A systematic review and meta-ethnography of client and therapist perspectives of the therapeutic alliance in the context of psychotherapy and suicidal experiences.

This review aimed to develop a conceptual model of the therapeutic alliance in the context of psychotherapy and suicidal experiences from therapist and client perspectives. The protocol was pre-registered on PROSPERO (CRD42021268273). MEDLINE, PsycINFO, Web of Science, Embase and CINAHL were systematically searched from database inception to April 2024. Eligible studies were peer-reviewed, qualitative, and included client and/or therapist's perspectives of the therapeutic alliance in the context of psychotherapy and suicidal experiences. Studies were critically appraised and analysed using a meta-ethnography approach involving a reciprocal translation of studies and line of argument synthesis. Thirty-seven papers were included, generating two overarching themes; 'Working on the edge' and 'Being ready, willing, and able to build an alliance in the context of suicidal experiences'. Therapeutic alliance in the context of suicidal experiences is unique, fluid, potentially lifesaving, and influenced by multiple inter-connected internal and external processes and systems. Clinical implications emphasise the need to improve training, supervision, and support for therapists to equip them with the additional skills required in navigating the intricacies of the therapeutic alliance with clients who have suicidal experiences. Flexibly interweaving risk assessment into therapeutic conversation was beneficial to the alliance with suicidal clients and enhanced their safety.

The cost-effectiveness of mental health interventions amongst prison populations: a systematic review (research letter to the editor).

The link between imprisonment and adverse mental health is well established and linked to both recidivism and prison misconduct, with negative consequences for prisoners, the prison system and society. To help minimise these impacts, appropriate mental health interventions are required. However, owing to finite resources to deliver healthcare in prisons, interventions must be both clinically and cost-effective. A systematic literature search was conducted using various medical and economic databases. The search aimed to identify full economic evaluations (comparing costs and consequences of two or more interventions) of mental health interventions for adult prisoners during incarceration. Results were intended to identify evidence gaps and highlight areas for future research. Only one publication met all eligibility requirements, with several limitations identified. This finding highlighted a clear lack of cost-effectiveness evidence for use by decision makers within the prison setting. This emphasises the need for future research to incorporate economic evaluation during the early stages of research design. Research should aim to incorporate both intervention costs and wider healthcare resource use, which may be affected, and generic outcomes, such as quality-adjusted life years (QALYs), which enable comparison across various disease areas and against pre-determined thresholds.

Reflections on working as and supervising trial therapists on trials of psychosocial interventions.

This editorial provides an overview of the challenges and benefits of working as and supervising trial therapists from the perspective of investigators and trial therapists. Key differences between trial therapy and standard care are considered, with recommendations for best practice.

Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation.

BACKGROUND & AIMS: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. METHODS: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. RESULTS: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. CONCLUSION: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. IMPACT AND IMPLICATIONS: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis.

Development of the Prevention of Suicide Behaviour in Prisons: Enhancing Access to Therapy (PROSPECT) logic model and implementation strategies.

AIMS AND METHOD: This study aimed to develop and articulate a logic model and programme theories for implementing a new cognitive-behavioural suicide prevention intervention for men in prison who are perceived to be at risk of death by suicide. Semi-structured one-to-one interviews with key stakeholders and a combination of qualitative analysis techniques were used to develop programme theories. RESULTS: Interviews with 28 stakeholders resulted in five programme theories, focusing on: trust, willingness and engagement; readiness and ability; assessment and formulation; practitioner delivering the 'change work' stage of the intervention face-to-face in a prison environment; and practitioner training, integrating the intervention and onward care. Each theory provides details of what contextual factors need to be considered at each stage, and what activities can facilitate achieving the intended outcomes of the intervention, both intermediate and long term. CLINICAL IMPLICATIONS: The PROSPECT implementation strategy developed from the five theories can be adapted to different situations and environments.

"Where Is My Place?" A Qualitative Study of Gay Men's Experiences of Social Support, Relationships and Community in Relation to Psychological Wellbeing and Distress.

This study aimed to understand young gay men's experiences of social support, relationships, community networks, talking about psychological distress, and their impact on distress and wellbeing. Eight verbatim transcriptions from semi-structured interviews with gay men aged 18-35 years were analyzed using Interpretative Phenomenological Analysis. Three super-ordinate themes were developed; 1) Growing up gay in a straight world: Developmental traumas, regarding men's experiences of homophobic abuse and exclusion and the internalized impact on their identities and identity concealment. 2) Belonging and not belonging within LGBTQ+ communities, encompassing men's varied experiences of LGBTQ+ communities and the corresponding impacts upon their wellbeing. 3) Relational responses to rejection, describing how men made sense of and managed their relationships within the context of the developmental traumas they had experienced growing up as gay men. These findings illuminate the psychological impact of experiencing multiple developmental traumas related to one's identity as a gay man, and how this influences lifelong relational behavior; and how experiences of social support, relationships and LGBTQ+ communities influence men's mental health. They provide a strong rationale for psychological interventions to acknowledge and address gay men's unique and adverse social experiences within their relationships, communities and societies.

