Objective:
To examine psychological distress in healthcare workers (HCWs) during the COVID-19 pandemic in April–May 2020.
Methods:
A cross-sectional survey examining demographic, employment and ...mental health characteristics of HCWs in a large metropolitan hospital in Australia.
Results:
HCWs showed significant symptoms of moderate-severe level depression (21%), anxiety (20%) and posttraumatic stress disorder (PTSD; 29%), associated with burnout, prior psychiatric history, profession and resilience.
Conclusion:
Despite low levels of COVID contact, moderate to high levels of psychological distress were reported. Continued monitoring and support for HCWs’ mental well-being is warranted as the COVID-19 pandemic develops.
Data from cohorts, registries, randomised trials, electronic medical records and administrative claims databases have increasingly been used to inform the use of therapies for neurological diseases. ...While novel sophisticated methods are enabling us to use existing data to guide treatment decisions, the complexity of statistical methodology is making appraisal of clinical evidence increasingly demanding. In this narrative review, we provide a brief overview of the most commonly used methods for evaluation of treatment effectiveness in neurology. This primer discusses complementarity of randomised and non-randomised study designs, sources of observational data, different forms of bias and the appropriate mitigation strategies, statistical significance, Bayesian approaches and provides an overview of multivariable regression models, propensity score-based models, causal inference, mediation analysis and Mendelian randomisation.
Alzheimer's disease (AD) is characterised by two cardinal pathologies, namely the extracellular accumulation amyloid-related aggregates, and the intracellular formation of tau-related neurofibrillary ...tangles (NFTs). While both pathologies disrupt cognitive function, a large body of evidence suggests that tau-pathology has a stronger relationship with the clinical manifestation of the disease compared to amyloid. Given the ordinal nature of histopathological staging systems, however, it is possible that the effect of amyloid pathology has been underestimated in clinicopathological studies.
We investigated this possibility using data from the National Alzheimer's Coordinating Center (NACC) database, which contains data from patients in the United States of America. Bayesian ordinal models were used to directly investigate the relative contribution of Braak NFT, diffuse plaque, and neuritic plaque staging to the severity of antemortem clinical impairment.
Data from 144 participants were included in the final analysis. Bayesian ordinal models revealed that Braak NFT stage was the only predictor of global cognitive status, clinical dementia stage, functional abilities, and neuropsychiatric symptoms. When compared directly, Braak NFT stage was a stronger predictor than diffuse or neuritic plaques across these domains.
These findings confirm that tau-related pathology is more strongly related to clinical status than amyloid pathology. This suggests that conventional clinical markers of disease progression might be insensitive to amyloid-pathology, and hence might be inappropriate for use as outcome measures in therapeutic trials that directly target amyloid.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy ...therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4–6 years after disease onset.
In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0–2 years (early) or 4–6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0–10, with higher scores indicating increased disability), at 6–10 years after disease onset, assessed with a linear mixed-effects model.
We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7–8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 SD 1·8 vs 3·5 SD 2·1; p<0·0001), with a difference between groups of −0·98 (95% CI −1·51 to −0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6–10 year follow-up period.
High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6–10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy.
National Health and Medical Research Council Australia and MS Society UK.
White matter development during childhood and adolescence is characterised by increasing white matter coherence and organisation. Commonly used scalar metrics, such as fractional anisotropy (FA), are ...sensitive to multiple mechanisms of white matter change and therefore unable to distinguish between mechanisms that change during development. We investigate the relationship between age and neurite density index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the age-classification accuracy of NDI compared with FA, in a developmental cohort.
Diffusion-weighted imaging data from 72 children and adolescents between the ages of 4–19 was collected (M=10.42, SD=3.99, 36 male). We compared NODDI metrics against conventional DTI metrics (fractional anisotropy FA, mean diffusivity MD, axial diffusivity AD and radial diffusivity RD) in terms of their relationship to age. An ROC analysis was also performed to assess the ability of each metric to classify older and younger participants.
NDI exhibited a stronger relationship with age (median R2=.60) compared with MD (median R2=.39), FA (median R2=.27), AD (median R2=.14), and RD (median R2=.35) in a high proportion of white matter tracts. When participants were divided into an older and younger group, NDI achieved the best classification (median area under the curve AUC=.89), followed by MD (median AUC=.81), FA (median AUC=.80), RD (median AUC=.81), and AD (median AUC=.64).
Our results demonstrate the sensitivity of NDI to age-related differences in white matter microstructural organisation over development. Importantly, NDI is more sensitive to such developmental changes compared to commonly used DTI metrics. This knowledge provides justification for implementing NODDI metrics in developmental studies.
•We show evidence supporting the use of NODDI instead of FA in the developing brain.•We provide a direct comparison between Neurite density index (NDI) and DTI metrics.•NDI is better at classifying subject age group than FA.•NDI explains more variance in white matter with age than FA.•Over development NDI is more sensitive to age related white matter differences.
•An original model for the response to disease modifying therapies for patients affected by Multiple Sclerosis is proposed and validated against patients’ data.•Solutions to the equations correctly ...reproduce published experiments where different drugs against relapses are used.•The model explains why different treatments maintain a high degree of similarity, with analogous dynamical features.•Our analysis illustrates how certain drugs may be overall more successful in lowering the rate of relapses than others, as clinically verified.
