Informing Dementia Support Programs That Serve Low-Income, Multilingual Communities in a Safety Net Health System: Use of Focus Groups to Identify Specific Needs.

The Centers of Medicare and Medicaid Services recently announced a new voluntary nationwide model. This model aims to provide comprehensive, standard care for people living with dementia and their unpaid caregivers and to enhance health equity in dementia care. However, little is known about the needs of older adults with dementia and their caregivers in a multiethnic and multicultural patient population of a safety net health system. The aim of this study is to include their voices. We conducted four focus groups in English and Spanish to investigate the common needs and barriers unique to the care of patients within the Los Angeles County healthcare system. Using qualitative, iterative analyses of the transcripts, we identified four domains of concern from the dyads (persons with dementia and their caregivers): need for education for dyad-centered care, barriers to resources, dyad safety, and caregiver burden and insight. These domains are interconnected, and the way this patient population experiences these domains may differ compared to those in well-resourced or predominantly English-speaking healthcare settings. Therefore, the identified domains serve as potential building blocks for dementia support programs inclusive of underserved, multicultural populations.

Meta-Analyses of Two Treatment Regimens for Retinal Vein Occlusion.

BACKGROUND AND OBJECTIVES: To pool available data on the change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and number of injections as reported by treat and extend (T&E) and pro re nata (PRN) regimens for retinal vein occlusion (RVO). MATERIALS AND METHODS: After PubMed was queried, separate random effect models were fitted to the data extracted and the Wald test was used to compare the estimates of the two independent meta-analyses. RESULTS: Fourteen T&E and 29 PRN studies were included in two independent meta-analyses. No significant difference was observed in BCVA (+14.74 [+11.52, +17.96] in T&E vs +15.90 [+14.24, + 17.56] in PRN, P = 0.530) or CRT improvements (-259.56 [-189.02, -330.09] in T&E vs -256.58 [-226.57, -286.48] in PRN, P = 0.939). More injections over 12 months were observed in T&E regimens (7.48 [6.32, 8.65] vs 5.13 [4.20, 6.06] in PRN, P = 0.002). CONCLUSION: Although more injections may be required, T&E achieves similar functional and anatomic benefits as compared to PRN regimens. [Ophthalmic Surg Lasers Imaging Retina 2023;54:244-250.].

Utility of hand-held ultrasound for image acquisition and interpretation by trained Kenyan providers.

BACKGROUND: Point-of-care ultrasound (POCUS) plays a prominent role in the timely recognition and management of multiple medical, surgical, and obstetric conditions. A POCUS training program for primary healthcare providers in rural Kenya was developed in 2013. A significant challenge to this program is the acquisition of reasonably priced ultrasound machines with adequate image quality and the ability to transmit images for remote review. The goal of this study is to compare the utility of a smartphone-connected, hand-held ultrasound with a traditional ultrasound device for image acquisition and interpretation by trained healthcare providers in Kenya. METHODS: This study took place during a routine re-training and testing session for healthcare providers who had already received POCUS training. The testing session involved a locally validated Observed Structured Clinical Exam (OSCE) that assessed trainees' skills in performing the Extended Focused Assessment with Sonography for Trauma (E-FAST) and focused obstetric exams. Each trainee performed the OSCE twice, once using a smartphone-connected hand-held ultrasound and once using their notebook ultrasound model. RESULTS: Five trainees obtained a total of 120 images and were scored on image quality and interpretation. Overall E-FAST imaging quality scores were significantly higher for the notebook ultrasound compared to the hand-held ultrasound but there was no significant difference in image interpretation. Overall focused obstetric image quality and image interpretation scores were the same for both ultrasound systems. When separated into individual E-FAST and focused obstetric views, there were no statistically significant differences in the image quality or image interpretation scores between the two ultrasound systems. Images obtained using the hand-held ultrasound were uploaded to the associated cloud storage using a local 3G-cell phone network. Upload times were 2-3 min. CONCLUSION: Among POCUS trainees in rural Kenya, the hand-held ultrasound was found to be non-inferior to the traditional notebook ultrasound for focused obstetric image quality, focused obstetric image interpretation, and E-FAST image interpretation. However, hand-held ultrasound use was found to be inferior for E-FAST image quality. These differences were not observed when evaluating each E-FAST and focused obstetric views separately. The hand-held ultrasound allowed for rapid image transmission for remote review.

The CD8α-PILRα interaction maintains CD8+ T cell quiescence.

