The Andes-Amazon-Atlantic pathway: A foundational hydroclimate system for social-ecological system sustainability.

The Amazon River Basin's extraordinary social-ecological system is sustained by various water phases, fluxes, and stores that are interconnected across the tropical Andes mountains, Amazon lowlands, and Atlantic Ocean. This "Andes-Amazon-Atlantic" (AAA) pathway is a complex hydroclimatic system linked by the regional water cycle through atmospheric circulation and continental hydrology. Here, we aim to articulate the AAA hydroclimate pathway as a foundational system for research, management, conservation, and governance of aquatic systems of the Amazon Basin. We identify and describe the AAA pathway as an interdependent, multidirectional, and multiscale hydroclimate system. We then present an assessment of recent (1981 to 2020) changes in the AAA pathway, primarily reflecting an acceleration in the rates of hydrologic fluxes (i.e., water cycle intensification). We discuss how the changing AAA pathway orchestrates and impacts social-ecological systems. We conclude with four recommendations for the sustainability of the AAA pathway in ongoing research, management, conservation, and governance.

Adjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus.

Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.

Problem gambling in psychotic disorders: A systematic review and meta-analysis of prevalence.

INTRODUCTION: Problem gambling (PBG) is more common in people with mental health disorders, including substance use, bipolar, and personality disorders, than in the general population. Although individuals with psychotic disorders might be expected to be more vulnerable to PBG, fewer studies have focused on this comorbidity. The aim of this review was to estimate the prevalence of PBG in people with psychotic disorders. METHODS: Medline (Ovid), EMBASE, PsycINFO (Ovid), CINAHL, CENTRAL, Web of science, and ProQuest were searched on November 1, 2023, without language restrictions. Observational and experimental studies including individuals with psychotic disorders and reporting the prevalence of PBG were included. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal for systematic reviews of prevalence data. The pooled prevalence of PBG was calculated using a fixed effects generalized linear mixed model and presented through forest plots. RESULTS: Of 1271 records screened, 12 studies (n = 3443) were included. The overall prevalence of PBG was 8.7% (95% CI = 7.8%-9.7%, I2 = 69%). A lower prevalence was found in studies with a low risk of bias (5.6%; 95% CI = 4.4%-7.0%) compared with studies with a moderate risk of bias (10.4%; 95% CI = 9.2%-11.7%). Different methods used to assess PBG also contributed to the heterogeneity found. CONCLUSION: This meta-analysis found substantial heterogeneity, partly due to the risk of bias of the included studies and a lack of uniformity in PBG assessment. Although more research is needed to identify those at increased risk for PBG, its relatively high prevalence warrants routine screening for gambling in clinical practice.

Advance care planning as perceived by marginalized populations: Willing to engage and facing obstacles.

BACKGROUND: Health disparities exist in end-of-life (EOL) care. Individuals and communities that are marginalized due to their race, ethnicity, income, geographic location, language, or cultural background experience systemic barriers to access and receive lower quality EOL care. Advance care planning (ACP) prepares patients and their caregivers for EOL decision-making for the purpose of promoting high-quality EOL care. Low engagement in ACP among marginalized populations is thought to have contributed to disparity in EOL care. To advance health equity and deliver care that aligns with the goals and values of each individual, there is a need to improve ACP for marginalized populations. AIM: To describe how patients from marginalized populations experience and perceive ACP. METHODS: We used an interpretive phenomenological approach with semi-structured qualitative interviews. Participants were recruited from four primary care clinics and one nursing home in a US Pacific Northwest city. Thirty patients from marginalized populations with serious illness participated in individual interviews between January and December 2021. Participants were asked to describe their experiences and perceptions about ACP during the interviews. RESULTS: The mean age of 30 participants was 69.5; 19 (63%) were women; 12 (40%) identified as Asian/Pacific Islanders, 10 (33%) as Black; and 9 (30%) were non-native English speakers. Our three key findings were: 1) patients from marginalized populations are willing to engage in ACP; 2) there were multiple obstacles to engaging in ACP; and 3) meaningful ACP conversations could happen when clinicians listen. Although participants from marginalized populations were willing to engage in ACP, a fragmented and restrictive healthcare system and clinicians' biased behaviors or lack of interest in knowing their patients were obstacles. Participants who felt their clinicians took time and listened were encouraged to engage in ACP. CONCLUSION: Patients from marginalized populations are willing to engage in ACP conversations despite a common belief otherwise. However, obstacles to meaningful ACP conversations with healthcare providers exist. Clinicians need to be aware of these obstacles and listen to build trust and engage marginalized patients in mutually meaningful ACP conversations.

Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.

CONTEXT: Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. OBJECTIVE: The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. DESIGN: The International Study of Inflammation in Covid-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients. SETTING: Ten hospitals in the United States and Europe. PARTICIPANTS: Adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. MAIN OUTCOME MEASURES: Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body-mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. RESULTS: Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI≥35), those with BMI>40 (n=485) had 55% higher odds of the composite outcome (95% CI[1.21 to 1.98]) compared to non-obese individuals (BMI<30, n=2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. CONCLUSION: Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes.

Potential tools for predicting response to chemotherapy in OC: Assessment of immune dysbiosis, participant's self-rated health and microbial dynamics.

Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance mechanisms contribute to poor OC 5-year survival rates. Peripheral inflammation is linked to various disease states and we previously identified unique peritoneal microbial features predictive of OC. We hypothesized that unique peripheral immune profiles and peritoneal microbial features may be predictive of disease-free interval (time to recurrence) and response to chemotherapy in participants with OC. We also investigated self-rated health (SRH) scores in the context of peripheral inflammation as a potential screening tool for OC. Blood and peritoneal fluid were collected from participants with OC or a benign adnexal mass (BPM). Lymphocyte populations were analyzed using Fluorescence Activated Cell Sorting, serum cytokine levels were analyzed using the Human Th17 Magnetic Bead Panel assay and peritoneal fluid microbial features were analyzed using Next Generation Sequencing (NGS). Participants completed a standardized questionnaire on self-rated physical and emotional health. Participants were classified into three chemotherapy response categories: platinum-refractory, platinum-resistant or platinum-sensitive. A significant positive correlation was found between elevated inflammatory status on the day of surgery and longer disease-free interval. SRH measures did not correlate with immune status in participants with OC or a BPM. We identified a correlation between peritoneal microbial features and chemotherapy response. We conclude that immune dysbiosis may be useful in predicting OC recurrence. The immune findings reported here set the framework for additional studies utilizing immune profiles to predict platinum-based chemotherapy responsiveness in OC.

Development of a core set of outcome measures to be applied toward breast cancer-related lymphedema core outcome domains.

PURPOSE: For breast cancer survivors (BCS) living with breast cancer-related lymphedema (BCRL), what outcome measures (OMs) are recommended to be used to measure standardized outcome domains to fully assess the burden of the disease and efficacy of interventions? An integral component of a standardized core outcome set (COS) are the OMs used to measure the COS. METHODS: A supplemental online survey was linked to a Delphi study investigating a COS for BCRL. OMs were limited to a maximum of 10 options for each outcome domain (OD). There were 14 ODs corresponding to the International Classification of Functioning, Disability, and Health (ICF) framework and respondents rated the OMs with a Likert level of recommendation. The feasibility of the listed OMs was also investigated for most outpatient, inpatient, and research settings. RESULTS: This study identified 27 standardized OMs with a few ODs having 2-3 highly recommended OMs for proper measurement. A few of the recommended OMs have limitations with reliability due to being semi-quantitative measures requiring the interpretation of the rater. CONCLUSION: Narrowing the choices of OMs to 27 highly recommended by BCRL experts may reduce selective reporting, inconsistency in clinical use, and variability of reporting across interdisciplinary healthcare fields which manage or research BCRL. There is a need for valid, reliable, and feasible OMs that measure tissue consistency. Measures of upper extremity activity and motor control need further research in the BCS with BCRL population.

Biomarkers of chronic inflammation and cognitive decline: A prospective observational study.

We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment (n = 97) or dementia (n = 59), compared to those with normal cognitive function (n = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline.

Certolizumab pegol in the treatment of axial spondyloarthritis.

Axial spondyloarthritis is a chronic, immune-mediated systemic inflammatory disease encompassing ankylosing spondylitis and nonradiographic axial spondyloarthritis. TNF inhibitors are the preferred second line therapy for patients with active axial spondyloarthritis. Certolizumab pegol is a TNF inhibitor approved for treatment of both. Three large phase III trials (RAPID-axSpA, C-axSpAnd and C-OPTIMISE) and one large phase IV trial (CIMAX) establish its clinical efficacy in treatment of active disease and maintenance of remission for both diseases. Real world evidence demonstrates clinical efficacy and benefits including reduced bone loss, reduced risk of uveitis, safety in pregnancy and lactation and index drug survival of 10 years. It is generally well tolerated, though can be associated with increased risk of serious infections.

