Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.

BACKGROUND: Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. METHODS: The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. FINDINGS: From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0·200 [95% CI -0·256 to -0·144] in the hearing intervention group and -0·202 [-0·258 to -0·145] in the control group; difference 0·002 [-0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. INTERPRETATION: The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. FUNDING: US National Institutes of Health.

Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis.

The merger of photoredox catalysis with transition metal catalysis, termed metallaphotoredox catalysis, has become a mainstay in synthetic methodology over the past decade. Metallaphotoredox catalysis has combined the unparalleled capacity of transition metal catalysis for bond formation with the broad utility of photoinduced electron- and energy-transfer processes. Photocatalytic substrate activation has allowed the engagement of simple starting materials in metal-mediated bond-forming processes. Moreover, electron or energy transfer directly with key organometallic intermediates has provided novel activation modes entirely complementary to traditional catalytic platforms. This Review details and contextualizes the advancements in molecule construction brought forth by metallaphotocatalysis.

Ablation Rates and Long-Term Outcome Following Low-Dose Radioiodine for Differentiated Thyroid Cancer in the West of Scotland: A Retrospective Analysis.

OBJECTIVE: Low-dose radioiodine is an accepted means of remnant ablation in patients with low- to intermediate-risk differentiated thyroid cancer (DTC) based on the results of several phase III trials. We evaluated the rate of ablation success and long-term recurrence outcomes in the first 3 years of implementing this practice at our institution. METHODS: Patients who received 1.1 to 1.2 gigabecquerel (30 millicurie) were identified retrospectively from the radionuclide database, January 1, 2012, to December 31, 2014, inclusive. Successful ablation was defined as Iodine-131uptake <0.1% on diagnostic scan and Tg level <2.0 ng/mL at 6 to 8 months after treatment. Follow-up was conducted annually for 10 years and relapse rates were determined based on the available clinical, radiological, and biochemical information. RESULTS: We identified 114 patients, 109 of whom had dual response assessment. The median age was 43 years (range, 14 to 80 years). Almost 70% had T1 or T2 tumors, with T3 and T4 tumors recorded in 27% and 2.5% of patients, respectively. Nodal staging was performed in just over 30% and involved lymph nodes were detected in 21% (N1a 8% and N1b 13%). Ablation success based on diagnostic scan alone was 94.7% (108/114), Tg alone 94.7% (108/114), and on both modalities was 90.4% (103/114). CONCLUSION: Remnant ablation was achieved in >90%, and the corresponding clinical recurrence rate was only 1.8% despite the inclusion of patients with locally advanced disease. Low-dose radioiodine is effective and may be suitable for a proportion of patients with higher-risk DTC.

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.

Peripheral Neuropathy and Vision and Hearing Impairment in US Adults With and Without Diabetes.

We aimed to assess the associations of peripheral neuropathy (PN) with vision and hearing impairment among adults aged ≥40 years who attended the lower-extremity disease exam for the National Health and Nutrition Examination Survey (United States, 1999-2004). Overall, 11.8% (standard error (SE), 0.5) of adults had diabetes, 13.2% (SE, 0.5) had PN (26.6% (SE, 1.4) with diabetes, 11.4% (SE, 0.5) without diabetes), 1.6% (SE, 0.1) had vision impairment, and 15.4% (SE, 1.1) had hearing impairment. The prevalence of vision impairment was 3.89% (95% CI: 2.99, 5.05) among adults with PN and 1.29% (95% CI: 1.04, 1.60) among adults without PN (P < 0.001). After adjustment, PN was associated with vision impairment overall (odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.03, 2.13) and among adults without diabetes (OR = 1.80, 95% CI: 1.17, 2.77) but not among adults with diabetes (P for interaction = 0.018). The prevalence of hearing impairment was 26.5% (95% CI: 20.4, 33.7) among adults with PN and 14.2% (95% CI: 12.4, 16.3) among adults without PN (P < 0.001). The association of PN with moderate/severe hearing impairment was significant overall (OR = 2.55, 95% CI: 1.40, 4.64) and among adults without diabetes (OR = 3.26, 95% CI: 1.80, 5.91). Overall, these findings suggest an association between peripheral and audiovisual sensory impairment that is unrelated to diabetes.

