7 research outputs found

    Periscope Proteins are variable length regulators of bacterial cell surface interactions

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    Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system

    Collaborative action for person-centred coordinated care (P3C): an approach to support the development of a comprehensive system-wide solution to fragmented care

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    This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Fragmented care results in poor outcomes for individuals with complexity of need. Person-centred coordinated care (P3C) is perceived to be a potential solution, but an absence of accessible evidence and the lack of a scalable 'blue print' mean that services are 'experimenting' with new models of care with little guidance and support. This paper presents an approach to the implementation of P3C using collaborative action, providing examples of early developments across this programme of work, the core aim of which is to accelerate the spread and adoption of P3C in United Kingdom primary care settings. METHODS: Two centrally funded United Kingdom organisations (South West Collaboration for Leadership in Applied Health Research and Care and South West Academic Health Science Network) are leading this initiative to narrow the gap between research and practice in this urgent area of improvement through a programme of service change, evaluation and research. Multi-stakeholder engagement and co-design are core to the approach. A whole system measurement framework combines outcomes of importance to patients, practitioners and health organisations. Iterative and multi-level feedback helps to shape service change while collecting practice-based data to generate implementation knowledge for the delivery of P3C. The role of the research team is proving vital to support informed change and challenge organisational practice. The bidirectional flow of knowledge and evidence relies on the transitional positioning of researchers and research organisations. RESULTS: Extensive engagement and embedded researchers have led to strong collaborations across the region. Practice is beginning to show signs of change and data flow and exchange is taking place. However, working in this way is not without its challenges; progress has been slow in the development of a linked data set to allow us to assess impact innovations from a cost perspective. Trust is vital, takes time to establish and is dependent on the exchange of services and interactions. If collaborative action can foster P3C it will require sustained commitment from both research and practice. This approach is a radical departure from how policy, research and practice traditionally work, but one that we argue is now necessary to deal with the most complex health and social problems.This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. TS’s current post at the University of Oxford is funded by the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford Health NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. This research was also funded by the South West Academic health Science Network (AHSN). The views expressed are those of the authors and not necessarily those of the AHSN.The NIHR CLAHRC Programme fund the substantive posts of HML, RB, NB, HW, TPS and MP as members of the South West Peninsula CLARHC. All other co-authors are members of the wider collaboration and are substantially employed by their respective organisations

    The Rehabilitation Effectiveness for Activities for Life (REAL) study: a national programme of research into NHS inpatient mental health rehabilitation services across England

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    Background: The REAL (Rehabilitation Effectiveness for Activities for Life) research programme, funded by the National Institute for Heath Research (NIHR) from 2009 to 2015, investigated NHS mental health rehabiliation services across England. The users of these services are people with longer-term, complex mental health problems, such as schizophrenia, who have additional problems that complicate recovery. Although only around 10% of people with severe mental illness require inpatient rehabilitation, because of the severity and complexity of their problems they cost 25–50% of the total mental health budget. Despite this, there has been little research to help clinicians and commissioners to plan and deliver effective treatments and services. This research aimed to address this gap. Methods: The programme had four phases. (1) A national survey, using quantitative and qualitative methods, was used to provide a detailed understanding of the scope and quality of NHS mental health rehabilitation services in England and the characteristics of those who use them. (2) We developed a training intervention for staff of NHS inpatient mental health rehabilitation units to facilitate service users’ activities. (3) The clinical effectiveness and cost-effectiveness of the staff training programme was evaluated through a cluster randomised controlled trial involving 40 units that scored below average on our quality assessment tool in the national survey. A qualitative process evaluation and a realistic evaluation were carried out to inform our findings further. (4) A naturalistic cohort study was carried out involving 349 service users of 50 units that scored above average on our quality assessment tool in the national survey, who were followed up over 12 months. Factors associated with better clinical outcomes were investigated through exploratory analyses. Results: Most NHS trusts provided inpatient mental health rehabilitation services. The quality of care provided was higher than that in similar facilities across Europe and was positively associated with service users’ autonomy. Our cluster trial did not find our staff training intervention to be clinically effective [coefficient 1.44, 95% confidence interval (CI) –1.35 to 4.24]; staff appeared to revert to previous practices once the training team left the unit. Our realistic review suggested that greater supervision and senior staff support could help to address this. Over half of the service users in our cohort study were successfully discharged from hospital over 12 months. Factors associated with this were service users’ activity levels [odds ratio (OR) 1.03, 95% CI 1.01 to 1.05] and social skills (OR 1.13, 95% CI 1.04 to 1.24), and the ‘recovery’ orientation of the unit (OR 1.04, 95% CI 1.00 to 1.08), which includes collaborative care planning with service users and holding hope for their progress. Quality of care was not associated with costs of care. A relatively small investment (£67 per service user per month) was required to achieve the improvement in everyday functioning that we found in our cohort study. Conclusions: People who require inpatient mental health rehabilitation are a ‘low-volume, high-needs’ group. Despite this, these services are able to successfully discharge most to the community within 18 months. Our results suggest that this may be facilitated by recovery-orientated practice that promotes service users’ activities and social skills. Further research is needed to identify effective interventions that enhance such practice to deliver these outcomes. Our research provides evidence that NHS inpatient mental health rehabilitation services deliver high-quality care that successfully supports service users with complex needs in their recovery. Main limitation: Our programme included only NHS, non-secure, inpatient mental health rehabilitation services. Trial registration: Current Controlled Trials ISRCTN25898179. Funding: The NIHR Programme Grants for Applied Research programme

