Self-managing symptoms of Long COVID: an education and strategies research protocol.

Post-acute sequelae of SARS-COV-2 (PASC) is growing in prevalence, and involves symptoms originating from the central neurological, cardiovascular, respiratory, gastrointestinal, autonomic nervous, or immune systems. There are non-specific symptoms such as fatigue, headaches, and brain fog, which cannot be ascribed to a single system. PASC places a notable strain on our healthcare system, which is already laden with a large number of acute-COVID-19 patients. Furthermore, it impedes social, academic and vocational functioning, and impacts family life, relationships, and work/financial life. The treatment for PASC needs to target this non-specific etiology and wide-ranging sequelae. In conditions similar to PASC, such as "chemo brain," and prolonged symptoms of concussion, the non-specific symptoms have shown to be effectively managed through education and strategies for self-management and Mindfulness interventions. However, such interventions have yet to be empirically evaluated in PASC to our knowledge. In response to this gap, we have developed a virtual education intervention synthesized by psychiatrists and clinical psychologists for the current study. We will undertake a two-phase randomized controlled trial to determine the feasibility (Phase 1; N = 90) and efficacy (Phase 2; sample sized based on phase 1 results) of the novel 8 week Education and Self-Management Strategies group compared to a mindfulness skills program, both delivered virtually. Main outcomes include confidence/ability to self-manage symptoms, quality of life, and healthcare utilization. This study stands to mitigate the deleterious intrusiveness of symptoms on everyday life in patients with PASC, and may also help to reduce the impact of PASC on the healthcare system. Clinical trial registration:https://classic.clinicaltrials.gov/ct2/show/NCT05268523; identifier NCT05268523.

The Toronto Concussion Study: a prospective investigation of characteristics in a cohort of adults from the general population seeking care following acute concussion, 2016-2020.

Purpose: There is limited research regarding the characteristics of those from the general population who seek care following acute concussion. Methods: To address this gap, a large cohort of 473 adults diagnosed with an acute concussion (female participants = 287; male participants = 186) was followed using objective measures prospectively over 16 weeks beginning at a mean of 5.1 days post-injury. Results: Falls were the most common mechanism of injury (MOI) (n = 137, 29.0%), followed by sports-related recreation (n = 119, 25.2%). Male participants were more likely to be injured playing recreational sports or in a violence-related incident; female participants were more likely to be injured by falling. Post-traumatic amnesia (PTA) was reported by 80 participants (16.9 %), and loss of consciousness (LOC) was reported by 110 (23.3%). In total, 54 participants (11.4%) reported both PTA and LOC. Male participants had significantly higher rates of PTA and LOC after their injury compared to their female counterparts. Higher initial symptom burden was associated with a longer duration of recovery for both male and female participants. Female participants had more symptoms and higher severity of symptoms at presentation compared to male participants. Female participants were identified to have a longer recovery duration, with a mean survival time of 6.50 weeks compared to 5.45 weeks in male participants (p < 0.0001). A relatively high proportion of female and male participants in this study reported premorbid diagnoses of depression and anxiety compared to general population characteristics. Conclusion: Although premorbid diagnoses of depression and/or anxiety were associated with higher symptom burden at the initial visit, the duration of symptoms was not directly associated with a pre-injury history of psychological/psychiatric disturbance. This cohort of adults, from the general population, seeking care for their acute concussion attained clinical and functional recovery over a period of 4-12 weeks.

Centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use and cognitive dysfunction in patients with SLE.