Working with suicidal mothers during the perinatal period: a reflexive thematic analysis study with mental health professionals.

BACKGROUND: Suicide is the leading cause of death in mothers postpartum and one of the most common causes of death during pregnancy. Mental health professionals who work in perinatal services can offer insights into the factors they perceive as being linked to mothers' suicidal ideation and behaviour, support offered to mothers and improvements to current practices. We aimed to explore the experiences and perceptions of perinatal mental health professionals who have worked with suicidal mothers during the perinatal period. METHOD: Semi-structured interviews were conducted face-to-face or via telephone with mental health professionals working in perinatal mental health inpatient or community services across England. Data were analysed using reflexive thematic analysis. RESULTS: From the professionals' (n = 15) accounts three main themes were developed from their interview data. The first, factors linked to suicidal ideation and behaviour, overarched two sub-themes: (1.1) the mother's context and (1.2) what the baby represents and what this means for the mother. These sub-themes described factors that professionals assessed or deemed contributory in relation to suicidal ideation and behaviour when a mother was under their care. The second main theme, communicating about and identifying suicidal ideation and behaviour, which outlined how professionals enquired about, and perceived, different suicidal experiences, encapsulated two sub-themes: (2.1) how to talk about suicide and (2.2) types of suicidal ideation and attempts. The third main theme, reducing suicidal ideation through changing how a mother views her baby and herself, focused on how professionals supported mothers to reframe the ways in which they viewed their babies and in turn themselves to reduce suicidal ideation. CONCLUSION: Professionals highlighted many factors that should be considered when responding to a mother's risk of suicide during the perinatal period, such as the support around her, whether the pregnancy was planned and what the baby represented for the mother. Professionals' narratives stressed the importance of adopting a tailored approach to discussing suicidal experiences with mothers to encourage disclosure. Our findings also identified psychological factors that professionals perceived as being linked to suicidal outcomes for mothers, such as self-efficacy; these factors should be investigated further.

African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models. CONCLUSIONS: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Single-cell transcriptomics stratifies organoid models of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of morbidity with limited treatment options. Thus, accurate in vitro systems to test new therapies are indispensable. While recently, human liver organoid models have emerged to assess steatotic liver disease, a systematic evaluation of their translational potential is still missing. Here, we evaluated human liver organoid models of MASLD, comparatively testing disease induction in three conditions: oleic acid, palmitic acid, and TGF-ß1. Through single-cell analyses, we find that all three models induce inflammatory signatures, but only TGF-ß1 promotes collagen production, fibrosis, and hepatic stellate cell expansion. In striking contrast, oleic acid ameliorates fibrotic signatures and reduces the hepatic stellate cell population. Linking data from each model to gene expression signatures associated with MASLD disease progression further demonstrates that palmitic acid and TGF-ß1 more robustly model inflammation and fibrosis. Our findings highlight the importance of stratifying MASLD organoid models by signatures of clinical disease progression, provide a single-cell reference to benchmark future organoid injury models, and allow us to study evolving steatohepatitis, fibrosis, and HSC susceptibility to injury in a dynamic, multi-lineage human in vitro system.

The interplay between suicidal experiences, psychotic experiences and interpersonal relationships: a qualitative study.

BACKGROUND: Suicidal thoughts, acts, plans and deaths are considerably more prevalent in people with non-affective psychosis, including schizophrenia, compared to the general population. Social isolation and interpersonal difficulties have been implicated in pathways which underpin suicidal experiences in people with severe mental health problems. However, the interactions between psychotic experiences, such as hallucinations and paranoia, suicidal experiences, and the presence, and indeed, absence of interpersonal relationships is poorly understood and insufficiently explored. The current study sought to contribute to this understanding. METHODS: An inductive thematic analysis was conducted on transcripts of 22, individual, semi-structured interviews with adult participants who had both non-affective psychosis and recent suicidal experiences. A purposive sampling strategy was used. Trustworthiness of the analysis was assured with researcher triangulation. RESULTS: Participants relayed both positive and negative experiences of interpersonal relationships. A novel conceptual model is presented reflecting a highly complex interplay between a range of different suicidal experiences, psychosis, and aspects of interpersonal relationships. Three themes fed into this interplay, depicting dynamics between perceptions of i. not mattering and mattering, ii. becoming disconnected from other people, and iii. constraints versus freedom associated with sharing suicidal and psychotic experiences with others. CONCLUSION: This study revealed a detailed insight into ways in which interpersonal relationships are perceived to interact with psychotic and suicidal experiences in ways that can be both beneficial and challenging. This is important from scientific and clinical perspectives for understanding the complex pathways involved in suicidal experiences. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03114917), 14th April 2017. ISRCTN (reference ISRCTN17776666 .); 5th June 2017). Registration was recorded prior to participant recruitment commencing.

