A Pragmatic Clinical Trial of Hearing Screening in Primary Care Clinics: Effect of Setting and Provider Encouragement.

OBJECTIVES: The prevalence of hearing loss increases with age. Untreated hearing loss is associated with poorer communication abilities and negative health consequences, such as increased risk of dementia, increased odds of falling, and depression. Nonetheless, evidence is insufficient to support the benefits of universal hearing screening in asymptomatic older adults. The primary goal of the present study was to compare three hearing screening protocols that differed in their level of support by the primary care (PC) clinic and provider. The protocols varied in setting (in-clinic versus at-home screening) and in primary care provider (PCP) encouragement for hearing screening (yes versus no). DESIGN: We conducted a multisite, pragmatic clinical trial. A total of 660 adults aged 65 to 75 years; 64.1% female; 35.3% African American/Black completed the trial. Three hearing screening protocols were studied, with 220 patients enrolled in each protocol. All protocols included written educational materials about hearing loss and instructions on how to complete the self-administered telephone-based hearing screening but varied in the level of support provided in the clinic setting and by the provider. The protocols were as follows: (1) no provider encouragement to complete the hearing screening at home, (2) provider encouragement to complete the hearing screening at home, and (3) provider encouragement and clinical support to complete the hearing screening after the provider visit while in the clinic. Our primary outcome was the percentage of patients who completed the hearing screening within 60 days of a routine PC visit. Secondary outcomes following patient access of hearing healthcare were also considered and consisted of the percentage of patients who completed and failed the screening and who (1) scheduled, and (2) completed a diagnostic evaluation. For patients who completed the diagnostic evaluation, we also examined the percentage of those who received a hearing loss intervention plan by a hearing healthcare provider. RESULTS: All patients who had provider encouragement and support to complete the screening in the clinic completed the screening (100%) versus 26.8% with encouragement to complete the screening at home. For patients who were offered hearing screening at home, completion rates were similar regardless of provider encouragement (26.8% with encouragement versus 22.7% without encouragement); adjusted odds ratio of 1.25 (95% confidence interval 0.80-1.94). Regarding the secondary outcomes, roughly half (38.9-57.1% depending on group) of all patients who failed the hearing screening scheduled and completed a formal diagnostic evaluation. The percentage of patients who completed a diagnostic evaluation and received a hearing loss intervention plan was 35.0% to 50.0% depending on the group. Rates of a hearing loss intervention plan by audiologists ranged from 28.6% to 47.5% and were higher compared with those by otolaryngology providers, which ranged from 15.0% to 20.8% among the groups. CONCLUSIONS: The results of the pragmatic clinical trial showed that offering provider encouragement and screening facilities in the PC clinic led to a significantly higher rate of adherence with hearing screening associated with a single encounter. However, provider encouragement did not improve the significantly lower rate of adherence with home-based hearing screening.

Telementoring initiative for newborn care providers in Kenya, Pakistan and Tanzania.

OBJECTIVES: To support governments' efforts at neonatal mortality reduction, UNICEF and the American Academy of Pediatrics launched a telementoring project in Kenya, Pakistan and Tanzania. METHODS: In Fall 2019, an individualised 12-session telementoring curriculum was created for East Africa and Pakistan after site visits that included care assessment, patient data review and discussion with faculty and staff. After the programme, participants, administrators and UNICEF staff were surveyed and participated in focus group discussions. RESULTS: Participants felt the programme improved knowledge and newborn care. Qualitative analysis found three common themes of successful telementoring: local buy-in, use of existing training or clinical improvement structures, and consideration of technology needs. CONCLUSIONS: Telementoring has potential as a powerful tool in newborn education. It offers more flexibility and easier access than in-person sessions. This project has the potential for scale-up, particularly when physical distancing and travel restrictions are the norm.

A pragmatic clinical trial of hearing screening in primary care clinics: cost-effectiveness of hearing screening.

