Comprehensive Audiologic Analyses After Cisplatin-Based Chemotherapy.

Importance: Cisplatin is highly ototoxic but widely used. Evidence is lacking regarding cisplatin-related hearing loss (CRHL) in adult-onset cancer survivors with comprehensive audiologic assessments (eg, Words-in-Noise [WIN] tests, full-spectrum audiometry, and additional otologic measures), as well as the progression of CRHL considering comorbidities, modifiable factors associated with risk, and cumulative cisplatin dose. Objective: To assess CRHL with comprehensive audiologic assessments, including the WIN, evaluate the longitudinal progression of CRHL, and identify factors associated with risk. Design, Setting, and Participants: The Platinum Study is a longitudinal study of cisplatin-treated testicular cancer survivors (TCS) enrolled from 2012 to 2018 with follow-up ongoing. Longitudinal comprehensive audiologic assessments at Indiana University and Memorial Sloan Kettering Cancer Center included 100 participants without audiometrically defined profound hearing loss (HL) at baseline and at least 3.5 years from their first audiologic assessment. Data were analyzed from December 2013 to December 2022. Exposures: Factors associated with risk included cumulative cisplatin dose, hypertension, hypercholesterolemia, diabetes, tobacco use, physical inactivity, body mass index, family history of HL, cognitive dysfunction, psychosocial symptoms, and tinnitus. Main Outcomes and Measures: Main outcomes were audiometrically measured HL defined as combined-ears high-frequency pure-tone average (4-12 kHz) and speech-recognition in noise performance measured with WIN. Multivariable analyses evaluated factors associated with risk for WIN scores and progression of audiometrically defined HL. Results: Median (range) age of 100 participants at evaluation was 48 (25-67) years; median (range) time since chemotherapy: 14 (4-31) years. At follow-up, 78 (78%) TCS had audiometrically defined HL; those self-reporting HL had 2-fold worse hearing than TCS without self-reported HL (48 vs 24 dB HL; P < .001). A total of 54 (54%) patients with self-reported HL showed clinically significant functional impairment on WIN testing. Poorer WIN performance was associated with hypercholesterolemia (ß = 0.88; 95% CI, 0.08 to 1.69; P = .03), lower-education (F1 = 5.95; P = .004), and severity of audiometrically defined HL (ß̂ = 0.07; 95% CI, 0.06 to 0.09; P < .001). CRHL progression was associated with hypercholesterolemia (ß̂ = -4.38; 95% CI, -7.42 to -1.34; P = .01) and increasing age (ß̂ = 0.33; 95% CI, 0.15 to 0.50; P < .001). Importantly, relative to age-matched male normative data, audiometrically defined CRHL progression significantly interacted with cumulative cisplatin dose (F1 = 5.98; P = .02); patients given 300 mg/m2 or less experienced significantly less progression, whereas greater temporal progression followed doses greater than 300 mg/m2. Conclusions and Relevance: Follow-up of cisplatin-treated cancer survivors should include strict hypercholesterolemia control and regular audiological assessments. Risk stratification through validated instruments should include querying hearing concerns. CRHL progression relative to age-matched norms is likely associated with cumulative cisplatin dose; investigation over longer follow-up is warranted.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results From the ACHIEVE Trial.

BACKGROUND: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. METHODS: Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. RESULTS: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29-3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm -05:59 pm). CONCLUSIONS: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

Cross-Sectional Associations of Peripheral Hearing, Brain Imaging, and Cognitive Performance With Speech-in-Noise Performance: The Aging and Cognitive Health Evaluation in Elders Brain Magnetic Resonance Imaging Ancillary Study.

