The effects of different types of organisational workplace mental health interventions on mental health and wellbeing in healthcare workers: a systematic review.

OBJECTIVE: To determine if and which types of organisational interventions conducted in small and medium size enterprises (SMEs) in healthcare are effective on mental health and wellbeing. METHODS: Following PRISMA guidelines, we searched six scientific databases, assessed the methodological quality of eligible studies using QATQS and grouped them into six organisational intervention types for narrative synthesis. Only controlled studies with at least one follow-up were eligible. RESULTS: We identified 22 studies (23 articles) mainly conducted in hospitals with 16 studies rated of strong or moderate methodological quality. More than two thirds (68%) of the studies reported improvements in at least one primary outcome (mental wellbeing, burnout, stress, symptoms of depression or anxiety), most consistently in burnout with eleven out of thirteen studies. We found a strong level of evidence for the intervention type "Job and task modifications" and a moderate level of evidence for the types "Flexible work and scheduling" and "Changes in the physical work environment". For all other types, the level of evidence was insufficient. We found no studies conducted with an independent SME, however five studies with SMEs attached to a larger organisational structure. The effectiveness of workplace mental health interventions in these SMEs was mixed. CONCLUSION: Organisational interventions in healthcare workers can be effective in improving mental health, especially in reducing burnout. Intervention types where the change in the work environment constitutes the intervention had the highest level of evidence. More research is needed for SMEs and for healthcare workers other than hospital-based physicians and nurses.

Implementing Reporting Standards for Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease.

PURPOSE OF REVIEW: There is considerable interest in using polygenic risk scores (PRSs) for assessing risk of atherosclerotic cardiovascular disease (ASCVD). A barrier to the clinical use of PRSs is heterogeneity in how PRS studies are reported. In this review, we summarize approaches to establish a uniform reporting framework for PRSs for coronary heart disease (CHD), the most common form of ASCVD. RECENT FINDINGS: Reporting standards for PRSs need to be contextualized for disease specific applications. In addition to metrics of predictive performance, reporting standards for PRSs for CHD should include how cases/control were ascertained, degree of adjustment for conventional CHD risk factors, portability to diverse genetic ancestry groups and admixed individuals, and quality control measures for clinical deployment. Such a framework will enable PRSs to be optimized and benchmarked for clinical use.

Supporting employees with mental illness and reducing mental illness-related stigma in the workplace: an expert survey.

An expert survey was designed to support the development of a workplace-based multi-country intervention tackling depression, anxiety, and mental illness-related stigma in small- and medium-sized enterprises (SMEs). Academic experts and representatives of SME organisations, specific sector organisations, labour or advocacy groups, and occupational health organisations, were contacted across eight European countries and Australia. The survey comprised closed and open text questions to assess expert opinion about interventions for employees with mental health difficulties, interventions supporting their managers, and anti-stigma interventions. The survey was available in six languages. The online platform Qualtrics was used for data collection. Quantitative data was analysed through descriptive statistics and qualitative data was analysed through thematic analysis. Sixty-five of 146 experts responded, representing a 42% response rate. Results showed only 26.2% of experts agreed that employees could speak openly about mental health issues, and 81.5% of experts indicated a large or medium unmet need for support for employees with mental health issues. Psychoeducational materials, face-to-face workshops and interventions based on cognitive behavioural therapy were ranked most likely to be taken up by employees. Experts rated as most useful for managers' guidelines on how to act if an employee has mental health issues (67.7%). The greatest number of experts indicated workshops of people with lived experience of mental illness (80.0%) and awareness campaigns (78.5%) were most required to tackle stigma. Responses were consistent between experts from different countries and areas of expertise. Experts in this multinational survey assessed that interventions supporting mental health in the workplace and tackling stigma are greatly needed. A multicomponent intervention with a wide range of materials and tools is supported.

Cross-Walk Comparison of the DVBIC-TBICoE and LIMBIC-CENC Combat-Related Concussion Prospective Longitudinal Study Datasets.

OBJECTIVE: To describe and compare cohorts between 2 large, longitudinal, federally-funded TBI studies of Service members and veterans across demographic, self-report, and neuropsychological variables. DESIGN: Analysis of data from the DVBIC-TBICoE and LIMBIC-CENC prospective longitudinal studies (PLS). SETTING: Recruitment locations spanning Department of Defense and Veterans Affairs hospitals across the U.S. PARTICIPANTS: 1463 participants (N=1463) enrolled in the DVBIC-TBICoE study and divided among non-injured (NIC) (n=191), injured control (IC) (n=349), mild TBI (mTBI) (n=682), and (severe, moderate, penetrating, and complicated mild traumatic brain injury (smcTBI) (n=241) subgroups. 1550 participants enrolled in the LIMBIC-CENC study and divided between IC (n=285) and mTBI (n=1265) subgroups. IC and mTBI study groups were compared across demographic and military characteristics, self-reported symptoms, and neuropsychological test scores. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Neurobehavioral Symptom Inventory, PTSD Checklist-Military Version, TBI quality of life, Test of Premorbid Functioning, Wechsler Adult Intelligence Scale-IV Visual Puzzles, Symbol Search, Coding, Letter-Number Sequencing, and Digit Span, Trail Making Test, Delis-Kaplan Executive Functioning System Verbal Fluency, Letter Fluency, and Category Fluency, California Verbal Learning Test-II, and Grooved Pegboard. RESULTS: Compared with DVBIC-TBICoE, LIMBIC-CENC participants have higher enrollment age, education level, proportion of Black race, and time from injury as well as less combat deployments and are less likely to be married. The distribution of military service branches also differed. Further, symptom profiles differed between cohorts. LIMBIC-CENC participants endorsed higher posttraumatic stress disorder symptomatology. DVBIC-TBICoE study IC participants endorsed higher somatosensory and vestibular symptoms (medium effect sizes). Other symptom measure differences had very small effect sizes (≤0.2). Differences were found on many cognitive test results, but are difficult to interpret given the demographic differences and generally very small effect sizes. CONCLUSIONS: The heavy use of National Institutes of Health common data elements in both studies and collaboration with the DVBIC-TBICoE study team on development of the LIMBIC-CENC assessment battery enabled this comparative analysis. Results highlight unique differences in study cohorts and add perspective and interpretability for assimilating past and future findings.

Developing a framework for evaluation: a Theory of Change for complex workplace mental health interventions.

BACKGROUND: There is a gap between the necessity of effective mental health interventions in the workplace and the availability of evidence-based information on how to evaluate them. The available evidence outlines that mental health interventions should follow integrated approaches combining multiple components related to different levels of change. However, there is a lack of robust studies on how to evaluate multicomponent workplace interventions which target a variety of outcomes at different levels taking into account the influence of different implementation contexts. METHOD: We use the MENTUPP project as a research context to develop a theory-driven approach to facilitate the evaluation of complex mental health interventions in occupational settings and to provide a comprehensive rationale of how these types of interventions are expected to achieve change. We used a participatory approach to develop a ToC involving a large number of the project team representing multiple academic backgrounds exploiting in tandem the knowledge from six systematic reviews and results from a survey among practitioners and academic experts in the field of mental health in SMEs. RESULTS: The ToC revealed four long-term outcomes that we assume MENTUPP can achieve in the workplace: 1) improved mental wellbeing and reduced burnout, 2) reduced mental illness, 3) reduced mental illness-related stigma, and 4) reduced productivity losses. They are assumed to be reached through six proximate and four intermediate outcomes according to a specific chronological order. The intervention consists of 23 components that were chosen based on specific rationales to achieve change on four levels (employee, team, leader, and organization). CONCLUSIONS: The ToC map provides a theory of how MENTUPP is expected to achieve its anticipated long-term outcomes through intermediate and proximate outcomes assessing alongside contextual factors which will facilitate the testing of hypotheses. Moreover, it allows for a structured approach to informing the future selection of outcomes and related evaluation measures in either subsequent iterations of complex interventions or other similarly structured programs. Hence, the resulting ToC can be employed by future research as an example for the development of a theoretical framework to evaluate complex mental health interventions in the workplace.

Outcome assessment of a complex mental health intervention in the workplace. Results from the MENTUPP pilot study.

OBJECTIVE: Multicomponent interventions are recommendable to achieve the greatest mental health benefits, but are difficult to evaluate due to their complexity. Defining long-term outcomes, arising from a Theory of Change (ToC) and testing them in a pilot phase, is a useful approach to plan a comprehensive and meaningful evaluation later on. This article reports on the pilot results of an outcome evaluation of a complex mental health intervention and examines whether appropriate evaluation measures and indicators have been selected ahead of a clustered randomised control trial (cRCT). METHODS: The MENTUPP pilot is an evidence-based intervention for Small and Medium Enterprises (SMEs) active in three work sectors and nine countries. Based on our ToC, we selected the MENTUPP long-term outcomes, which are reported in this article, are measured with seven validated scales assessing mental wellbeing, burnout, depression, anxiety, stigma towards depression and anxiety, absenteeism and presenteeism. The pilot MENTUPP intervention assessment took place at baseline and at 6 months follow-up. RESULTS: In total, 25 SMEs were recruited in the MENTUPP pilot and 346 participants completed the validated scales at baseline and 96 at follow-up. Three long-term outcomes significantly improved at follow-up (p < 0.05): mental wellbeing, symptoms of anxiety, and personal stigmatising attitudes towards depression and anxiety. CONCLUSIONS: The results of this outcome evaluation suggest that MENTUPP has the potential to strengthen employees' wellbeing and decrease anxiety symptoms and stigmatising attitudes. Additionally, this study demonstrates the utility of conducting pilot workplace interventions to assess whether appropriate measures and indicators have been selected. Based on the results, the intervention and the evaluation strategy have been optimised.

Genome-wide association and genotype by environment interactions for growth traits in U.S. Red Angus cattle.

BACKGROUND: Genotypic information produced from single nucleotide polymorphism (SNP) arrays has routinely been used to identify genomic regions associated with complex traits in beef and dairy cattle. Herein, we assembled a dataset consisting of 15,815 Red Angus beef cattle distributed across the continental U.S. and a union set of 836,118 imputed SNPs to conduct genome-wide association analyses (GWAA) for growth traits using univariate linear mixed models (LMM); including birth weight, weaning weight, and yearling weight. Genomic relationship matrix heritability estimates were produced for all growth traits, and genotype-by-environment (GxE) interactions were investigated. RESULTS: Moderate to high heritabilities with small standard errors were estimated for birth weight (0.51 ± 0.01), weaning weight (0.25 ± 0.01), and yearling weight (0.42 ± 0.01). GWAA revealed 12 pleiotropic QTL (BTA6, BTA14, BTA20) influencing Red Angus birth weight, weaning weight, and yearling weight which met a nominal significance threshold (P ≤ 1e-05) for polygenic traits using 836K imputed SNPs. Moreover, positional candidate genes associated with Red Angus growth traits in this study (i.e., LCORL, LOC782905, NCAPG, HERC6, FAM184B, SLIT2, MMRN1, KCNIP4, CCSER1, GRID2, ARRDC3, PLAG1, IMPAD1, NSMAF, PENK, LOC112449660, MOS, SH3PXD2B, STC2, CPEB4) were also previously associated with feed efficiency, growth, and carcass traits in beef cattle. Collectively, 14 significant GxE interactions were also detected, but were less consistent among the investigated traits at a nominal significance threshold (P ≤ 1e-05); with one pleiotropic GxE interaction detected on BTA28 (24 Mb) for Red Angus weaning weight and yearling weight. CONCLUSIONS: Sixteen well-supported QTL regions detected from the GWAA and GxE GWAA for growth traits (birth weight, weaning weight, yearling weight) in U.S. Red Angus cattle were found to be pleiotropic. Twelve of these pleiotropic QTL were also identified in previous studies focusing on feed efficiency and growth traits in multiple beef breeds and/or their composites. In agreement with other beef cattle GxE studies our results implicate the role of vasodilation, metabolism, and the nervous system in the genetic sensitivity to environmental stress.

Finding the right words: Articulating the value of mental health promotion. A focus group study.

The Lapinlahti Hospital initiative in Helsinki has transformed a disused psychiatric hospital into an open site for mental health promotion. The current study uses qualitative methods to explore how the initiative may promote population mental health. The phenomenological study comprised of data from 7 focus group including 28 participants. Resulting data were thematically analysed to articulate how the initiative supports mental wellbeing in different ways. Mental health benefits were categorized into three themes; mental health value, civil values and common values which were comprised of nine subthemes; paradigm shift, social inclusion, personal meaning, regeneration, ambience, stigma, sustainability, democracy and environment. Mental health promotion emphasises the impact of daily environments in which people live their lives. Results from this study support the use of broad based actions which promote different components of mental wellbeing simultaneously. Psychiatric hospitals may offer historically meaningful sites for such actions.

'If we would change things outside we wouldn't even need to go in ' supporting recovery via community-based actions: A focus group study on psychiatric rehospitalization.

BACKGROUND: Psychiatric rehospitalization is a complex phenomenon in need of more person-centred approaches. The current paper aimed to explore how community-based actions and daily life influence mental health and rehospitalization. DESIGN, SETTING AND PARTICIPANTS: The qualitative study included focus group data from six European countries including 59 participants. Data were thematically analysed following an inductive approach deriving themes and subthemes in relation to facilitators and barriers to mental health. RESULTS: Barriers consisted of subthemes (financial difficulty, challenging family circumstances and stigma), and facilitators consisted of three subthemes (complementing services, signposting and recovery). The recovery subtheme consisted of a further five categories (family and friends, work and recreation, hope, using mental health experience and meaning). DISCUSSION: Barriers to mental health largely related to social determinants of mental health, which may also have implications for psychiatric rehospitalization. Facilitators included community-based actions and aspects of daily life with ties to personal recovery. By articulating the value of these facilitators, we highlight benefits of a person-centred and recovery-focused approach also within the context of psychiatric rehospitalization. CONCLUSIONS: This paper portrays how person-centred approaches and day-to-day community actions may impact psychiatric rehospitalization via barriers and facilitators, acknowledging the social determinants of mental health and personal recovery. PATIENT OR PUBLIC CONTRIBUTION: The current study included participants with experience of psychiatric rehospitalization from six different European countries. Furthermore, transcripts were read by several of the focus group participants, and a service user representative participated in the entire research process in the original study.

Instruments to evaluate mental well-being in old age: a systematic review.

OBJECTIVE: The aim of this study is to identify and appraise existing instruments to evaluate mental well-being in old age. METHOD: Systematic literature searches in PubMed, PsycINFO, ProQuest Research Library, AgeLine and CINAHL databases were performed. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline was used to assess the measurement properties, reported according to the Preferred Reporting Items for Systematic Reviews and meta-Analysis (PRISMA) statement. For each measurement property, results were classified as positive, negative or indeterminate. The quality level of evidence was rated as high, moderate, low or very low following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 28 instruments were found. Most instruments evaluated different dimensions of mental well-being, including various subscales. The quality was adequate overall. Six instruments showed high quality (Perceived Well-Being Scale-PWB, Salamon-Conte Life Satisfaction in the Elderly Scale-SCLSES, Herth Hope Scale-HHS, Life Satisfaction Index Third Age-LSITA, Meaning in Life Scale-MLS, and SODdisfazione dell'Anziano-SODA), and other six a moderate level (Scale of Happiness of the Memorial University of Newfoundland-MUNSH, Six Scales of Psychological Well-Being-PWBS, Valuation Of Life-VOL, Life Satisfaction Scale for Chinese Elders-LSS-C, Meaningful Activity Participation Assessment-MAPA and Will To Life-WTL). CONCLUSION: This review provides the first comprehensive synthesis of instruments assessing mental well-being in older populations. The PWB, SCLSES, HHS, LSITA, MLS and SODA were the most appropriated instruments. An instrument that specifically measures mental well-being in the oldest old age group (aged 80 plus) and that considers its multidimensional nature is needed.

Visualisation of cholesterol and ganglioside GM1 in zebrafish models of Niemann-Pick type C disease and Smith-Lemli-Opitz syndrome using light sheet microscopy.

Lysosomal storage diseases are the most common cause of neurodegeneration in children. They are characterised at the cellular level by the accumulation of storage material within lysosomes. There are very limited therapeutic options, and the search for novel therapies has been hampered as few good small animal models are available. Here, we describe the use of light sheet microscopy to assess lipid storage in drug and morpholino induced zebrafish models of two diseases of cholesterol homeostasis with lysosomal dysfunction: First, Niemann-Pick type C disease (NPC), caused by mutations in the lysosomal transmembrane protein NPC1, characterised by intralysosomal accumulation of cholesterol and several other lipids. Second, Smith-Lemli-Opitz syndrome (SLOS), caused by mutations in 7-dehydrocholesterol reductase, which catalyses the last step of cholesterol biosynthesis and is characterised by intralysosomal accumulation of dietary cholesterol. This is the first description of a zebrafish SLOS model. We find that zebrafish accurately model lysosomal storage and disease-specific phenotypes in both diseases. Increased cholesterol and ganglioside GM1 were observed in sections taken from NPC model fish, and decreased cholesterol in SLOS model fish, but these are of limited value as resolution is poor, and accurate anatomical comparisons difficult. Using light sheet microscopy, we were able to observe lipid changes in much greater detail and identified an unexpected accumulation of ganglioside GM1 in SLOS model fish. Our data demonstrate, for the first time in zebrafish, the immense potential that light sheet microscopy has in aiding the resolution of studies involving lysosomal and lipid disorders.

Genome-wide association and genotype by environment interactions for growth traits in U.S. Gelbvieh cattle.

BACKGROUND: Single nucleotide polymorphism (SNP) arrays have facilitated discovery of genetic markers associated with complex traits in domestic cattle; thereby enabling modern breeding and selection programs. Genome-wide association analyses (GWAA) for growth traits were conducted on 10,837 geographically diverse U.S. Gelbvieh cattle using a union set of 856,527 imputed SNPs. Birth weight (BW), weaning weight (WW), and yearling weight (YW) were analyzed using GEMMA and EMMAX (via imputed genotypes). Genotype-by-environment (GxE) interactions were also investigated. RESULTS: GEMMA and EMMAX produced moderate marker-based heritability estimates that were similar for BW (0.36-0.37, SE = 0.02-0.06), WW (0.27-0.29, SE = 0.01), and YW (0.39-0.41, SE = 0.01-0.02). GWAA using 856K imputed SNPs (GEMMA; EMMAX) revealed common positional candidate genes underlying pleiotropic QTL for Gelbvieh growth traits on BTA6, BTA7, BTA14, and BTA20. The estimated proportion of phenotypic variance explained (PVE) by the lead SNP defining these QTL (EMMAX) was larger and most similar for BW and YW, and smaller for WW. Collectively, GWAAs (GEMMA; EMMAX) produced a highly concordant set of BW, WW, and YW QTL that met a nominal significance level (P ≤ 1e-05), with prioritization of common positional candidate genes; including genes previously associated with stature, feed efficiency, and growth traits (i.e., PLAG1, NCAPG, LCORL, ARRDC3, STC2). Genotype-by-environment QTL were not consistent among traits at the nominal significance threshold (P ≤ 1e-05); although some shared QTL were apparent at less stringent significance thresholds (i.e., P ≤ 2e-05). CONCLUSIONS: Pleiotropic QTL for growth traits were detected on BTA6, BTA7, BTA14, and BTA20 for U.S. Gelbvieh beef cattle. Seven QTL detected for Gelbvieh growth traits were also recently detected for feed efficiency and growth traits in U.S. Angus, SimAngus, and Hereford cattle. Marker-based heritability estimates and the detection of pleiotropic QTL segregating in multiple breeds support the implementation of multiple-breed genomic selection.

Determinants of multidimensional mental wellbeing in the oldest old: a rapid review.

PURPOSE: Improved life expectancy imposes new challenges for policy-makers. The growing oldest-old age group (defined as 80 and over) is often characterised by increased support needs. Greater attention to wellbeing in this population group is necessary, and may well require a shift in social policy focus. The current review seeks to explore current research on determinants of mental wellbeing for the oldest old. METHODS: An iterative rapid review approach was used to review existing literature in line with four dimensions of mental wellbeing defined by the European Welfare Models and Mental Wellbeing in Final Years of Life (EMMY) study; functional, social, personal and environmental. A specific focus on articles employing multidimensional definitions of mental wellbeing was adopted. RESULTS: Multidimensional indicators reflect the multifaceted and multidirectional dynamics of wellbeing in very old age. Considerable variety in both measures and terminology was found within the literature making precise comparison difficult. The current review takes steps towards comparability by focusing on studies implementing multiple measures of mental wellbeing including evaluative, hedonistic and eudaimonic factors. Clearly defined and multifaceted measures of mental wellbeing are needed to sharpen evidence used in policy development, appraisal and evaluation in light of the considerable diversity of health and functional states experienced in later life. CONCLUSIONS: Previous studies appear to line up the four main dimensions of mental wellbeing identified in the EMMY study. Actively improving opportunities for older adults to produce benefits to society can be done via a stronger focus on resources such as mental wellbeing.

Understanding frames: A qualitative exploration of standing frame use for young people with cerebral palsy in educational settings.

BACKGROUND: Consensus opinion supports standing frame use as part of postural management for nonambulant young people with cerebral palsy. Most young people with cerebral palsy in the United Kingdom, who use standing frames, use them at nursery or school, rather than at home. In this paper we report professionals' and parents' experiences and views of standing frame use specifically in educational settings. This research was conducted as part of a large mixed methods study to determine the acceptability and inform the design of a future trial of standing frames. METHODS: Qualitative methods were used: focus groups with educational professionals, parents and clinicians (paediatricians, physiotherapists and occupational therapists) were convened. Data were analysed thematically using framework analysis. RESULTS: Five focus groups were conducted. The overarching theme "flexibility" encompassed four subordinate themes: (i) "balancing education and therapy," which described the way education professionals had to juggle different priorities from health professionals within a multi-disciplinary team; (ii) "young people's autonomy," which highlighted participants' belief that standing frame use should be centred on the individual young person and their needs; (iii) "working within logistical boundaries," which demonstrated that "ideal" standing frame use was not always possible due to logistical issues (e.g., staffing and standing frame availability); and (iv) "competence and confidence," which highlighted that educational professionals felt that they lacked the training to confidently position young people in their standing frame. CONCLUSIONS: This paper highlights the complexity of standing frame use in the educational setting. If a standing frame programme is prescribed to be delivered in an educational setting, strong multidisciplinary and interagency communication is essential to balance therapy versus education. Training is required to ensure staff are competent in using the standing frame with the young person understanding their individual requirements. A flexible approach-inclusive of the young person's needs, logistical demands and resource-is necessary.

Interventions to mitigate the effects of poverty and inequality on mental health.

PURPOSE: To review psychosocial and policy interventions which mitigate the effects of poverty and inequality on mental health. METHODS: Systematic reviews, controlled trials and realist evaluations of the last 10 years are reviewed, without age or geographical restrictions. RESULTS: Effective psychosocial interventions on individual and family level, such as parenting support programmes, exist. The evidence for mental health impact of broader community-based interventions, e.g. community outreach workers, or service-based interventions, e.g. social prescribing and debt advice is scarce. Likewise, the availability of evidence for the mental health impact of policy level interventions, such as poverty alleviation or youth guarantee, is quite restricted. CONCLUSIONS: The social, economic, and physical environments in which people live shape mental health and many common mental disorders. There are effective early interventions to promote mental health in vulnerable groups, but it is necessary to both initiate and facilitate a cross-sectoral approach, and to form partnerships between different government departments, civic society organisations and other stakeholders. This approach is referred to as Mental Health in All Policies and it can be applied to all public policy levels from local policies to supranational.

Biofluid, Imaging, Physiological, and Functional Biomarkers of Mild Traumatic Brain Injury and Subconcussive Head Impacts.

Post-concussive symptoms are frequently reported by individuals who sustain mild traumatic brain injuries (mTBIs) and subconcussive head impacts, even when evidence of intracranial pathology is lacking. Current strategies used to evaluate head injuries, which primarily rely on self-report, have a limited ability to predict the incidence, severity, and duration of post-concussive symptoms that will develop in an individual patient. In addition, these self-report measures have little association with the underlying mechanisms of pathology that may contribute to persisting symptoms, impeding advancement in precision treatment for TBI. Emerging evidence suggests that biofluid, imaging, physiological, and functional biomarkers associated with mTBI and subconcussive head impacts may address these shortcomings by providing more objective measures of injury severity and underlying pathology. Interest in the use of biomarker data has rapidly accelerated, which is reflected by the recent efforts of organizations such as the National Institute of Neurological Disorders and Stroke and the National Academies of Sciences, Engineering, and Medicine to prioritize the collection of biomarker data during TBI characterization in acute-care settings. Thus, this review aims to describe recent progress in the identification and development of biomarkers of mTBI and subconcussive head impacts and to discuss important considerations for the implementation of these biomarkers in clinical practice.

Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.

BACKGROUND: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRSCHD) for 5 genetic ancestry groups. METHODS: We derived ancestry-specific and multi-ancestry PRSCHD based on pruning and thresholding (PRSPT) and ancestry-based continuous shrinkage priors (PRSCSx) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.1 million participants from 5 major genetic ancestry groups. Following training and optimization in the Million Veteran Program, we evaluated the best-performing PRSCHD in 176,988 individuals across 9 diverse cohorts. RESULTS: Multi-ancestry PRSPT and PRSCSx outperformed ancestry-specific PRSPT and PRSCSx across a range of tuning values. Two best-performing multi-ancestry PRSCHD (ie, PRSPTmult and PRSCSxmult) and 1 ancestry-specific (PRSCSxEUR) were taken forward for validation. PRSPTmult demonstrated the strongest association with CHD in individuals of South Asian ancestry and European ancestry (odds ratio per 1 SD [95% CI, 2.75 [2.41-3.14], 1.65 [1.59-1.72]), followed by East Asian ancestry (1.56 [1.50-1.61]), Hispanic/Latino ancestry (1.38 [1.24-1.54]), and African ancestry (1.16 [1.11-1.21]). PRSCSxmult showed the strongest associations in South Asian ancestry (2.67 [2.38-3.00]) and European ancestry (1.65 [1.59-1.71]), lower in East Asian ancestry (1.59 [1.54-1.64]), Hispanic/Latino ancestry (1.51 [1.35-1.69]), and the lowest in African ancestry (1.20 [1.15-1.26]). CONCLUSIONS: The use of summary statistics from a large multi-ancestry genome-wide meta-analysis improved the performance of PRSCHD in most ancestry groups compared with single-ancestry methods. Despite the use of one of the largest and most diverse sets of training and validation cohorts to date, improvement of predictive performance was limited in African ancestry. This highlights the need for larger genome-wide association study datasets of underrepresented populations to enhance the performance of PRSCHD.

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed effects of covariate stratification and interaction on body mass index (BMI) PGS (PGSBMI) across four cohorts of European (N=491,111) and African (N=21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R2 differences among strata. Covariates with the largest differences included age, sex, blood lipids, physical activity, and alcohol consumption, with R2 being nearly double between best and worst performing quintiles for certain covariates. 28 covariates had significant PGSBMI-covariate interaction effects, modifying PGSBMI effects by nearly 20% per standard deviation change. We observed overlap between covariates that had significant R2 differences among strata and interaction effects - across all covariates, their main effects on BMI were correlated with their maximum R2 differences and interaction effects (0.56 and 0.58, respectively), suggesting high-PGSBMI individuals have highest R2 and increase in PGS effect. Using quantile regression, we show the effect of PGSBMI increases as BMI itself increases, and that these differences in effects are directly related to differences in R2 when stratifying by different covariates. Given significant and replicable evidence for context-specific PGSBMI performance and effects, we investigated ways to increase model performance taking into account non-linear effects. Machine learning models (neural networks) increased relative model R2 (mean 23%) across datasets. Finally, creating PGSBMI directly from GxAge GWAS effects increased relative R2 by 7.8%. These results demonstrate that certain covariates, especially those most associated with BMI, significantly affect both PGSBMI performance and effects across diverse cohorts and ancestries, and we provide avenues to improve model performance that consider these effects.

Barriers and facilitators to implementing workplace interventions to promote mental health: qualitative evidence synthesis.

BACKGROUND: Despite growing interest in workplace mental health interventions, evidence of their effectiveness is mixed. Implementation science offers a valuable lens to investigate the factors influencing successful implementation. However, evidence synthesis is lacking, especially for small-to-medium-sized enterprises (SMEs) and for specific work sectors. The objectives of this review are to establish the scope of research with explicit analysis of implementation aspects of workplace mental health interventions and to identify barriers and facilitators to implementation in general and within SMEs and selected sectors. METHODS: A systematic scoping review and meta-synthesis of mixed methods process evaluation research from 11 databases, with the evaluation of methodological quality (MMAT) and confidence in findings (CERQual), was conducted. We selected information-rich studies and synthesised them using domains within the Nielsen and Randall implementation framework: context, intervention activities, implementation; and mental models. RESULTS: We included 43 studies published between 2009 and 2022, of which 22 were rated as information-rich to be analysed for barriers and facilitators. Most studies were conducted in healthcare. Facilitators reflecting 'high confidence' included: relevant and tailored content, continuous and pro-active leadership buy-in and support, internal or external change agents/champions, assistance from managers and peers, resources, and senior-level experience and awareness of mental health issues. Healthcare sector-specific facilitators included: easy accessibility with time provided, fostering relationships, clear communication, and perceptions of the intervention. Stigma and confidentiality issues were reported as barriers overall. Due to the small number of studies within SMEs reported findings did not reach 'high confidence'. A lack of studies in construction and Information and Communication Technology meant separate analyses were not possible. CONCLUSIONS: There is dependable evidence of key factors for the implementation of workplace mental health interventions which should be used to improve implementation. However, there is a lack of studies in SMEs and in a larger variety of sectors. SYSTEMATIC REVIEW REGISTRATION: Research Registry ( reviewregistry897 ).