Association Between Adult-Onset Hearing Loss and Income: A Systematic Review.

INTRODUCTION: Hearing loss has been shown to be associated with both negative health outcomes and low socioeconomic position, including lower income. Despite this, a thorough review of the existing literature on this relationship has not yet been performed. OBJECTIVES: To evaluate available literature on the possible association between income and adult-onset hearing loss. DESIGN: A search was conducted in eight databases for all relevant literature using terms focused on hearing loss and income. Studies reporting the presence or absence of an association between income and hearing loss, full-text English-language access, and a predominantly adult population (≥18 years old) were eligible. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. RESULTS: The initial literature search yielded 2994 references with three additional sources added through citation searching. After duplicate removal, 2355 articles underwent title and abstract screening. This yielded 161 articles eligible for full-text review resulting in 46 articles that were included in qualitative synthesis. Of the included studies, 41 of 46 articles found an association between income and adult-onset hearing loss. Due to heterogeneity among study designs, a meta-analysis was not performed. CONCLUSIONS: The available literature consistently supports an association between income and adult-onset hearing loss but is limited entirely to cross-sectional studies with the directionality remaining unknown. An aging population and the negative health outcomes associated with hearing loss, emphasize the importance of understanding and addressing the role of social determinants of health in the prevention and management of hearing loss.

The association of hearing loss with frailty among community-dwelling older adults: findings from the National Health and Aging Trends Study.

BACKGROUND: The identification of modifiable risk factors is crucial for the prevention and/or reversal of frailty, which is associated with significant morbidity and mortality. Hearing loss affects two-thirds of older adults in the United States (U.S.) and is associated with physical and cognitive decline which may increase frailty risk. We investigated the association of hearing loss and hearing aid use with frailty and pre-frailty in a nationally representative sample of older adults in the U.S. METHODS: Cross-sectional analysis of the National Health and Aging Trends Study (2021 round). The better-hearing ear pure-tone average (BPTA) at speech-frequencies (0.5-4 kHz) was modeled continuously (per 10 dB) and categorically (no ≤ 25 dB, mild 26-40 dB, moderate or greater > 40 dB hearing loss). Hearing aid use was self-reported. The physical frailty phenotype (frail, pre-frail, robust) was determined based on Fried criteria: unintentional weight loss, exhaustion, low physical activity, weakness, slow walking speed. We used multinomial multivariable regression adjusted for sociodemographic and health characteristics (odds ratios [95% Confidence Intervals]). RESULTS: Among 2,361 participants (mean age = 81 years, 56% female, 19% Black), 860 (36%) had mild and 864 (37%) had moderate or greater hearing loss. Worse hearing was associated with greater odds of being frail versus robust (OR = 1.20 [1.05-1.38] per 10 dB difference). Categorically, moderate or greater hearing loss was associated with greater odds of being frail (OR = 1.84 [1.01-3.08]) and pre-frail (OR = 1.46 [1.01-2.10]) versus robust. Among 1,724 participants with hearing loss, compared to hearing aid users (N = 522), nonusers had greater odds of being frail (OR = 2.54 [1.54-4.18]) and pre-frail (OR = 1.51 [1.05-2.17]) versus robust, and frail versus pre-frail (OR = 1.68 [1.04-2.72]). CONCLUSIONS: In a nationally representative sample of older adults in the U.S., using gold-standard hearing measures and a validated frailty phenotype, hearing loss and lack of hearing aid use was cross-sectionally associated with frailty and pre-frailty. Future longitudinal studies are needed to establish if hearing loss is a risk factor for frailty, which may have significant clinical importance.

Concurrent hearing and vision impairment and 8-year memory decline in community-dwelling older adults.

