The mediating role of reflective functioning and general psychopathology in the relationship between childhood conduct disorder and adult aggression among offenders.

BACKGROUND: The nature of the pathway from conduct disorder (CD) in adolescence to antisocial behavior in adulthood has been debated and the role of certain mediators remains unclear. One perspective is that CD forms part of a general psychopathology dimension, playing a central role in the developmental trajectory. Impairment in reflective functioning (RF), i.e., the capacity to understand one's own and others' mental states, may relate to CD, psychopathology, and aggression. Here, we characterized the structure of psychopathology in adult male-offenders and its role, along with RF, in mediating the relationship between CD in their adolescence and current aggression. METHODS: A secondary analysis of pre-treatment data from 313 probation-supervised offenders was conducted, and measures of CD symptoms, general and specific psychopathology factors, RF, and aggression were evaluated through clinical interviews and questionnaires. RESULTS: Confirmatory factor analyses indicated that a bifactor model best fitted the sample's psychopathology structure, including a general psychopathology factor (p factor) and five specific factors: internalizing, disinhibition, detachment, antagonism, and psychoticism. The structure of RF was fitted to the data using a one-factor model. According to our mediation model, CD significantly predicted the p factor, which was positively linked to RF impairments, resulting in increased aggression. CONCLUSIONS: These findings highlight the critical role of a transdiagnostic approach provided by RF and general psychopathology in explaining the link between CD and aggression. Furthermore, they underscore the potential utility of treatments focusing on RF, such as mentalization-based treatment, in mitigating aggression in offenders with diverse psychopathologies.

The positive and negative consequences of stress and its relationship with coping in medical students: A qualitative study.

Rates of mental health problems among medical students have prompted efforts to reduce stress during medical training. However, stress can be motivating and is a feature of clinical work. This qualitative study explores what makes an experience stressful, and how medical students respond to such experiences. In-depth interviews were conducted with a purposive sample of 15 medical students. Experiences were distressing when they threatened students' self-perception, goals or coping mechanisms, or when they reminded the student of distressing past events. Moderate stress was motivating and could build resilience. Students selected coping mechanisms based on their availability, acceptability, likely outcome and their previous experience of using these mechanisms. Social support, extra-curricular activities and exercise were helpful. High levels of distress, poor self-esteem and course factors, including remote placements, impaired engagement with coping strategies. Perception of stressors as being insurmountable or beyond one's control, led to increasing distress and the adoption of avoidant coping strategies. University strategies need to consider the beneficial effects of stress and seek to bolster coping resources as well as minimising unnecessary sources of stress.

Safe Implementation of a Next-Generation Surgical Robot: First Analysis of 2,083 Cases in the Versius Surgical Registry.

OBJECTIVE: To present the first report of data from the Versius Surgical Registry, a prospective, multicenter data registry with ongoing collection across numerous surgical indications, developed to accompany the Versius Robotic Surgical System into clinical practice. BACKGROUND: A data registry can be utilized to minimize risk to patients by establishing the safety and effectiveness of innovative medical devices and generating a thorough evidence base of real-world data. METHODS: Surgical outcome data were collected and inputted through a secure online platform. Preoperative data included patient age, sex, body mass index, surgical history, and planned procedures. Intraoperative data included operative time, complications during surgery, conversion from robot-assisted surgery to an alternative surgical technique, and blood loss. Postoperative outcome data included length of hospital stay, complications following surgery, serious adverse events, return to the operating room, readmission to the hospital, and mortality within 90 days of surgery. RESULTS: This registry analysis included 2083 cases spanning general, colorectal, hernia, gynecologic, urological, and thoracic indications. A considerable number of cases were recorded for cholecystectomy (n=539), anterior resection (n=162), and total laparoscopic hysterocolpectomy (n=324) procedures. The rates of conversion to an alternative technique, serious adverse events, and 90-day mortality were low for all procedures across all surgical indications. CONCLUSIONS: We report the large-scale analysis of the first 2083 cases recorded in this surgical registry, with substantial data collected for cholecystectomies, anterior resections, and total laparoscopic hysterectomies. The extensive surgical outcome data reported here provide real-world evidence for the safe implementation of the surgical robot into clinical practice.

