Purpose
The purpose of this study was to qualitatively explore perceptions related to COVID-19 vaccination intention among African American and Latinx participants and suggest intervention ...strategies.
Approach
Ninety minute virtual focus groups (N = 8), segmented by county, race and ethnicity were conducted with stakeholders from 3 vulnerable Alabama counties.
Participants
Participants (N = 67) were primarily African American and Latinx, at least 19 years, and residents or stakeholders in Jefferson, Mobile, and Dallas counties.
Setting
Focus groups took place virtually over Zoom.
Methods
The semi-structured guide explored perceptions of COVID-19, with an emphasis on barriers and facilitators to vaccine uptake. Focus groups lasted approximately 90 minutes and were audio recorded, transcribed, and analyzed by a team of 3 investigators, according to the guidelines of Thematic Analysis using NVivo 12. To provide guidance in the development of interventions to decrease vaccine hesitancy, we examined how themes fit with the constructs of the Health Belief Model.
Results
We found that primary themes driving COVID-19 vaccine hesitancy, ordered from most to least discussed, are mistrust, fear, and lack of information. Additionally, interventions to decrease vaccine hesitancy should be multi-modal, community engaged, and provide consistent, comprehensive messages delivered by trusted sources.
Macrophages are important players in the maintenance of tissue homeostasis
. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma
, and their role in ...CNS physiology has not been sufficiently well studied. Given their continuous interaction with the cerebrospinal fluid (CSF) and strategic positioning, we refer to these cells collectively as parenchymal border macrophages (PBMs). Here we demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation of PBMs that express high levels of CD163 and LYVE1 (scavenger receptor proteins), closely associated with the brain arterial tree, and show that LYVE1
PBMs regulate arterial motion that drives CSF flow. Pharmacological or genetic depletion of PBMs led to accumulation of extracellular matrix proteins, obstructing CSF access to perivascular spaces and impairing CNS perfusion and clearance. Ageing-associated alterations in PBMs and impairment of CSF dynamics were restored after intracisternal injection of macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients with Alzheimer's disease (AD) and from non-AD individuals point to changes in phagocytosis, endocytosis and interferon-γ signalling on PBMs, pathways that are corroborated in a mouse model of AD. Collectively, our results identify PBMs as new cellular regulators of CSF flow dynamics, which could be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and AD.
Food insecurity (FI) is defined as limited or uncertain access to sufficient food for a healthy and active lifestyle. Our objective was to explore how the coronavirus disease 2019 (COVID-19) pandemic ...affected the FI status of pediatric patients and their families through interviewing caregivers who screen positive for FI.
Caregivers of all hospitalized patients at a tertiary children's hospital who screen positive for FI with a two-question screening tool were approached about enrolling in the study. Those who consented completed a presurvey and participated in a semistructured individual interview. Interviews were audio recorded, transcribed, and analyzed according to the guidelines of thematic analysis using NVivo 12.
Interviews were conducted with 15 caregivers between July 2021 and January 2022. Caregivers were 100% female and 80% Black, 13% White, and 7% Hispanic/Latinx, with a mean age of 33 years. Seventy-three percent did not experience FI until the COVID-19 pandemic. Themes include lost wages, mothers forced out of the workforce due to childcare limitations, inflation and shortages of goods, increased stress/anxiety for caregivers and children, the centrality of extended family support, and the necessity/inadequacy of federal food programs.
The COVID-19 pandemic impacted unemployment and poverty and consequently exacerbated FI. Our findings point to the need to focus on proximal societal solutions, such as federal policies aimed at food assistance and childcare. Understanding the challenges related to FI that caregivers and patients experience can improve screening, support, and treatment of patients presenting for care and inform the design of necessary interventions for individuals and communities beyond COVID-19.
Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 ...is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease.
We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer's disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating CDR=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test total score, and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models.
In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=–4·28 × 10–2 SE 0·013, p=0·0012), but not high cortical uptake in PiB-PET (β=–5·51 × 10–3 0·011, p=0·63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by Aβ42 in CSF (r=0·56 0·22, p=0·011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=–0·67 0·25, p=0·0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0·45 0·21, p=0·035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between Aβ42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0·46 0·22), p=0·040) and diminished cognitive decline (r=0·67 0·22, p=0·0020).
Our findings in autosomal dominant Alzheimer's disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing.
German Research Foundation, US National Institutes of Health.
Although disparities in surgical outcomes are well-documented, our understanding of how socioecological factors drive these disparities remains limited. Comprehensive and efficient assessment tools ...are needed. This study’s objective was to develop and assess the acceptability and feasibility of a comprehensive tool evaluating socioecological determinants of health in patients requiring colorectal surgery.
In the first phase, a comprehensive socioecological determinant of health assessment tool was developed. A review of validated socioecological health evaluation instruments was conducted, and a 2-step modified Delphi method addressed the length, clarity, appropriateness, and redundancy of each instrument. A comprehensive tool was then finalized. In the second phase, the tool was tested for acceptability and feasibility in adult patients requiring colorectal surgery using a theory-guided framework at 3 Alabama hospitals. Relationships between survey responses and measures of acceptability and feasibility were evaluated using results from initial pilot tests of the survey.