BACKGROUND: Hearing and vision impairments are risk factors for cognitive decline; less is known about dual sensory impairment. This study quantifies the association between dual sensory impairment and 8-year change in memory among older adults. METHODS: Data (N = 5552) were from the National Health and Aging Trends Study. Memory (immediate/delayed word recall, subjective memory) was measured annually (2011 to 2019). Hearing and vision impairments were measured by self-report. Association between dual sensory impairment and 8-year change in memory was assessed using multivariate linear mixed effect models and generalized logistic mixed models. RESULTS: Rate of memory decline was most accelerated among participants with dual sensory impairment. For example, 8-year decline in delayed word recall was -1.03 (95% confidene interval: -1.29, -0.77) for dual sensory impairment versus -0.79 (-0.92, -0.67) for single and -0.56 (-0.63, -0.48) for no impairment. CONCLUSION: Older adults with dual sensory impairment may be at particularly higher risk for cognitive decline.

Development, assessment, and monitoring of audiologic treatment fidelity in the aging and cognitive health evaluation in elders (ACHIEVE) randomised controlled trial.

OBJECTIVE: Studies investigating hearing interventions under-utilise and under-report treatment fidelity planning, implementation, and assessment. This represents a critical gap in the field that has the potential to impede advancements in the successful dissemination and implementation of interventions. Thus, our objective was to describe treatment fidelity planning and implementation for hearing intervention in the multi-site Ageing and Cognitive Health Evaluation in Elders (ACHIEVE) randomised controlled trial. DESIGN: Our treatment fidelity plan was based on a framework defined by the National Institutes of Health Behaviour Change Consortium (NIH BCC), and included strategies to enhance study design, provider training, and treatment delivery, receipt, and enactment. STUDY SAMPLE: To assess the fidelity of the ACHIEVE hearing intervention, we distributed a checklist containing criteria from each NIH BCC core treatment fidelity category to nine raters. RESULTS: The ACHIEVE hearing intervention fidelity plan satisfied 96% of NIH BCC criteria. Our assessment suggested a need for including clear, objective definitions of provider characteristics and non-treatment aspects of intervention delivery in future fidelity plans. CONCLUSIONS: The ACHIEVE hearing intervention fidelity plan can serve as a framework for the application of NIH BCC fidelity strategies for future studies and enhance the ability of researchers to reliably implement evidence-based interventions.

Oxidase reactions in photoredox catalysis.

The nature of the terminal oxidant in oxidation reactions is an important reaction variable that can profoundly impact the mechanism, efficiency, and practicality of a synthetic protocol. One might reasonably categorize catalytic oxidation reactions into either "oxygenase" type reactions, in which the oxidant serves as an atom- or group-transfer reagent, or "oxidase" type reactions, where the oxidant is involved in catalyst turnover but does not become structurally incorporated into the product. As the field of photoredox catalysis has matured over the past decade, many successful oxygenase-type photoreactions have been reported. The development of photocatalytic oxidase reactions, on the other hand, has been somewhat slower. This tutorial review presents selected examples of some of the key classes of terminal oxidants that have been used in the design of photoredox oxidase transformations, along with the mechanistic features and benefits of each.

Copper-Mediated Radical-Polar Crossover Enables Photocatalytic Oxidative Functionalization of Sterically Bulky Alkenes.

Oxidative heterofunctionalization reactions are among the most attractive methods for the conversion of alkenes and heteroatomic nucleophiles into complex saturated heterocycles. However, the state-of-the-art transition-metal-catalyzed methods to effect oxidative heterofunctionalizations are typically limited to unhindered olefins, and different nucleophilic partners generally require quite different reaction conditions. Herein, we show that Cu(II)-mediated radical-polar crossover allows for highly efficient and exceptionally mild photocatalytic oxidative heterofunctionalization reactions between bulky tri- and tetrasubstituted alkenes and a wide variety of nucleophilic partners. Moreover, we demonstrate that the broad scope of this transformation arises from photocatalytic alkene activation and thus complements existing transition-metal-catalyzed methods for oxidative heterofunctionalization. More broadly, these results further demonstrate that Cu(II) salts are ideal terminal oxidants for photoredox applications and that the combination of photocatalytic substrate activation and Cu(II)-mediated radical oxidation can address long-standing challenges in catalytic oxidation chemistry.

