Search

Introduction The prevalence of multiple long-term conditions (M-LTCs) increases as adults age and impacts quality of life and health outcomes. To help people manage these conditions, complex behaviour change interventions are used, often based on research conducted in those with single LTCs. However, the needs of those with M-LTCs can differ due to complex health decision-making and engagement with multiple health and care teams.Objectives The aim of this review is to identify whether current interventions are effective for people living with M-LTCs, and which outcomes are most appropriate to detect this change.Methods Five databases (MEDLINE, Embase, PsycINFO, CINAHL and Web of Science) were systematically searched, between January 1999 and January 2022, to identify randomised controlled trials evaluating effectiveness of behaviour change interventions in people with M-LTCs. Intervention characteristics, intervention effectiveness and outcome measures were meta-analysed and narratively synthesised.Results 53 eligible articles were included. Emotional well-being and psychological distress (depression and anxiety) outcomes were most amenable to change (emotional well-being: standardised mean difference (SMD) 0.31 (95% CI 0.04 to 0.58); depression psychological distress: SMD −0.45 (95% CI –0.73 to −0.16); anxiety psychological distress: SMD −0.14 (95% CI –0.28 to 0.00)), particularly for interventions with a collaborative care approach. Interventions targeting those with a physical and mental health condition and those with cognitive and/or behavioural activation approach saw larger reductions in psychological distress outcomes. Interventions that lasted for longer than 6 months significantly improved the widest variety of outcomes.Conclusion Complex interventions can be successfully delivered to those with M-LTCs. These are most effective at reducing psychological distress in those with physical and mental LTCs. Further research is needed to identify the effective components of interventions for people with two or more physical LTCs and which outcome is most appropriate for detecting this change.

Abstract The GGGGCC hexanucleotide repeat expansion mutation in the chromosome 9 open reading frame 72 (C9orf72) gene is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). In this study, we demonstrate that the zinc finger (ZF) transcriptional regulator Yin Yang 1 (YY1) binds to the promoter region of the planar cell polarity gene Fuzzy to regulate its transcription. We show that YY1 interacts with GGGGCC repeat RNA via its ZF and that this interaction compromises the binding of YY1 to the Fuzzy YY1 promoter sites, resulting in the downregulation of Fuzzy transcription. The decrease in Fuzzy protein expression in turn activates the canonical Wnt/β-catenin pathway and induces synaptic deficits in C9ALS/FTD neurons. Our findings demonstrate a C9orf72 GGGGCC RNA-initiated perturbation of YY1–Fuzzy transcriptional control that implicates aberrant Wnt/β-catenin signalling in C9ALS/FTD-associated neurodegeneration. This pathogenic cascade provides a potential new target for disease-modifying therapy.

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 (IMP2ART) 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 IMP2ART 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 IMP2ART 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.

The challenges of building and sustaining a creative career are well-established, as is the degree to which opportunities are either opened or foreclosed through the complex intersectionality of inequalities. Yet creative aspirants persist in pursuing creative work, sustaining themselves through survival strategies variously theorised as ‘hope labour’ and ‘aspirational labour’. Drawing upon data from an arts mentoring programme, this article explores how ideas of ‘luck’, ‘chance’ and ‘opportunity’ are implicated within such labour as sense-making resources for managing difficulties and justifying persistence in the face of precarity. It argues that the take up of these resources can function as a valuable discursive tool that also contributes to an enabling ‘repertoire of shared myths’ which sustains the career work of artists and many creative workers.