T cell quiescence is essential for maintaining a broad repertoire against a large pool of diverse antigens from microbes and tumors, but the underlying molecular mechanisms remain largely unknown. We show here that CD8α is critical for the maintenance of CD8+ T cells in a physiologically quiescent state in peripheral lymphoid organs. Upon inducible deletion of CD8α, both naïve and memory CD8+ T cells spontaneously acquired activation phenotypes and subsequently died without exposure to specific antigens. PILRα was identified as a ligand for CD8α in both mice and humans, and disruption of this interaction was able to break CD8+ T cell quiescence. Thus, peripheral T cell pool size is actively maintained by the CD8α-PILRα interaction in the absence of antigen exposure.

Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection.

BACKGROUND: Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study. METHODS: Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data. RESULTS: Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores. CONCLUSIONS: Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.

Prevalence of Alpha-1 Antitrypsin Deficiency, Self-Reported Behavior Change, and Health Care Engagement Among Direct-to-Consumer Recipients of a Personalized Genetic Risk Report.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an autosomal co-dominant condition that predisposes to emphysema, cirrhosis, panniculitis, and vasculitis. Underrecognition has prompted efforts to enhance early detection and testing of at-risk individuals. Direct-to-consumer (DTC) genetic testing represents an additional method of detection. RESEARCH QUESTION: The study addressed three questions: (1) Does a DTC testing service identify previously undetected individuals with AATD? (2) What was the interval between initial AATD-related symptoms and initial diagnosis of AATD in such individuals? and (3) What was the behavioral impact of learning about a new diagnosis of AATD through a DTC test? STUDY DESIGN AND METHODS: In this cross-sectional study, 195,014 individuals responded to a survey within the 23andMe, Inc. research platform. RESULTS: Among 195,014 study participants, the allele frequency for the PI∗S and PI∗Z AATD variants was 21.6% (6.5% for PI∗Z and 15.1% for PI∗S); 0.63% were PI∗ZZ, half of whom reported having a physician confirm the diagnosis. Approximately 27% of those with physician-diagnosed AATD reported first becoming aware of AATD through the DTC test. Among those newly aware participants, the diagnostic delay interval was 22.3 years. Participants frequently shared their DTC test results with health care providers (HCPs) and the reported impact of learning a diagnosis of AATD was high. For example, 51.1% of PI∗ZZ individuals shared their DTC result with an HCP. The OR for PI∗ZZ smokers to report smoking reduction as a result of receiving the DTC result was 1.7 (95% CI = 1.4-2.2) compared with those without a Z allele and for reduced alcohol consumption this was 4.0 (95% CI = 2.6-5.9). INTERPRETATION: In this largest available report on DTC testing for AATD, this test, in combination with clinical follow-up, can help to identify previously undiagnosed AATD patients. Moreover, receipt of the DTC AATD report was associated with positive behavior change, especially among those with risk variants.

Feasibility of pneumoperitoneum diagnosis using point-of-care ultrasound: a pilot study using a fresh cadaver model.

AIMS: To assess the accuracy of point-of-care ultrasound (PoCUS) in the hands of two trained and blinded emergency physicians (EPs) in detecting very small amounts of free intraperitoneal air injected intra-abdominally, using a fresh human cadaver model. MATERIAL AND METHODS: Fifteen cadavers were injected on 3 occasions with predefined quantities of free intraperitoneal air ranging from 0-10 mL. Seven cadavers were injected in the mid-epigastrium (ME), while 8 were injected in the left lower quadrant (LLQ). Each cadaver was scanned after each of the 3 injections by 2 trained and blinded EPs, resulting in 45 scans per sonographer. Scans were performed using previously validated and standardized techniques. All scans were recorded, time-stamped and labeled. For each scan the sonographers indicated "yes" or "no" to whether pneumoperitoneum was detected. A chi square analysis was performed to determine the sensitivity and specificity of PoCUS utilized by each sonographer of pneumoperitoneum based on the location and volume of air injected. RESULTS: Free air (0.25-10 mL) injected into the ME was successfully diagnosed in 36/42 instances (86% sensitivity), but only detected in 10/36 instances when injected into the LLQ (28% sensitivity). Both EPs detected all air injections of ≥2 mL into the ME. CONCLUSION: Detection of free air originating from the midepigastric region may become a future PoCUS indication for adequately trained EPs.

Anti-Asian American Racism: A Wake-Up Call for Population-Based Cancer Research.

