Childhood Adversity and Mental Health Outcomes Among University Students: A Longitudinal Study.

BACKGROUND: Mental health concerns are common among university students and maybe elevated among those with specific risk exposures. The study examined the association between childhood adversities and mental health outcomes among undergraduate university students and assessed whether psychosocial and behavioral factors mediate those associations. METHODS: The Queen's University Student Well-Being and Academic Success Survey identified two large cohorts of first-year undergraduate students entering university in Fall 2018 and 2019 (n = 5,943). At baseline, students reported sociodemographic information, family-related mental health history, childhood physical abuse, sexual abuse, peer bullying, and parental separation or divorce. Baseline and follow-up surveys in Spring 2019, Fall 2019, and Spring 2020 included validated measures of anxiety (7-item Generalized Anxiety Disorder) and depressive symptoms (9-item Patient Health Questionnaire ), non-suicidal self-harm, and suicidality, along with psychological processes and lifestyle variables. Repeated measures logistic regression using Generalized Estimating Equations was used to characterize the associations between childhood adversities and mental health outcomes and examine potential mediation. RESULTS: Adjusting for age, gender, ethnicity, familial mental illness, and parental education, any childhood abuse (odds ratio: 2.89; 95% confidence interval, 2.58 to 3.23) and parental separation or divorce (odds ratio: 1.29; 95% confidence interval, 1.12 to 1.50) were significantly associated with a composite indicator of mental health outcomes (either 9-item Patient Health Questionnaire score ≥10 or 7-item Generalized Anxiety Disorderscore ≥10 or suicidality or self-harm). The association with childhood abuse weakened when adjusted for perceived stress, self-esteem, and insomnia (odds ratio: 2.05; 95% confidence interval, 1.80 to 2.34), and that with parental divorce weakened when adjusted for self-esteem (odds ratio: 1.17; 95% confidence interval, 1.00 to 1.36). CONCLUSION: Childhood abuse and parental separation or divorce were associated with mental health concerns among university students. Childhood adversities may impact later mental health through an association with stress sensitivity, self-esteem, and sleep problems. The findings suggest that prevention and early intervention focusing on improving sleep, self-esteem, and coping with stress while considering the individual risk profile of help-seeking students may help support student mental health.

Transitions to campus mental health care in university students: Determinants and predictors.

Background: Access to university mental health services is poorly characterized. Our objectives were to (1) assess patterns of access and (2) explore predictability of contact with student mental health services. Participants: Data derived from the U-Flourish study, which includes a survey of successive cohorts of incoming undergraduate students attending Queen's University, located in Ontario, Canada (Cohort 1: 2018, Cohort 2: 2019). Methods: Survey data sets were deterministically linked to administrative data provided by Student Wellness Services. Analyses included cross-tabulation, logistic and negative binomial regression. Predictive modeling used LASSO regression. Results: Baseline symptoms were robust determinants of access. For example, a PHQ-9 rating in the severe range (≥ 20) was associated with an OR of 9.71 (95% CI: 4.46-21.1). A predictive algorithm did not outperform cut point-based interpretation of PHQ-9 or GAD-7 ratings. Conclusions: Self-reported symptoms are consistently associated with service use, supporting the widespread use of symptom screens.

Cognitive-Behavioral Social Skills Training Adapted for Youth at Clinical High Risk for Psychosis.

Interventions for functional impairments in adolescents and young adults at clinical high risk (CHR) for psychosis are needed. Cognitive-Behavioral Social Skills Training (CBSST) has been found to improve functioning in patients with schizophrenia. The CBSST manual was adapted for CHR and implemented across 3 sites. The key changes that were made were to present a focus of normalization and destigmatization of attenuated psychotic symptoms and since CBSST has a major focus on role plays, problem solving and challenging thoughts, examples of these were changed to be more appropriate for this young CHR population. We describe the manual modifications and present fidelity data to examine the success of training and supervision methods in a multi-site randomized controlled trial of CBSST in CHR youth. Fidelity was high and comparable across sites. Case vignettes are presented to demonstrate how CBSST techniques were adapted for UHR individuals to target functional impairments.

Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group.

BACKGROUND: Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. METHODS: We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. RESULTS: The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. CONCLUSIONS: Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives. REGISTRATION: PROSPERO: CRD42018108393.

Identifying Possible Outcome Domains from Existing Outcome Measures to Inform an OMERACT Core Domain Set for Safety in Rheumatology Trials.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Safety Working Group objective was to identify harm domains from existing outcome measurements in rheumatology. METHODS: Systematically searching the MEDLINE database on January 24, 2017, we identified full-text articles that could be used for harm outcomes in rheumatology. Domains/items from the identified instruments were described and the content synthesized to provide a preliminary framework for harm outcomes. RESULTS: From 435 possible references, 24 were read in full text and 9 were included: 7 measurement instruments were identified. Investigation of domains/items revealed considerable heterogeneity in the grouping and approach. CONCLUSION: The ideal way to assess harm aspects from the patients' perspective has not yet been ascertained.

Developing an OMERACT Core Outcome Set for Assessing Safety Components in Rheumatology Trials: The OMERACT Safety Working Group.

OBJECTIVE: Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions. METHODS: The safety issue has previously been discussed at OMERACT, but without a consistent approach to ensure harms were included in COS. Our methods include (1) identifying harmful outcomes in trials of interventions studied in patients with rheumatic diseases by a systematic literature review, (2) identifying components of safety that should be measured in such trials by use of a patient-driven approach including qualitative data collection and statistical organization of data, and (3) developing a COS through consensus processes including everyone involved. RESULTS: Members of OMERACT including patients, clinicians, researchers, methodologists, and industry representatives reached consensus on the need to continue the efforts on developing a COS for safety in rheumatology trials. There was a general agreement about the need to identify safety-related outcomes that are meaningful to patients, framed in terms that patients consider relevant so that they will be able to make informed decisions. CONCLUSION: The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach.

Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis.

OBJECTIVE: To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. DESIGN: Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis. DATA SOURCES: Trials were identified from Medline, Embase, and Central databases from inception to 19 January 2016; abstracts from two major rheumatology meetings from 2009 to 2015; two trial registers; and hand searches of Cochrane reviews. STUDY SELECTION CRITERIA: Randomized or quasi-randomized trials that compared methotrexate with any other DMARD or combination of DMARDs and contributed to the network of evidence between the treatments of interest. MAIN OUTCOMES: American College of Rheumatology (ACR) 50 response (major clinical improvement), radiographic progression, and withdrawals due to adverse events. A comparison between two treatments was considered statistically significant if its credible interval excluded the null effect, indicating >97.5% probability that one treatment was superior. RESULTS: 158 trials were included, with between 10 and 53 trials available for each outcome. In methotrexate naive patients, several treatments were statistically superior to oral methotrexate for ACR50 response: sulfasalazine and hydroxychloroquine ("triple therapy"), several biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated probability of ACR50 response was similar between these treatments (range 56-67%), compared with 41% with methotrexate. Methotrexate combined with adalimumab, etanercept, certolizumab, or infliximab was statistically superior to oral methotrexate for inhibiting radiographic progression, but the estimated mean change over one year with all treatments was less than the minimal clinically important difference of 5 units on the Sharp-van der Heijde scale. Triple therapy had statistically fewer withdrawals due to adverse events than methotrexate plus infliximab. After an inadequate response to methotrexate, several treatments were statistically superior to oral methotrexate for ACR50 response: triple therapy, methotrexate plus hydroxychloroquine, methotrexate plus leflunomide, methotrexate plus intramuscular gold, methotrexate plus most biologics, and methotrexate plus tofacitinib. The probability of response was 61% with triple therapy and ranged widely (27-70%) with other treatments. No treatment was statistically superior to oral methotrexate for inhibiting radiographic progression. Methotrexate plus abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments. CONCLUSIONS: Triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine) and most regimens combining biologic DMARDs with methotrexate were effective in controlling disease activity, and all were generally well tolerated in both methotrexate naive and methotrexate exposed patients.