Human T cell generation is restored in CD3δ severe combined immunodeficiency through adenine base editing.

CD3δ SCID is a devastating inborn error of immunity caused by mutations in CD3D, encoding the invariant CD3δ chain of the CD3/TCR complex necessary for normal thymopoiesis. We demonstrate an adenine base editing (ABE) strategy to restore CD3δ in autologous hematopoietic stem and progenitor cells (HSPCs). Delivery of mRNA encoding a laboratory-evolved ABE and guide RNA into a CD3δ SCID patient's HSPCs resulted in a 71.2% ± 7.85% (n = 3) correction of the pathogenic mutation. Edited HSPCs differentiated in artificial thymic organoids produced mature T cells exhibiting diverse TCR repertoires and TCR-dependent functions. Edited human HSPCs transplanted into immunodeficient mice showed 88% reversion of the CD3D defect in human CD34+ cells isolated from mouse bone marrow after 16 weeks, indicating correction of long-term repopulating HSCs. These findings demonstrate the preclinical efficacy of ABE in HSPCs for the treatment of CD3δ SCID, providing a foundation for the development of a one-time treatment for CD3δ SCID patients.

Complete responses in AL amyloidosis are unequal: the impact of free light chain mass spectrometry in AL amyloidosis.

ABSTRACT: Amyloidogenic serum free light chains (sFLCs) drive disease progression in AL amyloidosis. Matrix-assisted laser desorption/ionization time of flight mass spectrometry-based FLC assay (FLC-MS) has greater sensitivity than conventional sFLC assays allowing for the detection of serological residual disease. We report the utility of FLC-MS in a large series of patients with AL amyloidosis assessing the impact of FLC-MS negativity after treatment on overall survival (OS) and organ response rates. Serum samples were analyzed using FLC-MS at diagnosis and at 6 and 12 months after treatment. The impact of FLC-MS negativity over standard hematologic responses on survival and organ response was assessed. A total of 487 patients were included; 290 (59%) and 349 (71.5%) had cardiac and renal involvement, respectively. There was 100% concordance between the light chain (LC) fibril type and LC isotype identified by FLC-MS. At 6 and 12 months, 81 (16.6%) and 101 (20.7%) were FLC-MS negative. Of those achieving a conventional hematologic complete response (CR) at 6 and 12 months, 45 (27.7%) and 64 (39%) were FLC-MS negative. At 12 months, median OS for CR + FLC-MS negative was not reached vs 108 months in CR + FLC-MS positive (P = .024). At 12 months, 70% of patients with FLC-MS negativity (vs 50% FLC-MS positive) achieved a cardiac response (P = .015). In a multivariate analysis, FLC-MS negativity at 12 months was an independent predictor of better outcomes. FLC-MS can detect persistent monoclonal light chains in a significant proportion of patients in a conventional hematologic CR. FLC-MS assessment promises to be a new standard for response assessment in AL amyloidosis.

Applications of Grounded Theory Methodology to Investigate Hearing Loss: A Methodological Qualitative Systematic Review With Developed Guidelines.