Based on reported trends in relapse incidence among patients with relapsing-remitting multiple sclerosis, an original model for the response to disease modifying therapies is proposed. With a population approach and separate states for patients accounting for their risk of relapses, a system of nonlinear equations is formulated, similarly to established epidemiological models. Different parameters describe the effect of drugs and treatment switch in reducing the frequency of relapses. The model allows for a good fit to previously published data for experiments where different drugs are used. It also shows that different treatments maintain a high degree of similarity, with analogous dynamical features: a pre-treatment increment in relapse frequency leading to a distinct peak, a rapid drop after treatment switch and a plateau corresponding to a new base relapse activity, which seems dependant on the treatment chosen. A sensitivity analysis shows that the uncertainty in the initial proportions of different populations and the frequency of relapses can modify the overall dynamics of the response to treatment. Drugs are observed to induce effects that depend on patient sample’s intrinsic characteristics, producing two clearly distinct and independent dynamics of relapse response. This confirms the clinical observation that certain drugs may be overall more successful in lowering the rate of relapses more significantly than others, notwithstanding the fact that patients behave differently across experiments.
ABSTRACT
BACKGROUND AND PURPOSE
Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing ...solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space DTI‐ALPS parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD).
METHODS
All 36 participants imaged on a Siemens 3.0T Tim Trio. Single‐SE diffusion weighted Echo‐planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI‐ALPS parameter was calculated in these regions and correlated with cognitive status, Mini‐Mental State Examination (MMSE), and ADASCog11 measures.
RESULTS
Significant correlations were found between DTI‐ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI‐ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028).
CONCLUSION
Further work is needed to determine the utility of DTI‐ALPS index in larger elderly cohorts and whether it measures glymphatic activity.
OBJECTIVETo investigate the hypothesis that patients diagnosed with psychogenic nonepileptic seizures (PNES) on video-EEG monitoring (VEM) have increased mortality by comparison to the general ...population.
METHODSThis retrospective cohort study included patients evaluated in VEM units of 3 tertiary hospitals in Melbourne, Australia, between January 1, 1995, and December 31, 2015. Diagnosis was based on consensus opinion of experienced epileptologists and neuropsychiatrists at each hospital. Mortality was determined in patients diagnosed with PNES, epilepsy, or both conditions by linkage to the Australian National Death Index. Lifetime history of psychiatric disorders in PNES was determined from formal neuropsychiatric reports.
RESULTSA total of 5,508 patients underwent VEM. A total of 674 (12.2%) were diagnosed with PNES, 3064 (55.6%) with epilepsy, 175 (3.2%) with both conditions, and 1,595 (29.0%) received other diagnoses or had no diagnosis made. The standardized mortality ratio (SMR) of patients diagnosed with PNES was 2.5 (95% confidence interval CI 2.0–3.3). Those younger than 30 had an 8-fold higher risk of death (95% CI 3.4–19.8). Direct comparison revealed no significant difference in mortality rate between diagnostic groups. Among deaths in patients diagnosed with PNES (n = 55), external causes contributed 18%, with 20% of deaths in those younger than 50 years attributed to suicide, and “epilepsy” was recorded as the cause of death in 24%.
CONCLUSIONSPatients diagnosed with PNES have a SMR 2.5 times above the general population, dying at a rate comparable to those with drug-resistant epilepsy. This emphasizes the importance of prompt diagnosis, identification of risk factors, and implementation of appropriate strategies to prevent potential avoidable deaths.
•A multi-level discourse analysis examined language in temporal lobe epilepsy (TLE).•When retelling personal memories, disturbed fluency, cohesion, and coherence emerges.•Over repetitions they ...consistently produce a vague account.•This possibly relates to the neurolinguistic demands of recalling personal events.
Aside from deficits identified in single-word level retrieval, individuals with temporal lobe epilepsy (TLE) exhibit clinical oddities, such as circumstantiality in their language production. Circumstantiality refers to the use of language which is pedantic, repetitive, and overly detailed. This becomes particularly evident when elicitation tasks impose minimal structure, or when impersonal narratives are retold over consecutive occasions. Personal reminiscence is highly specific and localised in time, placing unique demands on cognitive-linguistic systems. It is hypothesised that the nature of this elicitation paradigm will produce a unique psycholinguistic phenotype in those with TLE. Among controls there is a compression of output for impersonal narratives, meaning that they use fewer words over less time and are more fluent. The opposite effect is observed when personal narratives are retold.
To investigate the micro- and macrolinguistic processes underpinning personal discourse production in TLE, we examined the elicited language output of 15 surgically naïve individuals with TLE and 14 healthy controls. Participants were asked to recall and re-tell an autobiographical memory on four immediately consecutive occasions, representing an alternative unstructured elicitation. Following transcription and coding of output, a detailed multi-level discourse analysis of output volume, fluency, cohesion, and coherence was conducted.
As anticipated, a distinctly different pattern emerged in TLE when compared with controls who did not compress their output volume across repetitions but instead produced greater novelty, and a more coherent and refined account over time. Individuals with TLE consistently told a less distinct story across repetitions, with disturbances in fluency, cohesion, and coherence.
This reflects a reduced capacity to produce a coherent mental representation, in all likelihood related to the neurolinguistic demands of recalling and retelling specific personal events.
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