Genome editing and kidney health.

Genome editing technologies, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas in particular, have revolutionized the field of genetic engineering, providing promising avenues for treating various genetic diseases. Chronic kidney disease (CKD), a significant health concern affecting millions of individuals worldwide, can arise from either monogenic or polygenic mutations. With recent advancements in genomic sequencing, valuable insights into disease-causing mutations can be obtained, allowing for the development of new treatments for these genetic disorders. CRISPR-based treatments have emerged as potential therapies, especially for monogenic diseases, offering the ability to correct mutations and eliminate disease phenotypes. Innovations in genome editing have led to enhanced efficiency, specificity and ease of use, surpassing earlier editing tools such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENs). Two prominent advancements in CRISPR-based gene editing are prime editing and base editing. Prime editing allows precise and efficient genome modifications without inducing double-stranded DNA breaks (DSBs), while base editing enables targeted changes to individual nucleotides in both RNA and DNA, promising disease correction in the absence of DSBs. These technologies have the potential to treat genetic kidney diseases through specific correction of disease-causing mutations, such as somatic mutations in PKD1 and PKD2 for polycystic kidney disease; NPHS1, NPHS2 and TRPC6 for focal segmental glomerulosclerosis; COL4A3, COL4A4 and COL4A5 for Alport syndrome; SLC3A1 and SLC7A9 for cystinuria and even VHL for renal cell carcinoma. Apart from editing the DNA sequence, CRISPR-mediated epigenome editing offers a cost-effective method for targeted treatment providing new avenues for therapeutic development, given that epigenetic modifications are associated with the development of various kidney disorders. However, there are challenges to overcome, including developing efficient delivery methods, improving safety and reducing off-target effects. Efforts to improve CRISPR-Cas technologies involve optimizing delivery vectors, employing viral and non-viral approaches and minimizing immunogenicity. With research in animal models providing promising results in rescuing the expression of wild-type podocin in mouse models of nephrotic syndrome and successful clinical trials in the early stages of various disorders, including cancer immunotherapy, there is hope for successful translation of genome editing to kidney diseases.

Adiponectin Reduces Glomerular Endothelial Glycocalyx Disruption and Restores Glomerular Barrier Function in a Mouse Model of Type 2 Diabetes.

Adiponectin has vascular anti-inflammatory and protective effects. Although adiponectin protects against the development of albuminuria, historically, the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnCs). In diabetes, eGlx dysfunction occurs before podocyte damage; hence, we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD). Globular adiponectin (gAd) activated AMPK signaling in human GEnCs through AdipoR1. It significantly reduced eGlx shedding and the tumor necrosis factor-α (TNF-α)-mediated increase in syndecan-4 (SDC4) and MMP2 mRNA expression in GEnCs in vitro. It protected against increased TNF-α mRNA expression in glomeruli isolated from db/db mice and against expression of genes associated with glycocalyx shedding (namely, SDC4, MMP2, and MMP9). In addition, gAd protected against increased glomerular albumin permeability (Ps'alb) in glomeruli isolated from db/db mice when administered intraperitoneally and when applied directly to glomeruli (ex vivo). Ps'alb was inversely correlated with eGlx depth in vivo. In summary, adiponectin restored eGlx depth, which was correlated with improved glomerular barrier function, in diabetes.

EXPERTS II - How are patient and caregiver participation in health and social care shaped by experienced burden of treatment and social inequalities? Protocol for a qualitative synthesis.

Background: The workload health and social care service users and caregivers take on, and their capacity to do this work is important. It may play a key part in shaping the implementation of innovations in health service delivery and organisation; the utilisation and satisfaction with services; and the outcomes of care. Previous research has often focused on experiences of a narrow range of long-term conditions, and on factors that shape adherence to self-care regimes. Aims: With the aim of deriving policy and practice implications for service redesign, this evidence synthesis will extend our understanding of service user and caregiver workload and capacity by comparing how they are revealed in qualitative studies of lived experience of three kinds of illness trajectories: long-term conditions associated with significant disability (Parkinson's disease, schizophrenia); serious relapsing remitting disease (Inflammatory Bowel Disease, bipolar disorder); and rapidly progressing acute disease (brain cancer, early onset dementia). Methods: We will review and synthesise qualitative studies of lived experience of participation in health and social care that are shaped by interactions between experienced treatment burdens, social inequalities and illness trajectories. The review will involve:   1.  Construction of a theory-informed coding manual; systematic search of bibliographic databases to identify, screen and quality assess full-text papers.   2.  Analysis of papers using manual coding techniques, and text mining software; construction of taxonomies of service user and caregiver work and capacity.   3.  Designing a model of core components and identifying common factors across conditions, trajectories, and contexts.   4.  Work with practitioners, and a Patient and Public Involvement (PPI) group, to explore the validity of the models produced; to develop workload reduction strategies; and to consider person-centred service design. Dissemination: We will promote workload reduction models to support service users and caregivers and produce policy briefs and peer-reviewed publications for practitioners, policy-makers, and researchers.