Emotional dysregulation in childhood and disordered eating and self-harm in adolescence: prospective associations and mediating pathways.

BACKGROUND: Emotional dysregulation may be a risk factor for disordered eating and self-harm in young people, but few prospective studies have assessed these associations long-term, or considered potential mediators. We examined prospective relationships between childhood emotional dysregulation and disordered eating and self-harm in adolescence; and social cognition, emotional recognition, and being bullied as mediators. METHODS: We analysed Avon Longitudinal Study of Parents and Children data on 3,453 males and 3,481 females. We examined associations between emotional dysregulation at 7 years and any disordered eating and any self-harm at 16 years with probit regression models. We also assessed whether social cognition (7 years), emotional recognition (8 years) and bullying victimisation (11 years) mediated these relationships. RESULTS: Emotional dysregulation at age 7 years was associated with disordered eating [fully adjusted probit B (95% CI) = 0.082 (0.029, 0.134)] and self-harm [fully adjusted probit B (95% CI) = 0.093 (0.036, 0.150)] at age 16 years. There was no evidence of sex interactions or difference in effects between self-harm and disordered eating. Mediation models found social cognition was a key pathway to disordered eating (females 51.2%; males 27.0% of total effect) and self-harm (females 15.7%; males 10.8% of total effect). Bullying victimisation was an important pathway to disordered eating (females 17.1%; males 10.0% of total effect), but only to self-harm in females (15.7% of total effect). Indirect effects were stronger for disordered eating than self-harm. CONCLUSIONS: In males and females, emotional dysregulation in early childhood is associated with disordered eating and self-harm in adolescence and may be a useful target for prevention and treatment. Mediating pathways appeared to differ by sex and outcome, but social cognition was a key mediating pathway for both disordered eating and self-harm.

"Pouring their heart out in Sainsbury's": qualitative study of young people's, parents' and mental health practitioners' experiences of adapting to remote online mental health appointments during COVID-19.

BACKGROUND: During the COVID-19 pandemic, technologies such as videoconferencing were used to deliver mental health appointments remotely online. For many people, this was a change from previous methods of mental healthcare receipt and delivery. We aimed to explore in-depth how practitioners, young people and parents in the UK experienced this transition. METHODS: We used qualitative methods to collect data, triangulating between free-text online survey data (n = 38), focus groups (n = 5) (3 young adult groups (total n = 11); 2 practitioner groups (total n = 7)), and semi-structured interviews (practitioners n = 8; parents n = 4). Data were analysed using reflexive thematic analysis. RESULTS: Participants held mixed views about remote appointments, which were encompassed within the five themes of: home as clinic; disrupted therapeutic relationships; difficulties with engagement; uncontained risk; and scope of care provision. While appointments at home could be regarded as more comfortable, naturalistic and accessible, it was also recognised that remoteness compromised practitioner control with consequences for their ability to monitor patient engagement, manage risk and ensure confidentiality when others were present in the home. This could create an additional burden for parents as they tried to facilitate appointments but felt unsupported in this role. Relatedly, remoteness was seen to hinder interpersonal communication, formation of trust, communication of empathy and opportunities to observe body language, all of which were deemed important to building and maintaining effective therapeutic relationships. Despite this, others thought the anonymity of a remote exchange may allow earlier disclosure. There was disagreement as to whether remote provision narrowed or expanded the scope of practice. CONCLUSIONS: While some had positive views of remote mental health appointments, others found them challenging. Findings highlight key areas requiring attention and mitigation in future offerings of remote provision, namely: risk management, parental burden, and problematic engagement.

Impact of early intervention on the population prevalence of common mental disorders: 20-year prospective study.

