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Introduction: Digital clinical decision support (CDS) tools are of growing importance in supporting healthcare professionals in understanding complex clinical problems and arriving at decisions that improve patient outcomes. CDS tools are also increasingly used to improve antimicrobial stewardship (AMS) practices in healthcare settings. However, far fewer CDS tools are available in lowerand middle-income countries (LMICs) and in animal health settings, where their use in improving diagnostic and treatment decision-making is likely to have the greatest impact. The aim of this study was to evaluate digital CDS tools designed as a direct aid to support diagnosis and/or treatment decisionmaking, by reviewing their scope, functions, methodologies, and quality. Recommendations for the development of veterinary CDS tools in LMICs are then provided., Methods: The review considered studies and reports published between January 2017 and October 2023 in the English language in peer-reviewed and gray literature., Results: A total of 41 studies and reports detailing CDS tools were included in the final review, with 35 CDS tools designed for human healthcare settings and six tools for animal healthcare settings. Of the tools reviewed, the majority were deployed in high-income countries (80.5%). Support for AMS programs was a feature in 12 (29.3%) of the tools, with 10 tools in human healthcare settings. The capabilities of the CDS tools varied when reviewed against the GUIDES checklist., Discussion: We recommend a methodological approach for the development of veterinary CDS tools in LMICs predicated on securing sufficient and sustainable funding. Employing a multidisciplinary development team is an important first step. Developing standalone CDS tools using Bayesian algorithms based on local expert knowledge will provide users with rapid and reliable access to quality guidance on diagnoses and treatments. Such tools are likely to contribute to improved disease management on farms and reduce inappropriate antimicrobial use, thus supporting AMS practices in areas of high need., Competing Interests: HY, AH, and SB were employed by Ausvet. AC was employed by Ausvet Europe. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yusuf, Hillman, Stegeman, Cameron and Badger.)

Background: A quarter of People with Intellectual Disabilities (PwID) have epilepsy compared with 1% of the general population. Epilepsy in PwID is a bellwether for premature mortality, multimorbidity and polypharmacy. This group depends on their care provider to give relevant information for management, especially epilepsy. There is no research on care status relationship and clinical characteristics of PwID and epilepsy., Aim: Explore and compare the clinical characteristics of PwID with epilepsy across different care settings., Method: A retrospective multicentre cohort study across England and Wales collected information on seizure characteristics, intellectual disability severity, neurodevelopmental/biological/psychiatric comorbidities, medication including psychotropics/anti-seizure medication, and care status. Clinical characteristics were compared across different care settings, and those aged over and younger than 40 years., Results: Of 618 adult PwID across six centres (male:female = 61%:39%), 338 (55%) received professional care whereas 258 (42%) lived with family. Significant differences between the care groups existed in intellectual disability severity ( P = 0.01), autism presence ( P < 0.001), challenging behaviour ( P < 0.001) and comorbid physical conditions ( P = 0.008). The two groups did not vary in intellectual disability severity/genetic conditions/seizure type and frequency/psychiatric disorders. The professional care cohort experienced increased polypharmacy ( P < 0.001) and antipsychotic/psychotropic use ( P < 0.001/ P = 0.008).The over-40s cohort had lower autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) comorbidity ( P < 0.001/ P = 0.007), increased psychiatric comorbidity and challenging behaviour ( P < 0.05), physical multimorbidity ( P < 0.001), polypharmacy ( P < 0.001) and antipsychotic use ( P < 0.001) but reduced numbers of seizures ( P = 0.007)., Conclusion: PwID and epilepsy over 40 years in professional care have more complex clinical characteristics, increased polypharmacy and antipsychotic prescribing but fewer seizures.

Background: People with intellectual disabilities (ID) die on an average 20 years earlier to the general population. They have higher rates of multimorbidity and polypharmacy. Around 25% of people with ID report chronic constipation. The England Learning Disabilities Mortality Review found that nearly 25% of deaths identified constipation as a long-term health problem. However, the likely risk factors for constipation related harm are poorly enumerated. We sought to identify possible specific high-risk factors by examining the clinical characteristics of people with ID admitted to hospital with constipation., Methods: Data of people with ID admitted with constipation in two general hospitals covering a population of 1.3 million from 2017 to 2022 were reported using the STROBE guideline for cohort studies. Collected data included age, gender, intellectual disability severity, recorded medication, presenting complaint and co-morbidities. The medication anticholinergic burden was calculated using the anticholinergic burden scale. Continuous variables were summarised by mean and standard deviation if normally distributed, with categorical variables summarised by the number and percentage in each category., Results: Of 46 admissions (males 52%), 57% had moderate to profound ID, 37% had epilepsy, 41% prescribed antiseizure medication (ASM) and 45% were on laxatives. Average age was 46 years. The anticholinergic burden score mean was 2.3 and median, one., Conclusions: We can hypothesise that people with more severe ID, suffering from epilepsy and on ASM may be more at risk of developing severe constipation. Some admissions may be avoided with earlier use of laxatives in the community., (© 2023 The Authors. Journal of Intellectual Disability Research published by John Wiley & Sons and MENCAP.)

The guidelines released by the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) in 2022 and those released in 2021 by the European Society of Cardiology (ESC) play a crucial role in offering evidence-based recommendations for the diagnosis and management of heart failure (HF). This comprehensive review aims to provide an overview of these guidelines, incorporating insights from relevant clinical trials. While there is considerable alignment between the two sets of guidelines, certain notable differences arise due to variations in publication timelines, which we will outline. By presenting this summary, our objective is to empower clinicians to make informed decisions regarding HF management in their own practice, and facilitate the development of more harmonized guidelines in the future., (© 2023. The Author(s).)

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems., Competing Interests: none., (Copyright: © 2023 Garnier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A portion of problem behavior is maintained by multiple reinforcement contingencies. Treating multiply controlled problem behavior may be more complex than treating problem behavior maintained by a single contingency. Several approaches for addressing multiply controlled problem behavior have been described in the literature. The purpose of this review is to provide practitioners with an overview of function-based approaches for addressing multiply controlled problem behavior. In particular, we present guidelines for functional analysis and treatment. We also describe strengths and limitations of published treatment approaches and discuss strategies for mitigating these limitations. Finally, we describe areas for future research., Competing Interests: Conflicts of InterestsThe authors have no relevant financial or nonfinancial interests to disclose., (© Association for Behavior Analysis International 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Computational phenotyping (CP) technology uses facial recognition algorithms to classify and potentially diagnose rare genetic disorders on the basis of digitised facial images. This AI technology has a number of research as well as clinical applications, such as supporting diagnostic decision-making. Using the example of CP, we examine stakeholders' views of the benefits and costs of using AI as a diagnostic tool within the clinic. Through a series of in-depth interviews (n ​= ​20) with: clinicians, clinical researchers, data scientists, industry and support group representatives, we report stakeholder views regarding the adoption of this technology in a clinical setting. While most interviewees were supportive of employing CP as a diagnostic tool in some capacity we observed ambivalence around the potential for artificial intelligence to overcome diagnostic uncertainty in a clinical context. Thus, while there was widespread agreement amongst interviewees concerning the public benefits of AI assisted diagnosis, namely, its potential to increase diagnostic yield and enable faster more objective and accurate diagnoses by up skilling non specialists and thereby enabling access to diagnosis that is potentially lacking, interviewees also raised concerns about ensuring algorithmic reliability, expunging algorithmic bias and that the use of AI could result in deskilling the specialist clinical workforce. We conclude that, prior to widespread clinical implementation, on-going reflection is needed regarding the trade-offs required to determine acceptable levels of bias and conclude that diagnostic AI tools should only be employed as an assistive technology within the dysmorphology clinic., Competing Interests: The authors have no conflicts of interest to declare. This work was carried out while SB was a member of the Ethox Centre at the University of Oxford., (© 2023 The Authors.)