Our experiences of illness are often complex. We may have to work hard too. We may need to monitor and record symptoms: take up different diets and physical activity; use different drugs and medical devices; develop expertise in using websites and information technology; coordinate input from health and care services; sometimes we have to work out how to pay for the services we need. How we get through this work is affected by our capacity to do it, and that is shaped by personal and wider resources, we can draw on. All of this is also affected by the services that are available to us, and by the ways our chances in life are shaped by income, ethnicity, education, gender, and age. The kinds of illnesses we have and how they progress, mean that these factors change over time. We call these changes trajectories. To better understand service user work and capacity, we will review published studies that tell us about people's everyday experiences of living with illnesses. We focus on three rarely studied trajectories. These are long-term conditions associated with significant disability; serious relapsing remitting disease; and rapidly progressing acute disease. We will first use existing research to build a framework in which we can describe and understand relevant aspects of the published studies. We will use this framework to extract relevant information from the studies. This will enable us to make a model of common features of service user work and capacity across different conditions, their trajectories, service organisation and delivery, and patterns of social and economic disadvantage. Finally, we will work with groups of service users and caregivers, and with health and social care professionals to apply the model to the development of strategies to reduce workload and improve service design for people with complex health problems.

Implementing a nurse-delivered cognitive behavioural therapy intervention to reduce the impact of hot flushes/night sweats in women with breast cancer: a qualitative process evaluation of the MENOS4 trial.

BACKGROUND: Hot flushes and night sweats are life-altering symptoms experienced by many women after breast cancer treatment. A randomised controlled trial (RCT) was conducted to explore the effectiveness of breast care nurse (BCN)-led group cognitive behavioural therapy (CBT). This paper reported findings from a qualitative process evaluation to optimise the CBT intervention and explore the determinants of implementation into routine practice. METHODS: Qualitative process evaluation occurred in parallel with the RCT to explore patient and healthcare staff experiences and perspectives using semi-structured interviews pre-and post-intervention. Normalisation Process Theory (NPT) informed data collection, analysis, and reporting of findings. The analysis involved inductive thematic analysis, NPT coding manual and subsequent mapping onto NPT constructs. RESULTS: BCNs (n = 10), managers (n = 2), surgeons (n = 3) and trial participants (n = 8) across six recruiting sites took part. All stakeholders believed group CBT met a need for non-medical hot flushes/night sweats treatment, however, had little exposure or understanding of CBT before MENOS4. BCNs believed the work fitted with their identity and felt confident in delivering the sessions. Despite little understanding, patients enrolled onto group CBT because the BCNs were trusted to have the knowledge and understanding to support their needs and despite initial scepticism, reported great benefit from group-based participation. Both managers and surgeons were keen for BCNs to take responsibility for all aspects of CBT delivery, but there were some tensions with existing clinical commitments and organisational priorities. CONCLUSIONS: Both healthcare staff and patient participants believe BCN-led group CBT is a beneficial service but barriers to long-term implementation into routine care suggest there needs to be multi-level organisational support. TRIAL REGISTRATION: NCT02623374 - Last updated 07/12/2015 on ClinicalTrials.gov PRS.

Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome.

Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2, encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03-mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9-mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches.

Maintaining long-term physical activity after cancer: a conceptual framework to inform intervention development.