Since the start of the COVID-19 pandemic, Asian Americans have been subjected to rising overt discrimination and violent hate crimes, highlighting the health implications of racism toward Asian Americans. As Asian Americans are the only group for whom cancer is the leading cause of death, these manifestations of anti-Asian racism provoke the question of the impact of racism across the cancer continuum for Asian Americans. In this Commentary, we describe how the myth of the "model minority" overlooks the diversity of Asian Americans. Ignoring such diversity in sociocultural trends, immigration patterns, socioeconomic status, health behaviors, and barriers to care masks disparities in cancer risk, access to care, and outcomes across Asian American populations. We recommend cancer epidemiologists, population science researchers, and oncology providers direct attention toward: (i) studying the impacts of structural and personally mediated racism on cancer risk and outcomes; (ii) ensuring studies reflect the uniqueness of individual ethnic groups, including intersectionality, and uncover underlying disparities; and (iii) applying a critical race theory approach that considers the unique lived experiences of each group. A more nuanced understanding of cancer health disparities, and how drivers of these disparities are associated with race and differ across Asian American ethnicities, may elucidate means through which these disparities can be alleviated.

Role for OCT in detecting hemi-macular ganglion cell layer thinning in patients with multiple sclerosis and related demyelinating diseases.

OBJECTIVE: Investigations have found associations of homonymous thinning of the macular ganglion cell/ inner-plexiform layer (GCIPL) with demyelinating lesions in the post-chiasmal visual pathway among patients with multiple sclerosis (MS). Retinal thinning may also occur through retrograde trans-synaptic degeneration, a process by which lesions in post-geniculate visual pathway structures lead to thinning of the GCIPL across thalamic synapses. The purpose of our study was to determine the frequency of homonymous hemimacular thinning that occurs in association with post-chiasmal visual pathway demyelinating lesions in patients with MS and other demyelinating diseases. METHODS: Adult patients with demyelinating diseases (MS, neuromyelitis optica spectrum disorder [NMOSD], myelin oligodendrocyte glycoprotein antibody disease (anti-MOG)) who were participants in an ongoing observational study of visual pathway structure and function were analyzed for the presence of hemimacular GCIPL thinning on OCT scans. Brain MRI scans were examined for the presence of post-geniculate visual pathway demyelinating lesions. RESULTS: Among 135 participants in the visual pathway study, 5 patients (3.7%) had homonymous hemimacular GCIPL thinning. Eleven patients (8.1%) had a whole+half pattern of GCIPL thinning, characterized by hemimacular thinning in one eye and circumferential macular thinning in the contralateral eye. All but one patient with homonymous hemimacular thinning had demyelinating lesions in the post-geniculate visual pathway; however, these lesions were located in both cerebral hemispheres. CONCLUSION: Homonymous hemimacular thinning in the GCIPL by OCT is associated with post-chiasmal visual pathway demyelinating lesions but it appears to be a relatively uncommon contributor to GCIPL loss. Patients with this pattern of GCIPL often fail to complain of hemifield visual loss. Future studies with prospective and detailed MR imaging may be able to more closely associate demyelinating lesions in anatomically appropriate regions of the post-chiasmal visual pathways with homonymous hemimacular thinning.

Afferent and Efferent Visual Markers of Alzheimer's Disease: A Review and Update in Early Stage Disease.

Vision, which requires extensive neural involvement, is often impaired in Alzheimer's disease (AD). Over the last few decades, accumulating evidence has shown that various visual functions and structures are compromised in Alzheimer's dementia and when measured can detect those with dementia from those with normal aging. These visual changes involve both the afferent and efferent parts of the visual system, which correspond to the sensory and eye movement aspects of vision, respectively. There are fewer, but a growing number of studies, that focus on the detection of predementia stages. Visual biomarkers that detect these stages are paramount in the development of successful disease-modifying therapies by identifying appropriate research participants and in identifying those who would receive future therapies. This review provides a summary and update on common afferent and efferent visual markers of AD with a focus on mild cognitive impairment (MCI) and preclinical disease detection. We further propose future directions in this area. Given the ease of performing visual tests, the accessibility of the eye, and advances in ocular technology, visual measures have the potential to be effective, practical, and non-invasive biomarkers of AD.

Teaching Geriatrics and Transitions of Care to Internal Medicine Resident Physicians.