In 2017, Washington State passed a law requiring life-safety alerts and warnings to be delivered to its residents in languages they understand. In response, King County Emergency Management and its partners developed an inclusive emergency communications plan to address this challenge. A key goal of this plan was the development of a trusted partner network (TPN), run by volunteers from the county's various language and ethnic groups, to relay timely life-safety alerts to their communities, in order to save additional lives and property. This paper outlines the development of the TPN from concept to activation, and shares the lessons learned along the way. It also describes the limitations of the programme and the various factors that jurisdictions should consider before replicating such a programme.

Background: As the use of AI becomes more pervasive, and computerised systems are used in clinical decision-making, the role of trust in, and the trustworthiness of, AI tools will need to be addressed. Using the case of computational phenotyping to support the diagnosis of rare disease in dysmorphology, this paper explores under what conditions we could place trust in medical AI tools, which employ machine learning., Methods: Semi-structured qualitative interviews (n = 20) with stakeholders (clinical geneticists, data scientists, bioinformaticians, industry and patient support group spokespersons) who design and/or work with computational phenotyping (CP) systems. The method of constant comparison was used to analyse the interview data., Results: Interviewees emphasized the importance of establishing trust in the use of CP technology in identifying rare diseases. Trust was formulated in two interrelated ways in these data. First, interviewees talked about the importance of using CP tools within the context of a trust relationship; arguing that patients will need to trust clinicians who use AI tools and that clinicians will need to trust AI developers, if they are to adopt this technology. Second, they described a need to establish trust in the technology itself, or in the knowledge it provides-epistemic trust. Interviewees suggested CP tools used for the diagnosis of rare diseases might be perceived as more trustworthy if the user is able to vouchsafe for the technology's reliability and accuracy and the person using/developing them is trusted., Conclusion: This study suggests we need to take deliberate and meticulous steps to design reliable or confidence-worthy AI systems for use in healthcare. In addition, we need to devise reliable or confidence-worthy processes that would give rise to reliable systems; these could take the form of RCTs and/or systems of accountability transparency and responsibility that would signify the epistemic trustworthiness of these tools. words 294., (© 2022. The Author(s).)

Introduction: Electronic information systems (EIS) that implement a 'One Health' approach by integrating antimicrobial resistance (AMR) data across the human, animal and environmental health sectors, have been identified as a global priority. However, evidence on the availability, technical capacities and effectiveness of such EIS is scarce., Methods: Through a qualitative synthesis of evidence, this systematic scoping review aims to: identify EIS for AMR surveillance that operate across human, animal and environmental health sectors; describe their technical characteristics and capabilities; and assess whether there is evidence for the effectiveness of the various EIS for AMR surveillance. Studies and reports between 1 January 2000 and 21 July 2021 from peer-reviewed and grey literature in the English language were included., Results: 26 studies and reports were included in the final review, of which 27 EIS were described. None of the EIS integrated AMR data in a One Health approach across all three sectors. While there was a lack of evidence of thorough evaluations of the effectiveness of the identified EIS, several surveillance system effectiveness indicators were reported for most EIS. Standardised reporting of the effectiveness of EIS is recommended for future publications. The capabilities of the EIS varied in their technical design features, in terms of usability, data display tools and desired outputs. EIS that included interactive features, and geospatial maps are increasingly relevant for future trends in AMR data analytics., Conclusion: No EIS for AMR surveillance was identified that was designed to integrate a broad range of AMR data from humans, animals and the environment, representing a major gap in global efforts to implement One Health approaches to address AMR., Competing Interests: Competing interests: None, all authors are employed by the Ausvet Group via its companies Ausvet and Ausvet Europe., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We present an analytic computation of the two-loop QCD corrections to ud[over ¯]→W^{+}bb[over ¯] for an on-shell W boson using the leading color and massless bottom quark approximations. We perform an integration-by-parts reduction of the unpolarized squared matrix element using finite field reconstruction techniques and identify an independent basis of special functions that allows an analytic subtraction of the infrared and ultraviolet poles. This basis is valid for all planar topologies for five-particle scattering with an off-shell leg.

Objective: Improving antimicrobial stewardship in the livestock sector requires an understanding of the motivations for antimicrobial use and the quantities consumed. However,detailed information on antimicrobial use in livestock sectors is lacking. This cross-sectional study aimed to better understand antimicrobial use in the beef feedlot sector in Australia., Design: A self-administered questionnaire asking about antimicrobial use and reasons for use was designed and mailed to beef feedlot operators in Australia. Respondents were asked to report the percentage of animals treated, purpose of use, and disease conditions targeted for 26antimicrobial agents., Results: In total, 83 of 517 (16.1%) beef feedlot operators completed the survey. Monensin (61.0%of respondents) and virginiamycin (19.5%of respondents) were the most commonly reported in-feed antimicrobials. In-feed antimicrobial agents were most frequently used by respondents for treatment of gastrointestinal diseases (52.8%). Antimicrobials were used for growth promotion by 42.1% of respondents, with most (85.7%) reporting the use of ionophores(a group of compounds not used in human medicine). Short-acting penicillin(69.1%), short-acting oxytetracycline, and tulathromycin (both 57.3%) werethe most common injectable antimicrobial agents used. Injectable antimicrobials were most frequently used to treat respiratory (72.3%) and musculoskeletal (67.5%) conditions., Conclusion: Overall,the use of antimicrobials was appropriate for the purpose indicated, and there was a strong preference for drugs of low-importance in human medicine. The data described here stand to be a strong influence on the implementation of an antimicrobial stewardship program in the sector., (© 2019 Australian Veterinary Association.)

Purpose: Abusive head trauma (AHT) can have debilitating sequelae for children who survive. A retrospective medical record review was used to describe short-term developmental outcomes of children with AHT and identify predictors of poorer outcomes., Method: Children with AHT who received follow up by the hospital's rehabilitation department for 12 to 24 months post-injury were included in this review. Data for 85 children were collected on hearing, vision, gross motor, fine motor, speech and language, cognition, play, adaptive functioning, behaviour and personal-social skills., Results: Global assessment found 42% of children had a good recovery, 34% had a moderate disability and 24% had a severe disability. For whom there was data, more than half had abnormal cognition, behaviour and personal-social skills, whilst more than a third had abnormal speech and language, neurological signs on last assessment, vision, play skills, and gross and fine motor skills. Factors that predicted poorer prognosis across all developmental domains included paediatric intensive care unit admission, longer length of hospital stay, breathing difficulty and lower Glasgow Coma Scale on presentation., Conclusion: This study highlights the substantial number of children who have abnormal development in the short-term post-AHT and assists in identifying those who require extensive long-term follow up.

