Feasibility study to inform the design of a UK multi-centre randomised controlled trial of prophylactic antibiotics for the prevention of recurrent cellulitis of the leg

Background: This paper describes the results of a feasibility study for a randomised controlled trial (RCT). Methods: Twenty-nine members of the UK Dermatology Clinical Trials Network (UK DCTN) expressed an interest in recruiting for this study. Of these, 17 obtained full ethics and Research & Development (R&D) approval, and 15 successfully recruited patients into the study. A total of 70 participants with a diagnosis of cellulitis of the leg were enrolled over a 5-month period. These participants were largely recruited from medical admissions wards, although some were identified from dermatology, orthopaedic, geriatric and general surgery wards. Data were collected on patient demographics, clinical features and willingness to take part in a future RCT. Results: Despite being a relatively common condition, cellulitis patients were difficult to locate through our network of UK DCTN clinicians. This was largely because patients were rarely seen by dermatologists, and admissions were not co-ordinated centrally. In addition, the impact of the proposed exclusion criteria was high; only 26 (37%) of those enrolled in the study fulfilled all of the inclusion criteria for the subsequent RCT, and were willing to be randomised to treatment. Of the 70 participants identified during the study as having cellulitis of the leg (as confirmed by a dermatologist), only 59 (84%) had all 3 of the defining features of: i) erythema, ii) oedema, and iii) warmth with acute pain/tenderness upon examination. Twenty-two (32%) patients experienced a previous episode of cellulitis within the last 3 years. The median time to recurrence (estimated as the time since the most recent previous attack) was 205 days (95% CI 102 to 308). Service users were generally supportive of the trial, although several expressed concerns about taking antibiotics for lengthy periods, and felt that multiple morbidity/old age would limit entry into a 3-year study. Conclusion: This pilot study has been crucial in highlighting some key issues for the conduct of a future RCT. As a result of these findings, changes have been made to i) the planned recruitment strategy, ii) the proposed inclusion criteria and ii) the definition of cellulitis for use in the future trial

Dinosaur tracks from the Kilmaluag Formation (Bathonian, Middle Jurassic) of Score Bay, Isle of Skye, Scotland, UK

Tracks of a juvenile theropod dinosaur with footprint lengths of between 2 and 9 cm as well as adults of the same ichnospecies with footprints of about 15–25 cm in length were found in the Bathonian (Middle Jurassic) Kilmaluag Formation of Score Bay, northwestern Trotternish Peninsula, Isle of Skye, Scotland, UK. Two footprint sizes occur together on the same bedding plane in the central portion of Score Bay, both in situ and on loose blocks. Another horizon containing footprints above this was also identified. The footprints from the lowest horizon were produced in a desiccated silty mud that was covered with sand. A close association of both adults and juveniles with similar travel direction indicated by the footprints may suggest post-hatching care in theropod dinosaurs. Other footprints, produced on a rippled sandy substrate, have been found on the slightly higher bedding plane at this locality. Loose blocks found 130 m to the northeast in the central part of Score Bay have not been correlated with any in situ sediments, but were preserved in a similar manner to those from the higher bedding plane. These tracks represent the youngest dinosaur remains yet found in Scotland

Molecular Characterization Reveals Diverse and Unknown Malaria Vectors in the Western Kenyan Highlands.

The success of mosquito-based malaria control is dependent upon susceptible bionomic traits in local malaria vectors. It is crucial to have accurate and reliable methods to determine mosquito species composition in areas subject to malaria. An unexpectedly diverse set of Anopheles species was collected in the western Kenyan highlands, including unidentified and potentially new species carrying the malaria parasite Plasmodium falciparum. This study identified 2,340 anopheline specimens using both ribosomal DNA internal transcribed spacer region 2 and mitochondrial DNA cytochrome oxidase subunit 1 loci. Seventeen distinct sequence groups were identified. Of these, only eight could be molecularly identified through comparison to published and voucher sequences. Of the unidentified species, four were found to carry P. falciparum by circumsporozoite enzyme-linked immunosorbent assay and polymerase chain reaction, the most abundant of which had infection rates comparable to a primary vector in the area, Anopheles funestus. High-quality adult specimens of these unidentified species could not be matched to museum voucher specimens or conclusively identified using multiple keys, suggesting that they may have not been previously described. These unidentified vectors were captured outdoors. Diverse and unknown species have been incriminated in malaria transmission in the western Kenya highlands using molecular identification of unusual morphological variants of field specimens. This study demonstrates the value of using molecular methods to compliment vector identifications and highlights the need for accurate characterization of mosquito species and their associated behaviors for effective malaria control

