Brain Re-Irradiation Or Chemotherapy: a phase II randomised trial of re-irradiation and chemotherapy in patients with recurrent glioblastoma (BRIOChe) - protocol for a multi-centre open-label randomised trial.

INTRODUCTION: Glioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM. METHODS AND ANALYSIS: BRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent's three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival. ETHICS AND DISSEMINATION: BRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines. TRIAL REGISTRATION NUMBER: ISRCTN60524.

The thermal breadth of temperate and tropical freshwater insects supports the climate variability hypothesis.

Climate change involves increases in mean temperature and changes in temperature variability at multiple temporal scales but research rarely considers these temporal scales. The climate variability hypothesis (CVH) provides a conceptual framework for exploring the potential effects of annual scale thermal variability across climatic zones. The CVH predicts ectotherms in temperate regions tolerate a wider range of temperatures than those in tropical regions in response to greater annual variability in temperate regions. However, various other aspects of thermal regimes (e.g. diel variability), organisms' size and taxonomic identity are also hypothesised to influence thermal tolerance. Indeed, high temperatures in the tropics have been proposed as constraining organisms' ability to tolerate a wide range of temperatures, implying that high annual maximum temperatures would be associated with tolerating a narrow range of temperatures. We measured thermal regimes and critical thermal limits (CTmax and CTmin) of freshwater insects in the orders Ephemeroptera (mayflies), Plecoptera (stoneflies) and Trichoptera (caddisflies) along elevation gradients in streams in temperate and tropical regions of eastern Australia and tested the CVH by determining which variables were most correlated with thermal breadth (T br = CTmax - CTmin). Consistent with the CVH, T br tended to increase with increasing annual temperature range. T br also increased with body size and T br was generally wider in Plecoptera than in Ephemeroptera or Trichoptera. We also find some support for a related hypothesis, the climate extreme hypothesis (CEH), particularly for predicting upper thermal limits. We found no evidence that higher annual maximum temperature constrained individuals' abilities to tolerate a wide range of temperatures. The support for the CVH we document suggests that temperate organisms may be able to tolerate wider ranges of temperatures than tropical organisms. There is an urgent need to investigate other aspects of thermal regimes, such as diel temperature cycling and minimum temperature.

Unravelling the mystery of endemic versus translocated populations of the endangered Australian lungfish (Neoceratodus forsteri).

The Australian lungfish is a primitive and endangered representative of the subclass Dipnoi. The distribution of this species is limited to south-east Queensland, with some populations considered endemic and others possibly descending from translocations in the late nineteenth century shortly after European discovery. Attempts to resolve the historical distribution of this species have met with conflicting results based on descriptive genetic studies. Understanding if all populations are endemic or some are the result of, or influenced by, translocation events, has implications for conservation management. In this work, we analysed the genetic variation at three types of markers (mtDNA genomes, 11 STRs and 5196 nuclear SNPs) using the approximate Bayesian computation (ABC) algorithm to compare several demographic models. We postulated different contributions of Mary River and Burnett River gene pools into the Brisbane River and North Pine River populations, related to documented translocation events. We ran the analysis for each marker type separately, and we also estimated the posterior probabilities of the models combining the markers. Nuclear SNPs have the highest power to correctly identify the true model among the simulated datasets (where the model was known), but different marker types typically provided similar answers. The most supported demographic model able to explain the real dataset implies that an endemic gene pool is still present in the Brisbane and North Pine Rivers and coexists with the gene pools derived from past documented translocation events. These results support the view that ABC modelling can be useful to reconstruct complex historical translocation events with contemporary implications, and will inform ongoing conservation efforts for the endangered and iconic Australian lungfish.

Relaxation of Natural Selection in the Evolution of the Giant Lungfish Genomes.

Nonadaptive hypotheses on the evolution of eukaryotic genome size predict an expansion when the process of purifying selection becomes weak. Accordingly, species with huge genomes, such as lungfish, are expected to show a genome-wide relaxation signature of selection compared with other organisms. However, few studies have empirically tested this prediction using genomic data in a comparative framework. Here, we show that 1) the newly assembled transcriptome of the Australian lungfish, Neoceratodus forsteri, is characterized by an excess of pervasive transcription, or transcriptional leakage, possibly due to suboptimal transcriptional control, and 2) a significant relaxation signature in coding genes in lungfish species compared with other vertebrates. Based on these observations, we propose that the largest known animal genomes evolved in a nearly neutral scenario where genome expansion is less efficiently constrained.