BACKGROUND: Hearing loss is a high prevalence condition among older adults, is associated with higher-than-average risk for poor health outcomes and quality of life, and is a public health concern to individuals, families, communities, professionals, governments, and policy makers. Although low-cost hearing screening (HS) is widely available, most older adults are not asked about hearing during health care visits. A promising approach to addressing unmet needs in hearing health care is HS in primary care (PC) clinics; most PC providers (PCPs) do not inquire about hearing loss. However, no cost assessment of HS in community PC settings has been conducted in the United States. Thus, this study conducted a cost-effectiveness analysis of HS using results from a pragmatic clinic trial that compared three HS protocols that differed in the level of support and encouragement provided by the PC office and the PCPs to older adults during their routine visits. Two protocols included HS at home (one with PCP encouragement and one without) and one protocol included HS in the PC office. METHODS: Direct costs of the HS included costs of: (1) educational materials about hearing loss, (2) PCP educational and encouragement time, and (3) access to the HS system. Indirect costs for in-office HS included cost of space and minimal staff time. Costs were tracked and modeled for each phase of care during and following the HS, including completion of a diagnostic assessment and follow-up with the recommended treatment plan. RESULTS: The cost-effectiveness analysis showed that the average cost per patient is highest in the patient group who completed the HS during their clinic visit, but the average cost per patient who failed the HS is by far the lowest in that group, due to the higher failure rate, that is, rate of identification of patients with suspected hearing loss. Estimated benefits of HS in terms of improvements in quality of life were also far greater when patients completed the HS during their clinic visit. CONCLUSIONS: Providing HS to older adults during their PC visit is cost-effective and accrues greater estimated benefits in terms of improved quality of life. TRIAL REGISTRATION: clinicaltrials.gov (Registration Identification Number: NCT02928107).

Controlling for Lexical Factors in the Word Auditory Recognition and Recall Measure.

PURPOSE: The purpose of this study was to confirm that lexical factors associated with the Word Auditory Recognition and Recall Measure (WARRM) items have minimal impact WARRM scores. As the WARRM test was designed to minimize the impact of lexical factors, we hypothesized that lexical factors would have no effect on WARRM recognition or recall. METHOD: This report provides a complementary analysis to the original study. Generalized linear mixed models were applied to examine the effects of lexical factors (frequency, neighborhood density, neighborhood frequency) on the WARRM recognition and recall scores. RESULTS: There were no significant effects of lexical factors on WARRM recognition or recall. These null effects were attributed to selection and distribution of words on the WARRM, and the balancing of lexical factors for each set size. CONCLUSIONS: Word selection and test design of the WARRM successfully controlled for potential effects of lexical factors on recognition and recall.

Impact of Effortful Word Recognition on Supportive Neural Systems Measured by Alpha and Theta Power.

OBJECTIVES: The goal of this study was to use theta and alpha electroencephalography (EEG) frequency power and self-report measures to examine performance monitoring, cognitive inhibition, and perceived effort required for speech understanding in noise. It was hypothesized that with a linear increase in word recognition task difficulty, there would be a linear increase in listening effort and word recognition performance would decrease in the challenging conditions. In addition, theta and alpha power would have an inverted U-shape across easy to challenging listening conditions. The inverted U-shape would reflect the neural underpinnings of listening effort that cannot be measured by task performance alone. DESIGN: EEG data were collected in 34 normal-hearing adults (18 to 33 years old) during the Words-In-Noise (WIN) test, which was presented in sound field. EEG frequency data were averaged and analyzed at three frontal channels for theta power (4 to 8 Hz), which is thought to reflect performance monitoring, and three parietal channels for alpha power (8 to 12 Hz), which is thought to reflect cognitive inhibition. A ten-point visual analog scale was administered after each WIN signal-to-noise ratio (SNR) condition to capture self-reported required and invested listening effort (RLE and ILE, respectively). The WIN SNR conditions were presented in descending and random order. RESULTS: The SNR presentation (descending or random SNR) had a null effect on word recognition performance; however, presentation did have an effect on theta power, alpha power, and ILE. When controlling for presentation, there were significant effects of SNR and presentation on both theta and alpha frequency power. Theta and alpha power had an inverted U-shape as a function of SNR from easy to challenging, with peak power in the moderate SNR conditions. RLE and ILE both significantly increased as task difficulty increased as expected; however, RLE showed a stronger relation to task performance than ILE. Alpha power was a significant predictor of RLE, ILE, and WIN performance when controlling for SNR. CONCLUSIONS: The elevated theta and alpha power in the easy to moderate SNRs and alpha power predicting self-reported listening effort suggest the activation of supportive neural systems during word recognition that could be considered a marker of listening effort. Moreover, the measures of neural support systems and listening effort were independent from task performance, which is a key element to further understanding the neural bases for listening effort. In the context of the broader literature, these results are consistent with (1) a parietal alpha role in supporting inhibitory control to suppress irrelevant information and (2) a frontal theta role in supporting performance monitoring in difficult listening conditions where speech recognition is feasible.

Impact of Hearing Aid Use on Falls and Falls-Related Injury: Results From the Health and Retirement Study.