Background This interview study forms part of a mixed methods process evaluation of the Survivors’ Rehabilitation Evaluation after Cancer (SURECAN) trial to understand the experiences of participants (who are living with and beyond cancer) in receiving a form of acceptance and commitment therapy, and therapists providing the intervention. SURECAN is a multi-centre, pragmatic, individual participant randomised controlled trial of an intervention based on acceptance and commitment therapy supplemented by support for return to meaningful work and/or physical activity (ACT+). This qualitative study addresses the ways in which participants believe they benefit from ACT+ (or not), and how the ACT+ intervention might best be implemented into routine National Health Service (NHS) care. Methods The study investigates experiences of ACT+ by different participants to understand how we can optimise the ACT+ intervention and its delivery (assuming the intervention is successful). We will conduct individual interviews with participants who have taken part in the active arm of the SURECAN trial to understand their experiences of engaging with and receiving ACT+, their perceptions of the impact of the therapy, and relevant contextual factors influencing these experiences. In particular, we will focus on comparing our interview findings between those trial participants who improved and those who failed to improve (or worsened), in terms of quality of life following ACT+. Additionally, we will conduct individual interviews with therapists who have delivered ACT+ as part of the SURECAN trial, to understand their experiences of delivering ACT+. Conclusions Consistent with other qualitative protocols, this protocol is not registered. Instead, it is shared as a means of documenting ahead of time, how we are endeavouring to understand the ways in which a newly trialled talking therapy is received by patients and therapists, and how (if successful) it might be incorporated into the NHS.

Background: Electronic templates are frequently used in long-term condition (LTC) reviews (for example, asthma) to act as reminders and improve documentation; however, they can restrict patient-centred care and opportunities for patients to discuss concerns and self-management. Aim: The IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) programme aimed to develop a patient-centred asthma review template that encourages supported self-management. Design & setting: This was a mixed-methods study, which integrated qualitative and systematic review data, primary care Professional Advisory Group feedback, and qualitative data from clinician interviews. Method: Aligned with the Medical Research Council complex intervention framework, a template was developed in the following three phases: (1) development phase, which consisted of a qualitative exploration with clinicians and patients, a systematic review, and prototype template development; (2) feasibility pilot phase, which involved feedback from clinicians (n = 7); and (3) pre-piloting phase, which consisted of delivering the template within the IMP2ART implementation strategy (incorporating the template with patient and professional resources) and eliciting clinician feedback (n = 6). Results: Template development was guided by the preliminary qualitative work and the systematic review. A prototype template was developed with an opening question to establish patient agendas, and a closing prompt to confirm agendas have been addressed and an asthma action plan provided. The feasibility pilot identified refinements needed, including focusing the opening question on asthma. Pre-piloting ensured integration with the IMP2ART strategy. Conclusion: Following the multi-stage development process, the implementation strategy, including the asthma review template, is now being tested in a cluster randomised controlled trial.

The perturbations in bile acids (BAs) in alcohol‐associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine‐conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple‐comparison adjusted P

Background The minimum clinically effective dose, and whether this is received in randomised controlled trials (RCTs) of complex self-management interventions in long-term conditions (LTCs), can be unclear. The Template for Intervention Description and Replication (TIDieR) checklist states that dose should be clearly reported to ensure validity and reliable implementation.Objectives To identify whether the expected minimum clinically effective dose, and the dose participants received is reported within research articles and if reporting has improved since the TIDieR checklist was published.Methods Four databases were systematically searched (MEDLINE, PsycINFO, AMED and CINAHL) to identify published reports between 2008 and 2022 for RCTs investigating complex self-management interventions in LTCs. Data on reporting of dose were extracted and synthesised from the eligible articles.Results 94 articles covering various LTCs including diabetes, stroke and arthritis were included. Most complex interventions involved behaviour change combined with education and/or exercise. The maximum dose was usually reported (n=90; 97.8%), but the expected minimum clinically effective dose and the dose received were reported in only 28 (30.4%) and 62 (67.4%) articles, respectively. Reporting of the expected minimum clinically effective dose and the dose participants received did not improve following the publication of the TIDieR checklist in 2014.Conclusions Interpreting results and implementing effective complex self-management interventions is difficult when researchers’ reporting of dose is not in line with guidelines. If trial findings indicate benefit from the intervention, clear reporting of dose ensures reliable implementation to standard care. If the results are non-significant, detailed reporting enables better interpretation of results, that is, differentiating between poor implementation and lack of effectiveness. This ensures quality of interventions and validity and generalisability of trial findings. Therefore, wider adoption of reporting the TIDieR checklist dose aspects is strongly recommended. Alternatively, customised guidelines for reporting dose in complex self-management interventions could be developed.PROSPERO registration number CRD42020180988.