PURPOSE: This paper describes a conceptual framework of maintenance of physical activity (PA) and its application to future intervention design. METHODS: Evidence from systematic literature reviews and in-depth (N = 27) qualitative interviews with individuals with cancer were used to develop a conceptual framework of long-term physical activity behaviour. Determinants of long-term PA were listed and linked with domains of the Theoretical Domains Framework which in turn were linked to associated behaviour change techniques (BCTs) and finally to proposed mechanisms of action (MoA). RESULTS: The conceptual framework is presented within the context of non-modifiable contextual factors (such as demographic and material resources) and in the presence of learnt and adapted behavioural determinants of skills, competence and autonomous motivation that must be established as part of the initiation of physical activity behaviour. An inventory of 8 determinants of engagement in long-term PA after cancer was developed. Clusters of BCTs are presented along with proposed MoA which can be tested using mediation analysis in future trials. CONCLUSION: Understanding the processes of PA maintenance after cancer and presentation of implementable and testable intervention components and mechanisms of action to promote continued PA can inform future intervention development. IMPLICATIONS FOR CANCER SURVIVORS: This resource can act as a starting point for selection of intervention components for those developing future interventions. This will facilitate effective support of individuals affected by cancer to maintain PA for the long term.

How do illness identity, patient workload and agentic capacity interact to shape patient and caregiver experience? Comparative analysis of lung cancer and chronic obstructive pulmonary disease.

Some patients have to work hard to manage their illness. When this work outweighs capacity (the resources available to patients to undertake the illness workload and other workloads such as that of daily life), this may result in treatment burden, associated with poor health outcomes for patients. This cross-sectional, comparative qualitative analysis uses an abductive approach to identify, characterise and explain treatment burden in chronic obstructive pulmonary disease (COPD) and lung cancer. It uses complementary qualitative methods (semi-structured interviews with patients receiving specialist care n = 19, specialist clinicians n = 5; non-participant observation of specialist outpatient consultations in two English hospitals [11 h, 52 min] n = 41). The findings underline the importance of the diagnostic process in relation to treatment burden; whether diagnosis is experienced as a biographically disruptive shock (as with lung cancer) or is insidiously biographically erosive (as with COPD).

Implementing primary care diabetes prevention for women with previous gestational diabetes: a mixed-methods study.

BACKGROUND: The implementation of diabetes prevention for women with previous gestational diabetes (GDM) has been stymied by many barriers that are located within routine general practice (GP). We aimed to unpack the GP factors and understand the mechanisms that explain why a diabetes prevention intervention for this population succeeds or fails. METHODS: We performed a mixed-methods study with a Normalization Process Theory framework that included clinical audits, semistructured interviews, and focus groups within mixed urban and rural primary care practices in Victoria, Australia. Staff of primary care practices and external support staff who provide services to women with previous GDM participated in a 12-month quality improvement collaborative intervention. We compared diabetes screening and prevention activity planning with the strategies and factors identified through a process evaluation of full-, moderate-, and low-active participating practices. RESULTS: The intervention doubled screening rates (26%-61%) and 1-in-10 women received a diabetes prevention planning consultation. Critical improvement factors were: mothers being seen as participants in the quality improvement work; staff collectively building care strategies; staff taking a long-term care of a community perspective rather than episodic service delivery; and feedback processes being provided and acted on across the practice. The observable factors from the external perspective were: leadership by identified practice staff, reminder systems in action and practice staff driving the process collectively. CONCLUSIONS: Successful engagement in diabetes prevention for women with previous GDM requires proactive building of the critical improvement factors and audit feedback into routine GP.

Factors that influence patient preferences for virtual consultations in an orthopaedic rehabilitation setting: a qualitative study.

OBJECTIVES: To identify, characterise and explain factors that influence patient preferences, from the perspective of patients and clinicians, for virtual consultations in an orthopaedic rehabilitation setting. DESIGN: Qualitative study using semi-structured interviews and abductive analysis. SETTING: A physiotherapy and occupational therapy department situated within a tertiary orthopaedic centre in the UK. PARTICIPANTS: Patients who were receiving orthopaedic rehabilitation for a musculoskeletal problem. Occupational therapists, physiotherapists or therapy technicians involved in the delivery of orthopaedic rehabilitation for patients with a musculoskeletal problem. RESULTS: Twenty-two patients and 22 healthcare professionals were interviewed. The average interview length was 48 minutes. Four major factors were found to influence preference: the situation of care (the ways that patients understand and explain their clinical status, their treatment requirements and the care pathway), the expectations of care (influenced by a patients desire for contact, psychological status, previous care and perceived requirements), the demands on the patient (due to each patients respective social situation and the consequences of choice) and the capacity to allocate resources to care (these include financial, infrastructural, social and healthcare resources). CONCLUSION: This study has identified key factors that appear to influence patient preference for virtual consultations in orthopaedic rehabilitation. A conceptual model of these factors, derived from empirical data, has been developed highlighting how they combine and compete. A series of questions, based on these factors, have been developed to support identification of preferences in a clinical setting.

