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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Following a health technology assessment, the Health Service Executive (HSE) supported reimbursement of dupilumab subject to a managed access protocol (MAP) being implemented. Reimbursement is restricted to a subgroup of the fully licensed indication, that is, moderate-to-severe refractory atopic dermatitis (AD) in adults and adolescents 12 years and older. This study provides an overview of the first year of the MAP.
Methods
All reimbursement applications submitted to the HSE Medicines Management Programme between 1 April 2021 and 31 March 2022 were reviewed. Key demographic and clinical characteristics of the approved population were analyzed. Reimbursement claims data within the specified period were extracted from the HSE Primary Care Reimbursement Services national pharmacy claims database. All data were compiled and analyzed using SPSS Statistics 27. Expenditure estimates were based on wholesale prices and were exclusive of value-added tax, fees, and confidential rebates.
Results
During the study period, 382 applications were submitted, 96 percent (n=365) of which were approved. Among approved patients, the mean age was 35 years (range 12 to 79 years), the mean number of years between AD diagnosis and approval was 22.65 years (range 1 to 78 years), and 65 percent (n=238) were men. The mean Eczema Area and Severity Index score was 28.72 and the mean (Children’s) Dermatology Life Quality Index score was 19.72. Approved patients who had unsuccessfully tried other systemic immunosuppressants had trialed up to five different medicines (mean=1.6). Year one expenditure was EUR2.4million, with 70 percent of approved patients accessing treatment.
Conclusions
Most applications submitted through the MAP were approved. These patients met the predefined evidence-based eligibility criteria for treatment. Patient numbers were higher than estimated, suggesting that the MAP did not hinder access. Utilizing health technology management by way of a MAP has facilitated access to expensive medicines for patients with the greatest need, while controlling expenditure for the payer.
Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.
Methods
A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.
Results
Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.
Conclusions
The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.
Tape rolls are often used for multiple patients despite recommendations by manufacturers for single-patient use. We developed a survey to query Health Care Personnel about their tape use practices and beliefs and uncovered behaviors that put patients at risk for hospital-acquired infections due to tape use.
Advances in artificial intelligence (AI) have great potential to help address societal challenges that are both collective in nature and present at national or transnational scale. Pressing challenges in healthcare, finance, infrastructure and sustainability, for instance, might all be productively addressed by leveraging and amplifying AI for national-scale collective intelligence. The development and deployment of this kind of AI faces distinctive challenges, both technical and socio-technical. Here, a research strategy for mobilising inter-disciplinary research to address these challenges is detailed and some of the key issues that must be faced are outlined.
In this chapter, we discuss the relationship of individual personal thriving to fairness and worthiness by exploring the concept of epistemic injustice. Epistemic injustice refers to the rejection of people’s capacity as knowers, such that these individuals are treated as being less knowledgeable and less believable than other people, frequently on the basis of their social identities. In the first half of the chapter, we will explain how epistemic injustices take place and how they interrupt human thriving. In the second half of the chapter, we will profile the ways that psychologists and others can work to prevent epistemic injustice.
This chapter will present a composite method of analysis for embodied movement data, developed in the first author's doctoral project (in progress at time of writing), which considered attitudes towards the body in English primary schools. This project sought to understand embodied experiences and their pedagogical implications, suggesting that heightened embodied awareness might support a more perceptive and responsive pedagogy. It drew heavily on the first author's career as a dancer and aerialist specialising in creative movement. Residencies in three schools over the course of nine months consisted of weekly, one- hour sessions of creative movement play with at least two classes in each school, over the course of six weeks in the pilot school and the first enquiry school, and ten weeks in the second enquiry school.
Children were mainly aged 7 to 11 and attended in whole- class groups. Class teachers supported, sometimes joining in and sometimes observing the movement. Data generated included: interviews with staff, video of the children moving using both high- quality video and infrared cameras, and drawings and voice- recorded comments made by the children at the end of the sessions. These different data types were used to triangulate and cross reference during later stages of analysis, which are not discussed in this chapter.