Barriers and opportunities for evidence-based health service planning: the example of developing a Decision Analytic Model to plan services for sexually transmitted infections in the UK

Decision Analytic Models (DAMs) are established means of evidence-synthesis to differentiate between health interventions. They have mainly been used to inform clinical decisions and health technology assessment at the national level, yet could also inform local health service planning. For this, a DAM must take into account the needs of the local population, but also the needs of those planning its services. Drawing on our experiences from stakeholder consultations, where we presented the potential utility of a DAM for planning local health services for sexually transmitted infections (STIs) in the UK, and the evidence it could use to inform decisions regarding different combinations of service provision, in terms of their costs, cost-effectiveness, and public health outcomes, we discuss the barriers perceived by stakeholders to the use of DAMs to inform service planning for local populations, including (1) a tension between individual and population perspectives; (2) reductionism; and (3) a lack of transparency regarding models, their assumptions, and the motivations of those generating models

Improving identification of familial hypercholesterolaemia in primary care: Derivation and validation of the familial hypercholesterolaemia case ascertainment tool (FAMCAT)

Objective: Heterozygous familial hypercholesterolaemia (FH) is a common autosomal dominant disorder. The vast majority of affected individuals remain undiagnosed, resulting in lost opportunities for preventing premature heart disease. Better use of routine primary care data offers an opportunity to enhance detection. We sought to develop a new predictive algorithm for improving identification of individuals in primary care who could be prioritised for further clinical assessment using established diagnostic criteria. Methods: Data were analysed for 2,975,281 patients with total or LDL-cholesterol measurement from 1 Jan 1999 to 31 August 2013 using the Clinical Practice Research Datalink (CPRD). Included in this cohort study were 5050 documented cases of FH. Stepwise logistic regression was used to derive optimal multivariate prediction models. Model performance was assessed by its discriminatory accuracy (area under receiver operating curve [AUC]). Results: The FH prediction model (FAMCAT), consisting of nine diagnostic variables, showed high discrimination (AUC 0.860, 95% CI 0.848–0.871) for distinguishing cases from non-cases. Sensitivity analysis demonstrated no significant drop in discrimination (AUC 0.858, 95% CI 0.845–0.869) after excluding secondary causes of hypercholesterolaemia. Removing family history variables reduced discrimination (AUC 0.820, 95% CI 0.807–0.834), while incorporating more comprehensive family history recording of myocardial infraction significantly improved discrimination (AUC 0.894, 95% CI 0.884–0.904). Conclusion: This approach offers the opportunity to enhance detection of FH in primary care by identifying individuals with greatest probability of having the condition. Such cases can be prioritised for further clinical assessment, appropriate referral and treatment to prevent premature heart disease

Reducing recurrent care proceedings: initial evidence from new interventions

The English family justice system faces a crisis of recurrence. As many as one in four birth mothers involved in public law care proceedings in English family courts are likely to reappear in a subsequent set of proceedings within seven years. These mothers are involved in up to one-third of total care applications, as they are – by definition – linked to more than one child . Few birth mothers experiencing the removal of a child to care are offered any follow-up support, despite often facing multiple challenges including poverty, addiction, domestic violence and mental health problems. Since 2011, however, a number of new services have been established to begin to address their unmet needs. This article summarises the findings of the first academic-led evaluation of two of these initiatives. Presenting evidence from a mixed-methods evaluative study, it concludes that the new services were able to foster relationships that ‘worked’ in reducing recurrent proceedings. None of the women engaging with the services went on to experience what could be described as a ‘rapid repeat pregnancy’ within the evaluation window. Just as significantly, a number of clients reported some improvement in their psychological functioning, and the practitioners involved reported positively on their experience of delivering and managing innovative services. The article closes with a discussion of the challenges of evaluating personalised, strengths-based interventions and the possibilities of evidencing empowerment in these cases