PURPOSE: Population-based evidence in the interrelationships among hearing, brain structure, and cognition is limited. This study aims to investigate the cross-sectional associations of peripheral hearing, brain imaging measures, and cognitive function with speech-in-noise performance among older adults. METHOD: We studied 602 participants in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) brain magnetic resonance imaging (MRI) ancillary study, including 427 ACHIEVE baseline (2018-2020) participants with hearing loss and 175 Atherosclerosis Risk in Communities Neurocognitive Study Visit 6/7 (2016-2017/2018-2019) participants with normal hearing. Speech-in-noise performance, as outcome of interest, was assessed by the Quick Speech-in-Noise (QuickSIN) test (range: 0-30; higher = better). Predictors of interest included (a) peripheral hearing assessed by pure-tone audiometry; (b) brain imaging measures: structural MRI measures, white matter hyperintensities, and diffusion tensor imaging measures; and (c) cognitive performance assessed by a battery of 10 cognitive tests. All predictors were standardized to z scores. We estimated the differences in QuickSIN associated with every standard deviation (SD) worse in each predictor (peripheral hearing, brain imaging, and cognition) using multivariable-adjusted linear regression, adjusting for demographic variables, lifestyle, and disease factors (Model 1), and, additionally, for other predictors to assess independent associations (Model 2). RESULTS: Participants were aged 70-84 years, 56% female, and 17% Black. Every SD worse in better-ear 4-frequency pure-tone average was associated with worse QuickSIN (-4.89, 95% confidence interval, CI [-5.57, -4.21]) when participants had peripheral hearing loss, independent of other predictors. Smaller temporal lobe volume was associated with worse QuickSIN, but the association was not independent of other predictors (-0.30, 95% CI [-0.86, 0.26]). Every SD worse in global cognitive performance was independently associated with worse QuickSIN (-0.90, 95% CI [-1.30, -0.50]). CONCLUSIONS: Peripheral hearing and cognitive performance are independently associated with speech-in-noise performance among dementia-free older adults. The ongoing ACHIEVE trial will elucidate the effect of a hearing intervention that includes amplification and auditory rehabilitation on speech-in-noise understanding in older adults. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25733679.

Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

OBJECTIVE: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment. STUDY DESIGN: Randomized, controlled, single-site, early phase II, superiority trial. SETTING: Tertiary academic medical center. PARTICIPANTS: One hundred fifty participants aged 55 to 75 years with early ARHL (severity defined as borderline to moderate) and amnestic mild cognitive impairment will be included. INTERVENTIONS: Participants will be randomized 1:1 to a best practice hearing intervention or a health education control. MAIN OUTCOME MEASURES: The primary study outcome is cognition measured by the Alzheimer Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite. Secondary outcomes include additional measures of cognition, social engagement, and brain organization/connectivity. RESULTS: Trial enrollment will begin in early 2024. CONCLUSIONS: After its completion in 2028, the EARHLI trial should offer evidence on the effect of hearing treatment versus a health education control on cognitive performance, social engagement, and brain organization/connectivity in 55- to 75-year-old community-dwelling adults with early ARHL and amnestic mild cognitive impairment.

Elementos de datos comunes para la artrogriposis múltiple congénita: Un marco internacional.

OBJETIVO: Para facilitar los estudios multicéntricos y la investigación clínica internacional, este estudio pretende identificar de forma consensuada los elementos de datos estandarizados para la artrogriposis múltiple congénita (AMC). MÉTODO: Estudio de métodos mixtos de grupos de discusión y tres rondas de encuestas Delphi modificadas para llegar a un consenso utilizando dos escalas de clasificación por niveles. RESULTADOS: En total, 45 expertos clínicos y adultos con experiencia vivida (incluidos 12 miembros de un consorcio de AMC) participaron en este estudio procedentes de 11 países: Norteamérica, Europa y Australia. Los CDEs incluyen 321 elementos de datos y 19 medidas estandarizadas en varios dominios desde el desarrollo fetal hasta la edad adulta. Los elementos de datos relativos a los rasgos fenotípicos del CDEs se mapearon de acuerdo con la Ontología de Fenotipos Humanos. Se identificaron como principales facilitadores la estructura de gobernanza universal, protocolos operados de forma local y los planes de sostenibilidad, mientras que los principales obstáculos observados son la capacidad limitada para compartir datos y la necesidad de una infraestructura informática federada. INTERPRETACIÓN: La recopilación de datos sistemáticos sobre la AMC mediante CDEs permitirá investigar las vías etiológicas, describir el perfil epidemiológico y establecer correlaciones genotipo­fenotipo de forma estandarizada. Los CDEs propuestos facilitarán las colaboraciones multidisciplinares internacionales mejorando los estudios a gran escala y las oportunidades para compartir datos, translación de conocimiento y difusión.

Treating Benign Ovarian Lesions in the Pediatric Population: A Single Institution's Retrospective Investigation of Laparoscopy Versus Open Repair.

