[This corrects the article DOI: 10.3389/fnins.2025.1516746.].

IntroductionAging is the primary risk factor for sporadic Alzheimer's disease. Chronic low-grade inflammation associated with aging drives cognitive impairment through multiple mechanisms involving oxidative stress, insulin resistance, and dysregulation of metabolic, immunologic, and hematologic systems.MethodsIn a 7-month, randomized, double-blind, placebo-controlled trial (NCT04669028), we investigated the safety and activity of bezisterim, a first-in-class, oral, blood–brain barrier–permeable, anti-inflammatory agent on cognitive, molecular, biochemical, physiological, and biological aging parameters in a subset of 50 mild-to-moderate probable Alzheimer's disease participants. These participants had source-document-verified clinical measures and samples, and they completed the protocol. This study focuses on epigenetic, metabolic, biomarker, and cognitive measures in the exploratory biomarker population that completed the protocol.ResultsBezisterim was associated with non-significant directional improvements in multiple measures of cognitive and functional performance compared to placebo, with correlations to biological age (determined by DNA methylation “clocks”) and to metabolism, inflammation, and dementia biomarkers. In addition, clinical measures correlated with the extent of DNA methylation of certain cytosine-phosphate-guanine (CpG) sites in genes associated with metabolic inflammation and neurodegeneration.DiscussionThe results suggest the possible use of bezisterim to target the multifactorial processes underlying dementia.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04669028, Identifier: NCT04669028.

Purpose: Adolescents and children have experienced challenges that have increasingly and negatively impacted their mental health. School personnel are uniquely positioned to recognize and support students experiencing such challenges; however, their knowledge and training are often inadequate. Methods: To investigate knowledge and training gaps for teachers in areas of youth mental health, a 45-item survey assessing encounters, knowledge, and confidence in supporting mental health problems was administered to 441 school personnel. Youth Mental Health First Aid (YMHFA) training was offered twice monthly from 10/2022 - 6/2023, and 147 of the 441 individuals were trained and reassessed. General linear and ordinal regressions modeled pre-training levels and post-training changes by job category and school grade. Results: Fifty-six percent of respondents reported checking with students about their personal lives "frequently" or "all the time". Seventy-nine percent, 58 % and 33 % encountered students with anxiety, depression, and panic attacks respectively, either "frequently" or "all the time". Forty-six percent encountered a student contemplating suicide or having a psychotic episode at least "sometimes," and 15 % reported that a drug overdose was not a rare event. Job and grade affected frequency (p < 0.0001), with counselors/specialists having more frequent interactions with students than teachers and administrators. Training significantly improved school personnel's knowledge and confidence in handling youth mental health crises (p < 0.0001). Discussion: School personnel frequently encounter students with mental health issues. YMHFA training for teachers and staff could be offered to increase mental health knowledge, and confidence in identifying and responding to student mental health crises.

The four-meter gait speed (4MGS) is a recommended physical performance test in older adults but is challenging to implement clinically. We developed a smartphone application (App) with a four-meter ribbon for remote 4MGS testing at home. This study aimed to assess the validity and reliability of this smartphone App-based assessment of the home 4MGS. We assessed the validity of the smartphone App by comparing it against a gold standard video assessment of the 4MGS conducted by study staff visiting community-dwelling older adults and against the stopwatch-based measurement. Moreover, we assessed the test–retest reliability in two supervised sessions and three additional sessions performed by the participants independently, without staff supervision. The 4MGS measured by the smartphone App was highly correlated with video-based 4MGS (r = 0.94), with minimal differences (mean = 0.07 m/s, ± 1.96 SD = 0.12) across a range of gait speeds. The test–retest reliability for the smartphone App 4MGS was high (ICC values: 0.75 to 0.93). The home 4MGS in older adults can be measured accurately and reliably using a smartphone in the pants pocket and a four-meter strip of ribbon. Leveraging existing technology carried by a significant portion of the older adult population could overcome barriers in busy clinical settings for this well-established objective mobility test.

