School-Based Interventions and Art Therapy for Children Exposed to Trauma

This literature review examined childhood trauma as a growing public health issue in the United States. Childhood trauma or adverse childhood experiences (ACEs) can lead to negative health outcomes. Adults who were exposed to trauma early in life may face challenges such as depression, anxiety, substance abuse, intimate partner violence, incarceration, obesity, and low work performance. ACEs impact key areas of development when toxic levels of stress hormones are repeatedly released in the brain. Negative outcomes for traumatized children include struggling with social relationships, difficulty with emotional regulation, low academic achievement, and behavioral problems. Grounded in child-centered therapy and an underlying theme of hope, the commonalities between methods are highlighted to support a multi-modal approach to treatment. More diverse and informed treatment options in school can aid in breaking the intergenerational cycles of trauma and better the lives of children and families. Findings included that adverse childhood experiences are common in the United States, the impact of trauma is unique to each individual, and a variety of methods can be used to begin a healing process

The Association Between Early-life Written Language Skills and Late-life Cognitive Resilience to Alzheimer's Disease

As the population ages, projections suggest that the number of individuals living with age-related diseases such as Alzheimer’s disease will increase. Prevention of Alzheimer’s disease is a major priority since there is currently no cure for the disease. Cognitive resilience is a hypothetical construct designed to explain why some individuals manage to avoid cognitive changes despite the presence of Alzheimer neuropathology. Educational attainment is one of the well-documented examples of building cognitive resilience since high levels of educational attainment have been associated with delayed onset of cognitive impairment. Written language skills developed in early life may reflect the development of early intellect and are essential to educational attainment. Weak early-life written language skills (i.e., low idea density and low grammatical complexity) have been associated with poor cognitive function in later life. However, there is limited understanding of the influence of written language skills and their potential contribution to cognitive resilience. This research aimed to assess the association between written language skills and cognitive resilience using data from the Nun Study. The Nun Study is a longitudinal study of aging in religious sisters who were a minimum of 75 years of age at baseline. Idea density and grammatical complexity were determined using coded autobiographies. Autobiographies were obtained from archival records and were written at a mean age of 22 years. Cognitive resilience was operationalized based on whether individuals met the clinical diagnosis of dementia at last assessment prior to death according to DSM-IV criteria while fulfilling Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropathologic criteria (“definite” or “probable”) or National Institute on Aging and Reagan Institute (NIA-RI) neuropathologic criteria (“definite”, “intermediate” or “high” likelihood) for Alzheimer’s disease. Analyses included descriptive analyses (univariate and bivariate) as well as logistic regression models. The purpose of this project was to strengthen current knowledge on the potential association between early-life written language skills and late-life resilience to cognitive impairment. This study also aimed to better understand the implications of indicators of cognitive and brain reserve on this potential relationship. Based on descriptive and multivariable analyses, a relationship between written language skills (idea density and grammatical complexity) was found particularly in the CERAD sample where cognitive resilience was defined using CERAD criteria for Alzheimer neuropathology. In logistic regression models adjusting for standard covariates (age and APOE), low idea density was associated with decreased likelihood of cognitive resilience (Odds Ratio (OR): 0.15, 95% Confidence Interval (CI): 0.02-0.72). These findings meant that higher idea density (vs. low) was associated with six times greater odds of cognitive resilience. Similarly, low grammatical complexity was significantly associated with cognitive resilience in adjusted models for age and APOE (OR: 0.13, 95% CI: 0.03-0.50). That is, the odds of cognitive resilience in later life increased seven-fold among those with higher grammatical complexity compared to those with low grammatical complexity. Further analyses also suggested that grammatical complexity remained a significant predictor of cognitive resilience in the presence of indicators of cognitive (education) and brain (cerebral infarcts and cortical atrophy) reserve. In comparison, idea density was significant when separately adjusted for presence or number of infarcts along with standard covariates. However, idea density was not significant in a few full models (e.g., including adjustments for standard covariates (age and APOE), cortical atrophy and presence of infarcts, or standard covariates and education). These findings suggested the strong influences of both education and structural brain changes on the relationship between idea density and cognitive resilience. Future studies should aim to assess whether other forms of writing from early life (e.g., written language in social media) can also be associated with cognition in later life. Findings from this research contribute to the understanding of cognitive resilience and provide the foundation for further exploration into the influence of written language on the prevention of Alzheimer’s disease