Exploring maintenance of physical activity behaviour change among people living with and beyond gastrointestinal cancer: a cross-sectional qualitative study and typology.

OBJECTIVES: In the last decade, there has been a rapid expansion of physical activity (PA) promotion programmes and interventions targeting people living with and beyond cancer (LWBC). The impact that these initiatives have on long-term maintenance of PA remains under-researched. This study sought to explore the experiences of participants in order to characterise those who have and have not successfully sustained increases in PA following participation in a PA intervention after a diagnosis of gastrointestinal (GI) cancer, and identify barriers and facilitators of this behaviour. DESIGN: Cross-sectional qualitative study. Semi-structured interviews with participants who had previously taken part in a PA programme in the UK, explored current and past PA behaviour and factors that promoted or inhibited regular PA participation. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Themes and subthemes were identified. Differences between individuals were recognised and a typology of PA engagement was developed. PARTICIPANTS: Twenty-seven individuals (n=15 male, mean age=66.3 years) with a diagnosis of GI cancer who had participated in one of four interventions designed to encourage PA participation. SETTING: UK. RESULTS: Seven themes were identified: disease processes, the role of ageing, emotion and psychological well-being, incorporating PA into everyday life, social interaction, support and self-monitoring and competing demands. A typology with three types describing long-term PA engagement was generated: (1) maintained PA, (2) intermittent PA, (3) low activity. Findings indicate that identifying an enjoyable activity that is appropriate to an individual's level of physical functioning and is highly valued is key to supporting long-term PA engagement. CONCLUSION: The typology described here can be used to guide stratified and personalised intervention development and support sustained PA engagement by people LWBC.

Use of virtual consultations in an orthopaedic rehabilitation setting: how do changes in the work of being a patient influence patient preferences? A systematic review and qualitative synthesis.

OBJECTIVES: To systematically review qualitative studies reporting the use of virtual consultations within an orthopaedic rehabilitation setting and to understand how its use changes the work required of patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement, we conducted a systematic review of papers to answer the research question 'How do changes in the work of being a patient when using communication technology influence patient preferences?' Electronic databases were searched for studies meeting the inclusion criteria in April 2020. RESULTS: The search strategy identified 2057 research articles from the database search. A review of titles and abstracts using the inclusion criteria yielded 21 articles for full-text review. Nine studies were included in the final analysis. Six studies explored real-time video conferencing and three explored telephone consultations. The use of communication technology changes the work required of patients. Such changes will impact on expectations for care, resources required of patients, the environment of receiving care and patient-clinician interactions. This adjustment of the work required of patients who access orthopaedic rehabilitation using communication technology will impact on their experience of receiving care. It is proposed that changes in the work of being a patient will influence preferences for or against the use of communication technology consultations for orthopaedic rehabilitation. CONCLUSION: We found that the use of communication technology changes the work of being a patient. The change in work required of patients can be both burdensome (it makes it harder for patients to access their care) and beneficial (it makes it easier for patients to access their care). This change will likely to influence preferences. Keeping the concept of patient work at the heart of pathway redesign is likely to be a key consideration to ensure successful implementation. PROSPERO REGISTRATION NUMBER: CRD42018100896.

Effectiveness of nurse-led group CBT for hot flushes and night sweats in women with breast cancer: Results of the MENOS4 randomised controlled trial.

