Development and Validation of a Postprocedural Model to Predict Outcome After Endovascular Treatment for Ischemic Stroke

JAMA Neurology · 2023 · 37 citations

• Medicine
• Cardiology
• Internal medicine

Importance: Outcome prediction after endovascular treatment (EVT) for ischemic stroke is important to patients, family members, and physicians. Objective: To develop and validate a model based on preprocedural and postprocedural characteristics to predict functional outcome for individual patients after EVT. Design, Setting, and Participants: A prediction model was developed using individual patient data from 7 randomized clinical trials, performed between December 2010 and December 2014. The model was developed within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration and external validation in data from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry of patients treated in clinical practice between March 2014 and November 2017. Participants included patients from multiple centers throughout different countries in Europe, North America, East Asia, and Oceania (derivation cohort), and multiple centers in the Netherlands (validation cohort). Included were adult patients with a history of ischemic stroke from an intracranial large vessel occlusion in the anterior circulation who underwent EVT within 12 hours of symptom onset or last seen well. Data were last analyzed in July 2022. Main Outcome(s) and Measure(s): A total of 19 variables were assessed by multivariable ordinal regression to predict functional outcome (modified Rankin Scale [mRS] score) 90 days after EVT. Variables were routinely available 1 day after EVT. Akaike information criterion (AIC) was used to optimize model fit vs model complexity. Probabilities for functional independence (mRS 0-2) and survival (mRS 0-5) were derived from the ordinal model. Model performance was expressed with discrimination (C statistic) and calibration. Results: A total of 781 patients (median [IQR] age, 67 [57-76] years; 414 men [53%]) constituted the derivation cohort, and 3260 patients (median [IQR] age, 72 [61-80] years; 1684 men [52%]) composed the validation cohort. Nine variables were included in the model: age, baseline National Institutes of Health Stroke Scale (NIHSS) score, prestroke mRS score, history of diabetes, occlusion location, collateral score, reperfusion grade, NIHSS score at 24 hours, and symptomatic intracranial hemorrhage 24 hours after EVT. External validation in the MR CLEAN Registry showed excellent discriminative ability for functional independence (C statistic, 0.91; 95% CI, 0.90-0.92) and survival (0.89; 95% CI, 0.88-0.90). The proportion of functional independence in the MR CLEAN Registry was systematically higher than predicted by the model (41% vs 34%), whereas observed and predicted survival were similar (72% vs 75%). The model was updated and implemented for clinical use. Conclusion and relevance: The prognostic tool MR PREDICTS@24H can be applied 1 day after EVT to accurately predict functional outcome for individual patients at 90 days and to provide reliable outcome expectations and personalize follow-up and rehabilitation plans. It will need further validation and updating for contemporary patients.

Dyadic Parent/Caregiver-Infant Interventions Initiated in the First 6 Months of Life to Support Early Relational Health: A Meta-Analysis

medRxiv (Cold Spring Harbor Laboratory) · 2022 · 6 citations

• Medicine
• Clinical psychology
• Psychology

ABSTRACT Importance In 2021, the American Academy of Pediatrics published a policy statement seeking to create a paradigm shift away from a focus on childhood toxic stress and toward the emphasis on early relational health (ERH) as a buffer for childhood adversity and promoter of life-course resilience. A comprehensive appraisal of the efficacy of contemporary parent/caregiver-child interventions in – primarily – improving ERH, and – secondarily – enhancing child well-being and neurodevelopment is needed to guide widespread implementation and policy. Objective Determine the effectiveness of contemporary early dyadic parent/caregiver-infant interventions on ERH, child socio-emotional functioning and development, and parent/caregiver mental health. Data Sources PubMed, Medline, Cinhal, ERIC, and PsycInfo were searched on April 28, 2022. Additional sources: clinical trial registries (clinicaltrials.gov, ISRCTN Registry, EU Clinical Trials Register, Australian New Zealand Clinical Trials Registry), contacting authors of unpublished/ongoing studies, backward/forward reference-searching. Study Selection Studies targeting parent/caregiver-infant dyads and evaluating effectiveness of a dyadic intervention were eligible. Study selection was performed in duplicate, using Covidence. Data Extraction and Synthesis Cochrane’s methodological guidance presented per PRISMA guidelines. Data extraction and risk of bias assessment were completed in duplicate with consensuses by first author. Data were pooled using inverse-variance random effects models. Main Outcomes and Measures The primary outcome domain was ERH. Secondary outcome domains were child socio-emotional functioning and development, and parent/caregiver mental health, and were only considered in studies where at least one ERH outcome was also measured. The association between dose of intervention and effect estimates was explored. Results 93 studies (14,993 parent/caregiver-infant dyads) met inclusion criteria. Based on very low to moderate quality of evidence, we found significant non-dose-dependent intervention effects on several measures of ERH, including bonding, parent/caregiver sensitivity, attachment, and dyadic interactions, and a significant effect on parent/caregiver anxiety, but no significant effects on other child outcomes. Conclusion Current evidence does not support the notion that promoting ERH through early dyadic interventions ensures optimal child development, despite effectively promoting ERH outcomes. Given the lack of an association with dose of intervention, the field is ripe for novel, innovative, cost-effective, potent ERH intervention strategies that effectively and equitably improve meaningful long-term child outcomes.

