Clinical Practice Guideline: Age-Related Hearing Loss Executive Summary.

OBJECTIVE: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with an explanation of the support in the literature, the evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the Guideline Development Group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life. (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related quality of life at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing.

Clinical Practice Guideline: Age-Related Hearing Loss.

OBJECTIVE: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life (QOL). (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related QOL at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing.

Use of the electronic medical record to screen for high-risk geriatric patients in the emergency department.

Older adults with multimorbidities have the highest rate of emergency department (ED) usage. These patients are typically on numerous medications, may have underlying dementia, and often present with falls and delirium. Identifying these high-risk older adults for possible intervention is challenging in the ED setting since available screening methods are manual and resource-intensive. The objective is to study the electronic medical record (EMR) use for identifying high-risk older adults in ED. This feasibility study is conducted in an academic ED with 67 000 total and 24% geriatric (age ≥ 65 years) annual visits, American College of Emergency Physician (ACEP) accredited Level 1 Geriatric Emergency Department with an ED-based geriatric consultation program by incorporating criteria from existing manual geriatric screening instruments and the 4M framework into an automated EMR screen to identify high-risk geriatric patients. ED providers are then alerted by an EMR Best Practice Alert (BPA) if high-risk status is identified. Initial development and impact on geriatric ED consults are reported. During the study period, 7450 patient encounters occurred; 1836 (24.6%) encounters involved patients who were 65 years or older. A total of 1398 (76.1%) high-risk ED encounters resulted in BPA alerts using the EMR automated screen. BPA alerts resulted in 82 (5.9%) geriatric evaluations. We conclude that using the EMR to automate screening for older adults for high-risk geriatric conditions in the ED is feasible. An automated EMR screen with a BPA to ED providers identified a well-defined cohort of older patients appropriate for further ED geriatric evaluation.

Racial, ethnic and neighborhood socioeconomic differences in incidence of dementia: A regional retrospective cohort study.

BACKGROUND: Evidence on the effects of neighborhood socioeconomic disadvantage on dementia risk in racially and ethically diverse populations is limited. Our objective was to evaluate the relative extent to which neighborhood disadvantage accounts for racial/ethnic variation in dementia incidence rates. Secondarily, we evaluated the spatial relationship between neighborhood disadvantage and dementia risk. METHODS: In this retrospective study using electronic health records (EHR) at two regional health systems in Northeast Ohio, participants included 253,421 patients aged >60 years who had an outpatient primary care visit between January 1, 2005 and December 31, 2015. The date of the first qualifying visit served as the study baseline. Cumulative incidence of composite dementia outcome, defined as EHR-documented dementia diagnosis or dementia-related death, stratified by neighborhood socioeconomic deprivation (as measured by Area Deprivation Index) was determined by competing-risk regression analysis, with non-dementia-related death as the competing risk. Fine-Gray sub-distribution hazard ratios were determined for neighborhood socioeconomic deprivation, race/ethnicity, and clinical risk factors. The degree to which neighborhood socioeconomic position accounted for racial/ethnic disparities in the incidence of composite dementia outcome was evaluated via mediation analysis with Poisson rate models. RESULTS: Increasing neighborhood disadvantage was associated with increased risk of EHR-documented dementia diagnosis or dementia-related death (most vs. least disadvantaged ADI quintile HR = 1.76, 95% confidence interval = 1.69-1.84) after adjusting for age and sex. The effect of neighborhood disadvantage on this composite dementia outcome remained after accounting for known medical risk factors of dementia. Mediation analysis indicated that neighborhood disadvantage accounted for 34% and 29% of the elevated risk for composite dementia outcome in Hispanic and Black patients compared to White patients, respectively. CONCLUSION: Neighborhood disadvantage is related to the risk of EHR-documented dementia diagnosis or dementia-related death and accounts for a portion of racial/ethnic differences in dementia burden, even after adjustment for clinically important confounders.

Integration of a pharmacist-led pharmacogenomic service in a geriatric clinic: Barriers and outcomes.

