In vivo CAR T-cell generation in non-human primates using lentiviral vectors displaying a multi-domain fusion ligand.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high cost and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVecTM platform, a lentiviral vector capable of generating CAR T-cells in vivo. Here we describe the incorporation of T cell activation and costimulatory signals onto the surface of VivoVecTM particles (VVPs) in the form of a multi-domain fusion protein and show enhanced in vivo transduction and improved CAR-T cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into non-human primates resulted in the robust generation of anti-CD20 CAR T-cells and the complete depletion of B cells for more than 10 weeks. These data validate the VivoVecTM platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies.

Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT): optometric exam improves access and utilization of eye care services.

PURPOSE: To describe the benefits of optometric evaluation for detection of vision-affecting conditions in the context of community-based eye health screenings and identify factors associated with having a recent dilated eye exam. METHODS: Enrolled participants were age 40 and older, living independently in affordable housing developments in New York City. Eye health screening failure and criteria for seeing the on-site study optometrist were defined as visual acuity 20/40 or worse in either eye, intraocular pressure 23-29 mmHg, or an unreadable fundus image. The optometrist conducted a manifest refraction using loose lenses and used a portable slit lamp and ophthalmoscope to perform a non-dilated anterior and posterior segment ocular health evaluation. Demographics, social determinants of health, eye health screening results, and rates of suspected ophthalmic conditions were recorded. To determine factors associated with having a recent dilated eye exam, which was the main outcome for this statistical analysis, a stepwise multivariate logistic regression was performed. RESULTS: A total of 708 participants were screened, 308 attended the optometric exam; mean age 70.7 ± 11.7 [standard deviation (SD)] years. Among this subgroup, 70.1% identified as female, 54.9% self-identified as African American, 39% as Hispanic/Latino, and 26.6% Dominican ethnicity; 78.2% (241/308) had not undergone a dilated eye exam within the last year, 71.4% reported they did not have an eye care provider. Stepwise multivariate logistic regression analysis indicated that participants who self-reported having cataracts (odds ratio (OR) 2.15; 95% confidence interval (CI) 1.03-4.47; p = 0.041), self-reported having glaucoma/glaucoma suspect (OR 5.60; 95% CI 2.02-15.43; p = 0.001), or spoke Spanish as their primary language (OR 3.25; 95% CI 1.48-7.11; p = 0.003) had higher odds of having a recent dilated eye exam. CONCLUSIONS: This community-based screening initiative demonstrated the effectiveness of optometric exams in detecting vision-affecting conditions and identified factors associated with having a recent dilated eye exam. Optometrists play a vital role in increasing access to eye care for high-risk, underserved populations. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04271709).

Survival analysis on subchondral bone length for total knee replacement.

OBJECTIVE: Use subchondral bone length (SBL), a new MRI-derived measure that reflects the extent of cartilage loss and bone flattening, to predict the risk of progression to total knee replacement (TKR). METHODS: We employed baseline MRI data from the Osteoarthritis Initiative (OAI), focusing on 760 men and 1214 women with bone marrow lesions (BMLs) and joint space narrowing (JSN) scores, to predict the progression to TKR. To minimize bias from analyzing both knees of a participant, only the knee with a higher Kellgren-Lawrence (KL) grade was considered, given its greater potential need for TKR. We utilized the Kaplan-Meier survival curves and Cox proportional hazards models, incorporating raw and normalized values of SBL, JSN, and BML as predictors. The study included subgroup analyses for different demographics and clinical characteristics, using models for raw and normalized SBL (merged, femoral, tibial), BML (merged, femoral, tibial), and JSN (medial and lateral compartments). Model performance was evaluated using the time-dependent area under the curve (AUC), Brier score, and Concordance index to gauge accuracy, calibration, and discriminatory power. Knee joint and region-level analyses were conducted to determine the effectiveness of SBL, JSN, and BML in predicting TKR risk. RESULTS: The SBL model, incorporating data from both the femur and tibia, demonstrated a predictive capacity for TKR that closely matched the performance of the BML score and the JSN grade. The Concordance index of the SBL model was 0.764, closely mirroring the BML's 0.759 and slightly below JSN's 0.788. The Brier score for the SBL model stood at 0.069, showing comparability with BML's 0.073 and a minor difference from JSN's 0.067. Regarding the AUC, the SBL model achieved 0.803, nearly identical to BML's 0.802 and slightly lower than JSN's 0.827. CONCLUSION: SBL's capacity to predict the risk of progression to TKR highlights its potential as an effective imaging biomarker for knee osteoarthritis.