OBJECTIVES: Falls are considered a significant public health issue and falls risk increases with age. There are many age-related physiologic changes that occur that increase postural instability and the risk for falls (i.e., age-related sensory declines in vision, vestibular, somatosensation, age-related orthopedic changes, and polypharmacy). Hearing loss has been shown to be an independent risk factor for falls. The primary objective of this study was to determine if hearing aid use modified (reduced) the association between self-reported hearing status and falls or falls-related injury. We hypothesized that hearing aid use would reduce the impact of hearing loss on the odds of falling and falls-related injury. If hearing aid users have reduced odds of falling compared with nonhearing aid users, then that would have an important implications for falls prevention healthcare. DESIGN: Data were drawn from the 2004-2016 surveys of the Health and Retirement Study (HRS). A generalized estimating equation approach was used to fit logistic regression models to determine whether or not hearing aid use modifies the odds of falling and falls injury associated with self-reported hearing status. RESULTS: A total of 17,923 individuals were grouped based on a self-reported history of falls. Self-reported hearing status was significantly associated with odds of falling and with falls-related injury when controlling for demographic factors and important health characteristics. Hearing aid use was included as an interaction in the fully-adjusted models and the results showed that there was no difference in the association between hearing aid users and nonusers for either falls or falls-related injury. CONCLUSIONS: The results of the present study show that when examining self-reported hearing status in a longitudinal sample, hearing aid use does not impact the association between self-reported hearing status and the odds of falls or falls-related injury.

The Association Between Hearing Loss and Surgical Complications in Older Adults.

OBJECTIVES: In this study, we sought to evaluate whether older patients with hearing loss who underwent surgery were at greater risk of postsurgical complications, increased inpatient length-of-stay (LOS), and hospital readmission. DESIGN: This was a retrospective cohort study of patients receiving surgery at a tertiary medical center. Utilizing electronic health record data from two merged datasets, we identified patients 65 years and older, undergoing major surgery between January 1, 2014 and January 31, 2017, and who had audiometric evaluation before surgery. Patients were classified as having either normal hearing or hearing loss based on pure-tone average in the better ear. A Generalized Estimating Equations approach was used to fit multivariable regression models for outcome variables of interest. RESULTS: Of patients ≥65 years undergoing major surgery in our time frame, a total of 742 surgical procedures were performed on 621 patients with available audiometric data. After adjusting for age, sex, race, and comorbidities, hearing loss was associated with an increase in the odds of developing postoperative complications. Every 10 dB increase in hearing loss was associated with a 14% increase in the odds of developing a postoperative complication (odds ratio = 1.14, 95% confidence interval = 1.01-1.29, p = 0.031). Hearing loss was not significantly associated with increased hospital LOS, 30-day readmission, or 90-day readmission. CONCLUSIONS: Hearing loss was significantly associated with developing postoperative complications in older adults undergoing major surgery. Screening for hearing impairment may be a useful addition to the preoperative assessment and perioperative management of older patients undergoing surgery.

A Systematic Review on the Association Between Vestibular Dysfunction and Balance Performance in Children With Hearing Loss.

OBJECTIVES: The objective of this study was to understand the functional impact of vestibular dysfunction on balance control in children with hearing loss. The vestibular system is an important contributor to maintaining balance. In adults, vestibular dysfunction is known to lead to unsteadiness and falls. Considerably less is known about the effects of vestibular dysfunction in children with hearing loss. DESIGN: We conducted a systematic review in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included articles on children with hearing loss who underwent vestibular and balance testing. The Downs and Black checklist was used to assess the risk of bias. RESULTS: A total of 20 articles were included in this systematic review, of which, 17 reported an association between vestibular dysfunction and balance abnormalities in children with hearing loss. Bias (as measured by the Downs and Black Checklist) was a concern, as most studies were nonblinded cohort studies or case series selected through convenience sampling. CONCLUSIONS: Research to date has predominantly found that children with concomitant hearing loss and vestibular impairment tend to perform more poorly on balance measures than either children with hearing loss and normal vestibular function or children with both normal-hearing and normal vestibular function. A standardized approach to assessing both vestibular function and balance would better characterize the impact of vestibular dysfunction in children with hearing loss at the population level.

Development of Abbreviated Versions of the Word Auditory Recognition and Recall Measure.