Satisfaction With Quality of Health Care Among Medicare Beneficiaries With Functional Hearing Loss.

BACKGROUND/OBJECTIVES: Nearly 38 million Americans have hearing loss. Understanding how sensory deficits such as hearing loss, which limit communication, impact satisfaction has implications for Medicare value-based reimbursement mechanisms. The aim of this study was to characterize the association of functional hearing loss and dissatisfaction with quality of health care over the past year among Medicare beneficiaries. METHODS: Cross-sectional study of satisfaction with quality of health care among Medicare beneficiaries with self-reported trouble hearing from the 2015 Medicare Current Beneficiaries Survey. There were 11,441 Medicare beneficiaries representing a 48.6 million total weighted nationally representative sample. RESULTS: Forty-eight percent of Medicare beneficiaries reported a little or a lot of trouble hearing. Medicare beneficiaries with a little trouble hearing (odds ratio=1.496; 95% confidence interval, 1.079-2.073; P=0.016) and a lot of trouble hearing (odds ratio=1.769; 95% confidence interval, 1.175-2.664; P=0.007) had 49.6% and 76.9% higher odds of being dissatisfied with the quality of their health care over the previous year, respectively. CONCLUSIONS: Medicare beneficiaries with functional hearing loss had higher odds of dissatisfaction with health care over the past year compared to those without functional hearing loss. Given Medicare's reliance on patient satisfaction as a value-based measure for hospital reimbursement, interventions to address hearing loss in the health care system are needed.

Association of Hearing Loss With Neuropsychiatric Symptoms in Older Adults With Cognitive Impairment.

Neuropsychiatric symptoms (NPS) in persons with dementia (PWD) are common and can lead to poor outcomes, such as institutionalization and mortality, and may be exacerbated by sensory loss. Hearing loss is also highly prevalent among older adults, including PWD. OBJECTIVE: This study investigated the association between hearing loss and NPS among community- dwelling patients from a tertiary memory care center. DESIGN, SETTING, AND PARTICIPANTS: Participants of this cross-sectional study were patients followed at the Johns Hopkins Memory and Alzheimer's Treatment Center who underwent audiometric testing during routine clinical practice between October 2014 and January 2017. OUTCOME MEASUREMENTS: Included measures were scores on the Neuropsychiatric Inventory-Questionnaire and the Cornell Scale for Depression in Dementia. RESULTS: Participants (n = 101) were on average 76 years old, mostly female and white, and had a mean Mini-Mental State Examination score of 23. We observed a positive association between audiometric hearing loss and the number of NPS (b = 0.7 per 10 dB; 95% confidence interval [CI]: 0.2, 1.1; t = 2.86; p = 0.01; df = 85), NPS severity (b = 1.3 per 10 dB; 95% CI: 0.4, 2.5; t = 2.13; p = 0.04; df = 80), and depressive symptom severity (b = 1.5 per 10 dB; 95% CI: 0.4, 2.5; t = 2.83; p = 0.01; df = 89) after adjustment for demographic and clinical characteristics. Additionally, the use of hearing aids was inversely associated with the number of NPS (b = -2.09; 95% CI -3.44, -0.75; t = -3.10; p = 0.003; df = 85), NPS severity (b = -3.82; 95% CI -7.19, -0.45; t = -2.26; p = 0.03; df = 80), and depressive symptom severity (b = -2.94; 95% CI: -5.93, 0.06; t = 1.70; p = 0.05; df = 89). CONCLUSION: Among patients at a memory clinic, increasing severity of hearing loss was associated with a greater number of NPS, more severe NPS, and more severe depressive symptoms, while hearing aid use was associated with fewer NPS, lower severity, and less severe depressive symptoms. Identifying and addressing hearing loss may be a promising, low-risk, non-pharmacological intervention in preventing and treating NPS.

Hearing impairment and missing cognitive test scores in a population-based study of older adults: The Atherosclerosis Risk in Communities neurocognitive study.

