ABSTRACT
Objective: To examine the natural history of neurological symptoms in mild COVID-19. Background: Various neurological manifestations have been reported with COVID-19, mostly in retrospective studies of hospitalized patients. There are few data on patients with mild COVID19. Design/Methods: Consenting participants in the ALBERTA HOPE COVID-19 trial( NCT04329611, hydroxychloroquine vs placebo for 5-days), managed as outpatients, were prospectively assessed 3-months and 1-year after their positive test. They completed detailed neurological symptom questionnaires, Telephone Montreal Cognitive Assessment(T-MoCA), Kessler Psychological Distress Scale(K10), and the EQ-5D-3L(quality-of-life). Informants completed the Mild Behavioural Impairment Checklist(MBI-C) and Informant Questionnaire on Cognitive Decline(IQCODE). We tracked healthcare utilization and neurological investigations using medical records. Results: Among 198 patients (median age:45, IQR:37-54, 43.9% female);28(14.1%) had preexisting neurological/psychiatric disorders. Among 179 patients with symptom assessments, 139(77.7%) reported ≥1 neurological symptom, the most common being anosmia/dysgeusia(56.3%), myalgia(42.6%), and headache(41.8%). Symptoms generally began within 1-week of illness(median:6-days, IQR:4-8). Most resolved after 3-months;40 patients(22.3%) reported persistent symptoms at 1-year, with 27(15.1%) reporting no improvement. Persistent symptoms included confusion(50%), headache(52.5%), insomnia(40%), and depression(35%). Body mass index, prior neurologic/psychiatric history, asthma, and lack of full-time employment were associated with presence and persistence of neurological symptoms;only female sex was independently associated on multivariable logistic regression(aOR:5.04, 95%CI:1.58-16.1). Patients with persistent symptoms had more hospitalizations and family physician visits, worse MBI-C scores, and were less often independent for instrumental daily activities at 1-year(77.8% vs 98.2%, p=0.005). Patients with any or persistent neurological symptoms had greater psychological distress defined as K10≥20(aOR:21.0, 95%CI:1.96-225) and worse quality-of-life ratings(mean EQ-5D VAS:67.0 vs 82.8, p=0.0002). 50.0% of patients had T-MoCA<18 at 3-months versus 42.9% at 1-year;patients reporting memory complaints were more likely to have informant-reported cognitive-behavioural decline (aOR[1-year IQCODE>3.3]:12.7, 95%CI:1.08-150). Conclusions: Neurological symptoms were commonly reported in survivors of mild COVID-19 and persisted in one in five patients 1-year later. These symptoms were associated with worse patient-reported outcomes.
ABSTRACT
Surgical processes are rapidly being adapted to address the COVID-19 pandemic, with changes in procedures and responsibilities being made to protect both patients and medical teams. These process changes put new cognitive demands on the medical team and increase the likelihood of miscommunication, lapses in judgment, and medical errors. We describe two process model driven cognitive aids, referred to as the Narrative View and the Smart Checklist View, generated automatically from models of the processes. The immediate perceived utility of these cognitive aids is to support medical simulations, particularly when frequent adaptations are needed to quickly respond to changing operating room guidelines.
ABSTRACT
Background: Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (PwMS). Currently, no treatments exist that substantially modify the course of clinical progression in MS, one of the greatest unmet needs in clinical practice. Characterizing the determinants of clinical progression is essential for the development of novel therapeutic agents and treatment approaches that target progression in PwMS. Objectives: The overarching aim of CanProCo is to evaluate a wide spectrum of factors associated with the onset and rate of disease progression in MS, and to describe how these factors interact with one another to influence progression. Methods: CanProCo is a prospective, observational cohort study aiming to recruit 1000 individuals with radiologically-isolated syndrome (RIS), relapsing-remitting MS (RRMS), and primary-progressive MS (PPMS) within 10-15 years of disease onset, and 50 healthy controls (HCs) from five large academic MS centers in Canada. Participants undergo detailed clinical evaluations annually. A subset of participants enrolled within 5-10 years of disease onset (n=500) also have blood, cerebrospinal fluid, and MRIs collected facilitating study of biological measures (e.g. single-cell RNAsequencing[ scRNASeq]), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician- assessed, health-system based), and environmental factors as determinants contributing to the differential progression in MS. Results: Recruitment commenced in April/May 2019 and n=536 patients have been recruited to date (RRMS=457, PPMS=35, RIS=25, HC=19). Baseline age, sex distribution, and Expanded Disability Status Scale (EDSS) scores (median, range) of each subgroup are: RRMS=38 years, 73% female, EDSS=1.5 (0-6.0);PPMS=52 years, 40% female, EDSS=4.0 (1.5-6.5);RIS=41 years, 68% female, EDSS=0 (0-3.0);HC=37 years, 63% female. Recruitment has surpassed the 50% target but has been paused due to the COVID-19 pandemic. scRNASeq on frozen blood samples has been validated. Conclusions: Halting the progression of MS is a fundamental clinical need to improve the lives of PwMS. Achieving this requires leveraging transdisciplinary approaches to better characterize mechanisms underlying clinical progression. CanProCo is the first prospective cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions.
ABSTRACT
Background: Previously, we used frequency domain nearinfrared spectroscopy (fdNIRS), a non-invasive imaging modality, to show that brain hypoxia exists in a subset of MS patients. Currently, there is limited knowledge on the effects of hypoxia in MS. However, some studies suggest that hypoxia may exacerbate inflammation of the central nervous system (CNS). It is important to elucidate the time-course of hypoxia in relation to inflammation to further understand its role in MS. Objectives: The aim of the present study was to use fdNIRS to determine if hypoxia in MS resolves quickly or if it is a chronic condition. Methods: We used fdNIRS to quantify cortical microvasculature hemoglobin saturation (StO2) in 55 controls and 85 MS patients. StO2 values that were 2 standard deviations (SD) below the control mean were defined as hypoxic (<55.7%). Arterial oxygen saturation (SaO2) was measured using a pulse oximeter to confirm that reduced StO2 was not systemic in origin. To determine whether the temporal pattern of StO2 relates to changes in acute CNS inflammation, we recruited a subset of MS patients (hypoxic: n=12;normoxic: n=7) for a longitudinal study. We measured StO2 once a week for 4 consecutive weeks, and then once a month for 5 subsequent months. Due to COVID-19- related lab closures, we were only able to obtain StO2 data for the first 8 weeks for 13 of these patients (hypoxic: n=8;normoxic: n=5). Results: StO2 in MS patients was significantly lower compared to controls (57.6±7.6% vs. 62.3±3.6%, respectively, p=0.002), with no differences in SaO2. For the longitudinal study, we found that StO2 values for normoxic and hypoxic MS groups did not change significantly over the course of 8 weeks (F(9, 36.9) =1.44, p=0.255). Conclusions: To our knowledge, we are the first group to use fdNIRS to identify a subset of MS patients who experience persistent brain hypoxia. As hypoxia in MS patients persists beyond 4 weeks, we argue that it can present as a chronic condition. This indicates that, in these patients, physiological responses such as angiogenesis have not occurred or are not sufficient to result in resolution of hypoxia. With such chronic hypoxia we would predict that in these patients, some symptoms may be a result of this chronic hypoxia. Also, we argue that such chronic hypoxia could exacerbate and further stimulate a pathological immune response (a hypoxia inflammation cycle).