OBJECTIVE: Cognitive dysfunction (CD) is detectable in approximately 40% of patients with SLE. Despite this high prevalence, there are no approved pharmacological treatment options for this detrimental condition. Preliminary murine studies show potential for targeting microglial activation as a treatment of SLE-CD, which may be ameliorated with centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use. The aim of this study is to determine if there is an association of cACEi/cARB use with cognitive function in a human SLE cohort. METHODS: The American College of Rheumatology neuropsychological battery was administered to patients with consecutive SLE at a single academic health centre at baseline, 6 and 12 months. Scores were compared with sex-matched and age-matched control subjects. Clinical and demographic data were gathered at each visit. The primary outcome was CD defined as dysfunction in two or more cognitive domains. The primary predictor was a total cumulative dose of cACEi/cARB in milligrams per kilogram, recorded as an equivalent ramipril dose. Odds of CD with respect to cACEi/cARB use were determined through generalised linear mixed modelling. RESULTS: A total of 300 patients, representing 676 visits, completed this study. One hundred sixteen (39%) met the criteria for CD. Fifty-three participants (18%) were treated with a cACEi or cARB. Mean cumulative dose was 236 mg/kg (calculated as equivalent ramipril dose). Cumulative cACEi/cARB dose was not protective against SLE-CD. Caucasian ethnicity, current employment status and azathioprine cumulative dose were each associated with reduced odds of SLE-CD. Increasing Fatigue Severity Scale score was associated with increased odds of CD. CONCLUSIONS: In a single-centre SLE cohort, cACEi/cARB use was not associated with absence of CD. Many important confounders may have influenced the results of this retrospective study. A randomised trial is required to accurately determine if cACEi/cARB is a potential treatment for SLE-CD.

Preliminary efficacy and predictors of response to a remotely-delivered symptom self-management program for persistent symptoms after concussion.

BACKGROUND: More than a quarter of adults with concussion endure prolonged symptoms of >3 months. We developed the Concussion Education Self-Management program to help people manage persisting symptoms. Here, we assess feasibility, preliminary efficacy, and correlates of response. METHODS: N = 80 adults participated in the program; ages ranged from 18 to 65 years and time post-injury ranged from 6 months to 18 years. Weekly sessions, delivered remotely and in groups, comprised education and strategies for management of cognitive, emotional, and physical symptoms. Primary outcome: Confidence to self-manage symptoms. Secondary outcomes: Quality of life; mood/anxiety/stress. Predictors of response: Self-reported cognitive, emotional and physical symptoms at intake. RESULTS: Pre- to post-program improvements were observed in confidence to self-manage, p < 0.03; quality of life, p < 0.001; depression, p < 0.001; anxiety, p < 0.001; and stress, p < 0.001. Considering confidence to self-manage, those with fewer cognitive and physical symptoms benefitted more (p's < 0.0005 and p < 0.01, respectively). DISCUSSION: This program shows promise for improving self-management of prolonged symptoms. Those with high symptom burden may need extra sessions to benefit. This is a cost-effective and scalable program that can reach people regardless of geographic location or impediments to travel.

"Don't Just Study our Distress, Do Something": Implementing and Evaluating a Modified Stepped-Care Model for Health Care Worker Mental Health During the COVID-19 Pandemic.

OBJECTIVE: Throughout the COVID-19 pandemic, there have been concerns about the mental health of health care workers (HCW). Although numerous studies have investigated the level of distress among HCW, few studies have explored programs to improve their mental well-being. In this paper, we describe the implementation and evaluation of a program to support the mental health of HCW at University Health Network (UHN), Canada's largest healthcare network. METHODS: Using a quality improvement approach, we conducted a needs assessment and then created and evaluated a modified stepped-care model to address HCW mental health during the pandemic. This included: online resources focused on psychoeducation and self-management, access to online support and psychotherapeutic groups, and self-referral for individual care from a psychologist or psychiatrist. We used ongoing mixed-methods evaluation, combining quantitative and qualitative analysis, to improve program quality. RESULTS: The program is ongoing, running continuously throughout the pandemic. We present data up to November 30, 2021. There were over 12,000 hits to the UHN's COVID mental health intranet web page, which included self-management resources and information on group support. One hundred and sixty-six people self-referred for individual psychological or psychiatric care. The mean wait time from referral to initial appointment was 5.4 days, with an average of seven appointments for each service user. The majority had moderate to severe symptoms of depression and anxiety at referral, with over 20% expressing thoughts of self-harm or suicide. Post-care user feedback, collected through self-report surveys and semistructured interviews, indicated that the program is effective and valued. CONCLUSIONS: Development of a high-quality internal mental health support for HCW program is feasible, effective, and highly valued. By using early and frequent feedback from multiple perspectives and stakeholders to address demand and implement changes responsively, the program was adjusted to meet HCW mental health needs as the pandemic evolved.

