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Background: Almost no research has been published reporting on evaluations of the effectiveness of psychological interventions for people with severe to profound intellectual disabilities and depression. This paper describes the development and initial feasibility testing of an adapted Behavioural Activation therapy (BeatIt2) for this population. Method: Phase 1 of the study examined participant recruitment and willingness to be randomised in the context of a planned Randomised Controlled Trial (RCT). Phase 2 examined the feasibility of delivering the intervention. Results: Twenty adults with a severe or profound intellectual disability and clinically significant depression were recruited to Phase 1 of the study. In Phase 2, there was 100% participant retention for those recruited to the study at 6‐month follow‐up. The BeatIt2 therapy was reported to be acceptable for participants. Conclusion: COVID disruption meant that it was not possible to complete the planned feasibility RCT. The positive findings suggest that additional evaluation of BeatIt2 is warranted.

BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.Trial registrationPROSPERO Registration number: CRD42023376769., Funding Agencies|National Institute for Health and Care Research (NIHR) School for Primary Care Research [589]

This research proposes a mobile and cloud-based framework for the automatic detection of diabetic foot ulcers and conducts an investigation of its performance. The system uses a cross-platform mobile framework which enables the deployment of mobile apps to multiple platforms using a single TypeScript code base. A deep convolutional neural network was deployed to a cloud-based platform where the mobile app could send photographs of patient's feet for inference to detect the presence of diabetic foot ulcers. The functionality and usability of the system were tested in two clinical settings: Salford Royal NHS Foundation Trust and Lancashire Teaching Hospitals NHS Foundation Trust. The benefits of the system, such as the potential use of the app by patients to identify and monitor their condition are discussed.

Objectives. The Strengthening Families Programme 10–14 (SFP10-14) is a USA-developed universal group-based intervention aiming to prevent substance misuse by strengthening protective factors within the family. This study evaluated a proportionate universal implementation of the adapted UK version (SFP10-14UK) which brought together families identified as likely/not likely to experience/present challenges within a group setting. Design. Pragmatic cluster-randomised controlled effectiveness trial, with families as the unit of randomisation and embedded process and economic evaluations. Setting. The study took place in seven counties of Wales, UK. Participants. 715 families (919 parents/carers, 931 young people) were randomised. Interventions. Families randomised to the intervention arm received the SFP10-14 comprising seven weekly sessions. Families in intervention and control arms received existing services as normal. Outcome measures. Primary outcomes were the number of occasions young people reported drinking alcohol in the last 30 days; and drunkenness during the same period, dichotomised as ‘never’ and ‘1–2 times or more’. Secondary outcomes examined alcohol/tobacco/substance behaviours including: cannabis use; weekly smoking (validated by salivary cotinine measures); age of alcohol initiation; frequency of drinking >5 drinks in a row; frequency of different types of alcoholic drinks; alcohol-related problems. Retention: primary analysis included 746 young people (80.1%) (alcohol consumption) and 732 young people (78.6%) (drunkenness). Results. There was no evidence of statistically significant between-group differences 2 years after randomisation for primary outcomes (young people’s alcohol consumption in the last 30 days adjusted OR=1.11, 95% CI 0.72 to 1.71, p=0.646; drunkenness in the last 30 days adjusted OR=1.46, 95% CI 0.83 to 2.55, p=0.185). There were no statistically significant between-group differences for other substance use outcomes, or those relati

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination.

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

BACKGROUND: The current standard of care in rheumatoid arthritis (RA) requires regular assessment of disease activity (DA). All standard RA DA measurement instruments require joint counts to be undertaken by a healthcare professional with/without a blood test. Few healthcare providers have the capacity to assess patients as frequently as stipulated by guidelines. Patient Reported Outcome Measures (PROMs) could be an efficient and informative way to assess RA DA, which is highlighted by the SARS-COV-2 pandemic, as most consultations are remote rather than face-to-face. We aimed to assess all PROMs for RA DA against the internationally recognised COSMIN guidelines to provide evidence-based recommendations to select the most suitable PROMs. METHODS: Review registered on PROSPERO as CRD42020176176. The search strategy was based on a previous similar systematic review and expanded to include all articles up to January 2019. All identified articles were rated by two independent assessors following the COSMIN guidelines. RESULTS: 668 abstracts were identified, with 10 articles included. A further 21 were identified from a previous review. Ten PROMs were identified. There was insufficient evidence to place any of the identified PROMs into recommendation for use category A due to lack of evidence for content validity, as stipulated by the COSMIN guidelines. CONCLUSION: Lack of evidence of content validity limits suitable PROM selection, therefore none can be recommended for use. It is acknowledged that all included PROMs were developed before the COSMIN guidelines were published. Future research on PROMs for RA DA must provide evidence of content validity.