CONTEXT:Glycemic variability and hypoglycemia during diabetes treatment may impact therapeutic effectiveness and safety, even when glycated hemoglobin (HbA1c) reduction is comparable between therapies. OBJECTIVE:We employed masked continuous glucose monitoring (CGM) during a randomized trial of dapagliflozin plus saxagliptin (DAPA + SAXA) vs insulin glargine (INS) to compare glucose variability and patient-reported outcomes (PROs). DESIGN:24-week substudy of a randomized, open-label, 2-arm, parallel-group, phase 3b study. SETTING:Multicenter study (112 centers in 11 countries). PATIENTS:283 adults with type 2 diabetes (T2D) inadequately controlled with metformin ± sulfonylurea. INTERVENTIONS:DAPA + SAXA vs INS. MAIN OUTCOME MEASURES:Changes in CGM profiles, HbA1c, and PROs. RESULTS:Changes from baseline in HbA1c with DAPA + SAXA were similar to those observed with INS, with mean difference [95% confidence interval] between decreases of -0.12% [-0.37 to 0.12%], P = .33. CGM analytics were more favorable for DAPA + SAXA, including greater percent time in range (> 3.9 and ≤ 10 mmol/L; 34.3 ± 1.9 vs 28.5 ± 1.9%, P = .033), lower percent time with nocturnal hypoglycemia (area under the curve ≤ 3.9 mmol/L; 0.6 ± 0.5 vs 2.7 ± 0.5%, P = .007), and smaller mean amplitude of glycemic excursions (-0.7 ± 0.1 vs -0.3 ± 0.1 mmol/L, P = .017). Improvements in CGM were associated with greater satisfaction, better body weight image, less weight interference, and improved mental and emotional well-being. CONCLUSION:DAPA + SAXA and INS were equally effective in reducing HbA1c at 24 weeks, but people with T2D treated with DAPA + SAXA achieved greater time in range, greater reductions in glycemic excursions and variability, less time with hypoglycemia, and improved patient-reported health outcomes.

Research on COVID-19 vaccine hesitancy and misinformation endorsement among Spanish-speaking Americans is limited. This cross-sectional study used a Spanish-language survey from May–August 2021 among 483 Spanish speakers living in the US and Puerto Rico. We applied multivariable Poisson regression with robust error variances to assess the association between independent variables and binary outcomes for vaccine acceptance versus hesitance, as well as misinformation endorsement. Vaccine acceptance was associated with COVID-19 risk perception score (PR = 1.7 high vs. low perceived risk), opinion of government transparency (PR = 2.2 very transparent vs. not transparent), and trust in vaccine information (PR = 1.8 high vs. low). There was also an interaction between time spent on social media and social media as a main source of COVID-19 information (p = 0.0484). Misinformation endorsement was associated with opinion about government transparency (PR = 0.5 moderately vs. not transparent), trust in vaccine information (PR = 0.5 high vs. low trust), social media impact on vaccine confidence (PR = 2.1 decreased vs. increased confidence), distrust vaccines (PR = 1.9 distrust vs. trust), using vaccine information from Facebook (PR = 1.4 yes vs. no), and time spent on social media by those using social media as main source of COVID-19 vaccine information (p = 0.0120). Vaccine acceptance in respondents with high misinformation endorsement scores was 0.7 times those with low scores. These findings highlight the importance of effective information dissemination, the positive role of social media, and government transparency in boosting vaccine uptake among Spanish speakers in the US.