Examining the Connection: Traumatic Life Events, Substance Use, and Service Utilization Among Persons Admitted to Inpatient Psychiatry in Ontario

Background Experiencing traumatic life events and the symptoms that follow have been associated with an increased risk for other mental health conditions. Among individuals who have experienced traumatic life events, comorbidities such as substance use disorder are particularly common. Individuals with co-morbid trauma and substance use may be less responsive to treatment, are prone to relapses, and increased hospitalizations. Gaps in care for individuals with co-occurring trauma and substance use reflect the growing need to understand associations between trauma experiences and substance use to identify opportunities for improving care and outcomes. Using data from persons who experienced trauma prior to admission to inpatient psychiatry, the purposes of this dissertation are to (1) identify the classifications of both trauma and substance use, (2) examine the service complexity received by persons with trauma, and (3) examine whether trauma classifications, and the presence of social relationships are associated with early leaves from inpatient care. Methods A population based retrospective cohort was developed using interRAI Mental Health (RAI-MH) assessment data from all inpatient psychiatric assessments in Ontario, Canada between January 1, 2015, to December 31, 2019. The RAI-MH is a comprehensive assessment tool completed by clinical staff overseeing the care of the person. Completion of the assessment draws on multiple sources of information such as a review of the patient’s clinical records, interviews and observations, consultation with other clinical staff, family, and first responders (CIHI, 2023). The cohort included all persons in non-forensic and non-geriatric beds who were over the age of 18, and who had experienced a traumatic life event at some point prior to admission. Modelling and analyses were all conducted using SAS 9.4. Study 1: Data were included for individuals with an index admission stay of 72 hours or longer during the observational window. Patients were excluded if they were admitted from another psychiatric hospital or if their first episode was not an admission assessment. Patients were included if they triggered the Traumatic Life events CAP of the RAI-MH (N=10,125). Latent class analysis was used to determine underlying subgroups of patients based on their patterns of traumatic life events and substance use behaviour. An 8-class solution was selected based on comparisons of Akaike information criteria, Bayesian information criteria, adjusted Bayesian criteria, and entropy values. Study 2: Data from the Ontario Mental Health Reporting System were included for patients who triggered the Traumatic Life events CAP with no recent psychiatric assessments (i.e., no admissions within the last two years) (N=7,871). A service complexity variable was created based on length of stay (from date of admission to date of discharge, measured in days), the frequency of non-nursing formal care use, and nursing interventions in the prior 7 days. Descriptive statistics and bivariate associations between all demographic characteristics and level of service complexity were conducted. Logistic regression modelling was then used to assess the association between latent classes and the outcome (i.e., service complexity: low/moderate versus high service complexity). Odds ratios (unadjusted and adjusted), and 95% confidence intervals were reported for the initial and final models. Study 3: All records for individuals who triggered the Traumatic Life events CAP with an index admission over 72 hours between January 1, 2015 and December 31, 2019 were included (N=11,043). Early leaves were defined based on discharge status. The variable was coded into three different levels including unplanned leaves (patients who were discharged due to an absence without an approved leave, and persons discharged against medical advice), early leave (patients with short length of stays), and no early leave. Chi-squared tests were used to understand associations between demographic and clinical characteristics, and early leaves from inpatient stays. Multinomial logistic regression modelling was then used to assess the association between latent classifications of trauma and substance use, Clinical Assessment Protocols, demographic and clinical characteristics, the multi-level outcome of early leaves (i.e., unplanned, or short length of stay), and those who did not discharge prematurely. Results Study 1: Using latent class analysis, eight classifications of trauma and substance use were identified, ranging from low (i.e., Class 1: Interpersonal Issues, Without Substance use) to high (i.e., Class 8: Widespread Trauma, Alcohol & Cannabis Addiction) complexity patterns of traumatic life events and substance use indicators. Classes with similar profiles of trauma were differentiated by variations in substances use patterns. Furthermore, substance use patterns ranged from use of specific substances to widespread use and show variation in the presence of indicators of problematic use. Multinomial logistic regression models highlighted additional factors associated with class membership such