Brain charts for the human lifespan

Nature · 2022 · 1720 citations

• Computer Science
• Biology
• Neuroscience

, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Associations Between Neuropsychiatric Symptoms and Neuropathological Diagnoses of Alzheimer Disease and Related Dementias

JAMA Psychiatry · 2022 · 101 citations

• Medicine
• Psychiatry
• Pediatrics

IMPORTANCE: Understanding associations of Alzheimer disease (AD) and related dementias (ADRD) pathologies with common neuropsychiatric symptoms (NPS) may have implications for diagnosis and management. OBJECTIVE: To evaluate ADRD neuropathological diagnoses and NPS without consideration of clinical diagnosis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study evaluated 1808 brains from 39 sites in the US National Alzheimer Coordinating Center v. 10 collection for participants among whom the Neuropsychiatric Inventory Questionnaire (NPIQ) was administered annually. Brain autopsy diagnoses of AD, Lewy body disease (LBD), cerebral amyloid angiopathy, frontotemporal lobar degeneration, cerebrovascular disease, hippocampal sclerosis, and no known pathology were examined. Autopsy data collected from January 2012 to January 2018 were deidentified and compiled into the publicly available v. 10 database. Data were analyzed from February 2021 to August 2021. MAIN OUTCOMES AND MEASURES: The primary outcome was NPIQ domain score, if present at any time point, and mean NPIQ domain score during follow-up was secondary. Associations of ADRD diagnoses with 12 NPIQ symptom domains were examined in regression analyses, correcting for multiple comparisons. RESULTS: The study sample of 1808 adults had a mean (SD) age of 80.0 (11.0) years, and 987 participants (54.6%) were male. Apathy was the most prevalent NPS, reaching 80% (203 of 254 individuals) in those with hippocampal sclerosis. Cerebrovascular disease showed few NPS associations. Frontotemporal lobar degeneration was associated with increased apathy, increased disinhibition, and decreased psychosis and agitation compared with AD. Hippocampal sclerosis was associated with increased apathy (odds ratio, 2.60; 95% CI; 1.86-3.66, false discovery rate controlled P < .001) and disinhibition (odds ratio, 2.15; 95% CI, 1.63-2.84; false discovery rate controlled P < .001). In multiple regression analyses that included concomitant neuropathologies, the main findings remained. More severe pathology was consistently associated with increased NPS (eg, LBD was associated with an increase in hallucinations from brain stem [β, 0.23; 95% CI, 0.07-0.76; P = .02] to limbic [β, 1.69; 95% CI, 1.27-2.27; P < .001] to neocortical [β, 4.49; 95% CI, 3.27-6.16; P < .001] pathology). Hallucinations were more common in participants with AD and LBD (168 of 534 [31.5%]) compared with those with AD without LBD (152 of 704 [21.6%]) and those with LBD without AD (23 of 119 [19.6%]). CONCLUSIONS AND RELEVANCE: In this cohort study of 1808 brains from the US National Alzheimer Coordinating Center, patients with LBD and AD showed a higher prevalence of hallucinations compared with those with LBD without AD. Neuropsychiatric symptom criteria of apathy and disinhibition in behavioral variant frontotemporal lobar degeneration were supported in this study. In hippocampal sclerosis, the findings of increased apathy and disinhibition merit further investigation. Severity of neuropathology was associated with NPS severity, indicating that NPS may reflect underlying ADRD pathology and highlighting the importance of diagnosing and treating NPS.

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

Human Genetics · 2021 · 39 citations

• Computer Science
• Machine Learning
• Biology

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.