Background: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. Methods: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Results: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. Conclusions: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste l

David Gillespie,1,2 Nick Francis,3 Haroon Ahmed,4 Kerenza Hood,2 Carl Llor,5 Patrick White,6 Emma Thomas-Jones,2 Helen Stanton,2 Bernadette Sewell,7 Rhiannon Phillips,8 Gurudutt Naik,4 Hasse Melbye,9 Rachel Lowe,2 Nigel Kirby,2 Ann Cochrane,10 Janine Bates,2 Mohammed Fasihul Alam,11 Christopher Butler1 1Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, UK; 2Centre for Trials Research, School of Medicine, College of Biomedical & Life Sciences, Cardiff University, Cardiff, Wales, UK; 3Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, England, UK; 4Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, Wales, UK; 5University Institute in Primary Care Research Jordi Gol, Via Roma Health Centre, Barcelona, Spain; 6School of Population Health and Environmental Sciences, Kings College London, London, England, UK; 7Swansea Centre for Health Economics, Swansea University, Swansea, Wales, UK; 8Cardiff School of Sport & Health Science, Cardiff Metropolitan University, Cardiff, Wales, UK; 9General Practice Research Unit, Department of Community Medicine, UIT the Arctic University of Norway, Tromsø, Norway; 10York Trials Unit, Department of Health Sciences, University of York, York, England, UK; 11Department of Public Health, College of Health Sciences, QU-Health, Qatar University, Doha, QatarCorrespondence: David Gillespie, Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, England, OX2 6GG, UK, Email david.gillespie@phc.ox.ac.ukBackground: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing.Aim: To investigate the factors associated with post-consultation COPD health status in patients

Contains fulltext : 231082.pdf (Publisher’s version ) (Open Access)

BACKGROUND: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible. AIM: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care. DESIGN AND SETTING: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial). METHOD: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l). RESULTS: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85). CONCLUSION: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions.

This research proposes a mobile and cloud-based framework for the automatic detection of diabetic foot ulcers and conducts an investigation of its performance. The system uses a cross-platform mobile framework which enables the deployment of mobile apps to multiple platforms using a single TypeScript code base. A deep convolutional neural network was deployed to a cloud-based platform where the mobile app could send photographs of patient's feet for inference to detect the presence of diabetic foot ulcers. The functionality and usability of the system were tested in two clinical settings: Salford Royal NHS Foundation Trust and Lancashire Teaching Hospitals NHS Foundation Trust. The benefits of the system, such as the potential use of the app by patients to identify and monitor their condition are discussed., Comment: 10 pages, 2 figures, 1 table

This paper introduces the Diabetic Foot Ulcers dataset (DFUC2021) for analysis of pathology, focusing on infection and ischaemia. We describe the data preparation of DFUC2021 for ground truth annotation, data curation and data analysis. The final release of DFUC2021 consists of 15,683 DFU patches, with 5,955 training, 5,734 for testing and 3,994 unlabeled DFU patches. The ground truth labels are four classes, i.e. control, infection, ischaemia and both conditions. We curate the dataset using image hashing techniques and analyse the separability using UMAP projection. We benchmark the performance of five key backbones of deep learning, i.e. VGG16, ResNet101, InceptionV3, DenseNet121 and EfficientNet on DFUC2021. We report the optimised results of these key backbones with different strategies. Based on our observations, we conclude that EfficientNetB0 with data augmentation and transfer learning provided the best results for multi-class (4-class) classification with macro-average Precision, Recall and F1-score of 0.57, 0.62 and 0.55, respectively. In ischaemia and infection recognition, when trained on one-versus-all, EfficientNetB0 achieved comparable results with the state of the art. Finally, we interpret the results with statistical analysis and Grad-CAM visualisation., Comment: 4 pages, 6 figures and 3 tables