OBJECTIVES: The primary objective was to identify the proportion of patients who successfully completed PGx testing. Secondary objectives included determining the proportion of patients with actionable PGx results, determining the proportion of patients with a baseline medication intervention within 6 months of successfully completing PGx testing, and identifying barriers for not completing testing. DESIGN: This was a single center, non-interventional, retrospective cohort study, approved by the institutional review board. SETTING AND PARTICIPANTS: Patients included were 65 years of age or older and referred for PGx testing from geriatric outpatient clinics between May 1, 2019 and July 31, 2020. OUTCOME MEASURES: This study aimed to assess the implementation of pharmacist-led pharmacogenomics (PGx) in the care of community-dwelling older adults in an outpatient clinic. Little is known about the acceptance and impact of this type of service within this population. RESULTS: Of the 67 patients included, majority were female (78%), white (76%), and an average age of 78 years ± 5.98 SD. Majority were insured by Original Medicare or Medicaid (61%), had a history of cognitive impairment (84%), had a referring diagnosis of anxiety (40%) or depression (67%), and were prescribed a selective serotonin reuptake inhibitor (69%) at baseline. Majority successfully completed PGx testing (72%), with 72% having actionable PGx findings and 83% having a pharmacological intervention made thereafter. Nineteen patients did not complete testing (28%), with the primary barrier being not having an appointment scheduled (63%). CONCLUSION: This study demonstrated majority of older adults were accepting of PGx testing and majority of findings were relevant to clinical care of anxiety, depression, or cognitive impairment.

Health care utilization and potentially preventable adverse outcomes of high-need, high-cost middle-aged and older adults: Needs for integrated care models with life-course approach.

PURPOSE OF THE RESEARCH: The success of modern health care increases life expectancy and prolongs the days of having multimorbidity and functional limitations; the so-defined "high need, high cost (HNHC)" state represents the extreme scenarios of care burden and complexity. This study aims to explore health care utilization and the risk of preventable adverse outcomes stratified by age and HNHC state. MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Health Insurance (NHI) database. People aged ≥40 years were included and further stratified by age (middle-aged: 40-64 and older adults: 65) and HNHC state (top 10% of spending). Health care utilization and drug consumption across different groups were obtained. The multimorbidity frailty index (mFI) was developed for further analysis. Cox regression models were used to examine the associations between HNHC and adverse clinical outcomes (preventable hospitalizations, preventable emergency department visits, and mortality). RESULTS: HNHC participants were older, had a higher mFI and drug consumption, and had higher health care utilization. Compared with non-HNHC participants, HNHC participants exhibited a 4.4-fold and 2.4-fold higher risk of preventable hospitalizations in middle-aged (HR=4.41; 95% CI, 4.17-4.65, p<0.01) and older adults (HR=2.44; 95% CI, 2.34-2.55, p<0.01). Similar risks were observed for preventable emergency department visits and mortality (all p<0.01). CONCLUSIONS: The HNHC state substantially increased health care utilization, polypharmacy, and potentially preventable adverse outcomes after adjustment for frailty. Intervention studies developing integrated care models using the life-course approach are needed to improve the quality of health care systems in super-aged societies.

Impact of a collaboration revolving around virtual capacity evaluations.

OBJECTIVE: To assess the impact of virtual capacity assessments on access to medical care, community supports, and transitions to higher levels of care. STUDY SETTING: Virtual capacity evaluations of homebound suspected elder abuse/neglect/financial exploitation victims identified via exclusion criteria and initiated by Cuyahoga County adult protective services (APS) and conducted with Cleveland Clinic Geriatric Medicine. STUDY DESIGN: A retrospective chart review was conducted in conjunction with APS using their database to determine the outcomes of individuals who underwent virtual capacity evaluation from May 2020 through September 2021. Variables collected included completion of a statement of expert evaluation, guardianship assignment, offering community services, transfer to a higher level of care, and establishment of primary care. DATA COLLECTION/EXTRACTION: Data were extracted from medical records and the APS database. Outcomes were measured as percentages. PRINCIPAL FINDINGS: Fifty-four individuals underwent evaluation. Statements of expert evaluation were completed in 38 cases (70%). Guardianship was assigned in 28 cases (52%). Community services were offered to 51 (89%). Thirty-one (57%) remained at home. At baseline, only 23 (43%) were receiving primary care. Post evaluation, 44 (81%) were connected or reconnected to their medical provider. CONCLUSION: Of individuals who underwent our virtual capacity evaluations, most were able to remain at home, offered community services for support, and linked to primary care.