Patients' experiences of engaging with electronic Patient Reported Outcome Measures (PROMs) after the completion of radiation therapy for breast cancer: a pilot service evaluation.

INTRODUCTION: Over 60 % of people who develop breast cancer will receive radiation therapy (RT) as part of their treatment. Side effects of RT may include inflammation, erythema, desquamation and fatigue. Electronic Patient Reported Outcomes Measures (ePROMs) enable patients to report side effects prior to their scheduled post-RT appointment. This pilot service evaluation aims to explore patients' perceptions regarding the value of the ePROM system, ease of its use and barriers to using the system, after breast irradiation. METHODS: From July-November 2021, evaluation surveys were posted to 100 people who had received RT to their breast to explore their experience of using the ePROM. Ethical approval was obtained through Ulster University and the Western Health and Social Care Trust (WHSCT), Northern Ireland. RESULTS: Fifty-two people responded to the survey, of which 27 respondents indicated that they had accessed the ePROM. Despite few participants experiencing significant side effects, the majority of participants recommended the ePROM indicating that it was an important source of support. Those who experienced significant side effects found the system to be prompt and effective. Barriers to accessing the ePROM included technical issues with the link, concerns about confidentiality and forgetting to access the link. Access to the ePROM increased with higher education levels. CONCLUSIONS: This pilot service evaluation demonstrated that ePROMs are valued by patients and can provide rapid real-time access to support, offering individual care and reassurance. For patients with longer RT schedules (>10 fractions), the introduction of ePROMs during RT was viewed favourably by participants. All patients may benefit from the option of receiving ePROMs post-RT.

A community engagement training program for basic and translational cancer researchers.

PURPOSE: There is an increasing awareness of the importance of patient engagement in cancer research, but many basic and translational researchers have never been trained to do so. To address this unmet need, a 1-year patient engagement training program for researchers was developed. METHODS: Eleven researchers and eleven paired research advocates participated. This program, designed for virtual delivery, included 3 didactic modules focused on (1) Community Outreach and Engagement principles and methods, (2) Communication skills, and (3) Team Science. This was followed by longitudinal projects to be completed by the researcher/advocate pairs, including learning about the research project, and co-authoring abstracts, manuscripts and grant proposals. Monthly group meetings allowed pairs to share their experiences. The program culminated in the pairs creating and presenting oral abstracts for the University of Kansas Cancer Center's Annual Research Symposium. RESULTS: All participants indicated that the modules had a positive impact on their ability to collaborate in research. Both researcher self-evaluations and patient advocate evaluations of their researcher partner showed an improvement in researcher communication competency. Results from the Patient Engagement in Research Scale showed that advocates were highly engaged. Within 1 year after program completion, participating pairs have completed four abstracts and 9 grant proposals. CONCLUSION: The program will be modified based on participant feedback, and can be adapted for future cohorts if an increased number of sessions per month and shortened program duration are desired. The program's virtual format allows scalability across institutions to potentially benefit large cohorts of researchers.

Views on minimum unit pricing for alcohol before its introduction among people with alcohol dependence in Scotland: A qualitative interview study.

INTRODUCTION: Scotland implemented a minimum price per unit of alcohol (MUP) of £0.50 in May 2018 (1 UK unit = 10 mL/8 g ethanol). Some stakeholders expressed concerns about the policy having potential negative consequences for people with alcohol dependence. This study aimed to investigate anticipated impacts of MUP on people presenting to alcohol treatment services in Scotland before policy implementation. METHODS: Qualitative interviews were conducted with 21 people with alcohol dependence accessing alcohol treatment services in Scotland between November 2017 and April 2018. Interviews examined respondents' current and anticipated patterns of drinking and spending, effects on their personal life, and their views on potential policy impact. Interview data were thematically analysed using a constant comparison method. RESULTS: Three key themes were identified: (i) strategies used to manage the cost of alcohol and anticipated responses to MUP; (ii) broader effects of MUP; and (iii) awareness and preparedness for MUP. Respondents expected to be impacted by MUP, particularly those on low incomes and those with more severe dependence symptoms. They anticipated using familiar strategies including borrowing and reprioritising spending to keep alcohol affordable. Some respondents anticipated negative consequences. Respondents were sceptical about the short-term benefits of MUP for current drinkers but felt it might prevent harm for future generations. Respondents had concerns about the capacity of treatment services to meet support needs. DISCUSSION AND CONCLUSIONS: People with alcohol dependence identified immediate concerns alongside potential long-term benefits of MUP before its introduction. They also had concerns over the preparedness of service providers.

Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway.

The complement alternative pathway (AP) is implicated in numerous diseases affecting many organs, ranging from the rare hematological disease paroxysmal nocturnal hemoglobinuria (PNH), to the common blinding disease age-related macular degeneration (AMD). Critically, the AP amplifies any activating trigger driving a downstream inflammatory response; thus, components of the pathway have become targets for drugs of varying modality. Recent validation from clinical trials using drug modalities such as inhibitory antibodies has paved the path for gene targeting of the AP or downstream effectors. Gene targeting in the complement field currently focuses on supplementation or suppression of complement regulators in AMD and PNH, largely because the eye and liver are highly amenable to drug delivery through local (eye) or systemic (liver) routes. Targeting the liver could facilitate treatment of numerous diseases as this organ generates most of the systemic complement pool. This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA-targeting therapeutics ALN-CC5, ARO-C3, and IONIS-FB-LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years.

Acute, diel, and annual temperature variability and the thermal biology of ectotherms.

Global warming is increasing mean temperatures and altering temperature variability at multiple temporal scales. To better understand the consequences of changes in thermal variability for ectotherms it is necessary to consider thermal variation at different time scales (i.e., acute, diel, and annual) and the responses of organisms within and across generations. Thermodynamics constrain acute responses to temperature, but within these constraints and over longer time periods, organisms have the scope to adaptively acclimate or evolve. Yet, hypotheses and predictions about responses to future warming tend not to explicitly consider the temporal scale at which temperature varies. Here, focusing on multicellular ectothermic animals, we argue that consideration of multiple processes and constraints associated with various timescales is necessary to better understand how altered thermal variability because of climate change will affect ectotherms.

Cancer, Fertility and Me: Developing and Testing a Novel Fertility Preservation Patient Decision Aid to Support Women at Risk of Losing Their Fertility Because of Cancer Treatment.

Background: Women with a new cancer diagnosis face complex decisions about interventions aiming to preserve their fertility. Decision aids are more effective in supporting decision making than traditional information provision. We describe the development and field testing of a novel patient decision aid designed to support women to make fertility preservation treatment decisions around cancer diagnosis. Methods: A prospective, mixed-method, three stage study involving: 1) co-development of the resource in collaboration with a multi-disciplinary group of key stakeholders including oncology and fertility healthcare professionals and patient partners (n=24), 2) alpha testing with a group of cancer patients who had faced a fertility preservation treatment decision in the past (n=11), and oncology and fertility healthcare professionals and stakeholders (n=14) and, 3) beta testing with women in routine care who had received a recent diagnosis of cancer and were facing a fertility preservation treatment decision (n=41) and their oncology and fertility healthcare professionals (n=3). Ten service users recruited from a closed Breast Cancer Now Facebook group and the support group Cancer and Fertility UK also provided feedback on CFM via an online survey. Results: A 60-page paper prototype of the Cancer, Fertility and Me patient decision aid was initially developed. Alpha testing of the resource found that overall, it was acceptable to cancer patients, healthcare professionals and key stakeholders and it was considered a useful resource to support fertility preservation treatment decision-making. However, the healthcare professionals felt that the length of the patient decision aid, and elements of its content may be a barrier to its use. Subsequently, the prototype was reduced to 40 pages. During beta testing of the shortened version in routine care, women who received the resource described its positive impact on their ability to make fertility preservation decisions and support them at a stressful time. However, practical difficulties emerged which impacted upon its wider dissemination in clinical practice and limited some elements of the evaluation planned. Discussion: Women receiving the decision aid within the cancer treatment pathway found it helped them engage with decisions about fertility preservation, and make better informed, values-based care plans with oncology and fertility teams. More work is needed to address access and implementation of this resource as part of routine oncology care pathways.