Manhattan Vision Screening and Follow-Up Study: (NYC-SIGHT)Tele-Retinal Image Findings and Importance of Photography.

Purpose: To describe tele-retinal abnormality image findings from the Manhattan Vision Screening and Follow-up Study (NYC-SIGHT), which aims to investigate whether community-based eye health outreach strategies using telemedicine can improve visual outcomes among at-risk populations in Upper Manhattan. Methods: A 5-year prospective, cluster-randomized clinical trial was conducted. Eligible individuals aged 40 years and older were recruited from affordable housing developments and senior centers in New York City. Participants underwent on-site eye health screening (best-corrected visual acuity, intraocular pressure [IOP] measurements, and fundus photography). Fundus images were graded via telemedicine by a retina specialist. Multivariate logistic regression modeling was used to assess the factors associated with abnormal retinal findings requiring referral to ophthalmology. Results: Participants with a retinal abnormality on fundus photography (n = 157) were predominantly older adults, with a mean age of 68.4 ± 11.1 years, female (63.7%), African American (50.3%), and Hispanic (43.3%). A total of 32 participants in our study passed the vision and IOP screening but had an abnormal retinal image and ocular pathology that would have been missed without fundus photography. Individuals who self-identified as having preexisting glaucoma (odds ratio [OR] = 3.749, 95% confidence interval [CI] = 1.741-8.074, p = 0.0001) and had severe vision impairment (OR = 4.1034, 95% CI = 2.0740-8.1186, p = 0.000) at the screening had significantly higher odds of having an abnormal retinal image. Conclusion: This community-based study targeted populations at-risk for eye disease, improved access to eye care, detected a significant number of retinal image abnormalities requiring follow-up by using telemedicine, and provided evidence of the importance of fundus photography during eye health screenings. CTR number: NCT04271709.

Two-Year Outcomes of Cochlear Implant Use for Children With Unilateral Hearing Loss: Benefits and Comparison to Children With Normal Hearing.

OBJECTIVES: Children with severe-to-profound unilateral hearing loss, including cases of single-sided deafness (SSD), lack access to binaural cues that support spatial hearing, such as recognizing speech in complex multisource environments and sound source localization. Listening in a monaural condition negatively impacts communication, learning, and quality of life for children with SSD. Cochlear implant (CI) use may restore binaural hearing abilities and improve outcomes as compared to alternative treatments or no treatment. This study investigated performance over 24 months of CI use in young children with SSD as compared to the better hearing ear alone and to children with bilateral normal hearing (NH). DESIGN: Eighteen children with SSD who received a CI between the ages of 3.5 and 6.5 years as part of a prospective clinical trial completed assessments of word recognition in quiet, masked sentence recognition, and sound source localization at regular intervals out to 24-month postactivation. Eighteen peers with bilateral NH, matched by age at the group level, completed the same test battery. Performance at 24-month postactivation for the SSD group was compared to the performance of the NH group. RESULTS: Children with SSD have significantly poorer speech recognition in quiet, masked sentence recognition, and localization both with and without the use of the CI than their peers with NH. The SSD group experienced significant benefits with the CI+NH versus the NH ear alone on measures of isolated word recognition, masked sentence recognition, and localization. These benefits were realized within the first 3 months of use and were maintained through the 24-month postactivation interval. CONCLUSIONS: Young children with SSD who use a CI experience significant isolated word recognition and bilateral spatial hearing benefits, although their performance remains poorer than their peers with NH.

Cochlear Nerve Deficiency in Pediatric Unilateral Hearing Loss and Asymmetric Hearing Loss.

INTRODUCTION: The rates of cochlear nerve abnormalities and cochlear malformations in pediatric unilateral hearing loss (UHL) are conflicting in the literature, with important implications on management. The aim of this study was to investigate the incidence of cochlear nerve deficiency (CND) in pediatric subjects with UHL or asymmetric hearing loss (AHL). METHODS: A retrospective chart review of pediatric subjects <18 years of age evaluated for UHL or AHL with fine-cut heavily T2-weighted magnetic resonance imaging (MRI) between January 2014 and October 2019 (n = 291) at a tertiary referral center was conducted. MRI brain and computed tomography temporal bone were reviewed for the presence of inner ear malformations and/or CND. Status of the ipsilateral cochlear nerve and inner ear was evaluated. Pure tone average (PTA) at 500, 1,000 and 2,000 Hz was assessed. RESULTS: 204 subjects with UHL and 87 subjects with AHL were included. CND (aplasia or hypoplasia) was demonstrated in 61 pediatric subjects with UHL (29.9%) and 10 with AHL (11.5%). Ipsilateral cochlear malformations were noted in 25 subjects with UHL (12.3%) and 11 with AHL (12.6%), and ipsilateral vestibular malformations in 23 (11.3%) and 12 (13.8%) ears, respectively. Median PTA was statistically significantly higher in ears with CND (98.33) than ears with normal nerves (90.84). DISCUSSION/CONCLUSION: Imaging demonstrated a high incidence of inner ear malformations, particularly CND, in pediatric subjects with UHL. Auditory findings indicated CND cannot be ruled out by thresholds alone as some CND ears did demonstrate measurable hearing. Radiologic evaluation by MRI should be performed in all patients within this population to guide counseling and management of hearing loss based on etiology, with implications on candidacy for cochlear implantation.

