Effects of a Computerized Prescriber Order Entry System on Pharmacist Prescribing.

Background: In Alberta, pharmacists are eligible to obtain additional prescribing authority (APA). At the University of Alberta Hospital, a transition was made from a paper-based prescriber order entry system to a computerized prescriber order entry (CPOE) system. Objectives: The primary objective was to quantify any change in pharmacist prescribing after CPOE implementation. The secondary objective was to compare the paper-based and CPOE systems in terms of drug schedule, order type, medication class, and the pharmacist's area of clinical practice. Methods: A retrospective comparative review of pharmacist orders was completed using 2-week periods of data from each of the paper-based order entry system and the CPOE system, spaced 1 year apart (in January 2019 and January 2020). Results: Pharmacists prescribed a mean of 3.76 (95% confidence interval 1.97-5.96) more orders per day within the CPOE system than in the paper-based system (p < 0.001). Schedule I medications accounted for a higher proportion of pharmacists' prescriptions in the CPOE system than in the paper-based system (77.7% versus 70.5%, p < 0.001). In terms of order type, discontinuation orders accounted for a much higher proportion of pharmacists' orders in the CPOE system than in the paper-based order entry system (58.0% versus 19.8%, p < 0.001). Conclusions: This study showed that a CPOE system resulted in more use of APA by pharmacists, with schedule I medications accounting for a higher proportion of pharmacists' prescriptions. With the CPOE system, pharmacists used their prescribing privileges to discontinue a higher proportion of orders than was the case with the paper-based system. Therefore, the CPOE system is a potential facilitator of pharmacist prescribing.

Contexte: En Alberta, les pharmaciens peuvent obtenir des pouvoirs de prescription supplémentaires (PPS). À l'hôpital de l'Université de l'Alberta, le système de saisie des ordonnances est passé d'un système sur papier à un système de saisie électronique des ordonnances (SSEO) par les prescripteurs. Objectifs: L'objectif principal consistait à quantifier tout changement dans la prescription des pharmaciens après la mise en place du SSEO. L'objectif secondaire visait à comparer le système sur papier et le SSEO en matière d'annexe des médicaments, de type d'ordonnance, de catégorie de médicament et de domaine de pratique clinique du pharmacien. Méthodes: Un examen comparatif rétrospectif des ordonnances des pharmaciens a été réalisé à l'aide de périodes de données de 2 semaines provenant de chacun des systèmes (papier et électronique), avec un intervalle d'un an (janvier 2019 et janvier 2020). Résultats: Les pharmaciens prescrivaient en moyenne 3,76 (intervalle de confiance à 95 % 1,97­5,96) ordonnances de plus par jour avec le SSEO qu'avec le système sur papier (p < 0,001). La part des ordonnances de médicaments de l'annexe I était plus importante avec le SSEO qu'avec le système sur papier (77,7 % contre 70,5 %, p < 0,001). En ce qui concerne le type d'ordonnance, la part des ordonnances de cessation était beaucoup plus élevée avec le SSEO qu'avec le système de saisie sur papier (58,0 % contre 19,8 %, p < 0,001). Conclusions: Cette étude a démontré un plus grand recours au PPS lorsque les pharmaciens utilisaient un SSEO et les médicaments de l'annexe I représentant une proportion plus élevée des ordonnances. Avec le SSEO, les pharmaciens ont utilisé leur pouvoir de prescription pour interrompre une part plus élevée d'ordonnances que ce n'était le cas avec le système sur papier. Le SSEO est donc un facilitateur potentiel de la prescription par les pharmaciens.