Dementia Early-Stage Cognitive Aids New Trial (DESCANT) of memory aids and guidance for people with dementia: randomised controlled trial.

BACKGROUND: Common memory aids for people with dementia at home are recommended. However, rigorous evaluation is lacking, particularly what guidance or support is valued. OBJECTIVE: To investigate effects of memory aids and guidance by dementia support practitioners (DSPs) for people in early-stage dementia through a pragmatic, randomised controlled trial. METHODS: Of 469 people with mild-to-moderate dementia and their informal carers, 468 were randomised to a DSP with memory aids or to usual care plus existing dementia guide. Allocation was stratified by Trust/Health Board; time since first attendance at memory service; gender; age; and living with primary carer or not. Primary outcome was Bristol Activities of Daily Living Scale (BADLS) Score at 3 and 6 months (primary end-point). Secondary outcomes for people with dementia: quality of life (CASP-19; DEMQOL); cognition and functioning (Clinical Dementia Rating Scale; S-MMSE); capability (ICECAP-O); social networks (LSNS-R); and instrumental daily living activities (R-IDDD). Secondary outcomes for carers: psychological health (GHQ-12); sense of competence (SSCQ). RESULTS: DSPs were successfully trained, compliance was good and welcomed by participants. Mean 6 months BADLS Score increased to 14.6 (SD: 10.4) in intervention and 12.6 (SD: 8.1) in comparator, indicative of greater dependence in the activities of daily living. Adjusted between-group difference was 0.38 (95% CI: -0.89 to 1.65, p=0.56). Though this suggests greater dependency in the intervention group the difference was not significant. No differences were found in secondary outcomes. CONCLUSIONS: This intervention did not maintain independence in the activities of daily living with no improvement in other outcomes for people with dementia or carers. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN12591717.

Home-care providers as collaborators in commissioning arrangements for older people.

In England, care to support people living at home is largely commissioned by local authorities (statutory organisations with responsibility for social care in specific localities) from non-statutory home-care providers (for-profit, not-for-profit, voluntary). This paper explores how managers of these services perceive commissioning arrangements and their impact on home-care providers, the care workforce and service users. Little formal research of providers' experiences of working with local authorities in a commissioning model is available. A qualitative study employed semi-structured telephone interviews with 20 managers of for-profit home-care providers from 10 selected local authority areas in England. Data were analysed using thematic analysis to identify main and subsidiary themes. Home-care providers reported operating in a complex and changeable partnership with commissioners, characterised by: (a) relationships ranging from transactional to collaborative, (b) providers expressing a strong sense of public service motivation, (c) commissioning practices that were complex to negotiate, time-consuming and overly prescriptive, (d) frequent changes in commissioning practices and a perceived lack of strategic planning, which were reported as contributing to uncertainty and tension for providers and confusion for service users. Attempting to operate a market model with tightly prescribed contracts is likely to be unsustainable. An alternative approach based on a collaborative model of joint responsibility for providing home care is recommended drawing on a conceptual framework of principal-steward relationships in contracting.

Implementing the Dementia Early Stage Cognitive Aids New Trial (DESCANT) intervention: mixed-method process evaluation alongside a pragmatic randomised trial.

OBJECTIVES: The DESCANT (Dementia Early Stage Cognitive Aids New Trial) intervention provided a personalised care package designed to improve the cognitive abilities, function and well-being of people with early-stage dementia and their carers, by providing a range of memory aids, together with appropriate training and support. This sub-study aimed to assess implementation and identify contextual factors potentially associated with participant outcomes. METHOD: A mixed-methods approach was adopted alongside the pragmatic randomised trial. Data were obtained from intervention records and interviews with five dementia support practitioners across seven National Health Service Trusts in England and Wales. A reporting framework was constructed from available literature and data assessed by descriptive statistics and thematic analysis. RESULTS: Participation and engagement was high with 126 out of 128 participants completing the intervention with packages tailored to individual participants. Misplacing items and poor orientation to date and time were common areas of need. Memory aids frequently supplied included orientation clocks (91%), whiteboards (60%), calendars (43%) and notebooks (32%), plus bespoke items. Intervention duration and timing were broadly consistent with expectations. Variation reflected participants' needs, circumstances and preferences. Qualitative findings suggested a potentially positive impact on the well-being of people with dementia and their carers. Issues associated with successful roll-out of the intervention are explored in the discussion. CONCLUSION: Successful implementation increased confidence in future findings of the randomised trial. Depending on these, DESCANT may prove a scalable intervention with potential to improve the function and quality of life of people with dementia and their carers.

