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Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19.
BACKGROUND: Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. METHODS AND FINDINGS: We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms. CONCLUSIONS: Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.
Interoception has increasingly been the focus of psychiatric research, due to its hypothesized role in mental health. Existing interoceptive tasks either suffer from important methodological limitations, impacting their validity, or are burdensome and require specialized equipment, which limits their usage in vulnerable populations. We report on the development of the CARdiac Elevation Detection (CARED) task. Participants’ heart rate is recorded by a wearable device connected to a mobile application. Notifications are sent to participants’ mobile throughout the day over a period of 4 weeks. Participants are asked to state whether their heart rate is higher than usual, rate their confidence and describe the activity they were involved in when the notification occurred. Data (N = 30) revealed that 1/3 of the sample was classified as interoceptive and that participants presented overall good insight into their interoceptive abilities. Given its ease of administration and accessibility, the CARED task has the potential to be a significant asset for psychiatric and developmental research.
Informal (unpaid) carers are an integral part of all societies and the health and social care systems in the UK depend on them. Despite the valuable contributions and key worker status of informal carers, their lived experiences, wellbeing, and needs have been neglected during the COVID-19 pandemic. In this Health Policy, we bring together a broad range of clinicians, researchers, and people with lived experience as informal carers to share their thoughts on the impact of the COVID-19 pandemic on UK carers, many of whom have felt abandoned as services closed. We focus on the carers of children and young people and adults and older adults with mental health diagnoses, and carers of people with intellectual disability or neurodevelopmental conditions across different care settings over the lifespan. We provide policy recommendations with the aim of improving outcomes for all carers.
Anxiety disorders are common in adolescence but outcomes for adolescents are unclear and we do not know what factors moderate treatment outcome for this age group. We conducted meta-analyses to establish the effectiveness of psychological therapies for adolescent anxiety disorders in (i) reducing anxiety disorder symptoms, and (ii) remission from the primary anxiety disorder, compared with controls, and examine potential moderators of treatment effects. The protocol was registered with PROSPERO (CRD42018091744). Electronic databases (Web of Science, MEDLINE, Psycinfo, EMBASE) were searched from January 1990 to December 2019. 2511 articles were reviewed, those meeting strict criteria were included. Random effects meta-analyses were conducted. Analyses of symptom severity outcomes comprised sixteen studies (CBT k = 15, non-CBT k = 1; n = 766 adolescents), and analyses of diagnostic remission outcomes comprised nine (CBT k = 9; n = 563 adolescents). Post-treatment, those receiving treatment were significantly more likely to experience reduced symptom severity (SMD = 0.454, 95% CI 0.22-0.69) and remission from the primary anxiety disorder than controls (RR = 7.94, 95% CI 3.19-12.7) (36% treatment vs. 9% controls in remission). None of the moderators analysed were statistically significant. Psychological therapies targeting anxiety disorders in adolescents are more effective than controls. However, with only just over a third in remission post-treatment, there is a clear need to develop more effective treatments for adolescents, evaluated through high-quality randomised controlled trials incorporating active controls and follow-up data.
A Comparison of Cranial Cavity Extraction Tools for Non-contrast Enhanced CT Scans in Acute Stroke Patients
Cranial cavity extraction is often the first step in quantitative neuroimaging analyses. However, few automated, validated extraction tools have been developed for non-contrast enhanced CT scans (NECT). The purpose of this study was to compare and contrast freely available tools in an unseen dataset of real-world clinical NECT head scans in order to assess the performance and generalisability of these tools. This study included data from a demographically representative sample of 428 patients who had completed NECT scans following hospitalisation for stroke. In a subset of the scans (n = 20), the intracranial spaces were segmented using automated tools and compared to the gold standard of manual delineation to calculate accuracy, precision, recall, and dice similarity coefficient (DSC) values. Further, three readers independently performed regional visual comparisons of the quality of the results in a larger dataset (n = 428). Three tools were found; one of these had unreliable performance so subsequent evaluation was discontinued. The remaining tools included one that was adapted from the FMRIB software library (fBET) and a convolutional neural network- based tool (rBET). Quantitative comparison showed comparable accuracy, precision, recall and DSC values (fBET: 0.984 ± 0.002; rBET: 0.984 ± 0.003; p = 0.99) between the tools; however, intracranial volume was overestimated. Visual comparisons identified characteristic regional differences in the resulting cranial cavity segmentations. Overall fBET had highest visual quality ratings and was preferred by the readers in the majority of subject results (84%). However, both tools produced high quality extractions of the intracranial space and our findings should improve confidence in these automated CT tools. Pre- and post-processing techniques may further improve these results.