Assessing the Utility of the Montreal Cognitive Assessment in Screening for Cognitive Impairment in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Screening for cognitive impairment (CI) in systemic lupus erythematosus (SLE) relies on the American College of Rheumatology (ACR) neuropsychological battery (NB). By studying the concurrent criterion validity, our goal was to assess the Montreal Cognitive Assessment (MoCA) as a screening tool for CI compared to the ACR-NB and to evaluate the added value of the MoCA to the Automated Neuropsychological Assessment Metrics (ANAM). METHODS: A total of 285 adult SLE patients were administered the ACR-NB, MoCA, and ANAM. For the ACR-NB, patients were classified as having CI if there was a Z score of ≤-1.5 in ≥2 domains. The area under the curve (AUC) and sensitivities/specificities were determined. A discriminant function analysis was applied to assess the ability of the MoCA to differentiate between CI, undetermined CI, and non-CI patients. RESULTS: CI was not accurately identified by the MoCA compared to the ACR-NB (AUC of 0.66). Sensitivity and specificity were poor at 50% and 69%, respectively, for the cutoff of 26, and 80% and 45%, respectively, for the cutoff of 28. The MoCA had a low ability to identify CI status. The addition of the MoCA to the ANAM led to improvement on the AUC by only 2.5%. CONCLUSION: The MoCA does not have adequate concurrent criterion validity to accurately identify CI in patients with SLE. The low specificity of the MoCA may lead to overdiagnosis and concern among patients. Adding the MoCA to the ANAM does not substantially improve the accuracy of the ANAM. These results do not support using the MoCA as a screening tool for CI in patients with SLE.

Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment.

OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.

Association of mycophenolate and azathioprine use with cognitive function in systemic lupus.

OBJECTIVES: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. METHODS: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. RESULTS: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. CONCLUSION: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.

Future public health emergencies and disasters: sustainability and insights into support programs for healthcare providers.

BACKGROUND: The mental health of healthcare workers (HCWs) has been at the forefront throughout the COVID-19 pandemic. While workplace-based support programs have been developed in hospitals globally, few systematically collected data. While critical to their success, information on these programs and the experience of mental healthcare providers (MHP) who support colleagues is limited. The objective of this study was to explore the experiences of MHP caring for HCW colleagues within a novel workplace-based mental health support program during the COVID-19 pandemic, to provide insights on facilitators, areas for improvement and barriers to program sustainability. METHODS: This qualitative study used semi-structured interviews conducted by videoconference between September 2020 to October 2021. UHN CARES (University Health Network Coping and Resilience for Employees and Staff) Program was developed during the first wave of the COVID-19 pandemic in March 2020. It supports over 21,000 staff members within the UHN, Canada's largest academic health research institution, in Toronto, Canada. Purposive sampling was used to select 10 of the 22 MHP in the UHN CARES Program (n = 10). Using a critical realism framework, key components required to sustain a successful workplace-based mental health support program for HCWs and balance the needs of MHP were determined. RESULTS: Six psychiatrists and four psychologists (n = 10) with varying roles at UHN participated in 17 interviews, including seven repeat interviews exploring changes over time within the pandemic and program. Components which facilitated the success of the program included flexibility in scheduling, confidential health record storage, comprehensive administrative support, availability of resources and adaptive quality improvement approach. Recommendations for improvement included opportunities for peer supervision, triaging of cases, and managing HCW expectations. MHP found caring for HCWs to be meaningful and they utilized existing clinical skills during sessions. Challenges included working in a virtual setting, navigating boundaries when caring for colleagues, and managing the range of service users and their needs. CONCLUSIONS: These findings suggest how support programs can be structured for HCWs, how to provide support, and how to sustain this support, allowing health systems to balance the needs of HCWs and MHPs in preparation for future public health emergencies.