Background: Benign ovarian lesions in the pediatric population have variable risk of recurrence or development of metachronous lesions, leading to variations in operative approach. Our study compares outcomes with differing surgical approaches to better elucidate risk of recurrent or metachronous lesions, time to development of these lesions, and hospital length of stay to determine if one operative approach has superior outcomes. Methods: We retrospectively examined data from Indiana University Health facilities from 2002 to 2020. Patients ≤18 years old who underwent surgical management of a benign ovarian lesion were included. Patients were categorized as undergoing oophorectomy versus ovarian sparing surgery (OSS), with open and laparoscopic approaches. Significance was defined as P < .05. Results: We identified 127 patients who underwent an open (n = 65) versus laparoscopic (n = 55) surgical approach. Patients undergoing open surgery had a greater mean size of lesion (P = .05) and longer length of stay (P < .01). Complication rates (P = .1), rates of developing a metachronous or recurrent lesion postoperatively (P = .47), and time to formation of additional lesions were similar between groups (P = .25). The incidence of identifying an additional lesion after surgery was 14.2% (n = 18) in the mean time of 29.5 ± 31.6 months [SEM 7.5]. Risk of developing a metachronous lesion was similar regardless of the operative approach. Surgery for recurrent ovarian lesions was rare and occurred in only 1 case. Conclusions: Laparoscopic surgery was performed for smaller lesions and was associated with a shorter length of hospital stay. Laparoscopic and OSS was found to have no increased risk of developing metachronous lesions nor increased reoperative risk compared with traditional open and oophorectomy techniques.

Éléments de données communs pour l'arthrogrypose multiple congénitale: Un cadre international.

OBJECTIF: Afin de faciliter les études multisites et la recherche clinique d'envergure internationale, cette étude a pour but d'identifier des éléments de données communs (EDCs) normalisés et fondés sur un consensus pour l'arthrogrypose multiple congénitale (AMC). MÉTHODE: Une étude à méthodes mixtes comprenant plusieurs groupes de discussion et trois séries d'enquêtes Delphi modifiées pour parvenir à un consensus ont été menées. RÉSULTATS: Dans l'ensemble, 45 experts cliniques ainsi qu'adultes ayant une expérience vécue (dont 12 membres d'un consortium d'AMC) ont participé à cette étude à travers 11 pays en Amérique du Nord, Europe et Australie. Les EDCs comprennent 321 éléments de données et 19 mesures standardisées dans divers domaines, du développement du fœtus à l'âge adulte. Les éléments de données relatifs aux traits phénotypiques de l'AMC ont été cartographiés conformément à l'ontologie du phénotype humain (HPO). Une structure de gouvernance universelle, des protocoles de fonctionnement et des plans de développement durable ont été identifiés comme les principaux facilitateurs considérant que la capacité limitée de partage des données et la nécessité d'une infrastructure informatique fédérée étaient les principaux obstacles. INTERPRÉTATION: Une collecte de données systématiques sur l'AMC à l'aide d'EDCs permettra d'étudier sur les voies étiologiques, décrire le profil épidémiologique, et établir des corrélations génotype­phénotype de manière standardisée. Les EDCs proposés faciliteront les collaborations internationales multidisciplinaires en améliorant à grande échelle les études multicentriques, les possibilités de partage des données, ainsi que le transfert et la diffusion des connaissances.

Common data elements for arthrogryposis multiplex congenita: An international framework.

AIM: To facilitate multisite studies and international clinical research, this study aimed to identify consensus-based, standardized common data elements (CDEs) for arthrogryposis multiplex congenita (AMC). METHOD: A mixed-methods study comprising of several focus group discussions and three rounds of modified Delphi surveys to achieve consensus using two tiered-rating scales were conducted. RESULTS: Overall, 45 clinical experts and adults with lived experience (including 12 members of an AMC consortium) participated in this study from 11 countries in North America, Europe, and Australia. The CDEs include 321 data elements and 19 standardized measures across various domains from fetal development to adulthood. Data elements pertaining to AMC phenotypic traits were mapped according to the Human Phenotype Ontology. A universal governance structure, local operating protocols, and sustainability plans were identified as the main facilitators, whereas limited capacity for data sharing and the need for a federated informatics infrastructure were the main barriers. INTERPRETATION: Collection of systematic data on AMC using CDEs will allow investigations on etiological pathways, describe epidemiological profile, and establish genotype-phenotype correlations in a standardized manner. The proposed CDEs will facilitate international multidisciplinary collaborations by improving large-scale studies and opportunities for data sharing, knowledge translation, and dissemination.

