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Cognitive dispersion across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). However, little is known regarding brain changes underlying cognitive dispersion, and the association of cognitive dispersion with in vivo AD biomarkers and regional cerebral blood flow (CBF) has received limited study. We therefore examined associations among cognitive dispersion, amyloid-beta (Aβ) positivity, and regional CBF among older adults free of dementia.
One hundred and forty-eight Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent neuropsychological testing and neuroimaging. Pulsed arterial spin labeling (ASL) magnetic resonance imaging (MRI) was acquired to quantify CBF. Florbetapir positron emission tomography (PET) imaging determined Aβ positivity.
Adjusting for age, gender, education, and mean cognitive performance, older adults who were Aβ+ showed higher cognitive dispersion relative to those who were Aβ-. Across the entire sample, higher cognitive dispersion was associated with reduced CBF in inferior parietal and temporal regions. Secondary analyses stratified by Aβ status demonstrated that higher cognitive dispersion was associated with reduced CBF among Aβ+ individuals but not among those who were Aβ-.
Cognitive dispersion may be sensitive to early Aβ accumulation and cerebrovascular changes adjusting for demographics and mean neuropsychological performance. Associations between cognitive dispersion and CBF were observed among Aβ+ individuals, suggesting that cognitive dispersion may be a marker of brain changes among individuals on the AD continuum. Future studies should examine whether cognitive dispersion predicts brain changes in diverse samples and among those with greater vascular risk burden.
Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death.
Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995–2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2–5. Outcomes year 5–6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression.
Among 21 351, 9.3% took antipsychotics continuously year 2–5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53–2.56 and OR 2.60, 95% CI 1.91–3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05–1.48 and 2.04, 95% CI 1.64–2.53) and no antipsychotics (OR 2.00, 95% CI 1.69–2.38 and 5.64, 95% CI 4.56–6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10–1.47) and longer admissions (IRR 1.68, 95% CI 1.30–2.16) year 5–6 compared to continuous users. Mortality during year 5–6 did not differ between groups.
Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.
The authors designed a simulation training programme for foundation doctors beginning psychiatry placements across a large mental health trust. The simulation training aimed to improve the confidence, competence, and well-being of foundation doctors through exposing them to realistic psychiatry scenarios and teaching clinical skills in a safe environment.
Four clinical scenarios were filmed with a 360-degree camera, professional actress, and doctors working in psychiatry. The scenarios depicted the journey of a patient being admitted onto a psychiatry ward from the community. Various clinical skills were embedded into the videos including psychiatric history taking, risk assessment, managing acute distress, managing comorbid physical and mental health problems, using the Mental Health Act, and teamwork with colleagues. All videos were delivered to learners using simulation with head-mounted-displays (HMDs). Each video lasted 6–8 minutes and was accompanied by pre-briefing and de-briefing with experienced psychiatrists for a further 15–20 minutes. Participants rated their confidence regarding several skills in psychiatry on Likert scales from 1 to 5 immediately before and after the session. Wilcoxon signed rank tests were conducted to detect statistically significant differences in learner's median confidence ratings before and after the training. Free-text questions explored trainee's most and least favourite aspects of the simulation. A survey also was distributed to learners 2-months after the training to assess how it had influenced their clinical practice.
20 foundation doctors completed the training and provided feedback. Following the simulation training, there were statistically significant improvements in foundation doctor's confidence in: completing psychiatric assessments (p < 0.01), managing physical health problems in psychiatry (p < 0.05), managing acute distress (p < 0.01), reporting information to senior colleagues (p < 0.05), and containing anxiety when communicating with patients (p < 0.05). Trainees highlighted the debriefing, group discussions, and “interactive” simulation videos as the most useful aspects of the training. Some trainees enjoyed viewing the 360-degree videos, whilst others found the HMDs difficult to use. Of the 8 trainees who completed feedback 2 months after the training, 7 (87.5%) felt that it had helped them in their current roles. All trainees agreed (37.5%) or strongly agreed (62.5%) that the simulation scenarios were closely aligned to real-life clinical encounters.
Simulation training in psychiatry using 360-degree videos and HMDs is generally well-received amongst foundation doctors. Embedding simulation training into placement induction can improve the confidence and skills of junior doctors starting psychiatry placements.
To explore the effect of hindsight bias on retrospective reviews of clinical decision making prior to adverse incidents to inform future approaches to incident investigations.