Reliable assessment of the susceptibility of animal bacterial pathogens to antimicrobials is of paramount importance in the fight against antimicrobial resistance. This work aims to estimate the repeatability (intra-laboratory agreement) and reproducibility (inter-laboratory agreement) of the disc diffusion assay in veterinary laboratories to understand further if the assay has a role in the surveillance of antimicrobial resistance in animals. Seven major veterinary laboratories from all States in Australia participated, and each tested the same panel of isolates five times at three to four-week intervals, against six antimicrobial agents using Clinical and Laboratory Standards Institute protocols. The panel consisted of twenty different isolates from porcine Escherichia coli from clinical cases and a single reference strain (ATCC 25922). Laboratories were blinded to the identity of the isolates, replicates, and to each other. In total, 4200 inhibition zone diameters (mm) were collected, and analysed descriptively, graphically, and with linear mixed models. Regardless of the laboratories and isolate/antimicrobial combinations, the overall very major error rate (proportion of isolates classified as susceptible when actual status is resistant) was 1.6%; the major error rate (proportion of isolates classified as resistant when actual status is susceptible) was 1.6%; and the 'minor error' rate (proportion of isolates with intermediate susceptibility that measure fully susceptible or resistant or vice versa) was 2.4%. The variation between repeated measurements ranged between 4.4-7.2 mm depending on the antimicrobial agent assessed. The reproducibility was always more variable than the repeatability, which suggested some laboratory effects. The repeatability coefficient of disc diffusion was lowest for tetracycline (4.4 mm, 95% CI: 3.8-5.0 mm) and ampicillin (4.6 mm, 95% CI: 4.2-5.2 mm) and highest for trimethoprim-sulfamethoxazole (6.6 mm, 95% CI: 5.9-7.4 mm). The reproducibility coefficient of disc diffusion was lowest for gentamicin (5.4, 95% CI: 4.0-7.2) and highest for trimethoprim-sulfamethoxazole (7.2 mm, 95%CI: 4.5-11.7 mm). The precision of the disc diffusion assay was deemed satisfactory for use in a national surveillance program for clinical porcine E. coli isolates. However, measurement variation of the disc diffusion assay is of concern for isolates with marginal susceptibility or resistance due to increased risk of misclassification., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We compute the full-color two-loop five-gluon amplitude for the all-plus helicity configuration. In order to achieve this, we calculate the required master integrals for all permutations of the external legs, in the physical scattering region. We verify the expected divergence structure of the amplitude and extract the finite hard function. We further validate our result by checking the factorization properties in the collinear limit. Our result is fully analytic and valid in the physical scattering region. We express it in a compact form containing logarithms, dilogarithms, and rational functions.

This study evaluated the diagnostic test accuracy of disc diffusion relative to broth-microdilution for clinical Staphylococcus pseudintermedius isolated from dogs in Australia (n = 614). Accuracy of disc diffusion and broth-microdilution for oxacillin relative to mecA real-time PCR was also assessed. Each isolate had paired minimum inhibitory concentration and zone diameter values for ten antimicrobial agents. Data was dichotomised using Clinical and Laboratory Standards Institute susceptible and resistant clinical breakpoints. Test accuracy was reported using relative diagnostic sensitivity (RSe), specificity (RSp), likelihood ratio pairs, diagnostic odds ratio, and area-under-the receiver-operating characteristic (ROC AUC) analysis. Disc diffusion was found to have high test accuracy for most antimicrobials (ROC AUC range: 0.96 - 0.99) except rifampicin (ROC AUC = 0.80). The RSp of disc diffusion was high for all antimicrobials (range, 97.1%-100%). However, RSe was considerably variable (range, 35.7%-98.8%), particularly for amoxicillin-clavulanic acid (51.5%, 95% CI, 38.9%, 64.0%), cefoxitin (35.7%, 95% CI, 12.8%, 64.9%), and cephalothin (43.6%, 95% CI, 27.8%, 60.4%). When disc diffusion and broth-microdilution were compared to mecA real-time PCR, the overall accuracy of both assays was similar (ROC AUC, 0.99 respectively). However, the RSe for broth-microdilution (96.1%, 95% CI, 88.9%, 99.2%) was significantly higher than for disc diffusion (86.8%, 95% CI, 77.1%, 93.5%) (McNemars mid-p value 0.01). Overall, these findings demonstrate that for most antimicrobials, disc diffusion performed according to CLSI guidelines can be used to differentiate clinical S. pseudintermedius isolates that might otherwise be assessed by broth-microdilution, provided consideration is given to the performance estimates reported here., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In 2013, the Cambridge Clinical Research Facility (CCRF) set up a Children's Non-Executive Research Board to advise on service and facility development and research involving children and young people (CYP). In 2015, the Children's Experiences of Engaging in Research study (CHEER) was conceived to explore the Children's Board as a patient and public involvement initiative., Aim: To explore the views of CYP, staff and parents involved in the Children's Board with the view to describe their experiences of the selected mechanism of involvement (Children's Board) within the context of operation (CCRF)., Methods: A qualitative descriptive methodology involving qualitative content analysis of semi-structured interviews was used to derive descriptive summaries of the interview data., Setting and Participants: Interviews were carried out with staff ( n  = 5), children ( n  = 2) and parents (n = 2) who participated in the first or second Children's Board meetings., Results: Twelve descriptive summaries emerged: (1) CCRF 'role' perspective (2) purpose, remit and future direction (3) aspirations (4) learning as reciprocation (5) regular meetings, contact and feedback (6) expectation setting and ground rules (7) culture of PPI (8) surprise, underestimation and self-selection (9) reciprocity, incentivisation and participation (10) practicalities, timing and barriers (11) parental roles (12) event structure. These highlighted the importance of selecting the right mechanism of involvement in relation to context for involvement and the reductive biases adults and healthcare providers may unconsciously hold. Both of these aspects may affect the efficacy of PPI endeavours with CYP., Discussion and Conclusions: Mechanisms by which CYP are involved in research should be considered from the outset; taking into consideration both the setting and contextual features. Contextual and process factors important in the adult PPI realm were generally observed in this PPI initiative with CYP; however further research is required to explore unconscious biases and reductive perceptions in adult facilitators., Competing Interests: Ethics approval by National Research Ethics Service London-Chelsea was granted in October 2015, REC Reference: 15/LO/1364.Participant’s consented to anonymous publishing of their data.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Biomedical research aimed at the development of therapies for chronic and late-onset conditions increasingly concentrates on the early treatment of symptom-less disease. This broad trend is evidenced in prominent shifts in contemporary dementia research. Revised diagnostic criteria and new approaches to clinical trials propose a focus on earlier stages of disease and prompt concerns about the implications of communicating test results associated with the risk of developing dementia when no effective treatments are available. This article examines expectations of the implications of learning test results related to dementia risk, based on focus group research conducted in the UK and Spain. It points to the extended social and temporal aspects of the dementia risk experience. Three key dimensions of this risk experience are elaborated: living 'at risk', represented in efforts to reduce risk and plan for the future; 'with risk', through vigilance towards cognitive health and earlier or prolonged contact with healthcare services; and finally, 'beyond risk' through a cessation of the self in its current social, legal and financial form. A virtual abstract of this paper can be viewed at: https://www.youtube.com/channel/UC&#95;979cmCmR9rLrKuD7z0ycA., (© 2018 Foundation for the Sociology of Health & Illness.)

