Patient safety in Dutch primary care: a study protocol

<p>Abstract</p> <p>Background</p> <p>Insight into the frequency and seriousness of potentially unsafe situations may be the first step towards improving patient safety. Most patient safety attention has been paid to patient safety in hospitals. However, in many countries, patients receive most of their healthcare in primary care settings. There is little concrete information about patient safety in primary care in the Netherlands. The overall aim of this study was to provide insight into the current patient safety issues in Dutch general practices, out-of-hours primary care centres, general dental practices, midwifery practices, and allied healthcare practices. The objectives of this study are: to determine the frequency, type, impact, and causes of incidents found in the records of primary care patients; to determine the type, impact, and causes of incidents reported by Dutch healthcare professionals; and to provide insight into patient safety management in primary care practices.</p> <p>Design and methods</p> <p>The study consists of three parts: a retrospective patient record study of 1,000 records per practice type was conducted to determine the frequency, type, impact, and causes of incidents found in the records of primary care patients (objective one); a prospective component concerns an incident-reporting study in each of the participating practices, during two successive weeks, to determine the type, impact, and causes of incidents reported by Dutch healthcare professionals (objective two); to provide insight into patient safety management in Dutch primary care practices (objective three), we surveyed organizational and cultural items relating to patient safety. We analysed the incidents found in the retrospective patient record study and the prospective incident-reporting study by type of incident, causes (Eindhoven Classification Model), actual harm (severity-of-outcome domain of the International Taxonomy of Medical Errors in Primary Care), and probability of severe harm or death.</p> <p>Discussion</p> <p>To estimate the frequency of incidents was difficult. Much depended on the accuracy of the patient records and the professionals' consensus about which types of adverse events have to be recognized as incidents.</p

Cadherins and Pak1 Control Contact Inhibition of Proliferation by Pak1-βPIX-GIT Complex-Dependent Regulation of Cell-Matrix Signaling ▿

It is crucial for organ homeostasis that epithelia have effective mechanisms to restrict motility and cell proliferation in order to maintain tissue architecture. On the other hand, epithelial cells need to rapidly and transiently acquire a more mesenchymal phenotype, with high levels of cell motility and proliferation, in order to repair epithelia upon injury. Cross talk between cell-cell and cell-matrix signaling is crucial for regulating these transitions. The Pak1-βPIX-GIT complex is an effector complex downstream of the small GTPase Rac1. We previously showed that translocation of this complex from cell-matrix to cell-cell adhesion sites was required for the establishment of contact inhibition of proliferation. In this study, we provide evidence that this translocation depends on cadherin function. Cadherins do not recruit the complex by direct interaction. Rather, we found that inhibition of the normal function of cadherin or Pak1 leads to defects in focal adhesion turnover and to increased signaling by phosphatidylinositol 3-kinase. We propose that cadherins are involved in regulation of contact inhibition by controlling the function of the Pak1-βPIX-GIT complex at focal contacts

Involvement of RhoA, ROCK I and myosin II in inverted orientation of epithelial polarity

In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin–Darby canine kidney cells in three-dimensional collagen gel culture, blockade of β1-integrin by the AIIB2 antibody or expression of dominant-negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA–ROCK I–myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers

Polyisocyanide hydrogels as a tunable platform for mammary gland organoid formation

In the last decade, organoid technology has developed as a primary research tool in basic biological and clinical research. The reliance on poorly defined animal-derived extracellular matrix, however, severely limits its application in regenerative and translational medicine. Here, a well-defined, synthetic biomimetic matrix based on polyisocyanide (PIC) hydrogels that support efficient and reproducible formation of mammary gland organoids (MGOs) in vitro is presented. Only decorated with the adhesive peptide RGD for cell binding, PIC hydrogels allow MGO formation from mammary fragments or from purified single mammary epithelial cells. The cystic organoids maintain their capacity to branch for over two months, which is a fundamental and complex feature during mammary gland development. It is found that small variations in the 3D matrix give rise to large changes in the MGO: the ratio of the main cell types in the MGO is controlled by the cell–gel interactions via the cell binding peptide density, whereas gel stiffness controls colony formation efficiency, which is indicative of the progenitor density. Simple hydrogel modifications will allow for future introduction and customization of new biophysical and biochemical parameters, making the PIC platform an ideal matrix for in depth studies into organ development and for application in disease models