    Assertive Community Treatment for People With Alcohol Dependence: A Pilot Randomized Controlled Trial

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    Aims: A pilot randomized controlled trial (RCT) to assess the feasibility and potential efficacy of assertive community treatment (ACT) in adults with alcohol dependence. Methods: Single blind, individually randomized, pilot RCT of 12 months of ACT plus treatment as usual (TAU) versus TAU alone in adults (age 18+ years) with alcohol dependence and a history of previous unsuccessful alcohol treatment attending specialist community alcohol treatment services. ACT aimed to actively engage participants for 12 months with assertive, regular, minimum weekly contact. ACT was combined with TAU. TAU comprised access to the full range of services provided by the community teams. Primary outcome is mean drinks per drinking day and percent days abstinent at 12 months follow up. Analysis of covariance was conducted using 80% confidence intervals, appropriate in the context of a pilot trial. Results: A total of 94 participants were randomized, 45 in ACT and 49 in TAU. Follow-up was achieved with 98 and 88%, respectively at 12 months. Those in ACT had better treatment engagement, and were more often seen in their homes or local community than TAU participants. At 12 months the ACT group had more problems related to drinking and lower quality of life than TAU but no differences in drinking measures. The ACT group had a higher percentage of days abstinent but lower quality of life at 6 months. The ACT group had less unplanned healthcare use than TAU. Conclusions: An trial of ACT was feasible to implement in an alcohol dependent treatment population. Trial registration: ISRCTN2277553

    Study protocol: a mixed methods study to assess mental health recovery, shared decision-making and quality of life (Plan4Recovery)

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    BACKGROUND: Recovery in mental health care is complex, highly individual and can be facilitated by a range of professional and non-professional support. In this study we will examine how recovery from mental health problems is promoted in non-medical settings. We hypothesise a relationship between involvement in decisions about care, social support and recovery and quality of life outcomes. METHODS: We will use standardised validated instruments of involvement in decision-making, social contacts, recovery and quality of life with a random sample of people accessing non-statutory mental health social care services in Wales. We will add to this important information with detailed one to one case study interviews with people, their family members and their support workers. We will use a series of these interviews to examine how people build recovery over time to help us understand more about their involvement in decisions and the social links they build. DISCUSSION: We want to see how being involved in decisions about care and the social links people have are related to recovery and quality of life for people with experience of using mental health support services. We want to understand the different perspectives of the people involved in making recovery possible. We will use this information to guide further studies of particular types of social interventions and their use in helping recovery from mental health problems

    Assertive Community Treatment for alcohol dependence (ACTAD): study protocol for a randomised controlled trial

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    Background Alcohol dependence is a significant and costly problem in the UK yet only 6% of people a year receive treatment. Current service provision based on the treatment of acute episodes of illness and emphasising personal choice and motivation results in a small proportion of these patients engaging with alcohol treatment. There is a need for interventions targeted at the population of alcohol dependent patients who are hard to engage in conventional treatment. Assertive Community Treatment (ACT), a model of care based on assertive outreach, has been used for treating patients with severe mental illnesses and presents a promising avenue for engaging patients with primary alcohol dependence. So far there has been little research on this. Methods/Design In this single blind exploratory randomised controlled trial, a total of 90 alcohol dependent participants will be recruited from community addiction services. After completing a baseline assessment, they will be assigned to one of two conditions: (1) ACT plus care as usual, or (2) care as usual. Those allocated to the ACT plus care as usual will receive the same treatment that is routinely provided by services, plus a trained key worker who will provide ACT. ACT comprises intensive and assertive contact at least once a week, over 50% of contacts in the participant's home or local community, and comprehensive case management across social and health care, for a period of one year. All participants will be followed up at 6 months and 12 months to assess outcome post randomisation. The primary outcome measures will be alcohol consumption: mean drinks per drinking day and percentage of days abstinent measured by the Time Line Follow Back interview. Secondary outcome measures will include severity of alcohol dependence, alcohol related problems, motivation to change, social network involvement, quality of life, therapeutic relationship and service use. Other outcome variables are treatment engagement including completion of assessment, detoxification and aftercare. Discussion Results of this trial will help clarify the potential beneficial effects of ACT for people with alcohol dependence and provide information to design a definitive trial