We compute the leading-color contributions to five-gluon scattering at two loops in massless QCD. The integrands of all independent helicity amplitudes are evaluated using d-dimensional generalized unitarity cuts and finite field reconstruction techniques. Numerical evaluation of the integral basis is performed with sector decomposition methods to obtain the first benchmark results for all helicity configurations of a 2→3 scattering process in QCD.

The assessment of antimicrobial resistance in bacteria derived from animals is often performed using the disc diffusion assay. However broth-microdilution is the preferred assay for national antimicrobial resistance surveillance programs. This study aimed to evaluate the accuracy of disc diffusion relative to broth-microdilution across a panel of 12 antimicrobials using data from a collection of 994 clinical Escherichia coli isolates from animals. Disc diffusion performance was evaluated by diagnostic sensitivity, specificity, likelihood ratio pairs and receive-operating characteristic (ROC) analysis. Data was dichotomised using CLSI susceptible and resistant clinical breakpoints. In addition, disc diffusion breakpoints produced using diffusion Breakpoint Estimation Testing Software (dBETS) were evaluated. Analysis revealed considerable variability in performance estimates for disc diffusion susceptible and resistant breakpoints (AUC ranges: 0.78-0.99 and 0.92-1.0, respectively) across the panel of antimicrobials. Ciprofloxacin, tetracycline, and ampicillin estimates were robust across both breakpoints, whereas estimates for several antimicrobials including amoxicillin-clavulanic acid, cefoxitin and gentamicin were less favourable using susceptible breakpoints. Overall performance estimates were moderately improved when dBETS susceptible breakpoints were applied. For most antimicrobials, disc diffusion was accurate at predicting resistance of clinical E. coli from animals that could otherwise be determined by broth-microdilution. While disc diffusion is suboptimal for assessing the proportion of fully susceptible isolates for some drugs, sensitivity and specificity estimates provided here allow for the use of standard formula to correct this. For this reason, disc diffusion has applicability in national surveillance provided the performance of the assay is taken into account., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In clinical trials which target pathophysiological mechanisms associated with Alzheimer's disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer's dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants' experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer's disease biomarkers.

Reproductive genetic testing- PreNatal Diagnosis (PND) and Preimplantation Genetic Diagnosis (PGD)-for CDH1 mutations associated with Hereditary Diffuse Gastric Cancer (HDGC)is available in the UK. This qualitative interview study examined high-risk individuals' (n = 35) views of CDH1 reproductive genetic testing. Interviewees generally regarded reproductive genetic testing as an acceptable form of HDGC risk management. However, some were concerned that their genetic risks required them to plan reproduction and anticipated difficulties communicating this to reproductive partners. Individuals had a preference for PGD over PND because it avoided the need for a termination of pregnancy. However, those who had not yet had children expressed concerns about having to undergo IVF procedures and worries about their effectiveness and the need for embryo selection in PGD. It is suggested that high-risk individuals are provided with access to reproductive genetic counselling.

Individuals identified as at high risk of developing Hereditary Diffuse Gastric Cancer (HDGC) are advised to undergo prophylactic surgery - have their stomach removed - in their early twenties. Research with (older) cancer patients who undergo gastrectomy for curative reasons suggests that gastric resection has a number of physical and psychosocial sequelae. Because it is difficult to extrapolate the findings of studies of older cancer patients to younger healthy patients who are considering prophylactic total gastrectomy (PTG), the aim of this qualitative interview study was to determine the psychosocial implications of undergoing prophylactic surgery to manage genetic risk. Fourteen men and 13 women from the UK's Familial Gastric Cancer study who had undergone PTG were invited to participate in qualitative interviews. Most reported that undergoing surgery and convalescence was easier than anticipated. There was evidence that age affected experiences of PTG, with younger patients tending to report faster recovery times and more transient aftereffects. All saw the benefits of risk reduction as outweighing the costs of surgery. Surgery was described as having a range of physical impacts (disrupted appetite, weight loss, fatigue, GI symptoms) that had related psychological, social and economic implications. Those considering PTG need to be aware that its impact on quality of life is difficult to predict and negative sequelae may be ongoing for some individuals.

Background: An abdominal aortic aneurysm (AAA) (pathological enlargement of the aorta) is a condition that can occur as a person ages. It is most commonly seen in men older than 65 years of age. Progressive aneurysm enlargement can lead to rupture and massive internal bleeding, which is fatal unless timely repair can be achieved. Despite improvements in perioperative care, mortality remains high (approximately 50%) after conventional open surgical repair. Endovascular aneurysm repair (EVAR), a minimally invasive technique, has been shown to reduce early morbidity and mortality as compared to conventional open surgery for planned AAA repair. More recently emergency endovascular aneurysm repair (eEVAR) has been used successfully to treat ruptured abdominal aortic aneurysm (RAAA), proving that it is feasible in select patients; however, it is unclear if eEVAR will lead to significant improvements in outcomes for these patients or if indeed it can replace conventional open repair as the preferred treatment for this lethal condition. This is an update of the review first published in 2006., Objectives: To assess the advantages and disadvantages of emergency endovascular aneurysm repair (eEVAR) in comparison with conventional open surgical repair for the treatment of ruptured abdominal aortic aneurysm (RAAA). This will be determined by comparing the effects of eEVAR and conventional open surgical repair on short-term mortality, major complication rates, aneurysm exclusion (specifically endoleaks in the eEVAR treatment group), and late complications., Search Methods: For this update the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (last searched June 2016), CENTRAL (2016, Issue 5), and trials registries. We also checked reference lists of relevant publications., Selection Criteria: Randomised controlled trials in which participants with a clinically or radiologically diagnosed RAAA were randomly allocated to eEVAR or conventional open surgical repair., Data Collection and Analysis: Two review authors independently assessed studies identified for potential inclusion for eligibility. Two review authors also independently completed data extraction and quality assessment. Disagreements were resolved through discussion. We performed meta-analysis using fixed-effect models with odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous data and mean differences with 95% CIs for continuous data., Main Results: We included four randomised controlled trials in this review. A total of 868 participants with a clinical or radiological diagnosis of RAAA were randomised to receive either eEVAR or open surgical repair. Overall risk of bias was low, but we considered one study that performed randomisation in blocks by week and performed no allocation concealment and no blinding to be at high risk of selection bias. Another study did not adequately report random sequence generation, putting it at risk of selection bias, and two studies were underpowered. There was no clear evidence to support a difference between the two interventions for 30-day (or in-hospital) mortality (OR 0.88, 95% CI 0.66 to 1.16; moderate-quality evidence). There were a total of 44 endoleak events in 128 participants from three studies (low-quality evidence). Thirty-day complication outcomes (myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation, and respiratory failure) were reported in between one and three studies, therefore we were unable to draw a robust conclusion. We downgraded the quality of the evidence for myocardial infarction, renal complications, and respiratory failure due to imprecision, inconsistency, and risk of bias. Odds ratios for complications outcomes were OR 2.38 (95% CI 0.34 to 16.53; 139 participants; 2 studies; low-quality evidence) for myocardial infarction; OR 1.07 (95% CI 0.21 to 5.42; 255 participants; 3 studies; low-quality evidence) for renal complications; and OR 3.62 (95% CI 0.14 to 95.78; 32 participants; 1 study; low-quality evidence) for respiratory failure. There was low-quality evidence of a reduction in bowel ischaemia in the eEVAR treatment group, but very few events were reported (OR 0.37, 95% CI 0.14 to 0.94), and we downgraded the evidence due to imprecision and risk of bias. Six-month and one-year outcomes were evaluated in three studies, but only results from a single study could be used for each outcome, which showed no clear evidence of a difference between the interventions. We rated six-month mortality evidence as of moderate quality due to imprecision (OR 0.89, 95% CI 0.40 to 1.98; 116 participants)., Authors' Conclusions: The conclusions of this review are currently limited by the paucity of data. We found from the data available moderate-quality evidence suggesting there is no difference in 30-day mortality between eEVAR and open repair. Not enough information was provided for complications for us to make a well-informed conclusion, although it is possible that eEVAR is associated with a reduction in bowel ischaemia. Long-term data were lacking for both survival and late complications. More high-quality randomised controlled trials comparing eEVAR and open repair for the treatment of RAAA are needed to better understand if one method is superior to the other, or if there is no difference between the methods on relevant outcomes.