OBJECTIVES: The objective of this study was to develop and evaluate abbreviated versions of the Word Auditory Recognition and Recall Measure (WARRM) as part of an iterative process in the development of a feasible test for potential future clinical use. DESIGN: The three original WARRM (O-WARRM) randomizations were modified by altering the presentation paradigm. Instead of presenting 5 trials per set size with set size increasing from 2 to 6 as in the O-WARRM (n = 100 words), the experimental WARRM (E-WARRM) paradigm consisted of one trial from each of set sizes 2 to 6 to create a "run" (n = 20 words) with each randomization consisting of 5 runs (n = 100 words). A total of 24 younger listeners with normal hearing and 48 older listeners with hearing loss (OHL) were administered 1 randomization of the O-WARRM and 1 different randomization of the E-WARRM. RESULTS: The recognition and recall performances on the O-WARRM and all versions of the E-WARRM (five individual runs and overall) were similar within each listener group, with the younger listeners with normal hearing outperforming the OHL listeners on all measures. Correlation analyses revealed moderate to strong associations between the abbreviated WARRM runs and the O-WARRM for the OHL listener group. Hierarchical regression modeling suggested that run 1 of the E-WARRM was a good predictor of O-WARRM performance and that adding additional runs did not improve the prediction. Taken together, these findings suggest that administering one run from the E-WARRM warrants further examination for clinical use. Additional analyses revealed equivalent scores on all five runs from the three E-WARRM randomizations for both listener groups. CONCLUSIONS: Abbreviated versions of the O-WARRM were developed as part of this study. This was accomplished by modifying the original presentation paradigm and creating 15 unique "runs" among the original 3 randomizations. The resulting 15 runs could be considered 15 unique and abbreviated WARRM lists that have potential, in the future after further studies are conducted to establish important properties, for clinic use. The abbreviated WARRM lists may be useful for quantifying auditory working memory of listeners with hearing loss during the audiologic rehabilitation process.

Metabolic disposition of H3B-8800, an orally available small-molecule splicing modulator, in rats, monkeys, and humans.

H3B-8800, a novel orally available modulator of the SF3b complex, which potently and preferentially kills spliceosome-mutant tumor cells, is in clinical development for the treatment of advanced myeloid malignancies. We characterized the pharmacokinetics, metabolism and disposition of H3B-8800 in rats, monkeys and humans.In vitro, H3B-8800 is a substrate of CYP3A4/5, flavin-containing monooxygenases (FMOs) and P-glycoprotein (P-gp), and showed a favorable drug-drug interaction profile as a perpetrator.Following oral dosing of 14C-H3B-8800 in bile-duct cannulated SD rats, 54.7% of the dosed radioactivity was excreted in the bile, with less found in feces (36.8%). The low amount in urine (3.7%), suggests that renal elimination is a minor pathway of clearance for H3B-8800.In Long-Evans rats, radioactivity derived from 14C-H3B-8800 was rapidly absorbed, with the highest distribution in the ocular, metabolic/excretory, and gastrointestinal tract tissues. No radioactivity was detected in the central nervous system.Seven metabolites were observed in human plasma following 4 daily doses of 40 mg H3B-8800. H3B-68736 (N-desmethyl), H3B-77176 (N-oxide), and unchanged H3B-8800 were the prominent components in human plasma, at 27.3%, 18.1%, and 33.2%, respectively, of the total drug-related material in a pooled AUC0-24h sample. The same 7 metabolites were observed in monkey plasma.

Comparative implementation-effectiveness of three strategies to perform hearing screening among older adults in primary care clinics: study design and protocol.

BACKGROUND: The burden of hearing loss among older adults could be mitigated with appropriate care. This study compares implementation of three hearing screening strategies in primary care, and examines the reliability and validity of patient self-assessment, primary care providers (PCP) and diagnostic audiologists in the identification of 'red flag' conditions (those conditions that may require medical consultation and/or intervention). METHODS: Six primary care practices will implement one of three screening strategies (2 practices per strategy) with 660 patients (220 per strategy) ages 65-75 years with no history of hearing aid use or diagnosis of hearing loss. Strategies differ on the location and use of PCP encouragement to complete a telephone-based hearing screen (tele-HS). Group 1: instructions for tele-HS to complete at home and educational materials on warning signs and consequences of hearing loss. Group 2: PCP counseling/encouragement on importance of hearing screening, instructions to take the tele-HS from home, educational materials. Group 3: PCP counseling/encouragement, in-office tele-HS, and educational materials. Patients from all groups who fail the tele-HS will be referred for diagnostic audiological testing and medical evaluation, and complete a self-assessment of red flag conditions at this follow-up appointment. Due to the expected low incidence of ear disease in the PCP cohort, we will enroll a complementary population of patients (N = 500) from selected otolaryngology head and neck surgery clinics in a national practice-based research network to increase the likelihood of occurrence of medical conditions that might contraindicate hearing aid fitting. The primary outcome is the proportion of patients who complete the tele-HS within 2 months of the PCP appointment comparing Group 3 (PCP encouragement, in-office tele-HS, education) versus Groups 2 and 1 (education and tele-HS at home, with and without PCP encouragement, respectively). The several secondary outcomes include direct and indirect costs, patient, family and provider attitudes of hearing healthcare, and accuracy of red flag condition evaluations compared with expert medical assessment by an otolaryngology provider. DISCUSSION: Determining the relative effectiveness of three different strategies for hearing screening in primary care and the assessment accuracy of red flag conditions can each lead to practice and policy changes that will reduce individual, family and societal burden from hearing loss among older adults. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02928107; 10/10/2016 protocol version 1.