INTRODUCTION: Hearing impairment is associated with poor cognitive test performance in older adults. However, hearing's impact on cognitive test completion is poorly described, and missing cognitive data due to hearing impairment could misestimate the association. METHODS: We investigated if hearing impairment is associated with missing neurocognitive scores in 3678 adults (72-94 years). Hearing impairment was defined by the better-ear pure tone average of speech-frequency thresholds (0.5-4 kHz) >25 decibels. RESULTS: Hearing impairment was associated with greater missingness on all auditory-only tests, including Logical Memory (prevalence ratio [PR] comparing ≥ moderate impairment vs normal hearing:1.68, 95% confidence interval [CI] 1.26, 2.25) and Digits Backwards (PR 1.62; 95% CI 1.21, 2.17); and two non-auditory tests, Boston Naming (PR 1.61; 95% CI 1.21, 2.17) and Trail Making B (PR 1.55; 95% CI 1.29, 1.86). Models that imputed missing cognitive scores showed the strongest hearing-cognition associations. DISCUSSION: Older adults with hearing impairment are less likely to complete cognitive testing, thereby underestimating the hearing impairment-cognition relationship.

Could MicroRNAs Be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview.

Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with an annual incidence of <6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience and limited therapeutic options. There has been a growing interest in the field of microRNAs (miRNAs), a class of small non-coding RNAs of ∼22 nucleotides in length, because of their potential to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational repression by interacting with the 3' untranslated region (3'-UTR) of target mRNAs, as well as other regions and gene promoters, as well as activating translation or regulating transcription under certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few studies have been performed on RGCs. In this review, we summarize the data currently available regarding RGCs.

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.

BACKGROUND: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS: At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS: Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.

PURPOSE: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. METHODS: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. RESULTS: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. CONCLUSIONS: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.

The Hearing Intervention for the Aging and Cognitive Health Evaluation in Elders Randomized Control Trial: Manualization and Feasibility Study.

OBJECTIVES: This work describes the development of a manualized best-practice hearing intervention for older adults participating in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomized controlled clinical trial. Manualization of interventions for clinical trials is critical for assuring intervention fidelity and quality, especially in large multisite studies. The multisite ACHIEVE randomized controlled trial is designed to assess the efficacy of a hearing intervention on rates of cognitive decline in older adults. We describe the development of the manualized hearing intervention through an iterative process that included addressing implementation questions through the completion of a feasibility study (ACHIEVE-Feasibility). DESIGN: Following published recommendations for manualized intervention development, an iterative process was used to define the ACHIEVE-hearing intervention elements and create an initial manual. The intervention was then delivered within the ACHIEVE-Feasibility study using one-group pre-post design appropriate for assessing questions related to implementation. Participants were recruited from the Tampa, Florida area between May 2015 and April 2016. Inclusion criteria were cognitively healthy adults aged 70 to 89 with symmetrical mild-to-moderately severe sensorineural hearing loss. The ACHIEVE-Feasibility study sought to assess the implementation of the manualized hearing intervention by: (1) confirming improvement in expected outcomes were achieved including aided speech-in-noise performance and perception of disease-specific self-report measures; (2) determining whether the participants would comply with the intervention including session attendance and use of hearing aids; and (3) determining whether the intervention sessions could be delivered within a reasonable timeframe. RESULTS: The initial manualized intervention that incorporated the identified best-practice elements was evaluated for feasibility among 21 eligible participants and 9 communication partners. Post-intervention expected outcomes were obtained with speech-in-noise performance results demonstrating a significant improvement under the aided condition and self-reported measures showing a significant reduction in self-perceived hearing handicap. Compliance was excellent, with 20 of the 21 participants (95.2%) completing all intervention sessions and 19 (90.4%) returning for the 6-month post-intervention visit. Furthermore, self-reported hearing aid compliance was >8 hr/day, and the average daily hearing aid use from datalogging was 7.8 hr. Study completion was delivered in a reasonable timeframe with visits ranging from 27 to 85 min per visit. Through an iterative process, the intervention elements were refined, and the accompanying manual was revised based on the ACHIEVE-Feasibility study activities, results, and clinician and participant informal feedback. CONCLUSION: The processes for the development of a manualized intervention described here provide guidance for future researchers who aim to examine the efficacy of approaches for the treatment of hearing loss in a clinical trial. The manualized ACHIEVE-Hearing Intervention provides a patient-centered, yet standardized, step-by-step process for comprehensive audiological assessment, goal setting, and treatment through the use of hearing aids, other hearing assistive technologies, counseling, and education aimed at supporting self-management of hearing loss. The ACHIEVE-Hearing Intervention is feasible in terms of implementation with respect to verified expected outcomes, compliance, and reasonable timeframe delivery. Our processes assure intervention fidelity and quality for use in the ACHIEVE randomized controlled trial (ClinicalTrials.gov Identifier: NCT03243422).