Simon Read,1 James Morgan,2 David Gillespie,3 Claire Nollett,3 Marjorie Weiss,4 Davina Allen,1 Pippa Anderson,5 Heather Waterman1 1School of Healthcare Sciences, Cardiff University, Cardiff, Wales, UK; 2Cardiff and Vale University Health Board, Cardiff, Wales, UK; 3Centre for Trials Research, Cardiff University, Cardiff, Wales, UK; 4School of Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, UK; 5Swansea Centre for Health Economics, Swansea University, Swansea, Wales, UKCorrespondence: Simon ReadCardiff University, Room 12.14, Eastgate House, 35-43 Newport Road, Cardiff CF24 0AB, Wales, UKTel +44 2920 688930Email readsm@cardiff.ac.ukAbstract: Patient adherence to medication is an ongoing concern for clinicians, obfuscating treatment efficacy and resulting in wastage of medicine, reduced clinical benefit, and increased mortality. Despite this, procedural guidance on how clinicians should best engage patients regarding their medicine-taking is limited in the United Kingdom. Adherence for chronic conditions is notably complex, requiring clear education, communication, and behavioural shifts to initiate and sustain daily regimens successfully. This article explores current clinician guidance on assuring patient adherence to medication within the National Health Service, comparing it to that provided for healthcare workers in the field of behavioural change. Outlining the inertia of the former and the progress of the latter, we consider what steps should be taken to address this deficit, including greater focus on patient concerns, as well as knowledge translation for healthcare professionals in future adherence research. Current United Kingdom clinical guidance for assuring patient adherence is largely outdated based on inconclusive evidence for best practice. However, efforts to encourage behavioural change in the public health setting demonstrate evidence-based success. Integrating knowledge generated around adherence behaviour and the practical application

Every 20 seconds, a limb is amputated somewhere in the world due to diabetes. This is a global health problem that requires a global solution. The MICCAI challenge discussed in this paper, which concerns the automated detection of diabetic foot ulcers using machine learning techniques, will accelerate the development of innovative healthcare technology to address this unmet medical need. In an effort to improve patient care and reduce the strain on healthcare systems, recent research has focused on the creation of cloud-based detection algorithms. These can be consumed as a service by a mobile app that patients (or a carer, partner or family member) could use themselves at home to monitor their condition and to detect the appearance of a diabetic foot ulcer (DFU). Collaborative work between Manchester Metropolitan University, Lancashire Teaching Hospital and the Manchester University NHS Foundation Trust has created a repository of 4,000 DFU images for the purpose of supporting research toward more advanced methods of DFU detection. Based on a joint effort involving the lead scientists of the UK, US, India and New Zealand, this challenge will solicit original work, and promote interactions between researchers and interdisciplinary collaborations. This paper presents a dataset description and analysis, assessment methods, benchmark algorithms and initial evaluation results. It facilitates the challenge by providing useful insights into state-of-the-art and ongoing research. This grand challenge takes on even greater urgency in a peri and post-pandemic period, where stresses on resource utilization will increase the need for technology that allows people to remain active, healthy and intact in their home., Comment: 16 pages, 8 figures

We propose a new type of General Adversarial Network (GAN) to resolve a common issue with Deep Learning. We develop a novel architecture that can be applied to existing latent vector based GAN structures that allows them to generate on-the-fly images of any size. Existing GAN for image generation requires uniform images of matching dimensions. However, publicly available datasets, such as ImageNet contain thousands of different sizes. Resizing image causes deformations and changing the image data, whereas as our network does not require this preprocessing step. We make significant changes to the standard data loading techniques to enable any size image to be loaded for training. We also modify the network in two ways, by adding multiple inputs and a novel dynamic resizing layer. Finally we make adjustments to the discriminator to work on multiple resolutions. These changes can allow multiple resolution datasets to be trained on without any resizing, if memory allows. We validate our results on the ISIC 2019 skin lesion dataset. We demonstrate our method can successfully generate realistic images at different sizes without issue, preserving and understanding spatial relationships, while maintaining feature relationships. We will release the source codes upon paper acceptance.