Revisiting the ICHD-3 criteria for headache attributed to mild traumatic injury to the head: Insights from the Toronto Concussion Study Analysis of Acute Headaches Following Concussion.

BACKGROUND: There is limited prospective data on the prevalence, timing of onset, and characteristics of acute headache following concussion/mild traumatic brain injury. METHODS: Adults diagnosed with concussion (arising from injuries not related to work or motor vehicle accidents) were recruited from emergency departments and seen within one week post injury wherein they completed questionnaires assessing demographic variables, pre-injury headache history, post-injury headache history, and the Sport Concussion Assessment Tool (SCAT-3) symptom checklist, the Sleep and Concussion Questionnaire (SCQ) and mood/anxiety on the Brief Symptom Inventory (BSI). RESULTS: A total of 302 participants (59% female) were enrolled (mean age 33.6 years) and almost all (92%) endorsed post-traumatic headache (PTH) with 94% endorsing headache onset within 24 hours of injury. Headache location was not correlated with site of injury. Most participants (84%) experienced daily headache. Headache quality was pressure/squeezing in 69% and throbbing/pulsing type in 22%. Associated symptoms included: photophobia (74%), phonophobia (72%) and nausea (55%). SCAT-3 symptom scores, Brief Symptom Inventory and Sleep and Concussion Questionnaire scores were significantly higher in those endorsing acute PTH. No significant differences were found in week 1 acute PTH by sex, history of migraine, pre-injury headache frequency, anxiety, or depression, nor presence/absence of post-traumatic amnesia and self-reported loss of consciousness. CONCLUSIONS: This study highlights the very high incidence of acute PTH following concussion, the timing of onset and characteristics of acute PTH, the associated psychological and sleep disturbances and notes that the current ICHD-3 criteria for headaches attributed to mild traumatic injury to the head are reasonable, the interval between injury and headache onset should not be extended beyond seven days and could, potentially, be shorted to allow for greater diagnostic precision.

Validation of the automated neuropsychological assessment metrics for assessing cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis. METHODS: 300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs. RESULTS: Two models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results. CONCLUSION: We provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

Can Sport Concussion Assessment Tool (SCAT) Symptom Scores Be Converted to Rivermead Post-concussion Symptoms Questionnaire (RPQ) Scores and Vice Versa? Findings From the Toronto Concussion Study.

Background: The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Sports Concussion Assessment Tool (SCAT) are widely used self-report tools assessing the type, number, and severity of concussion symptoms. There are overlapping symptoms and domains, though they are scored differently. The SCAT consists of 22 questions with a 7-point Likert scale for a total possible score 132. The RPQ has 16 questions and a 5-point Likert scale for a total of 64 possible points. Being able to convert between the two scores would facilitate comparison of results in the concussion literature. Objectives: To develop equations to convert scores on the SCAT to the RPQ and vice versa. Methods: Adults (17-85 years) diagnosed with a concussion at a referring emergency department were seen in the Hull-Ellis Concussion and Research Clinic, a rapid access concussion clinic at Toronto Rehab-University Health Network (UHN) Toronto Canada, within 7 days of injury. The RPQ and SCAT symptom checklists as well as demographic questionnaires were administered to all participants at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 12, 16. Results: 215 participants had 1,168 matched RPQ and SCAT assessments. Total scores of the RPQ and the SCAT had a rho = 0.91 (p < 0.001); correlations were lower for sub-scores of specific symptom domains (range 0.74-0.87, p < 0.001 for all domain comparisons). An equation was derived to calculate SCAT scores using the number and severity of symptoms on the RPQ. Estimated scores were within 3 points of the observed total score on the SCAT. A second equation was derived to calculate the RPQ from the proportion weighted total score of the SCAT. This equation estimated corresponding scores within 3 points of the observed score on the RPQ. Conclusions: The RPQ and SCAT symptom checklists total scores are highly correlated and can be used to estimate the total score on the corresponding assessment. The symptom subdomains are also strongly correlated between the 2 scales however not as strongly correlated as the total score. The equations will enable researchers and clinicians to quickly convert between the scales and to directly compare concussion research findings.