An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) progression is associated with dysfunctional mitochondria and bioenergetics impairment. However, no data about the relationship between mitochondrial supercomplexes (hmwSC) formation and ATP production rates in HCC are available. Our group has developed an adenosine derivative, IFC-305, which improves mitochondrial function, and it has been proposed as a therapeutic candidate for HCC. We aimed to determine the role of IFC-305 on both mitochondrial structure and bioenergetics in a sequential cirrhosis-HCC model in rats. Our results showed that IFC-305 administration decreased the number and size of liver tumors, reduced the expression of tumoral markers, and reestablished the typical architecture of the hepatic parenchyma. The livers of treated rats showed a reduction of mitochondria number, recovery of the mtDNA/nDNA ratio, and mitochondrial length. Also, IFC-305 increased cardiolipin and phosphatidylcholine levels and promoted hmwSC reorganization with changes in the expression levels of hmwSC assembly-related genes. IFC-305 in HCC modified the expression of several genes encoding elements of electron transport chain complexes and increased the ATP levels by recovering the complex I, III, and V activity. We propose that IFC-305 restores the mitochondrial bioenergetics in HCC by normalizing the quantity, morphology, and function of mitochondria, possibly as part of its hepatic restorative effect.

Recruitment and baseline data of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study: A randomized trial of a hearing loss intervention for reducing cognitive decline.

INTRODUCTION: Hearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best-practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results. METHODS: Multiple strategies were used to recruit community-dwelling 70-84-year-old participants with adult-onset hearing loss who were free of substantial cognitive impairment from the parent ARIC study and de novo from the surrounding communities into the trial. Participants completed telephone screening, an in-person hearing, vision, and cognitive screening, and a comprehensive hearing assessment to determine eligibility. RESULTS: Over a 24-month period, 3004 telephone screenings resulted in 2344 in-person hearing, vision, and cognition screenings and 1294 comprehensive hearing screenings. Among 1102 eligible, 977 were randomized into the trial (median age = 76.4 years; 53.5% female; 87.8% White; 53.3% held a Bachelor's degree or higher). Participants recruited through the ARIC study were recruited much earlier and were less likely to report hearing loss interfered with their quality of life relative to participants recruited de novo from the community. Minor differences in baseline hearing or health characteristics were found by recruitment route (i.e., ARIC study or de novo) and by study site. DISCUSSION: The ACHIEVE study successfully completed enrollment over 2 years that met originally projected rates of recruitment. Substantial operational and scientific efficiencies during study startup were achieved through embedding this trial within the infrastructure of a longstanding and well-established observational study. Highlights: The ACHIEVE study tests the effect of hearing intervention on cognitive decline.The study is partially nested within an existing cohort study.Over 2 years, 977 participants recruited and enrolled.Eligibility assessed by telephone and in-person for hearing, vision, and cognitive screening.The ACHIEVE study findings will have significant public health implications.

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

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

Hearing loss and cognition: A protocol for ensuring speech understanding before neurocognitive assessment.

INTRODUCTION: Many neurocognitive evaluations involve auditory stimuli, yet there are no standard testing guidelines for individuals with hearing loss. The ensuring speech understanding (ESU) test was developed to confirm speech understanding and determine whether hearing accommodations are necessary for neurocognitive testing. METHODS: Hearing was assessed using audiometry. The probability of ESU test failure by hearing status was estimated in 2679 participants (mean age: 81.4 ± 4.6 years) using multivariate logistic regression. RESULTS: Only 2.2% (N = 58) of participants failed the ESU test. The probability of failure increased with hearing loss severity; similar results were observed for those with and without mild cognitive impairment or dementia. DISCUSSION: The ESU test is appropriate for individuals who have variable degrees of hearing loss and cognitive function. This test can be used prior to neurocognitive testing to help reduce the risk of hearing loss and compromised auditory access to speech stimuli causing poorer performance on neurocognitive evaluation.

Impact of pain and adverse health outcomes on long-term US testicular cancer survivors.

