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.

Interindividual and intraindividual variability in amnestic mild cognitive impairment (aMCI) measured with an online cognitive assessment.

INTRODUCTION: Mean cognitive performance is worse in amnestic mild cognitive impairment (aMCI) compared to control groups. However, studies on variability of cognitive performance in aMCI have yielded inconclusive results, with many differences in variability measures and samples from one study to another. METHODS: We examined variability in aMCI using an existing older adult sample (n = 91; 51 with aMCI, 40 with normal cognition for age), measured with an online self-administered computerized cognitive assessment (Cogniciti's Brain Health Assessment). Our methodology extended past findings by using pure measures of variability (controlling for confounding effects of group performance or practice), and a clinically representative aMCI sample (reflecting the continuum of cognitive performance between normal cognition and aMCI). RESULTS: Between-group t-tests showed significantly greater between-person variability (interindividual variability or diversity) in overall cognitive performance in aMCI than controls, although the effect size was with a small to moderate effect size, d = 0.44. No significant group differences were found in within-person variability (intraindividual variability) across cognitive tasks (dispersion) or across trials of a response time task (inconsistency), which may be because we used a sample measuring the continuum of cognitive performance. Exploratory correlation analyses showed that a worse overall score was associated with greater inter- and intraindividual variability, and that variability measures were correlated with each other, indicating people with worse cognitive performance were more variable. DISCUSSION: The current study demonstrates that self-administered online tests can be used to remotely assess different types of variability in people at risk of Alzheimer`s. Our findings show small but significantly more interindividual differences in people with aMCI. This diversity is considered as "noise" in standard assessments of mean performance, but offers an interesting and cognitively informative "signal" in itself.

Assessment of cardiovascular risk tools as predictors of cardiovascular disease events in systemic lupus erythematosus.

BACKGROUND: SLE is an independent risk factor for cardiovascular disease (CVD). This study aimed to determine which among QRISK2, QRISK3, Framingham Risk Score (FRS), modified Framingham Risk Score (mFRS) and SLE Cardiovascular Risk Equation (SLECRE) best predicts CVD. METHODS: This is a single-centre analysis on 1887 patients with SLE followed prospectively according to a standard protocol. Tools' scores were evaluated against CVD development at/within 10 years for patients with CVD and without CVD. For patients with CVD, the index date for risk score calculation was chosen as close to 10 years prior to CVD event. For patients without CVD, risk scores were calculated as close to 10 years prior to the most recent clinic appointment. Proportions of low-risk (<10%), intermediate-risk (10%-20%) and high-risk (>20%) patients for developing CVD according to each tool were determined, allowing sensitivity, specificity, positive/negative predictive value and concordance (c) statistics analysis. RESULTS: Among 1887 patients, 232 CVD events occurred. QRISK2 and FRS, and QRISK3 and mFRS, performed similarly. SLECRE classified the highest number of patients as intermediate and high risk. Sensitivities and specificities were 19% and 93% for QRISK2, 22% and 93% for FRS, 46% and 83% for mFRS, 47% and 78% for QRISK3, and 61% and 64% for SLECRE. Tools were similar in negative predictive value, ranging from 89% (QRISK2) to 92% (SLECRE). FRS and mFRS had the greatest c-statistics (0.73), while QRISK3 and SLECRE had the lowest (0. 67). CONCLUSION: mFRS was superior to FRS and was not outperformed by the QRISK tools. SLECRE had the highest sensitivity but the lowest specificity. mFRS is an SLE-adjusted practical tool with a simple, intuitive scoring system reasonably appropriate for ambulatory settings, with more research needed to develop more accurate CVD risk prediction tools in this population.

Identifying a Response for the Systemic Lupus Erythematosus Disease Activity 2000 Glucocorticoid Index.

OBJECTIVE: To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K Glucocorticoids (SLEDAI-2KG) indices in identifying responders to standard of care therapy. METHODS: Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI-2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow-up visit at 9 months, were studied. Response to standard of care therapy at first follow-up visit was assessed using the SLEDAI-2K and SLEDAI-2KG. The performances of the SLEDAI-2K and SLEDAI-2KG were compared using a cutoff point of 4. RESULTS: In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI-2K score of ≥4. The SLEDAI-2KG identified 142 (97.9%) responders among the SLEDAI-2K responders. More importantly, the SLEDAI-2KG identified 11 (25.6%) additional responders among SLEDAI-2K nonresponders (n = 43). This resulted from the ability of the SLEDAI-2KG to account for the decrease in glucocorticoids dose. CONCLUSION: The SLEDAI-2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI-2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI-2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI-2K, which could alter response rates in drug trials and observational studies.

Triaging the Terminally Ill-Development of the Responding to Urgency of Need in Palliative Care (RUN-PC) Triage Tool.