as homelessness, where those who were homeless were estimated to be 1.71-3.02 more likely to be in Class 3: Safety & Relationship Issues, Alcohol & Cannabis use, and 2.09-4.02 times more likely to be in Class 6: Widespread Trauma & Substance Addiction. Study 2: Service complexity ranged from 1 to 13, with the most common services being psychiatrist (84.3%), nurse practitioners or medical doctors (non-psychiatrists) (64.1%), and social workers (59.7%). High service complexity, defined as the upper quintile of formal care service use (scores of greater than or equal to 9), nursing interventions, and longer length of stay was observed in 18.1% of individuals with trauma. Compared to patients with few trauma experiences and no substance use, patients with more widespread trauma experiences and indicators of alcohol and cannabis addiction were 2.1 times (95% CI: 1.68-2.50) more likely to have high service complexity. Patients with safety and relationship traumas with alcohol and cannabis use, were less likely to have high service complexity compared to patients with interpersonal issues, without substance use (adj. OR: 0.70, 95% CI: 0.54-0.91). Characteristics such being female, having greater education, and being employed were associated with higher service complexity. Study 3: Multinomial logistic regression revealed that individuals in latent classes with patterns of substance use (e.g., Class 6: Widespread Trauma & Substance Addiction) were more likely to have unplanned early leaves compared to those without substance use (adj. OR: 4.17, 95% CI: 2.72-6.39). Individuals with interpersonal conflict (i.e., conflict in relationships and widespread interpersonal conflict) had increased odds of having early leaves that were unplanned. Persons in Class 4: Immigration with Interpersonal Issues, Alcohol & Cannabis Addiction (adj. OR: 0.68, 95% CI:0.56-0.83), and Class 8: Widespread Trauma, Alcohol & Cannabis Addiction (adj. OR:0.73, 95% CIL 0.60-0.89) were less likely to have early leaves that were short length of stays compared to all other classes. Discussion The findings highlight multi-dimensional experiences of both trauma and substance use. That is, experiences of trauma and patterns of substance use vary among patients with trauma admitted to inpatient psychiatry. Patterns of service use, and discharge status also varied. Differences identified suggest the need to consider the nuances of trauma to support patients, consider ongoing prevention of substance use, and address barriers in maintaining treatment. Study 1: When considering traumatic life events across the latent classes, experiences of trauma were diverse among inpatients: from those with a few traumatic life experiences centered around health and loss (Class 1) to those with widespread experiences that include accidents, health challenges, grief and loss, and other social circumstances (Class 8). In Ontario, there are few specialized programs in place for supporting trauma, except for several tertiary hospitals. Advances in publicly funded services outlined in provincial strategic plans may hold promise, such as the introduction of structured psychotherapy programs and specific resources to support the military and first responders (Ministry of Health, 2022). Increasingly, dual treatment options for both trauma and substance use (e.g., Concurrent Treatment of PTSD and Substance Use Disorders (COPE)) should be further explored (Persson et al., 2017). Further research should explore patterns of trauma and substance use in community mental health settings, and supporting clinician confidence in discussing traumatic life events with patients. Study 2: Nuances were observed when considering the relationship between latent classes of trauma and level of service complexity. Patients with indicators of substance addiction were more likely to have high service complexity. Findings highlight the importance of ensuring funding is allocated to public services for the continuation of care post-discharge. The RAI-MH can identify specific experiences and needs of persons with trauma that may be useful for informing further analyses on resource utilization and service planning. Given that economic costs data were not available, future research may consider the use of resource measurement and cost data to validate observed differences in service complexity. Study 3: The results of study 3 point to differences between early leaves that are unplanned versus short length of stays. Both discharge statuses reflect an important period for providing treatment and recognizing substance use. Latent classes with the highest likelihood of unplanned early leaves generally included indicators of substance use. An eagerness to return to the community to utilize substances may reflect early unplanned discharges in this study. Inpatient admissions highlight an important timeframe to intervene in ongoing substance use. Unplanned early leaves may also reflect individuals with complex trauma that would better be supported in longer-term specialized treatment programs. Other factors such as interpersonal conflict, and eating disorders were associated with early discharge status. Future studies should assess the association between social relationships, formal supports, and early leaves

