Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Vancomycin therapeutic drug monitoring in paediatrics.

AIM: Vancomycin guidelines for therapeutic drug monitoring (TDM) aim to maximise efficacy while minimising toxicity and resistance. Vancomycin is effective against Staphylococcus aureus when it achieves area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) > 400. Studies in children have shown that target trough concentrations poorly correlate to AUC/MIC > 400; however, they are used in practice for clinical convenience. This review in paediatric inpatients aims to audit performance against TDM guidelines and consider what changes are needed to optimise vancomycin monitoring. METHODS: Vancomycin prescriptions in patients younger than 18 years old were collected over a 15-month period. Primary outcome measures were vancomycin initial dose (mg/kg/day) and the timing and result of first trough concentration (mg/L). Secondary outcome measures were the numbers achieving recommended targets and whether appropriate dose adjustments were made in response to TDM. RESULTS: A total of 133 courses reached the time when TDM should occur. Average patient age was 6.5 years, and the average initial dose was 52.55 mg/kg/day (range 19.05-86.54 mg/kg). Only 25% of courses (n = 34) had a trough concentration measured at the recommended time. The mean trough concentration was 11.6 mg/L (range < 2.0-39.7). Of 40 patients with a low trough concentration, 50% continued without dose adjustment. CONCLUSION: As shown in the literature, there is a poor correlation between the vancomycin dose given and the trough concentration achieved. Given that recommendations for trough concentration monitoring are designed to simplify the process yet are poorly adhered to, a strategic plan to address these issues is needed.

Optical treatment of amblyopia in older children and adults is essential prior to enrolment in a clinical trial.

PURPOSE: Optical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults. METHODS: We examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e-ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial. RESULTS: Eighty participants (mean age 24.6 years, range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction. Sixteen out of 80 participants (20%) achieved better than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these participants attended additional follow-up and four (44%) showed further VA improvements. CONCLUSIONS: Improvements from optical treatment resulted in one-fifth of participants becoming ineligible for the main clinical trial. Studies investigating additional amblyopia therapies must include an appropriate optical treatment only phase and/or parallel treatment group regardless of patient age. Optical treatment of amblyopia in adult patients warrants further investigation.

Development and validation of a questionnaire assessing the quality of life impact of Colour Blindness (CBQoL).

BACKGROUND: Congenital colour vision deficiency (CVD), commonly called 'colour blindness', affects around 8% of men and 0.4% of women. Although many aspects of health (e.g. change in colour of urine) and healthcare (e.g. coloured medication, colour-coded diagnostic tests), and modern life depend upon colour coding (e.g. graphs, maps, signals), the impact of colour blindness on everyday life is not generally considered a topic of importance. This study is the first to create and validate a questionnaire measuring the quality of life (QoL) impact of being colour blind. METHODS: This study consisted of two phases. Firstly, the questionnaire design and development phase was led by an expert panel and piloted on a focus group. Secondly, an online sample of 128 men and 291 women filled in the questionnaire, and the psychometric properties of the questionnaire were analysed using principal components analysis (PCA). The scores of colour blind (CB) participants and normal-sighted controls, controlling for age and sex, were compared using matched t-tests. RESULTS: The PCA resulted in a questionnaire with three domains (or subscales): QoL for Health & Lifestyle, QoL for Work, and QoL for Emotions. Controlling for age, there was a significantly greater negative impact on QoL for CB people than normal-sighted controls in regards to confusion over colour in various aspects of their health (p = 5 × 10-7), work (p = 1.3 × 10-7), and emotional life (p = 6 × 10-5). CONCLUSION: Colour blindness can significantly impact quality of life for health, emotions, and especially careers. The tool developed here could be useful in future clinical studies to measure changes in CBQoL in response to therapy in conditions where colour vision is affected. We also discuss ways in which everyday problems related to colour vision might be reduced, for example, workplaces could avoid colour coding where a non-colour alternative is possible.

Healthcare librarians and the delivery of critical appraisal training: barriers to involvement.