BACKGROUND: The potential for early interventions to reduce the later prevalence of common mental disorders (CMD) first experienced in adolescence is unclear. AIMS: To examine the course of CMD and evaluate the extent to which the prevalence of CMD could be reduced by preventing adolescent CMD, or by intervening to change four young adult processes, between the ages of 20 and 29 years, that could be mediating the link between adolescent and adult disorder. METHOD: This was a prospective cohort study of 1923 Australian participants assessed repeatedly from adolescence (wave 1, mean age 14 years) to adulthood (wave 10, mean age 35 years). Causal mediation analysis was undertaken to evaluate the extent to which the prevalence of CMD at age 35 years in those with adolescent CMD could be reduced by either preventing adolescent CMD, or by intervening on four young adult mediating processes: the occurrence of young adult CMD, frequent cannabis use, parenting a child by age 24 years, and engagement in higher education and employment. RESULTS: At age 35, 19.2% of participants reported CMD; a quarter of these participants experienced CMD during both adolescence and young adulthood. In total, 49% of those with CMD during both adolescence and young adulthood went on to report CMD at age 35 years. Preventing adolescent CMD reduced the population prevalence at age 35 years by 3.9%. Intervening on all four young adult processes among those with adolescent CMD, reduced this prevalence by 1.6%. CONCLUSIONS: In this Australian cohort, a large proportion of adolescent CMD resolved by adulthood, and by age 35 years, the largest proportion of CMD emerged among individuals without prior CMD. Time-limited, early intervention in those with earlier adolescent disorder is unlikely to substantially reduce the prevalence of CMD in midlife.

Engaging communities in addressing air quality: a scoping review.

BACKGROUND: Exposure to air pollution has a detrimental effect on health and disproportionately affects people living in socio-economically disadvantaged areas. Engaging with communities to identify concerns and solutions could support organisations responsible for air quality control, improve environmental decision-making, and widen understanding of air quality issues associated with health. This scoping review aimed to provide an overview of approaches used to engage communities in addressing air quality and identify the outcomes that have been achieved. METHODS: Searches for studies that described community engagement in air quality activities were conducted across five databases (Academic Search Complete, CABI, GreenFILE, MEDLINE, Web of Science). Data on study characteristics, community engagement approach, and relevant outcomes were extracted. The review process was informed by a multi-stakeholder group with an interest in and experience of community engagement in air quality. Thirty-nine papers from thirty studies were included in the final synthesis. CONCLUSION: A range of approaches have been used to engage communities in addressing air quality, most notably air quality monitoring. Positive outcomes included increased awareness, capacity building, and changes to organisational policy and practice. Longer-term projects and further exploration of the impact of community engagement on improving air quality and health are needed as reporting on these outcomes was limited.

Developing good practice indicators to assist mental health practitioners to converse with young people about their online activities and impact on mental health: a two-panel mixed-methods Delphi study.

BACKGROUND: Online activity has been linked to poor mental health in children and young people, particularly those with existing vulnerability who may inadvertently or otherwise access harmful content. It is suggested health and social care practitioners should address online activity during mental health consultations, but guidance about acceptable or effective ways to do this is lacking. This study sought to derive good practice guidance to support mental health practitioners to engage young people in conversations about their online activities and impact on mental health. METHODS: A mixed-methods Delphi (consensus) study was conducted with a panel of mental health practitioners (n = 21) and a panel of young people (n = 22). Practitioners worked with children or young adults in the UK, mostly in statutory services (80.9%), in varied clinical roles, with 2 - 30 years of experience and most were female (87.5%). Young people were mostly female (77.3%), 13-22 years old, reported varied mental health diagnoses and had sought help from services. Across 3 rounds, panellists completed questionnaires which involved rating agreement with statements and answering open-ended questions. Iterative analysis informed subsequent questionnaire content. The percentage of participants rating their level of agreement with each statement was calculated. The threshold for inclusion as a good practice indicator (GPI) was 75% across both panels. Thematic analysis was used for free-text data. RESULTS: Twenty-seven GPIs emerged covering 'who' (which young people) should be asked about online activities, 'when', 'what' should be discussed, and with what 'outcome'. Panels agreed conversations should be initiated with all young people from first meeting and regularly thereafter, with 'red flags' indicating a conversation may be pertinent. Core topics were identified with additional areas for patients presenting with disordered eating or self-harm. Panels emphasised conversations should be fluid, normalised, and encourage reflection and self-awareness. CONCLUSIONS: Mental health practitioners could empower young people to exercise agency in relation to online safety and capitalise on positive features. Findings also identify training needs for practitioners. Further research should explore real-world application of the GPIs and transferability to underrepresented groups within our panels, such as males and younger children. Ethnicity and deprivation were not recorded.