(1) Background: Internal medicine (IM) resident physicians need to be trained to care for older adults and transition them safely across care settings. Objective: The study purpose was to evaluate the efficacy of a curriculum in geriatrics assessment and communication skills for transitions of care (TOCs) to IM resident physicians. (2) Methods: IM residents rotated for 4 weeks on the geriatrics consult service at a large public teaching hospital, where they received didactic lectures and clinical experience in consultation and transitional care. The curriculum was designed to meet consensus guidelines for minimum geriatrics competencies expected of IM residents. Previously validated and published assessment tools were used for geriatrics knowledge and attitudes. Locally developed tools were used to directly observe and rate communication skills, and self-assess geriatrics assessment and health literacy skills. The curriculum was evaluated using a quasi-experimental, nonrandomized, single-group pre- and post-test observational design. Data on 31 subjects were collected over 18 months and analyzed using mixed-effects models. (3) Results: Average knowledge scores improved from 65% to 74% (Δ9%, 95% CI 4-13%, p < 0.001). Communication skills improved by an average of 1.15 points (95% CI 0.66-1.64, p < 0.001) on a 9-point scale. Attitudes did not change significantly. Self-rated confidence in geriatrics assessment and health literacy skills improved modestly. (4) Conclusions: The curriculum is effective in teaching basic geriatrics knowledge and communication skills, and increasing self-confidence in geriatrics assessment skills. In settings where an inpatient geriatrics consult service is feasible, the curriculum may be a model for combining geriatrics and TOC training.

The SUN test of vision: Investigation in healthy volunteers and comparison to the mobile universal lexicon evaluation system (MULES).

OBJECTIVE: Tests of rapid automatized naming (RAN) have been used for decades to evaluate neurological conditions. RAN tests require extensive brain pathways involving visual perception, memory, eye movements and language. To the extent that different naming tasks capture varied visual pathways and related networks, we developed the Staggered Uneven Number (SUN) test of rapid number naming to complement existing RAN tests, such as the Mobile Universal Lexicon Evaluation System (MULES). The purpose of this investigation was to determine values for time scores for SUN, and to compare test characteristics between SUN and MULES. METHODS: We administered the SUN and MULES tests to healthy adult volunteers in a research office setting. MULES consists of 54 color photographs; the SUN includes 145 single- and multi-digit numbers. Participants are asked to name each number or picture aloud. RESULTS: Among 54 healthy participants, aged 33 ± 13 years (range 20-66), the average SUN time score was 45.2 ± 8.3 s (range 30-66). MULES test times were 37.4 ± 9.9 s (range 20-68). SUN and MULES time scores did not differ by gender, but were greater (worse) among older participants for MULES (rs = 0.43, P = .001). Learning effects between first and second trials were greater for the MULES; participants improved (reduced) their time scores between trials by 5% on SUN and 16% for MULES (P < .0001, Wilcoxon signed-rank test). CONCLUSION: The SUN is a new vision-based test that complements presently available picture- and number-based RAN tests. These assessments may require different brain pathways and networks for visual processing, visual memory, language and eye movements.

Using Lean Performance Improvement for Patient-Centered Medical Home Transformation at an Academic Public Hospital.

Although Lean performance improvement (PI) has been used in health care for more than 15 years, little is known about how Lean has been used in Patient-Centered Medical Home (PCMH) transformation. We describe our experience implementing Lean in our safety-net, primary care teaching clinic. To advance high value care, a culture of systematic, sustainable PI methods needed to be integrated into primary care and taught to resident physicians. Clinic leadership were trained in Lean methods, protected time was dedicated to PI for a stable, interdisciplinary team, then visual management was introduced, and resident physicians were integrated into the clinic's PI initiatives. Self-assessment using the PCMH Assessment tool demonstrated improvement in core features of the PCMH model. Process outcomes also revealed successful, sustainable integration of Lean into our primary care clinic and resident training, and early findings show improvements in clinical quality outcomes. Patient survey outcomes demonstrate improvement in patient experience. Lean can be used successfully to promote PCMH transformation and create a culture of continuous PI in an academic, safety-net primary care setting.

Geriatric Assessment in Multicultural Immigrant Populations.

While the traditional comprehensive geriatric assessment provides valuable information essential to caring for older adults, it often falls short in multicultural immigrant populations. The number of foreign-born older adults is growing, and in some regions of the United States of America (U.S.), they encompass a significant portion of the older adult population. To ensure we are caring for this culturally diverse population adequately, we need to develop a more culturally competent comprehensive geriatric assessment. In this review, we explore ways in which to do this, address areas unique to multicultural immigrant populations, and identify limitations of the current assessment tools when applied to these populations. In order to be more culturally sensitive, we should incorporate the concepts of ethnogeriatrics into a comprehensive geriatric assessment, by addressing topics like healthcare disparities, language barriers, health literacy, acculturation level, and culturally defined beliefs. Additionally, we must be sensitive to the limitations of our current assessment tools and consider how we can expand our assessment toolkit to address these limitations. We discuss the limitations in cognitive screening tests, delirium assessments, functional and mental health assessments, advance care planning, and elder abuse.

Aqueous-Soluble, Acid-Transforming Chitosan for Efficient and Stimuli-Responsive Gene Silencing.