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein.

According to the free drug hypothesis only the unbound drug is available to act at physiological sites of action, and as such the importance of plasma protein binding primarily resides in its impact on pharmacokinetics and pharmacodynamics. Of the major plasma proteins, alpha-1-acid glycoprotein (AAG) represents an intriguing one primarily due to the high affinity, low capacity properties of this protein. In addition, there are marked species and age differences in protein expression, homology and drug binding affinity. As such, a thorough understanding of drug binding to AAG can help aid and improve the translation of pharmacokinetic/pharmacodynamic (PK/PD) relationships from preclinical species to human as well as adults to neonates. This review provides a comprehensive overview of our current understanding of the biochemistry of AAG; endogenous function, impact of disease, utility as a biomarker, and impact on PK/PD. Experimental considerations are discussed as well as recommendations for understanding the potential impact of AAG on PK through drug discovery and early development.

Qualitative Analysis of Infant Safe Sleep Public Campaign Messaging.

The 1994 Back to Sleep public education campaign resulted in dramatic reductions in sleep-related infant deaths, but comparable progress in recent years has been elusive. We conducted qualitative analyses of recent safe sleep campaigns from 13 U.S. cities. Goals were to (a) determine whether the campaigns reflect the full range of American Academy of Pediatrics (AAP) 2011 safe sleep recommendations, (b) describe tone and framing of the messages (e.g., use of fear appeals), (c) describe targeting/tailoring of messages to priority populations, and (d) ascertain whether the campaigns have been evaluated for reach and/or effectiveness. Methods included computer-assisted analyses of campaign materials and key informant interviews. All campaigns included "ABC" (Alone, Back, Crib) messaging; many ignored other AAP recommendations such as breastfeeding, room-sharing, immunizations, and avoiding smoke exposure. Campaigns frequently targeted priority populations such as African Americans. Fear appeals were used in three quarters of the campaigns, and 60% of the fear-based campaigns used guilt/blame messaging. We did not find published evaluation data for any of the campaigns. More attention is needed in public education campaigns to the full range of AAP recommendations, and evaluations are needed to determine the impact of these interventions on knowledge, behavior, and health outcomes.

Mechanistic investigations into the species differences in pinometostat clearance: impact of binding to alpha-1-acid glycoprotein and permeability-limited hepatic uptake.

1. The plasma clearance of the first-in-class DOT1L inhibitor, EPZ-5676 (pinometostat), was shown to be markedly lower in human compared to the preclinical species, mouse, rat and dog. 2. This led to vertical allometry where various interspecies scaling methods were applied to the data, with fold-errors between 4 and 13. We had previously reported the elimination and metabolic pathways of EPZ-5676 were similar across species. Therefore, the aim of this work was to explore the mechanistic basis for the species difference in clearance for EPZ-5676, focusing on other aspects of disposition. 3. The protein binding of EPZ-5676 in human plasma demonstrated a non-linear relationship suggesting saturable binding at physiologically relevant concentrations. Saturation of protein binding was not observed in plasma from preclinical species. Kinetic determinations using purified serum albumin and alpha-1-acid glycoprotein (AAG) confirmed that EPZ-5676 is a high affinity ligand for AAG with a dissociation constant (Kd) of 0.24 µM. 4. Permeability limited uptake was also considered since hepatocyte CLint was much lower in human relative to preclinical species. Passive unbound CLint for EPZ-5676 was estimated using a correlation analysis of logD and data previously reported on seven drugs in sandwich cultured human hepatocytes. 5. Incorporation of AAG binding and permeability limited hepatic uptake into the well-stirred liver model gave rise to a predicted clearance for EPZ-5676 within 2-fold of the observed value of 1.4 mL min-1 kg-1. This analysis suggests that the marked species difference in EPZ-5676 clearance is driven by high affinity binding to human AAG as well as species-specific hepatic uptake invoking the role of transporters.

Tinnitus Self-Efficacy and Other Tinnitus Self-Report Variables in Patients With and Without Post-Traumatic Stress Disorder.