Clinician views on best practice community care for people with complex emotional needs and how it can be achieved: a qualitative study.

BACKGROUND: Individuals with Complex Emotional Needs (CEN) services, a working description to refer to the needs experienced by people who may have been diagnosed with a "personality disorder", face premature mortality, high rates of co-morbidity, service user and treatment costs. Service provision for this population is recurrently identified as needing to be transformed: there are serious concerns about quality, accessibility, fragmentation of the service system and the stigma and therapeutic pessimism service users encounter. Understanding clinician perspectives is vital for service transformation, as their views and experiences shed light on potential barriers to achieving good care, and how these might be overcome. In this study, we aimed to explore these views. METHODS: We used a qualitative interview design. A total of fifty participants from a range of professions across specialist and generic community mental health services across England who provide care to people with CEN took part in six focus groups and sixteen one-to-one interviews. We analysed the data using a thematic approach. FINDINGS: Main themes were: 1) Acknowledging the heterogeneity of needs: the need for a person-centred care approach and flexibility when working with CEN, 2) 'Still a diagnosis of exclusion': Exploring the healthcare provider-level barriers to providing care, and 3) Understanding the exclusionary culture: exploring the system-based barriers to providing care for CEN. Across these themes, staff highlighted in particular the need for care that was person-centred, relational, empathic, and trauma informed. Major barriers to achieving this are stigmatising attitudes and behaviour towards people with CEN, especially in generic mental health services, lack of development of coherent service systems offering clear long-term pathways and ready access to high quality treatment, and lack of well-developed structures for staff training and support. DISCUSSION: Overall, the findings point towards clinician views as generally congruent with those of service users, reinforcing the need for priorities towards systemwide change to ensure that best practice care is provided for people with CEN. Particularly prominent is the need to put in place systemwide training and support for clinicians working with CEN, encompassing generic and specialist services, and to challenge the stigma still experienced throughout the system. CONCLUSIONS: Staff working with this service user group report that delivering best practice care requires services to be flexible, integrated, and sustainably funded, and for staff to be supported through ongoing training and supervision.

Service user perspectives of community mental health services for people with complex emotional needs: a co-produced qualitative interview study.

BACKGROUND: There is consensus that services supporting people with complex emotional needs are part of a mental health care system in which change is needed. To date, service users' views and co-production initiatives have had little impact on the development of interventions and care. This needs to change, and our paper evidences the experiences and perspectives of a diverse range of people on how community services can best address the needs of people with complex emotional needs. METHODS: A co-produced qualitative research study. Lived experience researchers led data collection and analysis. Individual interviews were conducted with 30 people across England who had a diverse range of experiences and perspectives of using community services for complex emotional needs. Participants were asked about their experiences of using community services for their mental health, and views on how community services can best address their needs. Thematic analysis was used to analyse the data. RESULTS: Participants reported some experiences of good practice but also of experiences of severely stigmatising interventions, a lack of effective support and service fragmentation. Relational Practice was identified as the central overarching theme and describes how community services can best support people with complex emotional needs. This approach involves care delivered in a non-stigmatising, individualised and compassionate way and care that is trauma-informed. It involves care that is planned collaboratively with service users to ensure their multiple needs are addressed in a flexible, holistic and consistent way which accounts for the long-term and fluctuating nature of their needs. CONCLUSIONS: Relational practice approaches have potential to facilitate better community care for people with complex emotional needs. Research and service development are needed to examine how best to implement such approaches across the mental health service system. This work must be co-produced with people with relevant lived experience, their carers and the professionals who support them.

