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The decision tree analysis scoring systems is likely to be the most useful in routine clinical practice. First-line clinical trials are an appropriate option for patients with good PS and are recommended above any other option for second-line treatment, providing the patient is of adequate PS. Grade D. Research recommendations Prospective clinical trials of preoperative radiotherapy, postoperative radiotherapy after pleurectomy decortication and definitive radiotherapy after chemotherapy in MPM are required. [...]prospective randomised clinical trials are required to determine the role of radiotherapy for symptom control in MPM and the optimal dose fractionation.

\"The Routledge Handbook of Attachment: Theory provides a broadly based introduction to attachment theory and associated areas, written in an accessible style by experts from around the world. The book covers the basic theories of attachment and discusses the similarities and differences of the two predominant schools of attachment theory. The book provides an overview of current developments in attachment theory, explaining why it is important not only to understanding infant and early child development but also to adult personality and the care we provide to our children. The Routledge Handbook of Attachment: Theory provides detailed descriptions of the leading schools of attachment theory as well as discussions of this potentially confusing and contentious area, and includes a chapter on the neuropsychological basis of attachment. The book also examines other domains and diagnoses that can be confused with issues of attachment and assesses contexts when different approaches may be more suitable.Providing a comprehensive yet accessible introduction to the theories of attachment, The Routledge Handbook of Attachment: Theory is an indispensable guide for professionals working with children and families in community and court-based settings, clinical psychologists, psychiatrists and social workers, clinicians in training and students. \"-- Provided by publisher.

If immunized with an antigen of interest, transgenic mice with large portions of unrearranged human immunoglobulin loci can produce fully human antigen-specific antibodies; several such antibodies are in clinical use. However, technical limitations inherent to conventional transgenic technology and sequence divergence between the human and mouse immunoglobulin constant regions limit the utility of these mice. Here, using repetitive cycles of genome engineering in embryonic stem cells, we have inserted the entire human immunoglobulin variable-gene repertoire (2.7 Mb) into the mouse genome, leaving the mouse constant regions intact. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high-affinity antibodies with long human-like complementarity-determining region 3 (CDR3H), broad epitope coverage and strong signatures of somatic hypermutation. These mice provide a robust system for the discovery of therapeutic human monoclonal antibodies; as a surrogate readout of the human antibody response, they may also aid vaccine design efforts.

\"The Routledge Handbook of Attachment: Assessment provides, in one volume, a detailed discussion of the formal measurement tools available to assess attachment across the age range, including with families. It contains comprehensive chapters on many attachment-based validated procedures for assessing parenting and evaluating risk, to enable professionals to decide what type of assessment is appropriate, who should conduct it and the usefulness of the results. The book provides a detailed account of assessment measures of attachment to enable practitioners at all levels (including academic research workers) to decide which assessment procedure will best meet their need. The chapters are written by those who developed these tools and by people closely associated with them, and advocate an evidence-based model of assessment to increase fairness and transparency for families.Providing a practical guide to the uses of attachment theory and research in professional practice with adults, children, parents and families, and a detailed account of all the current evidence-based tools that can be used in assessment, The Routledge Handbook of Attachment: Assessment is ideal for professionals and clinicians wishing to commission or undertake assessments of attachment, as well as academic research workers and students. \"-- Provided by publisher.

Abstract Background IMPlementing IMProved Asthma self-management as RouTine (IMP 2 ART) is a programme of work developing and evaluating a strategy for implementing supported asthma self-management in UK primary care. The strategy encompasses patient-facing resources, professional education, and organisational approaches to embed supported self-management. This paper reports the development of a theoretically informed interprofessional education programme which aims to raise awareness of and enable healthcare professionals to deliver effective supported self-management. Methods Aligned with the Medical Research Council (MRC) Complex Intervention Framework, the multidisciplinary team developed educational content in three phases: (1) developmental phase, identifying educational and behaviour change theory to guide development, in consultation with a professional advisory group; (2) feasibility pilot phase, testing the education using a ‘think-aloud’ method; and (3) pre-pilot phase, delivering the education within the IMP 2 ART strategy. Results The developmental phase identified educational and behaviour change theory and the need to provide two education modules: (1) a team module to raise awareness of supported asthma self-management for the whole team and (2) an individual study module for those who conduct asthma reviews with patients. The feasibility pilot highlighted content and design features in need of refinement and the pre-pilot identified substantial changes to the delivery strategy for the education modules. Conclusions A multi-stage development process, aligned with the MRC Framework, contributed to the module design and delivery. Prior explorative work, multi-disciplinary team discussions, and professional advisory group consultation, informed the initial development, and in-practice testing and pre-pilot stages enabled refinement. In our experience, there were important benefits of working together as an educationalist/researcher team. The education programme, a core component of the implementation strategy, is now being tested in the IMP 2 ART UK-wide cluster randomised controlled trial.