We have undertaken focus groups with doctors of varying grades across the North West of England and North Wales. A vignette based on a real-life case from the publicly available NHS England Homicide Independent Investigation report database was presented to each group in one of three versions which differed in terms of the ending of the vignettes (i.e. suicide, homicide, no adverse incident). Using a semi-structured interview approach, the group participants were encouraged by the facilitators to reflect on issues relating to risk and risk management. All groups were provided with the same vignette which initially made no reference to the outcome and asked to comment on matters of risk and risk management. Halfway through the discussion, one of the three outcomes was disclosed, and further group discussion was held. The recorded interviews were transcribed and thematic analysis was undertaken using an adapted Framework Method.
Preliminary results (n = 10) indicate that participants identified the potential for significant harm, particularly to others, and identified evidence of key psychopathological and historical correlates to support assertive management of risk and admission to hospital.
Whilst knowledge of the outcome did not lead to participants changing their favoured management plans, it did alter how they appraised the case and led to participants constructing “narrative” explanations for the outcome given. The level of conviction participants held for their management plan reduced when their expectations about the outcome were confounded.
Participants presented with the suicide outcome vignette described their difficulties appraising risk to others and their over-sensitivity to that risk. Participants faced with the ‘no adverse outcome’ vignette perceived the original management plan far more favourably in hindsight. The groups that were presented with the homicide outcome vignette initially focused on both risks to self and others as well as the perceived need for further information. Following knowledge of the outcome, there was a tendency to highlight parts of the letter pertaining to risk to others which they previously had not given as much attention.
The initial analysis of our data confirms the findings from previous studies that hindsight colours the appraisal of adverse events. However, this study is novel in that it describes the nature of the thought processes underpinning the influence of hindsight on appraisals of risk.
The Homa Peninsula has been known to science since 1911, and fossil specimens from the area comprise many type specimens for common African mammalian paleospecies. Here we discuss the fauna and the paleoenvironmental information from the Homa Peninsula. The Homa Peninsula is a 200 km2 area in Homa Bay County, situated on the southern margin of the Winam Gulf of Lake Victoria in Kenya (Figure 29.1). Lake Victoria is estimated to be the third largest lake in the world, with a surface area of 68,900 km2 and a maximum length of approximately 616 km. Although its catchment is extensive, it is relatively shallow compared to any other lake of similar size, with a maximum depth of 84 m. Lake Victoria is located in a depression formed by the western and eastern branches of the East African Rift System (EARS), and is at an average elevation of 1135 m a.s.l. (Database for Hydrological Time Series of Inland Waters, 2017).
OBJECTIVES/GOALS: Heart failure (HF) is a clinical condition that notably affects the lives of patients in rural areas. The partnering of a rural satellite hospital with an urban academic medical center may provide geographically underrepresented populations with HF an opportunity to access controlled clinical trials (CCTs). METHODS/STUDY POPULATION: We report our experience in screening, consenting and enrolling subjects at the VCU Health Community Memorial Hospital (VCU-CMH) in rural South Hill, Virginia, that is part of the larger VCU Health network, with the lead institution being VCU Health Medical College of Virginia Hospitals (VCU-MCV), Richmond, VA. Subjects were enrolled in a clinical trial sponsored by the National Institutes of Health (ClinicalTrials.gov: NCT03797001) and assigned to treatment with an anti-inflammatory drug for HF or placebo. We used the electronic health record and remote guidance and oversight from the VCU-MCV resources using a closed-loop communication network to work with local resources at the facility to perform screening, consenting and enrollment. RESULTS/ANTICIPATED RESULTS: One hundred subjects with recently decompensated HF were screened between January 2019 and August 2021, of these 61 are enrolled to date: 52 (85 %) at VCU-MCV and 9 (15%) at VCU-CMH. Of the subjects enrolled at VCU-CMH, 33% were female, 77% Black, with a mean age of 52ï‚±10 years. DISCUSSION/SIGNIFICANCE: The use of a combination of virtual/remote monitoring and guidance of local resources in this trial provides an opportunity for decentralization and access of CCTs for potential novel treatment of HF to underrepresented individuals from rural areas.