Crisis interventions for adults with borderline personality disorder.

BACKGROUND: People diagnosed with borderline personality disorder (BPD) frequently present to healthcare services in crisis, often with suicidal thoughts or actions. Despite this, little is known about what constitutes effective management of acute crises in this population and what type of interventions are helpful at times of crisis. In this review, we will examine the efficacy of crisis interventions, defined as an immediate response by one or more individuals to the acute distress experienced by another individual, designed to ensure safety and recovery and lasting no longer than one month. This review is an update of a previous Cochrane Review examining the evidence for the effects of crisis interventions in adults diagnosed with BPD. OBJECTIVES: To assess the effects of crisis interventions in adults diagnosed with BPD in any setting. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to January 2022. We also checked reference lists, handsearched relevant journal archives and contacted experts in the field to identify any unpublished or ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing crisis interventions with usual care, no intervention or waiting list, in adults of any age diagnosed with BPD. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two studies with 213 participants. One study (88 participants) was a feasibility RCT conducted in the UK that examined the effects of joint crisis plans (JCPs) plus treatment as usual (TAU) compared to TAU alone in people diagnosed with BPD. The primary outcome was self-harm. Participants had an average age of 36 years, and 81% were women. Government research councils funded the study. Risk of bias was unclear for blinding, but low in the other domains assessed. Evidence from this study suggested that there may be no difference between JCPs and TAU on deaths (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.06 to 14.14; 88 participants; low-certainty evidence); mean number of self-harm episodes (mean difference (MD) 0.30, 95% CI -36.27 to 36.87; 72 participants; low-certainty evidence), number of inpatient mental health nights (MD 1.80, 95% CI -5.06 to 8.66; 73 participants; low-certainty evidence), or quality of life measured using the EuroQol five-dimension questionnaire (EQ-5D; MD -6.10, 95% CI -15.52 to 3.32; 72 participants; very low-certainty evidence). The study authors calculated an Incremental Cost Effectiveness Ratio of GBP -32,358 per quality-adjusted life year (QALY), favouring JCPs, but they described this result as "hypothesis-generating only" and we rated this as very low-certainty evidence.  The other study (125 participants) was an RCT conducted in Sweden of brief admission to psychiatric hospital by self-referral (BA) compared to TAU, in people with self-harm or suicidal behaviour and three or more diagnostic criteria for BPD. The primary outcome was use of inpatient mental health services. Participants had an average age of 32 years, and 85% were women. Government research councils and non-profit foundations funded the study. Risk of bias was unclear for blinding and baseline imbalances, but low in the other domains assessed. The evidence suggested that there is no clear difference between BA and TAU on deaths (RR 0.49, 95% CI 0.05 to 5.29; 125 participants; low-certainty evidence), mean number of self-harm episodes (MD -0.03, 95% CI -2.26 to 2.20; 125 participants; low-certainty evidence), violence perpetration (RR 2.95, 95% CI 0.12 to 71.13; 125 participants; low-certainty evidence), or days of inpatient mental health care (MD 0.70, 95% CI -14.32 to 15.72; 125 participants; low-certainty evidence). The study suggested that BA may have little or no effect on the mean number of suicide attempts (MD 0.00, 95% CI -0.06 to 0.06; 125 participants; very low-certainty evidence). We also identified three ongoing RCTs that met our inclusion criteria. The results will be incorporated into future updates of this review. AUTHORS' CONCLUSIONS: A comprehensive search of the literature revealed very little RCT-based evidence to inform the management of acute crises in people diagnosed with BPD. We included two studies of two very different types of intervention (JCP and BA). We found no clear evidence of a benefit over TAU in any of our main outcomes. We are very uncertain about the true effects of either intervention, as the evidence was judged low- and very low-certainty, and there was only a single study of each intervention. There is an urgent need for high-quality, large-scale, adequately powered RCTs on crisis interventions for people diagnosed with BPD, in addition to development of new crisis interventions.

Mental health before and during the COVID-19 pandemic in two longitudinal UK population cohorts.

BACKGROUND: The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences. AIMS: To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic. METHOD: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale. RESULTS: Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23-26%) compared with a pre-pandemic level of 13% (95% CI 12-14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression. CONCLUSIONS: These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.

Childhood adversity, pubertal timing and self-harm: a longitudinal cohort study.

BACKGROUND: The occurrence of early childhood adversity is strongly linked to later self-harm, but there is poor understanding of how this distal risk factor might influence later behaviours. One possible mechanism is through an earlier onset of puberty in children exposed to adversity, since early puberty is associated with an increased risk of adolescent self-harm. We investigated whether early pubertal timing mediates the association between childhood adversity and later self-harm. METHODS: Participants were 6698 young people from a UK population-based birth cohort (ALSPAC). We measured exposure to nine types of adversity from 0 to 9 years old, and self-harm when participants were aged 16 and 21 years. Pubertal timing measures were age at peak height velocity (aPHV - males and females) and age at menarche (AAM). We used generalised structural equation modelling for analyses. RESULTS: For every additional type of adversity; participants had an average 12-14% increased risk of self-harm by 16. Relative risk (RR) estimates were stronger for direct effects when outcomes were self-harm with suicidal intent. There was no evidence that earlier pubertal timing mediated the association between adversity and self-harm [indirect effect RR 1.00, 95% confidence interval (CI) 1.00-1.00 for aPHV and RR 1.00, 95% CI 1.00-1.01 for AAM]. CONCLUSIONS: A cumulative measure of exposure to multiple types of adversity does not confer an increased risk of self-harm via early pubertal timing, however both childhood adversity and early puberty are risk factors for later self-harm. Research identifying mechanisms underlying the link between childhood adversity and later self-harm is needed to inform interventions.

Standard set of patient-reported outcomes for personality disorder.

PURPOSE: The purpose of the article is to present standard set of outcomes for people with personality disorder (PD), in order to facilitate patient outcome measurement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) gathered a multidisciplinary international working group, consisting of 16 experts, including clinicians, nurses, psychologists, methodologists and patient representatives, to develop a standard set of outcome measures for people with PD. The Delphi method was used to reach consensus on the scope of the set, outcome domains, outcome measures, case-mix variables and time points for measuring outcomes in service users. For each phase, a project team prepared materials based on systematic literature reviews and consultations with experts. RESULTS: The working group decided to include PD, as defined by International Classification of Diseases 11th revision (ICD-11). Eleven core outcomes and three optional outcomes across four health domains (mental health, behaviour, functioning and recovery) were defined as those relevant for people with PD. Validated measures for the selected outcomes were selected, some covering more than one outcome. Case-mix variables were aligned to other ICHOM mental health standard sets and consisted of demographic factors and those related to the treatment that people received. The group recommended that most outcomes are measured at baseline and annually. CONCLUSION: The international minimum standard set of outcomes has the potential to improve clinical decision making through systematic measurement and comparability. This will be key in improving the standard of health care for people with PD across the world.

An exploration of the genetic epidemiology of non-suicidal self-harm and suicide attempt.

BACKGROUND: Empirical evidence supporting the distinction between suicide attempt (SA) and non-suicidal self-harm (NSSH) is lacking. Although NSSH is a risk factor for SA, we do not currently know whether these behaviours lie on a continuum of severity, or whether they are discrete outcomes with different aetiologies. We conducted this exploratory genetic epidemiology study to investigate this issue further. METHODS: We explored the extent of genetic overlap between NSSH and SA in a large, richly-phenotyped cohort (the Avon Longitudinal Study of Parents and Children; N = 4959), utilising individual-level genetic and phenotypic data to conduct analyses of genome-wide complex traits and polygenic risk scores (PRS). RESULTS: The single nucleotide polymorphism heritability of NSSH was estimated to be 13% (SE 0.07) and that of SA to be 0% (SE 0.07). Of the traits investigated, NSSH was most strongly correlated with higher IQ (rG = 0.31, SE = 0.22), there was little evidence of high genetic correlation between NSSH and SA (rG = - 0.1, SE = 0.54), likely due to the low heritability estimate for SA. The PRS for depression differentiated between those with NSSH and SA in multinomial regression. The optimal PRS prediction model for SA (Nagelkerke R2 0.022, p < 0.001) included ADHD, depression, income, anorexia and neuroticism and explained more variance than the optimal prediction model for NSSH (Nagelkerke R2 0.010, p < 0.001) which included ADHD, alcohol consumption, autism spectrum conditions, depression, IQ, neuroticism and suicide attempt. CONCLUSIONS: Our findings suggest that SA does not have a large genetic component, and that although NSSH and SA are not discrete outcomes there appears to be little genetic overlap between the two. The relatively small sample size and resulting low heritability estimate for SA was a limitation of the study. Combined with low heritability estimates, this implies that family or population structures in SA GWASs may contribute to signals detected.

Suicidality in family caregivers of people with long-term illnesses and disabilities: A scoping review.

An emerging body of international research suggests family caregivers may be a high-risk group for suicide, but the evidence has not been synthesised. Forty-eight peer-reviewed journal articles were included in this review, spanning low-, middle-, and high-income countries and a variety of illnesses and disabilities. The proportion of caregivers experiencing suicidal ideation ranged from 2.7% to 71%, with evidence of suicide attempts, deaths by suicide, and deaths by homicide-suicide also reported. Risk and protective factors varied across studies and there was little consideration of differences by caregiving relationship, type of illness/disability, or country. There is sufficient evidence to warrant concern for caregivers around the world and prompt action in policy and practice, but more rigorous research is required to draw clear, nuanced conclusions about risk and inform evidence-based prevention and intervention.

Correction: A Direct-to-Public Peer Support Program (Big White Wall) Versus Web-Based Information to Aid the Self-management of Depression and Anxiety: Results and Challenges of an Automated Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/23487.].

A Direct-to-Public Peer Support Program (Big White Wall) Versus Web-Based Information to Aid the Self-management of Depression and Anxiety: Results and Challenges of an Automated Randomized Controlled Trial.

BACKGROUND: Effective help for depression and anxiety reaches a small proportion of people who might benefit from it. The scale of the problem suggests the need for effective, safe web-based public health services delivered directly to the public. One model, the Big White Wall (BWW), offers peer support at low cost. As these interventions are delivered digitally, we tested whether a randomized controlled trial (RCT) intervention could also be fully delivered and evaluated digitally. OBJECTIVE: This study aims to determine the reach, feasibility, acceptability, baseline costs, and outcomes of a public health campaign for an automated RCT of the BWW, providing digital peer support and information, compared with a standard website used by the National Health Service Moodzone (MZ), to people with probable mild-to-moderate depression and anxiety disorder. The primary outcome was the change in self-rated well-being at 6 weeks, measured using the Warwick-Edinburgh Mental Well-Being Scale. METHODS: An 18-month campaign was conducted across Nottinghamshire, the United Kingdom (target population 914,000) to advertise the trial directly to the public through general marketing, web-based and social media sources, health services, other public services, and third-sector groups. The population reach of this campaign was examined by the number of people accessing the study website and self-registering to the study. A pragmatic, parallel-group, single-blind RCT was then conducted using a fully automated trial website in which eligible participants were randomized to receive either 6 months of access to BWW or signposted to MZ. Those eligible for participation were aged >16 years with probable mild-to-moderate depression or anxiety disorders. RESULTS: Of 6483 visitors to the study website, 1510 (23.29%) were eligible. Overall, 790 of 1510 (52.32%) visitors participated. Of 790 visitors, 397 (50.3%) were randomized to BWW and 393 (49.7%) to MZ. Their mean age was 38 (SD 13.8) years, 81.0% (640/790) were female, 93.4% (738/790) were White, and 47.4% (271/572) had no contact with health services in the previous 3 months. We estimated 3-month productivity losses of £1001.01 (95% CI 868.75-1133.27; US $1380.79; 95% CI 1198.35-1563.23) per person for those employed. Only 16.6% (131/790) participants completed the primary outcome assessment. There were no differences in the primary or secondary outcomes between the 2 groups. CONCLUSIONS: Most participants reached and those eligible for this trial of digital interventions were White women not in recent contact with health services and whose productivity losses represent a significant annual societal burden. A fully automated RCT recruiting directly from the public failed to recruit and retain sufficient participants to test the clinical effectiveness of this digital intervention, primarily because it did not personally engage participants and explain how these unfamiliar interventions might benefit them. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 12673428; https://www.isrctn.com/ISRCTN12673428. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.8061.