In Phase 1, a modified Delphi process led to the development of a comprehensive tool that included 31 socioecological determinants of health (88 questions). Results of acceptability and feasibility were globally positive (>65%) for all domains. Overall, 83% of participants agreed that others would have no trouble completing the survey, 90.4% of respondents reported the survey was not burdensome, 97.6% of patients reported having enough time to complete the survey, and 80.9% agreed the survey was well-integrated into their appointment.
An 88-item assessment tool measuring 31 socioecological determinants of health was developed with high acceptability and feasibility for patients who required colorectal surgery. This work aids in the development of research needed to understand and address surgical disparities.
The purpose of this study was to examine perceptions of COVID-19 related to prevention, coping, and testing of African American residents in under-resourced communities in Alabama.
Guided by the ...PRECEDE-PROCEED model, virtual focus groups were conducted in five urban and rural Alabama communities using secure Zoom meetings. Community residents and stakeholders (N = 36 total) participated; meetings were audio- and video-recorded, transcribed, and analyzed according to Thematic Analysis. Themes were organized by the PRECEDE portion of the model in Predisposing, Reinforcing, and Enabling barriers and facilitators in three focus areas: prevention, coping, and testing.
Prevention barriers included apathy, difficulty with social distancing, lack of information, mixed messages from authority figures, and lack of personal protective equipment (PPE). Prevention facilitators included concerns about contracting COVID-19, clear and consistent messages from trusted sources, contact tracing, and the provision of PPE. Coping barriers included food insecurity, mental health issues, isolation, economic hardships, lack of health care access, and issues with virtual schooling and church services, which were exacerbated by the inability to connect to the internet. Facilitators to coping included religious faith, increased physical activity, and a sense of hope. Testing barriers included misunderstanding, fear, mistrust, testing restrictions, and location of testing sites. Facilitators to testing included incentives, clear information from trusted sources, convenient testing locations, and free tests.
Gaining community members' perspectives can identify barriers and facilitators to prevention, coping, and testing and potentially improve outcomes. While addressing the social determinants of health (e.g. income, education, medical trust) would be an effective path by which to diminish health disparities related to COVID-19, there is an urgent need to mitigate the spread and severity of COVID-19 in vulnerable populations. Interventions should focus on downstream determinants, such as those emerging from our study.
In pediatric end-of-life (EOL) care, the partnership between physicians and parents is principally centered on communication and the parents’ decision-making role about the patient’s impending death. ...And, because parents are charged with EOL decision-making for their children, physicians are morally responsible to ensure that prognoses and treatment options are communicated to parents in a comprehendible way. Poor communication has been posited as a primary reason why the end-of-life (EOL) wishes of patients and surrogates are not implemented. This paper is based on findings from a qualitative study that utilized observation in a high-fidelity simulation and semi-structured interviews with physicians to explore narrative influences on pediatric EOL communication. The findings of this study, which revealed an inherent connection between communication, decision-making, and ethics, are reflected Habermas’ theory of Communicative Ethics (The theory of communicative action: reason and the rationalization of society, Beacon Press, Boston, 1984; The theory of communicative action: lifeworld and system: a critique of functionalist reason, Beacon Press, Boston, 1987). Therefore this paper proposes communicative ethics as an important model which, if utilized in physician education and training, could improve physician communication and in particular, physician–parent EOL communication.
BACKGROUND During pregnancy, upper airway resistance is increased, predisposing vulnerable women to pregnancy-related OSA. Elevation of the upper body increases upper airway cross-sectional area ...(CSA) and improves severity of OSA in a subgroup of nonpregnant patients (positional-dependent sleep apnea). We tested the hypothesis that elevated position of the upper body improves OSA early after delivery. METHODS Following institutional review board approval, we conducted a randomized, crossover study on two postpartum units of Massachusetts General Hospital. Women during the first 48 h after delivery were included. Polysomnography was performed in nonelevated and 45° elevated upper body position. Upper airway CSA was measured by acoustic pharyngometry in nonelevated, 45° elevated, and sitting body position. RESULTS Fifty-five patients were enrolled, and measurements of airway CSA obtained. Thirty patients completed polysomnography in both body positions. Elevation of the upper body significantly reduced apnea-hypopnea index (AHI) from 7.7 ± 2.2/h in nonelevated to 4.5 ± 1.4/h in 45° elevated upper body position (P = .031) during sleep. Moderate to severe OSA (AHI > 15/h) was diagnosed in 20% of postpartum patients and successfully treated by elevated body position in one-half of them. Total sleep time and sleep architecture were not affected by upper body elevation. Change from nonelevated to sitting position increased inspiratory upper airway CSA from 1.35 ± 0.1 cm2 to 1.54 ± 0.1 cm2 during wakefulness. Position-dependent increase in CSA and decrease in AHI were correlated ( r = 0.42, P = .022). CONCLUSIONS Among early postpartum women, 45° upper body elevation increased upper airway CSA and mitigated sleep apnea. Elevated body position might improve respiratory safety in women early after delivery. TRIAL REGISTRY ClinicalTrials.gov ; No.: NCT01719224; URL: www.clinicaltrials.gov
Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism moderates increases in cerebrospinal fluid (CSF) levels of tau and phosphorylated tau 181 (p-tau181), measured ...using immunoassay, and cognitive decline in presymptomatic dominantly inherited Alzheimer disease (DIAD). Advances in mass spectrometry show that CSF tau phosphorylation occupancy at threonine 181 and 217 (p-tau181/tau181, p-tau217/tau217) increases with initial β-amyloid (Aβ) aggregation, while phosphorylation occupancy at threonine 205 (p-tau205/tau205) and level of total tau increase when brain atrophy and clinical symptoms become evident.
