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)

Global CNS gene transfer for a childhood neurogenetic enzyme deficiency: Canavan disease.

The neurogenetic prototypic disease on which we chose to test our gene therapy strategy is Canavan disease (CD). CD is an autosomal recessive leukodystrophy associated with spongiform degeneration of the brain. At present the disease is uniformly fatal in affected probands. CD is characterized by mutations in the aspartoacylase (ASPA) gene, resulting in loss of enzyme activity. In this review, recent evidence is summarized on the etiology and possible treatments for CD. In particular, we discuss two gene delivery systems representing recent advances in both viral and liposome technology: a novel cationic liposome-polymer-DNA (LPD) complex, DCChol/DOPE-protamine, as well as recombinant adeno-associated virus (AAV) vectors

Do Clonal Plants Show Greater Division of Labour Morphologically and Physiologically at Higher Patch Contrasts?

When growing in reciprocal patches in terms of availability of different resources, connected ramets of clonal plants will specialize to acquire and exchange locally abundant resources more efficiently. This has been termed division of labour. We asked whether division of labour can occur physiologically as well as morphologically and will increase with patch contrasts.We subjected connected and disconnected ramet pairs of Potentilla anserina to Control, Low, Medium and High patch contrast by manipulating light and nutrient levels for ramets in each pair. Little net benefit of inter-ramet connection in terms of biomass was detected. Shoot-root ratio did not differ significantly between paired ramets regardless of connection under Control, Low and Medium. Under High, however, disconnected shaded ramets with ample nutrients showed significantly larger shoot-root ratios (2.8∼6.5 fold) than fully-lit but nutrient-deficient ramets, and than their counterparts under any other treatment; conversely, fully-lit but nutrient-deficient ramets, when connected to shaded ramets with ample nutrients, had significantly larger shoot-root ratios (2.0∼4.9 fold) than the latter and than their counterparts under any other treatment. Only under High patch contrast, fully-lit ramets, if connected to shaded ones, had 8.9% higher chlorophyll content than the latter, and 22.4% higher chlorophyll content than their isolated counterparts; the similar pattern held for photosynthetic capacity under all heterogeneous treatments.Division of labour in clonal plants can be realized by ramet specialization in morphology and in physiology. However, modest ramet specialization especially in morphology among patch contrasts may suggest that division of labour will occur when the connected ramets grow in reciprocal patches between which the contrast exceeds a threshold. Probably, this threshold patch contrast is the outcome of the clone-wide cost-benefit tradeoff and is significant for risk-avoidance, especially in the disturbance-prone environments

Atrial fibrillation in healthy adolescents after highly caffeinated beverage consumption: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Energy drinks and highly caffeinated drinks comprise some of the fastest growing products of the beverage industry, often targeting teenagers and young adults. Cardiac arrhythmias in children related to high caffeine consumption have not been well described in the literature. This case series describes the possible association between the consumption of highly caffeinated drinks and the subsequent development of atrial fibrillation in the adolescent population.</p> <p>Case presentations</p> <p>We report the cases of two Caucasian adolescent boys of 14 and 16 years of age at the time of presentation, each without a significant cardiac history, who presented with palpitations or vague chest discomfort or both after a recent history of excessive caffeine consumption. Both were found to have atrial fibrillation on electrocardiogram; one patient required digoxin to restore a normal sinus rhythm, and the other self-converted after intravenous fluid administration.</p> <p>Conclusion</p> <p>With the increasing popularity of energy drinks in the pediatric and adolescent population, physicians should be aware of the arrhythmogenic potential associated with highly caffeinated beverage consumption. It is important for pediatricians to understand the lack of regulation in the caffeine content and other ingredients of these high-energy beverages and their complications so that parents and children can be educated about the risk of cardiac arrhythmias with excessive energy drink consumption.</p

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”

Inter-and intraspecific variation in fern mating systems after long-distance colonization: the importance of selfing

<p>Abstract</p> <p>Background</p> <p>Previous studies on the reproductive biology of ferns showed that mating strategies vary among species, and that polyploid species often show higher capacity for self-fertilization than diploid species. However, the amount of intraspecific variation in mating strategy and selfing capacity has only been assessed for a few species. Yet, such variation may have important consequences during colonization, as the establishment of any selfing genotypes may be favoured after long-distance dispersal (an idea known as Baker's law).</p> <p>Results</p> <p>We examined intra-and interspecific variation in potential for self-fertilization among four rare fern species, of which two were diploids and two were tetraploids: <it>Asplenium scolopendrium </it>(2n), <it>Asplenium trichomanes </it>subsp. <it>quadrivalens </it>(4n), <it>Polystichum setiferum </it>(2n) and <it>Polystichum aculeatum </it>(4n). Sporophyte production was tested at different levels of inbreeding, by culturing gametophytes in isolation, as well as in paired cultures with a genetically different gametophyte. We tested gametophytes derived from various genetically different sporophytes from populations in a recently planted forest colonized through long-distance dispersal (Kuinderbos, the Netherlands), as well as from older, less disjunct populations.</p> <p>Sporophyte production in isolation was high for Kuinderbos genotypes of all four species. Selfing capacity did not differ significantly between diploids and polyploids, nor between species in general. Rather selfing capacity differed between genotypes within species. Intraspecific variation in mating system was found in all four species. In two species one genotype from the Kuinderbos showed enhanced sporophyte production in paired cultures. For the other species, including a renowned out crosser, selfing capacity was consistently high.</p> <p>Conclusions</p> <p>Our results for four different species suggest that intraspecific variation in mating system may be common, at least among temperate calcicole ferns, and that genotypes with high selfing capacity may be present among polyploid as well as diploid ferns. The surprisingly high selfing capacity of all genotypes obtained from the Kuinderbos populations might be due to the isolated position of these populations. These populations may have established through single-spore colonization, which is only possible for genotypes capable of self-fertilization. Our results therewith support the idea that selection for selfing genotypes may occur during long-distance colonization, even in normally outcrossing, diploid ferns.</p

Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Aβ levels

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD.</p> <p>Results</p> <p>Adeno-associated viral (AAV) vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition) three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits.</p> <p>Conclusion</p> <p>The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology <it>in vivo</it>, and demonstrate that whilst expression of Aβ42 alone is sufficient to initiate Aβ deposition, both Aβ40 and Aβ42 may contribute to cognitive deficits.</p

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