Resilencia: abordaje psicosocial, espiritual y educativo en el tratamiento del paciente adultos con obesidad / Resilence: psychosocial, spiriitual and educational approach for the treatment of adult patients with obesity

Introducción: El constructo de resiliencia es un proceso dinámico que puede ser abordado por todo ser humano si es que se cuenta con los recursos o se acompaña en la búsqueda de estos para construirlo. Conectar con la sensorialidad y la conciencia corporal contribuye a promover las diferentes leyes de la nutrición enunciadas por el Profesor Julio Escudero. El cuerpo se entrena para percibir mejor los estímulos, los cuales son importantes a la hora de nutrirse. Objetivos: Identificar estudios realizados sobre el abordaje de la resiliencia para el tratamiento de la enfermedad crónica; describir el abordaje multidisciplinario psicosocial, espiritual y educativo que propone la resiliencia para el tratamiento de los pacientes adultos con obesidad, interpretar y describir qué recursos involucran el trabajo corporal y el de movimiento en el tratamiento de los pacientes adultos obesos. Métodos: Diseño de revisión bibliográfica. Se hallaron 44 documentos. Se consultaron bases de datos electrónicas y se sumaron citas identificadas en búsquedas adicionales. Se utilizaron descriptores, términos libre y campos de búsqueda según criterios de inclusión. Resultados: La evidencia encontrada, fundamentalmente, relaciona enfermedades crónicas con el abordaje desde la resiliencia y, posteriormente, narra la asociación de la obesidad en relación con el abordaje terapéutico desde la resiliencia. Desde la intervención psicosocial, se ha demostrado que las técnicas que propone el modelo transteórico de Prochaska y Di Clemente (1982), asociándolas a la entrevista motivacional, resultan eficaces. El tratamiento cognitivo-comportamental también demostró eficacia. Con respecto a la espiritualidad como abordaje desde la resiliencia, los resultados son dispares. En cuanto al abordaje educativo, se han encontrado resultados favorecedores, especialmente, enfocados en la educación terapéutica brindada por los equipos de salud. La práctica de movimiento y de trabajo corporal ha demostrado resultados positivos al integrarla en talleres de educación terapéutica. Conclusión: Se evidencia un gran potencial al trabajar desde la resiliencia, incluyendo prácticas de danza-terapia, para el tratamiento de personas adultas con obesidad

Introduction: The resilience construct is a dynamic process that can be approached by every human being if they have the resources or are accompanied in the search for those resources to build it. Connecting with sensoriality and body awareness helps to promote the different laws of nutrition enunciated by Professor Escudero. The body trains itself to better perceive the stimuli which are important when it comes to nourishing itself. Objectives: To explore studies carried out on the resilience approach for the treatment of chronic disease; describe the multidisciplinary psychosocial, spiritual and educational approach proposed by resilience for the treatment of adult patients with obesity, identify which resources involve body work and movement in the treatment of obese adult patients. Methods: Literature review design. 44 documents were found. Electronic databases were consulted and citations identified in additional searches were added. Free term, descriptors and search fields were used according to inclusion criteria. Results: The evidence found fundamentally relates chronic diseases with the approach from resilience and subsequently narrates the association of obesity in relation to the therapeutic approach from resilience. From psychosocial intervention, it has been shown that the techniques proposed by the transtheoretical model of Prochaska and Di Clemente, associating them with motivational interviewing, are effective. Cognitive-behavioral treatment also demonstrated efficacy. With respect to spirituality as an approach from resilience, the results are disparate. Regarding the educational approach, favorable results have been found, especially focused on therapeutic education provided by health teams. The practice of movement and bodywork has shown positive results when integrated into therapeutic education workshops. Conclusion: There is evidence of great potential when working from resilience, including dance-therapy practices, for the treatment of adults with obesity

Smart Hydrogels for the Augmentation of Bone Regeneration by Endogenous Mesenchymal Progenitor Cell Recruitment.

The treatment of bone defects with recombinant bone morphogenetic protein-2 (BMP-2) requires high doses precluding broad clinical application. Here, a bioengineering approach is presented that strongly improves low-dose BMP-2-based bone regeneration by mobilizing healing-associated mesenchymal progenitor cells (MPCs). Smart synthetic hydrogels are used to trap and study endogenous MPCs trafficking to bone defects. Hydrogel-trapped and prospectively isolated MPCs differentiate into multiple lineages in vitro and form bone in vivo. In vitro screenings reveal that platelet-derived growth factor BB (PDGF-BB) strongly recruits prospective MPCs making it a promising candidate for the engineering of hydrogels that enrich endogenous MPCs in vivo. However, PDGF-BB inhibits BMP-2-mediated osteogenesis both in vitro and in vivo. In contrast, smart two-way dynamic release hydrogels with fast-release of PDGF-BB and sustained delivery of BMP-2 beneficially promote the healing of bone defects. Collectively, it is shown that modulating the dynamics of endogenous progenitor cells in vivo by smart synthetic hydrogels significantly improves bone healing and holds great potential for other advanced applications in regenerative medicine.

A Cohort Study of the Milk Microbiota of Healthy and Inflamed Bovine Mammary Glands From Dryoff Through 150 Days in Milk.

The objective of this longitudinal cohort study was to describe the milk microbiota of dairy cow mammary glands based on inflammation status before and after the dry period. Individual mammary quarters were assigned to cohorts based on culture results and somatic cell count (SCC) at dryoff and twice in the first 2 weeks post-calving. Mammary glands that were microbiologically negative and had low SCC (< 100,000 cells/mL) at all 3 sampling periods were classified as Healthy (n = 80). Microbiologically negative mammary glands that had SCC ≥150,000 cells/mL at dryoff and the first post-calving sample were classified as Chronic Culture-Negative Inflammation (CHRON; n = 17). Quarters that did not have both culture-negative milk and SCC ≥ 150,000 cells/mL at dryoff but were culture-negative with SCC ≥ 150,000 at both post-calving sampling periods were classified as Culture-Negative New Inflammation (NEWINF; n = 6). Mammary glands with bacterial growth and SCC ≥ 150,000 cells/mL at all 3 periods were classified as Positive (POS; n = 3). Milk samples were collected from all enrolled quarters until 150 days in milk and subjected to microbiota analysis. Milk samples underwent total DNA extraction, a 40-cycle PCR to amplify the V4 region of the bacterial 16S rRNA gene, and next-generation sequencing. Healthy quarters had the lowest rate of PCR and sequencing success (53, 67, 83, and 67% for Healthy, CHRON, NEWINF, and POS, respectively). Chao richness was greatest in milk collected from Healthy quarters and Shannon diversity was greater in milk from Healthy and CHRON quarters than in milk collected from glands in the NEWINF or POS cohorts. Regardless of cohort, season was associated with both richness and diversity, but stage of lactation was not. The most prevalent OTUs included typical gut- and skin-associated bacteria such as those in the phylum Bacteroidetes and the genera Enhydrobacter and Corynebacterium. The increased sequencing success in quarters with worse health outcomes, combined with the lack of bacterial growth in most samples and the high PCR cycle number required for amplification of bacterial DNA, suggests that the milk microbiota of culture-negative, healthy mammary glands is less abundant than that of culture-negative glands with a history of inflammation.

Understanding the Milk Microbiota.

The milk microbiota is an intriguing area of research because milk with no bacterial growth in culture was long thought to be sterile. Recent DNA sequencing techniques have been developed that do not require bacteria to be culturable, and DNA from new bacteria have been reported in milk from dairy cow mammary glands with or without mastitis. Methodologies and results vary among research groups, and not enough is known about the milk microbiota for the results to be used for diagnosis or prognosis of mastitis.

Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes.

Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin γ1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs.

Cell-Mediated Proteolytic Release of Growth Factors from Poly(Ethylene Glycol) Matrices.

Engineering in vitro tissue mimetics that resemble the corresponding living tissues requires the 3D arrangement of tissue progenitor cells and their differentiation by localized growth factor (GF) signaling cues. Recent technological advances open a large field of possibilities for the creation of complex GF arrangements. Additionally, cell-instructive biomaterials, which bind GFs by various mechanisms and release them with different kinetics depending on binding affinity, have become available. This paper describes the development of a matrix metalloproteinase (MMP)-degradable streptavidin-based linker module, which allows the release of immobilized GFs from synthetic biomimetic poly(ethylene glycol) hydrogels independently of the hydrogel degradation. The MMP-sensitive streptavidin linker is shown to efficiently bind biotinylated molecules, and as proof of concept, bone morphogenetic protein-2 (BMP-2) delivery via the MMP-degradable linker is used to induce osteogenic differentiation in C2C12 cells and mesenchymal stem cells. The results show a significantly increased net effect of proteolytically releasable BMP-2 in comparison to stably immobilized and soluble BMP-2. This study indicates that a GF delivery system directly responsive to cellular activity can have important implications for the synthesis of tissue mimetics and regenerative medicine, as it can influence the availability, the localization of effects, as well as efficacy of employed GFs.