Longitudinal relationships between cognitive domains and depression and anxiety symptoms in systemic lupus erythematosus.

OBJECTIVES: To examine i) the relationship between neuropsychological performance and depression and anxiety over time, and ii) the overlap between classification of cognitive dysfunction, anxiety, and depression in SLE. METHODS: 301 patients with SLE were included. Cognition was measured using a modified version of the ACR neuropsychological battery; cognitive dysfunction was defined as z-scores ≤-1.5 on ≥2 domains. Depression and anxiety were measured using the Beck Depression Inventory-II and the Beck Anxiety Inventory, respectively. All measures were assessed at baseline, 6, and 12 months. Their relationships were analyzed using Multiple Factor Analysis (MFA). RESULTS: Anxiety and depression and neuropsychological performance were stable across time. Factor analysis identified two dimensions explaining 42.2% of the variance in neuropsychological performance. The first dimension (33.1% of the variance) included primarily complex cognitive tests measuring executive function; verbal, visual, and working memory; and complex processing speed. The second dimension (9.1% of the variance) included primarily measures of simple information processing speed or motor dexterity. Anxiety and depression scores were consistently related to the first cognitive dimension. There was substantial overlap in participants classified with cognitive dysfunction and anxiety and depression. CONCLUSIONS: Depression and anxiety symptoms in SLE patients are related to a cognitive dimension incorporating memory, executive function and complex processing speed in a stable manner across one year. Many patients with cognitive dysfunction exhibit clinically significant anxiety and depression. Further research should examine whether cognition improves when anxiety and depression are treated and mechanistic links between anxiety and depression and cognitive dysfunction in SLE.

Insight into intraindividual variability across neuropsychological tests and its association with cognitive dysfunction in patients with lupus.

OBJECTIVE: Dispersion, or variability in an individual's performance across multiple tasks at a single assessment visit, has been associated with cognitive dysfunction (CD) in many neurodegenerative and neurodevelopmental disorders. We aimed to compute a dispersion score using neuropsychological battery (NB) tests and determine its association with CD in patients with SLE. METHODS: CD was defined as a z-score of ≤-1.5 on ≥2 domains of the NB. To compute a type of dispersion score known as the intraindividual SD (ISD), the SD of age-adjusted and sex-adjusted z-scores was calculated for each visit in each patient. To estimate the association between ISD and cognitive status (CD and non-CD), we used multilevel logistic regression, adjusting for clinically important covariates. RESULTS: A total of 301 adult patients with SLE completed the NB at baseline, 187 of whom were reassessed at 6 months and 189 at 12 months. CD was observed in 35.2% of patients at baseline, 27.8% at 6 months and 28.0% at 12 months. Prior to covariate adjustment, the mean ISD for non-CD was 1.10±0.31 compared with 1.50±0.70 for CD. After adjusting for ethnicity, education, employment, socioeconomic status and anxiety/depression, there was a statistically significant association between ISD and CD (OR for one-unit increase in ISD: 13.56, 95% CI 4.80 to 38.31; OR for 1/10th-unit increase in ISD: 1.30, 95% CI 1.17 to 1.44). Findings were valid across multiple sensitivity analyses. CONCLUSION: This is the first study to show that patients with SLE who were classified as having CD by the NB had more variability across the NB tests (ie, higher ISD score) compared with those who were not classified as having CD.

