"What Works" to Support LGBTQ+ Young People's Mental Health: An Intersectional Youth Rights Approach.

Despite overwhelming international evidence of elevated rates of poor mental health in LGBTQ+ youth compared to their cis-heterosexual peers, we know relatively little about effective mental health services for this population group. This study aims to produce the first early intervention model of "what works" to support LGBTQ+ youth with emerging mental health problems. Utilizing a mixed method case study, we collected data across 12 UK mental health service case study sites that involved: (a) interviews with young people, parents, and mental health practitioners (n = 93); (b) documentary analysis; (c) nonparticipant observation. The data analysis strategy was theoretical using the "explanation-building" analytical technique. Our analysis suggests an intersectional youth rights approach with 13 principles that must be enacted to provide good mental health services as advocated by the United Nations Convention on the Rights of the Child and World Health Organization. This approach should address the multiple forms of marginalization and stigmatization that LGBTQ+ youth may experience, enable informed independent decision-making, and uphold the right to freedom of safe self-expression. A rights-based approach to mental health services for LGBTQ+ young people is not prominent. This needs to change if we are to tackle this mental health inequality and improve the mental well-being of LGBTQ+ youth worldwide.

Reducing LGBTQ+ adolescent mental health inequalities: a realist review of school-based interventions.

BACKGROUND: LGBTQ+ young people have elevated rates of poor mental health in comparison to their cisgender heterosexual peers. School environment is a key risk factor and consistently associated with negative mental health outcomes for LGBTQ+ adolescents. AIMS: To examine how, why, for whom and in what context school-based interventions prevent or reduce mental health problems in LGBTQ+ adolescents. METHODS: A realist review methodology was utilised and focused on all types of school-based interventions and study designs. A Youth Advisory Group were part of the research team. Multiple search strategies were used to locate relevant evidence. Studies were subject to inclusion criteria and quality appraisal, and included studies were synthesised to produce a programme theory. Seventeen studies were included in the review. RESULTS: Eight intervention components were necessary to address LGBTQ+ pupils mental health: affirmative visual displays; external signposting to LGBTQ+ support; stand-alone input; school-based LGBTQ support groups; curriculum-based delivery; staff training; inclusion policies; trusted adult. Few school-based interventions for this population group were identified. CONCLUSIONS: The programme theory indicates that "to work" school-based interventions must have a "whole-school" approach that addresses specifically the dominant cis-heteronormative school environment and hence the marginalisation, silence, and victimisation that LGBTQ+ pupils can experience.

Respiratory Outcomes at 5-Year Follow-Up in Children with Mannose-Binding Lectin Deficiency: A Retrospective Cohort Study.

OBJECTIVE: Mannose-binding lectin deficiency may predispose children to having increased infection susceptibility. However, there is no conclusive evidence that mannose-binding lectin deficiency is associated with adverse respiratory consequences in children. We aimed to evaluate the effects of mannose-binding lectin deficiency (defined as a level of less than 0.6 mg/L) on clinical, radiological, and microbiological characteristics in children presenting with troublesome respiratory symptoms, as compared to those who are mannosebinding lectin-sufficient. MATERIAL AND METHODS: We conducted a retrospective cohort study to investigate the association between mannose-binding lectin deficiency and respiratory outcomes in children over a period of 10 years in a large teaching hospital. Children presenting with frequent or persistent respiratory symptoms such as a chronic wet cough lasting more than 4 weeks, recurrent lower respiratory tract infections (≥4 infections in a year), or severe respiratory tract infections requiring admission to intensive care or to high dependency unit were included in the study. RESULTS: The study showed no significant difference in clinical outcomes with mannose-binding lectin deficiency and sufficiency. Thirty-two percent of children with mannose-binding lectin deficiency and 30% of those with mannose-binding lectin sufficiency had positive respiratory microbiology. Twenty-three percent of children with mannose-binding lectin deficiency and 24% of those with mannose-binding lectin sufficiency had radiological changes on plain radiographs; also the prevalence of bronchiectasis was similar in both groups. The rates of admission to pediatric intensive care unit were comparable in the 2 groups. CONCLUSIONS: Children with mannose-binding lectin deficiency and sufficiency showed similar clinical, radiological, and microbiological characteristics. Our study suggests that there are no childhood adverse respiratory consequences with mannose-binding lectin deficiency.

Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts.

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom.

BACKGROUND: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care. OBJECTIVE: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients. METHODS: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data. RESULTS: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home. CONCLUSIONS: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.

Understanding How School-Based Interventions Can Tackle LGBTQ+ Youth Mental Health Inequality: A Realist Approach.

Globally, research indicates that LGBTQ+ young people have elevated rates of poor mental health in comparison with their cisgender heterosexual peers. The school environment is a major risk factor and is consistently associated with negative mental health outcomes for LGBTQ+ young people. The aim of this UK study was to develop a programme theory that explained how, why, for whom, and in what context school-based interventions prevent or reduce mental health problems in LGBTQ+ young people, through participation with key stakeholders. Online realist interviews were conducted in the UK with (1) LGBTQ+ young people aged between 13-18 years attending secondary schools (N = 10); (2) intervention practitioners (N = 9); and (3) school staff (N = 3). A realist retroductive data analysis strategy was employed to identify causal pathways across different interventions that improved mental health outcomes. The programme theory we produced explains how school-based interventions that directly tackle dominant cisgender and heterosexual norms can improve LGBTQ+ pupils' mental health. We found that context factors such as a 'whole-school approach' and 'collaborative leadership' were crucial to the delivery of successful interventions. Our theory posits three causal pathways that might improve mental health: (1) interventions that promote LGBTQ+ visibility and facilitate usualising, school belonging, and recognition; (2) interventions for talking and support that develop safety and coping; and (3) interventions that address institutional school culture (staff training and inclusion polices) that foster school belonging, empowerment, recognition, and safety. Our theoretical model suggests that providing a school environment that affirms and usualises LGBTQ+ identities and promotes school safety and belonging can improve mental health outcomes for LGBTQ+ pupils.

Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.

Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.

A case of wild-type rubella-associated cutaneous granuloma in ataxia telangiectasia.

Granulomatous skin disease is known to be associated with various primary immunodeficiencies, including ataxia telangiectasia (AT). Recent reports of persistence of live vaccine strain rubella within such cutaneous granulomas have raised concern regarding the safety of vaccination. Here we report a case of cutaneous granuloma in association with AT, demonstrating wild type, rather than vaccine strain rubella. This supports the persistence of rubella as a causative mechanism, but suggests it is not vaccine strain-specific, and thus may impact the decision of those considering not vaccinating this subset of children.

Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

Explaining effective mental health support for LGBTQ+ youth: A meta-narrative review.

This meta-narrative review on mental health early intervention support for LGBTQ+ â€‹youth aimed to develop a theoretical framework to explain effective mental health support. Using the RAMESES standards for meta-narrative reviews, we identified studies from database searches and citation-tracking. Data extraction and synthesis was conducted through conceptual coding in Atlas.ti. in two stages: 1) conceptual mapping of the meta-narratives; 2) comparing the key concepts across the meta-narratives to produce a theoretical framework. In total, 2951 titles and abstracts were screened and 200 full papers reviewed. 88 studies were included in the final review. Stage 1 synthesis identified three meta-narratives - psychological, psycho-social, and social/youth work. Stage 2 synthesis resulted in a non-pathological theoretical framework for mental health support that acknowledged the intersectional aspects of LGBTQ+ â€‹youth lives, and placed youth at the centre of their own mental health care. The study of LGBTQ+ â€‹youth mental health has largely occurred independently across a range of disciplines such as psychology, sociology, public health, social work and youth studies. The interdisciplinary theoretical framework produced indicates that effective early intervention mental health support for LGBTQ+ â€‹youth must prioritise addressing normative environments that marginalises youth, LGBTQ+ â€‹identities and mental health problems.

Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia.

Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978).