Axial spondyloarthritis is a chronic (long-lasting) autoimmune disease encompassing two other inflammatory conditions called ankylosing spondylitis and nonradiographic axial spondyloarthritis. A type of medicines, called tumor necrosis factor inhibitors, are the preferred second-line medicines for patients with active axial spondyloarthritis. Second line is treatment for a condition after the initial treatment has failed. Certolizumab pegol is one of these medicines approved for the treatment of both. Four large phase III or IV studies (RAPID-axSpA, C-axSpAnd, C-OPTIMISE and CIMAX) establish its effectiveness in the treatment of active disease and maintenance of remission (a period where disease symptoms have become less severe) for both diseases. Studies of its use in routine healthcare delivery show clinical efficacy (or effectiveness) and benefits including reduced bone loss, reduced risk of certain eye disease (uveitis), safety in pregnancy and lactation and 10-year effectiveness before the need for a medication change. It is generally well tolerated, though can be associated with increased risk of serious infections.

Intubation Decision Based on Illness Severity and Mortality in COVID-19: An International Study.

OBJECTIVES: To evaluate the impact of intubation timing, guided by severity criteria, on mortality in critically ill COVID-19 patients, amidst existing uncertainties regarding optimal intubation practices. DESIGN: Prospective, multicenter, observational study conducted from February 1, 2020, to November 1, 2022. SETTING: Ten academic institutions in the United States and Europe. PATIENTS: Adults (≥ 18 yr old) confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalized specifically for COVID-19, requiring intubation postadmission. Exclusion criteria included patients hospitalized for non-COVID-19 reasons despite a positive SARS-CoV-2 test. INTERVENTIONS: Early invasive mechanical ventilation (EIMV) was defined as intubation in patients with less severe organ dysfunction (Sequential Organ Failure Assessment [SOFA] < 7 or Pa o2 /F io2 ratio > 250), whereas late invasive mechanical ventilation (LIMV) was defined as intubation in patients with SOFA greater than or equal to 7 and Pa o2 /F io2 ratio less than or equal to 250. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality within 30 days of hospital admission. Among 4464 patients, 854 (19.1%) required mechanical ventilation (mean age 60 yr, 61.7% male, 19.3% Black). Of those, 621 (72.7%) were categorized in the EIMV group and 233 (27.3%) in the LIMV group. Death within 30 days after admission occurred in 278 patients (42.2%) in the EIMV and 88 patients (46.6%) in the LIMV group ( p = 0.28). An inverse probability-of-treatment weighting analysis revealed a statistically significant association with mortality, with patients in the EIMV group being 32% less likely to die either within 30 days of admission (adjusted hazard ratio [HR] 0.68; 95% CI, 0.52-0.90; p = 0.008) or within 30 days after intubation irrespective of its timing from admission (adjusted HR 0.70; 95% CI, 0.51-0.90; p = 0.006). CONCLUSIONS: In severe COVID-19 cases, an early intubation strategy, guided by specific severity criteria, is associated with a reduced risk of death. These findings underscore the importance of timely intervention based on objective severity assessments.

Guidelines and recommendations about virtual mental health services from high-income countries: a rapid review.

OBJECTIVES: This study reviewed existing recommendations for virtual mental healthcare services through the quadruple aim framework to create a set of recommendations on virtual healthcare delivery to guide the development of Canadian policies on virtual mental health services. DESIGN: We conducted a systematic rapid review with qualitative content analysis of data from included manuscripts. The quadruple aim framework, consisting of improving patient experience and provider satisfaction, reducing costs and enhancing population health, was used to analyse and organise findings. METHODS: Searches were conducted using seven databases from 1 January 2010 to 22 July 2022. We used qualitative content analysis to generate themes. RESULTS: The search yielded 40 articles. Most articles (85%) discussed enhancing patient experiences, 55% addressed provider experiences and population health, and 25% focused on cost reduction. Identified themes included: screen patients for appropriateness of virtual care; obtain emergency contact details; communicate transparently with patients; improve marginalised patients' access to care; support health equity for all patients; determine the cost-effectiveness of virtual care; inform patients of insurance coverage for virtual care services; increase provider training for virtual care and set professional boundaries between providers and patients. CONCLUSIONS: This rapid review identified important considerations that can be used to advance virtual care policy to support people living with mental health conditions in a high-income country.