Prediction of risk of prolonged post-concussion symptoms: Derivation and validation of the TRICORDRR (Toronto Rehabilitation Institute Concussion Outcome Determination and Rehab Recommendations) score.

BACKGROUND: Approximately 10% to 20% of people with concussion experience prolonged post-concussion symptoms (PPCS). There is limited information identifying risk factors for PPCS in adult populations. This study aimed to derive a risk score for PPCS by determining which demographic factors, premorbid health conditions, and healthcare utilization patterns are associated with need for prolonged concussion care among a large cohort of adults with concussion. METHODS AND FINDINGS: Data from a cohort study (Ontario Concussion Cohort study, 2008 to 2016; n = 1,330,336) including all adults with a concussion diagnosis by either primary care physician (ICD-9 code 850) or in emergency department (ICD-10 code S06) and 2 years of healthcare tracking postinjury (2008 to 2014, n = 587,057) were used in a retrospective analysis. Approximately 42.4% of the cohort was female, and adults between 18 and 30 years was the largest age group (31.0%). PPCS was defined as 2 or more specialist visits for concussion-related symptoms more than 6 months after injury index date. Approximately 13% (73,122) of the cohort had PPCS. Total cohort was divided into Derivation (2009 to 2013, n = 417,335) and Validation cohorts (2009 and 2014, n = 169,722) based upon injury index year. Variables selected a priori such as psychiatric disorders, migraines, sleep disorders, demographic factors, and pre-injury healthcare patterns were entered into multivariable logistic regression and CART modeling in the Derivation Cohort to calculate PPCS estimates and forward selection logistic regression model in the Validation Cohort. Variables with the highest probability of PPCS derived in the Derivation Cohort were: Age >61 years ([Formula: see text] = 0.54), bipolar disorder ([Formula: see text] = 0.52), high pre-injury primary care visits per year ([Formula: see text] = 0.46), personality disorders ([Formula: see text] = 0.45), and anxiety and depression ([Formula: see text] = 0.33). The area under the curve (AUC) was 0.79 for the derivation model, 0.79 for bootstrap internal validation of the Derivation Cohort, and 0.64 for the Validation model. A limitation of this study was ability to track healthcare usage only to healthcare providers that submit to Ontario Health Insurance Plan (OHIP); thus, some patients seeking treatment for prolonged symptoms may not be captured in this analysis. CONCLUSIONS: In this study, we observed that premorbid psychiatric conditions, pre-injury health system usage, and older age were associated with increased risk of a prolonged recovery from concussion. This risk score allows clinicians to calculate an individual's risk of requiring treatment more than 6 months post-concussion.

Metrics and definitions used in the assessment of cognitive impairment in systemic lupus erythematosus: A systematic review.

OBJECTIVE: To review: 1) degree of conformity to the American College of Rheumatology neuropsychological battery (ACR-NB) among studies that used a NB, 2) review definitions of cognitive impairment (CI) from studies that used a NB, and 3) characterize measurement tools used to assess CI in systemic lupus erythematosus (SLE). METHODS: The literature search was conducted in Ovid Medline, Embase, and PsycINFO for articles on CI in adult SLE patients. We reviewed studies that used a NB and compared their tests to the ACR-NB to assess the degree of conformity. Definitions of CI from studies that used a NB were reviewed when sufficient information was available. We reviewed and categorized CI measurement tools into four broad categories: NB, screening, incomplete/mixed batteries, and computerized batteries. RESULTS: Of 8727 references, 118 were selected for detailed review and 97 were included in the final analysis. Of 43 studies that used a NB, none of the studies used the ACR-NB exactly as published. Many studies supplemented with other tests. Overall, there was inconsistent use of ACR-NB tests. Definitions for CI varied, with cut-offs ranging from 1 to 3 standard deviations below normative values on domains/tests varying in type and number. The most frequently used measurement tool for assessing CI in SLE was a NB. Use of screening tests and computerized batteries have also increased over the last decade. CONCLUSION: The assessment and definition of CI in SLE remains heterogeneous. A consensus meeting to address existing inconsistencies should be considered to harmonize the field of CI in SLE.