OBJECTIVE:. To summarize knowledge and identify gaps in evidence about the relationship between social determinants of health (SDH) and postsepsis outcomes. DATA SOURCES:. We conducted a comprehensive search of PubMed/Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, and the Cochrane Library. STUDY SELECTION:. We identified articles that evaluated SDH as risk factors for mortality or readmission after sepsis hospitalization. Two authors independently screened and selected articles for inclusion. DATA EXTRACTION:. We dual-extracted study characteristics with specific focus on measurement, reporting, and interpretation of SDH variables. DATA SYNTHESIS:. Of 2,077 articles screened, 103 articles assessed risk factors for postsepsis mortality or readmission. Of these, 28 (27%) included at least one SDH variable. Inclusion of SDH in studies assessing postsepsis adverse outcomes increased over time. The most common SDH evaluated was race/ethnicity (n = 21, 75%), followed by payer type (n = 10, 36%), and income/wealth (n = 9, 32%). Of the studies including race/ethnicity, nine (32%) evaluated no other SDH. Only one study including race/ethnicity discussed the use of this variable as a surrogate for social disadvantage, and none specifically discussed structural racism. None of the studies specifically addressed methods to validate the accuracy of SDH or handling of missing data. Eight (29%) studies included a general statement that missing data were infrequent. Several studies reported independent associations between SDH and outcomes after sepsis discharge; however, these findings were mixed across studies. CONCLUSIONS:. Our review suggests that SDH data are underutilized and of uncertain quality in studies evaluating postsepsis adverse events. Transparent and explicit ontogenesis and data models for SDH data are urgently needed to support research and clinical applications with specific attention to advancing our understanding of the role racism and racial health inequities in postsepsis outcomes.

Abstract Background TANDEM is a randomised controlled trial of a complex healthcare intervention to improve the psychological and physical health of people living with chronic obstructive pulmonary disease (COPD) and anxiety and/or depression. Based on health psychology theory set out in a logic model, respiratory health professionals were recruited and trained to deliver a cognitive behavioural approach intervention (The TANDEM intervention) under the supervision of senior cognitive behavioural practitioners. Here, we describe the protocol for the process evaluation commissioned alongside the trial. A realist approach that includes attention to describing contexts and mechanisms has been adopted. Methods We set up a multi-disciplinary team to develop and deliver the process evaluation. The mixed-methods design incorporates quantitative process data; monitoring of intervention fidelity; qualitative interviews with patients, carers, health professionals (facilitators) and clinical supervisors about their perspectives on acceptability of the intervention; and exploration with all stakeholders (including management/policy-makers) on future implementation. Normalisation process theory (NPT) will inform data collection and interpretation with a focus on implementation. Quantitative process data will be analysed descriptively. Qualitative interview data will be analysed before the trial outcomes are known using analytic induction and constant comparison to develop themes. Findings from the different elements will be reported separately and then integrated. Conclusion Detailed description and analysis of study processes in a research trial such as TANDEM enables research teams to describe study contexts and mechanisms and to examine the relationship with outcomes. In this way, learning from the trial goes beyond the randomised control trial (RCT) model where effectiveness is prioritised and makes it possible to explore issues arising for post-trial study implementation. Trial registration ISRCTN ISRCTN59537391 . Registered on 20 March 2017. Trial protocol version 6.0, 22 April 2018. Process evaluation protocol version 4.0, 1 November 2020.