Insulin resistance, T2D, and chronic inflammation increase risk of developing mild cognitive impairment and Alzheimer’s disease (AD). We report here baseline data from a multicenter, randomized, placebo-controlled Phase 3 study (NCT04669028) in patients with mild to moderate AD evaluating the effects of NE3107, an oral small molecule, blood-brain permeable anti-inflammatory insulin sensitizer that binds extracellular signal-regulated kinase. Inclusion criteria are diagnosis and progression of AD, supportive brain scan and Hachinski scale to exclude vascular dementia, Clinical Dementia Rating (CDR) score of 1-2, and Mini Mental State Exam (MMSE) score of 14-24. Primary outcomes are changes in cognition and function from baseline to 30 wks. Secondary outcomes include changes in neuropsychological deficits, functional performance, and regulation of glycemia. Aβ+ subjects were older and had worse MMSE, ADAS-Cog12 and AD Composite Scores than Aβ-patients, but had less evidence of inflammation (lower CRP) and less insulin resistance (lower fasting glucose, less IFG and T2D, lower fasting insulin and HOMA2-IR, and less hypertension) (Table). Metabolic dysregulation (elevated C1q, increased CGM mean and MAGE, increased cholesterol, triglycerides, and waist-hip ratio) was also observed independent of Aβ and APOEε4 status. Inflammation and insulin resistance may contribute to AD even in the absence of classical risk markers for AD. Disclosure C.L.Reading: Employee; BioVie, Inc. C.Ahlem: Employee; Biovie, Inc. J.M.Palumbo: Employee; BioVie, Zynerba, Other Relationship; Merck Sharp & Dohme Corp. M.A.Testa: Stock/Shareholder; Phase V Technologies, Inc. D.C.Simonson: Stock/Shareholder; Phase V Technologies, Inc., GI Windows.

Introduction: Gait speed is a cardinal measure of mobility and frailty recommended to be assessed in all older adults with cancer (Dale, JCO, 2023). Four-meter gait speed (4MGS) is strongly predictive of mortality and hospitalization in older adults with hematologic malignancies (Liu, Blood, 2019). Remote monitoring technology can expand measurement of gait speed beyond the clinic (Clancy, JCO CCI, 2023), and smartphone applications (App) have been developed and validated to measure meaningful gait metrics via embedded internal motion sensors (Manor, JMIR Mhealth Uhealth, 2018). However, the validity and reliability of a smartphone App for remotely measuring gait speed in older adults is not known, nor is the feasibility of using an App to measure longitudinal gait speed in older adults with blood cancers. Methods: We conducted two studies to (1) determine the validity and reliability of a smartphone App in measuring 4MGS in community-dwelling older adults, and (2) determine the feasibility of measuring 4MGS weekly for six weeks in older adults with multiple myeloma (MM) and myelodysplastic syndromes (MDS). For the validity and reliability study, we enrolled adults aged ≥ 65 years living in an independent living housing facility. Each participant self-administered two supervised and three unsupervised gait assessments at home via the smartphone carried in their pocket, with the App providing multimedia instructions on how to complete the test. For each gait assessment, the participants walked back and forth along a 4-meter strip of ribbon for 45 seconds. For the first two supervised sessions, while the participants were self-administering the gait assessment, the study team concurrently captured their walking performance with a video camera (as a gold standard). For the following three unsupervised sessions, the participants administered the gait assessment App alone. We obtained the time for the first instance of walking along the 4-meter ribbon before turning and compared the gait speed (i.e. dividing 4 meters by the time) between the smartphone and the video capture. For the feasibility study, we enrolled patients age ≥73 years with either MDS or MM cared for at Dana-Farber Cancer Institute. Patients self-administered the gait assessment described above alone at home once a day for six weeks after a dedicated teaching session with study staff. We reported completion rates and participants' feedback regarding acceptability. Results: 14 older adults (77.2±6.3, 13 females) completed the validity and reliability study. The smartphone 4MGS demonstrated strong criterion validity yielding a high correlation with the camera 4MGS ( Figure 1) along with high reliability as demonstrated by high internal consistency and low measurement error ( Figure 2). The smartphone 4MGS also showed good test-retest reliability over three unsupervised sessions (intra-class correlation coefficient 0.78). In the feasibility study, 12 patients (79.3±3.14, 4 females, 50% MDS, 42% MM, and 8% both) were enrolled out of 19 contacted for recruitment (63%). To date, nine have completed the study: 9/9 completed at least one 4MGS test, 8/9 (89%) completed at least three weeks, and 3/9 (33%) completed all six weeks. When asked, “How important is measuring your function and mobility to you?” on a scale of 1 (low) to 5 (high), 7/9 participants answered 4 or 5. When asked to rate their experience completing the walking tests on a scale of 1 (very poor) to 5 (very good), 6/9 participants answered 4 or 5. When asked the degree to which one agrees with the statement, “I feel that the walking tests are too burdensome,” on scale of 1 (strongly disagree) to 5 (strongly agree), 9/9 patients answered 1 or 2. Conclusions: The App was both valid and reliable in measuring 4MGS in older adults' homes. User acceptance was also high, and the app was rated as minimally burdensome by patients with blood cancers with the majority completing at least three weekly home 4MGS tests. Our findings support using existing smartphone technology to assess a key measure of mobility and frailty in the homes of older adults with blood cancers, allowing for more frequent longitudinal assessment of how blood cancers and their treatments impact older adult mobility and frailty.

