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Background: Emerging evidence suggests the relationship between health literacy and health outcomes could be explained by cognitive abilities.Objective: To investigate to what degree cognitive skills explain associations between health literacy, performance on common health tasks, and functional health status.Design: Two face-to-face, structured interviews spaced a week apart with three health literacy assessments and a comprehensive cognitive battery measuring 'fluid' abilities necessary to learn and apply new information, and 'crystallized' abilities such as background knowledge.Setting: An academic general internal medicine practice and three federally qualified health centers in Chicago, Illinois.Patients: Eight hundred and eighty-two English-speaking adults ages 55 to 74.Measurements: Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM), Test of Functional Health Literacy in Adults (TOFHLA), and Newest Vital Sign (NVS). Performance on common health tasks were globally assessed and categorized as 1) comprehending print information, 2) recalling spoken information, 3) recalling multimedia information, 4) dosing and organizing medication, and 5) healthcare problem-solving.Results: Health literacy measures were strongly correlated with fluid and crystallized cognitive abilities (range: r=0.57 to 0.77, all p<0.001). Lower health literacy and weaker fluid and crystallized abilities were associated with poorer performance on healthcare tasks. In multivariable analyses, the association between health literacy and task performance was substantially reduced once fluid and crystallized cognitive abilities were entered into models (without cognitive abilities: β= -28.9, 95 % Confidence Interval (CI) -31.4 to -26.4, p; with cognitive abilities: β= -8.5, 95 % CI -10.9 to -6.0).Limitations: Cross-sectional analyses, English-speaking, older adults only.Conclusions: The most common measures used in health literacy studies are detecting individual differences in cognitive abilities, which may predict one's capacity to engage in self-care and achieve desirable health outcomes. Future interventions should respond to all of the cognitive demands patients face in managing health, beyond reading and numeracy. [ABSTRACT FROM AUTHOR]

Background: Older adults with multiple chronic conditions (MCC) and polypharmacy often face challenges with medication adherence. Nonadherence can lead to suboptimal treatment outcomes, adverse drug events, and poor quality of life., Objective: To facilitate medication adherence among older adults with MCC and polypharmacy in primary care, we are adapting a technology-enabled intervention previously implemented in a specialty clinic. The objective of this study was to obtain multilevel feedback to inform the adaptation of the proposed intervention (Phenotyping Adherence Through Technology-Enabled Reports and Navigation [PATTERN])., Methods: We conducted a formative qualitative study among patients, clinicians, and clinic administrators affiliated with a large academic health center in Chicago, Illinois. Patient eligibility included being aged 65 years or older, living with MCC, and contending with polypharmacy. Eligibility criteria for clinicians and administrators included being employed by any primary care clinic affiliated with the participating health center. Individual semistructured interviews were conducted remotely by a trained member of the study team using interview guides informed by the Exploration, Preparation, Implementation, and Sustainment Framework. Thematic analysis of interview audio recordings drew from the Rapid Identification of Themes from Audio Recordings procedures., Results: In total, we conducted 25 interviews, including 12 with clinicians and administrators, and 13 with patients. Thematic analysis revealed participants largely found the idea of technology-based medication adherence monitoring to be acceptable and appropriate for the target population in primary care, although several concerns were raised; we discuss these in detail., Conclusions: Our medication adherence monitoring intervention, adapted from specialty care, will be implemented in primary care. Formative interviews, informed by the Exploration, Preparation, Implementation, and Sustainment Framework and conducted among patients, clinicians, and administrators, have identified intervention adaptation needs. Results from this study could inform other interventions using the patient portal with older adults., (©Allison P Pack, Stacy C Bailey, Rachel O'Conor, Evelyn Velazquez, Guisselle Wismer, Fangyu Yeh, Laura M Curtis, Kenya Alcantara, Michael S Wolf. Originally published in JMIR Formative Research (https://formative.jmir.org), 17.10.2024.)

Abstract: Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Introduction: Annual cognitive screening in older adults is essential for early detection of cognitive impairment, yet primary care settings face time constraints that present barriers to routine screening. A remote cognitive screener completed on a patient's personal smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices and increase early detection of cognitive decline. MyCog Mobile is a promising new remote smartphone-based cognitive screening app for primary care settings. We propose a combined construct and clinical validation study of MyCog Mobile., Methods and Analysis: We will recruit a total sample of 300 adult participants aged 65 years and older. A subsample of 200 healthy adult participants and a subsample of 100 adults with a cognitive impairment diagnosis (ie, dementia, mild cognitive impairment, cognitive deficits or other memory loss) will be recruited from the general population and specialty memory care centres, respectively. To evaluate the construct validity of MyCog Mobile, the healthy control sample will self-administer MyCog Mobile on study-provided smartphones and be administered a battery of gold-standard neuropsychological assessments. We will compare correlations between performance on MyCog Mobile and measures of similar and dissimilar constructs to evaluate convergent and discriminant validity. To assess clinical validity, participants in the clinical sample will self-administer MyCog Mobile on a smartphone and be administered a Mini-Cog screener and these data will be combined with the healthy control sample. We will then apply several supervised model types to determine the best predictors of cognitive impairment within the sample. Area under the receiver operating characteristic curve, accuracy, sensitivity and specificity will be the primary performance metrics for clinical validity., Ethics and Dissemination: The Institutional Review Board at Northwestern University (STU00214921) approved this study protocol. Results will be published in peer-reviewed journals and summaries provided to the study's funders., Competing Interests: Competing interests: MW reports grants from the NIH, Gordon and Betty Moore Foundation, and Eli Lilly and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster, Lundbeck and GlaxoSmithKline outside the submitted work. All other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate patient-reported experiences of telehealth and disparities in access, use, and satisfaction with telehealth during the COVID-19 pandemic., Materials and Methods: We examined data from the fifth wave of the COVID-19 & Chronic Conditions (C3) study conducted between December 2020 and March 2021., Results: Of the 718 participants, 342 (47.6%) reported having a telehealth visit within the past 4 months. Participants who had a recent telehealth visit were younger, reported worse overall health and chronic illness burden, and living below poverty level. Among participants who had a telehealth visit, 66.7% reported telephone visits and most participants (57.6%) rated telehealth quality as better-or-equal-to in-person visits. Inadequate health literacy was associated with lower likelihood of reporting telehealth quality and usefulness. In multivariable analyses, lower patient activation (adjusted odds ratio (AOR) 0.19, 95% CI, 0.05-0.59) and limited English proficiency (AOR 0.12, 95% CI, 0.03-0.47) were less likely to report telehealth as being better than in-person visits; lower patient activation (AOR 0.06, 95% CI, 0.003-0.41) and income below poverty level (AOR 0.36, 95% CI, 0.13-0.98) were associated with difficulty remembering telehealth visit information., Discussion: Most participants reported usefulness and ease of navigating telehealth. Lower socioeconomic status, limited English proficiency, inadequate health literacy, lower educational attainment, and low patient activation are risks for poorer quality telehealth., Conclusion: The COVID pandemic has accelerated the adoption of telehealth, however, disparities in access and self-reported visit quality persist. Since telemedicine is here to stay, we identify vulnerable populations and discuss potential solutions to reduce healthcare disparities in telehealth use., Competing Interests: Ms Yoshino Benavente reports grants from the NIH and Gordon and Betty Moore Foundation. Ms Curtis reports grants from the NIH. Dr Serper reports personal fees from BioVie outside the submitted work. Dr Wolf reports grants from the NIH (NIA, NIDDK, NINR, NHLBI, NINDS), Gordon and Betty Moore Foundation, and Eli Lilly, and personal fees from Pfizer, Sanofi, Luto UK, GlaxoSmithKline, University of Westminster, and Lundbeck., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic., Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors., Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022., Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation., Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64)., Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Sex differences in AKI continue to be identified. Generally, women are protected from AKI when compared to men. Much of the protection exhibited in women is diminished after menopause. These sex and age effects have also been noted in animal models of AKI. Gonadal hormones, as modifiers of incidence, severity, and progression of AKI, have been offered as likely contributors to this sex and age effect. In animal models of AKI, estrogen and testosterone seem to modulate susceptibility. Questions remain however regarding cellular and molecular changes that are initiated by modulation of these hormones because both estrogen and testosterone have effects across cell types that play a role in AKI. Although findings have largely been informed by studies in males, molecular pathways that are involved in the initiation and progression of AKI may be modulated by gonadal hormones. Compounding the hormone-receptor effects are developmental effects of sex chromosomal complement and epigenetic influences that may confer sex-based baseline differences in gene and protein expression, and gene dosage effects of X inactivation and escape on molecular pathways. Elucidation of sex-based protection may afford a more complete view of AKI and potential therapeutic interventions. Furthermore, the effect on susceptibility to AKI in transgender patients, who receive life-altering and essential gender-affirming hormone therapy, requires greater attention. In this review, several potential contributors to the sex differences observed in humans and animal models are discussed., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Objective: Many older adults receive assistance in managing their chronic conditions. Yet complicating the utility of caregiver support is whether caregivers have sufficient skills to aid in older adults' health management at home. We examined associations between caregiver health literacy and performance on health tasks., Methods: Caregivers to older adults enrolled in a cognitive aging cohort were recruited to participate in a supplemental interview ( n  = 97). Caregivers completed one structured interview that included assessments of health literacy and health task performance., Results: Caregivers demonstrated a range of health literacy skills (44% adequate, 36% marginal, 20% low health literacy). In adjusted analyses, caregivers with marginal and low health literacy demonstrated worse overall performance on the health tasks, and poorer interpretation of health information presented on print documents and recall of spoken communication (p's < 0.05)., Conclusion: Caregivers with marginal or low health literacy demonstrated poorer performance on everyday health tasks that they commonly assist older adults with. The application of health literacy best-practices to support better training and capacity-building for caregivers is warranted., Innovation: Few studies have considered the health literacy skills of caregivers and its application to caregivers' abilities to carry out common supportive tasks., Competing Interests: Dr. O'Conor reports grants from the NIH outside of the submitted work. Dr. Wolf reports grants from the NIH, Gordon and Betty Moore Foundation, and Eli Lilly, and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster, Lundbeck and GlaxoSmithKline outside the submitted work. All other authors report no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V.)