Cerebral lateralisation of first and second languages in bilinguals assessed using functional transcranial Doppler ultrasound.
Background: Lateralised language processing is a well-established finding in monolinguals. In bilinguals, studies using fMRI have typically found substantial regional overlap between the two languages, though results may be influenced by factors such as proficiency, age of acquisition and exposure to the second language. Few studies have focused specifically on individual differences in brain lateralisation, and those that have suggested reduced lateralisation may characterise representation of the second language (L2) in some bilingual individuals. Methods: In Study 1, we used functional transcranial Doppler sonography (FTCD) to measure cerebral lateralisation in both languages in high proficiency bilinguals who varied in age of acquisition (AoA) of L2. They had German (N = 14) or French (N = 10) as their first language (L1) and English as their second language. FTCD was used to measure task-dependent blood flow velocity changes in the left and right middle cerebral arteries during phonological word generation cued by single letters. Language history measures and handedness were assessed through self-report. Study 2 followed a similar format with 25 Japanese (L1) /English (L2) bilinguals, with proficiency in their second language ranging from basic to advanced, using phonological and semantic word generation tasks with overt speech production. Results: In Study 1, participants were significantly left lateralised for both L1 and L2, with a high correlation (r = .70) in the size of laterality indices for L1 and L2. In Study 2, again there was good agreement between LIs for the two languages (r = .77 for both word generation tasks). There was no evidence in either study of an effect of age of acquisition, though the sample sizes were too small to detect any but large effects. Conclusion: In proficient bilinguals, there is strong concordance for cerebral lateralisation of first and second language as assessed by a verbal fluency task.
Latent change score models (LCSMs) are used across disciplines in behavioural sciences to study how constructs change over time. LCSMs can be used to estimate the trajectory of one construct (univariate) and allow the investigation of how changes between two constructs (bivariate) are associated with each other over time. This paper introduces the R package lcsm, a tool that aims to help users understand, analyse, and visualise different latent change score models. The lcsm package provides functions to generate model syntax for basic univariate and bivariate latent change score models with different model specifications. It is also possible to visualise different model specifications in simplified path diagrams. An interactive application illustrates the main functions of the package and demonstrates how the model syntax and path diagrams change based on different model specifications. This R package aims to increase the transparency of reporting analyses and to provide an additional resource to learn latent change score modelling.
PURPOSE: We investigated the impacts of the COVID-19 pandemic on the modality of formal cognitive assessments (in-person versus remote assessments). MATERIALS AND METHODS: We created a web-based survey with 34 items and collected data from 114 respondents from a range of health care professions and settings. We established the proportion of cognitive assessments which were face-to-face or via video or telephone conferencing, both pre- and post-March 2020. Further, we asked respondents about the assessment tools used and perceived barriers, challenges, and facilitators for the remote assessment of cognition. In addition, we asked questions specifically about the use of the Oxford Cognitive Screen. RESULTS: We found that the frequency of assessing cognition was stable compared to pre-pandemic levels. Use of telephone and video conferencing cognitive assessments increased by 10% and 18% respectively. Remote assessment increased accessibility to participants and safety but made observing the subtleties of behaviour during test administration difficult. The respondents called for an increase in the availability of standardised, validated, and normed assessments. CONCLUSIONS: We conclude that the pandemic has not been detrimental to the frequency of cognitive assessments. In addition, a shift in clinical practice to include remote cognitive assessments is clear and wider availability of validated and standardised remote assessments is necessary.IMPLICATIONS FOR REHABILITATIONWe caution the wider use and interpretation of remote formal cognitive assessments due to lack of validated, standardised, and normed assessments in a remote format.Clinicians should seek out the latest validation and normative data papers to ensure they are using the most up to date tests and respective cut offs.Support is needed for individuals who lack knowledge/have anxiety over the use of technology in formal cognitive assessments.