There is growing interest in the development of novel approaches to secondary prevention trials in Alzheimer's disease to facilitate screening and recruitment of research participants and to reduce the time and costs associated with clinical trials. Several international research collaborations are setting up research infrastructures that link existing research cohorts, studies or patient registries to establish 'trial-ready' or 'readiness' cohorts. From these cohorts, individuals are recruited into clinical trial platforms. In setting up such research infrastructures, researchers must make ethically challenging design decisions in at least three areas: re-contacting participants in existing research studies, obtaining informed consent for participation in a readiness cohort, and disclosure of Alzheimer's disease-related biomarkers. These ethical considerations have been examined by a dedicated workgroup within the European Prevention of Alzheimer's Dementia (EPAD) project, a trans-European longitudinal cohort and adaptive proof-of-concept clinical trial platform. This paper offers recommendations for the ethical management of re-contact, informed consent and risk disclosure which may be of value to other research collaborations in the process of developing readiness cohorts for prevention trials in Alzheimer's disease and other disease areas., Competing Interests: LT is an employee of Janssen R and D LLC, EFPIA co-lead of the IMI-EPAD project and member of the Johnson and Johnson BioResearch Ethics Committee. MM is an employee of Novartis Pharma AG. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of their employers or organizations. RM, EB, KT, SBe, SBa, DG, MS, CB and ER have no conflicts of interest with this paper.

Background: Current Alzheimer's disease (AD) research initiatives focus on cognitively healthy individuals with biomarkers that are associated with the development of AD. It is unclear whether biomarker results should be returned to research participants and what the psychological, behavioral and social effects of disclosure are. This systematic review therefore examines the psychological, behavioral and social effects of disclosing genetic and nongenetic AD-related biomarkers to cognitively healthy research participants., Methods: We performed a systematic literature search in eight scientific databases. Three independent reviewers screened the identified records and selected relevant articles. Results extracted from the included articles were aggregated and presented per effect group., Results: Fourteen studies met the inclusion criteria and were included in the data synthesis. None of the identified studies examined the effects of disclosing nongenetic biomarkers. All studies but one concerned the disclosure of APOE genotype and were conducted in the USA. Study populations consisted largely of cognitively healthy first-degree relatives of AD patients. In this group, disclosure of an increased risk was not associated with anxiety, depression or changes in perceived risk in relation to family history. Disclosure of an increased risk did lead to an increase in specific test-related distress levels, health-related behavior changes and long-term care insurance uptake and possibly diminished memory functioning., Conclusion: In cognitively healthy research participants with a first-degree relative with AD, disclosure of APOE ε4-positivity does not lead to elevated anxiety and depression levels, but does increase test-related distress and results in behavior changes concerning insurance and health. We did not find studies reporting the effects of disclosing nongenetic biomarkers and only one study included people without a family history of AD. Empirical studies on the effects of disclosing nongenetic biomarkers and of disclosure to persons without a family history of AD are urgently needed., Trial Registration: PROSPERO international prospective register for systematic reviews CRD42016035388 . Registered 19 February 2016.

Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit to undergo gastrectomy, or in whom the genetic testing result is unknown or ambiguous, are offered surveillance. Little is known about the factors that influence decisions to undergo or decline PTG, making it difficult to provide optimal support for those facing these decisions. Qualitative interviews were carried out with 35 high-risk individuals from the Familial Gastric Cancer Study in the UK. Twenty-seven had previously undergone PTG and eight had been identified as carrying a pathogenic CDH1 mutation but had declined surgery at the time of interview. The interviews explored the experience of decision-making and factors influencing risk-management decisions. The data suggest that decisions to proceed with PTG are influenced by a number of potentially competing factors: objective risk confirmation by genetic testing and/or receiving a positive biopsy; perceived familial cancer burden and associated risk perceptions; perceptions of post-surgical life; an increasing inability to tolerate endoscopic procedures; a concern that surveillance could miss a cancer developing and individual's life stage. These findings have implications for advising this patient group.

Objective: The aim of the study was to explore the feasibility of expanding a community service for early detection of psychosis into a local London prison for men in the United Kingdom., Methods: All new receptions to a local prison for men in South London were approached for routine screening. Those who met criteria for being at ultra-high-risk of psychosis were compared with a help-seeking sample from the community who met the same criteria. Clinical and sociodemographic characteristics were compared to determine whether the prison and community populations had similar profiles and mental health needs., Results: Of 891 prisoners screened, 44 (5%) met criteria for being at ultra-high risk of psychosis. The community sample consisted of 42 participants. Compared with the community group, prison participants had lower scores on almost all symptom measures, were less likely to have remained in school and completed exams, and were more likely to be in short-term accommodations and to be of black race-ethnicity. Lifetime use of illicit drugs was similar between the groups, but recent use was much higher in the prison group., Conclusions: Expanding community services into custodial settings should take into account the different environment and needs of the prisoner population. Specifically, early detection and intervention services should target a broad range of mental health problems rather than psychosis alone.

Objectives: A key aim of palliative care is to improve the quality-of-life of people with a life-threatening illness. Occupational therapists are well positioned to contribute to this aim due to their broad range of interventions, client-centeredness and focus on occupation. However, there is a limited understanding of how occupational therapy contributes to the end-of-life experience, which is crucial to providing optimal care. The aim of this study is to investigate the lived experience of occupational therapy in palliative care for people with a life-threatening illness., Method: A hermeneutic interpretive phenomenological approach was adopted. Semi-structured interviews were conducted with eight participants recruited from inpatient and outpatient sectors of a specialist palliative care hospital in Sydney, Australia., Results: The two themes developed from participant responses were: (1) occupational therapy provides comfort and safety and (2) trusting the occupational therapist to know what is needed., Significance of Results: This study gives insight into the ways in which people with a life-threatening illness experience occupational therapy in palliative care. In addition, it provides a starting point to guide practice that is attentive to the needs of people with a life-threatening illness at end-of-life, thus enhancing client-centered care.