Effects of a perioperative geriatric intervention for older adults with Cancer: A randomized clinical trial.

BACKGROUND: Older adults with gastrointestinal cancers undergoing surgery often experience poor outcomes, such as prolonged postoperative hospital length of stay (LOS), intensive care unit (ICU) use, hospital readmissions, and complications. Involvement of geriatricians in the care of older adults with cancer can improve outcomes. We conducted a randomized trial of a perioperative geriatric intervention (PERI-OP) in older patients with gastrointestinal cancer undergoing surgery. METHODS: From 9/2016-4/2019, we randomly assigned patients age ≥ 65 with gastrointestinal cancer planning to undergo surgical resection to receive PERI-OP or usual care. Patients assigned to PERI-OP met with a geriatrician preoperatively in the outpatient setting and postoperatively as an inpatient consultant. The primary outcome was postoperative hospital LOS. Secondary outcomes included postoperative ICU use, 90-day hospital readmission rates, and complication rates. We conducted intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: ITT analyses included 137/160 patients who underwent surgery (usual care = 68/78, intervention = 69/82). PP analyses included the 68 usual care patients and the 30/69 intervention patients who received the preoperative and postoperative intervention components. ITT analyses demonstrated no significant differences between intervention and usual care in postoperative hospital LOS (7.23 vs 8.21 days, P = 0.374), ICU use (23.2% vs 32.4%, P = 0.257), 90-day hospital readmission rates (21.7% vs 25.0%, P = 0.690), or complication rates (17.4% vs 20.6%, P = 0.668). In PP analyses, intervention patients had shorter postoperative hospital LOS (5.90 vs 8.21 days, P = 0.024), but differences in ICU use (13.3% vs 32.4%, P = 0.081), 90-day hospital readmission rates (16.7% vs 25.0%, P = 0.439), and complication rates (6.7% vs 20.6%, P = 0.137) remained non-significant. CONCLUSIONS: In this randomized trial, PERI-OP did not have a significant impact on postoperative hospital LOS, ICU use, hospital readmissions, or complications. However, the subgroup who received PERI-OP as planned experienced encouraging results. Future studies of PERI-OP should include efforts, such as telehealth, to ensure the intervention is delivered as planned.

Treatment and outcomes among patients ≥85 years hospitalized with community-acquired pneumonia.

Our objective was to describe community-acquired pneumonia (CAP) among patients ≥85 years and compare them to patients aged 65-74. This was a retrospective cohort study. The study setting included 638 hospitals in the USA participating in the Premier database from 2010 to 2015. The study participants were 488,382 adults aged ≥65 years hospitalized with CAP. Patients ≥85 years were more likely to be white (79.8% vs 76.2%), female (58.1% vs 48.3%), and admitted with aspiration pneumonia (17.1% vs 7.0%) as compared with those aged 65-75 years. They had higher rates of dementia (30.4% vs 7.8%), but lower rates of diabetes (11.2% vs 17.6%) and chronic obstructive pulmonary disease (25.5% vs 54.7%). While Staphylococcus aureus (33.4%) was the most common pathogen across all age groups, patients aged ≥85 were more likely to have Escherichia coli pneumonia (16.1% vs 10.7%) compared with those aged 65-74. In adjusted models, patients aged ≥85 had greater in-hospital mortality (OR 1.14, 95% CI 1.11 to 1.18), but were less likely to be admitted to the intensive care unit (OR 0.54, 95% CI 0.53 to 0.55) and receive mechanical ventilation (OR 0.47, 95% CI 0.46 to 0.48). They also had lower rates of acute kidney injury (OR 0.95, 95% CI 0.91 to 1.00) and Clostridium difficile infection (OR 0.91, 95% CI 0.85 to 0.99), shorter lengths of stay (mean multiplier 0.93, 95% CI 0.92 to 0.93) and lower cost (mean multiplier 0.81, 95% CI 0.80 to 0.81), and were more likely to be discharged to a skilled nursing facility (OR 2.19, 95% CI 2.15 to 2.24) or hospice (OR 2.19, 95% CI 2.11 to 2.27). In conclusion, patients aged ≥85 have different comorbidities and etiologies of CAP, receive less intense treatment, and have greater mortality than patients between 65 and 75 years.

