Mcfarlandbaxter5633

Adding stereotactic ablative radiotherapy (SABR) to standard treatment slowed 6-month disease progression in men with hormone-sensitive metastatic prostate cancer, allowing them to delay androgen deprivation therapy, according to findings from the phase II ORIOLE trial. Larger studies are needed to determine if SABR, alone or combined with immunotherapies, can prevent new metastases in some patients. ©2020 American Association for Cancer Research.Platelet-derived growth factor receptor-beta (PDGFRβ) is a receptor tyrosine kinase found in cells of mesenchymal origin such as fibroblasts and pericytes. Activation of this receptor is dependent on paracrine ligand induction, and its preferred ligand PDGFB is released by neighboring epithelial and endothelial cells. While expression of both PDGFRβ and PDGFB has been noted in patient breast tumors for decades, how PDGFB-to-PDGFRβ tumor-stromal signaling mediates breast cancer (BC) initiation, progression, and metastasis remains unclear. Here we demonstrate this paracrine signaling pathway mediates both primary tumor growth and metastasis; specifically, metastasis to the brain. Elevated levels of PDGFB accelerated orthotopic tumor growth and intracranial growth of mammary tumor cells while mesenchymal-specific expression of an activating mutant PDGFRβ (PDGFRβD849V) exerted pro-proliferative signals on adjacent mammary tumor cells. Stromal expression of PDGFRβD849V also promoted brain metastases of mammary tumor cells expressing high PDGFB when injected intravenously. In the brain, expression of PDGFRβD849V was observed within a subset of astrocytes, and aged mice expressing PDGFRβD849V exhibited reactive gliosis. Importantly, the PDGFR-specific inhibitor crenolanib significantly reduced intracranial growth of mammary tumor cells. In a tissue microarray comprised of 363 primary human breast tumors, high PDGFB protein expression was prognostic for brain metastases, but not metastases to other sites. Our results advocate the use of mice expressing PDGFRβD849V in their stromal cells as a preclinical model of BC-associated brain metastases (BCBM) and support continued investigation into the clinical prognostic and therapeutic use of PDGFB-to-PDGFRβ signaling in women with BC. Copyright ©2020, American Association for Cancer Research.As the UK shields 'high risk' patients and enforces social distancing measures, patients will be at risk of significantly reducing physical activity levels. We explore the evidence base for COVID-19-specific recommendations and exercise interventions to 'precondition' patients prior to infection and appraise the role of maximal oxygen uptake (VO2 max) as a risk-stratifying triage tool. We conclude that structured exercise programmes can be used to maintain physical activity levels and prevent deconditioning and that VO2 max has the potential to be used as a clinically relevant triage tool during the COVID-19 outbreak. © Royal College of Physicians 2020. All rights reserved.The European Medicines Agency defines excipients as the constituents of a pharmaceutical form apart from the active substance. Immediate hypersensitivity reactions (IHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of IHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to review the literature on allergy to pharmaceutical excipients and to record the IHRs described with various types of medications, specifically reactions due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient in order to obtain a list of the excipients most frequently involved for each type of medication.Adrenaline (epinephrine) is the first-line treatment for anaphylaxis and, therefore, is listed as an essential medication for the treatment of anaphylaxis by the World Health Organization (WHO). However, the availability of adrenaline autoinjectors (AAI) for use as first-aid treatment is limited to only 32% of all the world's 195 countries, most of which are high-income countries. The key issues leading to the lack of availability of AAIs include cost, national regulations, lack of regional evidence on the value of epinephrine, and limited accurate data about the epidemiology of anaphylaxis. For these reasons, regional and international allergy academies support initiatives to narrow these gaps. Our WHO Collaborating Centre is deeply involved in this process. This document aims to serve as a baseline to ensure the following (1) adequate access to affordable autoinjectors for all patients/societies; and (2) the development of disease-/patient-specific approaches. Therefore, we propose a 5-step action plan that aims to gather accurate epidemiological data on anaphylaxis and autoinjector consumption, confirm partnerships, strengthen awareness, and include AAIs in the WHO Model List of Essential Medicines. These aspects should be considered in combination. A prioritized research agenda should encapsulate all these steps within the framework a global initiative against anaphylaxis. More than calling for universal availability of autoinjectors for optimal management of anaphylaxis, we propose an action plan as the baseline for a global initiative against anaphylaxis. We strongly believe that combined efforts will ensure a strong public health and societal approach that will lead to optimal care of allergic patients and best practices in allergology.BACKGROUND Medications with lifestyle are the cornerstone of diabetes management and routine monitoring and follow-up are essential to the delivery of quality care. Documented follow-up rates by pharmacists for people with diabetes are low despite good uptake of initial medication assessments in medication review programs. OBJECTIVES Identify the barriers and facilitators to routine monitoring and follow-up for people with diabetes by community pharmacists. find more METHODS Pharmacists were invited to complete a survey designed using the Theoretical Domains Framework Version 2 TDF (v2) consisting of 39 questions based on the 14 domains of the TDFv2 with quantitative response options using a 7 point Likert scale and 2 open-ended questions. Baseline information about the respondents and their practice sites were summarized using descriptive statistics. Mean scores and standard deviations were calculated for each of the Likert scale responses. Responses to open-ended questions were analyzed and coded using an inductive thematic approach.