Translational success of fundamental virology: a VSV-vectored Ebola vaccine.

Ebola virus disease (EVD) caused by Ebola virus (EBOV) is a severe, often fatal, hemorrhagic disease. A critical component of the public health response to curb EVD epidemics is the use of a replication-competent, recombinant vesicular stomatitis virus (rVSV)-vectored Ebola vaccine, rVSVΔG-ZEBOV-GP (ERVEBO). In this Gem, we will discuss the past and ongoing development of rVSVΔG-ZEBOV-GP, highlighting the importance of basic science and the strength of public-private partnerships to translate fundamental virology into a licensed VSV-vectored Ebola vaccine.

Development of a core outcome set for breast cancer-related lymphedema: a Delphi study.

PURPOSE: For breast cancer survivors (BCS) living with breast cancer-related lymphedema (BCRL), what outcome domains (OD) should be measured to assess the burden of the disease and efficacy of interventions? A Core Outcome Set (COS) that promotes standardized measurement of outcomes within the constraints of time influenced by work environments is essential for patients and the multidisciplinary professionals that manage and research BCRL. METHODS: Using Delphi methodology, a multidisciplinary group of BCRL experts (physical and occupational therapists, physicians, researchers, physical therapist assistants, nurses, and massage therapist) completed two waves of online surveys. BCRL expert respondents that completed the first survey (n = 78) had an average of 26.5 years in practice, whereas, respondents who completed the second survey (n = 33) had an average of 24.9 years. ODs were included in the COS when consensus thresholds, ranging from 70% to 80%, were met. RESULTS: A total of 12 ODs made up the COS. Reaching a minimum consensus of 70%; volume, tissue consistency, pain, patient-reported upper quadrant function, patient-reported health-related quality of life, and upper extremity activity and motor control were recommended at different phases of the BCRL continuum in a time-constrained environment. Joint function, flexibility, strength, sensation, mobility and balance, and fatigue met an 80% consensus to be added when time and resources were not constrained. CONCLUSION: The COS developed in this study thoroughly captures the burden of BCRL. Using this COS may reduce selective reporting, inconsistency in clinical use, and variability of reporting across interdisciplinary healthcare fields, which manage or research BCRL.

Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population.

The COVID-19 pandemic led to the rapid and worldwide development of highly effective vaccines against SARS-CoV-2. However, there is significant individual-to-individual variation in vaccine efficacy due to factors including viral variants, host age, immune status, environmental and host genetic factors. Understanding those determinants driving this variation may inform the development of more broadly protective vaccine strategies. While host genetic factors are known to impact vaccine efficacy for respiratory pathogens such as influenza and tuberculosis, the impact of host genetic variation on vaccine efficacy against COVID-19 is not well understood. To model the impact of host genetic variation on SARS-CoV-2 vaccine efficacy, while controlling for the impact of non-genetic factors, we used the Diversity Outbred (DO) mouse model. We found that DO mice immunized against SARS-CoV-2 exhibited high levels of variation in vaccine-induced neutralizing antibody responses. While the majority of the vaccinated mice were protected from virus-induced disease, similar to human populations, we observed vaccine breakthrough in a subset of mice. Importantly, we found that this variation in neutralizing antibody, virus-induced disease, and viral titer is heritable, indicating that the DO serves as a useful model system for studying the contribution of genetic variation of both vaccines and disease outcomes.

Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids.

Natural products perennially serve as prolific sources of drug leads and chemical probes, fueling the development of numerous therapeutics. Despite their scarcity, natural products that modulate protein function through covalent interactions with lysine residues hold immense potential to unlock new therapeutic interventions and advance our understanding of the biological processes governed by these modifications. Phloroglucinol meroterpenoids constitute one of the most expansive classes of natural products, displaying a plethora of biological activities. However, their mechanism of action and cellular targets have, until now, remained elusive. In this study, we detail the concise biomimetic synthesis, computational mechanistic insights, physicochemical attributes, kinetic parameters, molecular mechanism of action, and functional cellular targets of several phloroglucinol meroterpenoids. We harness synthetic clickable analogues of natural products to probe their disparate proteome-wide reactivity and subcellular localization through in-gel fluorescence scanning and cell imaging. By implementing sample multiplexing and a redesigned lysine-targeting probe, we streamline a quantitative activity-based protein profiling, enabling the direct mapping of global reactivity and ligandability of proteinaceous lysines in human cells. Leveraging this framework, we identify numerous lysine-meroterpenoid interactions in breast cancer cells at tractable protein sites across diverse structural and functional classes, including those historically deemed undruggable. We validate that phloroglucinol meroterpenoids perturb biochemical functions through stereoselective and site-specific modification of lysines in proteins vital for breast cancer metabolism, including lipid signaling, mitochondrial respiration, and glycolysis. These findings underscore the broad potential of phloroglucinol meroterpenoids for targeting functional lysines in the human proteome.

