How do hospitals respond to feedback about blood transfusion practice? A multiple case study investigation

National clinical audits play key roles in improving care and driving system-wide change. However, effects of audit and feedback depend upon both reach (e.g. relevant staff receiving the feedback) and response (e.g. staff regulating their behaviour accordingly). This study aimed to investigate which hospital staff initially receive feedback and formulate a response, how feedback is disseminated within hospitals, and how responses are enacted (including barriers and enablers to enactment). Using a multiple case study approach, we purposively sampled four UK hospitals for variation in infrastructure and resources. We conducted semi-structured interviews with staff from transfusion-related roles and observed Hospital Transfusion Committee meetings. Interviews and analysis were based on the Theoretical Domains Framework of behaviour change. We coded interview transcripts into theoretical domains, then inductively identified themes within each domain to identify barriers and enablers. We also analysed data to identify which staff currently receive feedback and how dissemination is managed within the hospital. Members of the hospital’s transfusion team initially received feedback in all cases, and were primarily responsible for disseminating and responding, facilitated through the Hospital Transfusion Committee. At each hospital, key individuals involved in prescribing transfusions reported never having received feedback from a national audit. Whether audits were discussed and actions explicitly agreed in Committee meetings varied between hospitals. Key enablers of action across all cases included clear lines of responsibility and strategies to remind staff about recommendations. Barriers included difficulties disseminating to relevant staff and needing to amend feedback to make it appropriate for local use. Appropriate responses by hospital staff to feedback about blood transfusion practice depend upon supportive infrastructures and role clarity. Hospitals could benefit from support to disseminate feedback systematically, particularly to frontline staff involved in the behaviours being audited, and practical tools to support strategic decision-making (e.g. action-planning around local response to feedback)

Legitimatie van de nevengeul voor de Waal langs Varik : constructies van risico’s uit onzekerheden die redenen geven voor voorzorg : achtergrondrapport

“Wat is de legitimatie van de geprojecteerde nevengeul van de Waal bij Varik en Heesselt?” In het onderzoek dat heeft plaatsgevonden is specifiek gekeken naar de onderbouwing van de maatgevende afvoer van 18.000 m3/s bij Lobith eind 21e eeuw en naar de wijze waarop er in de planvorming met de onzekerheden rondom de maatgevende afvoer is omgegaan. Daarbij is in eerste instantie gekeken naar de onderbouwing die door de provincie en door het stafbureau van de Deltacommissaris is aangeleverd aan de bewoners. In tweede instantie moest er veel ruimer gezocht worden naar onderbouwende publicaties, want die onderbouwing had het karakter van “work in progress”

A multidimensional approach to assessing intervention fidelity in a process evaluation of audit and feedback interventions to reduce unnecessary blood transfusions: a study protocol

BACKGROUND: In England, NHS Blood and Transplant conducts national audits of transfusion and provides feedback to hospitals to promote evidence-based practice. Audits demonstrate 20% of transfusions fall outside guidelines. The AFFINITIE programme (Development & Evaluation of Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE) involves two linked, 2×2 factorial, cluster-randomised trials, each evaluating two theoretically-enhanced audit and feedback interventions to reduce unnecessary blood transfusions in UK hospitals. The first intervention concerns the content/format of feedback reports. The second aims to support hospital transfusion staff to plan their response to feedback and includes a web-based toolkit and telephone support. Interpretation of trials is enhanced by comprehensively assessing intervention fidelity. However, reviews demonstrate fidelity evaluations are often limited, typically only assessing whether interventions were delivered as intended. This protocol presents methods for assessing fidelity across five dimensions proposed by the Behaviour Change Consortium fidelity framework, including intervention designer-, provider- and recipient-levels. METHODS: (1) Design: Intervention content will be specified in intervention manuals in terms of component behaviour change techniques (BCTs). Treatment differentiation will be examined by comparing BCTs across intervention/standard practice, noting the proportion of unique/convergent BCTs. (2) Training: draft feedback reports and audio-recorded role-play telephone support scenarios will be content analysed to assess intervention providers' competence to deliver manual-specified BCTs. (3) Delivery: intervention materials (feedback reports, toolkit) and audio-recorded telephone support session transcripts will be content analysed to assess actual delivery of manual-specified BCTs during the intervention period. (4) Receipt and (5) enactment: questionnaires, semi-structured interviews based on the Theoretical Domains Framework, and objective web-analytics data (report downloads, toolkit usage patterns) will be analysed to assess hospital transfusion staff exposure to, understanding and enactment of the interventions, and to identify contextual barriers/enablers to implementation. Associations between observed fidelity and trial outcomes (% unnecessary transfusions) will be examined using mediation analyses. DISCUSSION: If the interventions have acceptable fidelity, then results of the AFFINITIE trials can be attributed to effectiveness, or lack of effectiveness, of the interventions. Hence, this comprehensive assessment of fidelity will be used to interpret trial findings. These methods may inform fidelity assessments in future trials. TRIAL REGISTRATION: ISRCTN 15490813 . Registered 11/03/2015

FHIT gene therapy prevents tumor development in Fhit-deficient mice

The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit+/- knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer

An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni

GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice

OBJECTIVE—Glucagon-like peptide-1 receptor (GLP-1R) ago-nists are used to treat type 2 diabetes, and transient GLP-1 administration improved cardiac function in humans after acute myocardial infarction (MI) and percutaneous revascularization. However, the consequences of GLP-1R activation before isch-emic myocardial injury remain unclear. RESEARCH DESIGN AND METHODS—We assessed the pathophysiology and outcome of coronary artery occlusion in normal and diabetic mice pretreated with the GLP-1R agonist liraglutide. RESULTS—Male C57BL/6 mice were treated twice daily for 7 days with liraglutide or saline followed by induction of MI. Survival was significantly higher in liraglutide-treated mice. Lira-glutide reduced cardiac rupture (12 of 60 versus 46 of 60; P 0.0001) and infarct size (21 2 % versus 29 3%, P 0.02) an

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: A systematic review

Glatiramer acetate and interferon-beta are approved first-line disease-modifying treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with cutaneous adverse events, which may influence treatment adherence and patient quality of life. In this systematic review, we aimed to provide an overview of the clinical spectrum and the incidence of skin reactions associated with DMTs. A systematic literature search was performed up to May 2011 in Medline, Embase, and Cochrane databases without applying restrictions in study design, language, or publishing date. Eligible for inclusion were articles describing any skin reaction related to DMTs in MS patients. Selection of articles and data extraction were performed by two authors independently. One hundred and six articles were included, of which 41 (39%) were randomized controlled trials or cohort studies reporting incidences of mainly local injection-site reactions. A large number of patients had experienced some form of localized injection-site reaction: up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation. Sixty-five case-reports involving 106 MS patients described a wide spectrum of cutaneous adverse events, the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated with local injection-site reactions and a wide spectrum of generalized cutaneous adverse events, in particular, the subcutaneous formulations. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT