OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group: Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set.

BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review. OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS. METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators. RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies. CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.

The Effects of Systemic Lupus-Related Cognitive Impairments on Activities of Daily Living and Life Role Participation: A Qualitative Framework Study.

OBJECTIVE: Cognitive impairment (CI) in systemic lupus erythematosus (SLE) negatively impacts health-related quality of life leading to activity limitations. This qualitative study aimed to (1) explore the effect of SLE-related CI on activities of daily living and life role participation and (2) describe factors influencing activity restriction and life role participation. METHODS: Semistructured, in-depth interviews of lived experience of CI in SLE were conducted with 24 participants with SLE. Sociodemographic and clinical data, and objective and subjective cognitive function, were collected to characterize participants. A qualitative thematic content analysis was undertaken guided by a framework analytical approach. RESULTS: Participants reported problems in multiple cognitive domains, with multiple perceived causes. CI was felt to impact work, social, domestic, and family life, health, and independence. Five overarching themes were represented in the data: (1) characterization of SLE-reported CI, (2) perceived cause of CI, (3) perceived impact of CI on activities of daily living and life role participation, (4) adaptations for managing CI, and (5) influence of CI adaptations on activities of daily living and life role participation. CONCLUSION: This study provides a better understanding of the patient experience of CI in SLE, how it impacts their lives, and what coping strategies they employ. It highlights the long-term challenges those with CI in SLE undergo and provides evidence for the urgent need to implement multidisciplinary treatment options. When managing CI, it may be beneficial to evaluate and understand available psychosocial support resources to help identify and reinforce relevant adaptations to improve health-related quality of life.

Exploring the Impact of Labour Mobility on the Mental Health and Wellbeing of Skilled Trades Workers in Ontario, Canada.

Labour mobility and subsequent workers migration is an increasing trend worldwide and can be a force that counteracts Canada's shortage of skilled labour. Supercommuting allows workers facing economic challenges to pursue more financially advantageous work opportunities in other regions. This study aimed to evaluate the "supercommuting" labour mobility model and its impact on long-distance mobile workers' mental health and wellbeing. We utilized a non-experimental research design using convenience sampling from workers who participated in Blue Branch Inc.'s (Hamilton, Canada) supercommuting labour mobility model. An online questionnaire collected demographic data, work-related data, occupational stress measures related to burnout, and job-related stress data. Data collection was started on 1 April 2021, and of the total 58 participants, the majority (44, 76%) were male, born outside Canada, and had an average age of 32.8 years. Workplace Safety (95%), full-time employment opportunity (95%), career advancement possibility (95%), and income and benefits (94.9%) were found to be the most crucial factors to keep study participants working in their current position. Of the 47 participants who experienced burnout, only one showed severe burnout in each domain (personal, work-related, and colleague-related). There is a great need for preventative burnout programs and supportive employer resources for those who engage in long-distance labour commuting. The study emphasizes the need to encourage policymakers to develop solutions for training future Ontario workers to support mobile employment and long-distance labour commuting.

Evaluating the Effectiveness of Return-to-Work Interventions for Individuals with Work-Related Mental Health Conditions: A Systematic Review and Meta-Analysis.

The workplace is a vital setting to support positive mental health. Mental health conditions in the workforce contribute to decreased work engagement and participation. There is existing literature on return-to-work (RTW) interventions for individuals with work-related mental health conditions, however, there lacks consensus on their effectiveness. Therefore, the primary aim of this systematic review was to synthesize the literature and evaluate the effectiveness of return-to-work interventions on return-to-work rates, quality of life, and psychological wellbeing for individuals with work-related mental health conditions. Selected articles were organized and identified using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and the Population/Intervention/Comparison/Outcome (PICO) framework. Quality assessment of the included studies was completed using the Critical Appraisal Skills Programme randomized controlled trials checklist and the Joanna Briggs Institute quasi-experimental studies checklist. A random effects meta-analysis model was performed using DerSimonian-Laird weighting to calculate standard mean difference and risk ratios to assess the impact of RTW interventions on return-to-work rates, absenteeism, stress symptoms, depression symptoms, and quality of life. A total of 28 out of 26,153 articles met the inclusion criteria. Diagnoses for participants in the studies ranged from work-related stress to work-related PTSD following exposure to a psychologically traumatizing event in the workplace. No significant differences were found for the meta-analyses examining return-to-work rates, absenteeism, depression, stress, and quality of life. The most effective interventions were found to be a multi-domain intervention (67% of participants RTW full time) and a health-focused intervention (85% RTW rate). Future research may consider establishing effective interventions to develop programs or policies supporting the RTW of employees and promote mental well-being among employees experiencing work-related mental health conditions.

Interaction-integrated linear mixed model reveals 3D-genetic basis underlying Autism.

Genetic interactions play critical roles in genotype-phenotype associations. We developed a novel interaction-integrated linear mixed model (ILMM) that integrates a priori knowledge into linear mixed models. ILMM enables statistical integration of genetic interactions upfront and overcomes the problems of searching for combinations. To demonstrate its utility, with 3D genomic interactions (assessed by Hi-C experiments) as a priori, we applied ILMM to whole-genome sequencing data for Autism Spectrum Disorders (ASD) and brain transcriptome data, revealing the 3D-genetic basis of ASD and 3D-expression quantitative loci (3D-eQTLs) for brain tissues. Notably, we reported a potential mechanism involving distal regulation between FOXP2 and DNMT3A, conferring the risk of ASD.

Engaging Employers in Apprentice Training: Focus Group Insights from Small-to-Medium-Sized Employers in Ontario, Canada.

Several factors have been identified to influence the registration and retention of apprentices in the construction trades. Employer engagement is a key factor to promote growth in apprenticeships in the construction trades as participation rates continue to be low among small-to-medium-sized employers. In this study, we evaluated the effectiveness of the Ontario Electrical League's (OEL) employer mentorship program through the perspectives of small-to-medium-sized employers using a qualitative approach. Two focus groups were conducted virtually with 11 employers. Focus group audio transcripts were recorded and transcribed for thematic analysis. Themes were generated using a data-driven approach to examine the relationships between mentorship program outcomes and perspectives on industry-related recruitment and retention barriers. Three themes were identified: (a) long-term apprentice recruitment and retention challenges; (b) equity and mental health in the workplace; and (c) industry challenges and mentorship program outcomes. Generally, this sample of employers appreciated the value of the OEL mentorship program through praise of the continued educational support, employer management expertise, hiring resources, and apprentice onboarding tools despite industry barriers in trade stigma, equity and mental health in the workplace, and recruitment and retention challenges. Industry partners should work with these small-to-medium-sized employers to develop workplace initiatives and engage external partners to provide ongoing apprenticeship mentorship support to address the recruitment and retention barriers identified in this study.

The City and the City: Tent Camps and Luxury Development in the NoMA Business Improvement District (BID) in Washington, D.C.

The NoMA Business Improvement District (BID) is one of Washington DC's fastest developing areas and has one of the city's largest concentrations of unhoused tent camps, many of which are located in underpasses that provide bits of protection and privacy. These underpasses were created during DC's City Beautiful Movement and have been the site of neoliberal antihomeless strategies. In this paper I explore the production of space in the NoMA area and how property owners, business associations, and government actors sanitized public space for wealthy newcomers while excluding poor and unhoused residents.

Examining burnout in the electrical sector in Ontario, Canada: A cross-sectional study.

Workers in the trades sectors often experience mental health issues and decreased work ability due to occupational stress, workplace hazards and living in danger or constant fear of injury. Understanding the impacts of psychosocial risk factors on construction workers' mental health can aid in decreasing workplace injuries, lessening disabilities and increasing worker productivity. In this study, we focus on understanding and assessing the mental health and wellness of individuals in the electrical sector that are members of the Employer Engagement Project (EEP) from the Ontario Electrical League (OEL). The subset of potential participants included electricians and plumbers in Ontario working for small to medium sized employers (SME). The recruitment took place in 2022, with a total of 82 participants who completed a survey collecting demographic information, assessing the importance and availability/satisfaction of workplace factors and stress-and burnout-related questions. The data were analyzed using IBM SPSS Statistics 29.0. Two-sample Mann-Whitney U tests were performed to test for associations between the availability of work-related factors and burnout scores among the participants. Burnout scores were determined using the Copenhagen Burnout Inventory. Our findings demonstrate that dissatisfaction of the following factors: Workload allocation, internal staff development opportunity and stable staffing/minimal turnover, were associated with high burnout levels. The findings indicate there may be a relationship between certain work-related factors and burnout levels experienced. There is a need for improvement of workload allocation in SMEs to help enhance the mental health and well-being of employees.

Mental Health Outcomes among Electricians and Plumbers in Ontario, Canada: Analysis of Burnout and Work-Related Factors.

(i) Background: Working in the electrical and plumbing sectors is physically demanding, and the incidence of physical injury and work disability is high. This study aimed to assess the mental health and well-being of skilled trades workers working in the electrical and plumbing sectors; (ii) Methods: Forty participants completed an online survey assessing burnout, work-related factors, and mental health issues. Data were analyzed to determine the association between demographics, the availability, and importance of work-related factors, and burnout using a two-sample Mann-Whitney U test; (iii) Results: Our findings showed that among the work-related factors, workplace safety, family commitments, income and benefits, and full-time employment opportunities might be crucial factors to keep study participants working at their current position. Financial support for external training, which was found to be the most important factor in preventing colleague-related burnout, was available to the satisfaction of approximately 50% of the participants; (iv) Conclusion: Work-related factors such as workplace safety and the availability and support for external training may be protective against all types of burnout among this population. Future studies may consider a larger sample size with a more diverse group of participants and perform an intersectional analysis to incorporate minority identities in the analyses.

Cytokine alterations in pediatric internalizing disorders: Systematic review and exploratory multi-variate meta-analysis.

Pediatric internalizing disorders are prevalent and characterized by a maladaptive cognitive, emotional response to a perceived stressor. The hypothesized effect of this response is observable changes in behavior mediated by homeostatic inflammatory cytokines. The aim of this study was to synthesize the literature and analyze the effect of cytokines on pediatric internalizing disorders. Influential moderating variables, including mean body mass index, fasting status at blood collection, participant sex, cytokine type, mean age, percentage of sample medicated, and diagnosis, were also assessed. A systematic literature search was performed in electronic databases (Medline, PubMed, and PsycINFO) from January 1, 1980 to June 15, 2022. Case-control studies of pediatric internalizing disorders, specifically anxiety and depression, were reviewed for their association with peripheral cytokine levels. Meta-analyses were performed using a random effects multi-variate model and effect sizes were calculated using Hedge's g for IL-2, CRP, IL-6, TNF-α, IL-1ß, IFN-γ, and IL-10. Thirty-three studies were reviewed and 28 studies were included in the meta-analysis (n = 1322 cases and n = 3617 controls). Peripheral cytokine levels were elevated in pediatric internalizing disorders compared to controls (Hedge's g = 0.19, p < 0.001). In the moderator analyses, depression diagnosis (Hedge's g = 0.18, p = 0.009) and non-fasting blood collection (Hedge's g = 0.20, p = 0.006) were significant. The meta-analytic findings are limited by methodological variation between studies, high heterogeneity, and low statistical power. Despite this, the findings suggest that elevated peripheral cytokine levels may play a role in the etiology and/or symptom maintenance of pediatric internalizing disorders.

Management of mood and anxiety disorders in patients receiving opioid agonist therapy: Review and meta-analysis.

BACKGROUND AND OBJECTIVES: Patients with opioid use disorders and mood and anxiety symptoms have a variable prognosis. Few randomized controlled trials (RCTs) have evaluated treatment of depression or anxiety in patients receiving opioid agonist therapies (OAT). This review evaluates studies of pharmacotherapy/psychotherapy for treating symptoms of depression or anxiety in patients receiving OAT. METHODS: Public databases were searched for clinical trials of pharmacotherapy or psychotherapy for managing depression or anxiety symptoms in adults receiving OAT. Subsequently, we conducted a random effects meta-analysis model of RCTs by antidepressants subclasses. RESULTS: In our literature search, we identified 22 RCTs, eight of which were eligible for meta-analysis. Seven studies evaluated antidepressants in patients already maintained on OAT; two studies reported significant results for antidepressant effects versus placebo. Similarly, two of the seven studies that initiated antidepressants with OAT had advantages over placebo. Meta-analysis of grouped data revealed that tricyclic antidepressants (TCAs) (n = 235) significantly improved mean depression scores (SMD = -2.35, 95%CI: [-4.35, -0.34], z = -2.29, p = .022) while Selective Serotonin Reuptake Inhibitors (SSRIs) (n = 311) were not significantly different than placebo (SMD = 0.47, 95%CI: [-0.35, 1.30], z = 1.12, p = .263). Four out of five studies that implemented psychotherapeutic approaches reported a greater reduction of depressive symptoms than the comparison group. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: To date, psychotherapy has the most documented evidence for efficacy. TCAs appears effective but with more adverse effects than SSRIs. Further studies of OAT and adjunct antidepressant treatments for dual diagnosis patients are warranted. (Am J Addict 2017;26:551-563).

Interaction between Methylation and CpG Single-Nucleotide Polymorphisms in the HTR2A Gene: Association Analysis with Suicide Attempt in Schizophrenia.

Dysfunctional mechanisms in the serotonergic system have been implicated in suicidal behavior among patients with schizophrenia. However, previous association analyses of major serotonin genes have provided inconsistent findings regarding their role in suicidal behavior. The goal of the current study was to identify single-nucleotide polymorphisms (SNP) within HTR2A that directly affect CpG methylation sites in schizophrenic patients with suicidal behavior. Furthermore, direct methylation analysis was performed using genomic DNA from peripheral leukocytes employing bisulfite pyrosequencing to assess the contributions of six CpG sites in HTR2A exon I in 67 schizophrenia patients assessed for lifetime suicide attempt. Potential methylation in 25 CpG SNPs across the entire HTR2A gene was analyzed considering their direct contribution to methylation. When we compared direct methylation between attempters and nonattempters, we found that only the polymorphic T102C (rs6313) was significantly different between the two groups (p = 0.02). Furthermore, in the potential methylation analysis, we found a nominal association with suicide attempt for six of the 25 SNPs analyzed, i.e. rs2770293 (p = 0.045), rs6313 (p = 0.033), rs17068986 (p = 0.029), rs4942578 (p = 0.024), rs1728872 (p = 0.014), and rs9534511 (p = 0.003). The results of this investigation provide preliminary evidence that the combined analysis of CpG SNPs and methylation may be useful for investigating the genetic and epigenetic factors involved in suicidal behavior.

Differential Allelic Expression of HTR1B in Suicide Victims: Genetic and Epigenetic Effect of the Cis-Acting Variants.

OBJECTIVES: In the present study, we tested the allelic imbalance of the C861G single nucleotide polymorphism (SNP) of HTR1B in the frontal cortex of suicide victims. METHODS: The study was conducted using 3 sets of samples. First, C861G allele-specific mRNA levels in the frontal cortex were compared between suicide (n = 13) and nonsuicide controls (n = 13) from the Stanley Medical Research postmortem brain collection. Second, we tested common variants in the HTR1B promoter for linkage disequilibrium (LD) with the C861G variant in an unrelated sample of suicide attempters (SA; n = 38) and non-SA (NSA; n = 42). Finally, we performed a family-based association study of the C861G and promoter variants in 162 nuclear families using suicidal behavior severity scores as phenotype. RESULTS: We observed no alterations in the C/G expression ratio in suicide victims compared to nonsuicide controls (p = 0.370). When comparing the LD between the C861G and cis-acting SNPs, we did not find any differences in SA and NSA. There was no association between preferential transmission of cis-acting SNPs and suicidal behavior severity scores in both maternal and paternal meiosis. CONCLUSIONS: We found several promoter variants in LD that may potentially influence the allelic imbalance in the C861G variant. However, no evidence of allelic imbalance nor parent-of-origin effects of the C861G variant was observed in suicidal behavior. Further research is required to assess this marker in larger cohorts.

Epigenetic studies of suicidal behavior.

Recent studies have shown an association between gene alterations by epigenetic mechanisms and suicidal behavior. These epigenetic mechanisms are mitotically, and in some cases meiotically, heritable changes in the genome through non-DNA sequence coding processes that alter gene expression as a result of variable changes in environmental stimuli. Genome-wide association studies have been inconsistent in elucidating the association between genes and suicidal behavior, thereby making the heritability of suicidal behavior is unclear. However, recent epigenetic studies have provided evidence that epigenetic mechanisms could deliver the missing link between the heritability of suicidal behavior and the interaction between environment and the genome. The present review provides an in-depth discussion of epigenetic mechanisms that may regulate gene expression in suicidal behavior. The findings of current epigenetic studies on suicidal behavior will also be discussed considering future epigenome-wide association studies on elucidating the contributions of environment and genome on suicidal behavior.

Meta-analysis of P300 waveform in panic disorder.

The P300 waveform has been inconsistently linked to the maladaptive information-processing characterized in panic disorder (PD). The purpose of this study was to synthesize previous event-related potential (ERP) findings and determine whether patients with PD have significant abnormalities in the P300 wave compared to controls. We performed a systematic literature search for studies published between 1980 and 2013 that reported P300 measurements in patients with PD and controls. Effect size estimates were computed using the restricted maximum likelihood model. We identified 14 ERP studies that analyzed P300 amplitude (461 PD and 355 controls), and 11 ERP studies that analyzed latency (320 PD and 282 controls). Patients with PD had reduced P300 amplitudes compared to controls, but this difference was non significant at midline electrodes (n = 14, ES -0.16; z = -1.55, p = 0.122). However, P300 amplitude was significantly reduced when analyzing the Pz electrode independently (n = 7, ES -0.48, z = -3.92, p < 0.001). No significant differences between cases and controls in P300 latency were observed at the midline electrodes (n = 11, ES 0.11, z = 0.64, p = 0.524). This meta-analysis included non-peer reviewed literature and ERP stimuli with varying levels of emotional salience, which may have introduced bias into the analysis. There is no robust evidence that P300 latency alterations are present in patients with PD; however, there are indications of reduced amplitude at Pz relative to controls. Reductions in amplitude may be associated with reduced neural resources allocated to contextual updating, selective attention, and neural inhibition mechanisms.

Lack of association between dopamine-ß hydroxylase gene and a history of suicide attempt in schizophrenia: comparison of molecular and statistical haplotype analyses.

OBJECTIVE(S): In the present study, we examined whether there was an association between dopamine-ß hydroxylase (DBH) promoter polymorphisms (a 5'-ins/del and a GTn repeats) and a history of suicide attempt in 223 chronic schizophrenia individuals using statistical and molecular analyses. Within the genetic association study design, we compared the statistical haplotype phase with the molecular phase produced by the amplicon size analysis. MATERIALS AND METHODS: The two DBH polymorphisms were analysed using the Applied Biosystem 3130 and the statistical analyses were carried out using UNPHASED v.3.1.5 and PHASE v.2.1.1 to determine the haplotype frequencies and infer the phase in each patient. Then, DBH polymorphisms were incorporated into the Haploscore analysis to test the association with a history of suicide attempt. RESULTS: In our sample, 62 individuals had a history of suicide attempt. There was no association between DBH polymorphisms and a history of suicide attempt across the different analytical strategies applied. There was no significant difference between the haplotype frequencies produced by the amplicon size analysis and statistical analytical strategies. However, some of the haplotype pairs inferred in the PHASE analysis were inconsistent with the molecular haplotype size measured by the ABI 3130. CONCLUSION: The amplicon size analysis proved to be the most accurate method using the haplotype as a possible genetic marker for future testing. Although the results were not significant, further molecular analyses of the DBH gene and other candidate genes can clarify the utility of the molecular phase in psychiatric genetics and personalized medicine.

The clinical utility of the auditory P300 latency subcomponent event-related potential in preclinical diagnosis of patients with mild cognitive impairment and Alzheimer's disease.

The present meta-analysis investigated the clinical utility of the auditory P300 latency event-related potential in differentiating patients with Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and unaffected controls. Effect size estimates were computed from mean P300 latency measurements at midline electrodes between patients and unaffected controls using the random effects restricted maximum likelihood model. The effects of clinical and ERP/EEG methological variables were assessed in a moderator analysis. P300 latency was found to be significantly prolonged in patients with AD (and MCI) compared to unaffected controls. Shortened P300 latencies were observed when comparing patients with MCI to patients with AD. Clinically relevant differences in P300 latency effect sizes were associated with mean age, interstimulus interval, stimulus difference, target frequency, reference electrode, and sampling rate. The meta-analytic findings provide robust statistical evidence for the use of the auditory P300 latency subcomponent as a biological marker of prodromal AD.

Meta-analysis of the endogenous N200 latency event-related potential subcomponent in patients with Alzheimer's disease and mild cognitive impairment.

OBJECTIVES: The N200 latency subcomponent has the potential to be an accurate neurophysiological marker of the cognitive deterioration seen in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: Standard mean difference (SMD) estimates of the N200 latency subcomponent were compared in three treatment groups: patients with AD, patients with MCI, and an unrelated elderly control group. RESULTS: Patients with AD had significantly prolonged N200 latencies compared to the control group, pooled SMD: 0.866 (95% CI: 0.517 to 1.214, z=4.87, p<0.001). Patients with MCI had significantly prolonged N200 latencies compared to the control group, pooled SMD: 0.578 (95% CI: 0.213 to 0.943, z=3.31, p=0.002). When comparing patients with AD and MCI the N200 latencies were similar, pooled SMD: 0.096 (95% CI: -0.261 to 0.453, z=0.53, p=0.598). CONCLUSION: The abnormalities present in the N200 latency subcomponent validate previous research that N200 latency is an informative indicator of information-processing deterioration in patients with cognitive impairment. SIGNIFICANCE: Clinically, measurements of N200 latency can be used as a risk assessment of elderly patients that may be progressing to mild cognitive impairment and/or Alzheimer's disease.