CONTEXT: Evidence-based resource allocation is receiving increasing attention as we strive for equity, transparency, and cost-effectiveness across health care. In the context of finite resources, which of our patients with terminal illness should be prioritized for urgent palliative care? OBJECTIVES: To develop the scoring system for the novel Responding to Urgency of Need in Palliative Care triage tool. METHODS: Online international discrete choice experiment involving palliative care clinicians to establish the relative importance of seven key attributes of palliative care triage identified during an earlier qualitative study. RESULTS: Participants (n = 772) were mainly female (79.9%) with a decade of clinical experience. All attributes contributed significantly (all P-values < 0.001) and independently to clinician assessment of urgency. This study found physical suffering (coefficient 3.45; 95% confidence interval: 3.24 to 3.66) was the most important determinant of urgency, followed by imminent dying (coefficient 1.56; 1.43 to 1.69), psychological suffering (coefficient 1.49; 1.37 to 1.60), caregiver distress (coefficient 1.47; 1.35 to 1.59), discrepancy between care needs and care arrangements (coefficient 1.14; 1.02 to 1.26), mismatch between current and desired site of care (coefficient 0.94; 0.85 to 1.03), and unmet communication needs (coefficient 0.84; 0.76 to 0.92). CONCLUSION: Palliative care triage, which is complex and contextual, has been made more transparent through this discrete choice experiment. The Responding to Urgency of Need in Palliative Care triage tool provides an important step toward evidence-based assessment of priority for palliative care. Further research is underway to determine the validity of the tool in clinical practice and its impact on patient and caregiver outcomes.

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.

Assessment of the psychometric properties of patient-reported outcomes of depression and anxiety in systemic lupus erythematosus.

OBJECTIVES: This study aimed to: 1) determine the prevalence of depression and anxiety in SLE patients using the Center for Epidemiological Studies-Depression Scale [CES-D], Hospital Anxiety and Depression Scale [HADS], and Beck Anxiety Inventory [BAI] questionnaires; 2) study the criterion validity, interpretability, and test-retest reliability of CES-D, HADS and BAI; and 3) evaluate their diagnostic accuracy when compared to the assessment of an independent psychiatric assessment using the Mini-International Neuropsychiatric Interview (MINI). METHODS: 159 consecutive SLE participants were screened for depression and anxiety using the CES-D, HADS, and BAI, and underwent the MINI. Sensitivity and specificity were evaluated against the MINI. Test-retest reliability was studied. Receiver operator characteristic (ROC) curves were utilized to determine the cut-off scores for CES-D, HADS and BAI. RESULTS: The prevalence of depression ranged from 29% (HADS-D) to 52% (CES-D) and the prevalence of anxiety ranged from 45% (BAI) to 50% (HADS-A). ROC showed similar performance for CES-D and HADS-D. The diagnostic accuracy of HADS-A outperformed BAI. Furthermore, these self-reported questionnaires demonstrated good to excellent test-retest reliability. Analyses exhibited optimal cut-offs for CES-D (26), BAI (19), HADS-A (6), and HADS-D (8) that optimized their sensitivity and specificity as screening metrics for depression and anxiety in SLE patients. CONCLUSIONS: Anxiety and depression are highly prevalent in patients with SLE. Patient-reported outcome questionnaires such as the CES-D, HADS, and BAI may be useful tools to screen for depression and anxiety in SLE. Our results suggest that SLE-specific cut-offs may improve diagnostic accuracy of current screening metrics in patients with lupus.

Expert Consensus on Screening and Assessment of Cognition in Psychiatry.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

"A monster that lives in our lives": experiences of caregivers of people with motor neuron disease and identifying avenues for support.

BACKGROUND: A developing body of evidence has provided valuable insight into the experiences of caregivers of people with motor neuron disease; however, understandings of how best to support caregivers remain limited. AIM: This study sought to understand concepts related to the motor neuron disease caregiver experience which could inform the development of supportive interventions. DESIGN: A qualitative thematic analysis of a one-off semistructured interview with caregivers was undertaken. SETTING/PARTICIPANTS: Caregivers of people with motor neuron disease were recruited from a progressive neurological diseases clinic in Melbourne, Australia. RESULTS: 15 caregivers participated. Three key themes were identified: (1) The Thief: the experience of loss and grief across varied facets of life; (2) The Labyrinth: finding ways to address ever changing challenges as the disease progressed; (3) Defying fate: being resilient and hopeful as caregivers tried to make the most of the time remaining. CONCLUSIONS: Caregivers are in need of more guidance and support to cope with experiences of loss and to adapt to changeable care giving duties associated with disease progression. Therapeutic interventions which target these experiences of loss and change are worth investigation. TRIAL REGISTRATION NUMBER: ACTRN12615000120572, pre-results.

Responding to urgency of need: Initial qualitative stage in the development of a triage tool for use in palliative care services.