Prostate radiotherapy is a well established curative oncology modality, which in future will use Magnetic Resonance Imaging (MRI)-based radiotherapy for daily adaptive radiotherapy target definition. However the time needed to delineate the prostate from MRI data accurately is a time consuming process. Deep learning has been identified as a potential new technology for the delivery of precision radiotherapy in prostate cancer, where accurate prostate segmentation helps in cancer detection and therapy. However, the trained models can be limited in their application to clinical setting due to different acquisition protocols, limited publicly available datasets, where the size of the datasets are relatively small. Therefore, to explore the field of prostate segmentation and to discover a generalisable solution, we review the state-of-the-art deep learning algorithms in MR prostate segmentation; provide insights to the field by discussing their limitations and strengths; and propose an optimised 2D U-Net for MR prostate segmentation. We evaluate the performance on four publicly available datasets using Dice Similarity Coefficient (DSC) as performance metric. Our experiments include within dataset evaluation and cross-dataset evaluation. The best result is achieved by composite evaluation (DSC of 0.9427 on Decathlon test set) and the poorest result is achieved by cross-dataset evaluation (DSC of 0.5892, Prostate X training set, Promise 12 testing set). We outline the challenges and provide recommendations for future work. Our research provides a new perspective to MR prostate segmentation and more importantly, we provide standardised experiment settings for researchers to evaluate their algorithms. Our code is available at https://github.com/AIEMMU/MRI\_Prostate., Comment: 10 pages

There has been a substantial amount of research involving computer methods and technology for the detection and recognition of diabetic foot ulcers (DFUs), but there is a lack of systematic comparisons of state-of-the-art deep learning object detection frameworks applied to this problem. DFUC2020 provided participants with a comprehensive dataset consisting of 2,000 images for training and 2,000 images for testing. This paper summarises the results of DFUC2020 by comparing the deep learning-based algorithms proposed by the winning teams: Faster R-CNN, three variants of Faster R-CNN and an ensemble method; YOLOv3; YOLOv5; EfficientDet; and a new Cascade Attention Network. For each deep learning method, we provide a detailed description of model architecture, parameter settings for training and additional stages including pre-processing, data augmentation and post-processing. We provide a comprehensive evaluation for each method. All the methods required a data augmentation stage to increase the number of images available for training and a post-processing stage to remove false positives. The best performance was obtained from Deformable Convolution, a variant of Faster R-CNN, with a mean average precision (mAP) of 0.6940 and an F1-Score of 0.7434. Finally, we demonstrate that the ensemble method based on different deep learning methods can enhanced the F1-Score but not the mAP., Comment: 19 pages, 18 figures, 10 tables

Nick A Francis,1 David Gillespie,2 Mandy Wootton,3 Patrick White,4 Janine Bates,2 Jennifer Richards,3 Hasse Melbye,5 Kerenza Hood,2 Christopher C Butler6 1Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, England, UK; 2Centre for Trials Research, Cardiff University, Cardiff, Wales, UK; 3Specialist Antimicrobial Chemotherapy Unit, Microbiology Cardiff, Public Health Wales, Cardiff, Wales, UK; 4School of Population Health and Environmental Sciences, King’s College London, London, England, UK; 5Department of Community Medicine, UIT the Arctic University of Norway, Tromsø, Norway; 6Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, UKCorrespondence: Nick A FrancisPrimary Care, Population Sciences and Medical Education, University of Southampton, Aldermoor Health Centre, Southampton SO16 5ST, UKEmail nick.francis@soton.ac.ukIntroduction: Identifying predictors of bacterial and viral pathogens in sputum from patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) may help direct management.Methods: We used data from a trial evaluating a C-reactive protein (CRP) point of care guided approach to managing COPD exacerbations in primary care. We used regression analyses to identify baseline clinical features, including CRP value in those randomized to testing, associated with bacterial, viral or mixed infections, defined by the presence of bacterial and viral pathogens in sputum, detected by culture or polymerase chain reaction (PCR), respectively.Results: Of 386 participants with baseline sputum samples, 79 (20.5%), 123 (31.9%), and 91 (23.6%) had bacterial, viral/atypical, and mixed bacterial/viral/atypical pathogens identified, respectively. Increasing sputum purulence assessed by color chart was associated with increased odds of finding bacterial and mixed (bacterial and viral/atypical) pathogens in sputum (area under the ROC curve (AUROC)

