Developing methods for the overarching synthesis of quantitative and qualitative evidence: the interweave synthesis approach

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordThe incorporation of evidence derived from multiple research designs into one single synthesis can enhance the utility of systematic reviews making them more worthwhile, useful and insightful. Methodological guidance for mixed-methods synthesis continues to emerge and evolve but broadly involves a sequential, parallel or convergent approach according to the degree of independence between individual syntheses before they are combined.We present two case studies in which we used novel and innovative methods to draw together the findings from individual but related quantitative and qualitative syntheses to aid interpretation of the overall evidence base. Our approach moved beyond making a choice between parallel, sequentialor convergent methods to interweave the findings of individual reviews and offers three key innovations to mixed-methods synthesis methods: i)The use of intersubjective questions to understand the findings of the individual reviews through different lenses, ii)Immersion of key reviewers in the entirety of the evidence base, and iii)Commencing the process during the final stages of the synthesis of individual reviews, at a point where reviewers are developing an understanding of initial findings. Underlying our approachis the process of exploration and identification of links between and across review findings; an approach that is fundamental to all evidence syntheses but usually occurs at the level of the study. Adapting existing methods for exploring and identifying patterns and links between and across studies to interweave the findings between and across reviews may prove valuable.NIHR Health Technology Assessment Programm

A review of standard pharmacological therapy for adult asthma - Steps 1 to 5

The aim of pharmacological therapy for asthma is to improve symptoms and lung function and minimise the risk of asthma attacks. The intensity of treatment is based on the level of asthma control and the potential risk of future deterioration. In the British asthma guidelines, treatments are divided into Step One to Five, with each Step signifying a need for an increase in therapy in response to symptoms or to prevent exacerbations. Treatments comprise of inhaled or systemic medications. Inhaled therapy includes short-acting and long-acting medication to improve symptoms and inhaled corticosteroids which reduce airway inflammation. Systemic treatments include medications which act on specific biological pathways, such as the leukotriene or IgE pathways, or systemic corticosteroids. In choosing a particular therapy, treatment benefits are balanced by the potential risks of medication-related adverse effects. This review will provide a practical guide to the key pharmacological therapies for adult asthma at Steps One to Five based on British guidelines and consider future options for new treatments

Impact of interventions to improve recovery of older adults following planned hospital admission on quality-of-life following discharge: linked-evidence synthesis

OBJECTIVES: To understand the impact of multicomponent interventions to improve recovery of older adults following planned hospital treatment, we conducted two systematic reviews, one of quantitative and one of qualitative evidence, and an overarching synthesis. These aimed to: • understand the effect of multicomponent interventions which aim to enhance recovery and/or reduce length of stay on patient-reported outcomes and health and social care utilisation • understand the experiences of patients, carers and staff involved in the delivery of interventions • understand how different aspects of the content and delivery of interventions may influence patient outcomes. REVIEW METHODS: We searched bibliographic databases including MEDLINE ALL, Embase and the Health Management Information Consortium, CENTRAL, and Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine Database, conducted forward and backward citation searching and examined reference lists of topically similar qualitative reviews. Bibliographic database searches were completed in May/June 2021 and updated in April 2022. We sought primary research from high-income countries regarding hospital inpatients with a mean/median age of minimum 60 years, undergoing planned surgery. Patients experienced any multicomponent hospital-based intervention to reduce length of stay or improve recovery. Quantitative outcomes included length of stay and any patient-reported outcome or experience or service utilisation measure. Qualitative research focused on the experiences of patients, carers/family and staff of interventions received. Quality appraisal was undertaken using the Effective Public Health Practice Project Quality Assessment Tool or an adapted version of the Wallace checklist. We used random-effects meta-analysis to synthesise quantitative data where appropriate, meta-ethnography for qualitative studies and qualitative comparative analysis for the overarching synthesis. RESULTS: Quantitative review: Included 125 papers. Forty-nine studies met criteria for further synthesis. Enhanced recovery protocols resulted in improvements to length of stay, without detriment to other outcomes, with minimal improvement in patient-reported outcome measures for patients admitted for lower-limb or colorectal surgery. Qualitative review: Included 43 papers, 35 of which were prioritised for synthesis. We identified six themes: ‘Home as preferred environment for recovery’, ‘Feeling safe’, ‘Individualisation of structured programme’, ‘Taking responsibility’, ‘Essential care at home’ and ‘Outcomes’. Overarching synthesis: Intervention components which trigger successful interventions represent individualised approaches that allow patients to understand their treatment, ask questions and build supportive relationships and strategies to help patients monitor their progress and challenge themselves through early mobilisation. DISCUSSION:  Interventions to reduce hospital length of stay for older adults following planned surgery are effective, without detriment to other patient outcomes. Findings highlight the need to reconsider how to evaluate patient recovery from the perspective of the patient. Trials did not routinely evaluate patient mid- to long-term outcomes. Furthermore, when they did evaluate patient outcomes, reporting is often incomplete or conducted using a narrow range of patient-reported outcome measures or limited through asking the wrong people the wrong questions, with lack of longer-term evaluation. Findings from the qualitative and overarching synthesis will inform policy-making regarding commissioning and delivering services to support patients, carers and families before, during and after planned admission to hospital. STUDY REGISTRATION: This trial is registered as PROSPERO registration number CRD42021230620