Cross-species evidence suggests that the ability to exert control over a stressor is a key dimension of stress exposure that may sensitize frontostriatal-amygdala circuitry to promote more adaptive responses to subsequent stressors. The present study examined neural correlates of stressor controllability in young adults. Participants (N = 56; Mage = 23.74, range = 18–30 years) completed either the controllable or uncontrollable stress condition of the first of two novel stressor controllability tasks during functional magnetic resonance imaging (fMRI) acquisition. Participants in the uncontrollable stress condition were yoked to age- and sex-matched participants in the controllable stress condition. All participants were subsequently exposed to uncontrollable stress in the second task, which is the focus of fMRI analyses reported here. A whole-brain searchlight classification analysis revealed that patterns of activity in the right dorsal anterior insula (dAI) during subsequent exposure to uncontrollable stress could be used to classify participants' initial exposure to either controllable or uncontrollable stress with a peak of 73% accuracy. Previous experience of exerting control over a stressor may change the computations performed within the right dAI during subsequent stress exposure, shedding further light on the neural underpinnings of stressor controllability.
During the Scientific Revolution, philosophers wondered how best to understand space. Many debates revolved around the account advanced in Descartes’s Principles of Philosophy (1644), and this chapter treats it as a focal point. Descartes argued for a return to the Aristotelian view that there is no difference in reality between space and matter, entailing that empty space—space empty of matter—is impossible. Over the next century, all kinds of philosophers attacked this position, and this chapter takes their rejections of Cartesian space as a starting point for exploring alternative views. A varied selection of philosophers who reject Cartesian space are discussed, in chronological order: Henry More, Samuel Clarke, Isaac Newton, Catharine Cockburn, and Gottfried Wilhelm Leibniz. The sheer breadth of alternative theories of space they advance demonstrates the metaphysical richness of this era. Nonetheless, there is a deep agreement among their alternatives: all the accounts agree on the features of space. This base agreement set the scene for Kant’s theory of space, advanced after the Scientific Revolution ended.
As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.
The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.
Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.
It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
UK universities re-opened in September 2020, amidst the coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November; however, outbreaks among university students occurred. We aimed to measure the University of Bristol staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020–03/07/2020), relaxed guidance period (04/07/2020–13/09/2020), ‘rule-of-six’ period (14/09/2020–04/11/2020) and the second lockdown (05/11/2020–25/11/2020). In total, 722 staff (4199 responses) and 738 students (1906 responses) were included in the study. For staff, daily contacts were higher in the relaxed guidance and ‘rule-of-six’ periods than the post-first lockdown and second lockdown. Mean student contacts dropped between the ‘rule-of-six’ and second lockdown periods. For both staff and students, the proportion meeting with groups larger than six dropped between the ‘rule-of-six’ period and the second lockdown period, although was higher for students than for staff. Our results suggest university staff and students responded to national guidance by altering their social contacts. Most contacts during the second lockdown were household contacts. The response in staff and students was similar, suggesting that students can adhere to social distancing guidance while at university. The number of contacts recorded for both staff and students were much lower than those recorded by previous surveys in the UK conducted before the COVID-19 pandemic.
Growing evidence indicates that Vitamin D deficiency is associated with psychotic symptoms. Although evidence suggesting a causal relationship is limited, theories regarding neuro-inflammatory modulation are promising. Alternatively, deficiency may signify chronic illness or poor functioning. Nevertheless, Vitamin D levels below 50nmol/L increase the risk of osteoporosis, muscle weakness, falls and fractures, thus identification and treatment are important.
The association between Vitamin D levels in patients within the Tameside Early Intervention in Psychosis Team (EIT) was studied, hypothesising a strong correlation.
The records of all patients in the EIT as of 01/07/2020, over the age of 16 years old (n = 183), were studied. The first Vitamin D level taken while under the EIT and the CGI scores closest to the date of this level were recorded. Vitamin D levels of 25nmol/L and under were classified as deficient, levels of 25.1 - 50nmol/L were insufficient.
45.90% (n = 84) of patients did not have their levels recorded. Of the 55% (n = 99) patients who had Vitamin D levels recorded, 49.50% (n = 49) were insufficient and 22.22% (n = 22) were deficient. Therefore, only 28.28% (n = 28) had either optimal or sufficient Vitamin D levels. The majority of Vitamin D levels were taken in Autumn (36.46% n = 36).
75.76% (n = 75) of patients had both vitamin D levels and CGI scores recorded, with an average of 35.65 days between date level and score recorded. A weak negative correlation between overall CGI scores and vitamin D level was calculated, producing Spearman R Correlation Coefficient of -0.15.
Almost 3/4 of the studied patients being assessed for psychotic symptoms had either insufficient or deficient levels of Vitamin D. The correlation between symptom severity and Vitamin D level was weak however. While we cannot comment on the causality of the relationship, it appears that there is an association between our studied patient group and Vitamin D insufficiency.