Theoretical foundations
Extending and adapting Rhythmanalysis (Lefebvre, 2004), we used creative dance practice for non- verbal interpretation of the intangible experience of the learner. Analysing primary, embodied, movement data through a series of dance- led lenses avoids immediately grappling with the limitations of translating movement into language, focusing instead on the perceptual level of these experiences and opening the possibility of deeper understanding. However, this approach does then consider what is entailed in the move to reflect and define through words, mindful that this translation will necessarily be occurring in research on embodiment, but also that words can usefully enrich and then invoke as data the movement language that is generated. The question is not then whether reflection and analysis through words should happen at all, but rather how and at what stage.
This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation.
Method
An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice.
Results
Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise.
Conclusion
Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.
Estimate the impact of 20 % flat-rate and tiered sugary drink tax structures on the consumption of sugary drinks, sugar-sweetened beverages and 100 % juice by age, sex and socio-economic position.
Design:
We modelled the impact of price changes – for each tax structure – on the demand for sugary drinks by applying own- and cross-price elasticities to self-report sugary drink consumption measured using single-day 24-h dietary recalls from the cross-sectional, nationally representative 2015 Canadian Community Health Survey-Nutrition. For both 20 % flat-rate and tiered sugary drink tax scenarios, we used linear regression to estimate differences in mean energy intake and proportion of energy intake from sugary drinks by age, sex, education, food security and income.
Setting:
Canada.
Participants:
19 742 respondents aged 2 and over.
Results:
In the 20 % flat-rate scenario, we estimated mean energy intake and proportion of daily energy intake from sugary drinks on a given day would be reduced by 29 kcal/d (95 % UI: 18, 41) and 1·3 % (95 % UI: 0·8, 1·8), respectively. Similarly, in the tiered tax scenario, additional small, but meaningful reductions were estimated in mean energy intake (40 kcal/d, 95 % UI: 24, 55) and proportion of daily energy intake (1·8 %, 95 % UI: 1·1, 2·5). Both tax structures reduced, but did not eliminate, inequities in mean energy intake from sugary drinks despite larger consumption reductions in children/adolescents, males and individuals with lower education, food security and income.
Conclusions:
Sugary drink taxation, including the additional benefit of taxing 100 % juice, could reduce overall and inequities in mean energy intake from sugary drinks in Canada.
Data compilations expand the scope of research; however, data citation practice lags behind advances in data use. It remains uncommon for data users to credit data producers in professionally meaningful ways. In paleontology, databases like the Paleobiology Database (PBDB) enable assessment of patterns and processes spanning millions of years, up to global scale. The status quo for data citation creates an imbalance wherein publications drawing data from the PBDB receive significantly more citations (median: 4.3 ± 3.5 citations/year) than the publications producing the data (1.4 ± 1.3 citations/year). By accounting for data reuse where citations were neglected, the projected citation rate for data-provisioning publications approached parity (4.2 ± 2.2 citations/year) and the impact factor of paleontological journals (n = 55) increased by an average of 13.4% (maximum increase = 57.8%) in 2019. Without rebalancing the distribution of scientific credit, emerging “big data” research in paleontology—and science in general—is at risk of undercutting itself through a systematic devaluation of the work that is foundational to the discipline.
Childhood obesity is a serious health epidemic affecting the world today. Children who are obese earlier in life are more likely to stay obese and have an increased risk of poorer health outcomes later in life, such as diabetes and cardiovascular diseases. Obesity is also associated with deficits in executive function. Executive function (EF) is comprised of several distinct but interrelated abilities including working memory, planning, inhibition, and flexibility. Prior research suggests that obesity drives brain changes which implicate executive function structures. Our aim is to examine the relationship between childhood obesity and executive function in children with neurodevelopmental disorders.
Participants and Methods:
These data are from an ongoing study on neural and behavioral phenotypes of executive functioning in children with developmental disabilities, primarily Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Only study participants with complete BMI and BRIEF data were included in these analyses (n = 184). 134 representing (72.8%) of the participants were Male, 49 representing (26.6%) were Female, and 1 representing (.5%) were Gender nonconforming. 50 representing (27.2%) of the participants were between 8-9 years, 55 representing (29.9%) were between 10-11 years, and 80 representing (43.0%) were between 12-13 years. Average age was 11 years. 11 representing (6.0%) of the participants were underweight, 115 representing (62.5%) were healthy, 29 representing (15.8%) were overweight, and 29 representing (15.8%) were obese. Average BMI was 19.0, ranging from 13.2 to 36.3. 106 representing (57.6%) of the participants identified as White, 65 representing (35.3%) identified as BIPOC (2 Asian, 31 Hispanic/Latinx, 32 Black) and 13 representing (4.4%) identified as other/unspecified. 114 representing (61.9%) of the participants had a diagnosis of ADHD, ASD, or comorbid ASD and ADHD, 70 representing (38.1%) had a diagnosis of other. Average FSIQ-2 score was 106.98. Parents were asked to complete the Behavior Rating Inventory of Executive Function (BRIEF-2) and the Inhibit, Shift, Working Memory (WM), Planning, and Global Executive Composite (GEC) scales were used as the dependent measure in analyses. BMI (kg/mA2) was calculated based on CDC 2000 growth charts and classified into 4 mutually exclusive categories—underweight, healthy, overweight, and obese. There was a prediction that higher BMI would be associated with lower executive function.
Results:
A one-way ANOVA revealed a statistically significant difference between groups (F(3,180) = 3.649, p = .014). A Tukey post hoc test revealed more Shift problems in the obese group (74.55 ± 11.7) compared to the overweight group (65.79 ± 11.6, p = .026). There was no statistically significant difference between the underweight/healthy and obese groups (p = .999/p = .054). There was no statistically significant difference in mean T-scores for the Inhibit, WM, Planning, or GEC scales.
Conclusions:
Childhood obesity and executive function deficits are significant risk factors for adult health outcomes. Obesity and elevated executive function T-scores for flexibility are related in a group of children with neurodevelopmental disorders. Future investigation will explore the role of cortical thickness and medication in these data.
Background: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in hospitalized patients in low- and middle-income countries (LMICs) is poorly described. Although risk factors for ESCrE clinical infection have been studied, little is known of the epidemiology of ESCrE colonization. Identifying risk factors for ESCrE colonization, which can predispose to infection, is therefore critical to inform antibiotic resistance reduction strategies. Methods: This study was conducted in 3 hospitals located in 3 districts in Botswana. In each hospital, we conducted ongoing surveillance in sequential units hospitalwide. All participants had rectal swabs collected which were inoculated onto chromogenic media followed by confirmatory testing using MALDI-TOF MS and VITEK-2. Data were collected via interview and review of the inpatient medical record on demographics, comorbidities, antibiotic use, healthcare exposures, invasive procedures, travel, animal contact, and food consumption. Participants with ESCrE colonization (cases) were compared to noncolonized participants (controls) using bivariable and multivariable analyses to identify risk factors for ESCrE colonization. Results: Enrollment occurred from January 15, 2020, to September 4, 2020, and 469 participants were enrolled. The median age was 42 years (IQR, 31–58) and 320 (68.2%) were female. The median time from hospital admission to date of sampling was 5 days (IQR, 3–12). There were 179 cases and 290 controls (ie, 38.2% of participants were ESCrE colonized). Independent risk factors for ESCrE colonization were a greater number of days on antibiotic, recent healthcare exposure, and tending swine prior to hospitalization. (Table). Conclusions: ESCrE colonization among hospitalized patients was common and was associated with several exposures. Our results suggest prior healthcare exposure may be important in driving ESCrE. The strong link to recent antibiotic use highlights the potential role of antibiotic stewardship interventions for prevention. The association with tending swine suggests that animal husbandry practices may play a role in community exposures, resulting in colonization detected at the time of hospital admission. These findings will help to inform future studies assessing strategies to curb further emergence of hospital ESCrE in LMICs.
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
Given the large mental health treatment gap in low- and middle-income countries (LMICs), particularly in post-conflict settings like Sierra Leone, and the limited healthcare infrastructure, understanding the wider benefits of evidence-based mental health interventions within households is critical. This study explored potential mental health spillover effects – the phenomenon of beneficial effects among nonparticipants – among cohabitating caregivers and partners of youth who participated in an evidence-based mental health intervention in Sierra Leone. We recruited a sub-sample of cohabitating caregivers and partners (N = 20) of youth intervention participants; caregivers had enrolled in a larger study investigating indirect benefits of the evidence-based intervention in Sierra Leone (MH117359). Qualitative interviews were conducted at two time points to explore the following: (a) potential mental health spillover effects and (b) through which mechanisms spillover may have occurred. Two trained coders reviewed transcripts and analyzed qualitative data, assisted by MaxQDA. Qualitative findings suggested that spillover effects likely occurred and supported three potential mechanisms: decreased caregiving burden, behavior changes among Youth Readiness Intervention participants and improved interpersonal relationships. Mental health spillover effects may occur following youth intervention participation in a post-conflict LMIC. Investing in evidence-based services may offer indirect benefits that extend beyond those directly receiving services.
The Advancing Mental Health Equality Collaborative is an innovative 3-year quality improvement programme led by the Royal College of Psychiatrists’ National Collaborating Centre for Mental Health (NCCMH). The collaborative was launched in July 2021 and involves 18 organisations across the UK who, with quality improvement support from the NCCMH, are working to understand the needs of their population and identify communities at risk of experiencing inequality to improve access, experience and outcomes of mental health care, support, and treatment for those populations.
Methods
An overarching driver diagram for the Collaborative was developed in collaboration with a wide range of stakeholders through steering group meetings, design workshops and remote consultation. This overarching driver diagram informs the development of population-specific driver diagrams, based on the population segments organisations selected to focus on. Each organisation was allocated an experienced quality improvement coach who supports them to apply a quality improvement approach to plan and deliver their projects, including support to generate insights based on data, staff and community engagement, carry out assets mapping, develop the project's aim and key drivers organisations need to work towards, identify measures, generate change ideas to be tested, and sustain successful changes.
Members of organisations taking part also attend quarterly learning sets where they come together to network, share challenges and ideas, and learn from each other.
Results
Populations identified by organisations include children and young people; Black, Asian and Ethnic minority men aged 18+ years; carer population; neurodivergent individuals with comorbid mental health diagnoses; Muslim women/Black women; refugees and forced migrants; women military veterans in Greater Manchester and Lancashire; Bangladeshi and Pakistani men and women in Oldham; Traveller community in Somerset. A number of initiatives are being tested by teams to improve access, experience and outcomes of mental health care, support, and treatment for these populations, such as offering mental health awareness sessions for refugees in a range of languages.
Conclusion
Addressing inequality in mental health care is a long and complex process. The AMHE collaborative is supporting teams to take an innovative approach to tackle this issue, by ensuring their projects are fully co-produced with those affected by inequality. This includes engaging representatives from the communities they are trying to improve access, experience and outcomes for in all aspects of their quality improvement projects; from design to generating ideas to test, and ensuring they measure what is important to these communities to determine whether improvements have been made.
With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.
This paper proposes a framework for comprehensive, collaborative, and community-based care (C4) for accessible mental health services in low-resource settings. Because mental health conditions have many causes, this framework includes social, public health, wellness and clinical services. It accommodates integration of stand-alone mental health programs with health and non-health community-based services. It addresses gaps in previous models including lack of community-based psychotherapeutic and social services, difficulty in addressing comorbidity of mental and physical conditions, and how workers interact with respect to referral and coordination of care. The framework is based on task-shifting of services to non-specialized workers. While the framework draws on the World Health Organization’s Mental Health Gap Action Program and other global mental health models, there are important differences. The C4 Framework delineates types of workers based on their skills. Separate workers focus on: basic psychoeducation and information sharing; community-level, evidence-based psychotherapeutic counseling; and primary medical care and more advanced, specialized mental health services for more severe or complex cases. This paper is intended for individuals, organizations and governments interested in implementing mental health services. The primary aim is to provide a framework for the provision of widely accessible mental health care and services.