Objectives: Emergency endovascular aneurysm repair (eEVAR) may improve outcomes for patients with ruptured abdominal aortic aneurysm (RAAA). The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA., Setting: A systematic review of relevant publications was performed. Randomised controlled trials (RCTs) comparing eEVAR with open surgical repair for RAAA were included., Participants: 3 RCTs were included, with a total of 761 patients with RAAA., Interventions: Meta-analysis was performed with fixed-effects models with ORs and 95% CIs for dichotomous data and mean differences with 95% CIs for continuous data., Primary and Secondary Outcome Measures: Primary outcome was short-term mortality. Secondary outcome measures included aneurysm-specific and general complication rates, quality of life and economic analysis., Results: Overall risk of bias was low. There was no difference between the 2 interventions on 30-day (or in-hospital) mortality, OR 0.91 (95% CI 0.67 to 1.22; p=0.52). 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation and respiratory failure. Reporting was incomplete, and no robust conclusion was drawn. For complication outcomes that did include at least 2 studies in the meta-analysis, there was no clear evidence to support a difference between eEVAR and open repair. Longer term outcomes and cost per patient were evaluated in only a single study, thus precluding definite conclusions., Conclusions: Outcomes between eEVAR and open repair, specifically 30-day mortality, are similar. However, further high-quality trials are required, as the paucity of data currently limits the conclusions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background. Several psychometric instruments are available for the diagnostic interview of subjects at ultra high risk (UHR) of psychosis. Their diagnostic comparability is unknown. Methods. All referrals to the OASIS (London) or CAMEO (Cambridgeshire) UHR services from May 13 to Dec 14 were interviewed for a UHR state using both the CAARMS 12/2006 and the SIPS 5.0. Percent overall agreement, kappa, the McNemar-Bowker χ (2) test, equipercentile methods, and residual analyses were used to investigate diagnostic outcomes and symptoms severity or frequency. A conversion algorithm (CONVERT) was validated in an independent UHR sample from the Seoul Youth Clinic (Seoul). Results. There was overall substantial CAARMS-versus-SIPS agreement in the identification of UHR subjects (n = 212, percent overall agreement = 86%; kappa = 0.781, 95% CI from 0.684 to 0.878; McNemar-Bowker test = 0.069), with the exception of the brief limited intermittent psychotic symptoms (BLIPS) subgroup. Equipercentile-linking table linked symptoms severity and frequency across the CAARMS and SIPS. The conversion algorithm was validated in 93 UHR subjects, showing excellent diagnostic accuracy (CAARMS to SIPS: ROC area 0.929; SIPS to CAARMS: ROC area 0.903). Conclusions. This study provides initial comparability data between CAARMS and SIPS and will inform ongoing multicentre studies and clinical guidelines for the UHR psychometric diagnostic interview.

Objective/background: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations., Methods: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline., Results: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses., Conclusion: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct., (Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Aim: This project explored the impact of a general practitioner (GP) training programme on referrals and pathways to care for people at high clinical risk of psychosis or with a first-episode psychosis. The resources needed to deliver the training were measured to help inform other teams considering this approach. Satisfaction with the training was also explored., Methods: All of the GP (48) practices in the London Borough of Southwark were approached. Presentations were given on the symptoms of a clinical high-risk state and the first signs of psychosis alongside information on how to access the teams. Referrals to the prodromal and first-episode teams 6 months before and after the training were recorded. Resources needed to deliver the training in terms of staff time were recorded. A questionnaire on attendees' satisfaction with the training was given., Results: Sixty percent of eligible practices received education. On average, it took 2 h for every two staff members each to deliver the training. Over the 12-month period, the teams received 148 referrals. The training led to a significant increase in referrals to the two specialized teams and a significant increase in direct referrals to the teams from GPs. Attendees were satisfied with the training., Conclusions: This study indicates that GP education programmes are a viable and acceptable way of increasing the identification of young people at high clinical risk for psychosis or with a first-episode psychosis and increasing direct referrals to specialist teams., (© 2014 Wiley Publishing Asia Pty Ltd.)

In addition to attenuated psychotic symptoms, individuals at high clinical risk of developing psychosis display a wide range of psychopathological features. Some of these may be subjectively perceived as more troubling than others and may therefore be more likely to trigger help-seeking behavior. We aimed at investigating the nature and prevalence of symptoms subjectively considered most distressing by high-risk individuals at the time of their presentation to early recognition services and to determine their impact on baseline and longitudinal functional and clinical outcomes. The clinical records of 221 clients meeting ultra-high risk (UHR) criteria and receiving care at a specialized early intervention service ("Outreach and Support in South London") between 2001 and 2011 were reviewed. Main outcome measures were reason to seek help as subjectively reported by the clients, comorbid DSM-IV SCID diagnoses, transition to psychosis, psychosocial functioning at baseline and after a median follow-up period of 4.5 years. Affective symptoms, i.e., depression and/or anxiety, were the most commonly reported subjective reasons to seek help (47.1%). Sub-threshold psychotic symptoms were reported by 39.8%. There was no significant association between subjective complaints at presentation and transition to psychosis. However, the group reporting affective symptoms as their main subjective reason to seek help at baseline had a significantly poorer longitudinal outcome in psychosocial functioning relative to the group reporting sub-threshold psychotic symptoms. Assessment of subjective complaints in UHR individuals at initial presentation may help to identify predictors of future functional outcome and tailor treatments accordingly., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population., Aims: To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis., Method: We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode., Results: The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment., Conclusions: Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes., (© The Royal College of Psychiatrists 2015.)