Introduction The number of people living with and beyond cancer is increasing rapidly. Many of them will experience ongoing physical or psychological sequelae as a result of their original cancer diagnosis or comorbidities arising from risk factors common to cancers and other long-term conditions. This poses the complex problem of managing cancer as a ‘chronic’ illness along with other existing comorbidities. This scoping review aims to map the literature available on multimorbidity in patients living with and beyond cancer, to explore, quantify and understand the impact of comorbid illnesses to inform work around cancer care in UK primary care settings.Methods and analysis This review will be guided by Joanna Briggs Institute Reviewer’s manual for scoping reviews. A systematic literature search using Medical Subject Heading and text words related to cancer survivors and multimorbidity will be performed in MEDLINE, CINAHL, Embase and Web of Science, from 1990. Results will be described in a narrative style, reported in extraction tables and diagrams, and where appropriate in themes and text.Ethics and dissemination The scoping review will undertake secondary analysis of published literature; therefore, ethics committee approval is not required. Results will be disseminated through a peer-reviewed scientific journal and presented in relevant conferences. The scoping review will inform understanding of the burden of multimorbidity for cancer survivors, thus allow families, practitioners, clinicians and researchers to take the steps necessary to improve patient-centred care.

Abstract Background Guidelines now call for a thorough and comprehensive description of the development of healthcare interventions to aid evaluation and understanding of the processes of change. This was the primary aim of this study but we also recognised that effective interventions are commonly not implemented in clinical practice. It is suggested that insufficient attention is given to the implementation process at the development phase of interventions. This study outlines the 5 step iterative process we adopted for considering both implementation and effectiveness issues from the outset of intervention development. We use the development of a complex intervention Tailored intervention for ANxiety and DEpression Management (TANDEM) in patients with chronic obstructive pulmonary disease to illustrate this process. Methods Intervention development built upon the Medical Research Council framework for developing complex interventions and the person-based approach for development of behavioural interventions. Building an expert team, specifying theory, qualitative data collection and pre-piloting were all critical steps in our intervention development and are described here. Results Contact with experts in the field, and explicitly building on previous work, ensured efficiency of design. Qualitative work suggested guiding principles for the intervention such as introducing mood in relation to breathlessness, and providing flexible tailoring to patients’ needs, whilst implementation principles focused on training selected respiratory professionals and requiring supervision to ensure standards of care. Subsequent steps of intervention development, pre-piloting and intervention refinement led to an intervention that was deemed acceptable and if successful will be ready for implementation. Conclusions The TANDEM study was developed efficiently by building on previous work and considering implementation issues from the outset, with the aim that if shown to be effective it will have more rapid translation in to the health care system with accelerated patient benefits. Trial registration ISRCTN ISRCTN59537391 . Registered on 20 March 2017. Protocol version 6.0, 22 April 2018.

ObjectivesTo evaluate the feasibility of a randomised trial of a modified, pre-existing, mindfulness meditation smartphone app for women with chronic pelvic pain.DesignThree arm randomised feasibility trial.SettingWomen were recruited at two gynaecology clinics in the UK. Interventions were delivered via smartphone or computer at a location of participants choosing.ParticipantsWomen were eligible for the study if they were over 18, had been experiencing organic or non-organic chronic pelvic pain for 6 months or more, and had access to a computer or smartphone. 90 women were randomised.InterventionsDaily mindfulness meditation delivered by smartphone app, an active control app which delivered muscle relaxation techniques, and usual care without app. Interventions were delivered over 60 days.Primary and secondary outcome measuresOutcomes included length of recruitment, follow-up rates, adherence to the app interventions, and clinical outcomes measured at baseline, two, three and 6 months.ResultsThe target sample size was recruited in 145 days. Adherence to the app interventions was extremely low (mean app use 1.8 days mindfulness meditation group, 7.0 days active control). Fifty-seven (63%) women completed 6-month follow-up, and 75 (83%) women completed at least one postrandomisation follow-up. The 95% CIs for clinical outcomes were consistent with no benefit from the mindfulness meditation app; for example, mean differences in pain acceptance scores at 60 days (higher scores are better) were −2.3 (mindfulness meditation vs usual care, 95% CI: −6.6 to 2.0) and −4.0 (mindfulness meditation vs active control, 95% CI: −8.1 to 0.1).ConclusionsDespite high recruitment and adequate follow-up rates, demonstrating feasibility, the extremely low adherence suggests a definitive randomised trial of the mindfulness meditation app used in this study is not warranted. Future research should focus on improving patient engagement.Trial registration numbersNCT02721108; ISRCTN10925965; Results.

