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Impact of the COVID-19 pandemic on people with epilepsy: Findings from the Brazilian arm of the COV-E study.
The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. OBJECTIVES: As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. METHODS: We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from May to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy. RESULTS: Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53), and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or canceled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19. CONCLUSION: Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic.
Outer retinal and choriocapillaris modifications in choroideremia: three differentially impaired retinal regions and the potential diagnostic role of the external limiting membrane.
BackgroundThe external limiting membrane (ELM) is formed by the apical processes of Müller cells attached to the inner segments of the photoreceptor cells. Both cells are implicated in the pathogenesis of choroideremia (CHM). The purpose of this study was to explore the diagnostic role of ELM in CHM.MethodsThe study was designed as observational case series. Sixteen CHM eyes were examined by multimodal imaging and were compared to healthy controls. The main outcome was the measurement of ELM thickness and reflectivity over the follow-up, and its relationship with other multimodal imaging quantitative parameters.ResultsBaseline ELM was characterized by 11 ± 1 µm of thickness and 0.68 ± 0.13 of reflectivity, resulting 8 ± 1 µm (p 0.05) at the last follow-up. Choriocapillaris (CC) analysis revealed 3 regions. The first was characterized by normal vessel density (VD). The second surrounding the partially preserved islet, showing significantly lower baseline VD and undergoing minor changes over the follow-up. The third was localized in the partially preserved islet, showing significantly lower VD at baseline, and resulted atrophic at the last follow-up. ELM reflectivity and ELM thickness correlated both with outer retinal atrophy progression and the CC status.ConclusionsELM may be considered a useful imaging biomarker in CHM. Its assessment confirmed a primary role of Müller cells impairment in the pathogenesis of CHM.
Cost-effectiveness of home-based stroke rehabilitation across Europe: A modelling study.
The aim of this study was to explore the cost-effectiveness of home-based versus centre-based rehabilitation in stroke patients across Europe. A state-transition cohort model was developed to simulate the impact of the intervention in 32 European countries. A cost-utility analysis was conducted from a societal perspective including healthcare, social care and informal care costs, and productivity losses. Health outcomes were expressed as QALYs. Sensitivity analyses were conducted concerning model input values and structural assumptions. Data were obtained from a population-based cohort and previously published studies. Across Europe, over 855,000 patients with stroke would be eligible for rehabilitation in 2017. Europe-wide implementation of home-based rehabilitation was estimated to produce 61,888 additional QALYs (95% CI: 3,609 to 118,679) and cost savings of €237 million (95% CI: -237 to 1,764) and of €352 million (95% CI: -340 to 2,237) in health- and social-care and societal costs, respectively. Under base case assumptions, home-based rehabilitation was found highly likely to be cost-effective (>90%), compared to centre-based rehabilitation, in most European countries (29 out of 32). Evidence from this study suggests that a shift from a centre-based to a home-based approach to stroke rehabilitation is likely to be good value for money in most European countries. Further research should be conducted to assess the generalisability of these findings to local settings.
Mapping brain structural differences and neuroreceptor correlates in Parkinson's disease visual hallucinations.
Parkinson's psychosis (PDP) describes a spectrum of symptoms that may arise in Parkinson's disease (PD) including visual hallucinations (VH). Imaging studies investigating the neural correlates of PDP have been inconsistent in their findings, due to differences in study design and limitations of scale. Here we use empirical Bayes harmonisation to pool together structural imaging data from multiple research groups into a large-scale mega-analysis, allowing us to identify cortical regions and networks involved in VH and their relation to receptor binding. Differences of morphometrics analysed show a wider cortical involvement underlying VH than previously recognised, including primary visual cortex and surrounding regions, and the hippocampus, independent of its role in cognitive decline. Structural covariance analyses point to the involvement of the attentional control networks in PD-VH, while associations with receptor density maps suggest neurotransmitter loss may be linked to the cortical changes.
COVID-19 vaccination rates, intent, and hesitancy in patients with solid organ and blood cancers: A multicenter study.
INTRODUCTION: People with cancer are at higher risk of serious illness and death from COVID-19 infection. We investigated COVID-19 vaccine uptake among patients with solid organ and blood cancers and explored factors related to hesitancy. METHODS: Cross-sectional online survey of adults with a history of cancer at three health services across metropolitan and regional Victoria. Vaccine hesitancy was measured by the validated Oxford COVID-19 vaccine hesitancy scale. RESULTS: There were 1073 respondents: 56% female; median age 62 years (range 23 - 91). Commonest tumor types included breast 29%, gastrointestinal 19%, hematological 15%, genitourinary 15%, and lung 8%. Thirty-six percent had metastatic disease, and 54% were receiving active anticancer treatment. Eighty-four percent of respondents indicated positive intent toward COVID-19 vaccination, 10% were undecided, and 6% indicated negative attitudes. At least one vaccine dose had been received by 65% of respondents, leaving 35% unvaccinated. Fifty-eight percent of unvaccinated patients answered that they would "definitely" or "probably" take a vaccine. Higher vaccine uptake was significantly associated with older age, male gender, English as first language, longer time since cancer diagnosis, and not being on current anticancer treatment. Concerns regarding vaccine side effects, particularly thrombosis, and the desire for clear medical advice were prominent among unvaccinated respondents. CONCLUSION: Despite being eligible for COVID-19 vaccination since March 2021, a substantial minority of patients with cancer remained unvaccinated as of August 2021. Targeted communication and educational resources addressing vaccine safety in the context of cancer are key to promoting vaccine uptake in this vulnerable population.
Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease, and only modest disease-modifying strategies have been established to date. Numerous clinical trials have been conducted in the past years, but have been severely hampered by the wide-ranging heterogeneity of both the biological origins and clinical characteristics of the disease. Thus, reliable biomarkers of disease activity are urgently needed to stratify patients into homogenous groups with aligned disease trajectories to allow a more effective design of clinical trial. In this review, the most promising candidate biomarkers in the cerebrospinal fluid (CSF) of patients with ALS will be summarised. Correlations between biomarker levels and clinical outcome parameters are discussed, while highlighting potential pitfalls and intercorrelations of these clinical parameters. Several CSF molecules have shown potential as biomarkers of progression and prognosis, but large, international, multicentric and longitudinal studies are crucial for validation. A more standardised choice of clinical endpoints in these studies, as well as the application of individualised models of clinical progression, would allow the quantification of disease trajectories, thereby allowing a more accurate analysis of the clinical implications of candidate biomarkers. Additionally, a comparative analysis of several biomarkers and ideally the application of a multivariate analysis including comprehensive genotypic, phenotypic and clinical characteristics collectively contributing to biomarker levels in the CSF, could promote their verification. Thus, reliable prognostic markers and markers of disease activity may improve clinical trial design and patient management in the direction of precision medicine.
Nightmares in People with COVID-19: Did Coronavirus Infect Our Dreams?
Introduction: A growing number of studies have demonstrated that the coronavirus disease-19 (COVID-19) pandemic has severely affected sleep and dream activity in healthy people. To date, no investigation has examined dream activity specifically in COVID-19 patients. Methods: As part of the International COVID-19 Sleep Study (ICOSS), we compared 544 COVID-19 participants with 544 matched-controls. A within-subjects comparison between pre-pandemic and pandemic periods computed separately for controls and COVID-19 participants were performed on dream recall and nightmare frequency (DRF; NF). Also, non-parametric comparisons between controls and COVID-19 participants were carried out. Further, we compared psychological measures between the groups collected during pandemic. Ordinal logistic regression to detect the best predictors of NF was performed. Results: We found that people reported greater dream activity during the pandemic. Comparisons between controls and COVID-19 participants revealed a) no difference between groups concerning DRF in the pre-pandemic period and during the pandemic; b) no difference between groups concerning nightmare frequency in the pre-pandemic period; and c) COVID-19 participants reported significantly higher NF than controls during pandemic (p = 0.003). Additionally, we showed that a) anxiety, depression, post-traumatic stress-disorder (PTSD) symptom scores were higher in COVID-19 participants than controls; and b) quality of life and health as well as wellbeing (WHO-5) scores were significantly higher in controls than COVID-19 participants. Finally, ordinal logistic regression indicates that DRF (p < 0.001), PTSD (p < 0.001), anxiety (p = 0.018), insomnia (p = 0.039), COVID-19 severity (p = 0.014), sleep duration (p = 0.003) and age (p = 0.001) predicted NF. Discussion: Our work shows strong associations between increased nightmares in those reporting having had COVID-19. This suggests that the more that people were affected by COVID-19, the greater the impact upon dream activity and quality of life.
The Impact of COVID-19 on Sleep Quality in People Living With Disabilities.
Background: Research exploring the impact of the COVID-19 pandemic on sleep in people with disabilities has been scarce. This study provides a preliminary assessment of sleep in people with disabilities, across two timepoints during the pandemic, with a focus on those with visual impairment (VI). Methods: Two online surveys were conducted between April 2020 and March 2021 to explore sleep quality using the Pittsburgh Sleep Quality Index (PSQI). A convenience sample of 602 participants completed the first survey and 160 completed the follow-up survey. Results: Across both timepoints, participants with disabilities reported significantly poorer global sleep quality and higher levels of sleep disturbance, use of sleep medication and daytime dysfunction than those with no disabilities. Participants with VI reported significantly higher levels of sleep disturbance and use of sleep medication at both timepoints, poorer global sleep quality, sleep duration and latency at time 1, and daytime dysfunction at time 2, than those with no disabilities. Global sleep quality, sleep duration, sleep efficiency, and self-rated sleep quality deteriorated significantly in participants with no disabilities, but daytime dysfunction increased in all three groups. Disability and state anxiety were significant predictors of sleep quality across both surveys. Conclusion: While sleep was consistently poorer in people with disabilities such as VI, it appears that the COVID-19 pandemic has had a greater impact on sleep in people with no disabilities. State anxiety and, to a lesser extent, disability, were significant predictors of sleep across both surveys, suggesting the need to address anxiety in interventions targeted toward improving sleep.