OBJECTIVE: Troublesome hot flushes and night sweats (HFNS) are experienced by many women after treatment for breast cancer, impacting significantly on sleep and quality of life. Cognitive behavioural therapy (CBT) is known to be effective for the alleviation of HFNS. However, it is not known if it can effectively be delivered by specialist nurses. We investigated whether group CBT, delivered by breast care nurses (BCNs), can reduce the impact of HFNS. METHODS: We recruited women with primary breast cancer following primary treatment with seven or more HFNS/week (including 4/10 or above on the HFNS problem rating scale), from six UK hospitals to an open, randomised, phase 3 effectiveness trial. Participants were randomised to Group CBT or usual care (UC). The primary endpoint was HFNS problem rating at 26 weeks after randomisation. Secondary outcomes included sleep, depression, anxiety and quality of life. RESULTS: Between 2017 and 2018, 130 participants were recruited (CBT:63, control:67). We found a 46% (6.9-3.7) reduction in the mean HFNS problem rating score from randomisation to 26 weeks in the CBT arm and a 15% (6.5-5.5) reduction in the UC arm (adjusted mean difference -1.96, CI -3.68 to -0.23, P = .039). Secondary outcomes, including frequency of HFNS, sleep, anxiety and depression all improved significantly. CONCLUSION: Our results suggest that specialist nurses can be trained to deliver CBT effectively to alleviate troublesome menopausal hot flushes in women following breast cancer in the NHS setting.

Malnutrition in community-dwelling older people: lessons learnt using a new procedure.

This article reports the implementation of a new procedure for screening and treatment of malnutrition in a community NHS trust in England. The barriers and facilitators to implementation were assessed with staff from Integrated Community and Older People's Mental Health teams. Data from interviews and surveys were collected at baseline, 2 months after initial training and 16 months after initial training as well as following deployment of a nutrition lead to embed new developments for nutritional care. The adoption of the procedure made screening and treatment of malnutrition simpler and more likely to be actioned. The benefit of a nutrition lead and local nutrition champions to support and empower staff (avoiding reliance on training alone) was shown to drive change for nutritional care across the community. Prioritisation and commitment of leadership at the organisational level are needed to embed and sustain malnutrition screening and treatment in routine practice.

Implementing professional behaviour change in teams under pressure: results from phase one of a prospective process evaluation (the Implementing Nutrition Screening in Community Care for Older People (INSCCOPe) project).

OBJECTIVES: To evaluate the implementation of a new procedure for screening and treatment of malnutrition for older people in community settings and to identify factors promoting or inhibiting its implementation as a routine aspect of care. DESIGN: Prospective process evaluation using mixed methods with pre/post-implementation measures. SETTING AND PARTICIPANTS: Community teams (nursing and allied health professionals) within a UK National Health Service Community Trust. 73 participants were recruited, of which 32 completed both pre-implemetation and post-implementation surveys. MAIN OUTCOME MEASURES: NoMAD survey for pre-post-intervention measures; telephone interviews exploring participant experiences and wider organisational/contextual processes. METHODS: Data prior to implementation of training, baseline (T0-survey and telephone interview) and 2 months following training (T1-follow-up survey). Quantitative data described using frequency tables reporting team type, healthcare provider role group and total study sample; analysis using Wilcoxon rank-sum (subgroup comparison) and Wilcoxon signed-rank (within-group observation point comparison) tests. Qualitative interview data (audio and transcription) analysed through directed content analysis using normalisation process theory. RESULTS: High support for nutrition screening and treatment indicated by participants. Concerns expressed around logistical, organisational and specialist dietetic support. Pre-post-training measures indicated a positive impact of training on knowledge of the new procedure; however, most implementation measures saw no significant changes between time points or between subgroups (training participants vs non-participants). Implementation barriers included the following: high levels of training non-completion; vulnerability to attrition of trained staff; lack of monitoring of post-intervention compliance and lack of access to dietetic support. CONCLUSION: Greater support necessary to support implementation in relation to monitoring of training completion, and organisational support for nutrition screening and treatment activity. Recommended changes to implementation design are as follows: appointment of a key person to support and monitor procedure compliance; adoption of training as an e-learning module within the existing organisational platform to increase participation in changeable working conditions.

HORIZONS protocol: a UK prospective cohort study to explore recovery of health and well-being in adults diagnosed with cancer.