Abstract Background Supported asthma self-management, incorporating an asthma action plan and annual clinical review, has been recommended by UK/global guidelines for over three decades. However, implementation remains poor, as only around a third of individuals receive basic asthma care, according to the UKs leading respiratory charity Asthma and Lung UK. A systematic review of implementation studies recommended that a whole systems approach targeting patients, healthcare professional education, and organisations is needed to improve implementation of supported asthma self-management in primary care. The IMPlementing IMProved Asthma self-management as RouTine (IMP 2 ART) is a national Hybrid-II implementation cluster randomised controlled trial that aims to evaluate such an approach. This paper describes the development of the implementation strategy for IMP 2 ART with particular focus on the integration of multiple level theories. Methods The Medical Research Council design and evaluation of complex interventions framework and the Person-Based Approach to intervention development were used as guidance for stages of strategy development. Specifically, we (i) set up a multidisciplinary team (including practicing and academic clinicians, health psychologists, public health and patient colleagues), (ii) reviewed and integrated evidence and theory, (iii) developed guiding principles, (iv) developed prototype materials, and (v) conducted a pre-pilot study before final refinement. Results The implementation strategy included resources for patients, team-based and individual healthcare professional education, practice audit and feedback, and an asthma review template, as well as a facilitator role accessible to primary care practices for 12 months. The synthesis of the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) and Capability, Opportunity, Motivation and Behaviour (COM-B) frameworks led to an evolved framework bringing together important implementation and behaviour change elements which will be used as a basis for the study process evaluation. Conclusions A description of rigorous implementation strategy development for the IMP 2 ART study is provided along with newly theorised integration of implementation and behaviour change science which may be of benefit to others targeting implementation in primary care. Trial registration ISRCTN15448074. Registered on 2nd December 2019.

Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra‐rare, blood‐clotting disorder. Management historically relies on plasma exchange and immunosuppression; however, a 10%–20% mortality rate is still observed. Caplacizumab binds to von Willebrand factor and directly inhibits platelet aggregation; addition of caplacizumab to historical treatment induced faster resolution of platelet count in clinical trials. In 2019, a modified‐Delphi study was conducted with UK experts, to develop consensus statements on management of acute TTP and the potential role of caplacizumab. An unmet need was acknowledged, and areas requiring improvement included: time to diagnosis and treatment initiation; time to platelet normalisation (TTPN) during which patients remain at risk of persistent microvascular thrombosis and organ damage; and incidence of subsequent exacerbations and relapses. Caplacizumab addition to historical treatment within 24 h (after confirmatory ADAMTS13 [a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13] assay) would significantly reduce TTPN, which directly influences acute outcomes, with manageable bleeding risk and reduced burden on healthcare systems. Expert panellists agree that poor outcomes in iTTP largely result from failure to rapidly control microvascular thrombosis. Use of caplacizumab during a confirmed iTTP episode could offer better control and may plausibly improve long‐term outcomes. However, this consensus must be validated with further clinical trials and robust real‐world evidence.

Asthma is a common long-term condition and major public health problem. Supported self-management for asthma that includes a written personalised asthma action plan, supported by regular professional review, reduces unscheduled consultations and improves asthma outcomes and quality of life. However, despite unequivocal inter/national guideline recommendations, supported self-management is poorly implemented in practice. The IMPlementing IMProved Asthma self-management as RouTine (IMP ART) implementation strategy has been developed to address this challenge. The aim of this implementation trial is to determine whether facilitated delivery of the IMP ART strategy increases the provision of asthma action plans and reduces unscheduled care in the context of routine UK primary care. IMP ART is a parallel group, cluster randomised controlled hybrid II implementation trial. One hundred forty-four general practices will be randomly assigned to either the IMP ART implementation strategy or control group. Following a facilitation workshop, implementation group practices will receive organisational resources to help them prioritise supported self-management (including audit and feedback; an IMP ART asthma review template), training for professionals and resources to support patients to self-manage their asthma. The control group will continue with usual asthma care. The primary clinical outcome is the between-group difference in unscheduled care in the second year after randomisation (i.e. between 12 and 24 months post-randomisation) assessed from routine data. Additionally, a primary implementation outcome of asthma action plan ownership at 12 months will be assessed by questionnaire to a random sub-group of people with asthma. Secondary outcomes include the number of asthma reviews conducted, prescribing outcomes (reliever medication and oral steroids), asthma symptom control, patients' confidence in self-management and professional support and resource use. A health economic analysis will assess cost-effectiveness, and a mixed methods process evaluation will explore implementation, fidelity and adaptation. The evidence for supported asthma self-management is overwhelming. This study will add to the literature regarding strategies that can effectively implement supported self-management in primary care to reduce unscheduled consultations and improve asthma outcomes and quality of life. ISRCTN15448074. Registered on 2 December 2019.

Currently the National Asthma and COPD audit programme (NACAP) only undertakes audit of COPD primary care in Wales due to its near complete data coverage. We aimed to determine if the quality of COPD primary care in the other UK nations is comparable with Wales. We found that English, Scottish, and Northern Irish practices were significantly worse than Welsh practices at recording coded lung function parameters used in COPD diagnosis (ORs: 0.51 [0.43-0.59], 0.29 [0.23-0.36], 0.42 [0.31-0.58], respectively) and referring appropriate patients for pulmonary rehabilitation (ORs: 0.10 [0.09-0.11], 0.12 [0.11-0.14], 0.22 [0.19-0.25], respectively). Completing national audits of primary care in Wales only may have led to improvements in care, or at least improvements in the recording of care in Wales that are not occurring elsewhere in the UK. This highlights the potential importance of audit in improving care quality and accurate recording of that care.