The Politics of LGBT+ Health Inequality: Conclusions from a UK Scoping Review.

This scoping review of UK evidence aimed to describe what is known about Lesbian, Gay, Bisexual, and Trans (LGBT+) health inequalities in relation to cancer, mental health, and palliative care to inform research, policy and public health interventions. Using a scoping review methodology, we identified studies from database searches, citation tracking, and expert consultation. The in/exclusion criteria was based on the PICOS framework. The data were charted and then summarised to map the theoretical approaches and the main types of evidence and identify knowledge gaps. In total, 279 articles were screened and 83 were included in the final review. We found that there is limited UK research examining LGBT+ health inequality in cancer, mental health and palliative care. We would argue that this thin evidence base is partly due to national policy discussions of LGBT+ health inequality that are framed within a depoliticised 'it's getting better' narrative, and an unwillingness to adequately acknowledge the unjust social and economic relations that produce LGBT+ health inequality. In addition, LGBT+ health inequality is depoliticised by existing public health explanatory theories, models and frameworks that exclude sexual orientation and gender diversity as dimensions of power that interlock with those of socio-economic, race and ethnicity. This is a barrier to developing public health interventions that can successfully tackle LGBT+ health inequality.

Family trouble: Heteronormativity, emotion work and queer youth mental health.

Conflict with the family about sexual orientation and gender diversity is a key risk factor associated with poor mental health in youth populations. Findings presented here derive from a UK study that employed an interdisciplinary critical mental health approach that de-pathologised emotional distress and conceptualised families as social and affective units that are created through everyday practices. Our aim was to explore how family relationships foster, maintain or harm the mental health and well-being of LGBTQ+ youth. Data were generated through exploratory visual, creative and digital qualitative methods in two phases. Phase 1 involved digital/paper emotion maps and interviews with LGBTQ+ youth aged 16 to 25 (n = 12) and family member/mentor interviews (n = 7). Phase 2 employed diary methods and follow-up interviews (n = 9). The data analytic strategy involved three stages: individual case analysis, cross-sectional thematic analysis and meta-interpretation. We found that family relationships impacted queer youth mental health in complex ways that were related to the establishment of their autonomous queer selves, the desire to remain belonging to their family and the need to maintain a secure environment. The emotion work involved in navigating identity, belonging and security was made difficult because of family heteronormativity, youth autonomy and family expectations, and had a stark impact on queer youth mental health and well-being. Improving the mental health of LGBTQ+ youth requires a much deeper understanding of the emotionality of family relationships and the difficulties negotiating these as a young person.

Psychological Correlates of Self-Harm within Gay, Lesbian and Bisexual UK University Students.

This study explores the association between lesbian, gay or bisexual (LGB) status and self-harm in UK higher education students. There is currently limited data on this association, and the role psychological variables have in potentially explaining this link, in UK students. We examine whether LGB status is associated with self-harm (both non-suicidal self-injury [NSSI] and suicide attempts [SA]), and whether 4 psychological variables (depression, anxiety, belongingness, self-esteem) mediate this association. A cross-sectional survey was used. UK university students (n = 707) completed an online survey including measures of self-harm, affective symptoms, belongingness, and self-esteem. Latent Variable Modelling (LVM) was used to test our hypotheses. LGB status remained associated with an elevated risk of NSSI and SA even after accounting for mediating factors. Self-esteem and (in the case of SA but not NSSI) thwarted belongingness, did, however, explain some of this association and were correlated with self-harm risk. The findings suggest that psychological factors may account for the association between LGB status and self-harm and, as such, prevention and intervention efforts directed at these psychological mediators may help to reduce self-harm risk in this population.

Conducting sexualities research: an outline of emergent issues and case studies from ten Wellcome-funded projects.

This letter seeks to synthesise methodological challenges encountered in a cohort of Wellcome Trust-funded research projects focusing on sexualities and health. The ten Wellcome Trust projects span a diversity of gender and sexual orientations and identities, settings; institutional and non-institutional contexts, lifecourse stages, and explore a range of health-related interventions.  As researchers, we originate from a breadth of disciplinary traditions, use a variety of research methods and data sources. Despite this breadth, four common themes are found across the projects: (i) inclusivity, representations and representativeness, (ii) lumping together of diverse groups, (iii) institutions and closed settings (iv) ethical and governance barriers.

Acquisition of Verb Meaning From Syntactic Distribution in Preschoolers With Autism Spectrum Disorder.

Purpose: Our goal was to investigate whether preschool children with autism spectrum disorder (ASD) can begin to learn new word meanings by attending to the linguistic contexts in which they occur, even in the absence of visual or social context. We focused on verbs because of their importance for subsequent language development. Method: Thirty-two children with ASD, ages 2;1-4;5 (years;months), participated in a verb-learning task. In a between-subjects design, they were randomly assigned to hear novel verbs in either transitive or intransitive syntactic frames while watching an unrelated silent animation or playing quietly with a toy. In an eye-tracking test, they viewed two video scenes, one depicting a causative event (e.g., boy spinning girl) and the other depicting synchronous events (e.g., boy and girl waving). They were prompted to find the referents of the novel verbs, and their eye gaze was measured. Results: Like typically developing children in prior work, children with ASD who had heard the verbs in transitive syntactic frames preferred to look to the causative scene as compared to children who had heard intransitive frames. Conclusions: This finding replicates and extends prior work on verb learning in children with ASD by demonstrating that they can attend to a novel verb's syntactic distribution absent relevant visual or social context, and they can use this information to assign the novel verb an appropriate meaning. We discuss points for future research, including examining individual differences that may impact success and contrasting social and nonsocial word-learning tasks directly.

Mental Health Staff Perceptions and Practice Regarding Self-Harm, Suicidality and Help-Seeking in LGBTQ Youth: Findings from a Cross-Sectional Survey in the UK.

Young people who identify as lesbian, gay, bisexual, transgender or queer (LGBTQ) experience higher levels of suicidality compared to heterosexual or cisgender peers, and face significant barriers accessing mental health services including prejudice from staff. In a cross-sectional survey, mental health staff who reported receiving LGBT awareness training were significantly more likely to report in relation to working with LGBT youth that they routinely discussed issues of sexuality and gender (χ2=8.782, df=2, p < 0.05); to feel that their organisation supported them to work with this group (χ2=14.401, df=2, p < 0.001); and report that they had access to adequate skills training that supported their work with suicidality and self-harm with this group (χ2=21.911, df=2, p <0.001). There is a need to enhance the mental health workforce in LGBTQ awareness, and these findings indicate that awareness training could impact positively on practice.

The social determinants of lesbian, gay, bisexual and transgender youth suicidality in England: a mixed methods study.

Background: Lesbian, gay, bisexual and transgender (LGBT) youth have a higher risk of suicidality and self-harm than heterosexual youth populations but little is known about the underlying mechanisms. We aimed to investigate the social determinants of this mental health inequality. Methods: A two-stage sequential mixed method study was conducted. Firstly, 29 semi-structured interviews with LGBT youth (aged 13-25 years old) were completed. Data was analysed thematically. Stage 2 involved a self-completed questionnaire employing an online community-based sampling strategy (n = 789). Logistic regression analysis was performed to predict suicidality. Results: Five social determinants explained suicidal risk: (i) homophobia, biphobia or transphobia; (ii) sexual and gender norms; (iii) managing sexual and gender identities across multiple life domains; (iv) being unable to talk; (v) other life crises. Youth who were transgender (OR = 1.50, P < 0.022), disabled (OR = 2.23, P < 0.000), had self-harmed (OR = 7.45, P < 0.000), were affected by abuse (OR = 2.14, P < 0.000), and affected by not talking about their emotions (OR = 2.43, P < 0.044) were most likely to have planned or attempted suicide. Conclusions: Public health universal interventions that tackle bullying and discrimination in schools, and selected interventions that provide specific LGBT youth mental health support could reduce LGBT mental health inequalities in youth suicidality.