INTRODUCTION: Understanding the impact of cancer and its treatment on people's everyday lives will help prepare people for what to expect, enable health professionals to predict likely recovery trajectories and shape care management according to needs. HORIZONS will recruit people awaiting treatment and follow them up at regular intervals to assess recovery of health and well-being. RESEARCH QUESTIONS: What impact does cancer diagnosis and treatment have on people's lives in the short, medium and long term? What are people's health and well-being outcomes, experiences and self-management activities over time across different cancer types and what influences these? How do people connect with and relate to others in mobilising resources that enable them to self-manage the consequences of cancer and treatment? METHODS AND ANALYSIS: HORIZONS is a multicentre, prospective cohort study exploring recovery of health and well-being in 3000 people diagnosed with breast cancer (<50 years), non-Hodgkin's lymphoma or gynaecological cancer. Recruitment will take place across National Health Service (NHS) sites in the UK between September 2016 and March 2019, before primary treatment starts. Participants will be identified through clinical teams and invited to complete questionnaires including assessments of quality of life, symptoms and functioning (Quality of Life in Adult Cancer Survivors; European Organisation for Research and Treatment Consortium Core quality of life questionnaire, EORTC-QLQ-C30), health status (EuroQol-5 dimensions, EQ-5D), self-efficacy, social support, social networks and lifestyle. Clinical data will also be collected. Descriptive statistics will characterise outcomes. Changes over time will be investigated. Factors that may influence recovery and self-management will be included in regression models to determine which influence health and well-being and self-management. ETHICS AND DISSEMINATION: Ethics and Health Research Authority approvals granted (IRAS Project ID: 202342, REC reference number 16/NW/0425). Adopted onto the National Institute for Health Research Clinical Research Network portfolio. We will engage with our Scientific Advisory Board, Tumour Specific Expert Panels, User Reference Group, Macmillan and the University of Southampton to ensure maximum publicity and benefit.

Systematic review and meta-analysis of maintenance of physical activity behaviour change in cancer survivors.

BACKGROUND: Physical activity can improve health and wellbeing after cancer and may reduce cancer recurrence and mortality. To achieve such long-term benefits cancer survivors must be habitually active. This review evaluates the effectiveness of interventions in supporting maintenance of physical activity behaviour change among adults diagnosed with cancer and explores which intervention components and contextual features are associated with effectiveness. METHODS: Relevant randomised controlled trials (RCTs) were identified by a search of Ovid Medline, Ovid Embase and PsychINFO. Trials including adults diagnosed with cancer, assessed an intervention targeting physical activity and reported physical activity behaviour at baseline and ≥ 3 months post-intervention were included. The behaviour change technique (BCT) taxonomy was used to identify intervention components and the Template for Intervention Description and Replication to capture contextual features. Random effect meta-analysis explored between and within group differences in physical activity behaviour. Standardised mean differences (SMD) describe effect size. RESULTS: Twenty seven RCTs were included, 19 were pooled in meta-analyses. Interventions were effective at changing long-term behaviour; SMD in moderate to vigorous physical activity (MVPA) between groups 0.25; 95% CI = 0.16-0.35. Within-group pre-post intervention analysis yielded a mean increase of 27.48 (95% CI = 11.48-43.49) mins/wk. of MVPA in control groups and 65.30 (95% CI = 45.59-85.01) mins/wk. of MVPA in intervention groups. Ineffective interventions tended to include older populations with existing physical limitations, had fewer contacts with participants, were less likely to include a supervised element or the BCTs of 'action planning', 'graded tasks' and 'social support (unspecified)'. Included studies were biased towards inclusion of younger, female, well-educated and white populations who were already engaging in some physical activity. CONCLUSIONS: Existing interventions are effective in achieving modest increases in physical activity at least 3 months post-intervention completion. Small improvements were also evident in control groups suggesting low-intensity interventions may be sufficient in promoting small changes in behaviour that last beyond intervention completion. However, study samples are not representative of typical cancer populations. Interventions should consider a stepped-care approach, providing more intensive support for older people with physical limitations and others less likely to engage in these interventions.

Patients and informal caregivers' experiences of burden of treatment in lung cancer and chronic obstructive pulmonary disease (COPD): a systematic review and synthesis of qualitative research.