OBJECTIVE: Individuals with tinnitus and co-occurring psychological conditions typically rate their tinnitus as more disturbing than individuals without such comorbidities. Little is known about how tinnitus self-efficacy, or the confidence that individuals have in their abilities to successfully manage the effects of tinnitus, is influenced by mental or psychological health (PH) status. The purpose of this study was to examine the influence of psychological state on tinnitus perceptions and tinnitus self-efficacy in individuals with chronic tinnitus. DESIGN: Observational study. Three groups (N = 199) were examined and included: (1) those with tinnitus without a concurrent psychological condition (tinnitus-only; n = 103), (2) those with tinnitus and concurrent PH condition other than post-traumatic stress disorder (PTSD; tinnitus + PH; n = 34), and (3) those with tinnitus and PTSD (tinnitus + PTSD; n = 62). The Self-Efficacy for Tinnitus Management Questionnaire (SETMQ) was administered. Responses on the SETMQ were compared among the groups, as well as to other indicators of tinnitus perception such as (1) the percentage of time tinnitus was audible (tinnitus awareness), (2) the percentage of time tinnitus was distressing/bothersome, (3) tinnitus loudness, (4) tinnitus handicap inventory scores, (5) subjective ratings of degree of hearing loss, and (6) subjective ratings of sound tolerance problems. RESULTS: The tinnitus + PTSD group reported significantly poorer tinnitus self-efficacy levels on average than the tinnitus-only group on all SETMQ subscales and poorer self-efficacy levels than the tinnitus + PH group for most subscales (except for routine management and devices). Tinnitus self-efficacy levels were similar between the tinnitus + PH and tinnitus-only groups except for the emotional response subscale in which the tinnitus-only patients reported higher self-efficacy on average than both the other groups. Group differences were not seen for tinnitus loudness ratings nor for the amount of time individuals were aware of their tinnitus. Group differences were observed for the percentage of time tinnitus was distressing/bothersome, self-reported degree of hearing loss, sound tolerance problems ratings, and responses on the tinnitus handicap inventory (THI). In general, the group differences revealed patient ratings for the tinnitus-only group were least severe, followed by the tinnitus + PH group, and the tinnitus + PTSD group rated tinnitus effects as most severe. With all patient responses, the tinnitus + PTSD group was found to be significantly more affected by tinnitus than the tinnitus-only group; in some cases, the responses were similar between the tinnitus + PTSD and tinnitus + PH group and in other cases, responses were similar between the tinnitus + PH group and the tinnitus-only group. CONCLUSIONS: Tinnitus self-efficacy, along with other self-assessed tinnitus characteristics, varied across groups distinguished by PH diagnoses. In general, individuals with tinnitus and concurrent PTSD reported significantly poorer tinnitus self-efficacy and more handicapping tinnitus effects when compared to individuals with other psychological conditions or those with tinnitus alone. The group differences highlighted the need to consider tinnitus self-efficacy in intervention strategies, particularly for patients with tinnitus and concurrent PTSD as the results reiterated the unique ability of PTSD to interact in powerful and disturbing ways with the tinnitus experience and with patients' coping ability.

Development of the Word Auditory Recognition and Recall Measure: A Working Memory Test for Use in Rehabilitative Audiology.

OBJECTIVES: The purpose of this study was to develop the Word Auditory Recognition and Recall Measure (WARRM) and to conduct the inaugural evaluation of the performance of younger adults with normal hearing, older adults with normal to near-normal hearing, and older adults with pure-tone hearing loss on the WARRM. DESIGN: The WARRM is a new test designed for concurrently assessing word recognition and auditory working memory performance in adults who may have pure-tone hearing loss. The test consists of 100 monosyllabic words based on widely used speech-recognition test materials. The 100 words are presented in recall set sizes of 2, 3, 4, 5, and 6 items, with 5 trials in each set size. The WARRM yields a word-recognition score and a recall score. The WARRM was administered to all participants in three listener groups under two processing conditions in a mixed model (between-subjects, repeated measures) design. The between-subjects factor was group, with 48 younger listeners with normal audiometric thresholds (younger listeners with normal hearing [YNH]), 48 older listeners with normal thresholds through 3000 Hz (older listeners with normal hearing [ONH]), and 48 older listeners with sensorineural hearing loss (older listeners with hearing loss [OHL]). The within-subjects factor was WARRM processing condition (no additional task or with an alphabet judgment task). The associations between results on the WARRM test and results on a battery of other auditory and memory measures were examined. RESULTS: Word-recognition performance on the WARRM was not affected by processing condition or set size and was near ceiling for the YNH and ONH listeners (99 and 98%, respectively) with both groups performing significantly better than the OHL listeners (83%). The recall results were significantly better for the YNH, ONH, and OHL groups with no processing (93, 84, and 75%, respectively) than with the alphabet processing (86, 77, and 70%). In both processing conditions, recall was best for YNH, followed by ONH, and worst for OHL listeners. WARRM recall scores were significantly correlated with other memory measures. In addition, WARRM recall scores were correlated with results on the Words-In-Noise (WIN) test for the OHL listeners in the no processing condition and for ONH listeners in the alphabet processing condition. Differences in the WIN and recall scores of these groups are consistent with the interpretation that the OHL listeners found listening to be sufficiently demanding to affect recall even in the no processing condition, whereas the ONH group listeners did not find it so demanding until the additional alphabet processing task was added. CONCLUSIONS: These findings demonstrate the feasibility of incorporating an auditory memory test into a word-recognition test to obtain measures of both word recognition and working memory simultaneously. The correlation of WARRM recall with scores from other memory measures is evidence of construct validity. The observation of correlations between the WIN thresholds with each of the older groups and recall scores in certain processing conditions suggests that recall depends on listeners' word-recognition abilities in noise in combination with the processing demands of the task. The recall score provides additional information beyond the pure-tone audiogram and word-recognition scores that may help rehabilitative audiologists assess the listening abilities of patients with hearing loss.