Organic Complexation of U(VI) in Reducing Soils at a Natural Analogue Site : Implications for Uranium Transport

Understanding the long-term fate, stability, and bioavailability of uranium (U) in the environment is important for the management of nuclear legacy sites and radioactive wastes. Analysis of U behavior at natural analogue sites permits evaluation of U biogeochemistry under conditions more representative of long-term equilibrium. Here, we have used bulk geochemical and microbial community analysis of soils, coupled with X-ray absorption spectroscopy and mu-focus X-ray fluorescence mapping, to gain a mechanistic understanding of the fate of U transported into an organic-rich soil from a pitchblende vein at the UK Needle's Eye Natural Analogue site. U is highly enriched in the Needle's Eye soils (similar to 1600 mg kg(-1)). We show that this enrichment is largely controlled by U(VI) complexation with soil organic matter and not U(VI) bioreduction. Instead, organic-associated U(VI) seems to remain stable under microbially-mediated Fe(III)-reducing conditions. U(IV) (as non-crystalline U(IV)) was only observed at greater depths at the site (>25 cm); the soil here was comparatively mineral-rich, organic-poor, and sulfate-reducing/methanogenic. Furthermore, nanocrystalline UO2, an alternative product of U(VI) reduction in soils, was not observed at the site, and U did not appear to be associated with Fe-bearing minerals. Organicrich soils appear to have the potential to impede U groundwater transport, irrespective of ambient redox conditions. (C) 2020 The Authors. Published by Elsevier Ltd.Peer reviewe

Auditory presentation and synchronization in Adobe Flash and HTML5/JavaScript Web experiments

Substantial recent research has examined the accuracy of presentation durations and response time measurements for visually presented stimuli in Web-based experiments, with a general conclusion that accuracy is acceptable for most kinds of experiments. However, many areas of behavioral research use auditory stimuli instead of, or in addition to, visual stimuli. Much less is known about auditory accuracy using standard Web-based testing procedures. We used a millisecond-accurate Black Box Toolkit to measure the actual durations of auditory stimuli and the synchronization of auditory and visual presentation onsets. We examined the distribution of timings for 100 presentations of auditory and visual stimuli across two computers with difference specs, three commonly used browsers, and code written in either Adobe Flash or JavaScript. We also examined different coding options for attempting to synchronize the auditory and visual onsets. Overall, we found that auditory durations were very consistent, but that the lags between visual and auditory onsets varied substantially across browsers and computer systems

Potential benefits of using a toolkit developed to aid in the adaptation of HTA reports: a case study considering positron emission tomography (PET) and Hodgkin's disease

<p>Abstract</p> <p>Background</p> <p>The preparation of HTA reports requires a great deal of time, effort and resource, and there is a desire to improve efficiency, avoid duplication of effort and facilitate the transfer of knowledge between countries. This is of particular importance for countries with more limited resources which have less capacity to produce their own reports. The aim of this study was to investigate the extent of duplication of published Health Technology Assessment (HTA) reports, on the same technology, for the same indication; using positron emission tomography (PET) for lung cancer and Hodgkin's disease as a case study. This was done in order to assess the potential usefulness of a toolkit developed to aid in the adaptation of HTA reports from one context or country to another.</p> <p>Methods</p> <p>A systematic search of the National Institute for Health Research (NIHR) CRD HTA database was conducted in June 2008 in order to identify full HTA reports containing information on the use of PET for lung cancer and Hodgkin's disease, written in English, and readily available on the web. The contents of the reports identified were then examined to assess the extent of duplication of content between reports and potential for the use of the toolkit.</p> <p>Results</p> <p>From 132 records of HTA reports about PET, 8 reports were identified as fulfilling all the criteria set, and therefore demonstrating potential duplication of effort. All these reports covered four similar domains, technology use, safety, effectiveness and economic evaluation. Five of the reports also considered organisational aspects.</p> <p>Conclusions</p> <p>There was some duplication of effort in the preparation of HTA reports concerned with the use of PET for lung cancer and Hodgkin's disease. This is an example of where resource could have been conserved and time saved by the use of a toolkit developed to aid in the adaptation of HTA reports from one context to another.</p