BACKGROUND: Palliative care services face the challenge of a workload increasing in volume and diversity. An evidence-based triage method to assess urgency of palliative care needs is required to ensure equitable, efficient and transparent allocation of specialist resources when managing waiting lists. AIM: As the initial stage of a mixed-method sequential design, this study aimed to explore palliative care providers' practices and attitudes towards triaging palliative care needs and their views regarding the implementation of a standardised approach. DESIGN: A qualitative study was conducted involving focus groups and interviews. Transcripts were subjected to deductive thematic analysis. SETTING/PARTICIPANTS: A total of 20 palliative care providers were purposively sampled to ensure representation across disciplines (primary, specialist; medicine, nursing and allied health), service types (inpatient, hospital liaison and community) and locations (metropolitan and rural). RESULTS: A series of markers of urgency were identified, including physical and psychological suffering, caregiver distress, discrepancy between care needs and care arrangements, mismatch between current site of care and desired site of death when in terminal phase and complex communication needs. Performance status and phase of disease were reported to be less informative when considered in isolation. Interpersonal and system-based barriers to the implementation of a palliative care triage tool were highlighted. CONCLUSION: The process of triage in the palliative care setting is complex but can be conceptualised using a limited number of domains. Further research is required to establish the relative value clinicians attribute to these domains and thus inform the development of an acceptable and useful evidence-based palliative care triage tool.

A self-care, problem-solving and mindfulness intervention for informal caregivers of people with motor neurone disease: A pilot study.

BACKGROUND: Informal caregivers of people with motor neurone disease (MND) take on an extensive role. Caregivers are at increased risk of experiencing psychological distress and burden, yet, there is a lack of intervention programmes to support them. AIM: The aim of this study was to investigate the feasibility and acceptability of a therapeutic group intervention promoting self-care, problem-solving and mindfulness to informal caregivers of people with MND. DESIGN: Pilot study that utilised a one-arm pre- and post-design. Acceptability of the intervention was assessed 2 weeks post intervention with a questionnaire designed specifically for this study. Feasibility was assessed with consent, adherence and reasons for non-participation, refusal and attrition. Participants completed baseline and follow-up (6-week post intervention) questionnaires for psychological morbidity, burden, problem-solving, mindfulness and preparedness. Settings/participants: Caregivers of people with a diagnosis of MND within the past 12 months who were 18 years or older; who could speak, read and write in English and who were attending a progressive neurological diseases clinic were eligible. RESULTS: A total of 13 caregivers participated in one of three group intervention sessions which were focused on self-care, problem-solving and mindfulness. The intervention appeared to be feasible and acceptable. All participants stated that they would recommend the intervention to others. The group format appeared to be highly valued. There was no significant change in measures between pre-intervention and 6 weeks post intervention. CONCLUSION: This pilot serves as an initial step for examining interventions for MND caregivers, with the hope of identifying effective, efficient and sustainable strategies to best support this group.

Factors to consider for motor neurone disease carer intervention research: A narrative literature review.

OBJECTIVE: The experience of caregiving in the context of motor neurone disease (MND) is extremely challenging. Over the past 15 years, quantitative and qualitative studies have delineated the psychosocial aspects of this experience, exploring its impact on caregivers' quality of life, rates of depression, distress, anxiety, and burden. Our paper aimed to provide an overview of the lived experience of MND caregivers, identifying the variables that can influence MND caregiver functioning that are relevant to the development of an intervention. METHOD: A narrative review was conducted, synthesizing the findings of literature retrieved from 2000 to early 2016. RESULTS: A total of 37 articles were included in the review. The articles varied considerably in terms of methodology and quality. The main influential aspects reported and identified were factors pertaining to the patient, factors intrinsic to the caregiver, relationship factors, and social support factors. SIGNIFICANCE OF RESULTS: There is evidence to support the fact that caregivers have poorer outcomes when they care for patients with a more severe clinical profile, poorer emotional health or neurobehavioral concerns, or when the caregivers themselves struggle with adaptive problem-solving and coping skills. The availability and use of social support are also likely to be important for caregiver psychosocial outcomes. Further investigation is required to clarify the influence of changes in the relationship with the patient. Significant factors affecting the caregiver experience are considered in relation to their amenability to psychosocial intervention. Recommendations are made regarding the optimal features of future psychosocial intervention research.

Further development of the Multiple Errands Test: standardized scoring, reliability, and ecological validity for the Baycrest version.

OBJECTIVES: (1) To determine the summary scores on the Baycrest Multiple Errands Test (BMET) that best discriminate between community dwelling people with traumatic brain injury or stroke and matched controls; (2) to determine interrater reliability; (3) to evaluate further the ecological validity. DESIGN: Case-control. SETTING: Large, university-affiliated health care center and participants' homes. PARTICIPANTS: People with acquired brain injury (n=27) and healthy matched controls (n=25). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: (1) BMET; (2) performance-based measure of instrumental activities of daily living: the Assessment of Motor and Process Skills; (3) self-report and significant other report of daily life function, the Dysexecutive Questionnaire, the Sickness Impact Profile, and the Mayo-Portland Adaptability Inventory. RESULTS: Performance on the BMET was significantly different between people with acquired brain injury and controls (P<.05); good to strong correlations (>.50) were found in more than one third of the correlations between the BMET and measures of IADL and everyday function. Interclass correlation coefficients (ICCs) on BMET summary scores were high (ICC=.71-.88), illustrating very good interrater reliability. CONCLUSIONS: This study extends the psychometric findings of the Multiple Errands Test, thus further confirming its value for clinical and research purposes. It is a reliable and ecologically valid assessment that provides a standard way of categorizing executive performance errors in a naturalistic environment.