Learning Together 1: an educational model for training GPs, paediatricians: initial findings.

Learning Together is primarily an educational intervention, where paediatric registrars [SpRs] and General Practice (GP) registrars [GPSTs] see children together in a primary care setting. Over a six month period in 2013/2014, 44 learning pairs were set up mainly in North East and Central London. Proof of concept for the model at scale was achieved. Reported learning demonstrated: clinical learning themes of new knowledge, skill and communication skills; and collaborative themes of ongoing collaboration, satisfaction with team working and change in attitudes. These themes were identified in both sets of trainees. The self-reported learning is backed up by the results of a retrospective notes review of four common conditions based on NICE guidelines; constipation, asthma, feverish illness and eczema (CAFE). Guidance adherence improved from 57% before the intervention in solo GP training consultations to 72% during the joint clinic intervention (p < 0.01). After the intervention when the GP registrars returned to normal consultations, guidance adherence was 77% compared to before the intervention (p < 0.01). In addition 99% of the parents, who handed in feedback forms or took part in interviews, reported a good experience of care, and 87% reported increased confidence to manage their children's health following the consultation. A second, linked article examines the cost utility of Learning Together in its South London extension

The Role Of Local Authorities In Health Issues: A Policy Document Analysis

Prior to the passing of the Health and Social Care Act 2012 the Communities and Local Government (CLG) Select Committee conducted an investigation into the proposed changes to the Public Health System in England. The Committee considered 40 written submissions and heard oral evidence from 26 expert witnesses. Their report, which included complete transcripts of both oral and written submissions, provided a rich and informed data on which to base an analysis of the proposed new public health system. This report analyses the main themes that emerged from the evidence submissions and forms part of our preliminary work for PRUComm’s PHOENIX project examining the development of the new public health system

3D Bioprinting of Mature Bacterial Biofilms for Antimicrobial Resistance Drug Testing

The potential to bioprint and study 3D bacterial biofilm constructs could have great clinical significance at a time when antimicrobial resistance is rising to dangerously high levels worldwide. In this study, clinically relevant bacterial species including Escherichia coli, Staphylococcus aureus (MSSA), Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were 3D bioprinted using a double-crosslinked alginate bioink to form mature bacteria biofilms, characterized by confocal laser scanning microscopy (CLSM) and fluorescent staining. Solid and porous bacteria-laden constructs were reproducibly bioprinted with thicknesses ranging from 0.25 to 4 mm. We demonstrated 3D bioprinting of thicker biofilms (>4 mm) than found in currently available in vitro models. Bacterial viability was excellent in the bioprinted constructs, with CLSM observation of bacterial biofilm production and maturation possible for at least 28 d in culture. Importantly, we observed the complete five-step biofilm life cycle in vitro following 3D bioprinting for the first time, suggesting the formation of mature 3D bioprinted biofilms. Bacterial growth was faster in thinner, more porous constructs whilst constructs crosslinked with BaCl 2 concentrations of above 10 mM had denser biofilm formation. 3D MRSA and MSSA biofilm constructs were found to show greater resistance to antimicrobials than corresponding two-dimensional (2D) cultures. Thicker 3D E. coli biofilms had greater resistance to tetracycline than thinner constructs over 7 d of treatment. Our methodology allowed for the precise 3D bioprinting of self-supporting 3D bacterial biofilm structures that developed biofilms during extended culture. 3D biofilm constructs containing bacterial biofilms produce a model with much greater clinical relevance compared to 2D culture models and we have demonstrated their use in antimicrobial testing

Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P&lt;0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Virtual reality relaxation for people with mental health conditions: a systematic review.

PURPOSE: Vulnerability to stress is linked to poor mental health. Stress management interventions for people with mental health conditions are numerous but they are difficult to implement and have limited effectiveness in this population. Virtual reality (VR) relaxation is an innovative intervention that aims to reduce stress. This review aimed to synthesize evidence of VR relaxation for people with mental health conditions (PROSPERO 269405). METHODS: Embase, Medline, PsycInfo, and Web of Science were searched until 17th September 2021. The review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Effective Public Health Practice Project (EPHPP) tool assessed methodological quality of studies. RESULTS: Searching identified 4550 studies. Eighteen studies (N = 848) were included in the review. Studies were published between 2008 and 2021. Eleven were conducted in Europe. Thirteen studies were controlled trials. Participants were mostly working-age adult outpatients experiencing anxiety or stress-related conditions. Other conditions included eating disorders, depression, bipolar disorder, and psychosis. Five studies tested inpatients. All studies used a range of nature-based virtual environments, such as forests, islands, mountains, lakes, waterfalls, and most commonly, beaches to promote relaxation. Studies provided evidence of the feasibility, acceptability, and short-term effectiveness of VR relaxation to increase relaxation and reduce stress. EPHPP ratings were 'strong' (N = 11), 'moderate' (N = 4), and 'weak' (N = 3). CONCLUSIONS: VR relaxation has potential as a low-intensity intervention to promote relaxation and reduce stress for adults with mental health conditions, especially anxiety and stress-related problems. Further research is warranted on this promising intervention