BACKGROUND: Many healthcare librarians are undertaking training in critical appraisal but a significant number are not cascading the training to their end-users. OBJECTIVES: To examine the barriers to healthcare librarian involvement in delivering critical appraisal training. METHODS: A questionnaire survey of 57 library services across 48 NHS Trust Library Services in north west England followed up with 21 semi-structured interviews. RESULTS: Two types of barriers were noted: extrinsic barriers (organisational, environmental, training, role expectations) and intrinsic barriers (knowledge, skills, attitude). CONCLUSIONS: These barriers are not mutually exclusive and by overcoming one of them it does not necessarily follow that healthcare librarians will engage in delivering critical appraisal skills training. The challenge lies in developing strategies to deal effectively with these barriers to encourage and support healthcare librarians in the delivery of critical appraisal training at a level at which they feel confident and able.

Evaluating clinical librarian services: a systematic review.

BACKGROUND: Previous systematic reviews have indicated limited evidence and poor quality evaluations of clinical librarian (CL) services. Rigorous evaluations should demonstrate the value of CL services, but guidance is needed before this can be achieved. OBJECTIVES: To undertake a systematic review which examines models of CL services, quality, methods and perspectives of clinical librarian service evaluations. METHODS: Systematic review methodology and synthesis of evidence, undertaken collaboratively by a group of 8 librarians to develop research and critical appraisal skills. RESULTS: There are four clear models of clinical library service provision. Clinical librarians are effective in saving health professionals time, providing relevant, useful information and high quality services. Clinical librarians have a positive effect on clinical decision making by contributing to better informed decisions, diagnosis and choice of drug or therapy. The quality of CL studies is improving, but more work is needed on reducing bias and providing evidence of specific impacts on patient care. The Critical Incident Technique as part of a mixed method approach appears to offer a useful approach to demonstrating impact. CONCLUSIONS: This systematic review provides practical guidance regarding the evaluation of CL services. It also provides updated evidence regarding the effectiveness and impact of CL services. The approach used was successful in developing research and critical appraisal skills in a group of librarians.

Safe haven: transforming relatives' rooms.

The quality of facilities available for relatives and carers of hospital patients, which is particularly important when distressing news is given, often receives little attention. This article outlines a project undertaken at a Liverpool trust to improve the environment of relatives' rooms. The project adopted an evidence-based, design-led approach and used standard hospital materials and suppliers to refurbish relatives' rooms. Audit and feedback from relatives and staff was used to inform the project, and literature on enhancing the healing environment was used to formulate a trust-wide standard for all relatives' rooms.

Adherence to home-based videogame treatment for amblyopia in children and adults.

Clinical relevance: Home-based videogame treatments are increasingly popular for amblyopia treatment. However, at-home treatments tend to be done in short sessions and with frequent disruptions, which may reduce the effectiveness of binocular visual stimulation. These treatment adherence patterns need to be accounted for when considering dose-response relationships and treatment effectiveness.Background: Home-based videogame treatments are increasingly being used for various sensory conditions, including amblyopia ('lazy eye'), but treatment adherence continues to limit success. To examine detailed behavioural patterns associated with home-based videogame treatment, we analysed in detail the videogame adherence data from the Binocular tReatment of Amblyopia with VideOgames (BRAVO) clinical trial (ACTRN12613001004752).Methods: Children (7-12 years), teenagers (13-17 years) and adults (≥ 18 years) with unilateral amblyopia were loaned iPod Touch devices with either an active treatment or placebo videogame and instructed to play for a total of 1-2 hours/day for six weeks at home. Objectively-recorded adherence data from device software were used to analyse adherence patterns such as session length, daily distribution of gameplay, use of the pause function, and differences between age groups. Objectively-recorded adherence was also compared to subjectively-reported adherence from paper-based diaries.Results: One hundred and five of the 115 randomised participants completed six weeks of videogame training. Average adherence was 65% (SD 37%) of the minimum hours prescribed. Game training was generally performed in short sessions (mean 21.5, SD 11.2 minutes), mostly in the evening, with frequent pauses (median every 4.1 minutes, IQR 6.1). Children played in significantly shorter sessions and paused more frequently than older age groups (p < 0.0001). Participants tended to over-report adherence in subjective diaries compared to objectively-recorded gameplay time.Conclusion: Adherence to home-based videogame treatment was characterised by short sessions interspersed with frequent pauses, suggesting regular disengagement. This complicates dose-response calculations and may interfere with the effectiveness of treatments like binocular treatments for amblyopia, which require sustained visual stimulation.