Introduction: COVID-19 is an unprecedented public health threat in modern times, especially for older adults or those with chronic illness. Beyond the threat of infection, the pandemic may also have longer-term impacts on mental and physical health. The COVID-19 & Chronic Conditions ('C3') study offers a unique opportunity to assess psychosocial and health/healthcare trajectories over 5 years among a diverse cohort of adults with comorbidities well-characterised from before the pandemic, at its onset, through multiple surges, vaccine rollouts and through the gradual easing of restrictions as society slowly returns to 'normal'., Methods and Analysis: The C3 study is an extension of an ongoing longitudinal cohort study of 'high-risk' adults (aged 23-88 at baseline) with one or more chronic medical conditions during the COVID-19 pandemic. Five active studies with uniform data collection prior to COVID-19 were leveraged to establish the C3 cohort; 673 adults in Chicago were interviewed during the first week of the outbreak. The C3 cohort has since expanded to include 1044 participants across eight survey waves (T 1 -T 8 ). Four additional survey waves (T 9 -T 12 ) will be conducted via telephone interviews spaced 1 year apart and supplemented by electronic health record and pharmacy fill data, for a total of 5 years of data post pandemic onset. Measurement will include COVID-19-related attitudes/behaviours, mental health, social behaviour, lifestyle/health behaviours, healthcare use, chronic disease self-management and health outcomes. Mental health trajectories and associations with health behaviours/outcomes will be examined in a series of latent group and mixed effects modelling, while also examining mediating and moderating factors., Ethics and Dissemination: This study was approved by Northwestern University's Feinberg School of Medicine Institutional Review Board (STU00215360). Results will be published in international peer-reviewed journals and summaries will be provided to the funders of the study., Competing Interests: Competing interests: SCB reports grants from the NIH, Merck, Pfizer, Gordon and Betty Moore Foundation, Retirement Research Foundation for Aging, Lundbeck, Gilead and Eli Lilly via her institution and personal fees from Sanofi, Pfizer, University of Westminster, Lundbeck, Gilead and Luto UK outside the submitted work. MW reports grants from the NIH, Gordon and Betty Moore Foundation, and Eli Lilly, and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster and Lundbeck outside the submitted work. All other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Many older adults receive assistance in managing chronic conditions. Yet complicating the utility of caregiver support is whether caregivers have sufficient skills to aid in a patient's self-care. Health literacy and cognition are important determinants of older adults' health outcomes, but few studies have examined caregiver health literacy, cognition and self-care skills and their relations to patient outcomes., Methods and Analysis: We will expand an ongoing cognitive ageing cohort study (LitCog) to enroll a parallel caregiver cohort. Caregivers are eligible if they are (1) ≥18 years of age, (2) provided care for ≥6 months and (3) assisted with at least one activity of daily living, instrumental activity of daily living or health management task. Caregivers will complete interviews at time points corresponding with the LitCog participant interviews. Caregivers will complete assessments of health literacy, self-care skills, cognitive function, caregiver healthcare task difficulty, caregiver burden, caregiver self-efficacy, activation, technology use, busyness and routine and relationship quality. Caregivers will self-report the nature and intensity of care provided, and their own health status. Associations between caregiver presence and caregiver capacity with patient outcomes will be examined in a series of regression models, and mediating and moderating factors will be tested., Ethics and Dissemination: The Institutional Review Board at Northwestern University has approved the study protocol (STU00026255). Results will be published in peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and caregivers., Competing Interests: Competing interests: MW reports grants from the NIH, Gordon and Betty Moore Foundation and Eli Lilly, and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster, Lundbeck and GlaxoSmithKline outside the submitted work. All other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess whether older adults with a cognitive impairment were more likely to report challenges interacting with medical providers, or to avoid needed medical care. Methods: Data for this exploratory, cross-sectional analysis were from older adults ( N = 493) ages 60-82 participating in the "LitCog" cohort study. Multivariable generalized linear models compared cognitive impairment (none, mild, moderate, severe) with validated measures of healthcare engagement. Results: A moderate cognitive impairment was associated with delays in medical care due to embarrassment (RR 5.34.95% CI 1.30-22.0) and discomfort asking the doctor questions (RR 4.07, 95% CI 1.00-16.5). Conclusions: Intermediate cognitive deficits , such as with mild cognitive impairment (MCI) or mild dementias, may impact meaningful engagement with healthcare systems, potentially affecting timely detection and appropriate management of cognitive concerns and other chronic medical conditions. More research is needed to understand mechanisms underlying this relationship.