SuPAR, biomarkers of inflammation, and severe outcomes in patients hospitalized for COVID-19: The International Study of Inflammation in COVID-19.

Severe coronavirus disease 2019 (COVID-19) is a hyperinflammatory syndrome. The biomarkers of inflammation best suited to triage patients with COVID-19 are unknown. We conducted a prospective multicenter observational study of adult patients hospitalized specifically for COVID-19 from February 1, 2020 to October 19, 2022. Biomarkers measured included soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, interleukin-6, procalcitonin, ferritin, and D-dimer. In-hospital outcomes examined include death and the need for mechanical ventilation. Patients admitted in the United States (US, n = 1962) were used to compute area under the curves (AUCs) and identify biomarker cutoffs. The combined European cohorts (n = 1137) were used to validate the biomarker cutoffs. In the US cohort, 356 patients met the composite outcome of death (n = 197) or need for mechanical ventilation (n = 290). SuPAR was the most important predictor of the composite outcome and had the highest AUC (0.712) followed by CRP (0.642), ferritin (0.619), IL-6 (0.614), D-dimer (0.606), and lastly procalcitonin (0.596). Inclusion of other biomarkers did not improve discrimination. A suPAR cutoff of 4.0 ng/mL demonstrated a sensitivity of 95.4% (95% CI: 92.4%-98.0%) and negative predictive value (NPV) of 92.5% (95% CI: 87.5%-96.9%) for the composite outcome. Patients with suPAR < 4.0 ng/mL comprised 10.6% of the cohort and had a 0.8% probability of the composite outcome. Applying this cutoff to the validation cohort yielded a sensitivity of 93.8% (90.4%-96.7%) and NPV of 95.5% (93.1%-97.8%) for the composite outcome. Among commonly measured biomarkers, suPAR offered stronger discriminatory ability and may be useful in triaging low-risk patients with COVID-19.

The effects of antipsychotic discontinuation or maintenance on the process of recovery in remitted first-episode psychosis patients - A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients. METHODS: CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach. RESULTS: Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2 = 0%; n = 128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups. CONCLUSIONS: Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.

Description of the Baseline Audiologic Characteristics of the Participants Enrolled in the Aging and Cognitive Health Evaluation in Elders Study.

PURPOSE: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a randomized clinical trial designed to determine the effects of a best-practice hearing intervention versus a successful aging health education control intervention on cognitive decline among community-dwelling older adults with untreated mild-to-moderate hearing loss. We describe the baseline audiologic characteristics of the ACHIEVE participants. METHOD: Participants aged 70-84 years (N = 977; Mage = 76.8) were enrolled at four U.S. sites through two recruitment routes: (a) an ongoing longitudinal study and (b) de novo through the community. Participants underwent diagnostic evaluation including otoscopy, tympanometry, pure-tone and speech audiometry, speech-in-noise testing, and provided self-reported hearing abilities. Baseline characteristics are reported as frequencies (percentages) for categorical variables or medians (interquartiles, Q1-Q3) for continuous variables. Between-groups comparisons were conducted using chi-square tests for categorical variables or Kruskal-Wallis test for continuous variables. Spearman correlations assessed relationships between measured hearing function and self-reported hearing handicap. RESULTS: The median four-frequency pure-tone average of the better ear was 39 dB HL, and the median speech-in-noise performance was a 6-dB SNR loss, indicating mild speech-in-noise difficulty. No clinically meaningful differences were found across sites. Significant differences in subjective measures were found for recruitment route. Expected correlations between hearing measurements and self-reported handicap were found. CONCLUSIONS: The extensive baseline audiologic characteristics reported here will inform future analyses examining associations between hearing loss and cognitive decline. The final ACHIEVE data set will be publicly available for use among the scientific community. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24756948.