-1647). In this study, pollen germination was restored and apyrase T-DNA double knockouts (DKO) apy1-1/apy1-1; apy2-1/apy2-1 were generated by complementation with AtAPY2 under the control of a pollen-specific promoter. The DKO phenotype displayed developmental defects including the lack of functional root and shoot meristems. In cotyledons, morphogenetic and patterning abnormalities were apparent, e.g., unlobed pavement cells and stomatal clusters. Another set of lines was created which carried either AtAPY1 or AtAPY2 under a dexamethasone-(DEX)-inducible promoter as an additional transgene to the pollen-specific gene construct. Application of DEX did not reverse the DKO phenotype to wild-type, but some inducible lines exhibited less severe defects even in the absence of the inducer, probably due to some background expression. However, even these DKO mutants were seedling-lethal and shared other defects regarding cell division, cell expansion and stomatal patterning. Taken together, the defects in the DKO mutants demonstrate that AtAPY1 and AtAPY2 are essential for normal plant development.

Aim of the studyThis prospective, controlled trial aimed to assess the effect of pharmacist-led medication reviews on the medication safety of psychiatric inpatients by the resolution of Drug-Related Problems (DRP). Both the therapy appropriateness measured with the Medication Appropriateness Index (MAI) and the number of unsolved DRP per patient were chosen as primary outcome measures.MethodsDepending on their time of admission, 269 psychiatric patients that were admitted to a psychiatric university hospital were allocated in control (09/2012-03/2013) or intervention group (05/2013-12/2013). In both groups, DRP were identified by comprehensive medication reviews by clinical pharmacists at admission, during the hospital stay, and at discharge. In the intervention group, recommendations for identified DRP were compiled by the pharmacists and discussed with the therapeutic team. In the control group, recommendations were not provided except for serious or life threatening DRP. As a primary outcome measure, the changes in therapy appropriateness from admission to discharge as well as from admission to three months after discharge (follow-up) assessed with the MAI were compared between both groups. The second primary outcome was the number of unsolved DRP per patient after completing the study protocol. The DRP type, the relevance and the potential of drugs to cause DRP were also evaluated.ResultsThe intervention led to a reduced MAI score by 1.4 points per patient (95% confidence interval [CI]: 0.8–2.0) at discharge and 1.3 points (95% CI: 0.7–1.9) at follow-up compared with controls. The number of unsolved DRP in the intervention group was 1.8 (95% CI: 1.5–2.1) less than in control.ConclusionThe pharmaceutical medication reviews with interdisciplinary discussion of identified DRP appears to be a worthy strategy to improve medication safety in psychiatry as reflected by less unsolved DRP per patient and an enhanced appropriateness of therapy. The promising results of this trial likely warrant further research that evaluates direct clinical outcomes and health-related costs.Trial RegistrationDeutsches Register Klinischer Studien (DRKS), DRKS00006358

BackgroundIn psychiatry, hospital stays and transitions to the ambulatory sector are susceptible to major changes in drug therapy that lead to complex medication regimens and common non-adherence among psychiatric patients. A multi-dimensional and inter-sectoral intervention is hypothesized to improve the adherence of psychiatric patients to their pharmacotherapy.Methods269 patients from a German university hospital were included in a prospective, open, clinical trial with consecutive control and intervention groups. Control patients (09/2012-03/2013) received usual care, whereas intervention patients (05/2013-12/2013) underwent a program to enhance adherence during their stay and up to three months after discharge. The program consisted of therapy simplification and individualized patient education (multi-dimensional component) during the stay and at discharge, as well as subsequent phone calls after discharge (inter-sectoral component). Adherence was measured by the “Medication Adherence Report Scale” (MARS) and the “Drug Attitude Inventory” (DAI).ResultsThe improvement in the MARS score between admission and three months after discharge was 1.33 points (95% CI: 0.73–1.93) higher in the intervention group compared to controls. In addition, the DAI score improved 1.93 points (95% CI: 1.15–2.72) more for intervention patients.ConclusionThese two findings indicate significantly higher medication adherence following the investigated multi-dimensional and inter-sectoral program.Trial RegistrationGerman Clinical Trials Register DRKS00006358

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Objectives The aim of the study was to determine the best database regarding accuracy, comprehensiveness and user-friendliness out of eight German and International databases. Methods Accuracy, comprehensiveness and ease of use of ABDA-database (ABDA), MediQ, Pharmavista, MMI Pharmindex, AiDKlinik (AIK), Lexi-Interact (LI), Epocrates and drugs.com were evaluated using 50 clinically relevant and 50 non-relevant drug interaction pairs. Accuracy was determined investigating sensitivity, specificity and positive and negative predictive values. Comprehensiveness was rated according to monograph components. Ease of use was evaluated by the time needed to assess the management of 10 clinically relevant interactions. The main outcome measure was the Total Score (TS) (max. 312.5 points) obtained by adding the specifically weighted points for accuracy, comprehensiveness and ease of use. Results LI ranked first in TS (243/312.5 points), followed by AIK (229/312.5 points). All databases showed high sensitivity. However, they had difficulties in clearly classifying an interaction as non-relevant, reflected in a low specificity. ABDA ranked first in accuracy because it dealt best with this problem. LI provided the most detailed monographs, reflected in a high Comprehensiveness Score. Results for comprehensiveness varied greatly, as the databases are designed for different needs. This also applied to Ease of Use Score, where AIK performed best. Conclusions LI proved to be the most recommendable database in our evaluation due to its superior comprehensiveness. All databases scored rather well on accuracy, but showed a tendency towards over-alerting.

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