To determine whether site-specific tau phosphorylation occupancy (ratio of phosphorylated to unphosphorylated tau) is associated with BDNF Val66Met in presymptomatic and symptomatic DIAD.
This cross-sectional cohort study included participants from the Dominantly Inherited Alzheimer Network (DIAN) and Aβ-positive cognitively normal older adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Data were collected from 2009 through 2018 at multicenter clinical sites in the United States, United Kingdom, and Australia, with no follow-up. DIAN participants provided a CSF sample and completed clinical and cognitive assessments. Data analysis was conducted between March 2020 and March 2021.
Mass spectrometry analysis was used to determine site-specific tau phosphorylation level; tau levels were also measured using immunoassay. Episodic memory and global cognitive composites were computed.
Of 374 study participants, 144 were mutation noncarriers, 156 were presymptomatic mutation carriers, and 74 were symptomatic carriers. Of the 527 participants in the network, 153 were excluded because their CSF sample, BDNF status, or both were unavailable. Also included were 125 Aβ-positive cognitively normal older adults in the ADNI. The mean (SD) age of DIAD participants was 38.7 (10.9) years; 43% were women. The mean (SD) age of participants with preclinical sporadic AD was 74.8 (5.6) years; 52% were women. In presymptomatic mutation carriers, compared with Val66 homozygotes, Met66 carriers showed significantly poorer episodic memory (d = 0.62; 95% CI, 0.28-0.95), lower hippocampal volume (d = 0.40; 95% CI, 0.09-0.71), and higher p-tau217/tau217 (d = 0.64; 95% CI, 0.30-0.97), p-tau181/tau181 (d = 0.65; 95% CI, 0.32-0.99), and mass spectrometry total tau (d = 0.43; 95% CI, 0.10-0.76). In symptomatic mutation carriers, Met66 carriers showed significantly poorer global cognition (d = 1.17; 95% CI, 0.65-1.66) and higher p-tau217/tau217 (d = 0.53; 95% CI, 0.05-1.01), mass spectrometry total tau (d = 0.78; 95% CI, 0.28-1.25), and p-tau205/tau205 (d = 0.97; 95% CI, 0.46-1.45), when compared with Val66 homozygotes. In preclinical sporadic AD, Met66 carriers showed poorer episodic memory (d = 0.39; 95% CI, 0.00-0.77) and higher total tau (d = 0.45; 95% CI, 0.07-0.84) and p-tau181 (d = 0.46; 95% CI, 0.07-0.85).
In DIAD, clinical disease stage and BDNF Met66 were associated with cognitive impairment and levels of site-specific tau phosphorylation. This suggests that pharmacological strategies designed to increase neurotrophic support in the presymptomatic stages of AD may be beneficial.
The current study is part of a community engaged planning phase and aimed to identify perceptions related to the prevalence of violent crime, crime contributors, the relationship between the ...community and law enforcement, and potential interventions and solutions. In March 2021, semistructured interviews were conducted with individuals from five groups who resided or worked in Bessemer, Alabama: (1) Law Enforcement, (2) Residents, (3) Civic Leaders, (4) Community Leaders, and (5) Victims of Crime. Interviews lasted approximately 60 min and were audio recorded, transcribed, and analyzed according to the guidelines of thematic analysis using NVivo 12. Emerging themes were examined in accordance with the CDC Social‐Ecological Model: A Framework for Prevention. Participants (N = 18) were 50.0% female and 77.8% African American with an age range of 25–59 (mean = 43.4 years). Themes that emerged related to crime were: (1) impact, (2) contributors, and (3) solutions. Results indicate that impacts of violent crime at the individual level focused on fear, which led to widespread mental health issues. Relationship level impacts included a lack of trust of law enforcement and neighbors, and community level impacts were decreased neighborhood social cohesion as well as decreased safety. At the societal level, the poor reputation of the city was consistently highlighted. For contributors of crime, being a youth under age 30, drugs, and money were discussed as factors at the individual level. At the relationship level, participants mentioned poor parenting and gangs as crime contributing factors to violent crime. Furthermore, contributing issues related to underresourced schools as well as a poor relationship with law enforcement were brought up at the community level. Similarly, poverty was the overarching contributing issue at the societal level. Solutions that emerged included: education and training in life skills, focusing on young people, family/parenting, conflict resolution programs, programs within schools, improved relationships with law enforcement, and inclusive economic opportunities. Intervention plans are discussed that can merge these stakeholder findings with other data sources.
PDF