Apathy is a common, disabling neuropsychiatric syndrome that occurs across many brain disorders and may be associated with diminished motivation in behavioural, cognitive, emotional and social domains. Assessment is complicated by the variability of symptoms across apathy domains and self-report from patients, which can be misleading due to their lack of insight. Independent evaluation by clinicians also has limitations though if it has to be performed with limited time. Caregiver reports are a viable alternative, but current assessments for them either do not distinguish between different apathy domains or are interview-based and take long to administer. In this study, we developed a brief caregiver questionnaire version of the recently developed Apathy Motivation Index (AMI), which is a self-report tool. We confirmed three apathy factors in this new caregiver measure (AMI-CG) that were also present in the AMI: Behavioural Activation, Emotional Sensitivity and Social Motivation. Furthermore, we validated the scores against more extensive caregiver interviews using the established Lillle apathy rating scale as well as patient self-reports of apathy, measures of depression, anhedonia, cognition, activities of daily living and caregiver burden across four different neurological conditions: Parkinson's disease, Alzheimer's disease, subjective cognitive impairment and limbic encephalitis. The AMI-CG showed good internal reliability, external validity and diagnostic accuracy. It also uncovered cases of social apathy overlooked by traditional instruments. Crucially, patients who under-rated their apathy compared to informants were more likely to have difficulties performing everyday activities and to be a greater burden to caregivers. The findings provide evidence for a multidimensional conceptualization of apathy and an instrument for efficient detection of apathy based on caregiver reports for use in clinical practice.
Increasing and decreasing interregional brain coupling increases and decreases oscillatory activity in the human brain
The origins of oscillatory activity in the brain are currently debated, but common to many hypotheses is the notion that they reflect interactions between brain areas. Here, we examine this possibility by manipulating the strength of coupling between two human brain regions, ventral premotor cortex (PMv) and primary motor cortex (M1), and examine the impact on oscillatory activity in the motor system measurable in the electroencephalogram. We either increased or decreased the strength of coupling while holding the impact on each component area in the pathway constant. This was achieved by stimulating PMv and M1 with paired pulses of transcranial magnetic stimulation using two different patterns, only one of which increases the influence exerted by PMv over M1. While the stimulation protocols differed in their temporal patterning, they were comprised of identical numbers of pulses to M1 and PMv. We measured the impact on activity in alpha, beta, and theta bands during a motor task in which participants either made a preprepared action (Go) or withheld it (No-Go). Augmenting cortical connectivity between PMv and M1, by evoking synchronous pre- and postsynaptic activity in the PMv–M1 pathway, enhanced oscillatory beta and theta rhythms in Go and No-Go trials, respectively. Little change was observed in the alpha rhythm. By contrast, diminishing the influence of PMv over M1 decreased oscillatory beta and theta rhythms in Go and No-Go trials, respectively. This suggests that corticocortical communication frequencies in the PMv–M1 pathway can be manipulated following Hebbian spike-timing–dependent plasticity.
Many metallic visual stimuli, especially the so-called precious metals, have long had a rich symbolic meaning for humans. Intriguingly, however, while metallic is used to describe sensations associated with pretty much every sensory modality, the descriptor is normally positively valenced in the case of vision while typically being negatively valenced in the case of those metallic sensations that are elicited by the stimulation of the chemical senses. In fact, outside the visual modality, metallic would often appear to be used to describe those sensations that are unfamiliar and unpleasant as much as to refer to any identifiable perceptual quality (or attribute). In this review, we assess those sensory stimuli that people choose to refer to as metallic, summarising the multiple, often symbolic, meanings of (especially precious) metals. The evidence of positively valenced sensation transference from metallic serviceware (e.g., plates, cups, and cutlery) to the food and drink with which it comes into contact is also reviewed.