Hospital admissions and place of death of residents of care homes receiving specialist healthcare services: A systematic review without meta-analysis.

AIM: To synthesize evidence on the ability of specialist care home support services to prevent hospital admission of older care home residents, including at end of life. DESIGN: Systematic review, without meta-analysis, with vote counting based on direction of effect. DATA SOURCES: Fourteen electronic databases were searched from January 2010 to January 2019. Reference lists of identified reviews, study protocols and included documents were scrutinized for further studies. REVIEW METHODS: Papers on the provision of specialist care home support that addressed older, long-term care home residents' physical health needs and provided comparative data on hospital admissions were included. Two reviewers undertook study selection and quality appraisal independently. Vote counting by direction of effect and binomial tests determined service effectiveness. RESULTS: Electronic searches identified 79 relevant references. Combined with 19 citations from an earlier review, this gave 98 individual references relating to 92 studies. Most were from the UK (22), USA (22) and Australia (19). Twenty studies were randomized controlled trials and six clinical controlled trials. The review suggested interventions addressing residents' general health needs (p < .001), assessment and management services (p < .0001) and non-training initiatives involving medical staff (p < .0001) can reduce hospital admissions, while there was also promising evidence for services targeting residents at imminent risk of hospital entry or post-hospital discharge and training-only initiatives. End-of-life care services may enable residents to remain in the home at end of life (p < .001), but the high number of weak-rated studies undermined confidence in this result. CONCLUSION: This review suggests specialist care home support services can reduce hospital admissions. More robust studies of services for residents at end of life are urgently needed. IMPACT: The review addressed the policy imperative to reduce the avoidable hospital admission of older care home residents and provides important evidence to inform service design. The findings are of relevance to commissioners, providers and residents.

Novel Selection Approaches to Identify Antibodies Targeting Neoepitopes on the C5b6 Intermediate Complex to Inhibit Membrane Attack Complex Formation.

The terminal pathway of complement is implicated in the pathology of multiple diseases and its inhibition is, therefore, an attractive therapeutic proposition. The practicalities of inhibiting this pathway, however, are challenging, as highlighted by the very few molecules in the clinic. The proteins are highly abundant, and assembly is mediated by high-affinity protein-protein interactions. One strategy is to target neoepitopes that are present transiently and only exist on active or intermediate complexes but not on the abundant native proteins. Here, we describe an antibody discovery campaign that generated neoepitope-specific mAbs against the C5b6 complex, a stable intermediate complex in terminal complement complex assembly. We used a highly diverse yeast-based antibody library of fully human IgGs to screen against soluble C5b6 antigen and successfully identified C5b6 neoepitope-specific antibodies. These antibodies were diverse, showed good binding to C5b6, and inhibited membrane attack complex (MAC) formation in a solution-based assay. However, when tested in a more physiologically relevant membrane-based assay these antibodies failed to inhibit MAC formation. Our data highlight the feasibility of identifying neoepitope binding mAbs, but also the technical challenges associated with the identification of functionally relevant, neoepitope-specific inhibitors of the terminal pathway.

Clinical Performance Status and Technical Factors Affecting Outcomes from Percutaneous Transhepatic Biliary Interventions; A Multicentre, Prospective, Observational Cohort Study.