Cognitive impairment (CI) and dementia can have profound social and emotional effects on older adults. Early detection of CI is imperative both to the identification of potentially treatable conditions and to provide services to minimize the effects of CI in cases of dementia. While primary care settings are ideal for identifying CI, it frequently goes undetected. We tailored a brief, iPad-based, cognitive assessment (MyCog) for primary care settings and piloted it in a sample of older adults. Eighty participants were recruited from an existing cohort study and completed a brief, in-person interview. CI was determined based on a diagnosis of dementia or CI in their medical record or based on a comprehensive cognitive battery performed within the past 18 months. MyCog had a sensitivity of 79% and specificity of 82%, offering a practical, scalable, primary care assessment for the routine case finding of cognitive impairment and dementia., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Prof. Curtis reports grants from the NIH (NIA, NIDDK, NINDS, NCI) and the Gordon and Betty Moore Foundation. Ms. Batio reports grants from the NIH (NIA, NIDDK, NINDS) and the Gordon and Betty Moore Foundation. Ms. Yoshino Benavente reports grants from the NIH (NIA, NINDS, NIDDK) and the Gordon and Betty Moore Foundation. Dr. Shono reports grants from the NIH (NIA). Dr. Nowinski reports grants and contracts from the NIH (NIA, NINDS, NICHD) and the FDA. Dr. Lovett reports grants from the NIH (NIA, NINDS). Dr. Yao reports grants from the NIH (NIA, NINDS). Dr. Gershon reports grants from the NIH (NIA, NINDS, NICHD, Office of the Director). Dr. Wolf reports grants from the NIH (NIA, NIDDK, NINR, NHLBI, NINDS), Gordon and Betty Moore Foundation, and Eli Lilly, and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster, and Lundbeck., (© The Author(s) 2023.)

Introduction: The lack of definitive means to prevent or treat cognitive impairment or dementia is driving intense efforts to identify causal mechanisms. Recent evidence suggests clinically meaningful declines in cognition might present as early as middle age. Studying cognitive changes in middle adulthood could elucidate modifiable factors affecting later cognitive and health outcomes, yet few cognitive ageing studies include this age group. The purpose of the MidCog study is to begin investigations of less-studied and potentially modifiable midlife determinants of later life cognitive outcomes., Methods and Analysis: MidCog is a prospective cohort study of adults ages 35-64, with two in-person interviews 2.5 years apart. Data will be collected from interviews, electronic health records and pharmacy fill data. Measurements will include health literacy, self-management skills, cognitive function, lifestyle and health behaviours, healthcare use, health status and chronic disease outcomes. Associations of health literacy and self-management skills with health behaviours and cognitive/health outcomes will be examined in a series of regression models, and moderating effects of modifiable psychosocial factors.Finally, MidCog data will be linked to an ongoing, parallel cohort study of older adults recruited at ages 55-74 in 2008 ('LitCog'; ages 70-90 in 2023), to explore associations between age, health literacy, self-management skills, chronic diseases, health status and cognitive function among adults ages 35-90., Ethics and Dissemination: The Institutional Review Board at Northwestern University has approved the MidCog study protocol (STU00214736). Results will be published in peer-reviewed journals and summaries will be provided to the funders of the study as well as patients., Competing Interests: Competing interests: SCB reports grants from the NIH, Merck, Pfizer, Gordon and Betty Moore Foundation, Retirement Research Foundation for Aging, Lundbeck, Gilead, and Eli Lilly via her institution and personal fees from Sanofi, Pfizer, University of Westminster, Lundbeck, Gilead, and Luto UK outside the submitted work. PCZ reports grants from the NIH and Vanda via her institution and personal consulting fees from Jazz, Eisai, Harmony and Sleep Number that are outside the submitted work. MW reports grants from the NIH, Gordon and Betty Moore Foundation, and Eli Lilly, and personal fees from Pfizer, Sanofi, Luto UK, University of Westminster, and Lundbeck outside the submitted work. RO’C is supported by a training grant from the National Institute on Aging (K01AG070107). All the other authors report no conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Older adults frequently defer decisions about their aging-in-place/long-term care (AIP-LTC) needs. As a result, when older adults experience worsening Alzheimer's disease, family members/friends become surrogate decision makers. We sought to understand what aspects of cognition impact older adult AIP-LTC planning., Methods: As part of the PlanYourLifespan (PYL)-LitCog study, we longitudinally examined AIP-LTC decision-making among a cohort (LitCog) of community-based older adults (65 years and older) recruited from hospital-associated primary care clinics in Chicago, Illinois, with extensive cognitive testing. PlanYourLifespan.org (PYL) is an evidence-based online intervention that facilitates AIP-LTC planning. Subjects underwent baseline testing, received the PYL online intervention, and then were surveyed at 1, 6, and 12 months about AIP-LTC decision-making. Cross-sectional logistic regression analysis was conducted examining cognitive variables that impacted AIP-LTC decision-making., Results: Of the 293 older adults interviewed (mean age 73.0 years, 40.4% non-White), subjects were more likely to have made AIP-LTC decisions if they had adequate inductive reasoning (ETS letter sets total-OR = 1.14 (95% CI = 1.03-1.27; p < 0.05)) and adequate working memory (size judgment span total-OR = 1.76 (95% CI = 1.13-2.73; p < 0.05)). There were no differences in decision-making observed in verbal abilities, long-term memory, or processing speed. All analyses were adjusted for participant gender, race, age, and decision-making response at baseline., Conclusion: Inductive reasoning and working memory are critical to AIP-LTC decision-making. Screening routinely for these specific cognitive domains is important in targeting and helping older adults prepare in time for their future AIP-LTC needs., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Nephrotoxicity is the dose-limiting side-effect of the chemotherapeutic agent cisplatin (Cp). Recent evidence points to renal protective actions of G protein-coupled estrogen receptor 1 (GPER1). In addition, it has been shown that GPER1 signaling elicits protective actions against acute ischemic injuries that involve multiple organ systems; however, the involvement of GPER1 signaling in Cp-induced acute kidney injury (AKI) remains unclear. This study tested whether genetic deletion of GPER1 exacerbates Cp-induced AKI in male mice. We subjected male mice, homozygous (homo) and heterozygous (het) knockout for the GPER1 gene, and wild-type (WT) littermates to Cp or saline injections and assessed markers for renal injury on the third day after injections. We also determined serum levels of proinflammatory markers in saline and Cp-treated mice. Given the protective role of heme oxygenase-1 (HO-1) in Cp-mediated apoptosis, we also investigated genotypic differences in renal HO-1 abundance, cell death, and proliferation by Western blotting, the TUNEL assay, and Ki67 immunostaining, respectively. Cp increased serum creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL) levels, the renal abundance of kidney injury molecule-1, and NGAL in all groups. Cp-induced AKI resulted in comparable histological evidence of injury in all genotypes. WT and homo mice showed greater renal HO-1 abundance in response to Cp. Renal HO-1 abundance was lower in Cp-treated homo, compared to Cp-treated WT mice. Of note, GPER1 deletion elicited a remarkable increase in renal apoptosis; however, no genotypic differences in cell proliferation were observed. Cp augmented kidney Ki67-positive counts, regardless of the genotype. Overall, our data do not support a role for GPER1 in mediating Cp-induced renal injury. GPER1 deletion promotes renal apoptosis and diminishes HO-1 induction in response to Cp, suggesting that GPER1 may play cytoprotective and anti-apoptotic actions in AKI. GPER1-induced regulation of HO-1 and apoptosis may offer novel therapeutic targets for the treatment of AKI.