COVID-19 in older adults.

The impact of COVID-19 varies by age group, and it has become clear that individuals over 65 years are disproportionately impacted by COVID-19 both in terms of severity of illness and mortality. Atypical presentations in older adults may result from pathophysiologic changes during aging and immune dysregulation because of the cumulative impact of chronic comorbidities. Herein we review the different clinical presentations of illness for older adults, the unique challenges faced by this population, and strategies for treatment.

Cognition and depression effects of androgen receptor axis-targeted drugs in men with prostate cancer: A systematic review.

CONTEXT: Novel androgen receptor axis-targeting drugs (ARATs) have been shown to improve outcomes in men with prostate cancer. Central nervous system androgen blockade may be harmful for older adults who may be at increased risk of adverse cognitive and psychologic effects. OBJECTIVE: To systematically evaluate the effect of ARATs on cognition and depression in men with metastatic prostate cancer. EVIDENCE ACQUISITION: We searched PubMed and EMBASE for articles published in English between September 2012 and September 2019 reporting cognition and depression outcomes in men receiving ARATs for metastatic prostate cancer using validated psychometric tools. The level of evidence and risk of bias were assessed using the GRADE approach for randomized clinical trials and observational studies. RESULTS: 15 reports studying 8954 men with metastatic castration-sensitive and -resistant, or non-metastatic castration-resistant prostate cancer were identified. Data were available for abiraterone, enzalutamide and apalutamide but not darolutamide. The mean (and 95% confidence interval) and median (and min-max) of the absolute scores and changes from baseline were included, when available. There was heterogeneity in the psychometric tools used which obviated statistical pooling of results. Very limited data assessing cognition suggested that abiraterone was associated with improved cognitive functioning or perhaps less cognitive harm versus enzalutamide. Fourteen reports assessed emotional wellbeing. ARATs reduced depressive symptoms when compared to prednisone alone or placebo but not compared to bicalutamide. Abiraterone may improve short-term emotional functioning relative to enzalutamide. The quality of evidence was low when examining ARAT effect on cognitive function and moderate when examining ARAT effect on depression. CONCLUSIONS: Depression was assessed more frequently than cognition in men receiving ARATs. Self-reported depression measures favored abiraterone over enzalutamide and both abiraterone and enzalutamide over placebo. Data evaluating apalutamide and darolutamide are lacking. Further studies of ARATs using validated clinician-based psycho-cognition tools along with self-reported measures in men with metastatic prostate cancer are needed.

Subjective Versus Objective Assessment of Cognitive Functioning in Primary Care.

PURPOSE: This study examined the clinical utility of highly efficient subjective and objective screens of cognitive impairment. METHOD: Participants (N = 124, age ≥ 65, mean = 73.59, SD = 6.26) completed a 2-item questionnaire of subjective memory functioning, a brief computerized cognitive test, and the Montreal Cognitive Assessment (MoCA). Next, participants were assigned to 1 of 4 conditions, based on their subjective (low/high) and objective (impaired/unimpaired) levels of cognitive functioning. Further analysis divided the sample into age-based groups (ie, age < 75, age ≥ 75). RESULTS: The proportion of participants in the impaired subsample (ie, MoCA < 26), who reported a high level of subjective concern about their memory, was low (ie, 0.15). Among unimpaired participants, analysis detected significant group differences across subjective memory levels (P < .0003) and age (P < .005) categories on one of the three tasks of the computerized test (ie, cognitive control). In contrast, the MoCA offered no differentiation between these groups. CONCLUSION: Screening protocols in which cognitive testing is administered subsequent to patient complaint are prone to underdiagnosis. In addition, common dementia screens are insensitive to subjective deficits and healthy cognitive aging. Therefore, they may lead to dismissing valid concerns that deserve preventive attention. Primary care needs efficient screening tools that are sensitive to prodromal decline.