Domain-Specific Antibodies Reveal Differences in the Membrane Topologies of Apolipoprotein L1 in Serum and Podocytes.

BACKGROUND: Circulating APOL1 lyses trypanosomes, protecting against human sleeping sickness. Two common African gene variants of APOL1, G1 and G2, protect against infection by species of trypanosomes that resist wild-type APOL1. At the same time, the protection predisposes humans to CKD, an elegant example of balanced polymorphism. However, the exact mechanism of APOL1-mediated podocyte damage is not clear, including APOL1's subcellular localization, topology, and whether the damage is related to trypanolysis. METHODS: APOL1 topology in serum (HDL particles) and in kidney podocytes was mapped with flow cytometry, immunoprecipitation, and trypanolysis assays that tracked 170 APOL1 domain-specific monoclonal antibodies. APOL1 knockout podocytes confirmed antibody specificity. RESULTS: APOL1 localizes to the surface of podocytes, with most of the pore-forming domain (PFD) and C terminus of the Serum Resistance Associated-interacting domain (SRA-ID), but not the membrane-addressing domain (MAD), being exposed. In contrast, differential trypanolytic blocking activity reveals that the MAD is exposed in serum APOL1, with less of the PFD accessible. Low pH did not detectably alter the gross topology of APOL1, as determined by antibody accessibility, in serum or on podocytes. CONCLUSIONS: Our antibodies highlighted different conformations of native APOL1 topology in serum (HDL particles) and at the podocyte surface. Our findings support the surface ion channel model for APOL1 risk variant-mediated podocyte injury, as well as providing domain accessibility information for designing APOL1-targeted therapeutics.

Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study.

BACKGROUND: The causal role of inflammatory markers on self-harm and suicidal risk has been studied using observational data, with conflicting results. Confounding and reverse causation can lead to bias, so we appraised question from a genetic perspective to protect against these biases. We measured associations between genetic liability for high levels of inflammatory markers Interleukin-6 (IL-6) and C-reactive protein (CRP) on self-harm, and conducted a secondary analysis restricted to self-harm with suicidal intent. METHODS: We conducted two sample and multivariable Mendelian randomisation (MR) to assess the effects of IL-6 and CRP on self-harm utilising existing data and conducting new genome wide association studies to instrument IL-6 and CRP, and for the outcome of self-harm. RESULTS: No single nucleotide polymorphisms (SNPs) reached genome-wide significance for self-harm, however 193 SNPs met suggestive significance levels (p < 5 × 10-6). We found no evidence of an association between our instruments for IL-6 and self-harm in the two-sample MR, however we found an inverse association between instruments for CRP and self-harm, indicating that higher levels of circulating CRP may protect against self-harm (inverse variance weighted OR 0.92, 95%CI 0.84, 1.01, p = 0.08; MR Egger OR 0.86, 95% CI 0.74, 1.00, p = 0.05). The direct effect estimate for IL-6 was slightly smaller in the multivariable MR than in the two sample MR, while the CRP effect estimates were consistent with the two sample MR (OR 0.92, SE 1.05, p = 0.09). CONCLUSIONS: Our findings are conflicting and indicate that IL-6 and CRP are not robust etiological markers of increased self-harm or suicide risk.