Abstract: The U.S. public health response to coronavirus disease 2019 (COVID-19) has been widely criticized as having downplayed the potential implications COVID-19 could have on one's personal health. Despite the unprecedented threat of COVID-19, many individuals still believed that it was not at all likely that they would become infected. We sought to investigate trends in adults' perceived susceptibility to COVID-19 over the first year of the pandemic, whether distinct trajectories emerged, and if these trajectories differed by participant socio-demographic characteristics.This was a longitudinal cohort study with 5 time points of data collection (March 13, 2020-March 3, 2021). Subjects included 627 adults living with ≥1 chronic conditions, who completed a baseline interview and at least one follow-up interview. In addition to collecting relevant socio-demographic characteristics, participants' perceived susceptibility to COVID-19 across time was assessed and classified into distinct trajectories.Nearly two-thirds (62.2%) of participants perceived themselves to be highly susceptible to COVID-19 from the onset of the pandemic ("early responders") and sustained this over a year, a third (29.0%) eventually perceived themselves to be highly susceptible ("late responders"), and 8.8% maintained a low likelihood of susceptibility throughout the pandemic ("non-responders"). In multivariable analyses, compared to White participants, Latinx participants were significantly more likely to be non-responders and report low likelihood of perceived susceptibility (Risk Ratio [RR]: 3.46; 95% confidence interval: 1.19, 10.1), as were Black participants (RR: 5.49; 95% confidence interval: 2.19, 13.8).A year into the COVID-19 pandemic, 1 out of 11 participants persistently did not think they might be susceptible and potentially infected. Future studies are needed to understand reasons why certain individuals, particularly those of racial/ethnic minorities, did not perceive themselves at risk for infection., Competing Interests: MSW reports grants from the NIH during the conduct of the study; grants from Merck, the Gordon and Betty Moore Foundation, the NIH, and Eli Lilly outside the submitted work; and personal fees from Sanofi, Pfizer, and Luto outside the submitted work. SCB reports grants from the NIH during the conduct of the study; grants from Merck, the NIH, and Eli Lilly outside the submitted work; grants and personal fees from the Gordon and Betty Moore Foundation outside the submitted work; and personal fees from Sanofi, Pfizer, and Luto outside the submitted work. LAO, LMC, MJK, RO, GAW, JYB, RML, MRE, and AMZ have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Examine COVID-19 knowledge, concerns, behaviors, stress, and sources of information among patients in a safety-net health system in Louisiana. Research assistants surveyed participants via structured telephone interviews from April to October 2020. The data presented in this study were obtained in the pre-vaccine availability period. Of 623 adult participants, 73.5% were female, 54.7% Black, and 44.8% lived in rural small towns; mean age was 48.69. Half (50.5%) had spoken to a healthcare provider about the virus, 25.8% had been tested for COVID-19; 11.4% tested positive. Small town residents were less likely to be tested than those in cities (21.1% vs 29.3%, p = 0.05). Knowledge of COVID-19 symptoms and ways to prevent the disease increased from (87.9% in the spring to 98.9% in the fall, p < 0.001). Participants indicating that the virus had 'changed their daily routine a lot' decreased from 56.9% to 39.3% (p < 0.001). The main source of COVID-19 information was TV, which increased over time, 66.1-83.6% (p < 0.001). Use of websites (34.2%) did not increase. Black adults were more likely than white adults (80.7% vs 65.6%, p < 0.001) to rely on TV for COVID-19 information. Participants under 30 were more likely to get COVID-19 information from websites and social media (58.2% and 35.8% respectively). This study provides information related to the understanding of COVID-19 in rural and underserved communities that can guide clinical and public health strategies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Inadequate adherence to prescribed immunosuppressive medication regimens among kidney transplant recipients is common, yet interventions are needed to support patients in sustaining adequate adherence to prescribed regimens and achieving optimal transplant outcomes., Objective: We examined the preliminary fidelity of a transplant center-based, multifaceted adherence monitoring strategy known as TAKE IT., Methods: The TAKE IT strategy includes: (1) routine, online, monthly patient self-report adherence assessments; (2) care alerts directed to nurses; (3) quarterly reports monitoring tacrolimus values and adherence trends; (4) support tools tailored to specific adherence concerns. A 2-arm, patient-randomized trial is underway at two large transplant centers (N=449). To evaluate the initial fidelity of TAKE IT, we investigated patient uptake of monthly adherence assessments during the course of a 3-month period, whether any disparities emerged, and the nature of any reported adherence concerns., Results: Among 202 patients randomized and exposed to TAKE IT for 3-months or more, 81% (164/202) completed an adherence assessment, 73% (148/202) completed at least two, and 57% (116/202) completed all monthly assessments. Overall, 50% (82/164) of kidney transplant recipients reported at least one adherence concern over the 3-month assessment period. The most common barriers were classified as regimen-related (eg, regimen complexity), cognitive (eg, forgetfulness), and medical (eg, side effects). Higher-income participants were more likely to complete all surveys compared to lower-income participants (P=.01)., Conclusions: TAKE IT demonstrated 81% (164/202) completion of an adherence assessment, 73% (148/202) completion of at least two, and 57% (116/202) completion of all monthly assessments during this brief, initial observation period. Among those that did respond to the online assessments, the majority demonstrated sustained engagement. Additional monitoring modalities could also be offered to meet patient preferences to ensure all patients' medication use can be properly monitored., Trial Registration: ClinicalTrials.gov NCT03104868; https://clinicaltrials.gov/ct2/show/NCT03104868., (©Esther S Yoon, Scott Hur, Laura M Curtis, Aiden H Wynia, Pauline Zheng, Sumi S Nair, Stacy C Bailey, Marina Serper, Peter P Reese, Daniela P Ladner, Michael S Wolf. Originally published in JMIR Formative Research (https://formative.jmir.org), 05.05.2022.)

Kidney health and manifestation of disease in transgender men, women, and nonbinary individuals are not well understood. Transgender individuals commonly receive gender-affirming hormone therapy (GAHT) to align their outward appearance with their gender. Recent attention to the differences in fundamental kidney parameters has identified that transgender individuals may manifest levels of these biomarkers differently than their cisgender counterparts. Improving understanding of the differences in biomarkers and in the development of kidney disease is essential to providing appropriate kidney care to this vulnerable population. In this review, we introduce the current information related to GAHT and kidney health and highlight the significant gaps in our understanding of how GAHT may affect kidney physiology and pathophysiology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) screening has been shown to decrease CRC mortality, yet significant disparities persist among those living in rural areas, from minority backgrounds, and those having low income. The purpose of this two-arm randomized controlled trial is to test the effectiveness and fidelity of a stepped care (increasing intensity as needed) approach to promoting 3-year adherence to CRC screening via fecal immunochemical testing (FIT) or colonoscopy in rural community clinics serving high rates of low-income and minority patients. We hypothesize that, compared to enhanced usual care (EUC), patients receiving the multifaceted CRC screening intervention will demonstrate higher rates of CRC screening completion over 3 years. Participants from six federally qualified health centers (FQHCs; N = 1200 patients) serving predominately low-income populations in rural Louisiana will be randomized to the intervention or EUC arm. All participants will receive health literacy-directed CRC counseling, simplified materials about both the FIT and colonoscopy procedures, and motivational interviewing to aid in the determination of test preference. Participants in the intervention arm will also receive motivational reminder messages from their primary care provider (via audio recording or tailored text) for either a scheduled colonoscopy or return of a completed FIT. Participants in the EUC arm will receive the standard follow-up provided by their clinic or colonoscopy facility. The primary outcome will be completion of either colonoscopy or annual FIT over 3 years. Results will provide evidence on the effectiveness of the intervention to decrease disparities in CRC screening completion related to health literacy, race, and gender. Trial registration:Clinicaltrials.gov Identifier NCT04313114., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) has demonstrated sex differences as illustrated in clinical and preclinical studies. In most cases, females show a significant resistance to AKI as manifested by renal indicators of injury, and thus much of the literature is derived from studies exclusively in males. Thermoneutral housing alters sex differences in acute injury of the liver, but has not been studied in the kidney. Thermoneutrality, the ambient temperature at which additional energy is not needed to maintain core body temperature, is regulated by mechanisms residing in mitochondria. Importantly, mitochondrial function plays an important role in induction and recovery of AKI. Mechanisms that regulate thermoneutrality include uncoupling proteins (UCPs) and one of its upstream regulators peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). PGC-1α has been extensively studied in AKI in males. UCP-2, a UCP expressed in the kidney, has been minimally studied in AKI in males. Expression of other UCPs in the kidney has not been well defined. No studies of either PGC-1α or UCPs have interrogated for a sex difference nor have they been investigated at thermoneutrality in the kidney. In this brief review, pathways of importance in thermoneutrality are described and related to pathways of importance in modulating susceptibility to AKI. Clarity in the understanding of the impact of thermoneutrality on AKI in altering susceptibility in females may expand our understanding of the critical role of mitochondrial function in this setting. Unique utilization of mitochondrial-based molecular pathways in females may then inform potential therapies., (© 2021 S. Karger AG, Basel.)

In a survey of older adults at higher risk for COVID-19 complications, we sought to describe expectations of trust in the safety and efficacy of a future COVID-19 vaccine, and level of hesitancy about receiving it. We also assessed whether these expectations were associated with known or suspected contributors to vaccine hesitancy, disparities in vaccine receipt, and potential targets for public health outreach. From May 1-22, 2020, we performed telephone surveys of 601 older adults with chronic conditions in metro Chicago about their COVID-19 experiences and levels of vaccine trust and hesitancy. All participants previously completed assessments of demographics, health status, health literacy and activation. Bivariate associations were performed using t-tests or one-way ANOVA, and multivariate analyses using least square means. Younger age (<60), Black race, greater complacency about contracting COVID-19, and lower confidence in state or local government were associated with significantly lower trust in a vaccine's safety and efficacy. Black race and greater complacency about contracting COVID-19 were associated with a significantly greater vaccine hesitancy. Amongst Black participants, vaccine hesitancy varied significantly by confidence in the federal government. Trust and hesitancy regarding a future COVID-19 vaccine were associated with age, race, complacency regarding contracting COVID-19, and confidence in government response to the pandemic, but not education, health literacy or activation. Therefore, efforts to vaccinate higher risk older adults must aim not only to educate and provide vaccine access, but engender trust in the vaccine development process and vaccination strategies at both the federal and the local level., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Objectives: Patient knowledge deficits related to opioid risks, including lack of knowledge regarding addiction, are well documented. Our objective was to characterize patients' perceptions of signs of addiction., Methods: This study utilized data obtained as part of a larger interventional trial. Consecutively discharged English-speaking patients, age >17 years, at an urban academic emergency department, with a new opioid prescription were enrolled from July 2015 to August 2017. During a follow-up phone interview 7 to 14 days after discharge, participants were asked a single question, "What are the signs of addiction to pain medicine?" Verbatim transcribed answers were analyzed using a directed content analysis approach and double coding. These codes were then grouped into themes., Results: There were 325 respondents, 57% female, mean age 43.8 years, 70.1% privately insured. Ten de novo codes were added to the 11 DSM-V criteria codes. Six themes were identified: (1) effort spent acquiring opioids, (2) emotional and physical changes related to opioid use, (3) opioid use that is "not needed, (4) increasing opioid use, (5) an emotional relationship with opioids, and (6) the inability to stop opioid use., Conclusions: Signs of addiction identified by opioid naive patients were similar to concepts identified in medical definitions. However, participants' understanding also included misconceptions, omissions, and conflated misuse behaviors with signs of addiction. Identifying these differences will help inform patient-provider risk communication, providing an opportunity for counseling and prevention., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American Society of Addiction Medicine.)

Malignancy relapse remains a major barrier to treatment success in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic graft-versus-host disease (cGVHD) markedly reduces hematologic malignancy relapse risk, but relapses still occur in these patients. Patients (n = 275) with moderate or severe cGVHD were enrolled on the National Cancer Institute (NCI) prospective cross-sectional natural history study (NCT00092235). Subjects were median 36 months after allo-HSCT and were followed subsequently for malignancy relapse and survival. Seventeen patients experienced relapse. In a multivariable model including time-dependent influences on relapse, risk factors associated with increased risk of relapse included shorter time from transplant to cGVHD evaluation (HR 0.279, 95% CI 0.078-0.995) and lower number of prior lines of systemic immunosuppressive therapy for cGVHD (HR 0.260, 95% CI 0.094-0.719). In a model excluding time-dependent influences on relapse risk, lower number of prior lines of systemic immunosuppressive therapy for cGVHD (HR 0.288, 95% CI 0.103-0.804), lower C4 complement level (HR 0.346, 95% CI 0.129-0.923), and higher body mass index (HR 3.222, 95% CI 1.156-8.974), were all associated with increased relapse risk. Parameters indicating cGVHD severity and activity are associated with risk of malignancy relapse. Classical predictors of relapse after allo-HSCT do not seem to be prognostic.

Acute kidney injury (AKI) remains a significant clinical problem through its diverse etiologies, the challenges of robust measurements of injury and recovery, and its progression to chronic kidney disease (CKD). Bridging the gap in our knowledge of this disorder requires bringing together not only the technical resources for research but also the investigators currently endeavoring to expand our knowledge and those who might bring novel ideas and expertise to this important challenge. The University of Alabama at Birmingham-University of California-San Diego O'Brien Center for Acute Kidney Injury Research brings together technical expertise and programmatic and educational efforts to advance our knowledge in these diverse issues and the required infrastructure to develop areas of novel exploration. Since its inception in 2008, this O'Brien Center has grown its impact by providing state-of-the-art resources in clinical and preclinical modeling of AKI, a bioanalytical core that facilitates measurement of critical biomarkers, including serum creatinine via LC-MS/MS among others, and a biostatistical resource that assists from design to analysis. Through these core resources and with additional educational efforts, our center has grown its investigator base to include >200 members from 51 institutions. Importantly, this center has translated its pilot and catalyst funding program with a $37 return per dollar invested. Over 500 publications have resulted from the support provided with a relative citation ratio of 2.18 ± 0.12 (iCite). Through its efforts, this disease-centric O'Brien Center is providing the infrastructure and focus to help the development of the next generation of researchers in the basic and clinical science of AKI. This center creates the promise of the application at the bedside of the advances in AKI made by current and future investigators.