Despite its promises for biomedical applications, the lack of solubility in a physiological solution, the limited molecular interactions with nucleic acids due to the rigid backbone, and the inefficient intracellular release limit the use of chitosan, a natural cationic polysaccharide, for gene delivery. In this study, a flexible, aqueous-soluble aminoethoxy branch was conjugated to the primary hydroxyl group of chitosan via an acid-cleavable ketal linkage, resulting in acid-transforming chitosan (ATC) with greatly increased aqueous solubility, improved siRNA complexation, and degradability in response to an acidic pH. Acid-hydrolysis of ketal linkages, which triggers the loss of the flexible, cationic aminoethoxy branch, transforms ATC to the native form of chitosan with low water solubility, reduces molecular interaction with siRNA, and cooperatively facilitates the cytosolic release of siRNA. The siRNA complexation by ATC resulted in stable polyplexes under a neutral physiological condition, rapid cytosolic siRNA release from the mildly acidic endosome/lysosome, and substantial silencing of GFP expression in cells, notably with minimal cytotoxicity. This study demonstrates a molecularly engineered natural polymer for a biomedical application.

Immunological Aspects of Cryoablation of Non-Small Cell Lung Cancer: A Comprehensive Review.

In cryoimmunotherapy, target tumors are treated with cryoablation to generate antitumor immune responses. Because immune checkpoint inhibitors have demonstrated that lung cancer can be an immunotherapy-responsive disease, there has been renewed interest in the immunological aspects of cryoablation of lung cancer. Herein, we review preclinical and clinical trials of cryoablation of primary lung tumors. We examine the magnitude of cryoablation-induced antitumor immune responses and the synergy between cryoablation and either other immunotherapies or molecular targeted therapies to improve treatment responses in advanced lung cancer. We further discuss a rationale for the addition of cryoablation to immune checkpoint inhibitors for the treatment of advanced lung cancer, which is currently under clinical investigation.

Temporal distribution of encapsulated bacteriophages during passage through the chick gastrointestinal tract.

Encapsulation of bacteriophages ("phage") protects phage against environmental deactivation and provides a product that is easy to handle for storage and application with animal feed as an antibiotic alternative. The objective of this study was to evaluate an orally administered, encapsulated phage for efficient phage release in the gastrointestinal tract (GIT) of young chicks receiving feed. An optimized formulation that consisted of 0.8% low molecular weight (MW) alginate, 2% ultra-low molecular weight alginate and 3% whey protein completely released the encapsulated phage within 60 min under simulated intestinal conditions. This product was given to broiler chicks to determine passage time and distribution of the viable phage within the GIT. Following a single oral dose of 109 plaque-forming unit (PFU)/chick, the major portion (peak concentration) of the encapsulated phage passed through the chick's GIT and was detected in the feces within 4 h, with low levels being continuously excreted for up to 24 h. In comparison, the passage of free phage through the GIT occurred faster as indicated by a peak concentration in feces after 1.5 h. In assessing the temporal phage distribution, both encapsulated and free phage treatments showed no apparent difference, both having low levels of 102 to 106 PFU/g of contents along the entire GIT after 1, 2 and 4 h. These low concentrations recovered in vivo led us to examine various exposure conditions (with feed, fecal material, and buffer solutions) that were suspected to have affected phage viability/infectivity during oral delivery, sample recovery, and enumeration by plaque assay. Results showed that the exposure conditions examined did not significantly reduce phage viability and could not account for the observed low phage levels following oral administration in chicks that are on feed. In conclusion, an oral encapsulated phage dose can take more than 4 h to completely move through the GIT of young chicks. Thus, repeated or higher doses may be necessary to attain higher phage concentrations in the GIT.

Accumulation of loading damage and unloading reperfusion injury--modeling of the propagation of deep tissue ulcers.

Deep tissue injury (DTI) occurs in deep muscles around bony prominences due to excessive and prolonged mechanical loading acting on the skin surface. The condition is clinically challenging because it can escape being noticed till the damage propagates all the way to the skin. In this study, a semi-3D finite element model of a human buttock was used to simulate the process of ulcer evolution based on our recent damage accumulation and repair theory for DTI. The theory included not only the loading damage, but also further reperfusion and inflammatory injuries upon unloading. The results showed that depending on the model parameters and loading conditions, a deep tissue ulcer may initiate around a bony prominence and expand to affect the entire tissue thickness. The damage evolution can be affected by the tissue healing rate, the loading-unloading pattern and the cushion stiffness. The results may help clinical workers appreciate the importance of proper patient turning and the appropriate choice of cushion.