The self-reference effect in dementia: Differential involvement of cortical midline structures in Alzheimer’s disease and behavioural-variant frontotemporal dementia

Encoding information in reference to the self enhances subsequent memory for the source of this information. In healthy adults, self-referential processing has been proposed to be mediated by the cortical midline structures (CMS), with functional differentiation between anterior-ventral, anterior-dorsal and posterior regions. While both Alzheimer’s disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) patients show source memory impairment, it remains unclear whether they show a typical memory advantage for self-referenced materials. We also sought to identify the neural correlates of this so-called ‘self-reference effect’ (SRE) in these patient groups. The SRE paradigm was tested in AD (n=16) and bvFTD (n=22) patients and age-matched healthy controls (n=17). In this task, participants studied pictures of common objects paired with one of two background scenes (sources) under self-reference or other-reference encoding instructions, followed by an item and source recognition memory test. Voxel-based morphometry was used to investigate correlations between SRE measures and regions of grey matter atrophy in the CMS. The behavioural results indicated that self-referential encoding did not ameliorate the significant source memory impairments in AD and bvFTD patients. Furthermore, the reduced benefit of self-referential relative to other-referential encoding was not related to general episodic memory deficits. Our imaging findings revealed that reductions in the SRE were associated with atrophy in the anterior-dorsal CMS across both patient groups, with additional involvement of the posterior CMS in AD and anterior-ventral CMS in bvFTD. These findings suggest that although the SRE is comparably reduced in AD and bvFTD, this arises due to impairments in different subcomponents of self-referential processing

Creating and Sharing Digital Instructional Activities: A Practical Tutorial

BCBAs may encounter situations, such as the current COVID-19 pandemic, that preclude them from providing traditional in-person ABA services to clients. When conditions prevent BCBAs and behavior technicians from working directly with clients, digital instructional activities designed by BCBAs and delivered via a computer or tablet may be a viable substitute. Google applications, including Google Slides, Google Forms, and Google Classroom, can be particularly useful for creating and sharing digital instructional activities. In the current paper, we provide task analyses for utilizing basic Google Slides functions, developing independent instructional activities, developing caregiver-supported instructional activities, and sharing activities with clients and caregivers. We also provide practical recommendations for implementing digital instructional activities with clients and caregivers

An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration\u27s ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels. For ARCOS from 2018 to 2019 and 2019 to 2020, total buprenorphine distribution in grams increased by 16.2% and 12.6%, respectively. South Dakota showed the largest statewide percentage increase in both 2018–2019 (66.1%) and 2019–2020 (36.7%). From 2018 to 2019, the ZIP codes ND-577 (156.4%) and VA-222 (−82.1%) had the largest and smallest percentage changes, respectively. From 2019 to 2020, CA-932 (250.2%) and IL-603 (−36.8%) were the largest and smallest, respectively. In both 2018–2019 and 2019–2020, PA-191 had the second highest increase in grams per 100K while OH-452 was the only ZIP code to remain in the top three largest decreases in grams per 100K in both periods. Among Medicaid patients in 2018, there was a nearly 2000-fold difference in prescriptions per 100k Medicaid enrollees between Kentucky (12 075) and Nebraska (6). Among Medicare enrollees in 2018, family medicine physicians and other primary care providers were the top buprenorphine prescribers. This study not only identified overall increases in buprenorphine availability but also pronounced state-level differences. Such geographic analysis can be used to discern which public policies and regional factors impact buprenorphine access

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

An Interprofessional Simulation to Address Health Misinformation and Vaccine Hesitancy