OBJECTIVES: Qualitative methodologies are commonly adopted in hearing loss research. Grounded theory methodology is increasingly used to establish novel theories explaining experiences related to hearing loss. Establishing and improving the quality of grounded theory studies has been emphasized as critical to ensuring theoretical trustworthiness. Thus, the primary aim of the present study was to systematically review hearing loss research studies that have applied grounded theory methodology and assess the methodological quality of those grounded theory applications. Secondarily aims were to (i) explore how grounded theory methodology has been applied to investigate hearing loss, and (ii) use the findings of the review to develop a set of guidelines to aid the future high-quality application of grounded theory methodology to hearing loss research. DESIGN: Original peer-reviewed studies applying grounded theory methodology and published in English were identified through systematic searches in 10 databases; Applied Social Sciences Index and Abstracts, British Nursing Index, Cumulative Index to Nursing and Allied Health Literature, EBSCO, Global Health, MEDLINE (OvidSP), PsycINFO, PubMed, Scopus, and Web of Science. The quality of studies was assessed according to 12 grounded theory principles using the Guideline for Reporting, Evaluating, and applying the core principles of Grounded Theory studies (GUREGT) tool. Data were analyzed using qualitative inductive thematic analysis. RESULTS: After the removal of duplicates, 155 articles were retrieved. Of those, 39 met the criteria for inclusion in the systematic review. An increase in the adoption of grounded theory methodology to investigate hearing loss was identified with the number of published studies tripling in the last 5 years. Critical appraisal using the GUREGT tool identified four studies as high-quality. Most included studies were of moderate study quality (n = 25), and 10 were classified as being of low study quality. Using inductive thematic analysis, the included studies investigated one of four areas relating to hearing loss: (a) Living with hearing loss, (b) Identity and hearing loss, (c) Coping strategies for hearing loss, and (d) Audiological counseling and rehabilitation. Analysis also identified four main grounded theory factors frequently overlooked in hearing loss research: the different schools of grounded theory, sampling strategy, sample size, and the depth of grounded theory application. CONCLUSIONS: Use of grounded theory methodology is increasing at a rapid rate in hearing loss research. Despite this, studies conducted in the field to date do not meet and apply the full spectrum of grounded theory principles, as outlined by the GUREGT tool. To improve methodological rigor in future studies using grounded theory, we propose a set of guidelines that address the most commonly overlooked methodological considerations in hearing loss studies to date. The guidelines are designed to aid researchers to achieve high methodological quality in any field, improve qualitative rigor, and promote theoretical credibility.

The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 Definitions.

Severe combined immunodeficiency (SCID) results from defects in the differentiation of hematopoietic stem cells into mature T lymphocytes, with additional lymphoid lineages affected in particular genotypes. In 2014, the Primary Immune Deficiency Treatment Consortium published criteria for diagnosing SCID, which are now revised to incorporate contemporary approaches. Patients with typical SCID must have less than 0.05 × 109 autologous T cells/L on repetitive testing, with either pathogenic variant(s) in a SCID-associated gene, very low/undetectable T-cell receptor excision circles or less than 20% of CD4 T cells expressing naive markers, and/or transplacental maternally engrafted T cells. Patients with less profoundly impaired autologous T-cell differentiation are designated as having leaky/atypical SCID, with 2 or more of these: low T-cell numbers, oligoclonal T cells, low T-cell receptor excision circles, and less than 20% of CD4 T cells expressing naive markers. These patients must also have either pathogenic variant(s) in a SCID-associated gene or reduced T-cell proliferation to certain mitogens. Omenn syndrome requires a generalized erythematous rash, absent transplacentally acquired maternal engraftment, and 2 or more of these: eosinophilia, elevated IgE, lymphadenopathy, hepatosplenomegaly. Thymic stromal defects and other causes of secondary T-cell deficiency are excluded from the definition of SCID. Application of these revised Primary Immune Deficiency Treatment Consortium 2022 Definitions permits precise categorization of patients with T-cell defects but does not imply a preferred treatment strategy.

Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.

Position statements of the Royal Australian and New Zealand College of Psychiatrists: An historical perspective.

OBJECTIVE: To review the concept, purpose, and subjects of Position Statements of the Royal Australian and New Zealand College of Psychiatrists since their inception in 1971, and to consider changes to enhance their value. METHOD: We scrutinised the procedure in producing, revising, and rescinding Position Statements, and the nature of the subjects covered. RESULTS: Position Statements were initiated by the College Board, various College committees and members. The format and procedures of revising and rescinding them varied considerably. We identified 11 subject areas encompassing professional practice and research, their association with societal developments, and the implications for College policy. CONCLUSION: Position Statements have proved to be a dynamic vehicle to keep abreast of significant changes in psychiatry. Methodical appraisal is required to optimise their objective in conveying College policies to members and relevant stakeholders.