The Concentration of 2-Propenyl Glucosinolate in Biofumigant Crops Influences Their Anti-Fungal Activity (In-Vitro) against Soil-Borne Pathogens

Abstract This study investigated the biofumigation potential of nine Brassica species/cultivars by determining the levels of 2-propenyl glucosinolate in their roots and shoots, and their in-vitro suppression of four major soil-borne pathogens of vegetable crops. Hydrolysis of 2-propenyl GSL produces volatile isothiocyanate (ITC) compounds which are known to have anti-fungal activity. HPLC results showed that 2-propenyl GSL only occurred in root and shoot residue of flowering plants of four Brassica cultivars developed for green manuring (Caliente 199 ® , Mustclean ® , Nemfix ® and BQ Mulch ® ) and in the standard (mustard seed meal) treatment Fumafert ® . Levels of 2-propenyl GSL varied several fold within the four Brassica cultivars, with 77-88% of the total concentrations recorded in the shoot tissues. In in vitro assays, the level of fungal suppression by volatiles emitted by hydrated shoot and root residues related to their content of 2-propenyl GSL, and the dose of residue applied to five soilborne test pathogens (S. minor, Rhizoctonia solani, Fusarium oxysporum, Pythium dissotocum and Rhizoctonia solani). The variation in 2-propenyl GLS levels found in the Brassica green manure crops tested provides scope for selecting cultivars with greater potential for biofumigation, and to control multiple soil-borne disease problems in vegetable farms

Molecular reductions in glucokinase activity increase counter-regulatory responses to hypoglycemia in mice and humans with diabetes.

OBJECTIVE: Appropriate glucose levels are essential for survival; thus, the detection and correction of low blood glucose is of paramount importance. Hypoglycemia prompts an integrated response involving reduction in insulin release and secretion of key counter-regulatory hormones glucagon and epinephrine that together promote endogenous glucose production to restore normoglycemia. However, specifically how this response is orchestrated remains to be fully clarified. The low affinity hexokinase glucokinase is found in glucose-sensing cells involved in glucose homeostasis including pancreatic β-cells and in certain brain areas. Here, we aimed to examine the role of glucokinase in triggering counter-regulatory hormonal responses to hypoglycemia, hypothesizing that reduced glucokinase activity would lead to increased and/or earlier triggering of responses. METHODS: Hyperinsulinemic glucose clamps were performed to examine counter-regulatory responses to controlled hypoglycemic challenges created in humans with monogenic diabetes resulting from heterozygous glucokinase mutations (GCK-MODY). To examine the relative importance of glucokinase in different sensing areas, we then examined responses to clamped hypoglycemia in mice with molecularly defined disruption of whole body and/or brain glucokinase. RESULTS: GCK-MODY patients displayed increased and earlier glucagon responses during hypoglycemia compared with a group of glycemia-matched patients with type 2 diabetes. Consistent with this, glucagon responses to hypoglycemia were also increased in I366F mice with mutated glucokinase and in streptozotocin-treated β-cell ablated diabetic I366F mice. Glucagon responses were normal in conditional brain glucokinase-knockout mice, suggesting that glucagon release during hypoglycemia is controlled by glucokinase-mediated glucose sensing outside the brain but not in β-cells. For epinephrine, we found increased responses in GCK-MODY patients, in β-cell ablated diabetic I366F mice and in conditional (nestin lineage) brain glucokinase-knockout mice, supporting a role for brain glucokinase in triggering epinephrine release. CONCLUSIONS: Our data suggest that glucokinase in brain and other non β-cell peripheral hypoglycemia sensors is important in glucose homeostasis, allowing the body to detect and respond to a falling blood glucose.Yousef Jameel Fund Sir Jukes Thorn Trust Elmore Fund Chang Gung University College of Medicin