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BACKGROUND: Online forums are widely used for mental health peer support. However, evidence of their safety and effectiveness is mixed. Further research focused on articulating the contexts in which positive and negative impacts emerge from forum use is required to inform innovations in implementation. OBJECTIVE: This study aimed to develop a realist program theory to explain the impacts of online mental health peer support forums on users. METHODS: We conducted a realist synthesis of literature published between 2019 and 2023 and 18 stakeholder interviews with forum staff. RESULTS: Synthesis of 102 evidence sources and 18 interviews produced an overarching program theory comprising 22 context-mechanism-outcome configurations. Findings indicate that users' perceptions of psychological safety and the personal relevance of forum content are foundational to ongoing engagement. Safe and active forums that provide convenient access to information and advice can lead to improvements in mental health self-efficacy. Within the context of welcoming and nonjudgmental communities, users may benefit from the opportunity to explore personal difficulties with peers, experience reduced isolation and normalization of mental health experiences, and engage in mutual encouragement. The program theory highlights the vital role of moderators in creating facilitative online spaces, stimulating community engagement, and limiting access to distressing content. A key challenge for organizations that host mental health forums lies in balancing forum openness and anonymity with the need to enforce rules, such as restrictions on what users can discuss, to promote community safety. CONCLUSIONS: This is the first realist synthesis of online mental health peer support forums. The novel program theory highlights how successful implementation depends on establishing protocols for enhancing safety and strategies for maintaining user engagement to promote forum sustainability. TRIAL REGISTRATION: PRO

Introduction Peer online mental health forums are commonly used and offer accessible support. Positive and negative impacts have been reported by forum members and moderators, but it is unclear why these impacts occur, for whom and in which forums. This multiple method realist study explores underlying mechanisms to understand how forums work for different people. The findings will inform codesign of best practice guidance and policy tools to enhance the uptake and effectiveness of peer online mental health forums. Methods and analysis In workstream 1, we will conduct a realist synthesis, based on existing literature and interviews with approximately 20 stakeholders, to generate initial programme theories about the impacts of forums on members and moderators and mechanisms driving these. Initial theories that are relevant for forum design and implementation will be prioritised for testing in workstream 2. Workstream 2 is a multiple case study design with mixed methods with several online mental health forums differing in contextual features. Quantitative surveys of forum members, qualitative interviews and Corpus-based Discourse Analysis and Natural Language Processing of forum posts will be used to test and refine programme theories. Final programme theories will be developed through novel triangulation of the data. Workstream 3 will run alongside workstreams 1 and 2. Key stakeholders from participating forums, including members and moderators, will be recruited to a Codesign group. They will inform the study design and materials, refine and prioritise theories, and codesign best policy and practice guidance. Ethics and dissemination Ethical approval was granted by Solihull Research Ethics Committee (IRAS 314029). Findings will be reported in accordance with RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) guidelines, published as open access and shared widely, along with codesigned tools. Trial registration number ISRCTN 62469166; the pr

Introduction Peer online mental health forums are commonly used and offer accessible support. Positive and negative impacts have been reported by forum members and moderators, but it is unclear why these impacts occur, for whom and in which forums. This multiple method realist study explores underlying mechanisms to understand how forums work for different people. The findings will inform codesign of best practice guidance and policy tools to enhance the uptake and effectiveness of peer online mental health forums. Methods and analysis In workstream 1, we will conduct a realist synthesis, based on existing literature and interviews with approximately 20 stakeholders, to generate initial programme theories about the impacts of forums on members and moderators and mechanisms driving these. Initial theories that are relevant for forum design and implementation will be prioritised for testing in workstream 2. Workstream 2 is a multiple case study design with mixed methods with several online mental health forums differing in contextual features. Quantitative surveys of forum members, qualitative interviews and Corpus-based Discourse Analysis and Natural Language Processing of forum posts will be used to test and refine programme theories. Final programme theories will be developed through novel triangulation of the data. Workstream 3 will run alongside workstreams 1 and 2. Key stakeholders from participating forums, including members and moderators, will be recruited to a Codesign group. They will inform the study design and materials, refine and prioritise theories, and codesign best policy and practice guidance. Ethics and dissemination Ethical approval was granted by Solihull Research Ethics Committee (IRAS 314029). Findings will be reported in accordance with RAMESES (Realist And MEta-narrative Evidence Syntheses: Evolving Standards) guidelines, published as open access and shared widely, along with codesigned tools. Trial registration number ISRCTN 62469166; the pr