PURPOSE: The purpose of this study was to evaluate the predictive value of a 'Modified Karnofsky Scoring System' on outcomes and provide real-world data regarding the UK practice of biliary interventions. MATERIALS AND METHODS: A prospective multi-centred cohort study was performed. The pre-procedure modified Karnofsky score, the incidence of sepsis, complications, biochemical improvement and mortality were recorded out to 30 days post procedure. RESULTS: A total of 292 patients (248 with malignant lesions) were suitable for inclusion in the study. The overall 7 and 30 day mortality was 3.1% and 16.1%, respectively. The 30 day sepsis rate was 10.3%. In the modified Karnofsky 'high risk' group the 7 day mortality was 9.7% versus 0% for the 'low risk' group (p = 0.002), whereas the 30 day mortality was 28.8% versus 13.3% (p = 0.003). The incidence of sepsis at 30 days was 19% in the high risk group versus 3.3% at the low risk group (p = 0.001) CONCLUSION: Percutaneous biliary interventions in the UK are safe and effective. Scoring systems such as the Karnofsky or the modified Karnofsky score hold promise in allowing us to identify high risk groups that will need more careful consideration and enhanced patient informed consent but further research with larger studies is warranted in order to identify their true impact on patient selection and outcomes post biliary interventions.

Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells.

Dry age-related macular degeneration (AMD) is characterised by loss of central vision and currently has no approved medical treatment. Dysregulation of the complement system is thought to play an important role in disease pathology and supplementation of Complement Factor I (CFI), a key regulator of the complement system, has the potential to provide a treatment option for AMD. In this study, we demonstrate the generation of AAV constructs carrying the human CFI sequence and expression of CFI in cell lines and in the retina of C57BL/6 J mice. Four codon optimised constructs were compared to the most common human CFI sequence. All constructs expressed CFI protein; however, most codon optimised sequences resulted in significantly reduced CFI secretion compared to the non-optimised CFI sequence. In vivo expression analysis showed that CFI was predominantly expressed in the RPE and photoreceptors. Secreted protein in vitreous humour was demonstrated to be functionally active. The findings presented here have led to the formulation of an AAV-vectored gene therapy product currently being tested in a first-in-human clinical trial in subjects with geographic atrophy secondary to dry AMD (NCT03846193).

The Dementia Early Stage Cognitive Aids New Trial (DESCANT) intervention: A goal attainment scaling approach to promote self-management.

OBJECTIVES: This study investigated goals identified by people with dementia and their carers to promote the self-management of symptoms and abilities; measured achievement using goal attainment scaling (GAS); and explored the reflections of Dementia Support Practitioners (DSPs) facilitating it. METHODS AND DESIGN: Within this pragmatic randomised trial, DSPs gave memory aids, training and support to people with mild to moderate dementia and their carers at home. Data were collected across seven NHS Trusts in England and Wales (2016-2018) and abstracted from intervention records and semi-structured interviews with DSPs delivering the intervention, supplemented by a subset of the trial dataset. Measures were created to permit quantification and descriptive analysis and interview data thematically analysed. A GAS measure for this intervention in this client group was derived. RESULTS: Engagement was high across the 117 participants and 293 goals were identified. These reflected individual circumstances and needs and enabled classification and assessment of their attainment. Seventeen goal types were identified across six domains: self-care, household tasks, daily occupation, orientation, communication, and well-being and safety. On average participants achieved nominally significant improvement regarding the specified goals of 1.4 with standard deviation of 0.6. Five interviews suggested that DSPs' experiences of goal setting were also positive. CONCLUSIONS: GAS is useful for assessing psychosocial interventions for people with early-stage dementia. It has a utility in identifying goals, promoting self-management and providing a personalised outcome measure. There is a strong case for exploring whether these clear benefits translate to other interventions in other populations in other places.

Complex care needs and devolution in Greater Manchester: a pilot study to explore social care innovation in newly integrated service arrangements for older people.