Introduction: The complexity of contemporary health care delivery underscores the need for future health care professionals to be adept at working in interprofessional teams and effectively managing the growing issue of medical misinformation. However, current health curricula often lack content on misinformation and have few, if any, opportunities for students to practice addressing misinformation with patients and colleagues. Methods: To address this gap, our cross-institutional team developed a novel interprofessional simulation exercise and accompanying prework toolkit designed to develop communication skills for managing difficult conversations about COVID-19 misinformation. Ten third-year medical and 10 third-year pharmacy students piloted the toolkit and participated in a simulated interprofessional office visit with a standardized patient. A thematic analysis was conducted to gather students’ feedback for quality improvement. Results: We found four central themes in the transcripts of the student debriefs: (1) learners recognized that addressing COVID misinformation is an important and challenging patient care topic; (2) learners used advanced communication skills to navigate difficult conversations; 3) learners explored how to collaborate interprofessionally through relationship-building and defining roles; and 4) learners experienced the power of an interprofessional team. Discussion: Students valued the opportunity to learn and practice strategies to explicitly address misinformation. They viewed motivational interviewing techniques and interprofessional collaboration as useful tools for navigating difficult conversations. Conclusions: Interprofessional simulation with a standardized patient can be meaningfully used to train health professional students in advanced communication skills, management of medical misinformation, and interprofessional collaborative competencies

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

County and Demographic Differences in Drug Arrests and Controlled Substance Use in Maine

. Introduction: The Diversion Alert Program (DAP) was established to curb misuse of drugs and help identify people who may need treatment for substance use disorder (SUD). Law enforcement compiled arrest data into a database accessible by health care providers. Our objectives were to identify regional and demographic differences in drug use and misuse in Maine. Methods: All arrests (N = 11 234) reported to the DAP from 2013 to 2018 were examined by county and arrestee demographics, and classified into families (opioids, stimulants, sedatives). The Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) tracks the distribution of controlled pharmaceuticals (Schedule II-III). Opioids were converted to oral morphine milligram equivalents (MMEs). County and zip-code maps were constructed. Results: The most arrests per capita occurred in Androscoggin, Knox, and Cumberland Counties. Opioids were the most common drug class in arrests in all counties except Aroostook County, where stimulants were most common. Medical distribution of opioids varied. Although buprenorphine doubled, many prescription opioids (eg, hydrocodone, fentanyl, oxymorphone) exhibited large (\u3e 50%) reductions in distribution. Methadone was the predominant opioid statewide (56.4% of total MMEs), although there were sizable differences between regions (Presque Isle = 8.6%, Bangor = 78.9%). Amphetamine distribution increased by 67.9%. Discussion: The DAP, a unique pharmacoepidemiological resource, revealed a 6-fold difference in drug arrests by county. Regional differences in methadone may be due to heterogeneities in methadone clinic distribution. Conclusions: The decrease in most prescription opioids, but increase in prescription stimulants, may warrant continued monitoring to improve public health

Safety of ECT in patients receiving an oral anticoagulant

Introduction: This study assessed the use, tolerability, and safety of anticoagulation via direct oral anticoagulants or warfarin in medical and psychiatric inpatients receiving ECT. Methods: This retrospective cohort study included 32 patients who received ECT while on either a direct oral anticoagulant (9) or warfarin (23) and spanned 247 encounters at Maine Medical Center between December 2012 and December 2018. Data are presented descriptively and analyzed using SPSS version 25 and Microsoft Excel version 2016. Results: Among the 247 ECT patient encounters, there were few major adverse effects of ECT in this medically complex population. These adverse effects included headache during 4 encounters (1.6%), respiratory distress during 2 encounters (0.8%) and a cardiovascular event during 1 encounter (0.4%). One patient (3.1%) who was receiving concurrent rivaroxaban and venlafaxine experienced gastrointestinal bleeding that was determined to be unrelated to ECT. One patient on fluoxetine and warfarin experienced hemoptysis thought to be secondary to epistaxis. No other major bleeding or clotting event occurred during an ECT session nor for the duration of the hospitalization. Discussion: Direct oral anticoagulants and warfarin appear safe in the treatment of patients with atrial fibrillation or acute venous thromboembolism who are receiving concomitant ECT. Prospective studies are needed to confirm these findings