ObjectivesTo determine whether a pre-existing smartphone app to teach mindfulness meditation is acceptable to women with chronic pelvic pain (CPP) and can be integrated into clinical practice within the National Health Service (NHS) CPP pathways, and to inform the design of a potential randomised clinical trial.DesignA prestudy patient and public involvement (PPI) group to collect feedback on the acceptability of the existing app and study design was followed by a three-arm randomised feasibility trial. In addition, we undertook interviews and focus groups with patients and staff to explore app usability and acceptability. We also obtained participant comments on the research process, such as acceptability of the study questionnaires.SettingTwo gynaecology clinics within Barts Health NHS, London, UK.ParticipantsPatients with CPP lasting ≥6 months with access to smartphone or personal computer and understanding of basic English.InterventionThe intervention was mindfulness meditation content plus additional pain module delivered by a smartphone app. Active controls received muscle relaxation content from the same app. Passive (waiting list) controls received usual care.Main outcome measuresThemes on user feedback, app usability and integration, and reasons for using/not using the app.ResultsThe use of the app was low in both active groups. Patients in the prestudy PPI group, all volunteers, were enthusiastic about the app (convenience, content, portability, flexibility, ease of use). Women contributing to the interview or focus group data (n=14), from a ‘real world’ clinic (some not regular app users), were less positive, citing as barriers lack of opportunities/motivation to use the app and lack of familiarity and capabilities with technology. Staff (n=7) were concerned about the potential need for extra support for them and for the patients, and considered the app needed organisational backing and peer acceptance.ConclusionThe opinions of prestudy PPI volunteers meeting in their private time may not represent those of patients recruited at a routine clinic appointment. It may be more successful to codesign/codevelop an app with typical users than to adapt existing apps for use in real-world clinical populations.Trial registration numberISRCTN10925965.

Importance:. Risk prediction models for patients with suspected sepsis have been derived on and applied to various outcomes, including readily available outcomes such as hospital mortality and ICU admission as well as longer-term mortality outcomes that may be more important to patients. It is unknown how selecting different outcomes influences model performance in patients at risk for sepsis. Objectives:. Evaluate the impact of outcome selection on risk model performance and weighting of individual predictor variables. Design, Setting, and Participants:. We retrospectively analyzed adults hospitalized with suspected infection from January 2014 to September 2017 at 12 hospitals. Main Outcomes and Measures:. We used routinely collected clinical data to derive logistic regression models for four outcomes: hospital mortality, composite ICU length of stay greater than 72 hours or hospital mortality, 30-day mortality, and 90-day mortality. We compared the performance of the models using area under the receiver operating characteristic curve and calibration plots. Results:. Among 52,184 admissions, 2,030 (4%) experienced hospital mortality, 6,659 (13%) experienced the composite of hospital mortality or ICU length of stay greater than 72 hours, 3,417 (7%) experienced 30-day mortality, and 5,655 (11%) experienced 90-day mortality. Area under the receiver operating characteristic curves decreased when hospital-based models were applied to predict 30-day (hospital mortality = 0.88–0.85; –0.03, composite ICU length of stay greater than 72 hours or hospital mortality = 0.90–0.81; –0.09) and 90-day mortality (hospital mortality = 0.88–0.81; –0.07, composite ICU length of stay greater than 72 hours or hospital mortality = 0.90–0.76; –0.14; all p < 0.01). Models were well calibrated for derived (root-mean-square error = 5–15) but not alternate outcomes (root-mean-square error = 8–35). Conclusions and Relevance:. Risk models trained to predict readily available hospital-based outcomes in suspected sepsis show poorer discrimination and calibration when applied to 30- and 90-day mortality. Interpretation and application of risk models for patients at risk of sepsis should consider these findings.