BACKGROUND: No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain. METHODS: Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a ß^ of more than 2 are clinically important and reported below. RESULTS: Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38-53 years; median time since chemotherapy = 10.7 years, IQR = 7.2-16.0 years), median adverse health outcomes number was 5 (IQR = 3-7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P < .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (ß^ = -3.72; P = .001), diabetes (ß^ = -4.41; P = .037), obesity (ß^ = -2.01; P = .036), and fatigue (ß^ = -8.58; P < .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (ß^ = 3.63; P = .0006). Risk factors for pain-related functional impairment included lower extremity location (ß^ = 2.15; P = .04) and concomitant peripheral artery disease (ß^ = 4.68; P < .001). Global physical health score reductions were associated with diabetes (ß^ = -3.81; P = .012), balance or equilibrium problems (ß^ = -3.82; P = .003), cognitive dysfunction (ß^ = -4.43; P < .0001), obesity (ß^ = -3.09; P < .0001), peripheral neuropathy score (ß^ = -2.12; P < .0001), and depression (ß^ = -3.17; P < .0001). CONCLUSIONS: Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment.

Humanin ameliorates TBI-related cognitive impairment by attenuating mitochondrial dysfunction and inflammation.

Traumatic brain injury (TBI) often results in a reduction of the capacity of cells to sustain energy demands, thus, compromising neuronal function and plasticity. Here we show that the mitochondrial activator humanin (HN) counteracts a TBI-related reduction in mitochondrial bioenergetics, including oxygen consumption rate. HN normalized the disruptive action of TBI on memory function, and restored levels of synaptic proteins (synapsin 1 and p-CREB). HN also counteracted TBI-related elevations of pro-inflammatory cytokines in plasma (TNF-α, INF-y, IL 17, IL 5, MCP 5, GCSF, RANNETS, sTNFRI) as well as in the hippocampus (gp-130 and p-STAT3). Gp-130 is an integral part of cytokine receptor impinging on STAT3 (Tyr-705) signaling. Furthermore, HN reduced astrocyte proliferation in TBI. The overall evidence suggests that HN plays an integral role in normalizing fundamental aspects of TBI pathology which are central to energy balance, brain function, and plasticity.

Depression and Health-Related Quality of Life Among Older Adults With Hearing Loss in the ACHIEVE Study.

Hearing loss is associated with cognitive/physical health; less is known about mental health. We investigated associations between hearing loss severity, depression, and health-related quality of life among older adults with unaided hearing loss. Data (N = 948) were from the Aging and Cognitive Health Evaluation in Elders Study. Hearing was measured by pure-tone average (PTA), Quick Speech-in-Noise (QuickSIN) test, and the Hearing Handicap Inventory for the Elderly (HHIE-S). Outcomes were validated measures of depression and health-related quality of life. Associations were assessed by negative binomial regression. More severe hearing loss was associated with worse physical health-related quality of life (ratio: .98, 95% CI: .96, 1.00). Better QuickSIN was associated with higher mental health-related quality of life (1.01 [1.00, 1.02]). Worse HHIE-S was associated with depression (1.24 [1.16, 1.33]) and worse mental (.97 [.96, .98]) and physical (.95 [ .93, .96]) health-related quality of life. Further work will test effects of hearing intervention on mental health.

Loneliness and Social Network Characteristics Among Older Adults With Hearing Loss in the ACHIEVE Study.

BACKGROUND: Hearing loss is linked to loneliness and social isolation, but evidence is typically based on self-reported hearing. This study quantifies the associations of objective and subjective hearing loss with loneliness and social network characteristics among older adults with untreated hearing loss. METHODS: This study uses baseline data (N = 933) from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study. Hearing loss was quantified by the better ear, speech-frequency pure tone average (PTA), Quick Speech-in-Noise test, and hearing-related quality of life. Outcomes were validated measures of loneliness and social network characteristics. Associations were assessed by Poisson, negative binomial, and linear regression adjusted for demographic, health, and study design characteristics. RESULTS: Participants were mean of 76.8 (4.0) years, 54.0% female, and 87.6% White. Prevalence of loneliness was 38%. Worse PTA was associated with a 19% greater prevalence of moderate or greater loneliness (prevalence ration [PR]: 1.19.95% CI: 1.06, 1.33). Better speech-in-noise recognition was associated with greater social network characteristics (eg, larger social network size [IRR: 1.04, 95% CI: 1.00, 1.07]). Worse hearing-related quality of life was associated with a 29% greater prevalence of moderate or greater loneliness (PR: 1.29, 95% CI: 1.19, 1.39) and worse social network characteristics (eg, more constricted social network size [IRR: 0.96, 95% CI: 0.91, 1.00]). CONCLUSIONS: Results suggest the importance of multiple dimensions of hearing to loneliness and social connectedness. Hearing-related quality of life may be a potentially useful, easily administered clinical tool for identifying older adults with hearing loss associated with greater loneliness and social isolation.

Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

An adenosine derivative prevents the alterations observed in metabolic syndrome in a rat model induced by a rich high-fat diet and sucrose supplementation.

Metabolic syndrome is a multifactorial disease with high prevalence worldwide. It is related to cardiovascular disease, diabetes, and obesity. Approximately 80% of patients with metabolic syndrome have some degree of fatty liver disease. An adenosine derivative (IFC-305) has been shown to exert protective effects in models of liver damage as well as on elements involved in central metabolism; therefore, here, we evaluated the effect of IFC-305 in an experimental model of metabolic syndrome in rats induced by a high-fat diet and 10% sucrose in drinking water for 18 weeks. We also determined changes in fatty acid uptake in the Huh-7 cell line. In the experimental model, increases in body mass, serum triglycerides and proinflammatory cytokines were induced in rats, and the adenosine derivative significantly prevented these changes. Interestingly, IFC-305 prevented alterations in glucose and insulin tolerance, enabling the regulation of glucose levels in the same way as in the control group. Histologically, the alterations, including mitochondrial morphological changes, observed in response to the high-fat diet were prevented by administration of the adenosine derivative. This compound exerted protective effects against metabolic syndrome, likely due to its action in metabolic regulation, such as in the regulation of glucose blood levels and hepatocyte fatty acid uptake.

Mechanisms for the interaction of the milk fat globule membrane with the plasma membrane of gut epithelial cells.

The milk fat globule membrane (MFGM) provides infants and adults with several health benefits. These are not derived solely from its unique composition, but also from arrangement of lipids in the MFGM that, in the case of newborns, could reach the intestine partially intact. Fluorochromes associated with lipid derivatives were used to prove a fusion process between the MFGM and the cellular membrane of differentiated Caco-2 cells. To explore the mechanism of this interaction, incubations of MFGM with Caco-2 cells were carried out in the presence of fusogenic agents or compounds that block other MFGM interaction pathways with cells. Confocal fluorescence microscopy provided visual evidence of the fusion process. Lastly, determination on the lipid profile of cells after their interaction with MFGM indicated a metabolic rearrangement of lipids leading to accumulation of triacylglycerols.

Green hospital pharmacy: A sustainable approach to the medication use process in a tertiary hospital. / [Artículo traducido] Farmacia hospitalaria ecológica: un enfoque sostenible del proceso de utilización de medicamentos en un hospital de tercer nivel.

BACKGROUND: Sustainable management of healthcare waste has a positive impact on the global environment. In order to reduce it, the sustainable practice of the pharmacotherapeutic process in all its stages is essential. OBJECTIVE: To analyse the sustainability strategies proposed by the pharmacy service to reduce drug waste derived from the pharmacotherapeutic process. SECONDARY OBJECTIVES: To analyse the stage of the pharmacotherapeutic process and the number and type of drugs involved. METHODS: The study was carried out in a tertiary-level hospital. To coordinate the proposals, a referent pharmacist from every pharmacy department area was selected. Four stages of the process were evaluated (management, validation, dispensing and compounding), patients concerned were classified as outpatients or inpatients, and drugs potentially involved were analysed by the administration route: Into oral or parenteral. RESULTS: Twenty eight ideas were proposed, which could affect more than 1200 drugs. 39.3% would affect the validation process, 17.9% the procurement management, 17.9% dispensing, and 7.1% the compounding. Implementation feasibility and acceptability of these proposals were evaluated. Those with the greatest potential were: Limiting the duration of treatments when possible, favouring the implementation of computer prescription order entry, favouring the use of the oral route over the parenteral route, and implementing computers in the preparation areas to avoid the use of paper guides. DISCUSION: In our study, many ideas have been proposed by hospital pharmacists to improve the sustainability of the medication use process. When assessing these proposals by impact and feasibility, according to our results, shorten as much as possible the duration of treatments, computerization of the medication use process, and oral administration over intravenous should be prioritized in order to reduce environmental impact.