PURPOSE Advances in digital health technology can overcome barriers to measurement of function and mobility for older adults with blood cancers, but little is known about how older adults perceive such technology for use in their homes. METHODS To characterize potential benefits and barriers associated with using technology for home functional assessment, we conducted three semistructured focus groups (FGs) in January 2022. Eligible patients came from the Older Adult Hematologic Malignancies Program at Dana-Farber Cancer Institute (DFCI), which includes adults 73 years and older enrolled during their initial consult with their oncologist. Eligible caregivers were 18 years and older and identified by enrolled patients as their primary caregiver. Eligible clinicians were practicing DFCI hematologic oncologists, nurse practitioners, or physician assistants with ≥2 years of clinical experience. A qualitative researcher led thematic analysis of FG transcripts to identify key themes. RESULTS Twenty-three participants attended the three FGs: eight patients, seven caregivers, and eight oncology clinicians. All participants valued function and mobility assessments and felt that technology could overcome barriers to their measurement. We identified three themes related to potential benefits: making it easier for oncology teams to consider function and mobility; providing standardized, objective data; and facilitating longitudinal data. We also identified four themes related to barriers to home functional assessment: concerns related to privacy and confidentiality, burden of measuring additional patient data, challenges in operating new technology, and concerns related to data improving care. CONCLUSION These data suggest that specific concerns raised by older patients, caregivers, and oncology clinicians must be addressed to improve acceptability and uptake of technology used to measure function and mobility in the home.

The COVID-19 pandemic has highlighted the adverse consequences created by an infodemic, specifically bringing attention to compliance with public health guidance and vaccine uptake. COVID-19 vaccine hesitancy is a complex construct that is related to health beliefs, misinformation exposure, and perceptions of governmental institutions. This study draws on theoretical models and current data on the COVID-19 infodemic to explore the association between the perceived risk of COVID-19, level of misinformation endorsement, and opinions about the government response on vaccine uptake. We surveyed a sample of 2697 respondents from the US, Canada, and Italy using a mobile platform between 21–28 May 2021. Using multivariate regression, we found that country of residence, risk perception of contracting and spreading COVID-19, perception of government response and transparency, and misinformation endorsement were associated with the odds of vaccine hesitancy. Higher perceived risk was associated with lower odds of hesitancy, while lower perceptions of government response and higher misinformation endorsement were associated with higher hesitancy.

Despite the availability of effective vaccines that lower mortality and morbidity associated with COVID-19, many countries including Italy have adopted strict vaccination policies and mandates to increase the uptake of the COVID-19 vaccine. Such mandates have sparked debates on the freedom to choose whether or not to get vaccinated. In this study, we examined the people's belief in vaccine choice as a predictor of willingness to get vaccinated among a sample of unvaccinated individuals in Italy. An online cross-sectional survey was conducted in Italy in May 2021. The survey collected data on respondents' demographics and region of residence, socioeconomic factors, belief in the freedom to choose to be vaccinated or not, risk perception of contracting and transmitting the disease, previous vaccine refusal, opinion on adequacy of government measures to address the pandemic, experience in requesting and being denied government aid during the pandemic, and intent to accept COVID-19 vaccination. The analysis employed binary logistic regression models using a hierarchical model building approach to assess the association between intent to accept vaccination and belief in the freedom to choose to vaccinate, while adjusting for other variables of interest. 984 unvaccinated individuals were included in the study. Respondents who agreed that people should be free to decide whether or not to vaccinate with no restrictions on their personal life had 85% lower odds of vaccine acceptance (OR = 0.15; 95% CI, 0.09,0.23) after adjusting for demographic and socioeconomic factors and their risk perception of contracting and transmitting COVID-19. Belief in the freedom to choose whether or not to accept vaccinations was a major predictor of COVID-19 vaccine acceptance among a sample of unvaccinated individuals in Italy in May 2021. This understanding of how individuals prioritize personal freedoms and the perceived benefits and risks of vaccines, when making health care decisions can inform the development of public health outreach, educational programs, and messaging.