Objective The aim of this study was to describe emergent approaches to integrated care for older people with complex care needs and investigate the viability of measuring integrated care. Methods A case study approach was used. Sites were recruited following discussion with senior staff in health and social care agencies. Service arrangements were categorised using a framework developed by the researchers. To investigate joint working within the sites, the development model for integrated care was adapted and administered to the manager of each service. Data were collected in 2018. Results Six case study sites were recruited illustrating adult social care services partnerships in services for older people with home care providers, mental health and community nursing services. Most were established in 2018. Service arrangements were characterised by joint assessment and informal face-to-face discussions between staff. The development of an infrastructure to promote partnership working was evident between adult social care and each of the other services and most developed with home care providers. There was little evidence of a sequential approach to the development of integrated working practices. Conclusion Components of partnerships promoting integrated care have been highlighted and understanding of the complexity of measuring integrated care enhanced. Means of information sharing and work force development require further consideration. What is known about the topic? The devolution of health and social care arrangements in Greater Manchester has aroused considerable interest in much wider arenas. Necessarily much of the focus in available material has been upon strategic development, analysis of broader trends and mechanisms and a concern with changes in the healthcare system. What does this paper add? The findings from this study will enable emerging approaches to be described and codified, and permit the specific social care contribution to the new arrangements to be discerned. The findings are relevant beyond the immediate context of Greater Manchester to wider integrated care. The evidence can be used by commissioners and services, providing a sound basis for further work as service systems develop. What are the implications for practitioners? This research is important because it is one of the first pieces of work to examine the new integrated care arrangements in Greater Manchester. By providing guidance to promote evidence-based practice, this study contributes to service development in Greater Manchester and the achievement of the broad national service objectives of improving user and carer experiences and ensuring value for money.

Protocol for Take-home naloxone In Multicentre Emergency (TIME) settings: feasibility study.

BACKGROUND: Opioids, such as heroin, kill more people worldwide by overdose than any other type of drug, and death rates associated with opioid poisoning in the UK are at record levels (World Drug Report 2018 [Internet]. [cited 2019 Nov 19]. Available from: http://www.unodc.org/wdr2018/; Deaths related to drug poisoning in England and Wales - Office for National Statistics [Internet]. [cited 2019 Nov 19]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2018registrations). Naloxone is an opioid antagonist which can be distributed in 'kits' for administration by witnesses in an overdose emergency. This intervention is known as take-home naloxone (THN). We know that THN can save lives on an individual level, but there is currently limited evidence about the effectiveness of THN distribution on an aggregate level, in specialist drug service settings or in emergency service settings. Notably, we do not know whether THN kits reduce deaths from opioid overdose in at-risk populations, if there are unforeseen harms associated with THN distribution or if THN is cost-effective. In order to address this research gap, we aim to determine the feasibility of a fully powered cluster randomised controlled trial (RCT) of THN distribution in emergency settings. METHODS: We will carry out a feasibility study for a RCT of THN distributed in emergency settings at four sites, clustered by Emergency Department (ED) and catchment area within its associated ambulance service. THN is a peer-administered intervention. At two intervention sites, emergency ambulance paramedics and ED clinical staff will distribute THN to adult patients who are at risk of opioid overdose. At two control sites, practice will carry on as usual. We will develop a method of identifying a population to include in an evaluation, comprising people at risk of fatal opioid overdose, who may potentially receive naloxone included in a THN kit.We will gather anonymised outcomes up to 1 year following a 12-month 'live' trial period for patients at risk of death from opioid poisoning. We expect approximately 100 patients at risk of opioid overdose to be in contact with each service during the 1-year recruitment period. Our outcomes will include deaths, emergency admissions, intensive care admissions, and ED attendances. We will collect numbers of eligible patients attended by participating in emergency ambulance paramedics and attending ED, THN kits issued, and NHS resource usage. We will determine whether to progress to a fully powered trial based on pre-specified progression criteria: sign-up of sites (n = 4), staff trained (≥ 50%), eligible participants identified (≥ 50%), THN provided to eligible participants (≥ 50%), people at risk of death from opioid overdose identified for inclusion in follow-up (≥ 75% of overdose deaths), outcomes retrieved for high-risk individuals (≥ 75%), and adverse event rate (< 10% difference between study arms). DISCUSSION: This feasibility study is the first randomised, methodologically robust investigation of THN distribution in emergency settings. The study addresses an evidence gap related to the effectiveness of THN distribution in emergency settings. As this study is being carried out in emergency settings, obtaining informed consent on behalf of participants is not feasible. We therefore employ novel methods for identifying participants and capturing follow-up data, with effectiveness dependent on the quality of the available routine data. TRIAL REGISTRATION: ISRCTN13232859 (Registered 16/02/2018).