Cerebral Blood Flow and Cardiovascular Risk Effects on Resting Brain Regional Homogeneity

Regional homogeneity (ReHo) is a measure of local functional brain connectivity that has been reported to be altered in a wide range of neuropsychiatric disorders. Computed from brain resting-state functional MRI time series, ReHo is also sensitive to fluctuations in cerebral blood flow (CBF) that in turn may be influenced by cerebrovascular health. We accessed cerebrovascular health with Framingham cardiovascular risk score (FCVRS). We hypothesize that ReHo signal may be influenced by regional CBF; and that these associations can be summarized as FCVRS→CBF→ReHo. We used three independent samples to test this hypothesis. A test-retest sample of N = 30 healthy volunteers was used for test-retest evaluation of CBF effects on ReHo. Amish Connectome Project (ACP) sample (N = 204, healthy individuals) was used to evaluate association between FCVRS and ReHo and testing if the association diminishes given CBF. The UKBB sample (N = 6,285, healthy participants) was used to replicate the effects of FCVRS on ReHo. We observed strong CBF→ReHo links (p\u3c2.5 × 10−3) using a three-point longitudinal sample. In ACP sample, marginal and partial correlations analyses demonstrated that both CBF and FCVRS were significantly correlated with the whole-brain average (p\u3c10−6) and regional ReHo values, with the strongest correlations observed in frontal, parietal, and temporal areas. Yet, the association between ReHo and FCVRS became insignificant once the effect of CBF was accounted for. In contrast, CBF→ReHo remained significantly linked after adjusting for FCVRS and demographic covariates (p\u3c10−6). Analysis in N = 6,285 replicated the FCVRS→ReHo effect (p = 2.7 × 10−27). In summary, ReHo alterations in health and neuropsychiatric illnesses may be partially driven by region-specific variability in CBF, which is, in turn, influenced by cardiovascular factors

A multi-omics strategy to understand PASC through the RECOVER cohorts: a paradigm for a systems biology approach to the study of chronic conditions

Post-Acute Sequelae of SARS-CoV-2 infection (PASC or “Long COVID”), includes numerous chronic conditions associated with widespread morbidity and rising healthcare costs. PASC has highly variable clinical presentations, and likely includes multiple molecular subtypes, but it remains poorly understood from a molecular and mechanistic standpoint. This hampers the development of rationally targeted therapeutic strategies. The NIH-sponsored “Researching COVID to Enhance Recovery” (RECOVER) initiative includes several retrospective/prospective observational cohort studies enrolling adult, pregnant adult and pediatric patients respectively. RECOVER formed an “OMICS” multidisciplinary task force, including clinicians, pathologists, laboratory scientists and data scientists, charged with developing recommendations to apply cutting-edge system biology technologies to achieve the goals of RECOVER. The task force met biweekly over 14 months, to evaluate published evidence, examine the possible contribution of each “omics” technique to the study of PASC and develop study design recommendations. The OMICS task force recommended an integrated, longitudinal, simultaneous systems biology study of participant biospecimens on the entire RECOVER cohorts through centralized laboratories, as opposed to multiple smaller studies using one or few analytical techniques. The resulting multi-dimensional molecular dataset should be correlated with the deep clinical phenotyping performed through RECOVER, as well as with information on demographics, comorbidities, social determinants of health, the exposome and lifestyle factors that may contribute to the clinical presentations of PASC. This approach will minimize lab-to-lab technical variability, maximize sample size for class discovery, and enable the incorporation of as many relevant variables as possible into statistical models. Many of our recommendations have already been considered by the NIH through the peer-review process, resulting in the creation of a systems biology panel that is currently designing the studies we proposed. This system biology strategy, coupled with modern data science approaches, will dramatically improve our prospects for accurate disease subtype identification, biomarker discovery and therapeutic target identification for precision treatment. The resulting dataset should be made available to the scientific community for secondary analyses. Analogous system biology approaches should be built into the study designs of large observational studies whenever possible