OBJECTIVE: To identify, characterise and explain common and specific features of the experience of treatment burden in relation to patients living with lung cancer or chronic obstructive pulmonary disease (COPD) and their informal caregivers. DESIGN: Systematic review and interpretative synthesis of primary qualitative studies. Papers were analysed using constant comparison and directed qualitative content analysis. DATA SOURCES: CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science searched from January 2006 to December 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary qualitative studies in English where participants were patients with lung cancer or COPD and/or their informal caregivers, aged >18 years that contain descriptions of experiences of interacting with health or social care in Europe, North America and Australia. RESULTS: We identified 127 articles with 1769 patients and 491 informal caregivers. Patients, informal caregivers and healthcare professionals (HCPs) acknowledged lung cancer's existential threat. Managing treatment workload was a priority in this condition, characterised by a short illness trajectory. Treatment workload was generally well supported by an immediacy of access to healthcare systems and a clear treatment pathway. Conversely, patients, informal caregivers and HCPs typically did not recognise or understand COPD. Treatment workload was balanced with the demands of everyday life throughout a characteristically long illness trajectory. Consequently, treatment workload was complicated by difficulties of access to, and navigation of, healthcare systems, and a fragmented treatment pathway. In both conditions, patients' capacity to manage workload was enhanced by the support of family and friends, peers and HCPs and diminished by illness/smoking-related stigma and social isolation. CONCLUSION: This interpretative synthesis has affirmed significant differences in treatment workload between lung cancer and COPD. It has demonstrated the importance of the capacity patients have to manage their workload in both conditions. This suggests a workload which exceeds capacity may be a primary driver of treatment burden. PROSPERO REGISTRATION NUMBER: CRD42016048191.

Implementation of self-management support in cancer care and normalization into routine practice: a systematic scoping literature review protocol.

BACKGROUND: Cancer survivors face a myriad of biopsychosocial consequences due to cancer and treatment that may be potentially mitigated through enabling their self-management skills and behaviors for managing illness. Unfortunately, the cancer system lags in its systematic provision of self-management support (SMS) in routine care, and it is unclear what implementation approaches or strategies work to embed SMS in the cancer context to inform health policy and administrator decision-making. METHODS/DESIGN: A comprehensive scoping review study of the literature will be conducted based on methods and steps identified by Arksey and O'Malley and experts in the field. Electronic searches will be conducted in multiple databases including CINAHL, CENTRAL, EMBASE, PsycINFO, MEDLINE, AMED, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE) (up to Issue 2, 2015), ISI Proceedings (Web of Science), PsychAbstracts, and Sociological Abstracts from January 1997 to November 5, 2018. Following the PRISMA-Extension for Scoping Reviews (PRISMA-ScR), two authors will independently screen all titles/abstracts to determine eligibility, data will be abstracted by one author and checked by a second author, and findings will be narratively summarized based on constructs of implementation in the Normalization Process Theory. DISCUSSION: This will be the first scoping review study to synthesize knowledge of implementation of SMS in the cancer care context and the implementation approaches and strategies on embedding in care. This information will be critical to inform health policy and knowledge end users about the necessary changes in care to embed SMS in practices and to stimulate future research.

What factors promote or inhibit implementation of a new procedure for screening and treatment of malnutrition in community settings? A prospective process evaluation of the Implementing Nutrition Screening in Community Care for Older People (INSCCOPe) project (UK).

INTRODUCTION: Malnutrition remains underdetected, undertreated and often overlooked by those working with older people in primary care in the UK. A new procedure for screening and treatment of malnutrition is currently being implemented by a large National Health Service (NHS) trust in England, incorporating a programme of training for staff working within Integrated Community Teams and Older People's Mental Health teams. Running in parallel, the Implementing Nutrition Screening in Community Care for Older People process evaluation study explores factors that may promote or inhibit its implementation and longer term embedding in routine care, with the aim of optimising sustainability and scalability. METHODS AND ANALYSIS: Implementation will be assessed through observation of staff within a single area of the trust, in addition to the procedure development and delivery group (PDDG). Data collection will occur at three observation points: prior to implementation of training, baseline (T0); 2 months following training (T1); and 8 months following training (T2). Observation points will consist of a survey and follow-up semistructured telephone interview with staff. Investigation of the PDDG will involve: observations of discussions around development of the procedure; semistructured telephone interviews prior to implementation, and at 6 months following implementation. Quantitative data will be described using frequency tables reporting by team type, healthcare provider role group, and total study sample (Wilcoxon rank-sum and Wilcoxon signed-rank tests may also be conducted if appropriate. Audio and transcription data will be analysed using Nomarlization Process Theory as a framework for deductive thematic analysis (using the NVIVO CAQDAS software package). ETHICS AND DISSEMINATION: Ethical approval for the study has been granted through institutional ethical review (Bournemouth University); NHS Research Ethics committee approval was not required. Dissemination will occur through presentations to academic and practitioner audiences and publication results in peer-reviewed academic journals.