Both traditional and social media information sources have disseminated information on the COVID-19 pandemic. The content shared may influence public opinion on different mitigation strategies, including vaccination. Misinformation can alter risk perception and increase vaccine hesitancy. This study aimed to explore the impact of using social media as the primary information source about the COVID-19 vaccine on COVID-19 vaccine hesitancy among people living in Canada. Secondary objectives identified other predictors of vaccine hesitancy and distinguished the effects of using traditional and social media sources. We used quota sampling of adults in Canada [N = 985] to conduct an online survey on the Pollfish survey platform between 21st and 28th May 2021. We then used bivariate chi-squared tests and multivariable logistic regression modeling to explore the associations between using social media as one's primary source of information about the COVID-19 vaccine and vaccine hesitancy. We further analyzed the association between specific types of channels of information and vaccine hesitancy. After controlling for covariates such as age, sex, race, and ethnicity, individuals reporting social media as their primary source of COVID-19 vaccine information versus those who had not used social media as their primary source of COVID-19 vaccine information had 50% higher odds of vaccine hesitancy. Among different channels of information, we found that information from television was associated with a 40% lower odds ratio for vaccine hesitancy. Since social media platforms play an essential role in influencing hesitancy in taking the COVID-19 vaccination, it is necessary to improve the quality of social media information sources and raise people's trust in information. Meanwhile, traditional media channels, such as television, are still crucial for promoting vaccination programs.

The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on individuals’ mental health. This study aimed to investigate how negative emotions toward the COVID-19 pandemic, including feeling anxious, depressed, upset, and stressed, were associated with COVID-19 vaccine acceptance in Sweden. The study is a cross-sectional online survey conducted between 21–28 May 2021, using three nested hierarchical logistic regression models to assess the association. The study included 965 unvaccinated individuals, 51.2% (n = 494) of whom reported their intention to get vaccinated. We observed graded positive associations between reported negative emotions and vaccine acceptance. Individuals who experienced economic stress had lower odds of vaccine acceptance while having a positive opinion of the government’s response to COVID-19 was associated with higher odds of being vaccine-acceptant. In conclusion, unvaccinated individuals experiencing negative emotions about the pandemic were more willing to get the vaccine. On the contrary, those with a negative opinion about the government’s response, and those that had experienced economic stress were less likely to accept the immunization.

Vaccine hesitancy is a key contributor to reduced COVID-19 vaccine uptake and remains a threat to COVID-19 mitigation strategies as many countries are rolling out the campaign for booster shots. The goal of our study is to identify and compare the top vaccine concerns in four countries: Canada, Italy, Sweden, and the USA and how these concerns relate to vaccine hesitancy. While most individuals in these countries are now vaccinated, we expect our results to be helpful in guiding vaccination efforts for additional doses, and more in general for other vaccines in the future. We sought to empirically test whether vaccine related concerns followed similar thematic issues in the four countries included in this study, and then to see how these themes related to vaccine hesitancy using data from a cross-sectional survey conducted in May 2021. We applied CFA and created vaccine concern scales for analysis. We then utilized these results in regression-based modeling to determine how concerns related to vaccine hesitancy and whether there were similar or different concerns by country. The results quantitatively highlight that the same vaccine related concerns permeated multiple countries at the same point in time. This implies that COVID-19 vaccination communications could benefit from global collaboration.