A Promising Subject-Level Classification Model for Acute Concussion Based on Cerebrovascular Reactivity Metrics.

Concussion imaging research has primarily focused on neuronal disruption with lesser emphasis directed toward vascular dysfunction. However, blood flow metrics may be more sensitive than measures of neuronal integrity. Vascular dysfunction can be assessed by measuring cerebrovascular reactivity (CVR)-the change in cerebral blood flow per unit change in vasodilatory stimulus. CVR metrics, including speed and magnitude of flow responses to a standardized well-controlled vasoactive stimulus, are potentially useful for assessing individual subjects following concussion given that blood flow dysregulation is known to occur with traumatic brain injury. We assessed changes in CVR metrics to a standardized vasodilatory stimulus during the acute phase of concussion. Using a case control design, 20 concussed participants and 20 healthy controls (HCs) underwent CVR assessment measuring blood oxygen-level dependent (BOLD) magnetic resonance imaging using precise changes in end-tidal partial pressure of CO2 (PETCO2). Metrics were calculated for the whole brain, gray matter (GM), and white matter (WM) using sex-stratification. A leave-one-out receiver operating characteristic (ROC) analysis classified concussed from HCs based on CVR metrics. CVR magnitude was greater and speed of response faster in concussed participants relative to HCs, with WM showing higher classification accuracy compared with GM. ROC analysis for WM-CVR metrics revealed an area under the curve of 0.94 in males and 0.90 in females for speed and magnitude of response respectively. These greater than normal responses to a vasodilatory stimulus warrant further investigation to compare the predictive ability of CVR metrics against structural injury metrics for diagnosis and prognosis in acute concussion.

Validity Evidence for the Use of Automated Neuropsychologic Assessment Metrics As a Screening Tool for Cognitive Impairment in Systemic Lupus Erythematosus.

OBJECTIVE: Screening for cognitive impairment in systemic lupus erythematosus (SLE) conventionally relies on the American College of Rheumatology (ACR) neuropsychologic battery (NB), which is not universally available. To develop a more accessible screening approach, we assessed validity of the Automated Neuropsychological Assessment Metrics (ANAM). Using the ACR NB as the gold standard for cognitive impairment classification, the objectives were 1) to measure overall discriminative validity of the ANAM for cognitive impairment versus no cognitive impairment, 2) to identify ANAM subtests and scores that best differentiate patients with cognitive impairment from those with no cognitive impairment, and 3) to derive ANAM composite indices and cutoffs. METHODS: A total of 211 consecutive adult patients, female and male, with SLE were administered the ANAM and ACR NB. 1) For overall discriminative validity of the ANAM, we compared patients with cognitive impairment versus those with no cognitive impairment on 4 scores. 2) Six ANAM models using different scores were developed, and the most discriminatory subtests were selected using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was calculated to establish ANAM validity against the ACR NB. 3) ANAM composite indices and cutoffs were derived for the best models, and sensitivities and specificities were calculated. RESULTS: Patients with no cognitive impairment performed better on most ANAM subtests, supporting ANAM's discriminative validity. Cognitive impairment could be accurately identified by selected ANAM subtests with top models, demonstrating excellent AUCs of 81% and 84%. Derived composite indices and cutoffs demonstrated sensitivity of 78-80% and specificity of 70%. CONCLUSION: This study provides support for ANAM's discriminative validity for cognitive impairment and utility for cognitive screening in adult SLE. Derived composite indices and cutoffs enhance clinical applicability.