The evidence to suggest that supplementation can reduce psychotic symptoms is limited however, supplementation can reduce the risk of osteoporosis and falls, therefore would improve patient care. Only 55% of the patients within the EIT had their Vitamin D levels tested. As a result of this study, the authors recommend that all patients in the EIT have their Vitamin D levels tested as part of their psychosis assessment.
The study is limited due to low numbers of patients studied and the fact that recorded CGI scores were often recorded at a later date to Vitamin D levels.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
What is time? Just like everything else in the world, our understanding of time has changed continually over time. This article tracks this question through the history of Western philosophy and looks at major answers from the likes of Aristotle, Kant, and McTaggart.
ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
We review evidence of racial discrimination as a critical and understudied form of adversity that has the potential to impact stress biology, particularly hypothalamic–pituitary–adrenal (HPA) axis activity. We highlight ethnic racial identity (ERI) as a positive regulatory influence on HPA axis activity, as indexed by levels of salivary cortisol. In past research by our group, Black individuals with high adolescent discrimination had low adult cortisol levels (hypocortisolism). Here, we present new analyses showing that ERI, measured prospectively from ages 12 through 32 in 112 Black and white individuals, is related to better-regulated cortisol levels in adulthood, particularly for Black participants. We also describe ongoing research that explores whether the promotion of ERI during adolescence can reduce ethnic–racial disparities in stress biology and in emotional health and academic outcomes.
Emily Feyes, The Ohio State University College of Veterinary Medicine; Dixie Mollenkopf, The Ohio State University College of Veterinary Medicine; Thomas Wittum, The Ohio State University College of Veterinary Medicine; Dubraska Diaz-Campos, The Ohio State University College of Veterinary Medicine; Rikki Horne, The Ohio State University College of Veterinary Medicine
Background: The Ohio State University College of Veterinary Medicine (OSU-CVM) Antimicrobial Stewardship Working Group (ASWG) uses monthly environmental surveillance to understand the effectiveness of our veterinary medical center (VMC) infection control and biosecurity protocols in reducing environmental contamination with multidrug resistant organisms. Monthly surveillance allows us to monitor trends in the recovery of these resistant organisms and address issues of concern that could impact our patients, clients, staff, and students. Methods: The OSU-CVM ASWG collects samples from >100 surfaces within the companion animal, farm animal, and equine sections of our hospital each month. Sampling has been continuous since January 2018. Samples are collected from both human–animal contact and human-only contact surfaces using Swiffer electrostatic cloths. These samples are cultured for recovery of Salmonella spp, extended-spectrum cephalosporin-resistant Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae (CPE), and methicillin-resistant Staphylococcus spp. Results: The recovery of these antibiotic resistant target organisms is low in the environment of our hospital. Recovery from human-only contact surfaces (19.8%) is very similar to recovery from human–animal contact surfaces (25.5%). We commonly recover Enterobacteriaceae (E.coli, Klebsiella spp, and Enterobacter spp) that are resistant to extended-spectrum cephalosporins (496 of 2,016; 24.6%) from the VMC environment. These antibiotic-resistant indicator bacteria are expected in a veterinary hospital setting where use the of β-lactam drugs is common. Recovery of both Salmonella spp and CPE has remained very low in our hospital environment over the past 19 months: 16 of 2,016 (0.7%) for Salmonella and 15 of 2,016 (0.8%) for CPE. Discussion: The active environmental surveillance component of our antimicrobial stewardship program has allowed us to reduce the threat of nosocomial infections within our hospital and address environmental contamination issues before they become a problem. Our consistently low recovery of resistant organisms indicates the effectiveness of our existing cleaning and disinfection protocols and biosecurity measures. Due to the nature of our patient population, we do expect to find resistant organisms in the patient-contact areas of the hospital environment. However, our similar rates of resistant organisms from human-only surfaces (eg, computer keyboards, door handles, telephones, and Cubex machines) indicates a need to improve our hand hygiene practices. These data are now supporting the implementation of a new hand hygiene campaign in our veterinary hospital.
SHEA endorses adhering to the recommendations by the CDC and ACIP for immunizations of all children and adults. All persons providing clinical care should be familiar with these recommendations and should routinely assess immunization compliance of their patients and strongly recommend all routine immunizations to patients. All healthcare personnel (HCP) should be immunized against vaccine-preventable diseases as recommended by the CDC/ACIP (unless immunity is demonstrated by another recommended method). SHEA endorses the policy that immunization should be a condition of employment or functioning (students, contract workers, volunteers, etc) at a healthcare facility. Only recognized medical contraindications should be accepted for not receiving recommended immunizations.