Healthcare librarians and the delivery of critical appraisal training: attitudes, level of involvement and support.

BACKGROUND: Although healthcare librarians are undertaking training in critical appraisal skills, what is not so clear is the impact of the training on the understanding and dissemination of these skills. OBJECTIVES: This study aims to examine the attitudes of healthcare librarians towards delivering critical appraisal training and their level of involvement. METHODS: A questionnaire survey of 57 library services across 48 NHS Trust Library Services in north-west England followed up with 21 semi-structured interviews. RESULTS: Seventy-three per cent of respondents felt that they ought to be involved in delivering critical appraisal training, however less than a third (29%) are actually involved. Librarians are involved in critical appraisal facilitation at various levels. CONCLUSIONS: Debate continues over the extent of librarian involvement in delivering critical appraisal training. As long as healthcare librarians recognise their own capabilities and identify the boundaries within which they feel comfortable then there is no reason why they should not be involved in delivering critical appraisal training.

Effectiveness of a Binocular Video Game vs Placebo Video Game for Improving Visual Functions in Older Children, Teenagers, and Adults With Amblyopia: A Randomized Clinical Trial.

Importance: Binocular amblyopia treatment using contrast-rebalanced stimuli showed promise in laboratory studies and requires clinical trial investigation in a home-based setting. Objective: To compare the effectiveness of a binocular video game with a placebo video game for improving visual functions in older children and adults. Design, Setting, and Participants: The Binocular Treatment of Amblyopia Using Videogames clinical trial was a multicenter, double-masked, randomized clinical trial. Between March 2014 and June 2016, 115 participants 7 years and older with unilateral amblyopia (amblyopic eye visual acuity, 0.30-1.00 logMAR; Snellen equivalent, 20/40-20/200) due to anisometropia, strabismus, or both were recruited. Eligible participants were allocated with equal chance to receive either the active or the placebo video game, with minimization stratified by age group (child, age 7 to 12 years; teenager, age 13 to 17 years; and adult, 18 years and older). Interventions: Falling-blocks video games played at home on an iPod Touch for 1 hour per day for 6 weeks. The active video game had game elements split between eyes with a dichoptic contrast offset (mean [SD] initial fellow eye contrast, 0.23 [0.14]). The placebo video game presented identical images to both eyes. Main Outcomes and Measures: Change in amblyopic eye visual acuity at 6 weeks. Secondary outcomes included compliance, stereoacuity, and interocular suppression. Participants and clinicians who measured outcomes were masked to treatment allocation. Results: Of the 115 included participants, 65 (56.5%) were male and 83 (72.2%) were white, and the mean (SD) age at randomization was 21.5 (13.6) years. There were 89 participants (77.4%) who had prior occlusion. The mean (SD) amblyopic eye visual acuity improved 0.06 (0.12) logMAR from baseline in the active group (n = 56) and 0.07 (0.10) logMAR in the placebo group (n = 59). The mean treatment difference between groups, adjusted for baseline visual acuity and age group, was -0.02 logMAR (95% CI, -0.06 to 0.02; P = .25). Compliance with more than 25% of prescribed game play was achieved by 36 participants (64%) in the active group and by 49 (83%) in the placebo group. At 6 weeks, 36 participants (64%) in the active group achieved fellow eye contrast greater than 0.9 in the binocular video game. No group differences were observed for any secondary outcomes. Adverse effects included 3 reports of transient asthenopia. Conclusions and Relevance: The specific home-based binocular falling-blocks video game used in this clinical trial did not improve visual outcomes more than the placebo video game despite increases in fellow eye contrast during game play. More engaging video games with considerations for compliance may improve effectiveness. Trial Registration: anzctr.org.au Identifier: ACTRN12613001004752.

Improving children's nurses' knowledge of caring for people with mental health problems.

[Figure: see text] The aim of this project was to provide training to nursing staff to improve their confidence and knowledge when caring for children and young people with mental health problems. A one-day bespoke training course was given to a purposeful sample of eight children's nurses. The nurses completed questionnaires before and after the training day and a third questionnaire three months after the course. All nurses reported an increase in knowledge and confidence when caring for young people with mental health problems.