Background: Several studies report a high prevalence of non-adherence to prescribed immunosuppressive (IS) medications among kidney transplant recipients (KTRs), yet few interventions have been effective for helping patients sustain appropriate post-transplant adherence. We describe a multifaceted, evidence-based, medication adherence monitoring strategy ('TAKE IT') that leverages available transplant center resources to identify potential medication non-adherence and other concerns earlier to prevent complications that could result from inadequate IS adherence., Methods: The TAKE IT strategy includes: 1) medication adherence mobile application; 2) routine, online patient self-reported adherence assessments; 3) care alert notifications via the electronic health record (EHR) directed to transplant coordinators; 4) quarterly adherence reports to monitor IS values and summarize adherence trends; 5) deployment of adherence support tools tailored to specific adherence concerns. To test the TAKE IT intervention, we will conduct a two-arm, patient-randomized controlled trial at two large, diverse transplant centers (Northwestern University, Mayo Clinic, AZ) with planned recruitment of 450 KTRs (n = 225 per site) within 2 years of transplantation and 2 years of follow-up. Study assessments will take place at baseline, 6 weeks, 6, 12, 18 and 24 months. The primary effectiveness outcome is medication adherence via pill count, secondary outcomes include self-reported adherence and clinical outcomes. Process outcomes and cost-effectiveness will also be examined., Conclusion: The TAKE IT trial presents an innovative approach to monitoring and optimizing medication adherence among a population taking complex medication regimens. This trial seeks to evaluate the effectiveness and feasibility of this strategy compared to usual care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Health literacy is often viewed as a static trait in longitudinal studies, which may over or underestimate an individual's ability to manage one's health., Objectives: We sought to examine health literacy over time among older adults using three widely used measures., Design: A prospective cohort study., Participants: Community-dwelling adults ages 55 to 74 at baseline with at least one follow-up visit (N = 656) recruited from one academic internal medicine clinic and six community health centers in Chicago, IL., Measures: Health literacy was measured using the Test of Functional Health Literacy in Adults (TOFHLA), Newest Vital Sign (NVS), and Rapid Estimate of Adult Literacy in Medicine (REALM) at baseline and up to three follow-up time points., Results: In unadjusted analyses, significant changes since baseline were found beginning at the second follow-up (mean (M) = 6.0 years, SD = 0.6) for the TOFHLA (M = - 0.9, SD = 0.95, p = 0.049) and the REALM (M = 0.3, SD = 2.5, p = 0.004) and at the last follow-up (M = 8.6 years, SD = 0.5) for the NVS (M = - 0.2, SD = 1.4, p = 0.02). There were non-linear effects of baseline age on TOFHLA and NVS scores over time (piecewise cubic spline p = 0.01 and p < 0.001, respectively) and no effect on REALM scores (B = 0.02, 95% CI - 0.01 to 0.04, p = 0.17) using multivariable mixed-effects linear regression models, controlling for race, education, income, and comorbidity., Conclusion: We found a negative relationship between age and health literacy over time as measured by the TOFHLA and NVS. Health literacy barriers appear to be more prevalent among individuals in later life, when self-care demands are similarly increasing. Clinicians might consider strategies to assess and respond to limited health literacy, particularly among patients 70 and older. REALM performance remained stable over 10 years of follow-up. This questions whether health literacy tools measure the same attribute. Prospective health literacy studies should carefully consider what measures to use, depending on their objective.

Objectives: Recent guidelines advise limiting opioid prescriptions for acute pain to a three-day supply; however, scant literature quantifies opioid use patterns after an emergency department (ED) visit. We sought to describe opioid consumption patterns after an ED visit for acute pain., Design: Descriptive study with data derived from a larger interventional study promoting safe opioid use after ED discharge., Setting: Urban academic emergency department (>88,000 annual visits)., Subjects: Patients were eligible if age >17 years, not chronically using opioids, and newly prescribed hydrocodone-acetaminophen and were included in the analysis if they returned the completed 10-day medication diary., Methods: Patient demographics and opioid consumption are reported. Opioid use is described in daily number of pills and daily morphine milligram equivalents (MME) both for the sample overall and by diagnosis., Results: Two hundred sixty patients returned completed medication diaries (45 [17%] back pain, 52 [20%] renal colic, 54 [21%] fracture/dislocation, 40 [15%] musculoskeletal injury [nonfracture], and 69 [27%] "other"). The mean age (SD) was 45 (15) years, and 59% of the sample was female. A median of 12 pills were prescribed. Patients with renal colic used the least opioids (total pills: median [interquartile range {IQR}] = 3 [1-7]; total MME: median [IQR] = 20 [10-50]); patients with back pain used the most (total pills: median [IQR] = 12 [7-16]; total MME: median [IQR] = 65 [47.5-100]); 92.5% of patients had leftover pills., Conclusions: In this sample, pill consumption varied by illness category; however, overall, patients were consuming low quantities of pills, and the majority had unused pills 10 days after their ED visit., (© 2020 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Steroid-refractory chronic graft-versus-host disease (cGVHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase 2 clinical trial (#NCT01688466) to determine the safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGVHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide 0.5 mg per day orally (n = 17; low-dose cohort) or 2 mg per day at a starting dose of 0.5 mg per day increasing to 2 mg per day over 6 weeks (n = 17; high-dose cohort). The primary endpoint was overall response rate (ORR) at 6 months according to the 2005 National Institutes of Health cGVHD Response Criteria. Thirty-two patients had severe sclerotic skin and received a median of 5 (range, 2-10) previous systemic therapies. ORR was 47% (95% confidence interval, 30-65) in the intention-to-treat analyses. All were partial responses, with no difference in ORR between the cohorts. ORR was 67% (45%-84%) in the 24 evaluable subjects at 6 months. Nine had improvement in National Institutes of Health joint/fascia scores (P = .018). Median change from the baseline in body surface area involvement of skin cGVHD was -7.5% (-10% to 35%; P = .002). The most frequent adverse events were lymphopenia, infection, and fatigue. Eight subjects in the high-dose cohort had dose decreases because of adverse events. There was 1 death in the low-dose cohort from bacterial pneumonia. Our data indicate antifibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and interleukin-2. Pomalidomide 0.5 mg per day is a safe and effective therapy for advanced corticosteroid-refractory cGVHD.