Background: Relatives of people with psychosis or bipolar disorder experience high levels of distress but typically are not offered the support they need. Peer online forums may offer a solution, but knowledge about who uses them, how and why is limited. The current study reported on online forum usage during the REACT (Relatives’ Education And Coping Toolkit) trial. Objective: We aimed to report: (1) who used the forum and why; (2) how sociodemographic factors are associated with participation; (3) the relationships between frequency, type of use, and outcomes; and (4) how the forum was used. Methods: Relationships between key socio-demographic characteristics, levels of forum use, and distress were statistically analysed. We used thematic and semantic analysis to understand the reasons relatives joined the forum and the key topics initiated by them. We also used the UCREL Semantic Analysis System (USAS) to compare how relatives and REACT Supporters (moderators) used the forum. Results: 348 participants with full forum use data from REACT were included in this study. The forum was accessed by 59% (207/348) of relatives across the whole age range with no significant associations between sociodemographic factors and forum participation, or between level/type of use and relatives’ distress levels. Relatives joined the forum primarily to find people in similar circumstances, express concerns and talk about stressful events. Relatives were concerned most about recent events, negative emotions linked to caring, experiences of conflict/threat, and concerns about suicide. These posts underscored both the challenges relatives were facing and that they felt safe to share these in this context. Conclusion: Whilst only a proportion of REACT participants engaged actively with its forum they are widely distributed across age and other sociodemographic groupings. Relatives used the forum for information, support and guidance and to offer detailed information about their experienc

Background. The likelihood of suicidal behaviour is elevated amongst people with psychosis or bipolar disorder. This study aimed to understand how carers experience supporting family members with psychosis or bipolar disorder who have also experienced suicidal behaviour. Methods. A qualitative thematic analysis of online peer forum posts was carried out on the Relatives Education and Coping Toolkit (REACT) website, an online intervention for carers of people with psychosis and bipolar disorder. Analysis was based on 178 posts by 29 forum users. Posts were selected based on their relevance to suicidal behaviour. Results. Three themes were generated. “Suicide as the ultimate threat” highlights fears emerging from carers’ difficulties with understanding and managing suicidal behaviour. “Bouncing from one crisis to another” reflects carers’ experiences of recurring crises and the challenges of relying on emergency healthcare support. “It definitely needs to be easier to get help” emphasises carers’ desires to be acknowledged by healthcare professionals and included in support offered to service users. Conclusions. Digital platforms, including online forums, brief interventions such as safety planning, and interagency crisis models, hold the potential to meet carers’ needs in this context. However, further research is required to investigate the effectiveness and implementation of these approaches.

BACKGROUND: Relatives of people with psychosis or bipolar disorder experience high levels of distress but are typically not offered the support they need. Online peer forums may offer a solution, but knowledge about who uses them, how, and why is limited. This study reported on online forum use during the Relatives Education and Coping Toolkit (REACT) trial. OBJECTIVE: We aimed to report who used the forum and why; how sociodemographic factors are associated with participation; the relationship among frequency, type of use, and outcomes; and how the forum was used. METHODS: The relationships between key sociodemographic characteristics, levels of forum use, and distress were statistically analyzed. We used thematic and semantic analyses to understand the reasons for relatives joining the forum and the key topics initiated by them. We also used the University Centre for Computer Corpus Research on Language Semantic Analysis System to compare how relatives and REACT supporters (moderators) used the forum. RESULTS: A total of 348 participants with full forum use data from REACT were included in this study. The forum was accessed by 59.4% (207/348) of the relatives across the entire age range, with no significant associations between sociodemographic factors and forum participation, or between level or type of use and relatives' distress levels. Relatives joined the forum primarily to find people in similar circumstances, express concerns, and talk about stressful events. Relatives were most concerned about recent events, negative emotions linked to caring, experiences of conflict or threat, and concerns about suicide. These posts underscored both the challenges the relatives were facing and the fact that they felt safe sharing them in this context. CONCLUSIONS: Although only a proportion of REACT participants engaged actively with its forum, they were widely distributed across age and other sociodemographic groupings. Relatives used the forum for information, support

Background. The likelihood of suicidal behaviour is elevated amongst people with psychosis or bipolar disorder. This study aimed to understand how carers experience supporting family members with psychosis or bipolar disorder who have also experienced suicidal behaviour. Methods. A qualitative thematic analysis of online peer forum posts was carried out on the Relatives Education and Coping Toolkit (REACT) website, an online intervention for carers of people with psychosis and bipolar disorder. Analysis was based on 178 posts by 29 forum users. Posts were selected based on their relevance to suicidal behaviour. Results. Three themes were generated. “Suicide as the ultimate threat” highlights fears emerging from carers’ difficulties with understanding and managing suicidal behaviour. “Bouncing from one crisis to another” reflects carers’ experiences of recurring crises and the challenges of relying on emergency healthcare support. “It definitely needs to be easier to get help” emphasises carers’ desires to be acknowledged by healthcare professionals and included in support offered to service users. Conclusions. Digital platforms, including online forums, brief interventions such as safety planning, and interagency crisis models, hold the potential to meet carers’ needs in this context. However, further research is required to investigate the effectiveness and implementation of these approaches.

BACKGROUND: Relatives of people with psychosis or bipolar disorder experience high levels of distress but are typically not offered the support they need. Online peer forums may offer a solution, but knowledge about who uses them, how, and why is limited. This study reported on online forum use during the Relatives Education and Coping Toolkit (REACT) trial. OBJECTIVE: We aimed to report who used the forum and why; how sociodemographic factors are associated with participation; the relationship among frequency, type of use, and outcomes; and how the forum was used. METHODS: The relationships between key sociodemographic characteristics, levels of forum use, and distress were statistically analyzed. We used thematic and semantic analyses to understand the reasons for relatives joining the forum and the key topics initiated by them. We also used the University Centre for Computer Corpus Research on Language Semantic Analysis System to compare how relatives and REACT supporters (moderators) used the forum. RESULTS: A total of 348 participants with full forum use data from REACT were included in this study. The forum was accessed by 59.4% (207/348) of the relatives across the entire age range, with no significant associations between sociodemographic factors and forum participation, or between level or type of use and relatives' distress levels. Relatives joined the forum primarily to find people in similar circumstances, express concerns, and talk about stressful events. Relatives were most concerned about recent events, negative emotions linked to caring, experiences of conflict or threat, and concerns about suicide. These posts underscored both the challenges the relatives were facing and the fact that they felt safe sharing them in this context. CONCLUSIONS: Although only a proportion of REACT participants engaged actively with its forum, they were widely distributed across age and other sociodemographic groupings. Relatives used the forum for information, support

There has been a growth in the number of web-based trials of web-based interventions, adding to an increasing evidence base for their feasibility and effectiveness. However, there are challenges associated with such trials, which researchers must address. This discussion paper follows the structure of the Down Your Drink trial methodology paper, providing an update from the literature for each key trial parameter (recruitment, registration eligibility checks, consent and participant withdrawal, randomization, engagement with a web-based intervention, retention, data quality and analysis, spamming, cybersquatting, patient and public involvement, and risk management and adverse events), along with our own recommendations based on designing the Relatives Education and Coping Toolkit randomized controlled trial for relatives of people with psychosis or bipolar disorder. The key recommendations outlined here are relevant for future web-based and hybrid trials and studies using iterative development and test models such as the Accelerated Creation-to-Sustainment model, both within general health research and specifically within mental health research for relatives. Researchers should continue to share lessons learned from conducting web-based trials of web-based interventions to benefit future studies.

Background The Relatives Education And Coping Toolkit (REACT) is an online supported self-management toolkit for relatives of people with psychosis or bipolar designed to improve access to NICE recommended information and emotional support. Aims Our aim was to determine clinical and cost-effectiveness of REACT including a Resource Directory (RD), versus RD-only. Methods A primarily online, observer-blind randomised controlled trial comparing REACT (including RD) with RD only (registration ). Participants were UK relatives aged > = 16, with high distress (assessed using the GHQ-28), and actively help-seeking, individually randomised, and assessed online. Primary outcome was relatives' distress (GHQ-28) at 24 weeks. Secondary outcomes were wellbeing, support, costs and user feedback. Results We recruited 800 relatives (REACT = 399; RD only = 401) with high distress at baseline (GHQ-28 REACT mean 40.3, SD 14.6; RD only mean 40.0, SD 14.0). Median time spent online on REACT was 50.8 min (IQR 12.4-172.1) versus 0.5 min (IQR 0-1.6) on RD only. Retention to primary follow-up (24 weeks) was 75% (REACT n = 292 (73.2%); RD-only n = 307 (76.6%)). Distress decreased in both groups by 24 weeks, with no significant difference between the two groups (- 1.39, 95% CI -3.60, 0.83, p = 0.22). Estimated cost of delivering REACT was 62.27 pound per person and users reported finding it safe, acceptable and convenient. There were no adverse events or reported side effects. Conclusions REACT is an inexpensive, acceptable, and safe way to deliver NICE-recommended support for relatives. However, for highly distressed relatives it is no more effective in reducing distress (GHQ-28) than a comprehensive online resource directory.

There has been a growth in the number of web-based trials of web-based interventions, adding to an increasing evidence base for their feasibility and effectiveness. However, there are challenges associated with such trials, which researchers must address. This discussion paper follows the structure of the Down Your Drink trial methodology paper, providing an update from the literature for each key trial parameter (recruitment, registration eligibility checks, consent and participant withdrawal, randomization, engagement with a web-based intervention, retention, data quality and analysis, spamming, cybersquatting, patient and public involvement, and risk management and adverse events), along with our own recommendations based on designing the Relatives Education and Coping Toolkit randomized controlled trial for relatives of people with psychosis or bipolar disorder. The key recommendations outlined here are relevant for future web-based and hybrid trials and studies using iterative development and test models such as the Accelerated Creation-to-Sustainment model, both within general health research and specifically within mental health research for relatives. Researchers should continue to share lessons learned from conducting web-based trials of web-based interventions to benefit future studies.

Background The Relatives Education And Coping Toolkit (REACT) is an online supported self-management toolkit for relatives of people with psychosis or bipolar designed to improve access to NICE recommended information and emotional support. Aims Our aim was to determine clinical and cost-effectiveness of REACT including a Resource Directory (RD), versus RD-only. Methods A primarily online, observer-blind randomised controlled trial comparing REACT (including RD) with RD only (registration ). Participants were UK relatives aged > = 16, with high distress (assessed using the GHQ-28), and actively help-seeking, individually randomised, and assessed online. Primary outcome was relatives' distress (GHQ-28) at 24 weeks. Secondary outcomes were wellbeing, support, costs and user feedback. Results We recruited 800 relatives (REACT = 399; RD only = 401) with high distress at baseline (GHQ-28 REACT mean 40.3, SD 14.6; RD only mean 40.0, SD 14.0). Median time spent online on REACT was 50.8 min (IQR 12.4-172.1) versus 0.5 min (IQR 0-1.6) on RD only. Retention to primary follow-up (24 weeks) was 75% (REACT n = 292 (73.2%); RD-only n = 307 (76.6%)). Distress decreased in both groups by 24 weeks, with no significant difference between the two groups (- 1.39, 95% CI -3.60, 0.83, p = 0.22). Estimated cost of delivering REACT was 62.27 pound per person and users reported finding it safe, acceptable and convenient. There were no adverse events or reported side effects. Conclusions REACT is an inexpensive, acceptable, and safe way to deliver NICE-recommended support for relatives. However, for highly distressed relatives it is no more effective in reducing distress (GHQ-28) than a comprehensive online resource directory.

Psychological models of bipolar disorder (BD), such as the Self Regulation Model (SRM; Leventhal, Nerenz & Steele, 1984), highlight the crucial role of beliefs about mood in relapse vulnerability. To date, no studies have directly compared these beliefs between people with and without BD. Based on the SRM, the current research examined beliefs about mood in people with and without BD, and explored the impact of current affect on these beliefs. Fifty euthymic people with a diagnosis of BD and fifty controls were recruited through an online screening study, clinical services and support organisations. Experience Sampling Methodology (ESM) was used to assess beliefs (according to the Brief Illness Perceptions Questionnaire; Broadbent, Petrie, Main & Weinman, 2006) across a typical week of everyday life. Data were analysed using multilevel modelling. Forty‐two people with a diagnosis of BD and fifty controls were included in analyses. Results indicated that the BD group reported less control over mood; a shorter duration of mood; less understanding of mood; and were more likely to report the cause of depressive symptoms as something internal, compared to controls. When controlling for current affect, the BD group also reported more positive consequences, made more internal attributions for hypomanic symptoms and reported less concern about mood, compared to controls. Findings suggest important differences in beliefs about mood between people with and without BD that are not the result of current affect. These beliefs may be particularly important in understanding underlying vulnerability to future relapse into depression and/or mania.

Background Alcohol use is a common problem in bipolar disorder (BD) and evidence indicates more promising outcomes for alcohol use than other substances. No trials have evaluated individual integrated motivational interviewing and cognitive behaviour therapy (MI-CBT) for problematic alcohol use in BD. We therefore assessed the feasibility and acceptability of a novel MI-CBT intervention for alcohol use in BD. Methods A single blind RCT was conducted to compare MI-CBT plus treatment as usual (TAU) with TAU only. MI-CBT was delivered over 20 sessions with participants followed up at 3, 6, 9 and 12 months post-randomisation. Primary outcomes were the feasibility and acceptability of MI-CBT (recruitment to target, retention to follow-up and therapy, acceptability of therapy and absence of adverse events). We also conducted preliminary analyses of alcohol and mood outcomes (frequency and severity of alcohol use and time to mood relapse). Results 44 participants were recruited with 75% retention to 6 and 12 months follow-up. Therapy participants attended a mean of 17.6 (SD 4.5) sessions. Therapy alliance and treatment fidelity were acceptable. Qualitative interviews indicated the intervention was experienced as collaborative, and helpful, in addressing mood and alcohol issues, although risk of overconfidence following therapy was also identified. Clinical outcomes did not differ between arms at 12 months follow-up. Limitations As a feasibility and acceptability trial any secondary results should be treated with caution. Conclusions Integrated MI-CBT is feasible and acceptable, but lack of clinical impact, albeit in a feasibility study, suggests need for further development. Potential adaptations are discussed.

Background Relatives caring for people with severe mental health problems find information and emotional support hard to access. Online support for self-management offers a potential solution. Objective To determine the clinical and cost-effectiveness of an online supported self-management tool for relatives, the Relatives’ Education And Coping Toolkit (REACT). Design A primarily online, single-blind, randomised controlled trial, comparing REACT plus a resource directory (RD) and treatment as usual (TAU), against the RD and TAU only, by measuring user distress and other wellbeing measures at start, 12 and 24 weeks. Participants 800 relatives across UK, aged 16 or over, with high levels of distress, access to Internet, and actively seeking help. Intervention REACT comprised 12 psychoeducation modules, peer support through a group forum, confidential messaging, and a comprehensive RD of national support. Trained relatives moderated the forum and responded to messages. Main outcome measure Participants’ distress, measured by the General Health Questionnaire (GHQ-28). Results Recruitment was via study website. Various online and offline strategies including social media directed potential participants to the site. Participants were randomised into two groups: REACT plus RD (n=399) or RD only (n=401). Retention at 24 weeks was 75% (REACT n=292; RD-only n=307). Mean GHQ-28 scores fell substantially across both groups over 24 weeks, from mean 40.2, standard deviation (SD) 14.3 to mean 30.5, SD 15.6, with no significant difference between groups (-1.39, 95% CI -3.60–0.83, p=0.22). At 12 weeks GHQ-28 scores were lower in the REACT arm than in RD-only (-2.08, 95% CI -4.14– -0.03, p=0.027), but of likely limited clinical significance. Accounting for missing data, which was associated with higher distress in the REACT arm (0.33, 95% CI -0.27–0.93, p=0.279), in a longitudinal model, there was no significant difference between groups over 24 weeks (-0.56, 95% CI–2.34–1.22, p=0.51

Background Alcohol use is a common problem in bipolar disorder (BD) and evidence indicates more promising outcomes for alcohol use than other substances. No trials have evaluated individual integrated motivational interviewing and cognitive behaviour therapy (MI-CBT) for problematic alcohol use in BD. We therefore assessed the feasibility and acceptability of a novel MI-CBT intervention for alcohol use in BD. Methods A single blind RCT was conducted to compare MI-CBT plus treatment as usual (TAU) with TAU only. MI-CBT was delivered over 20 sessions with participants followed up at 3, 6, 9 and 12 months post-randomisation. Primary outcomes were the feasibility and acceptability of MI-CBT (recruitment to target, retention to follow-up and therapy, acceptability of therapy and absence of adverse events). We also conducted preliminary analyses of alcohol and mood outcomes (frequency and severity of alcohol use and time to mood relapse). Results 44 participants were recruited with 75% retention to 6 and 12 months follow-up. Therapy participants attended a mean of 17.6 (SD 4.5) sessions. Therapy alliance and treatment fidelity were acceptable. Qualitative interviews indicated the intervention was experienced as collaborative, and helpful, in addressing mood and alcohol issues, although risk of overconfidence following therapy was also identified. Clinical outcomes did not differ between arms at 12 months follow-up. Limitations As a feasibility and acceptability trial any secondary results should be treated with caution. Conclusions Integrated MI-CBT is feasible and acceptable, but lack of clinical impact, albeit in a feasibility study, suggests need for further development. Potential adaptations are discussed.

Background Co-morbid substance misuse, particularly alcohol, is common in bipolar disorder (BD) and associated with worse treatment outcomes. Research into psychological interventions for substance misuse in BD is at an early stage and no studies have specifically targeted problematic alcohol use. This paper describes the context and protocol for a feasibility and acceptability randomised controlled trial (RCT) evaluating a novel intervention combining motivational interviewing and cognitive behavioural therapy (MI-CBT) for participants with BD and problematic alcohol use, developed in collaboration with people with lived experience of both issues. Methods and design: An RCT will assess the feasibility and acceptability of MI-CBT in addition to treatment as usual (TAU) with TAU alone. Participants will be recruited from across the North West of England through NHS services and self-referral. The primary outcomes will be the feasibility and acceptability of the intervention assessed by recruitment to target, adherence to intervention, retention rate at follow-up, absence of adverse events and qualitative analysis of participants' reported experiences of intervention. The effect size of the impact of the intervention on alcohol use and mood outcomes will also be estimated. In addition, we will explore number of potential process variables in therapy. Discussion This is the first RCT evaluating MI-CBT for BD and problematic alcohol use. Given the prevalence and impact of alcohol problems in BD this novel integrated intervention may have potential to offer important improvements in clinical and functional outcomes.

Background Co-morbid substance misuse, particularly alcohol, is common in bipolar disorder (BD) and associated with worse treatment outcomes. Research into psychological interventions for substance misuse in BD is at an early stage and no studies have specifically targeted problematic alcohol use. This paper describes the context and protocol for a feasibility and acceptability randomised controlled trial (RCT) evaluating a novel intervention combining motivational interviewing and cognitive behavioural therapy (MI-CBT) for participants with BD and problematic alcohol use, developed in collaboration with people with lived experience of both issues. Methods and design: An RCT will assess the feasibility and acceptability of MI-CBT in addition to treatment as usual (TAU) with TAU alone. Participants will be recruited from across the North West of England through NHS services and self-referral. The primary outcomes will be the feasibility and acceptability of the intervention assessed by recruitment to target, adherence to intervention, retention rate at follow-up, absence of adverse events and qualitative analysis of participants' reported experiences of intervention. The effect size of the impact of the intervention on alcohol use and mood outcomes will also be estimated. In addition, we will explore number of potential process variables in therapy. Discussion This is the first RCT evaluating MI-CBT for BD and problematic alcohol use. Given the prevalence and impact of alcohol problems in BD this novel integrated intervention may have potential to offer important improvements in clinical and functional outcomes.

Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: Host-Microbiome Interactions; Health and Infectious Diseases; Human Health and Food Security; Microbial Ecology in a Changing World; Environmental Processes; Functional Diversity; and Evolutionary Processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and diverse other organisms. Certain methods remain inadequate and currently limit progress in the field. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders, and policy makers, informing the future research agenda in microbial ecology

Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host-microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology.

Introduction Despite clinical guidelines recommendations, many relatives of people with psychosis or bipolar disorder do not currently receive the support they need. Online information and support may offer a solution. Methods and analysis This single-blind, parallel, online randomised controlled trial will determine clinical and cost-effectiveness of the Relatives Education And Coping Toolkit (REACT) (including an online resource directory (RD)), compared with RD only, for relatives of people with psychosis or bipolar disorder. Both groups continue to receive treatment as usual. Independent, web-based variable, block, individual randomisation will be used across 666 relatives. Primary outcome is distress at 24 weeks (measured by General Health Questionnaire; GHQ-28) compared between groups using analysis of covariance, adjusting for baseline score. Secondary clinical outcomes are carer well-being and support. Cost-effectiveness analysis will determine cost of a significant unit change (three-point reduction) in the GHQ-28. Costs include offering and supporting the intervention in the REACT arm, relevant healthcare care costs including health professional contacts, medications prescribed and time off (or ability to) work for the relative. Cost utility analysis will be calculated as the marginal cost of changes in quality-adjusted life years, based on EuroQol. We will explore relatives’ beliefs, perceived coping and amount of REACT toolkit use as possible outcome mediators. We have embedded two methodological substudies in the protocol to determine the relative effectiveness of a low-value (£10) versus higher value (£20) incentive, and an unconditional versus conditional incentive, on improving follow-up rates. Ethics and dissemination The trial has ethical approval from Lancaster National Research Ethics Service (NRES)Committee (15/NW/0732) and is overseen by an independent Data Monitoring and Ethics Committee and Trial Steering Committee. Protocol version 1.5 was a

Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: Host-Microbiome Interactions; Health and Infectious Diseases; Human Health and Food Security; Microbial Ecology in a Changing World; Environmental Processes; Functional Diversity; and Evolutionary Processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and diverse other organisms. Certain methods remain inadequate and currently limit progress in the field. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders, and policy makers, informing the future research agenda in microbial ecology

Introduction Despite clinical guidelines recommendations, many relatives of people with psychosis or bipolar disorder do not currently receive the support they need. Online information and support may offer a solution. Methods and analysis This single-blind, parallel, online randomised controlled trial will determine clinical and cost-effectiveness of the Relatives Education And Coping Toolkit (REACT) (including an online resource directory (RD)), compared with RD only, for relatives of people with psychosis or bipolar disorder. Both groups continue to receive treatment as usual. Independent, web-based variable, block, individual randomisation will be used across 666 relatives. Primary outcome is distress at 24 weeks (measured by General Health Questionnaire; GHQ-28) compared between groups using analysis of covariance, adjusting for baseline score. Secondary clinical outcomes are carer well-being and support. Cost-effectiveness analysis will determine cost of a significant unit change (three-point reduction) in the GHQ-28. Costs include offering and supporting the intervention in the REACT arm, relevant healthcare care costs including health professional contacts, medications prescribed and time off (or ability to) work for the relative. Cost utility analysis will be calculated as the marginal cost of changes in quality-adjusted life years, based on EuroQol. We will explore relatives’ beliefs, perceived coping and amount of REACT toolkit use as possible outcome mediators. We have embedded two methodological substudies in the protocol to determine the relative effectiveness of a low-value (£10) versus higher value (£20) incentive, and an unconditional versus conditional incentive, on improving follow-up rates. Ethics and dissemination The trial has ethical approval from Lancaster National Research Ethics Service (NRES)Committee (15/NW/0732) and is overseen by an independent Data Monitoring and Ethics Committee and Trial Steering Committee. Protocol version 1.5 was a

BACKGROUND AND AIMS.: It has been suggested that thermal imaging may provide alternative appropriate diagnostic information for Carpal Tunnel Syndrome (CTS). The aims of this study are to investigate the optimum method of data collection from thermal images of subjects with CTS, establish base line thermographic reference data in subjects with CTS, measure the effect of a thermal washout on these patients and compare pre/post surgery baseline thermographic data to assess the effects of surgery. METHODS: Patients who had a diagnosis of CTS and were waiting for decompression surgery were recruited. The study involved two data collection sessions, the first immediately before decompression surgery, the second 6 weeks after the operation. A baseline image was taken, cooling using a Cryo/Cuff took place, following removal of the Cryo/Cuff temperature data were sampled during rewarming. Data from pre and post operative images were extracted by mapping three areas defined on screen by using thermally inert markers. RESULTS: The most clinically significant results were seen in the temperature change in the distal portion of the 2nd and 5th digits of the symptomatic hand. The same difference was not seen in the proximal portion of the same digits or in the asymptomatic hand. The greatest increase in post operative temperature of the distal portion of the digits occurred in the 2nd digit which is supplied by the median nerve compared to the smaller increase in temperature in the 5th digit which is supplied by the ulnar nerve. DISCUSSION: Considering the underlying pathology where the median nerve is primarily affected in CTS this could have significant diagnostic implications. There would appear to be clinical implications in these findings with potential for this method to be developed further as a diagnostic thermal imaging test which would be better tolerated and more readily available than nerve conduction studies thus reducing waiting times for diagnostic testing to conf

Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host–microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology.

Background Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (5

Background Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (5

The clinical effectiveness of psychological interventions for bipolar disorder (BD) may be enhanced by having a coherent psychological model of BD, which amalgamates many of the concepts proposed in the existing psychological models of BD and some which are not. This PhD aimed to expand on the Self Regulation Model (SRM; Leventhal et al. , 1984) framework to enhance understanding of mood identification and regulation in BD. The mood management model proposed was tested using three methodologies (namely experience sampling, mood induction and a cross-sectional survey design) to provide insight into mood management processes in daily life, following controlled mood manipulation and in response to self-report questionnaires in a large sample of people with BD from across the North West of England and Nottingham. Demonstrating differences between euthymic bipolar participants and healthy controls regarding the psychological processes that underlie the self-regulation of mood may inform psychological interventions. Compared to healthy controls, people with BD reported more variability in mood, perceived more positive consequences, less personal control, less understanding, a shorter duration of mood and made more internal attributions for hypomanic and depressive experiences. Furthermore, while people with BD reported implementing helpful coping strategies (CS) to manage low mood, the most commonly used CS for mania were related to stimulating behaviours that would likely escalate mood and were rated as unhelpful by participants themselves. The current results support the application of the SRM to BD and the importance of expanding this model to explain mood management in BD. The clinical implications, limitations and avenues for future research are discussed.

Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host–microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology.

Background Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (5

Background Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (5

Background Group psychoeducation is a low-cost National Institute for Health and Care Excellence-recommended treatment for bipolar disorder. However, the clinical effectiveness and acceptability of this intervention are unclear compared with unstructured peer support matched for delivery and aim of treatment, and for previous bipolar history. We aimed to assess the clinical effectiveness and acceptability of structured group psychoeducation versus optimised unstructured peer support for patients with remitted bipolar disorder. Methods We did this pragmatic, multicentre, parallel-group, observer-blind, randomised controlled superiority trial at eight community sites in two regions in England. Participants aged 18 years or older with bipolar disorder and no episode in the preceding 4 weeks were recruited via self-referral or secondary care referral. Participants were individually randomly assigned (1:1), via a computer-generated stochastic allocation sequence, to attend 21 2-h weekly sessions of either structured group psychoeducation or optimised unstructured peer support. Randomisation was minimised by number of previous episodes (one to seven, eight to 19, or ≥20) and stratified by clinical site. Outcome assessors were masked to group allocation. The primary outcome was time from randomisation to next bipolar episode, with planned moderator analysis of number of previous bipolar episodes and qualitative interview of participant experience. We did analysis by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN62761948. Findings Between Sept 28, 2009, and Jan 9, 2012, we randomly assigned 304 participants to receive psychoeducation (n=153) or peer support (n=151); all (100%) participants had complete primary outcome data. Attendance at psychoeducation groups was higher than at peer-support groups (median 14 sessions [IQR three to 18] vs nine sessions [two to 17]; p=0·026). At 96 weeks, 89 (5

The clinical effectiveness of psychological interventions for bipolar disorder (BD) may be enhanced by having a coherent psychological model of BD, which amalgamates many of the concepts proposed in the existing psychological models of BD and some which are not. This PhD aimed to expand on the Self Regulation Model (SRM; Leventhal et al. , 1984) framework to enhance understanding of mood identification and regulation in BD. The mood management model proposed was tested using three methodologies (namely experience sampling, mood induction and a cross-sectional survey design) to provide insight into mood management processes in daily life, following controlled mood manipulation and in response to self-report questionnaires in a large sample of people with BD from across the North West of England and Nottingham. Demonstrating differences between euthymic bipolar participants and healthy controls regarding the psychological processes that underlie the self-regulation of mood may inform psychological interventions. Compared to healthy controls, people with BD reported more variability in mood, perceived more positive consequences, less personal control, less understanding, a shorter duration of mood and made more internal attributions for hypomanic and depressive experiences. Furthermore, while people with BD reported implementing helpful coping strategies (CS) to manage low mood, the most commonly used CS for mania were related to stimulating behaviours that would likely escalate mood and were rated as unhelpful by participants themselves. The current results support the application of the SRM to BD and the importance of expanding this model to explain mood management in BD. The clinical implications, limitations and avenues for future research are discussed.