Binocular treatment of amblyopia using videogames (BRAVO): study protocol for a randomised controlled trial.

BACKGROUND: Amblyopia is a common neurodevelopmental disorder of vision that is characterised by visual impairment in one eye and compromised binocular visual function. Existing evidence-based treatments for children include patching the nonamblyopic eye to encourage use of the amblyopic eye. Currently there are no widely accepted treatments available for adults with amblyopia. The aim of this trial is to assess the efficacy of a new binocular, videogame-based treatment for amblyopia in older children and adults. We hypothesise that binocular treatment will significantly improve amblyopic eye visual acuity relative to placebo treatment. METHODS/DESIGN: The BRAVO study is a double-blind, randomised, placebo-controlled multicentre trial to assess the effectiveness of a novel videogame-based binocular treatment for amblyopia. One hundred and eight participants aged 7 years or older with anisometropic and/or strabismic amblyopia (defined as ≥0.2 LogMAR interocular visual acuity difference, ≥0.3 LogMAR amblyopic eye visual acuity and no ocular disease) will be recruited via ophthalmologists, optometrists, clinical record searches and public advertisements at five sites in New Zealand, Canada, Hong Kong and Australia. Eligible participants will be randomised by computer in a 1:1 ratio, with stratification by age group: 7-12, 13-17 and 18 years and older. Participants will be randomised to receive 6 weeks of active or placebo home-based binocular treatment. Treatment will be in the form of a modified interactive falling-blocks game, implemented on a 5th generation iPod touch device viewed through red/green anaglyphic glasses. Participants and those assessing outcomes will be blinded to group assignment. The primary outcome is the change in best-corrected distance visual acuity in the amblyopic eye from baseline to 6 weeks post randomisation. Secondary outcomes include distance and near visual acuity, stereopsis, interocular suppression, angle of strabismus (where applicable) measured at baseline, 3, 6, 12 and 24 weeks post randomisation. Treatment compliance and acceptability will also be assessed along with quality of life for adult participants. DISCUSSION: The BRAVO study is the first randomised controlled trial of a home-based videogame treatment for older children and adults with amblyopia. The results will indicate whether a binocular approach to amblyopia treatment conducted at home is effective for patients aged 7 years or older. TRIAL REGISTRATION: This trial was registered in Australia and New Zealand Clinical Trials Registry ( ACTRN12613001004752 ) on 10 September 2013.

Body surface mapping versus the standard 12 lead ECG in the detection of myocardial infarction amongst emergency department patients: a Bayesian approach.

OBJECTIVE: To determine if body surface mapping (BSM) is better than the standard 12 lead ECG in the diagnosis of acute myocardial infarction amongst emergency department patients. SETTING: A University affiliated inner-city emergency department. PARTICIPANTS: People presenting to an emergency department with symptoms compatible with myocardial ischaemia/infarction. MAIN OUTCOME MEASURES: Myocardial infarction as defined by either standard 12 lead ECG changes with associated cardiac marker rise, Troponin T >0.1 microg/ml at > 12 h or autopsy/surgical findings of fresh macroscopic infarction. RESULTS: BSM had an overall sensitivity of 47.1% versus 40% for the 12 lead ECG (P < 0.001). Specificity for the BSM was 85.6% versus 93.7% for the 12 lead ECG (P < 0.001). These findings were consistent for low/moderate and high risk subgroups. Bayesian analysis demonstrates that indiscriminate use of BSM would result in a clinically important overdiagnosis of myocardial infarction amongst emergency department patients. CONCLUSIONS: BSM has a higher sensitivity, but a lower specificity for the diagnosis of myocardial infarction.

A novel method for the detection of transient myocardial ischaemia using body surface electrocardiac mapping.