Beyond genome-wide association studies: Investigating the role of noncoding regulatory elements in primary sclerosing cholangitis.

BACKGROUND: Genome-wide association studies (GWAS) have identified 30 risk loci for primary sclerosing cholangitis (PSC). Variants within these loci are found predominantly in noncoding regions of DNA making their mechanisms of conferring risk hard to define. Epigenomic studies have shown noncoding variants broadly impact regulatory element activity. The possible association of noncoding PSC variants with regulatory element activity has not been studied. We aimed to (1) determine if the noncoding risk variants in PSC impact regulatory element function and (2) if so, assess the role these regulatory elements have in explaining the genetic risk for PSC. METHODS: Available epigenomic datasets were integrated to build a comprehensive atlas of cell type-specific regulatory elements, emphasizing PSC-relevant cell types. RNA-seq and ATAC-seq were performed on peripheral CD4+ T cells from 10 PSC patients and 11 healthy controls. Computational techniques were used to (1) study the enrichment of PSC-risk variants within regulatory elements, (2) correlate risk genotype with differences in regulatory element activity, and (3) identify regulatory elements differentially active and genes differentially expressed between PSC patients and controls. RESULTS: Noncoding PSC-risk variants are strongly enriched within immune-specific enhancers, particularly ones involved in T-cell response to antigenic stimulation. In total, 250 genes and >10,000 regulatory elements were identified that are differentially active between patients and controls. CONCLUSIONS: Mechanistic effects are proposed for variants at 6 PSC-risk loci where genotype was linked with differential T-cell regulatory element activity. Regulatory elements are shown to play a key role in PSC pathophysiology.

Developing a consensus of recovery from suicidal ideations and behaviours: A Delphi study with experts by experience.

BACKGROUND: Understanding recovery in mental health has received significant attention and consequently, recovery has been incorporated into health policy across many countries in the Global North. In comparison, the concept of 'recovery' from suicidal thoughts and behaviours has received little attention. However, the few studies in this area appear to suggest that recovery is a complex and an idiosyncratic process with many contributing factors. This can present a challenge for clinicians and services seeking to become more recovery focused. Thus, it seems of importance to develop a consensus on how recovery from suicidal thoughts and behaviours is conceptualised. AIM: The study aimed to use the Delphi design to establish a consensus of how recovery is defined by those with lived experience of suicidal thoughts and behaviours. The Delphi method draws on the expertise of a panel, often involving clinicians, researchers and lived experience experts to develop consensus over a topic by inviting them to rate the importance of, often a series of statements to a given topic area. METHOD: Lived experience experts were asked to complete two rounds of questionnaires distributed online to capture their views on recovery. RESULTS: A total of 196 individuals gave their views on the first round of the study and 97 gave their views on the second round. A final list of 110 statements was developed that 80% or more of participants defined as essential or important. Statements covered items that were important in defining, facilitation and hindering the process of recovery. CONCLUSION: Findings are consistent with the wider literature that suggests that recovery is an idiosyncratic process, but with many commonly shared features. Here we also show that a comprehensive definition of recovery must include factors that hinder the process of recovery. Implications and recommendations for practice, policy development and future research are discussed.

Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.

BACKGROUND AND AIMS: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA). APPROACH AND RESULTS: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events. CONCLUSIONS: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

What emotions do male prisoners experience in the lead-up to suicide and violence? A participatory visual method study.

Rates of suicide and violence are higher amongst male prisoners than the general population. This study aimed to explore the emotional experiences of male prisoners in the distal and immediate lead-up to acts of suicide and violence. Nine male prisoners created drawings of their emotions in the lead-up to an act of suicide and/or violence. Accompanying verbal interview data was collected to explore the narrative of these drawings. Polytextual thematic analysis was conducted on both the visual and audio data. Three themes were found. 'The outside picture' depicted the emotions that male prisoners exhibited externally. 'The inside picture' illustrated the internal emotions felt by male prisoners which were often complex and abstract. 'The complexity of the picture' denotes the complicated relationship between emotions and suicide/violence. Male prisoners experience a range of emotions in the lead up to acts of suicide and violence, with a similar set of emotions being experienced immediately prior to both suicide and violence. This study has illustrated the benefits of using a novel and creative methodology, and has demonstrated that future research with male prisoners could benefit from adopting a participatory visual methodology.