Previous studies have demonstrated that analysing whisker movements and locomotion allows us to quantify the behavioural consequences of sensory, motor and cognitive deficits in rodents. Independent whisker and feet trackers exist but there is no fully-automated, open-source software and hardware solution, that measures both whisker movements and gait. New method We present the LocoWhisk arena and new accompanying software (ARTv2) that allows the automatic detection and measurement of both whisker and gait information from high-speed video footage. Results We demonstrate the new whisker and foot detector algorithms on high-speed video footage of freely moving small mammals, and show that whisker movement and gait measurements collected in the LocoWhisk arena are similar to previously reported values in the literature. Comparison with existing method(s) We demonstrate that the whisker and foot detector algorithms, are comparable in accuracy, and in some cases significantly better, than readily available software and manual trackers. Conclusion The LocoWhisk system enables the collection of quantitative data from whisker movements and locomotion in freely behaving rodents. The software automatically records both whisker and gait information and provides added statistical tools to analyse the data. We hope the LocoWhisk system and software will serve as a solid foundation from which to support future research in whisker and gait analysis.

Background Approximately 20% of stroke patients experience clinically significant levels of anxiety at some point after stroke. Physicians can treat these patients with antidepressants or other anxiety-reducing drugs, or both, or they can provide psychological therapy. This review looks at available evidence for these interventions. This is an update of the review first published in October 2011. Objectives The primary objective was to assess the effectiveness of pharmaceutical, psychological, complementary, or alternative therapeutic interventions in treating stroke patients with anxiety disorders or symptoms. The secondary objective was to identify whether any of these interventions for anxiety had an effect on quality of life, disability, depression, social participation, caregiver burden, or risk of death. Search methods We searched the trials register of the Cochrane Stroke Group (January 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2017, Issue 1: searched January 2017); MEDLINE (1966 to January 2017) in Ovid; Embase (1980 to January 2017) in Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1937 to January 2017) in EBSCO; and PsycINFO (1800 to January 2017) in Ovid. We conducted backward citation searches of reviews identified through database searches and forward citation searches of included studies. We contacted researchers known to be involved in related trials, and we searched clinical trials registers for ongoing studies. Selection criteria We included randomised trials including participants with a diagnosis of both stroke and anxiety for which treatment was intended to reduce anxiety. Two review authors independently screened and selected titles and abstracts for inclusion. Data collection and analysis Two review authors independently extracted data and assessed risk of bias. We performed a narrative review. We planned to do a meta-analysis but were unable to do so

David Gillespie,1 Daniel Farewell,2 Lucy Brookes-Howell,1 Christopher C Butler,3 Samuel Coenen,4–6 Nick A Francis,2 Paul Little,7 Beth Stuart,7 Theo Verheij,8 Kerenza Hood1 On behalf of the GRACE consortium 1Centre for Trials Research, College of Biomedical & Life Sciences, 2Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, 3Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK; 4Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), 5Centre for General Practice, Department of Primary and Interdisciplinary Care (ELIZA), 6Clinical Epidemiology and Medical Statistics, Department of Epidemiology and Social Medicine (ESOC), University of Antwerp, Antwerp, Belgium; 7Aldermoor Health Centre, Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 8Department of General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Aim: To investigate the determinants of adherence to amoxicillin in patients with acute lower respiratory tract infection.Materials and methods: Three European data sets were used. Adherence data were collected using self-reported diaries. Candidate determinants included factors relating to patient, condition, therapy, health care system/provider, and the study in which the patient participated. Logistic and Cox regression models were used to investigate the determinants of initiation, implementation, and discontinuation of amoxicillin.Results: Although initiation differed across samples, implementation and discontinuation were similar. Determinants of initiation were days waited before consulting, duration of prescription, and being in a country where a doctor-issued sick certificate is required for being off work for <7 days. Implementation was higher for older participants or those with abnormal auscultation.