Musical Scents: On the Surprising Absence of Scented Musical/Auditory Events, Entertainments, and Experiences
The matching of scents with music is both one of the most natural (or intuitive) of crossmodal correspondences and, at the same time, one of the least frequently explored combinations of senses in an entertainment and multisensory experiential design context. This narrative review highlights the various occasions over the last century or two when scents and sounds have coincided, and the various motivations behind those who have chosen to bring these senses together: This has included everything from the masking of malodour to the matching of the semantic meaning or arousal potential of the two senses, through to the longstanding and recently-reemerging interest in the crossmodal correspondences (now that they have been distinguished from the superficially similar phenomenon of synaesthesia, with which they were previously often confused). As such, there exist a number of ways in which these two senses can be incorporated into meaningful multisensory experiences that can potentially resonate with the public. Having explored the deliberate combination of scent and music (or sound) in everything from “scent-sory” marketing through to fragrant discos and olfactory storytelling, I end by summarizing some of the opportunities around translating such unusual multisensory experiences from the public to the private sphere. This will likely be via the widespread dissemination of sensory apps that promise to convert (or translate) from one sense (likely scent) to another (e.g., music), as has, for example already started to occur in the world of music selections to match the flavour of specific wines.
Crossmodal semantic congruence interacts with object contextual consistency in complex visual scenes to enhance short-term memory performance
Object sounds can enhance the attentional selection and perceptual processing of semantically-related visual stimuli. However, it is currently unknown whether crossmodal semantic congruence also affects the post-perceptual stages of information processing, such as short-term memory (STM), and whether this effect is modulated by the object consistency with the background visual scene. In two experiments, participants viewed everyday visual scenes for 500 ms while listening to an object sound, which could either be semantically related to the object that served as the STM target at retrieval or not. This defined crossmodal semantically cued vs. uncued targets. The target was either in-or out-of-context with respect to the background visual scene. After a maintenance period of 2000 ms, the target was presented in isolation against a neutral background, in either the same or different spatial position as in the original scene. The participants judged the same vs. different position of the object and then provided a confidence judgment concerning the certainty of their response. The results revealed greater accuracy when judging the spatial position of targets paired with a semantically congruent object sound at encoding. This crossmodal facilitatory effect was modulated by whether the target object was in-or out-of-context with respect to the background scene, with out-of-context targets reducing the facilitatory effect of object sounds. Overall, these findings suggest that the presence of the object sound at encoding facilitated the selection and processing of the semantically related visual stimuli, but this effect depends on the semantic configuration of the visual scene.
The serotonin (5-HT) system, particularly the 5-HT 2C receptor, has consistently been implicated in behavioural control. However, while some studies have focused on the role 5-HT 2C receptors plays in regulating motivation to work for reward, others have highlighted its importance in response restraint. To date, it is unclear how 5-HT transmission at this receptor regulates the balance of response invigoration and restraint in anticipation of future reward. In addition, it remains to be established how 5-HT 2C receptors gate the influence of internal versus cue-driven processes over reward-guided actions. To elucidate these issues, we investigated the effects of administering the 5-HT 2C receptor antagonist SB242084, both systemically and directly into the nucleus accumbens core (NAcC), in rats performing a Go/No-Go task for small or large rewards. The results were compared to administration of d -amphetamine into the NAcC, which has previously been shown to promote behavioural activation. Systemic perturbation of 5-HT 2C receptors – but crucially not intra-NAcC infusions – consistently boosted rats’ performance and instrumental vigour on Go trials when they were required to act. Concomitantly, systemic administration also reduced their ability to withhold responding for rewards on No-Go trials, particularly late in the holding period. Notably, these effects were often apparent only when the reward on offer was small. By contrast, inducing a hyperdopaminergic state in the NAcC with d -amphetamine strongly impaired response restraint on No-Go trials both early and late in the holding period, as well as speeding action initiation. Together, these findings suggest that 5-HT 2C receptor transmission, outside the NAcC, shapes the vigour of ongoing goal-directed action as well as the likelihood of responding as a function of expected reward.