BACKGROUND: The limitations of the 12-lead ECG in the detection of myocardial ischaemia are well known. This study sought to test the hypothesis that a Body Surface Mapping (BSM) system can detect and localise the transient regional ischaemia induced by elective percutaneous coronary intervention (PCI) in patients with stable angina. METHODS AND RESULTS: 25 patients undergoing elective single vessel PCI were studied: 11 with RCA lesions, 9 with LAD lesions and 5 with circumflex lesions. Patients had BSM readings every 30 s following the inflation of a dilating balloon in the target vessel for 1 min. BSMs were analysed for ST segment change at 60 ms after the J point (ST60). Peak ST changes were analysed and colour map reconstruction made. Characteristic ST segment changes in each arterial domain were observed following inflation of the balloon. Maximal change occurred in a standard V lead on only 2/46 occasions. Statistically significant rapid rise and fall of ST 60 readings were observed indicating the onset recovery and location of the transient ischaemia. A novel method for the presentation of colour map reconstruction that removes baseline noise has been developed. CONCLUSIONS: These data confirm the hypothesis that this BSM system can detect and display transient myocardial ischaemia. BSM may represent a novel clinical tool for the assessment of clinical ischaemia.

A pragmatic critical appraisal instrument for search filters: introducing the CADTH CAI.

OBJECTIVE: To identify or develop a critical appraisal instrument (CAI) to aid in the selection of search filters for use in systematic review searching. The CAI is to be used by experienced searchers without specialized training in statistics or search filter design. METHODS: Through extensive searching and consultation, one candidate instrument was identified. Through expert consultation and several rounds of testing, the instrument was extensively revised to become the Canadian Agency for Drugs and Technologies in Health (CADTH) CAI. RESULTS: The CADTH CAI consists of ten questions and can be applied by experienced searchers with a moderate knowledge of search filter methodology. CONCLUSION: The CADTH CAI provides experienced searchers with a means of selecting the search filter that is most methodologically sound.

Evaluation of methodological search filters--a review.

OBJECTIVES: The objectives of the study were: to provide an overview of approaches to methodological search filter development; to identify and critically review the stages of methodological search filter development; to devise a search filter appraisal checklist based on the review. METHODS: An iterative approach to searching was employed utilizing health and library databases, the world wide web and citation searching. Further systematic methods included hand searching of key journals in the field of search filter development, contacting known experts in the field and scanning reference lists of relevant papers to identify additional studies. Altogether, 51 potentially relevant papers were found, of which 20 met the inclusion criteria. RESULTS: Four stages of search filter development were identified from the literature (search term selection, identification of a gold standard, evaluation and validation). Variations in the methods used to approach these four stages were identified, most importantly in the extent to which search filters are tested and validated. CONCLUSION: Awareness of the process and limitations involved in search filter development is essential to make an informed decision on the applicability and validity of search filters. The findings of this review indicate a considerable agenda for future research, in particular, to improve the quality of reporting of search filters and to inform users on their use and application. Based on the review, guidance in the appraisal process of search filters is given in the form of a checklist.

Awareness, use and opinions of methodological search filters used for the retrieval of evidence-based medical literature-a questionnaire survey.

The aim of this study was to determine the level of awareness of methodological search filters among health and academic librarians in the UK and Ireland, their use of filters and views on the perceived benefits, limitations and ways to increase usage of search filters. A random proportional sample of health and academic librarians were surveyed by telephone and fax. Overall, 88% (196/224) completed the telephone survey to establish awareness and use of filters. Eighty-four per cent (51/61) completed a fax survey focusing in more depth on usability issues surrounding filters. Results indicate a high level of awareness of methodological filters, but low level of usage. Furthermore, a high level of awareness did not necessarily correlate with a high level of knowledge or understanding. Examination of responses revealed limitations and recommendations beyond those reported in the literature and highlights the relationship between understanding and effective use of filters. Improved dissemination and publication of filters is required to better inform librarians on the concept of filters and how to use them effectively.

Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro.

In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility. We demonstrate that fascin is not detectable in normal colonic epithelium, but is dramatically up-regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could participate in tumor invasive behavior, we developed a cell culture model to examine the effect of fascin expression on the adhesive interactions, invasiveness, and differentiation of colonic epithelial cells. We report marked effects on the organization of cell-surface protrusions, actin cytoskeleton, and focal adhesions in the absence of alterations in the protein levels of the major components of these structures. These effects correlate with alterations in cell movements on two-dimensional matrix, and increased invasiveness in three-dimensional matrix. The cells also show increased proliferation and decreased capacity for normal glandular differentiation in collagen gels. We propose that up-regulation of fascin, by promoting the formation of protrusive, actin-based, cell-motility structures, could be a significant component in the acquisition of invasive phenotype in colonic carcinoma.