This article explores one aspect of increased managerialism, the impact of the expansion of rules in organizations. Discussing findings from a recent large-scale Canadian research project with social workers, this paper addresses some of the effects of the proliferation of rules, including their ethical implications, and considers the usefulness of different theoretical accounts of the rule-bending individual. The research indicated that although rules did serve as technologies to regulate and normalize practitioners’ behaviours, they were not monolithic in their consequences. Typologies, which divided individuals in terms of their responses to rules, were useful but insufficient explanations of the observed effects. The paper suggests that practitioners will use discretion to deal with the complexity of situations, the contradictory nature of the rules, and to resist being positioned as subjects in ways they found problematic, outcomes that support Lipsky’s classic premises. Other findings were that the increase of rules, through their complexity and contradiction, promoted ‘rogue’ or rule-bending behaviour. A further outcome was that practitioners who perceived part of their responsibility to be change agents towards societal transformation encountered particular difficulties, because the expansion of rules impacted negatively on the availability of their time and energy.

Background: There is limited evidence for public health policy-makers on the health impacts of urban regeneration programmes. Objectives: To assess whether or not the London 2012 Olympic and Paralympic Games, and related urban regeneration, were associated with an increase in physical activity and mental health and well-being; to assess whether or not any benefits were sustained over time; and to capture the experiences of residents of the Olympic host boroughs. Design: Quasi-experimental prospective cohort study of adolescents and their parents/carers, with a nested qualitative longitudinal study of families. Setting: London boroughs of Newham, Barking and Dagenham, Tower Hamlets and Hackney. Participants: A cohort of 2254 adolescents in 25 schools; a repeat cross-sectional study of parents/carers and a sample of 20 families for the qualitative study. Intervention: The London 2012 Olympic and Paralympic Games, and urban regeneration primarily associated with the redevelopment of the Olympic Park for legacy use. Primary outcome measures: Change in the proportion of respondents meeting physical activity recommendations (using self-reported physical activity); change in the proportion of respondents reporting depression and anxiety and change in well-being score. Main results: At 6 months, adolescents who became inactive were less likely to come from the intervention borough (Newham) than from comparison boroughs [risk ratio (RR) = 0.69, 95% confidence interval (CI) 0.51 to 0.93]. At 18 months, there were no statistically significant differences between intervention and comparison boroughs for all adolescent physical activity and screen-time transitions. Those who visited the Olympic Park more than once a month were the least likely to remain inactive (RR 0.11, 95% CI 0.02 to 0.48) and the least likely to become inactive (RR 0.38, 95% CI 0.24 to 0.60) compared with those who were active at baseline and at the 18-month follow-up. No impacts on parental/carer physical activity were observed. Adolescents who were ‘no longer depressed’ (RR 1.53, 95% CI 1.07 to 2.20) or ‘remained depressed’ (RR 1.78, 95% CI 1.12 to 2.83) at 6 months were more likely to be from the intervention borough. For well-being, there was no association between boroughs and change in well-being between baseline and the 6-month follow-up. At 18 months’ follow-up, adolescents who ‘remained depressed’ (RR 1.93, 95% CI 1.01 to 3.70) were more likely to be from the intervention borough than from comparison boroughs. No associations were observed for well-being at 18 months. There was limited evidence of change for parental mental health and well-being. The qualitative study found that residents generally welcomed the unexpected chance to live in a cleaner, safer and more unified environment. The findings suggested that the Games temporarily alleviated certain stressors in the social and physical environment. Overall, the Games lessened participants’ sense of social exclusion and appeared to generate a sense of inclusion and respite, even if this was only temporary. Study limitations include the potential for adolescents to not be assigned the correct level of exposure to urban regeneration and the effect of reductions in central and local public budgets owing to the UK Government’s deficit reduction programme. Conclusions: This study provided the highest quality data to date on the short- and medium-term social and health impacts of sporting mega-events. We found limited evidence that the London 2012 Olympic and Paralympic Games had a positive effect on adolescent or parental physical activity, mental health or well-being. Funding: The National Institute for Health Research Public Health Research programme.