Background: Approximately 20% of stroke patients experience anxiety at some point after stroke. Objectives: To determine if any treatment for anxiety after stroke decreases the proportion of patients with anxiety disorders or symptoms, and to determine the effect of treatment on quality of life, disability, depression, social participation, risk of death or caregiver burden. Search methods: We searched the trials register of the Cochrane Stroke Group (October 2010), CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (1950 to October 2010), EMBASE (1947 to October 2010), PsycINFO (1806 to October 2010), Allied and Complementary Medicine database (AMED) (1985 to October 2010), Cumulative Index to Nursing and Allied Health (CINAHL) (1982 to October 2010), Proquest Digital Dissertations (1861 to October 2010), and Psychological Database for Brain Impairment Treatment Efficacy (PsycBITE) (2004 to October 2010). In an effort to identify further published, unpublished and ongoing trials, we searched trial registries and major international stroke conference proceedings, scanned reference lists, and contacted select individuals known to the review team who are actively involved in psychological aspects of stroke research, and the Association of the British Pharmaceutical Industry. Selection criteria: Two review authors independently screened and selected titles and abstracts for inclusion in the review. Randomised trials of any intervention in patients with stroke where the treatment of anxiety was an outcome were eligible. Data collection and analysis: Two review authors independently extracted data for analysis. We performed a narrative review. A meta-analysis was planned but not carried out as studies were not of sufficient quality to warrant doing so. Main results: We included two trials (three interventions) involving 175 participants with co-morbid anxiety and depression in the review. Both trials used the Hamilton Anxiety Scale (HAM-A) to assess anxiety, and neith

Within this project we assess whether wildflower strips and companion plants increase the control of cabbage pests Plutella xylostella L. (Lepidoptera: Plutellidae), Mamestra brassicae L. (Lepidoptera: Noctuidae) and Pieris rapae L. (Lepidoptera: Pieridae) by (1) naturally occurring parasitoids and predators and (2) mass‐releasedn Trichogramma brassciae (Bezdenko) (Hymenoptera: Trichogrammatidae) parasitoids. Two organic cabbage fields were used for this study: adjacent to each field a wildflower strip was sown and companion plants (Centaurea cyanus L. (Asteraceae)) intermixed within the crop. Within each field ~15,000 M. brassicae eggs were placed out to determine the parasitism rates by mass‐released T. brassicae and to assess the levels of egg predation. Over 1,000 lepidopteran larvae were collected and screened for hymenopteran and tachinid parasitoid DNA using a multiplex PCR assay. Invertebrate generalist predators (n=1,063) were collected for DNA‐based gut content analysis. The wildflower strip had a significant positive effect on M. brassicae egg parasitism rates as rates increased 5‐fold in the vicinity to the strip. Moreover, companion plants enhanced invertebrate predation on M. brassicae eggs. Both, the release of T. brassicae and the use of companion plants, however, did not significantly increase egg parasitism rates. The infestation of plants by caterpillars increased with distance to the wildflower strip and there was a trend of decreasing larval parasitism rates with distance to the strip. Currently the invertebrate predators are being molecularly analysed to assess predation on unparasitized and parasitized lepidopteran pests.

Doel Ons doel was in kaart te brengen hoe vaak huisartsen in verschillende Europese landen antibiotica voorschrijven voor acute hoest, en welk effect dit heeft op het ziektebeloop. Methode Wij verrichtten een cross-sectioneel prospectief observationeel onderzoek onder volwassen patiënten in 13 Europese landen die met een nieuwe of verergerende hoest bij de huisarts kwamen of bij wie de huisarts een infectie van de lage luchtwegen vermoedde. De huisartsen noteerden bij presentatie de symptomen en welk beleid zij volgden, de patiënten hielden 28 dagen een symptoomdagboek bij. Onze primaire uitkomstmaten waren het voorschrijven van antibiotica en het beloop van de symptomen in de tijd. Resultaten Aan het onderzoek namen 384 huisartsen deel, die 3402 patiënten includeerden. Van 3296 (97%) patiënten ontvingen de onderzoekers een volledig registratieformulier en van 2560 (75%) patiënten een compleet symptoomdagboek. De ernst van de symptomen bij presentatie (gescoord door de huisarts op een schaal van 0 tot 100) varieerde van 19 in Spanje en Italië tot 38 in Zweden. In gemiddeld 53% van de episoden schreven de artsen antibiotica voor, maar dit varieerde per land van 20% tot bijna 90% (België 25,9%, Nederland 41,5%). Ook na correctie voor klinische presentatie en demografische kenmerken bleven de verschillen aanzienlijk. Noorse huisartsen schreven het minst vaak antibiotica voor (OR 0,18; 95%-BI 0,11 tot 0,30), Slowaakse het vaakst (OR 11,2; 95%-BI 6,20 tot 20,27). Ook het soort antibioticum varieerde sterk. Amoxicilline, het meest voorgeschreven middel, werd in Noorwegen het minst vaak gegeven (3% van de voorgeschreven antibiotica), in Engeland het vaakst (83%). Fluorochinolonen werden in sommige landen helemaal niet voorgeschreven, maar in Italië aan 18% van de patiënten. Patiënten die geen antibiotica kregen, herstelden nagenoeg even snel als patiënten die wel antibiotica kregen. Conclusie De variatie in de klinische presentatie biedt geen verklaring voor de grote versc