Pilot Randomized Trial of a Transdisciplinary Geriatric and Palliative Care Intervention for Older Adults With Cancer.

BACKGROUND: Oncologists often struggle with managing the unique care needs of older adults with cancer. This study sought to determine the feasibility of delivering a transdisciplinary intervention targeting the geriatric-specific (physical function and comorbidity) and palliative care (symptoms and prognostic understanding) needs of older adults with advanced cancer. METHODS: Patients aged ≥65 years with incurable gastrointestinal or lung cancer were randomly assigned to a transdisciplinary intervention or usual care. Those in the intervention arm received 2 visits with a geriatrician, who addressed patients' palliative care needs and conducted a geriatric assessment. We predefined the intervention as feasible if >70% of eligible patients enrolled in the study and >75% of eligible patients completed study visits and surveys. At baseline and week 12, we assessed patients' quality of life (QoL), symptoms, and communication confidence. We calculated mean change scores in outcomes and estimated intervention effect sizes (ES; Cohen's d) for changes from baseline to week 12, with 0.2 indicating a small effect, 0.5 a medium effect, and 0.8 a large effect. RESULTS: From February 2017 through June 2018, we randomized 62 patients (55.9% enrollment rate [most common reason for refusal was feeling too ill]; median age, 72.3 years; cancer types: 56.5% gastrointestinal, 43.5% lung). Among intervention patients, 82.1% attended the first visit and 79.6% attended both. Overall, 89.7% completed all study surveys. Compared with usual care, intervention patients had less QoL decrement (-0.77 vs -3.84; ES = 0.21), reduced number of moderate/severe symptoms (-0.69 vs +1.04; ES = 0.58), and improved communication confidence (+1.06 vs -0.80; ES = 0.38). CONCLUSIONS: In this pilot trial, enrollment exceeded 55%, and >75% of enrollees completed all study visits and surveys. The transdisciplinary intervention targeting older patients' unique care needs showed encouraging ES estimates for enhancing patients' QoL, symptom burden, and communication confidence.

Integrating assessment of cognitive status in elderly cardiovascular care.

Cardiovascular clinicians tend to pay little attention to issues related to cognition, and yet those caring for older adults will encounter a variety of conditions that may lead to cognitive impairment. Most commonly, these include cardiovascular disease-specific conditions such as cerebrovascular disease or heart failure, but may also include neurodegenerative conditions, mood disorders, medication side effects and polypharmacy, and nutritional deficiencies and metabolic derangements among others. This review presents evidence supporting the importance of assessing cognitive status in older adults with cardiovascular disease, and suggests a practical approach to assessment and management of cognitive impairment in this population when it is found. Special attention is paid to the importance of collaboration between cardiovascular and geriatric specialists, and the value it may bring to patients.

Machine Learning Enhances the Efficiency of Cognitive Screenings for Primary Care.