Sleep and daytime problems during the COVID-19 pandemic and effects of coronavirus infection, confinement and financial suffering: a multinational survey using a harmonised questionnaire.
OBJECTIVES: Sleep is important for human health and well-being. No previous study has assessed whether the COVID-19 pandemic impacts sleep and daytime function across the globe. METHODS: This large-scale international survey used a harmonised questionnaire. Fourteen countries participated during the period of May-August 2020. Sleep and daytime problems (poor sleep quality, sleep onset and maintenance problems, nightmares, hypnotic use, fatigue and excessive sleepiness) occurring 'before' and 'during' the pandemic were investigated. In total, 25 484 people participated and 22 151 (86.9%) responded to the key parameters and were included. Effects of COVID-19, confinement and financial suffering were considered. In the fully adjusted logistic regression models, results (weighted and stratified by country) were adjusted for gender, age, marital status, educational level, ethnicity, presence of sleep problems before COVID-19 and severity of the COVID-19 pandemic in each country at the time of the survey. RESULTS: The responders were mostly women (64%) with a mean age 41.8 (SD 15.9) years (median 39, range 18-95). Altogether, 3.0% reported having had COVID-19; 42.2% reported having been in confinement; and 55.9% had suffered financially. All sleep and daytime problems worsened during the pandemic by about 10% or more. Also, some participants reported improvements in sleep and daytime function. For example, sleep quality worsened in about 20% of subjects and improved in about 5%. COVID-19 was particularly associated with poor sleep quality, early morning awakening and daytime sleepiness. Confinement was associated with poor sleep quality, problems falling asleep and decreased use of hypnotics. Financial suffering was associated with all sleep and daytime problems, including nightmares and fatigue, even in the fully adjusted logistic regression models. CONCLUSIONS: Sleep problems, fatigue and excessive sleepiness increased significantly worldwide during the first phase of the COVID-19 pandemic. Problems were associated with confinement and especially with financial suffering.
Somnotate: An accurate, robust, and flexible sleep stage classifier for the experimentalist
AbstractManual sleep stage annotation is a time-consuming but often essential step in the analysis of sleep data. To address this bottleneck we need automated approaches that exhibit high levels of performance, are robust under different experimental conditions, are accessible, and meet the specific needs of sleep scientists. Here we develop an unbiased framework for assessing automated performance against a consensus derived from multiple experienced researchers. We then construct a new sleep stage classifier that combines automated feature extraction using linear discriminant analysis, with inference based on vigilance state-dependent contextual information using a hidden Markov model. This produces annotation accuracies that exceed expert performance on rodent electrophysiological data. We demonstrate that the classifier is robust to errors in the training data, compatible with different recording configurations, and maintains high performance during experimental interventions including sleep deprivation and optogenetic manipulations. Finally, the classifier quantifies and reports its certainty, which can be leveraged to identify ambiguous epochs for further examination. Ambiguous epochs are shown to include unsuccessful transitions between vigilance states, which may offer new insight into the mechanisms underlying sleep-wake dynamics. We call our classifier ‘Somnotate’ and make an implementation available to the neuroscience community.
A Comparison of T2 Relaxation-Based MRI Stroke Timing Methods in Hyperacute Ischemic Stroke Patients: A Pilot Study.
Background: T2 relaxation-based magnetic resonance imaging (MRI) signals may provide onset time for acute ischemic strokes with an unknown onset. The ability of visual and quantitative MRI-based methods in a cohort of hyperacute ischemic stroke patients was studied. Methods: A total of 35 patients underwent 3T (3 Tesla) MRI (<9-hour symptom onset). Diffusion-weighted (DWI), apparent diffusion coefficient (ADC), T1-weighted (T1w), T2-weighted (T2w), and T2 relaxation time (T2) images were acquired. T2-weighted fluid attenuation inversion recovery (FLAIR) images were acquired for 17 of these patients. Image intensity ratios of the average intensities in ischemic and non-ischemic reference regions were calculated for ADC, DWI, T2w, T2 relaxation, and FLAIR images, and optimal image intensity ratio cut-offs were determined. DWI and FLAIR images were assessed visually for DWI/FLAIR mismatch. Results: The T2 relaxation time image intensity ratio was the only parameter with significant correlation with stroke duration (r = 0.49, P = .003), an area under the receiver operating characteristic curve (AUC = 0.77, P