Patient portals promote self-management, but require skills with electronic health information which can be measured by a patient's eHealth literacy. We aimed to describe eHealth literacy among a population of kidney transplant (KT) and liver transplant (LT) recipients and to investigate the relationship between eHealth literacy and Web-based patient portal utilization. We conducted phone surveys (August 2016-March 2017) among 178 KT and 110 LT recipients at two large transplant centers, including the eHealth Literacy Scale (eHEALS) and items assessing routine portal usage. Portal users were defined as routine if usage was every day, weekly, or monthly. The mean eHEALS score was 30.9 (SD: 5.4), and 45.4% routinely used the patient portal more than a few times per month. Routine users had higher eHealth literacy than non-routine users and non-users (31.97 vs. 29.97 vs. 28.20, p < .001). Routine users had higher eHealth literacy scores compared with non-users after adjusting for transplant organ type, age, educational level, employment status, mobile Internet access, and transplant center (OR: 1.10, 95% CI: 1.03-1.17). KT and LT recipients who routinely use patient portals have high eHealth literacy compared with other diseased populations, which should be leveraged by encouraging routine usage to improve post-transplant health and medication adherence., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Injured tubule epithelium stimulates a profibrotic milieu that accelerates loss of function in chronic kidney disease (CKD). This study tested the role of signal transducer and activator of transcription 1 (STAT1) in the progressive loss of kidney function in aristolochic acid (AA) nephropathy, a model of CKD. Mean serum creatinine concentration increased in wild-type (WT) littermates treated with AA, whereas Stat1 -/- mice were protected. Focal increases in the apical expression of kidney injury molecule (KIM)-1 were observed in the proximal tubules of WT mice with AA treatment but were absent in Stat1 -/- mice in the treatment group as well as in both control groups. A composite injury score, an indicator of proximal tubule injury, was reduced in Stat1 -/- mice treated with AA. Increased expression of integrin-β 6 and phosphorylated Smad2/3 in proximal tubules as well as interstitial collagen and fibronectin were observed in WT mice following AA treatment but were all decreased in AA-treated Stat1 -/- mice. The data indicated that STAT1 activation facilitated the development of progressive kidney injury and interstitial fibrosis in AA nephropathy.

Objectives: Physical distancing precautions during the COVID-19 pandemic may challenge the provision of tangible support many middle age and older adults receive in managing their health. We examined the association between unmet tangible support needs and self-management behaviors and mental health status during the stay-at-home orders in Chicago and New York., Methods: We used data from the COVID-19 & Chronic Conditions study collected between May 1st and May 22nd, 2020. A total of 801 middle age and older adults with ≥1 chronic condition in Chicago and New York City completed the telephone interview. Adequacy of tangible social support was measured using a brief, validated scale that determined whether an individual needed assistance managing his or her health, and if yes, whether this need was met. Participants reported their level of difficulty engaging in self-management behaviors using 2 discrete items; they also self-reported medication adherence using the ASK-12 medication adherence scale. Mental health status was measured using the depression and anxiety PROMIS short-form instruments., Results: Participants' mean age was 63 years; 30% identified as Black, 26% identified as Latino, and 12% identified unmet support needs. Inadequacy of tangible support was associated with greater difficulty managing one's health and accessing medications due to COVID-19, as well as poorer medication adherence, increased anxiety and depressive symptoms, and poorer overall well-being ( P 's < .05)., Conclusions: Perceived unmet support needs during stay-at-home orders were associated with greater difficulty engaging in self-management behaviors and poorer overall well-being. Two brief items quickly identified individuals with unmet support needs.

Accurate understanding of COVID-19 safety recommendations early in the outbreak was complicated by inconsistencies in public health and media messages. We sought to characterize high-risk adults' knowledge of COVID-19 symptoms, prevention strategies, and prevention behaviors. We used data from the Chicago COVID-19 Comorbidities (C3) survey collected between March 13 thru March 20, 2020. A total of 673 predominately older adults with ≥ 1 chronic condition completed the telephone interview. Knowledge was assessed by asking participants to name three symptoms of COVID-19 and three actions to prevent infection. Participants were then asked if and how they had changed plans due to coronavirus. Most participants could identify three symptoms (71.0%) and three preventive actions (69.2%). Commonly reported symptoms included: fever (78.5%), cough (70.6%), and shortness of breath (45.2%); preventive actions included: washing hands (86.5%) and social distancing (86.2%). More than a third of participants reported social distancing themselves (38.3%), and 28.8% reported obtaining prescription medication to prepare for the outbreak. In multivariable analyses, no participant characteristics were associated with COVID-19 knowledge. Women were more likely than men, and Black adults were less likely than White adults to report practicing social distancing. Individuals with low health literacy were less likely to report obtaining medication supplies. In conclusion, though most higher-risk individuals were aware of social distancing as a prevention strategy early in the outbreak, less than half reported enacting it, and racial disparities were apparent. Consistent messaging and the provision of tangible resources may improve future adherence to safety recommendations.

Lewisite and many other similar arsenicals are warfare vesicants developed and weaponized for use in World Wars I and II. These chemicals, when exposed to the skin and other epithelial tissues, cause rapid severe inflammation and systemic damage. Here, we show that topically applied arsenicals in a murine model produce significant acute kidney injury (AKI), as determined by an increase in the AKI biomarkers NGAL and KIM-1. An increase in reactive oxygen species and ER stress proteins, such as ATF4 and CHOP, correlated with the induction of these AKI biomarkers. Also, TUNEL staining of CHOP-positive renal tubular cells suggests CHOP mediates apoptosis in these cells. A systemic inflammatory response characterized by a significant elevation in inflammatory mediators, such as IL-6, IFN-α, and COX-2, in the kidney could be the underlying cause of AKI. The mechanism of arsenical-mediated inflammation involves activation of AMPK/Nrf2 signaling pathways, which regulate heme oxygenase-1 (HO-1). Indeed, HO-1 induction with cobalt protoporphyrin (CoPP) treatment in arsenical-treated HEK293 cells afforded cytoprotection by attenuating CHOP-associated apoptosis and cytokine mRNA levels. These results demonstrate that topical exposure to arsenicals causes AKI and that HO-1 activation may serve a protective role in this setting., (© 2020 New York Academy of Sciences.)

Background: The US outbreak of coronavirus disease 2019 (COVID-19) accelerated rapidly over a short time to become a public health crisis., Objective: To assess how high-risk adults' COVID-19 knowledge, beliefs, behaviors, and sense of preparedness changed from the onset of the US outbreak (March 13-20, 2020) to the acceleration phase (March 27-April 7, 2020)., Design: Longitudinal, two-wave telephone survey., Participants: 588 predominately older adults with ≥ 1 chronic condition recruited from 4 active, federally funded studies in Chicago., Main Measures: Self-reported knowledge of COVID-19 symptoms and prevention, related beliefs, behaviors, and sense of preparedness., Key Results: From the onset to the acceleration phase, participants increasingly perceived COVID-19 to be a serious public health threat, reported more changes to their daily routine and plans, and reported greater preparedness. The proportion of respondents who believed they were "not at all likely" to get the virus decreased slightly (24.9 to 22.4%; p = 0.04), but there was no significant change in the proportion of those who were unable to accurately identify ways to prevent infection (29.2 to 25.7%; p 0.14). In multivariable analyses, black adults and those with lower health literacy were more likely to report less perceived susceptibility to COVID-19 (black adults: relative risk (RR) 1.62, 95% confidence interval (CI) 1.07-2.44, p = 0.02; marginal health literacy: RR 1.96, 95% CI 1.26-3.07, p < 0.01). Individuals with low health literacy remained more likely to feel unprepared for the outbreak (RR 1.80, 95% CI 1.11-2.92, p = 0.02) and to express confidence in the federal government response (RR 2.11, 95% CI 1.49-3.00, p < 0.001) CONCLUSIONS: Adults at higher risk for COVID-19 continue to lack critical knowledge about prevention. While participants reported greater changes to daily routines and plans, disparities continued to exist in perceived susceptibility to COVID-19 and in preparedness. Public health messaging to date may not be effectively reaching vulnerable communities.