The scope of this analysis is to identify specific challenges experienced by government officials during the COVID-19 pandemic when communicating with the public. The review included five EU member states: Italy, Germany, Finland, Croatia, and Spain, and focused on the first calendar year of the pandemic (February-December 2020), with implications for preparedness and response efforts. The ultimate goal was to identify preparedness efforts needed for future crisis in the area of emergency risk communication. This analysis draws upon a rapid scoping literature review and discussions with government officials leading or supporting the public communications efforts at the Ministries of Health. The ECDC preparedness logic and competency models were adopted as theoretical frameworks for organising this analysis. Our findings indicate that the pandemic highlighted the need to more effectively integrate risk communication approaches and strategies across government units, to better tailor communication messages to the different segments of the population, develop partnerships with public and private companies (i.e., social media companies), and leverage the use of analytical tools (e.g., social media data analysis) to tackle the infodemic and potential spread of misinformation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in K-12 schools was rare during in 2020-2021; few studies included Centers for Disease Control and Prevention (CDC)-recommended screening of asymptomatic individuals. We conduct a prospective observational study of SARS-CoV-2 screening in a mid-sized suburban public school district to evaluate the incidence of asymptomatic corona virus disease 2019 (COVID-19), document frequency of in-school transmission, and characterize barriers and facilitators to asymptomatic screening in schools. Staff and students undergo weekly pooled testing using home-collected saliva samples. Identification of >1 case in a school prompts investigation for in-school transmission and enhancement of safety strategies. With layered mitigation measures, in-school transmission even before student or staff vaccination is rare. Screening identifies a single cluster with in-school staff-to-staff transmission, informing decisions about in-person learning. The proportion of survey respondents self-reporting comfort with in-person learning before versus after implementation of screening increases. Costs exceed $260,000 for assays alone; staff and volunteers spend 135-145 h per week implementing screening.

We appreciated the article recently published by Pergolotti and Sattar regarding the importance of measuring functional status of older adults with cancer as a core domain of the geriatric assessment (GA) [1]. Patient-reported and physical performance measures can be used together to improve treatment decision-making and individualization of care. Obtaining these measures in valid, feasible, and sustainable ways is of special interest to us.

Recent polls report that approximately 18% of healthcare workers are still skeptical about getting vaccinated. These professionals play a key role as communicators to their patients and community members. Understanding their concerns and informational needs, as well as those of other essential workers, is important for building an effective communication strategy for the whole population. This study presents the results of a survey of 1,591 hesitant U.S. essential workers, conducted in December 2020, when they were the only group eligible for the vaccine, aiming to describe their concerns regarding the COVID-19 vaccine and related policies. Results show that freedom of choice, concerns about equal access to the vaccine and being able to live a life with no restrictions once vaccinated, were important issues since the early days of the distribution campaign. Vaccine communication campaigns and distribution policies should address both non-medical and medical concerns with the same relevance.

Despite the effectiveness of the COVID-19 vaccine, global vaccination distribution efforts have thus far had varying levels of success. Vaccine hesitancy remains a threat to vaccine uptake. This study has four objectives: (1) describe and compare vaccine hesitancy proportions by country; (2) categorize vaccine-related concerns; (3) rank vaccine-related concerns; and (4) compare vaccine-related concerns by country and hesitancy status in four countries—the United States, Canada, Sweden, and Italy. Using the Pollfish survey platform, we sampled 1000 respondents in Canada, Sweden, and Italy and 750 respondents in the United States between 21–28 May 2021. Results showed vaccine-related concerns varied across three topical areas—vaccine safety and government control, vaccine effectiveness and population control, and freedom. For each thematic area, the top concern was statistically significantly different in each country and among the hesitant and non-hesitant subsamples within each county. Concerns related to freedom were the most universal. Understanding the specific concerns among individuals when it comes to the COVID-19 vaccine can help to inform public communications and identify which, if any, salient narratives are global.