Background: The long-term functional status of subjects at ultra high risk for psychosis (HR) is relatively under investigated. This study explores baseline predictors of long-term functional outcome in HR subjects who did not convert to psychosis during a 6 years follow-up period., Methods: A total of 154 HR were followed up for an average of 6 years. The primary outcome variable was global assessment of functioning at the last follow-up visit as assessed with the Global Assessment of Functioning tool. A multinomial logistic regression was performed to identify potential predictors of functional outcome., Results: Baseline and follow-up data on functioning was available for 92 HR. Twenty-four (43%) individuals who did not convert to psychosis reported poor functioning at follow-up. Baseline scores in the GAF (Exp(b) = 0.857; 95% CIs: 0.75/0.97), employment status (Exp(b) = 0.029; 95% CIs: 0.00/0.268), and CAARMS total scores (Exp(b) = 1.976; 95% CIs: 1.00/1.14) predicted functional outcome in HR subjects at 6 years., Conclusions: Despite the preventive treatments received, many individuals who did not convert to full-blown psychosis in the longer term do not functionally remit. These individuals are lower functioning, unemployed and have higher symptom loading at the time of their presentation to the prodromal clinic. Our study suggests the need for innovative treatments targeting long term functional status beyond the prevention of psychosis onset in the HR population., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: An abdominal aortic aneurysm (AAA) (pathological enlargement of the aorta) can develop in both men and women as they grow older. It is most commonly seen in men over the age of 65 years. Progressive aneurysm enlargement can lead to rupture and massive internal bleeding, a fatal event unless timely repair can be achieved. Despite improvements in perioperative care, mortality remains high (approximately 50%) after conventional open surgical repair. A newer minimally invasive technique, endovascular aneurysm repair (EVAR), has been shown to reduce early morbidity and mortality as compared to conventional open surgery for planned AAA repair. Emergency endovascular aneurysm repair (eEVAR) has been used successfully to treat ruptured abdominal aortic aneurysm (RAAA), proving that it is feasible in selected patients. However, it is not yet known if eEVAR will lead to significant improvements in outcomes for these patients or indeed if it can replace conventional open repair as the preferred treatment for this lethal condition., Objectives: To assess the advantages and disadvantages of emergency endovascular aneurysm repair (eEVAR) in comparison with conventional open surgical repair for the treatment of ruptured abdominal aortic aneurysm (RAAA). This will be determined by the effect on short-term mortality, major complication rates, aneurysm exclusion, and late complications when compared with the effects in patients who have had conventional open repair of RAAA., Search Methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and CENTRAL (2014, Issue 2). Reference lists of relevant publications were also checked., Selection Criteria: Randomised controlled trials in which patients with a clinically or radiologically diagnosed RAAA were randomly allocated to eEVAR or conventional open surgical repair., Data Collection and Analysis: Studies identified for potential inclusion were independently assessed for eligibility by at least two review authors. Data extraction and quality assessment were also completed independently by two review authors. Disagreements were resolved through discussion. Meta-analysis was performed using fixed-effect models with odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous data and mean differences with 95% CIs for continuous data., Main Results: Three randomised controlled trials were included in this review. A total of 761 patients with a clinical or radiological diagnosis of RAAA were randomised to receive either eEVAR or open surgical repair. Overall risk of bias was low but one study did not adequately report random sequence generation, putting it at risk of selection bias, two studies did not report on outcomes identified in their protocol, indicating reporting bias, and one study was underpowered. There was no clear evidence to support a difference between the two interventions on 30-day (or in-hospital) mortality, OR of 0.91 (95% CI 0.67 to 1.22; P = 0.52). The 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, re-operation, amputation, and respiratory failure. Individual complication outcomes were reported in only one or two studies and therefore no robust conclusion can currently be drawn. For complication outcomes that did include at least two studies in the meta-analysis there was no clear evidence to support a difference between eEVAR and open repair. Six-month outcomes were evaluated in only a single study, which included mortality and re-operation, with no clear evidence of a difference between the interventions and no overall association. Cost per patient was only evaluated in a single study and therefore no overall associations can currently be derived., Authors' Conclusions: The conclusions of this review are currently limited by the paucity of data. From the data available there is no difference in the outcomes evaluated in this review between eEVAR and open repair, specifically 30-day mortality. Not enough information was provided for complications in order to make a well informed conclusion at this time. Long-term data are lacking for both survival and late complications. More high quality, randomised controlled trials comparing eEVAR and open repair for the treatment of RAAA are needed in order to better understand if one method is superior to the other, or if there is no difference between the methods on relevant outcomes.

Background: Despite the widespread recognition that obesity in pregnant women is associated with adverse outcomes for mother and child, there is no intervention proven to reduce the risk of these complications. The primary aim of this randomised controlled trial is to assess in obese pregnant women, whether a complex behavioural intervention, based on changing diet (to foods with a lower glycemic index) and physical activity, will reduce the risk of gestational diabetes (GDM) and delivery of a large for gestational age (LGA) infant. A secondary aim is to determine whether the intervention lowers the long term risk of obesity in the offspring., Methods/design: Multicentre randomised controlled trial comparing a behavioural intervention designed to improve glycemic control with standard antenatal care in obese pregnant women.Inclusion criteria; women with a BMI ≥30 kg/m2 and a singleton pregnancy between 15+0 weeks and 18+6 weeks' gestation. Exclusion criteria; pre-defined, pre-existing diseases and multiple pregnancy. Randomisation is on-line by a computer generated programme and is minimised by BMI category, maternal age, ethnicity, parity and centre. Intervention; this is delivered by a health trainer over 8 sessions. Based on control theory, with elements of social cognitive theory, the intervention is designed to improve maternal glycemic control. Women randomised to the control arm receive standard antenatal care until delivery according to local guidelines. All women have a 75 g oral glucose tolerance test at 27+0- 28+6 weeks' gestation.Primary outcome; Maternal: diagnosis of GDM, according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Neonatal; infant LGA defined as >90th customised birth weight centile.Sample size; 1546 women to provide 80% power to detect a 25% reduction in the incidence of GDM and a 30% reduction in infants large for gestational age., Discussion: All aspects of this protocol have been evaluated in a pilot randomised controlled trial, with subsequent optimisation of the intervention. The findings of this trial will inform whether lifestyle mediated improvement of glycemic control in obese pregnant women can minimise the risk of pregnancy complications., Trial Registration: Current controlled trials; ISRCTN89971375.

Introduction. Systemic effects of ruptured abdominal aortic aneurysm (rAAA) may be altered by the mode of surgery. This study aimed to determine systemic effects of endovascular aneurysm repair (EVAR) compared to open repair (OR). Patients and Methods. Consecutive patients with rAAA were repaired by OR or EVAR according to computerised tomographic (CT) findings. Renal function was monitored by estimated glomerular filtration rate (eGFR), serum urea and creatinine, and urinary albumin creatinine ratio (ACR). Hepatic function was assessed postoperatively for 5 days. Intestinal function was determined by the paracetamol absorption test. Intestinal permeability was assessed by urinary lactulose/mannitol ratio. Results. 30 rAAA patients were included. Fourteen had eEVAR and sixteen eOR. Serum urea were higher in eOR, while creatinine was similar between groups. Hepatic function showed no intergroup difference. Paracetamol absorption was increased in eEVAR group at day 3 compared to day 1 (P = 0.03), with no similar result in eOR (P = 0.24). Peak lactulose/mannitol ratio was higher in eOR (P = 0.03), with higher urinary L/M ratio in eOR at day 3 (P = 0.02). Clinical intestinal function returned quicker in eEVAR (P = 0.02). Conclusion. EVAR attenuated the organ dysfunction compared to open repair. However, a larger comparative trial would be required to validate this. The clinical trial is registered with reference number EUDRACT: 2013-003373-12.

