Effect evaluation of an interprofessional medication therapy management approach for multimorbid patients in primary care: a cluster-randomized controlled trial in community care (WestGem study protocol)

Background: Pharmaceutical practice worldwide is developing towards patient care. Medication Review (MR) and Medication Therapy Management (MTM) are evolving as the most prominent services in pharmaceutical care and have a strong potential to provide a large benefit for patients and society. MTMs can only be performed in an interprofessional, collaborative setting. Several international studies have explored the effects of a MTM on the quality of therapy and costs. For Germany the data is still deficient. This study aims to provide data on the effects of an interprofessional MTM regarding quality of therapy, quality of life, costs and cost-effectiveness. Method/Design: The study is designed as a cluster-randomized controlled trial in primary care, involving 12 outpatient clinics (clusters) and 165 patients. Primary care units are allocated to interventions using a Stepped Wedge Design. All units are initially assigned to the control group. After a 6 month observation period, general practitioners (GP) are randomly allocated to one of three groups and the interprofessional medication therapy management approach is implemented sequentially per each group with a lag of 3 months between. The primary outcome is the change in the quality of therapy measured by the MAI (Medication Appropriateness Index). Secondary outcomes include changes in the number of drug related problems, medication complexity, changes in drug-adherence, changes in health-status and function, quality of life, direct costs and the incremental cost-effectiveness ratio. The acceptance of the interprofessional Medication Therapy Management approach is assessed by qualitative methods. Discussion: The patient interview and brown bag review are activities, typically provided by the pharmacist. In this trial the patient is blinded to the pharmacist. The strength of having the patient blinded to the pharmacists is to exclude skepticism of the patient toward unknown pharmacies, which might be a major confounder in a regional and community setting. A weakness is that some patient related data might reach the pharmacists in a way, which might differ from self-acquired data

Constitutive activation of oncogenic PDGFRalpha-mutant proteins occurring in GIST patients induces receptor mislocalisation and alters PDGFRalpha signalling characteristics.

BACKGROUND: Gastrointestinal stromal tumours (GIST) are mainly characterised by the presence of activating mutations in either of the two receptor tyrosine kinases c-KIT or platelet-derived growth factor receptor-alpha (PDGFRalpha). Most mechanistic studies dealing with GIST mutations have focused on c-KIT and far less is known about the signalling characteristics of the mutated PDGFRalpha proteins. Here, we study the signalling capacities and corresponding transcriptional responses of the different PDGFRalpha proteins under comparable genomic conditions. RESULTS: We demonstrate that the constitutive signalling via the oncogenic PDGFRalpha mutants favours a mislocalisation of the receptors and that this modifies the signalling characteristics of the mutated receptors. We show that signalling via the oncogenic PDGFRalpha mutants is not solely characterised by a constitutive activation of the conventional PDGFRalpha signalling pathways. In contrast to wild-type PDGFRalpha signal transduction, the activation of STAT factors (STAT1, STAT3 and STAT5) is an integral part of signalling mediated via mutated PDGF-receptors. Furthermore, this unconventional STAT activation by mutated PDGFRalpha is already initiated in the endoplasmic reticulum whereas the conventional signalling pathways rather require cell surface expression of the receptor. Finally, we demonstrate that the activation of STAT factors also translates into a biologic response as highlighted by the induction of STAT target genes. CONCLUSION: We show that the overall oncogenic response is the result of different signatures emanating from different cellular compartments. Furthermore, STAT mediated responses are an integral part of mutated PDGFRalpha signalling

Sorption-desorption of atrazine and simazine by model soil colloidal components

Sorption-desorption of atrazine and simazine on montmorillonite, ferrihydrite, and humic acid was determined using the batch equilibration procedure. Sorption of atrazine and simazine was higher on humic acid than on montmorillonite. Ferrihydrite does not sorb triazine herbicides. Enhanced sorption of atrazine and simazine on montmorillonite was measured after increasing the surface acidity of the clay. Results indicate sorption of s-triazine herbicides on montmorillonite as protonated species must be preceded by sorption as molecular species on hydrophobic microsites of the clay unless the pH of the bulk solution is close to the pK(a) of the herbicide. In this latter case, cation exchange would be also operative. Sorption-desorption of atrazine and simazine was more hysteretic for humic acid than for montmorillonite, indicating that these herbicides desorb more difficultly from organic matter than from montmorillonite because of the contribution of hydrophobic interactions with humic acid. It is suggested that, besides organic matter, smectites of low charge density and high surface acidity should increase the retention of s-triazine herbicides in soils.Peer Reviewe

Priority Setting and Influential Factors on Acceptance of Pharmaceutical Recommendations in Collaborative Medication Reviews in an Ambulatory Care Setting - Analysis of a Cluster Randomized Controlled Trial (WestGem-Study)

Background Medication reviews are recognized services to increase quality of therapy and reduce medication risks. The selection of eligible patients with potential to receive a major benefit is based on assumptions rather than on factual data. Acceptance of interprofessional collaboration is crucial to increase the quality of medication therapy. Objective The research question was to identify and prioritize eligible patients for a medication review and to provide evidence-based criteria for patient selection. Acceptance of the prescribing general practitioner to implement pharmaceutical recommendations was measured and factors influencing physicians' acceptance were explored to obtain an impression on the extent of collaboration in medication review in an ambulatory care setting. Methods Based on data of a cluster-randomized controlled study (WestGem-study), the correlation between patient parameters and the individual performance in a medication review was calculated in a multiple logistic regression model. Physician's acceptance of the suggested intervention was assessed using feedback forms. Influential factors were analyzed. Results The number of drugs in use (p = 0.001), discrepancies between prescribed and used medicines (p = 0.014), the baseline Medication Appropriateness Index score (p0.05) and a low kidney function (p>0.05) do not predetermine the outcome. Longitudinal patient care with repeated reviews showed higher interprofessional acceptance and superior patient benefit. A total of 54.9% of the recommendations in a medication review on drug therapy were accepted for implementation. Conclusions The number of drugs in use and medication reconciliation could be a first rational step in patient selection for a medication review. Most elderly, multimorbid patients with polymedication experience a similar chance of receiving a benefit from a medication review. Longitudinal patient care should be preferred over confined medication reviews. The acceptance of medication reviews by physicians supports further implementation into health care systems

CONSORT flow diagram of the WestGem-study.

<p>CONSORT flow diagram of the WestGem-study.</p

Results of the multiple logistic regressions after automatic selection, approach 1, early detectable parameters and approach 2, later detectable parameters.

<p>Results of the multiple logistic regressions after automatic selection, approach 1, early detectable parameters and approach 2, later detectable parameters.</p

Patient characteristics for the ITT group and for eligible patients of the acceptance analysis.

<p>Data is presented as mean (SD) unless otherwise indicated.</p

Baseline characteristics of the studied patient group (N = 129).

<p>Data is presented as mean ± SD unless otherwise indicated.</p