Negotiation in strategy making teams : group support systems and the process of cognitive change

This paper reports on the use of a Group Support System (GSS) to explore at a micro level some of the processes manifested when a group is negotiating strategy-processes of social and psychological negotiation. It is based on data from a series of interventions with senior management teams of three operating companies comprising a multi-national organization, and with a joint meeting subsequently involving all of the previous participants. The meetings were concerned with negotiating a new strategy for the global organization. The research involved the analysis of detailed time series data logs that exist as a result of using a GSS that is a reflection of cognitive theory

Optimal prescribing of drugs to prevent CVD and drugs that cause dependency: an evidence gap map

This is the final version.Protocol for systematic review which aims to to map the quantitative and qualitative systematic review evidence available to inform the optimal prescribing of statins, antihypertensives and drugs which can cause dependency (DCD) and the point at which this evidence could be used to inform decision making in the patient care pathway for each type of medication

Resistance exercise initiates mechanistic target of rapamycin (mTOR) translocation and protein complex co-localisation in human skeletal muscle

This is the final version. Available from the publisher via the DOI in this record.The mechanistic target of rapamycin (mTOR) is a central mediator of protein synthesis in skeletal muscle. We utilized immunofluorescence approaches to study mTOR cellular distribution and protein-protein co-localisation in human skeletal muscle in the basal state as well as immediately, 1 and 3 h after an acute bout of resistance exercise in a fed (FED; 20 g Protein/40 g carbohydrate/1 g fat) or energy-free control (CON) state. mTOR and the lysosomal protein LAMP2 were highly co-localised in basal samples. Resistance exercise resulted in rapid translocation of mTOR/LAMP2 towards the cell membrane. Concurrently, resistance exercise led to the dissociation of TSC2 from Rheb and increased in the co-localisation of mTOR and Rheb post exercise in both FED and CON. In addition, mTOR co-localised with Eukaryotic translation initiation factor 3 subunit F (eIF3F) at the cell membrane post-exercise in both groups, with the response significantly greater at 1 h of recovery in the FED compared to CON. Collectively our data demonstrate that cellular trafficking of mTOR occurs in human muscle in response to an anabolic stimulus, events that appear to be primarily influenced by muscle contraction. The translocation and association of mTOR with positive regulators (i.e. Rheb and eIF3F) is consistent with an enhanced mRNA translational capacity after resistance exercise.Biotechnology and Biological Science Research Council (BBSRC)Natural Sciences and Engineering Research Council (NSERC)China Scholarship CouncilNational Institute of Arthritis and Musculoskeletal and Skin DiseasesDepartment of Defens

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays

Background: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing – enlisting help from the public – is a sufficiently accurate method to score such samples. Methods: We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers – bladder/ki67, lung/EGFR, and oesophageal/CD8 – to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants’ accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. Results: We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). Conclusions: These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains