Understanding the Impacts of Online Mental Health Peer Support Forums: Realist Synthesis.

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: PROSPERO CRD42022352528; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=352528.

mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.

BACKGROUND: Mutations in the gene MTARC1 (mitochondrial amidoxime-reducing component 1) protect carriers from metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MTARC1 encodes the mARC1 enzyme, which is localized to the mitochondria and has no known MASH-relevant molecular function. Our studies aimed to expand on the published human genetic mARC1 data and to observe the molecular effects of mARC1 modulation in preclinical MASH models. METHODS AND RESULTS: We identified a novel human structural variant deletion in MTARC1, which is associated with various biomarkers of liver health, including alanine aminotransferase levels. Phenome-wide Mendelian Randomization analyses additionally identified novel putatively causal associations between MTARC1 expression, and esophageal varices and cardiorespiratory traits. We observed that protective MTARC1 variants decreased protein accumulation in in vitro overexpression systems and used genetic tools to study mARC1 depletion in relevant human and mouse systems. Hepatocyte mARC1 knockdown in murine MASH models reduced body weight, liver steatosis, oxidative stress, cell death, and fibrogenesis markers. mARC1 siRNA treatment and overexpression modulated lipid accumulation and cell death consistently in primary human hepatocytes, hepatocyte cell lines, and primary human adipocytes. mARC1 depletion affected the accumulation of distinct lipid species and the expression of inflammatory and mitochondrial pathway genes/proteins in both in vitro and in vivo models. CONCLUSIONS: Depleting hepatocyte mARC1 improved metabolic dysfunction-associated steatotic liver disease-related outcomes. Given the functional role of mARC1 in human adipocyte lipid accumulation, systemic targeting of mARC1 should be considered when designing mARC1 therapies. Our data point to plasma lipid biomarkers predictive of mARC1 abundance, such as Ceramide 22:1. We propose future areas of study to describe the precise molecular function of mARC1, including lipid trafficking and subcellular location within or around the mitochondria and endoplasmic reticulum.

The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population Using a Comprehensive Genomic Panel.

PURPOSE: Next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. PATIENTS AND METHODS: We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS in 107 Saudi Arabian patients without a family history of CRC. RESULTS: Approximately 98% of patients had genetic alterations. Frequent mutations were observed in BRCA2 (79%), CHEK1 (78%), ATM (76%), PMS2 (76%), ATR (74%), and MYCL (73%). The APC gene was not included in the panel. Statistical analysis using the Cox proportional hazards model revealed an unusual positive association between poorly differentiated tumors and survival rates (p = 0.025). Although no significant univariate associations between specific mutations or overall mutation rate and overall survival were found, our preliminary analysis of the molecular markers for CRC in a predominantly Arab population can provide insights into the molecular pathways that play a significant role in the underlying disease progression. CONCLUSIONS: These results may help optimize personalized therapy when drugs specific to a patient's mutation profile have already been developed.

Improving Peer Online Forums (iPOF): protocol for a realist evaluation of peer online mental health forums to inform practice and policy.

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 protocol for the realist synthesis in workstream one is prospectively registered at PROSPERO CRD42022352528.

Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel.

Family history is an important factor in determining hereditary cancer risk for many cancer types. The emergence of next-generation sequencing (NGS) has expedited the discovery of many hereditary cancer susceptibility genes and the development of rapid, affordable testing kits. Here, a 30-gene targeted NGS panel for hereditary cancer risk assessment was tested and validated in a Saudi Arabian population. A total of 310 subjects were screened, including 57 non-cancer patients, 110 index patients with cancer and 143 of the cancer patients' family members, 16 of which also had cancer. Of the 310 subjects, 119 (38.4%) were carriers of pathogenic or likely pathogenic variants (PVs) affecting one or more of the following genes: TP53, ATM, CHEK2, CDH1, CDKN2A, BRCA1, BRCA2, PALB2, BRIP1, RAD51D, APC, MLH1, MSH2, MSH6, PMS2, PTEN, NBN/NBS1 and MUTYH. Among 126 patients and relatives with a history of cancer, 49 (38.9%) were carriers of PVs or likely PVs. Two variants in particular were significantly associated with the occurrence of a specific cancer in this population (APC c.3920T>A - colorectal cancer/Lynch syndrome (p = 0.026); TP53 c.868C>T; - multiple colon polyposis (p = 0.048)). Diverse variants in BRCA2, the majority of which have not previously been reported as pathogenic, were found at higher frequency in those with a history of cancer than in the general patient population. There was a higher background prevalence of genetic variants linked to familial cancers in this cohort than expected based on prevalence in other populations.

Clinicopathologic and genomic characterizations of brain metastases using a comprehensive genomic panel.

Central nervous system (CNS) metastasis is the most common brain tumor type in adults. Compared to their primary tumors, these metastases undergo a variety of genetic changes to be able to survive and thrive in the complex tissue microenvironment of the brain. In clinical settings, the majority of traditional chemotherapies have shown limited efficacy against CNS metastases. However, the discovery of potential driver mutations, and the development of drugs specifically targeting affected signaling pathways, could change the treatment landscape of CNS metastasis. Genetic studies of brain tumors have so far focused mainly on common cancers in western populations. In this study, we performed Next Generation Sequencing (NGS) on 50 pairs of primary tumors, including but not limited to colorectal, breast, renal and thyroid tumors, along with their brain metastatic tumor tissue counterparts, from three different local tertiary centers in Saudi Arabia. We identified potentially clinically relevant mutations in brain metastases that were not detected in corresponding primary tumors, including mutations in the PI3K, CDK, and MAPK pathways. These data highlight the differences between primary cancers and brain metastases and the importance of acquiring and analyzing brain metastatic samples for further clinical management.

Caring for a Family Member with Psychosis or Bipolar Disorder Who Has Experienced Suicidal Behaviour: An Exploratory Qualitative Study of an Online Peer-Support Forum.

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.

Use of an Online Forum for Relatives of People With Psychosis and Bipolar Disorder: Mixed Methods Study.

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, and guidance and to offer detailed information about their experiences. The topics raised highlighted the burden carried by relatives and the potential value of easy-access, moderated, peer-supported forums in helping relatives to manage the challenges they faced.

Effect of Novel Biotherapeutic Elevating Angiopoietin 1 on Progression of Diabetic Nephropathy in Diabetic/Obese Mice.

Diabetic nephropathy is a leading cause of end-stage renal disease, characterized by endothelial dysfunction and a compromised glomerular permeability barrier. Dysregulation of the angiopoietin 1 (ANGPT1)/angiopoietin 2 (ANGPT2) signaling axis is implicated in disease progression. We recently described the discovery of an IgG1 antibody, O010, with therapeutic potential to elevate circulating endogenous ANGPT1, a tyrosine kinase with Ig and epidermal growth factor (EGF) homology domains-2 (TIE2) agonist. Studies are described that detail the effect of various ANGPT1-elevating strategies to limit progression of renal dysfunction in diabetic-obese (db/db) mice. Results demonstrate that adeno-associated virus- or DNA minicircle-directed overexpression of ANGPT1 elicits a reduction in albuminuria (56%-73%) and an improvement in histopathology score (18% reduction in glomerulosclerosis). An improved acetylcholine response in isolated aortic rings was also observed indicative of a benefit on vascular function. In separate pharmacokinetic studies, an efficacious dose of the ANGPT1 DNA minicircle increased circulating levels of the protein by >80%, resulting in a concomitant suppression of ANGPT2. At a dose of O010-producing maximal elevation of circulating ANGPT1 achievable with the molecule (60% increase), no suppression of ANGPT2 was observed in db/db mice, suggesting insufficient pathway engagement; no reduction in albuminuria or improvement in histopathological outcomes were observed. To pinpoint the mechanism resulting in lack of efficacy, we demonstrate, using confocal microscopy, an interference with TIE2 translocation to adherens junctions, resulting in a loss of protection against vascular permeability normally conferred by ANGPT1. Results demonstrated the essential importance of ANGPT1 to maintain the glomerular permeability barrier, and, due to interference of O010 with this process, led to the discontinuation of the molecule for clinical development. SIGNIFICANCE STATEMENT: This body of original research demonstrates that elevation of systemic angiopoietin 1 (ANGPT1) is protective against diabetic nephropathy. However, using a novel biotherapeutic approach to elevate systemic ANGPT1 renoprotection was not observed; we demonstrate that protection was lost due to interference of the therapeutic with ANGPT1/ tyrosine kinase with Ig and EGF homology domains-2 translocation to adherens junctions. Thus, the clinical development of the antibody was terminated.

Find the silver lining or ignore the cloud? Cognitive reappraisal versus visual attention training.

This study contrasted the efficacy of two strategies for emotion regulation, cognitive reappraisal (CR) and attentional control (AC), while using eye-tracking to examine gaze fixation patterns associated with each strategy. Participants (n = 98 undergraduates) viewed emotionally negative and neutral slides before and after one of three training conditions: CR training (verbal instructions to reframe interpretations of negative images), AC training (gaze-contingent feedback emphasizing fixation away from negative portions of images), or a no-training control condition. CR training led to the most beneficial consequences for self-reported emotion ratings; AC training improved emotion ratings more than the no-training control but not as much as CR. AC training led to significantly reduced time fixating gaze on negative content, whereas CR did not alter gaze fixations compared with the no-training control. Moreover, among the AC group, participants who looked away from negative content to a greater extent reported more beneficial change in emotional self-report, whereas that same pattern was not evident in the CR or no-training group. The findings add to evidence that CR training is more effective than distraction-related strategies and that CR does not necessitate gaze changes to be effective. Together, the findings contribute to furthering knowledge about distinct cognitive mechanisms involved in different strategies of emotion regulation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Contraception Use and Attitudes Among Women Seeking Pregnancy Termination: Descriptive Cross-Sectional Survey.

OBJECTIVE: Unintended pregnancy has been linked to poor health and social outcomes for both mother and child. Efforts to reduce unintended pregnancies have been challenged by many financial, social, religious, and cultural factors. This study aimed to investigate how contraception use and misuse in a cohort of females seeking termination of pregnancy contribute to unintended pregnancies. METHODS: We conducted a cross-sectional study with women presenting to a women's health clinic for pregnancy termination from April to December 2017. Consenting participants completed a self-administered, confidential questionnaire that included questions on demographic, ethnic, and social characteristics, as well as behaviours and attitudes related to contraception. Data analysis used descriptive statistics. RESULTS: Data were collected from 334 women; about half (45%) had used contraception at the time of conception, representing a variety of different methods. Contraceptive use was associated with higher education, stable relationship status, and ethnic majority status but not with previous pregnancies or immigration status. Among contraceptive users, imperfect and inconsistent use of contraception (50% and 31%, respectively), and method failure (48%), including condom breakage, were cited as reasons for the current pregnancy. Non-users reported perceived low risk of pregnancy (55%), concerns about contraception (47%), and problems accessing contraception (27%). While the majority of participants were aware of emergency contraception, only 52% reported ever using it. Most participants (89%) planned to use contraception in the future. CONCLUSION: Our study highlights contraceptive behaviours and patterns of individuals seeking abortion. Patient-centered contraceptive counselling in order to facilitate contraceptive choice and access can include information about the most effective contraceptives and the need for back-up contraception methods.

Serum D-dimer should not be used in the diagnosis of venous thromboembolism within 28 days of total knee replacement surgery.

BACKGROUND: Serum D-dimer is frequently used to rule out a diagnosis of venous thromboembolism (VTE), a recognised complication following total knee replacement (TKR). TKR is known to cause a rise in D-dimer levels, reducing its specificity. Previous studies have demonstrated that D-dimer remains elevated within 10 days of TKR and therefore should be avoided. The aim of this study was to determine whether serum D-dimer tests are clinically appropriate in identifying VTE when performed within 28 days of TKR. METHODS: Case notes for patients who had a serum D-dimer test performed for clinically suspected VTE at ≥ 28 days following TKR were retrospectively reviewed for a 6-year period. Demographics, D-dimer result, time after surgery and further radiological investigations were recorded. RESULTS: Fifty patients underwent D-dimer tests at ≥ 28 days following surgery (median 60 days, range 29-266); 48 of these patients had a positive result. Of these, five had confirmed VTE on radiological investigations. Serum D-dimer was raised in 96% of the patients. Only 10.42% of these patients had confirmed VTE. No patients with negative D-dimers had confirmed VTE. CONCLUSIONS: These findings suggest that serum D-dimer remains raised for at least 28 days and possibly considerably longer following TKR. Serum D-dimer should not be used in patients with clinically suspected VTE within this period because of its unacceptably low specificity of 4.44% and positive predictive value of 10.42%, which can lead to a delay in necessary further radiological investigations, waste of resources and unnecessary exposure to harm.

A web-based, peer-supported self-management intervention to reduce distress in relatives of people with psychosis or bipolar disorder: the REACT RCT.

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: The objective was to determine the clinical effectiveness and cost-effectiveness of an online supported self-management tool for relatives: the Relatives' Education And Coping Toolkit (REACT). DESIGN AND SETTING: This was a primarily online (UK), single-blind, randomised controlled trial, comparing REACT plus a resource directory and treatment as usual with the resource directory and treatment as usual only, by measuring user distress and other well-being measures at baseline and at 12 and 24 weeks. PARTICIPANTS: A total of 800 relatives of people with severe mental health problems across the UK took part; relatives who were aged ≥ 16 years, were experiencing high levels of distress, had access to the internet and were actively seeking help were recruited. INTERVENTION: REACT comprised 12 psychoeducation modules, peer support through a group forum, confidential messaging and a comprehensive resource directory of national support. Trained relatives moderated the forum and responded to messages. MAIN OUTCOME MEASURE: The main outcome was the level of participants' distress, as measured by the General Health Questionnaire-28 items. RESULTS: Various online and offline strategies, including social media, directed potential participants to the website. Participants were randomised to one of two arms: REACT plus the resource directory (n = 399) or the resource directory only (n = 401). Retention at 24 weeks was 75% (REACT arm, n = 292; resource directory-only arm, n = 307). The mean scores for the General Health Questionnaire-28 items reduced substantially across both arms over 24 weeks, from 40.2 (standard deviation 14.3) to 30.5 (standard deviation 15.6), with no significant difference between arms (mean difference -1.39, 95% confidence interval -3.60 to 0.83; p = 0.22). At 12 weeks, the General Health Questionnaire-28 items scores were lower in the REACT arm than in the resource directory-only arm (-2.08, 95% confidence interval -4.14 to -0.03; p = 0.027), but this finding is likely to be of limited clinical significance. Accounting for missing data, which were associated with higher distress in the REACT arm (0.33, 95% confidence interval -0.27 to 0.93; p = 0.279), in a longitudinal model, there was no significant difference between arms over 24 weeks (-0.56, 95% confidence interval -2.34 to 1.22; p = 0.51). REACT cost £142.95 per participant to design and deliver (£62.27 for delivery only), compared with £0.84 for the resource directory only. A health economic analysis of NHS, health and Personal Social Services outcomes found that REACT has higher costs (£286.77), slightly better General Health Questionnaire-28 items scores (incremental General Health Questionnaire-28 items score adjusted for baseline, age and gender: -1.152, 95% confidence interval -3.370 to 1.065) and slightly lower quality-adjusted life-year gains than the resource directory only; none of these differences was statistically significant. The median time spent online was 50.8 minutes (interquartile range 12.4-172.1 minutes) for REACT, with no significant association with outcome. Participants reported finding REACT a safe, confidential environment (96%) and reported feeling supported by the forum (89%) and the REACT supporters (86%). No serious adverse events were reported. LIMITATIONS: The sample comprised predominantly white British females, 25% of participants were lost to follow-up and dropout in the REACT arm was not random. CONCLUSIONS: An online self-management support toolkit with a moderated group forum is acceptable to relatives and, compared with face-to-face programmes, offers inexpensive, safe delivery of National Institute for Health and Care Excellence-recommended support to engage relatives as peers in care delivery. However, currently, REACT plus the resource directory is no more effective at reducing relatives' distress than the resource directory only. FUTURE WORK: Further research in improving the effectiveness of online carer support interventions is required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN72019945. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 32. See the NIHR Journals Library website for further project information.

Relatives of people with severe mental health problems need better access to information and emotional support. The Relatives' Education And Coping Toolkit (REACT) is a website designed to do this. It includes lots of information presented in text and video, an online forum for relatives to share knowledge and experience, a messaging system where they can ask questions in confidence and a comprehensive directory of contact details for national organisations offering relevant support. Trained relatives support the forum and messaging. In the UK, we recruited 800 relatives of people with severe mental health problems: all were aged ≥ 16 years, had high levels of distress, had access to the internet and wanted help. We divided them into two equal groups: one group received REACT (including the resource directory), whereas the other group received the resource directory only. To ensure that there were no differences between groups at the start, relatives were allocated to the two groups randomly, so they had an equal chance of being in either group. We followed up with both groups at 12 and 24 weeks, and received data from approximately three-quarters of the participants. This trial found that REACT was acceptable, safe and inexpensive to deliver (£62.27 per relative), compared with face-to-face interventions, and that relatives using it felt well supported. However, once we accounted for missing data (relatives who dropped out of the trial or did not complete the follow-up questionnaires), there were no significant differences between the groups. There was no evidence that REACT increased relatives' quality of life or saved money for the NHS.

Methodological Challenges in Web-Based Trials: Update and Insights From the Relatives Education and Coping Toolkit Trial.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2017-016965.

Clinical effectiveness of a web-based peer-supported self-management intervention for relatives of people with psychosis or bipolar (REACT): online, observer-blind, randomised controlled superiority trial.

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 ISRCTN72019945). 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 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. TRIAL REGISTRATION: ISRCTN72019945 prospectively registered 19/11/2015.

Follow-up of Metal-on-Metal Hip Replacements at a Large District Hospital and the Implementation of Medicines and Healthcare Products Regulatory Agency Guidelines: A Review of 297 Patients.

BACKGROUND: Medicines and Healthcare products Regulatory Agency (MHRA) guidance for patients with metal-on-metal (MoM) hip replacements was provided in 2012 and updated in 2017 to assist in the early detection of soft-tissue reactions due to metal wear debris. A large number of MoM hip replacements were undertaken at our hospital trust. A program of recall for all patients with MoM hip replacements was undertaken and MHRA guidelines were implemented. In this study, we aimed to investigate the effectiveness of the revised MHRA guidelines in the detection of early adverse reactions to metal debris and to re-evaluate the indications for metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) and revision surgery. METHODS: Identification and recall of all patients with MoM hip replacements from 2001 were conducted by using theatre logs, patient records, clinical coding information, and consultant logbooks. Two senior arthroplasty consultants reviewed X-rays and patient records. Postal questionnaires were forwarded to patients, together with requests for general practitioners to complete cobalt and chromium blood tests. The two consultant-led review of MOM replacements was undertaken with further radiological investigations (X-rays, MARS-MRI) performed according to the 2017 guidance with support of consultant radiologists. RESULTS: Of 674 identified patients, 297 were available for review: 26 patients did not have MoM implants, 36 were untraceable, 59 refused follow-up, 87 moved out of area, 147 had died, and 22 already had revision. Of 297 patients, 126 were women and 171 were men; age range was 39 to 95 years (mean age, 69 years); 126 had resurfacing and 171 had MoM replacements. Twenty-six patients had elevated metal ions. Thirty-three patients underwent MARS-MRI: MARS-MRI results were positive in 17 and negative in 16. Of 17 patients with positive MARS-MRI, 10 patients were asymptomatic and seven were waiting revision. CONCLUSIONS: Positive MARS-MRI can often occur in the absence of elevated metal ion levels; elevated blood metal ion levels do not mean MARS-MRI will be positive. All patients with MoM replacements were at risk. It is imperative to assess patients regularly for symptoms that may raise clinical suspicion and maintain a low threshold to performing MARS-MRI.

Differences in beliefs about mood between people with and without bipolar disorder.

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 50 controls were recruited through an online screening study, clinical services, and support organizations. 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 50 controls were included in the analyses. Results indicated that the BD group reported less control over mood, a shorter duration of mood, and less understanding of mood and were more likely to report the cause of depressive symptoms as something internal, compared with 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 with 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.

Feasibility and acceptability of integrated psychological therapy versus treatment as usual for people with bipolar disorder and co-morbid alcohol use: A single blind randomised controlled trial.

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.