BACKGROUND: Incorporation of cognitive screening into the busy primary care will require the development of highly efficient screening tools. We report the convergence validity of a very brief, self-administered, computerized assessment protocol against one of the most extensively used, clinician-administered instruments-the Montreal Cognitive Assessment (MoCA). METHOD: Two hundred six participants (mean age = 67.44, standard deviation [SD] = 11.63) completed the MoCA and the computerized test. Three machine learning algorithms (ie, Support Vector Machine, Random Forest, and Gradient Boosting Trees) were trained to classify participants according to the clinical cutoff score of the MoCA (ie, < 26) from participant performance on 25 features of the computerized test. Analysis employed Synthetic Minority Oversampling TEchnic to correct the sample for class imbalance. RESULTS: Gradient Boosting Trees achieved the highest performance (accuracy = 0.81, specificity = 0.88, sensitivity = 0.74, F1 score = 0.79, and area under the curve = 0.81). A subsequent K-means clustering of the prediction features yielded 3 categories that corresponded to the unimpaired (mean = 26.98, SD = 2.35), mildly impaired (mean = 23.58, SD = 3.19), and moderately impaired (mean = 17.24, SD = 4.23) ranges of MoCA score ( F = 222.36, P < .00). In addition, compared to the MoCA, the computerized test correlated more strongly with age in unimpaired participants (ie, MoCA ≥26, n = 165), suggesting greater sensitivity to age-related changes in cognitive functioning. CONCLUSION: Future studies should examine ways to improve the sensitivity of the computerized test by expanding the cognitive domains it measures without compromising its efficiency.

Geriatrics update 2018: Challenges in mental health, mobility, and postdischarge care.

A review of articles on geriatric topics from 2017 and 2018 revealed evidence supporting exercise for the elderly, early mobility for hospitalized patients, and oral anticoagulant therapy for atrial fibrillation to support cognitive function, and evidence against antipsychotic drugs for dementia-associated behaviors. No silver bullet was found for Alzheimer prevention or therapy.

Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition.

The Rho/ROCK pathway is activated in differentiated hepatic stellate cells (HSCs) and is necessary for assembly of actin stress fibers, contractility, and chemotaxis. Despite the importance of this pathway in HSC biology, physiological inhibitors of the Rho/ROCK pathway in HSCs are not known. We demonstrate that adenosine induces loss of actin stress fibers in the LX-2 cell line and primary HSCs in a manner indistinguishable from Rho/ROCK inhibition. Loss of actin stress fibers occurs via the A2a receptor at adenosine concentrations above 10 muM, which are present during tissue injury. We further demonstrate that loss of actin stress fibers is due to a cyclic adenosine monophosphate, protein kinase A-mediated pathway that results in Rho inhibition. Furthermore, a constitutively active Rho construct can inhibit the ability of adenosine to induce loss of actin stress fibers. Actin stress fibers are required for HSC contraction, and we demonstrate that adenosine inhibits endothelin-1 and lysophosphatidic acid-mediated HSC contraction. We propose that adenosine is a physiological inhibitor of the Rho pathway in HSCs with functional consequences, including loss of HSC contraction.

Adenosine inhibits cytosolic calcium signals and chemotaxis in hepatic stellate cells.

Adenosine is produced during cellular hypoxia and apoptosis, resulting in elevated tissue levels at sites of injury. Adenosine is also known to regulate a number of cellular responses to injury, but its role in hepatic stellate cell (HSC) biology and liver fibrosis is poorly understood. We tested the effect of adenosine on the cytosolic Ca2+ concentration, chemotaxis, and upregulation of activation markers in HSCs. We showed that adenosine did not induce an increase in the cytosolic Ca2+ concentration in LX-2 cells and, in addition, inhibited increases in the cytosolic Ca2+ concentration in response to ATP and PDGF. Using a Transwell system, we showed that adenosine strongly inhibited PDGF-induced HSC chemotaxis in a dose-dependent manner. This inhibition was mediated via the A(2a) receptor, was reversible, was reproduced by forskolin, and was blocked by the adenylate cyclase inhibitor 2,5-dideoxyadenosine. Adenosine also upregulated the production of TGF-beta and collagen I mRNA. In conclusion, adenosine reversibly inhibits Ca2+ fluxes and chemotaxis of HSCs and upregulates TGF-beta and collagen I mRNA. We propose that adenosine provides 1) a "stop" signal to HSCs when they reach sites of tissue injury with high adenosine concentrations and 2) stimulates transdifferentiation of HSCs by upregulating collagen and TGF-beta production.