Advancements in combat casualty care have resulted in a significant reduction in mortality when compared with previous wars as current research has focused much attention on preventable death. Hemorrhage from extremity vascular injury remains a leading cause of potentially preventable death on the modern battlefield and recent estimates suggest an increase in this injury pattern compared with previous wars. Injuries of this severity cause an early and profound coagulopathy that is often present at admission to the emergency department (ED). Standard damage control principles are routinely applied to achieve rapid hemorrhage control, and to initiate a hemostatic resuscitation plan that will correct metabolic imbalances and prevent the onset or progression of a traumatic coagulopathy. Only when this lifesaving sequence is properly executed, can the military trauma patient be expected to withstand the metabolic perturbations of a complicated operation like extremity revascularization. Standard surgical doctrine and experience has taught surgeons that the operative patient needs to be adequately resuscitated before embarking on a taxing operative course. The time needed for adequate resuscitation was the single greatest barrier to limb salvage during the Korean conflict. Convincing modern data show that acidosis and traditional resuscitation techniques using liberal amounts of crystalloid and packed red blood cells (PRBCs) can exacerbate coagulopathy. One report has recently demonstrated a survival benefit with early correction of these physiologic derangements. Given modern advances, it seems logical to optimize those strategies that promote early recovery from the metabolic consequences of hemorrhagic shock., Published in the Jnl. of Trauma Injury, Infection, and Critical Care, Feb Supplement 2008, v64, n2, p599-S107.

The molecular mechanisms by which the AP-1 transcription factor c-Jun exerts its biological functions are not clearly understood. In addition to its well established role in transcriptional regulation of gene expression, several reports have suggested that c-Jun may also regulate cell behavior by non-transcriptional mechanisms. Here, we report that small interfering RNA-mediated depletion of c-Jun from mammalian cells results in inhibition of 28 S and 18 S rRNA accumulation. Moreover, we show that c-Jun depletion results in partial translocation of RNA helicase DDX21, implicated in rRNA processing, from the nucleolus to the nucleoplasm. We demonstrate that DDX21 translocation is rescued by exogenous c-Jun expression and that c-Jun depletion inhibits rRNA binding of DDX21. Furthermore, the direct interaction between c-Jun and DDX21 regulates nucleolar localization of DDX21. These results demonstrate that in addition to its transcriptional effects, c-Jun regulates rRNA processing and nucleolar compartmentalization of the rRNA processing protein DDX21. Thus, our results demonstrate a nucleolar mechanism through which c-Jun can regulate cell behavior. Moreover, these results suggest that the phenotypes observed previously in c-Jun-depleted mouse models and cell lines could be partly due to the effects of c-Jun on rRNA processing.

Traumatic hemorrhage and vascular injury management have been concerns for both civilian and military physicians. During the 20th century, advances in technique allowed surgeons to focus on vascular repair, restoration of perfusion, limb salvage, and life preservation. Military surgeons such as Makins, DeBakey, Hughes, Rich and others made significant contributions to the field of surgery in general and vascular surgery in particular. Casualties from combat in Afghanistan and Iraq confront physicians and surgeons with devastating injuries. The current generation of providers is challenged with applying contemporary care while expanding upon the lessons taught by our predecessors. The objective of this report is to review the historical experience with managing military upper extremity arterial injuries and compare that experience with current management., Published in Perspectives in Vascular Surgery and Endovascular Therapy v18, n2, p141-145, Jun 2006.

The treatment of wartime injuries has led to advances in the diagnosis and treatment of vascular trauma. Recent experience has stimulated a reappraisal of the management of such injuries, specifically assessing the effect of explosive devices on injury patterns and treatment strategies. The objective of this report is to provide a single-institution analysis of injury patterns and management strategies in the care of modern wartime vascular injuries., Presented at the 2004 Joint Annual Meeting of the Society for Vascular Surgery/American Association for Vascular Surgery, Anaheim, California, June 3-6, 2004. The original document contains color images. Pub. in Journal of Fascular Surgery, v41 n4, p638-44, Apr 2005.