Attending Nurse Practitioners in Long-Term Care Homes Evaluation

Introduction In 2014, the Ontario Ministry of Health and Long-Term Care (MOHLTC) announced funding for 75 nurse practitioners (NPs) over three years in long-term care (LTC) homes. This evaluation was approved by ICES’ Applied Health Research Question (AHRQ) team, a portfolio which answers questions from stakeholders having impact on healthcare policy. Objectives and Approach The purpose of this project is to evaluate the impact of the first thirty NPs hired. Changes will be evaluated using key outcome measures of resident care (e.g., early hospital discharge, emergency room bed days) identified through a literature review conducted by the MOHLTC. LTC home residents were identified using all individuals with claims in OHIP during the 2016-17 fiscal year with a location of a LTC home. LTC homes with a hired NP were considered to be cases and all other LTC homes were considered to be controls. Results For part one of this evaluation, case and control LTC homes were stratified by bed size, Case Mix Index, rurality and Local Health Integration Network. Hospitalization records and emergency visits (from Discharge Abstract Database and National Ambulatory Care Reporting System) were determined for LTCH residents 6 months before and after the NP hire date of October 1, 2016. Overall, the rate of hospital admissions (per 100 residents) increased by 3.44% (8.51% to 11.94%) following the NP hire date; whereas, the rate of hospital admissions increased by 2.29% (6.55% to 8.83%) among controls. Following the NP hire date, the rate of emergency department visits also increased by 3.15% among cases (16.62% to 19.77%) in comparison to a 2.31% increase among controls (12.55% to 14.86%). Conclusion/Implications The findings from this evaluation will inform further implementation strategies of the NP program and guide decision-making of future funding opportunities. In summary, the results will inform policies to strengthen care of LTC homes and improve the quality of care of residents

Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated. Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009). The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcome

Comparative genomics and host resistance against infectious diseases.

The large size and complexity of the human genome have limited the identification and functional characterization of components of the innate immune system that play a critical role in front-line defense against invading microorganisms. However, advances in genome analysis (including the development of comprehensive sets of informative genetic markers, improved physical mapping methods, and novel techniques for transcript identification) have reduced the obstacles to discovery of novel host resistance genes. Study of the genomic organization and content of widely divergent vertebrate species has shown a remarkable degree of evolutionary conservation and enables meaningful cross-species comparison and analysis of newly discovered genes. Application of comparative genomics to host resistance will rapidly expand our understanding of human immune defense by facilitating the translation of knowledge acquired through the study of model organisms. We review the rationale and resources for comparative genomic analysis and describe three examples of host resistance genes successfully identified by this approach

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Identity correlates of academic achievement : how influential are self, academic and ethnic identity statuses among college students?

The purpose of the study was to examine the effect of different identity statuses on academic achievement among a sample of students attending a community college. There were three identities of interest: ego, academic and ethnic. Participants’ overall grade point average was used as the measure of academic achievement. Identity was conceptualized using the Eriksonian-Marcian theoretical approach with ego and academic identities having four statuses: (a) achieved, (b) foreclosed, (c) diffused and (d) moratorium. The ethnic identity had two statuses: (a) commitment (achieved) and (b) exploration. A total of 163 students participated in the study. The data were analyzed using a series of path analyses. Results revealed that in the ego identity model, the status with the strongest direct effect was the ego identity diffused status. In the academic identity model, the status with the strongest direct effect was the academic moratorium status. In the ethnic identity model, the statuses had similar direct effects on academic achievement. The academic moratorium identity emerged as the most salient identity status. The findings have implications for educators and students as to how identity impacts students’ performance in the classroom.Ph.D

Protopathic Stimulant Use Among Children With Symptoms of ADHD

The purpose of the current study was to examine protopathic stimulant use among children with the symptoms of ADHD but do not have a diagnosis of ADHD. Protopathic or prodromal stimulant use refers to the use of stimulants by children with the symptoms of ADHD prior to a diagnosis of ADHD. In the current study, we examined children with the symptoms of ADHD who received stimulant treatment across time and with respect to several background variables. Our results indicate that these children who receive stimulant treatment without a diagnosis of ADHD are significantly more like to be eventually diagnosed with ADHD than not. Results also indicate that these children who receive stimulant treatment but do not yet have a diagnosis of ADHD are significantly more likely to have insurance that does not pay for diagnostic procedures. These results are discussed in view of treatment