What is important to service users and staff when implementing suicide-focused psychological therapies for people with psychosis into mental health services?

Introduction: Suicide is a leading cause of death globally. People with psychosis are at increased risk of suicide death and up to half experience suicidal thoughts and/or engage in suicidal behaviors in their lifetime. Talking therapies can be effective in alleviating suicidal experiences. However, research is yet to be translated into practice, demonstrating a gap in service provision. The barriers and facilitators in therapy implementation require a thorough investigation including the perspectives of different stakeholders such as service users and mental health professionals. This study aimed to investigate stakeholders' (health professionals and service users) perspectives of implementing a suicide-focused psychological therapy for people experiencing psychosis in mental health services. Methods: Face-to-face, semi-structured interviews with 20 healthcare professionals and 18 service users were conducted. Interviews were audio recorded and transcribed verbatim. Data were analyzed and managed using reflexive thematic analysis and NVivo software. Results: For suicide-focused therapy to be successfully implemented in services for people with psychosis, there are four key aspects that need to be considered: (i) Creating safe spaces to be understood; (ii) Gaining a voice; (iii) Accessing therapy at the right time; and (iv) Ensuring a straightforward pathway to accessing therapy. Discussion: Whilst all stakeholders viewed a suicide-focused therapy as valuable for people experiencing psychosis, they also recognize that enabling successful implementation of such interventions will require additional training, flexibility, and resources to existing services.

A systematic review of the co-occurrence of self-harm and aggression: Is dual harm a unique behavioural construct?

Introduction: Dual harm is the co-occurrence of self-harm and aggression during an individual's lifetime. It is unclear whether sufficient evidence exists for dual harm as a unique clinical entity. This systematic review aimed to examine whether there are psychological factors that are uniquely associated with dual harm when compared to those who have engaged in sole harm (self-harm alone, aggression alone) and no harmful behaviours. Our secondary aim was to conduct a critical appraisal of the literature. Methods: The review searched PsycINFO, PubMed, CINAHL, and EThOS on September 27, 2022, resulting in 31 eligible papers that represented 15,094 individuals. An adapted version of the Agency for Healthcare Research and Quality was used to assess risk of bias and a narrative synthesis was conducted. Results: The included studies assessed differences in mental health problems, personality, and emotion related factors between the different behavioural groups. We found weak evidence that dual harm is an independent construct with unique psychological characteristics. Rather, our review suggests that dual harm results from the interaction of psychological risk factors that are associated with self-harm and aggression. Discussion: The critical appraisal identified numerous limitations within the dual harm literature. Clinical implications and recommendations for future research are provided. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197323, identifier CRD42020197323.

Acceptability of a novel suicide prevention psychological therapy for people who experience non-affective psychosis.

OBJECTIVES: Suicide is a leading cause of death worldwide. People experiencing psychosis are at increased risk of death by suicide. Talking therapies can alleviate suicidal thoughts, plans, and attempts. Therapies need to also be acceptable to recipients. The aim of this study was to investigate the views on psychological therapy for people experiencing psychosis and suicidality using the Theoretical Framework of Acceptability. DESIGN: Qualitative interview study. METHODS: Participants were recruited from a randomised controlled trial comparing suicide prevention psychological therapy with treatment as usual. Individuals had a diagnosis of non-affective psychosis and experience of suicidal thoughts, plans and/or attempts. To assess the acceptability of the therapy, semi-structured interviews were conducted with 20 participants randomised to receive therapy. Data were deductively analysed using an adaptation of the Theoretical Framework of Acceptability. RESULTS: Interviews (Mean = 45 min) were conducted and audio recorded with 21 participants. Data were organised into six themes: 1. Affective attitude, 2. Burden, 3. Alliance, 4. Intervention coherence, 5. Perceived effectiveness, and 6. Self-efficacy. There was no evidence of issues relating to domains of ethicality and opportunity costs associated with receiving therapy. CONCLUSIONS: Talking about suicide was difficult and, at times, distressing, but it was perceived to be useful for understanding experiences. To be acceptable, it is important for therapists to ensure that clients' understanding of therapy aligns with expectations of effectiveness and to invest in building strong therapeutic alliances. Future research will benefit from examining therapists' experiences of delivering therapy through different modes (e.g. online, telephone).