A Randomized Control Trial: Supplementing Hearing Aid Use with Listening and Communication Enhancement (LACE) Auditory Training.

OBJECTIVE: To examine the effectiveness of the Listening and Communication Enhancement (LACE) program as a supplement to standard-of-care hearing aid intervention in a Veteran population. DESIGN: A multisite randomized controlled trial was conducted to compare outcomes following standard-of-care hearing aid intervention supplemented with (1) LACE training using the 10-session DVD format, (2) LACE training using the 20-session computer-based format, (3) placebo auditory training (AT) consisting of actively listening to 10 hr of digitized books on a computer, and (4) educational counseling-the control group. The study involved 3 VA sites and enrolled 279 veterans. Both new and experienced hearing aid users participated to determine if outcomes differed as a function of hearing aid user status. Data for five behavioral and two self-report measures were collected during three research visits: baseline, immediately following the intervention period, and at 6 months postintervention. The five behavioral measures were selected to determine whether the perceptual and cognitive skills targeted in LACE training generalized to untrained tasks that required similar underlying skills. The two self-report measures were completed to determine whether the training resulted in a lessening of activity limitations and participation restrictions. Outcomes were obtained from 263 participants immediately following the intervention period and from 243 participants 6 months postintervention. Analyses of covariance comparing performance on each outcome measure separately were conducted using intervention and hearing aid user status as between-subject factors, visit as a within-subject factor, and baseline performance as a covariate. RESULTS: No statistically significant main effects or interactions were found for the use of LACE on any outcome measure. CONCLUSIONS: Findings from this randomized controlled trial show that LACE training does not result in improved outcomes over standard-of-care hearing aid intervention alone. Potential benefits of AT may be different than those assessed by the performance and self-report measures utilized here. Individual differences not assessed in this study should be examined to evaluate whether AT with LACE has any benefits for particular individuals. Clinically, these findings suggest that audiologists may want to temper the expectations of their patients who embark on LACE training.

Effects of Vocal Emotion on Memory in Younger and Older Adults.

BACKGROUND/STUDY CONTEXT: Emotional content can enhance memory for visual stimuli, and older adults often perform better if stimuli portray positive emotion. Vocal emotion can enhance the accuracy of word repetition in noise when vocal prosody portrays attention-capturing emotions such as fear and pleasant surprise. In the present study, the authors examined the effect of vocal emotion on the accuracy of repetition and recall in younger and older adults when words are presented in quiet or in a background of competing babble. METHODS: Younger and older adults (Mage = 20 and 72 years, respectively) participated. Lists of 100 items (carrier phrase plus target word) were presented in recall sets of increasing size. Word repetition accuracy was tested after each item and recall after each trial in each set size. In Experiment 1, one list spoken in a neutral voice and another with emotion (fear, pleasant surprise, sad, neutral) were presented in quiet (n = 24 per group). In Experiment 2, participants (n = 12 per group) were presented the emotional list in noise. RESULTS: In quiet, word repetition accuracy was near perfect for both groups and did not vary systematically with set size for the list spoken in a neutral voice; however, for the emotional list, repetition was less accurate, especially for the older group. Recall in quiet was higher for younger than older adults; collapsed over groups, recall was higher for the neutral than for the emotional list and it decreased with increasing set size. In noise, emotion-specific effects emerged; word repetition for the older group and word recall for both groups (more for younger than older) was best for fear or pleasant surprise and worst for sad. CONCLUSION: In quiet, vocal emotion reduced the word repetition accuracy of the older group and recall accuracy for both groups. In noise, there were emotion-specific effects on the repetition accuracy of older adults and the recall accuracy of both groups. Both groups, but especially the younger group, performed better for items portraying fear or pleasant surprise and worse for items portraying sadness or neutral emotion. The emotion-specific effects on word repetition cascade to recall, especially in older listeners.

A Pilot Study to Evaluate a Residual Inhibition Technique in Hearing Aids for Suppression of Tinnitus.