Home Dialysis Modalities: Educational Barriers to Utilization.

In the United States, an increasing number of individuals are being diagnosed with end stage renal disease requiring renal replacement therapy. Home dialysis modalities are an available option in lieu of in-center hemodialysis therapy for these individuals, but are vastly underutilized in the U.S. for multiple reasons. Both healthcare providers and individuals requiring renal replacement therapy are frequently unaware these modalities are an available alternative to in-center hemodialysis and of the potential benefits related to home modality use. Lack of healthcare provider and patient education regarding home modalities is a primary factor related to underutilization.

Enzyme responsive GAG-based natural-synthetic hybrid hydrogel for tunable growth factor delivery and stem cell differentiation.

We describe an enzymatically formed chondroitin sulfate (CS) and poly(ethylene glycol) (PEG) based hybrid hydrogel system, which by tuning the architecture and composition of modular building blocks, allows the application-specific tailoring of growth factor delivery and cellular responses. CS, a negatively charged sulfate-rich glycosaminoglycan of the extracellular matrix (ECM), known for its growth factor binding and stem cell regulatory functions, is used as a starting material for the engineering of this biomimetic materials platform. The functionalization of CS with transglutaminase factor XIII specific substrate sequences is utilized to allow cross-linking of CS with previously described fibrin-mimetic TG-PEG hydrogel precursors. We show that the hydrogel network properties can be tuned by varying the degree of functionalization of CS as well as the ratio and concentrations of PEG and CS precursors. Taking advantage of TG-PEG hydrogel, compatible tagged bio-functional building blocks, including RGD peptides or matrix metalloproteinase sensitive domains, can be incorporated on demand allowing the three-dimensional culture and expansion of human bone marrow mesenchymal stem cells (BM-MSCs). The binding of bone morphogenetic protein-2 (BMP-2) in a CS concentration dependent manner and the BMP-2 release mediated osteogenic differentiation of BM-MSCs indicate the potential of CS-PEG hybrid hydrogels to promote regeneration of bone tissue. Their modular design allows facile incorporation of additional signaling elements, rendering CS-PEG hydrogels a highly flexible platform with potential for multiple biomedical applications.

Dual Role of Mesenchymal Stem Cells Allows for Microvascularized Bone Tissue-Like Environments in PEG Hydrogels.

In vitro engineered tissues which recapitulate functional and morphological properties of bone marrow and bone tissue will be desirable to study bone regeneration under fully controlled conditions. Among the key players in the initial phase of bone regeneration are mesenchymal stem cells (MSCs) and endothelial cells (ECs) that are in close contact in many tissues. Additionally, the generation of tissue constructs for in vivo transplantations has included the use of ECs since insufficient vascularization is one of the bottlenecks in (bone) tissue engineering. Here, 3D cocultures of human bone marrow derived MSCs (hBM-MSCs) and human umbilical vein endothelial cells (HUVECs) in synthetic biomimetic poly(ethylene glycol) (PEG)-based matrices are directed toward vascularized bone mimicking tissue constructs. In this environment, bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor-2 (FGF-2) promotes the formation of vascular networks. However, while osteogenic differentiation is achieved with BMP-2, the treatment with FGF-2 suppressed osteogenic differentiation. Thus, this study shows that cocultures of hBM-MSCs and HUVECs in biological inert PEG matrices can be directed toward bone and bone marrow-like 3D tissue constructs.

Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering.

Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

Inhibition of angiogenesis by antioxidant micelles.

Antioxidant micelles capable of scavenging reactive oxygen species (ROS) are prepared from poly(ethylene glycol)-b-poly(dopamine) block copolymers. The micelles inhibit tube formation of human umbilical vein endothelial cells (HUVECs) by scavenging endogenous ROS. Furthermore, the micelles inhibit angiogenesis in the chicken ex ovo chorioallantoic membrane assay. The results show that antioxidant micelles containing catechol moieties may be useful in anti-angiogenic therapy to treat various diseases such as cancer.