Subcutaneous panniculitis-like T-cell lymphoma in two unrelated individuals with BENTA disease.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous non-Hodgkin lymphoma involving CD8+ T cells, the genetic underpinnings of which remain incompletely understood. Here we report two unrelated patients with B cell Expansion with NF-κB and T cell Anergy (BENTA) disease and a novel presentation of SPTCL. Patient 1 presented early in life with recurrent infections and B cell lymphocytosis, linked to a novel gain-of-function (GOF) CARD11 mutation (p.Lys238del). He developed SPTCL-like lesions and membranoproliferative glomerulonephritis by age 2, treated successfully with cyclosporine. Patient 2 presented at 13 months with splenomegaly, lymphadenopathy, and SPTCL with evidence of hemophagocytic lymphohistiocytosis. Genetic analysis revealed two in cis germline GOF CARD11 variants (p.Glu121Asp/p.Gly126Ser). Autologous bone marrow transplant resulted in SPTCL remission despite persistent B cell lymphocytosis. These cases illuminate an unusual pathological manifestation for BENTA disease, suggesting that CARD11 GOF mutations can manifest in cutaneous CD4+and CD8+ T cell malignancies.

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy.

PURPOSE: Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)-associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. METHODS: This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. RESULTS: All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. CONCLUSION: Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.

Warmth and reciprocity with mothers, and young children's resilience to exposure to community violence in Colombia: findings from the La Sabana Parent-Child Study.

BACKGROUND: Exposure to community violence is common worldwide and is associated with emotional and behavioural problems in children. Little is known about sources of resilience. Building on our previous work on the contribution of callous-unemotional (CU) traits to child aggression in Colombia, we examined whether positive parenting is protective for children whose families are exposed to community violence. METHODS: Families were recruited from three demographically contrasting regions of Colombia. The sample comprised 235 children aged 3.5 years and their mothers, of whom 220 (93%) were followed up at age 5.0 years. Positive parenting was assessed as the average of maternal warmth and reciprocity, and as praise, and negative parenting as the average of negative affect and conflict seen in video recordings of standardized procedures. CU traits and oppositional defiant disorder were assessed by maternal report at ages 3.5 and 5.0 years, and mothers reported exposure to community violence over the 18 months between assessments. A range of potential confounds was included in adjusted analyses. RESULTS: In the families who were exposed to community violence, but not in the unexposed, maternal warmth and reciprocity were associated prospectively with lower CU traits (interaction, p = .007). In the exposed group maternal warmth and reciprocity explained 10% of the variance (ß = -.34, p = .001). Maternal praise was not associated with CU traits. Maternal negative parenting predicted higher CU traits as the main effect but not in interaction with community violence exposure. CONCLUSIONS: Maternal warmth and reciprocity with young children may promote resilience in the face of community violence. Programmes to enhance these protective processes may be needed especially where prospects for reducing community violence are limited. The centrality of parents for these children highlights the plight of those exposed to community violence, and also either separated from parents or orphaned.

Longitudinal associations between early childhood irritability and adolescent depression symptoms in autistic children are mediated by peer relationships but not educational engagement.

In the general population, irritability is associated with later depression. Despite irritability being more prevalent in autistic children, the long-term sequelae are not well explored. We tested whether irritability in early childhood predicted depression symptoms in autistic adolescents, and whether associations could be explained by difficulties in peer relationships and lower educational engagement. Analyses tested the longitudinal associations between early childhood irritability (ages 3-5) and adolescent depression symptoms (age 14) in a prospective inception cohort of autistic children (N = 390), followed from early in development shortly after they received a clinical diagnosis. Mediators were measured in mid-childhood (age 10) by a combination of measures, from which latent factors for peer relationships and educational engagement were estimated. Results showed early childhood irritability was positively associated with adolescent depression symptoms, and this association remained when adjusting for baseline depression. A significant indirect pathway through peer relationships was found, which accounted for around 13% of the association between early childhood irritability and adolescent depression, suggesting peer problems may partially mediate the association between irritability and later depression. No mediation effects were found for education engagement. Results highlight the importance of early screening and intervention for co-occurring irritability and peer problems in young autistic children.

La prise en charge de la neutropénie fébrile chez les enfants et les adolescents immunocompétents.

La neutropénie fébrile est une manifestation clinique fréquente en pédiatrie, qui peut être associée à une infection bactérienne invasive. Cependant, le risque de ce type d'infection est faible chez les enfants et les adolescents autrement en santé qui font de la fièvre et présentent une neutropénie, la plupart des cas étant causés par une infection virale. Les enfants âgés de six mois à 18 ans qui ont l'air bien, ne souffrent pas d'un cancer, sont considérés comme immunocompétents et présentent un premier épisode de neutropénie, sans autres facteurs de risque, n'ont généralement pas besoin d'antibiotiques empiriques. Cependant, une évaluation approfondie est indiquée, y compris une anamnèse et un examen physique complets, de même qu'une hémoculture lorsque la numération absolue des neutrophiles est inférieure à 0,5 × 109/L. Il est recommandé d'assurer un suivi étroit, de reprendre l'hémogramme et de donner des conseils préventifs stricts.

Management of febrile neutropenia in immunocompetent children and youth.

Febrile neutropenia is a common clinical presentation in children that can be associated with invasive bacterial infection (IBI). However, in otherwise healthy children and youth with fever and neutropenia, the risk for IBI is low, with most cases being caused by viral infections. Well-appearing, non-oncologic, and presumed immunocompetent children aged 6 months to 18 years experiencing a first episode of neutropenia, with no additional risk factors, typically do not require empiric antibiotics. However, a thorough assessment, including complete history and physical exam, is indicated, and a blood culture should be performed when the absolute neutrophil count is <0.5 × 109/L. Close follow-up, a repeat complete blood count, and strong anticipatory guidance are recommended.

Predictors of language regression and its association with subsequent communication development in children with autism.

BACKGROUND: Language regression, broadly defined as the loss of acquired language skills in early childhood, is a distinctive feature of autism. Little is known about the factors underlying regression or the prognosis of children who exhibit regression. We examine potential predictors of language regression and test its association with language development in a prospective longitudinal sample of children with autism spectrum disorder (ASD) from diagnosis to age 10 years. METHODS: We analysed data from Pathways in ASD, a prospective longitudinal study of 421 children enrolled around the time of an autism diagnosis between 2 and 5 years. Autism Diagnostic Interview-Revised data were available for 408 children, of whom 90 (22%) were classified as having language regression. RESULTS: Demographic and other health factors including caregiver education, family income, child sex, reported seizures, and age of enrolment did not differ between children with and without language regression. Children with language regression walked earlier and attained first words sooner than those without regression. However, both groups attained phrase speech at comparable ages. Those with regression exhibited greater delays in expressive and receptive communication over the follow-up period, although this effect was attenuated when accounting for baseline differences in motor and cognitive ability. Overall, those with language regression continued to exhibit expressive but not receptive communication delay compared to those without regression. Communication trajectories were heterogeneous to age 10 years, irrespective of regression status. CONCLUSIONS: Although language regression can be alarming, our findings confirm that its occurrence does not necessarily foreshadow worse developmental outcomes relative to those without regression. Although a discrepancy in age-equivalent communication skills may persist, this can be expected to be of less practical importance with rising average levels of skills. Future studies need to account for the significant variability in language trajectories by considering factors beyond developmental regression.

Socio-demographic disparities in receipt of clinical health care services during the COVID-19 pandemic for Canadian children with disability.

BACKGROUND: Little is known about the experience of receiving in-person and virtual clinical health care services during the COVID-19 pandemic for Canadian children with developmental disabilities and delays facing multiple layers of vulnerability (e.g., low income, low educational attainment families). We examined the relationship between socio-demographic factors and the receipt of these services (physical and mental health services) during COVID-19 for Canadian children with these conditions. METHODS: Data collected in Canada for the Global Report on Developmental Delays, Disorders and Disabilities were used. The survey: (1) was developed and disseminated in collaboration with caregivers of children with disabilities, (2) included topics such as response to the pandemic and receipt of services and supports, and (3) documented the experiences of a non-random convenience sample of caregivers of children (any age) with these conditions during and prior to the pandemic. We used four logistic regression models to assess the association between socio-demographic factors and receipt of services. RESULTS: Being a single parent, having low educational attainment (high school or less), having low income (making less than $40,000 per year), working less than full time (working part-time, working reduced hours due to COVID, retired, stay home parent or student), as well as male gender and older age of the child with disability were factors associated with decreased likelihood of receiving services. CONCLUSION: Our findings point to the need for tailoring services for families of children with disabilities, particularly low socioeconomic status families, to ensure continuity of care during public health emergencies.

Mechanistic understanding of the combined immunodeficiency in complete human CARD11 deficiency.

BACKGROUND: Germline pathogenic variants impairing the caspase recruitment domain family member 11 (CARD11)-B cell chronic lymphocytic leukemia/lymphoma 10 (BCL10)-MALT1 paracaspase (MALT1) (CBM) complex are associated with diverse human diseases including combined immunodeficiency (CID), atopy, and lymphoproliferation. However, the impact of CARD11 deficiency on human B-cell development, signaling, and function is incompletely understood. OBJECTIVES: This study sought to determine the cellular, immunological, and biochemical basis of disease for 2 unrelated patients who presented with profound CID associated with viral and fungal respiratory infections, interstitial lung disease, and severe colitis. METHODS: Patients underwent next-generation sequencing, immunophenotyping by flow cytometry, signaling assays by immunoblot, and transcriptome profiling by RNA-sequencing. RESULTS: Both patients carried identical novel pathogenic biallelic loss-of-function variants in CARD11 (c.2509C>T; p.Arg837∗) leading to undetectable protein expression. This variant prevented CBM complex formation, severely impairing the activation of nuclear factor-κB, c-Jun N-terminal kinase, and MALT1 paracaspase activity in B and T cells. This functional defect resulted in a developmental block in B cells at the naive and type 1 transitional B-cell stage and impaired circulating T follicular helper cell (cTFH) development, which was associated with impaired antibody responses and absent germinal center structures on lymph node histology. Transcriptomics indicated that CARD11-dependent signaling is essential for immune signaling pathways involved in the development of these cells. Both patients underwent hematopoietic stem cell transplantations, which led to functional normalization. CONCLUSIONS: Complete human CARD11 deficiency causes profound CID by impairing naive/type 1 B-cell and cTFH cell development and abolishing activation of MALT1 paracaspase, NF-κB, and JNK activity. Hematopoietic stem cell transplantation functionally restores impaired signaling pathways.

The Moderating Role of Maternal Praise and Positivity in the Association Between Callous-Unemotional (CU) Traits and Later Aggression: A Prospective Study in Preschool Children in Colombia.

Our previous findings in the UK and Colombia show that CU traits predict later aggression specifically among children who are already aggressive. We hypothesised that this effect would be reduced in the presence of maternal praise and positivity. In a sample of 220 mothers and children from Colombia, mother-child interactions were coded for maternal praise and positivity, and mothers reported on children's CU traits at age 3.5 and aggression at ages 3.5 and 5 years. The results show three-way interactions between CU traits, child aggression and observed parenting at age 3.5 years in the prediction of later child aggression, and two-way interactions indicating a protective effect of positive parenting in the high aggressive children. Based on our finding, it is plausible that positive parenting may modify the effect of CU traits in the highly vulnerable group of children who are already aggressive in early childhood.

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers.

PURPOSE: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study's objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention. METHODS: We analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management. RESULTS: Infections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented. CONCLUSION: Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS. TRIAL REGISTRATION: NCT01186913.

What does safety in mental healthcare transitions mean for service users and other stakeholder groups: An open-ended questionnaire study.

BACKGROUND: Historically, safety mental health research has tended to focus on risks of homicide, suicide and deaths. Although wider safety issues are now recognized in regards to mental health services, the safety of mental health transitions, a key research and policy priority according to World Health Organisation, has not been explored. OBJECTIVE: The purpose of this study was to investigate perceptions of safety in mental health transitions (hospital to community) amongst five stakeholder groups. DESIGN AND SETTING: An online, international cross-sectional, open-ended questionnaire. PARTICIPANTS: There were five stakeholder participant groups: service users; families/carers; mental health-care professionals; researchers; and end users of research. RESULTS: Ninety-three participants from 12 different countries responded. Three overarching themes emerged: 'individual/clinical', 'systems/services' and 'human, behavioural and social' elements of safe mental health transitions. Whilst there was a great focus on clinical elements from researchers and healthcare professionals, service users and carers considered safety in terms of human, behavioural and social elements of transitional safety (ie loneliness, emotional readiness for discharge) and systems/services (ie inter-professional communication). DISCUSSION: Safety in mental health-care transitions is perceived differently by service users and families compared to healthcare professionals and researchers. Traditional safety indicators for care transitions such as suicide, self-harm and risk of adverse drug events are raised as important. However, service users and families in particular have a much wider perception of transitions safety. CONCLUSION: Future quality and safety research and policy should consider including a service user voice and consider integration of psychosocial elements in discharge interventions.

Emotion Recognition Performance in Children with Callous Unemotional Traits is Modulated by Co-occurring Autistic Traits.

OBJECTIVE: Atypical emotion recognition (ER) is characteristic of children with high callous unemotional (CU) traits. The current study aims to 1) replicate studies showing ER difficulties for static faces in relation to high CU-traits; 2) test whether ER difficulties remain when more naturalistic dynamic stimuli are used; 3) test whether ER performance for dynamic stimuli is moderated by eye-gaze direction and 4) assess the impact of co-occurring autistic traits on the association between CU and ER. METHODS: Participants were 292 (152 male) 7-year-olds from the Wirral Child Health and Development Study (WCHADS). Children completed a static and dynamic ER eye-tracking task, and accuracy, reaction time and attention to the eyes were recorded. RESULTS: Higher parent-reported CU-traits were significantly associated with reduced ER for static expressions, with lower accuracy for angry and happy faces. No association was found for dynamic expressions. However, parent-reported autistic traits were associated with ER difficulties for both static and dynamic expressions, and after controlling for autistic traits, the association between CU-traits and ER for static expressions became non-significant. CU-traits and looking to the eyes were not associated in either paradigm. CONCLUSION: The finding that CU-traits and ER are associated for static but not naturalistic dynamic expressions may be because motion cues in the dynamic stimuli draw attention to emotion-relevant features such as eyes and mouth. Further, results suggest that ER difficulties in CU-traits may be due, in part, to co-occurring autistic traits. Future developmental studies are required to tease apart pathways toward the apparently overlapping cognitive phenotype.

Improving mental health care transitions through information capture during admission to inpatient mental health services: a quality improvement study.

BACKGROUND: Many interventions aim to improve the transition from ward to community at the time of discharge, with varying success. Guidelines suggest that discharge planning should begin at admission, but in reality this is ideal rather than standard practice. We aimed to develop a novel information capture tool during admission that facilitates and accelerates discharge. METHODS: A quality improvement study to develop, implement and evaluate a novel tool that improves information capture upon admission to acute mental health wards within a single English National Health Service (NHS) trust. We developed the tool by synthesising existing evidence and working with multi-agency and multi-disciplinary professionals in two co-design workshops. During implementation the tool was piloted on three wards. Ethnographic observations (145 h) and interviews (45) were used to evaluate the implementation of the tool across the three wards. Thematic synthesis was used to consolidate the findings. RESULTS: The tool developed considerably as the process evolved. The finished product is a list of 10 information categories that should be captured from external agencies upon admission to hospital to facilitate discharge planning to community settings. Reported advantages of the tool were: (1) facilitating confidence in junior staff to legitimately question the suitability of a patient for an acute ward (2) collecting and storing essential information in a single accessible place that can be used throughout the care pathway and (3) collecting information from the services/agencies to which patients will eventually be discharged. CONCLUSIONS: Improving the quality of information at admission has the potential to facilitate and accelerate discharge. The novel tool provides a framework for capturing this information that can be incorporated into existing information systems. However, the introduction of the tool exacerbated complex, fragile distributed team dynamics, highlighting the importance of sociocultural context in information flow transitional interventions within distributed teams.