Tinnitus acoustic therapy is defined as any use of sound where the intent is to alter the tinnitus perception and/or the reactions to tinnitus in a clinically beneficial way. The parameters of sound that may cause beneficial effects, however, are currently only theorized with limited data supporting their effectiveness. Residual inhibition is the temporary suppression or elimination of tinnitus that is usually observed following appropriate auditory stimulation. Our pilot study investigated the effects of a therapeutic acoustic stimulus that was individually customized to maximize residual inhibition of tinnitus and extend its duration to determine if there could be a sustained suppression of the tinnitus signal (i.e., reduced tinnitus loudness) and a reduction in the psychological and emotional reactions to tinnitus. This pilot study had two objectives: (1) to evaluate the feasibility of residual inhibition technique therapy through daily use of hearing aids and (2) to determine its effects by measuring reactionary changes in tinnitus with the Tinnitus Functional Index (TFI) and perceptual changes in tinnitus loudness. A total of 20 adults (14 males, 6 females; mean age: 58 years, SD = 12.88) with chronic tinnitus were enrolled in a four-visit study that consisted of the following: (1) baseline visit and initiation of the intervention period, (2) a 1-month postintervention visit, (3) 2-month postintervention visit and initiation of a wash-out period, and (4) a 3-month visit to assess the wash-out period and any lasting effects of the intervention. The intervention consisted of fitting bilateral hearing aids and creating an individualized residual inhibition stimulus that was streamed via Bluetooth from a smartphone application to the hearing aids. The participants were instructed to wear the hearing aids and stream the residual inhibition stimulus all waking hours for the 2-month intervention period. During the wash-out period, the participants were instructed to use the hearing aids for amplification, but the residual inhibition stimulus was discontinued. At all visits, the participants completed the TFI, study-specific self-report measures to document perceptions of tinnitus, a psychoacoustic test battery consisting of tinnitus loudness and pitch matching, and a residual inhibition test battery consisting of minimum masking and minimum residual inhibition levels. At the end of the trial, participants were interviewed about the study experience and acceptability of the residual inhibition treatment technique. Repeated measures analyses of variance (ANOVA) were conducted on the two main outcomes (TFI total score and tinnitus loudness) across all four visits. The results showed a significant main effect of visit on the TFI total score ( p < 0.0001). Specifically, the results indicated a significant reduction in TFI total scores from baseline to the 1-month post-intervention period, which remained stable across the 2-month post-intervention period and the wash-out period. The ANOVA results did not show a significant change in tinnitus loudness as a function of visit ( p = 0.480). The majority of the participants reported a positive experience with the study intervention at their exit interview. This pilot study demonstrated that residual inhibition as a sound therapy for tinnitus, specifically through the daily use of hearing aids, was feasible and acceptable to individuals suffering from chronic tinnitus. In addition, participants showed improvement in reactions to tinnitus as demonstrated by sustained reduction in TFI scores on average over the course of the treatment period. Achieving residual inhibition may also provide patients a feeling of control over their tinnitus, and this may have a synergistic effect in reducing the psychological and emotional distress associated with tinnitus. There was no significant reduction in long-term tinnitus loudness resulting from the residual inhibition treatment; however, the current pilot study may not have had sufficient power to detect such a change. The combination of tinnitus suppression and improved psychosocial/emotional reactions to tinnitus may result in a better quality of life in both the short and long term. A larger-scale study is needed to determine the validity of using residual inhibition as a clinical therapy option and to ascertain any effects on both perception and reactions to tinnitus.

The pre-clinical absorption, distribution, metabolism and excretion properties of IPI-926, an orally bioavailable antagonist of the hedgehog signal transduction pathway.

1. IPI-926 is a novel semisynthetic cyclopamine derivative that is a potent and selective Smoothened inhibitor that blocks the hedgehog signal transduction pathway. 2. The in vivo clearance of IPI-926 is low in mouse and dog and moderate in monkey. The volume of distribution is high across species. Oral bioavailability ranges from moderate in monkey to high in mouse and dog. Predicted human clearance using simple allometry is low (24 L h(-1)), predicted volume of distribution is high (469 L) and predicted half-life is long (20 h). 3. IPI-926 is highly bound to plasma proteins and has minimal interaction with human α-1-acid glycoprotein. 4. In vitro metabolic stability ranges from stable to moderately stable. Twelve oxidative metabolites were detected in mouse, rat, dog, monkey and human liver microsome incubations and none were unique to human. 5. IPI-926 is not a potent reversible inhibitor of CYP1A2, 2C8, 2C9 or 3A4 (testosterone). IPI-926 is a moderate inhibitor of CYP2C19, 2D6 and 3A4 (midazolam) with KI values of 19, 16 and 4.5 µM, respectively. IPI-926 is both a substrate and inhibitor (IC50 = 1.9 µM) of P-glycoprotein. 6. In summary, IPI-926 has desirable pre-clinical absorption, distribution, metabolism and excretion properties.