Objectives: To determine the prevalence of cognitive impairment no dementia (CIND) among a diverse, community-based population, and establish associations between CIND and health literacy, chronic disease self-management and functional health status., Methods: 863 primary care adults without dementia aged 55-74. Adjusted logistic and linear regressions were used to assess associations between CIND (None, Mild, Moderate/Severe) and outcomes., Results: 36 % participants exhibited CIND. It was strongly associated with limited health literacy (Newest Vital Signs: Mild [OR 3.25; 95 % CI 1.93, 5.49], Moderate/Severe [OR 6.45; 95 % CI 3.16, 13.2]; Test of Functional Health Literacy in Adults: Mild [OR 3.46; 95 % CI 2.08, 5.75], Moderate/Severe [OR 8.82; 95 % CI 4.87, 16.0]; all p's < 0.001) and poor chronic disease self-management (Mild [B = -11.2; 95 % CI -13.5, -8.90], Moderate/Severe CI [B = -21.0; 95 % CI -23.6, -18.4]; both p's < 0.001). Associations between CIND and functional health status were non-significant., Conclusions: CIND was prevalent in this cohort, and strongly associated with requisite skills for managing everyday health needs., Practice Implications: Attention to subtle declines in chronic disease self-care may assist with CIND identification and care management within this population. When CIND is observed, clinicians should also expect and address difficulties with self-management., Competing Interests: Declaration of Competing Interest SDP receives research support from Omron Healthcare and previously received grant support from Pfizer, Inc. MSW receives research funding from Amgen and Merck, Sharpe & Dohme. He also has served as a paid consultant to Luto U.K., Pfizer and AB Imbev Foundation. RML, LMC, JWG, DC and AF have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The average readability level in the USA is a sixth grade level and for patients with chronic disease it is lower. Cirrhosis is a prevalent chronic disease that requires complex knowledge and instructions to manage. No research has been done about the understandability of online educational content for cirrhotic patients. Patients can find online materials curated by both general health platforms and high-volume liver transplant centers, and thus these materials were analyzed., Methods: After determining exclusion criteria, the websites of the top 20 general health platform results and the websites of the top 20 high-volume hepatology centers were analyzed. Readability was assessed using the Patient Education Materials Assessment Tool (Audiovisual Materials) (PEMAT-A/V), Flesch-Kincaid Grade Level tests, word counts, sentence counts, words per sentence, and time for an average sixth grader to read., Results: The mean grade level readabilities were 12.3 and 11.3 for the general resources and the transplant center resources, respectively. The online resources ranged from 9 to 389 sentences requiring an average of 9.8 min to read. The mean PEMAT-A/V scores were 70.05% for the general resources and 72.45% for the transplant center resources. There was a statistically significant difference in the Flesch-Kincaid grade level, sentence number, words per sentence, word count, and time for an average sixth grader to read the general resources and transplant center resources (P < 0.05)., Conclusions: The online resources both from health platforms and hepatology centers available to patients with cirrhosis are too long and complex and underscore the need for simpler and shorter resources., Competing Interests: Conflict of Interest None to declare.

Chronic graft-versus-host disease (cGVHD) is the leading late complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients receive multiple lines of systemic therapy until cGVHD resolves, but about 15% remain on systemic treatment for more than 7 years after cGVHD diagnosis. This study describes the clinical and biological factors of patients who present with cGVHD persisting for ≥7 years (persistent cGVHD). Patients with persistent cGVHD (n = 38) and those with cGVHD for <1 year (early cGVHD) (n = 83) were enrolled in a prospective cross-sectional natural history study. Patients in the persistent cGVHD group were a median of 10.2 years from cGVHD diagnosis (range 7-27 years). Fifty-eight percent of persistent cGVHD patients (22/38) were receiving systemic immunosuppression, compared to 88% (73/83) in the early cGVHD group. In multivariable analysis, bone marrow (BM) stem cell source, presence of ENA autoantibodies, higher NIH lung score, higher platelet counts, and higher IgA levels were significantly associated with persistent cGVHD. A high sensitivity panel of serum biomarkers including seven cytokines diagnostic for cGVHD was analyzed and showed significantly lower levels of BAFF and CXCL10 in patients with persistent cGVHD. In conclusion, standardly accepted clinical measures of disease severity may not accurately reflect disease activity in patients with persistent cGVHD. However, many patients with persistent cGVHD are still receiving systemic immunosuppression despite lacking evidence of disease activity. Development of reliable clinical biomarkers of cGVHD activity may help guide future systemic treatments., (© 2020 Wiley Periodicals, Inc.)

Introduction: The purpose of this report is to describe barriers and solutions to the implementation and optimization of a pragmatic trial that tests an evidence-based, patient-centered, low literacy intervention promoting diabetes self-care in rural primary care clinics., Methods: The two-arm pragmatic trial has been implemented in six rural family medicine clinics in Arkansas. It tests a self-management education and counseling intervention for patients with type 2 diabetes compared to enhanced usual care. Barriers and solutions were identified as issues arose and through interviews with clinic directors and clinic administrators and a focus group, interviews, and tracking reports with clinic health coaches who delivered the intervention., Results: Barriers to optimizing enrollment, intervention delivery, and data collection were addressed through targeted education of and relationship building with leadership, changing enrollment oversight, and ongoing training of health coaches., Conclusions: Successful implementation and optimization of this pragmatic clinical trial in rural primary care clinics was achieved through establishing common goals with clinic leadership, minimizing demands on clinic staff and administration, frequent contact and ongoing support of health coaches, and collaborative troubleshooting of issues with delivering the intervention., (© 2020 The Author(s).)

Objectives: We sought to investigate older patients' ability to correctly and efficiently dose multidrug regimens over nearly a decade and to explore factors predicting declines in medication self-management., Design: Longitudinal cohort study funded by the National Institute on Aging., Setting: One academic internal medicine clinic and six community health centers., Participants: Beginning in 2008, 900 English-speaking adults, aged 55 to 74 years, were enrolled in the study, completing a baseline (T1) assessment. To date, 303 participants have completed the same assessment 9 years postbaseline (T4)., Measurements: At T1, subjects were given a standardized, seven-drug regimen and asked to demonstrate how they would take medicine over 24 hours. The number of dosing errors made and times per day that a participant would take medicine were recorded. Health literacy was measured via the Newest Vital Sign, and cognitive decline was measured by the Mini-Mental State Examination., Results: Participants on average made 2.9 dosing errors (SD = 2.5 dosing errors; range = 0-21 dosing errors) of 21 potential errors at T1 and 5.0 errors (SD = 2.1 errors; range = 1-18 errors; P < .001) at T4. In a multivariate model, limited literacy (β = .69; 95% confidence interval [CI] = .18-1.20; P = .01), meaningful cognitive decline (β = 1.72; 95% CI = .70-2.74; P = .01), number of chronic conditions (β = .21; 95% CI = .07-.34; P = .01), and number of baseline dosing errors (β = -.76; 95% CI = -.85 to -.67; P < .001) were significant, independent predictors of changes in dosing errors. Most patients overcomplicated their daily medication schedule; no sociodemographic characteristics were predictive of poor regimen organization in multivariate models. In a multivariate model, there were no significant predictors of changes in regimen consolidation over time, except regimen consolidation at T1., Conclusions: Older patients frequently overcomplicated drug regimens and increasingly made more dosing errors over 9 years of follow-up. Patients with limited literacy, cognitive decline, and multimorbidity were at greatest risk for errors. J Am Geriatr Soc 68:569-575, 2020., (© 2019 The American Geriatrics Society.)