People with asthma from ethnic minority groups experience significant morbidity. Culturally-specific interventions to reduce asthma morbidity are rare. We tested the hypothesis that a culturally-specific education programme, adapted from promising theory-based interventions developed in the USA, would reduce unscheduled care for South Asians with asthma in the UK.A cluster randomised controlled trial, set in two east London boroughs. 105 of 107 eligible general practices were randomised to usual care or the education programme. Participants were south Asians with asthma aged 3 years and older with recent unscheduled care. The programme had two components: the Physician Asthma Care Education (PACE) programme and the Chronic Disease Self Management Programme (CDSMP), targeted at clinicians and patients with asthma respectively. Both were culturally adapted for south Asians with asthma. Specialist nurses, and primary care teams from intervention practices were trained using the PACE programme. South Asian participants attended an outpatient appointment; those registered with intervention practices received self-management training from PACE-trained specialist nurses, a follow-up appointment with PACE-trained primary care practices, and an invitation to attend the CDSMP. Patients from control practices received usual care. Primary outcome was unscheduled care.375 south Asians with asthma from 84 general practices took part, 183 registered with intervention practices and 192 with control practices. Primary outcome data were available for 358/375 (95.5%) of participants. The intervention had no effect on time to first unscheduled attendance for asthma (Adjusted Hazard Ratio AHR = 1.19 95% CI 0.92 to 1.53). Time to first review in primary care was reduced (AHR = 2.22, (1.67 to 2.95). Asthma-related quality of life and self-efficacy were improved at 3 months (adjusted mean difference -2.56, (-3.89 to -1.24); 0.44, (0.05 to 0.82) respectively.A multi-component education programme adapted for south Asians with asthma did not reduce unscheduled care but did improve follow-up in primary care, self-efficacy and quality of life. More effective interventions are needed for south Asians with asthma.

A variety of nanoscale scaffolds, including virus-like particles (VLPs), are being developed for biomedical applications; however, little information is available about their in vivo behavior. Targeted nanoparticles are particularly valuable as diagnostic and therapeutic carriers because they can increase the signal-to-background ratio of imaging agents, improve the efficacy of drugs, and reduce adverse effects by concentrating the therapeutic molecule in the region of interest. The genome-free capsid of bacteriophage MS2 has several features that make it well-suited for use in delivery applications, such as facile production and modification, the ability to display multiple copies of targeting ligands, and the capacity to deliver large payloads. Anti-EGFR antibodies were conjugated to MS2 capsids to construct nanoparticles targeted toward receptors overexpressed on breast cancer cells. The MS2 agents showed good stability in physiological conditions up to 2 days and specific binding to the targeted receptors in in vitro experiments. Capsids radiolabeled with 64Cu isotopes were injected into mice possessing tumor xenografts, and both positron emission tomography-computed tomography (PET/CT) and scintillation counting of the organs ex vivo were used to determine the localization of the agents. The capsids exhibit surprisingly long circulation times (10-15% ID/g in blood at 24 h) and moderate tumor uptake (2-5% ID/g). However, the targeting antibodies did not lead to increased uptake in vivo despite in vitro enhancements, suggesting that extravasation is a limiting factor for delivery to tumors by these particles.