Introduction. Maximum diameter of an abdominal aortic aneurysm (AAA) is the main indication for surgery. This study compared colour duplex ultrasound (CDU) and computed tomography (CT) in assessing AAA diameter. Patients and Methods. Patients were included if they had both scans performed within 90 days. Pearson's correlation coefficient, paired t-test, and limits of agreement (LOA) were calculated for the whole group. Subgroup analysis of small (<5.0 cm), medium (5.0-6.5 cm), and large (>6.5 cm) aneurysms was performed. A P value of <0.05 was considered statistically significant. Results. 389 patients were included, giving 130 pairs of tests for comparison. Excellent correlation was in the whole group (r = 0.95) and in the subgroups (r = 0.94; 0.69; 0.96, resp.). Small LOA between the two imaging modalities was found in all subgroups. Conclusion. Small aneurysms can be accurately measured using CDU. CDU is preferable for small AAAs, but cannot supplant CT for planning aortic intervention.

Introduction: The study aim was to assess the relationship between the presence of antibodies to Chlamydia pneumoniae and abdominal aortic aneurysm (AAA) incidence., Patients and Methods: Consecutive AAA patients and AAA-free controls were recruited prospectively. Serum samples from both groups were examined to determine Immunoglobulin (Ig) A and IgG titres against Chlamydia pneumoniae by ELISA and C-reactive protein (CRP) concentrations. Results were expressed as mean (SD) or median (IQR) and compared using χ (2) and Mann-Whitney U tests. A P value of <0.05 was considered statistically significant., Results: Each study group (AAA/nAAA) comprised 250 patients. 196 (78.7%) AAA patients had positive IgA antichlamydial antibody titres, compared to 181 (72.4%) in the control group (P = 0.008, OR 2.0, 95% CI 1.2-3.5). However, positive IgG antibody titres were similar (191 versus 203; P = 0.222, OR 0.7, 95% CI 0.4-1.3). Average CRP concentrations were higher in AAA individuals. IgA or IgG antibody titres were not related to CRP concentrations., Conclusions: These results demonstrated that the frequent incidence of Chlamydia pneumoniae antibodies within the general population makes it difficult to relate its presence to AAA development, despite the high IgA antibody titres. In addition, raised CRP concentrations in AAA patients are not related to the presence of antichlamydial antibodies.

Introduction: Prevention of psychosis has become a major objective of modern clinical psychiatry. An increasing number of new services have been established in Europe and in the world. The OASIS team has become an established model where clinical practice and research are fully integrated in the field of preventative interventions in psychosis., Method: Comprehensive analysis of different clinical and service measures describing the 2001-2011 implementation of the OASIS team., Results: Over the last decade, the OASIS team has received a total of 1102 referrals, mostly young males from ethnic minorities. After the assessment, 35% were diagnosed with an At Risk Mental State (ARMS) while 32% were already psychotic. Within the ARMS, 70% met the inclusion criteria for the attenuated psychotic symptoms subgroup, 1% met the inclusion criteria for the genetic deterioration syndrome, 9% met inclusion criteria for a brief and self-limited intermittent psychotic episode and the others met inclusion criteria for more than one subgroup. Most of them had at least one comorbid diagnosis, mainly relating to anxiety and depressive domains. The majority of the OASIS clients received cognitive behavioural therapy alone or in combination with antidepressants/antipsychotics. Over the 2-year follow-up time, 44 subjects (15.2%) developed a frank psychotic episode., Conclusions: The OASIS service represents one of the largest and most established prodromal services in the world. The burden of research evidence and the translational impact produced on the clinical practice support the OASIS as a model for the development of similar services., (Copyright © 2012. Published by Elsevier SAS.)

Introduction: Depletion of Kupffer cells by gadolinium chloride (GdCl(3)) reduces the systemic response during sepsis. The study aim was to investigate the effect of this depletion on hepatic proinflammatory cytokine response to portal endotoxaemia., Methods: Sixteen Wistar rats were randomised to receive either saline IV (n = 8) or GdCl(3) (10 mg/kg IV, n = 8) six days after bile duct ligation (BDL). 24 h later the animals were perfused for 2 h, using isolated hepatic perfusion. Aliquots of effluent perfusate were collected at 20-min intervals for cytokine analysis. Sections of liver were sampled and the hepatic Kupffer cell number of each group was measured using ED1 immunohistochemistry., Results: Pre-treatment with GdCl(3) resulted in significantly reduced serum bilirubin concentrations but significantly elevated serum ALP and AST levels compared to the control group. It was also associated with a significant reduction in Kupffer cell numbers and a corresponding significant reduction in hepatic TNFα and IL-6 production in response to portal endotoxaemia., Conclusions: Pre-treatment with GdCl(3) in jaundiced animals reduced Kupffer cell numbers, attenuated liver enzyme abnormalities and reduced TNFα and IL-6 in response to portal endotoxaemia. Hepatic Kupffer cells, therefore, play a significant role in the development of an exaggerated inflammatory response in obstructive jaundice., (Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Carcinoembryonic antigen (CEA), a marker for colorectal adenocarcinoma, can monitor disease progression and treatment response. This study aims to determine the accuracy of CEA in the detection and resectability of colorectal liver metastases. Patients with primary colorectal cancer were divided into three groups: resectable hepatic metastases (group 1), unresectable metastases (group 2), and disease-free cases (group 3). The CEA concentration was recorded pre- and post-hepatectomy in group 1 and on radiological confirmation of disease state in the other groups. It was expressed as median (95% confidence interval [CI]), with predictors of concentration determined. Group 1 (n=141) had pre-operative CEA of 8.9 (4.6-13.1), with 38.1% of patients being normal. Maximum tumour diameter correlated with CEA level (r=0.41, P<0.0001). Post-hepatectomy CEA was 2.3 (1.9-2.7; P<0.0001), with 81.1% of patients being normal. Group 2 (n=158) had CEA of 20.6 (9.4-31.9). Group 3 (n=361) had CEA of 2.0 (1.8-2.2). Sensitivity of CEA pre- and post-hepatectomy was 61.2% and 69.3%, respectively, while specificity was 79.8% for both groups. Concentration was elevated in hepatic colorectal metastases but is not a marker of resectability. A CEA reduction post-resection indicates that it may be used as an indicator of treatment response, while CEA is increased by tumour burden and lesion size.

Introduction. Ruptured abdominal aortic aneurysm (rAAA) causes a significant inflammatory response. The study aims to investigate this response following endovascular and open repair of ruptured AAA. Patients and Methods. Consecutive rAAA patients had either endovascular aneurysm repair (EVAR) or open repair (OR). Blood samples were taken for cytokines, lipid hydroperoxides (LOOH), antioxidants, and neutrophil elastase/ α 1-anti-trypsin complexes (NE/AAT) before surgery, 6 hours after clamp release and 1, 3, 5 days postoperatively. Results. 30 patients were included in the study, with 14 undergoing eEVAR and 16 eOR, with comparable baseline comorbidities, age, and parameters. IL-6 peaked higher in eOR patients (P = 0.04), while p75TNFr was similar between groups except at day 5 (P = 0.04). The NE/AAT concentrations were higher in eOR patients (P = 0.01), particularly in the first postoperative day, and correlated with blood (r = 0.398, P = 0.029) and platelet (r = 0.424, P = 0.020) volume transfused. C-reactive protein rose and lipid hydroperoxide fell in both groups without significant intergroup difference. Vitamins C and E, lycopene, and β -carotene levels were similar between groups. Conclusion. EVAR is associated with lower systemic inflammatory response compared to OR. Its increased future use may thereby improve outcomes for patients.