Modular poly(ethylene glycol) matrices for the controlled 3D-localized osteogenic differentiation of mesenchymal stem cells.

The in vitro formation of physiologically relevant engineered tissues is still limited by the availability of adequate growth-factor-presenting cell-instructive biomaterials, allowing simultaneous and three-dimensionally localized differentiation of multiple tissue progenitor cells. Together with ever improving technologies such as microfluidics, printing, or lithography, these biomaterials could provide the basis for generating provisional cellular constructs, which can differentiate to form tissue mimetics. Although state-of-the-art biomaterials are endowed with sophisticated modules for time- and space-controlled positioning and release of bioactive molecules, reports on 3D arrangements of differentiation-inducing growth factors are scarce. This paper describes the stable and localized immobilization of biotinylated bioactive molecules to a modular, Factor XIII-cross-linked poly(ethylene glycol) hydrogel platform using a genetically engineered streptavidin linker. Linker incorporation is demonstrated by Western blot, and streptavidin functionality is confirmed by capturing biotinylated alkaline phosphatase (ALP). After optimizing bone morphogenetic protein 2 (BMP-2) biotinylation, streptavidin-modified hydrogels are able to bind and present bioactive BMP-2-biotin. Finally, with this immobilization scheme for BMP-2, the specific osteogenic differentiation of mesenchymal stem cells is demonstrated by inducing ALP expression in confined 3D areas. In future, this platform together with other affinity-based strategies will be useful for the local incorporation of various growth factors for engineering cell-responsive constructs.

Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing.

Growth factors (GFs) are critical in tissue repair, but their translation to clinical use has been modest. Physiologically, GF interactions with extracellular matrix (ECM) components facilitate localized and spatially regulated signaling; therefore, we reasoned that the lack of ECM binding in their clinically used forms could underlie the limited translation. We discovered that a domain in placenta growth factor-2 (PlGF-2(123-144)) binds exceptionally strongly and promiscuously to ECM proteins. By fusing this domain to the GFs vascular endothelial growth factor-A, platelet-derived growth factor-BB, and bone morphogenetic protein-2, we generated engineered GF variants with super-affinity to the ECM. These ECM super-affinity GFs induced repair in rodent models of chronic wounds and bone defects that was greatly enhanced as compared to treatment with the wild-type GFs, demonstrating that this approach may be useful in several regenerative medicine applications.

Proteolytic processing regulates placental growth factor activities.

Placental growth factor (PlGF) is a critical mediator of blood vessel formation, yet mechanisms of its action and regulation are incompletely understood. Here we demonstrate that proteolytic processing regulates the biological activity of PlGF. Specifically, we show that plasmin processing of PlGF-2 yields a protease-resistant core fragment comprising the vascular endothelial growth factor receptor-1 binding site but lacking the carboxyl-terminal domain encoding the heparin-binding domain and an 8-amino acid peptide encoded by exon 7. We have identified plasmin cleavage sites, generated a truncated PlGF118 isoform mimicking plasmin-processed PlGF, and explored its biological function in comparison with that of PlGF-1 and -2. The angiogenic responses induced by the diverse PlGF forms were distinct. Whereas PlGF-2 increased endothelial cell chemotaxis, vascular sprouting, and granulation tissue formation upon skin injury, these activities were abrogated following plasmin digestion. Investigation of PlGF/Neuropilin-1 binding and function suggests a critical role for heparin-binding domain/Neuropilin-1 interaction and its regulation by plasmin processing. Collectively, here we provide new mechanistic insights into the regulation of PlGF-2/Neuropilin-1-mediated tissue vascularization and growth.

A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells.

Growth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system's performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.

Clinical and financial advantages of moist wound management.

Best practice wound management includes moist wound healing and using advanced wound care products that promote efficient use of nursing time. Moist wound healing is the key that enables wounds to heal more rapidly with less pain and less scarring, which increases patient satisfaction while decreasing costs.