Diet quality and hearing loss among middle-older aged adults in the USA: findings from National Health and Nutrition Examination Survey.

OBJECTIVE: To examine the associations between overall diet quality and hearing function among middle-older aged adults in the USA. DESIGN: Cross-sectional analysis. Diet quality was examined using the Mediterranean Diet Score (MDS), using data from a single 24 h dietary recall. Hearing function was objectively measured by audiometry assessments and hearing loss, including high- and low-frequency hearing loss, was defined as pure-tone averages at specific ranges of hearing frequencies >25 dB. Weighted logistic regression analyses were performed to examine the associations of MDS (scored 0-9, categorized at the median as ≤3 or >3) with hearing loss and high- and low-frequency hearing loss. SETTING: National Health and Nutrition Examination Surveys 2000-2006 and 2009-2012. PARTICIPANTS: Adults aged ≥50 years (n 1639) with valid dietary and audiometry assessments. RESULTS: After adjusting for potential confounders, a non-significant trend for a protective association of higher MDS was observed for hearing loss (OR = 0·78; 95 % CI 0·49, 1·23). A significant inverse association was observed for high-frequency hearing loss (OR = 0·64; 95 % CI 0·43, 0·95). No association was found for low-frequency hearing loss among women; however, higher MDS was significantly associated with higher odds of low-frequency hearing loss among men (OR = 2·63; 95 % CI 1·39, 4·95). CONCLUSIONS: Among middle-older aged adults, adherence to a Mediterranean-style diet was inversely associated with hearing loss, including those at high hearing frequencies, among older adults. However, a detrimental association was observed at low hearing frequencies among men. Future investigations with a longitudinal design are needed to clarify the associations between diet quality and hearing loss.

Accompaniment to healthcare visits: the impact of sensory impairment.

BACKGROUND: Millions of older adults in the United States experience hearing, vision, and dual sensory impairment (concurring hearing and vision impairment) yet little research exists on their needs in interactions with the healthcare system. This piece aims to determine the use of accompaniment in healthcare interactions by persons with sensory impairment. METHODS: These cross-sectional analyses included data from the 2015 Medicare Current Beneficiaries Survey and survey weighting provided by Centers for Medicare and Medicaid Services. Adjusted odds of reporting accompaniment to healthcare visits and given reasons for accompaniment among United States Medicare beneficiaries with self-reported sensory impairment (hearing, vision, and dual sensory impairment) were examined. RESULTS: After excluding observations with missing data, 10,748 Medicare beneficiaries remained representing a 46 million total weighted nationally representative sample, of which 88.9% reported no sensory impairment, 5.52% reported hearing impairment, 3.56% reported vision impairment, and 0.93% reported dual sensory impairment. Those with vision impairment and dual sensory impairment had 2.139 (95% confidence interval [CI] =1.605-2.850) and 2.703 (CI = 1.549-4.718) times the odds of reporting accompaniment to healthcare visits relative to those without sensory impairment. A secondary analysis suggests communication needs as the primary reason for accompaniment among persons with hearing loss, while those with vision impairment were more likely to indicate transportation needs. CONCLUSIONS: Healthcare accompaniment is common for persons with sensory loss and healthcare systems should consider accommodations for and leveraging accompaniment to improve healthcare for persons with sensory impairments. In light of the current COVID-19 pandemic, as hospitals limit visitors to reduce the spread of infection, arrangements should be made to ensure that the communication and transportation needs of those with sensory impairment are not neglected.