American Cochlear Implant Alliance Task Force Guidelines for Clinical Assessment and Management of Cochlear Implantation in Children With Single-Sided Deafness.

More children with single-sided deafness (SSD) are receiving cochlear implants (CIs) due to the expansion of CI indications. This unique group of pediatric patients has different needs than the typical recipient with bilateral deafness and requires special consideration and care. The goal of cochlear implantation in these children is to provide bilateral input to encourage the development of binaural hearing. Considerations for candidacy and follow-up care should reflect and measure these goals. The purpose of this document is to review the current evidence and provide guidance for CI candidacy, evaluation, and management in children with SSD.

Delaying Cochlear Implantation Impacts Postoperative Speech Perception of Nontraditional Pediatric Candidates.

INTRODUCTION: As pediatric cochlear implant (CI) candidacy expands, children with greater degrees of residual hearing are receiving CIs. These nontraditional candidates have audiometric thresholds that meet adult manufacturer labeling but are better than current pediatric guidelines allow. The purpose of this study was to determine the impact of delayed cochlear implantation on speech perception in nontraditional pediatric CI recipients. METHODS: Pediatric CI recipients with a history of progressive hearing loss and a preoperative 4-frequency pure-tone average of ≤75 dB HL at the time of implantation were considered for this retrospective study. Preoperative serial audiograms and word recognition scores were reviewed, and a method was created to establish a date when each individual ear 1st met nontraditional candidacy. The length of time between the date of candidacy and implantation was calculated and defined as the "delay time." A multiple linear regression investigated delay time, age at surgery, surgery type (1st vs. 2nd side), and array type as predictive factors of maximum postoperative Consonant-Nucleus-Consonant (CNC) word scores. A one-way ANCOVA was performed comparing the postoperative CNC scores between subjects grouped by delay time. RESULTS: A significant regression was found (F(4, 38) = 5.167, p = 0.002, R2 = 0.353). Both age at implantation (p = 0.023) and delay time (p = 0.002) predicted CNC word scores. Longer delay time was associated with poorer word recognition scores, while older age at implantation correlated with higher CNC word scores in this progressive hearing loss group. A significant difference was noted between subjects implanted with <1 year of delay and those with 3 or more years of delay (p = 0.003). All ears implanted within a year of candidacy achieved word recognition abilities that are generally accepted as above average (M = 84.91). CONCLUSION: CI candidacy for adults has evolved to allow for greater degrees of residual hearing, while audiometric guidelines for children have not changed since 2000. Our findings suggest that delay of cochlear implantation, even for children with significant levels of residual hearing, leads to poorer outcomes. Modified candidacy guidelines for children should be established to expedite referral to multidisciplinary CI teams and minimize delays in this population.

Recommendations for Measuring the Electrically Evoked Compound Action Potential in Children With Cochlear Nerve Deficiency.

OBJECTIVES: This study reports a method for measuring the electrically evoked compound action potential (eCAP) in children with cochlear nerve deficiency (CND). DESIGN: This method was developed based on experience with 50 children with CND who were Cochlear Nucleus cochlear implant users. RESULTS: This method includes three recommended steps conducted with recommended stimulating and recording parameters: initial screen, pulse phase duration optimization, and eCAP threshold determination (i.e., identifying the lowest stimulation level that can evoke an eCAP). Compared with the manufacturer-default parameters, the recommended parameters used in this method yielded a higher success rate for measuring the eCAP in children with CND. CONCLUSIONS: The eCAP can be measured successfully in children with CND using recommended parameters. This specific method is suitable for measuring the eCAP in children with CND in clinical settings. However, it is not suitable for intraoperative eCAP recordings due to the extensive testing time required.

Electric-Acoustic Stimulation Outcomes in Children.

OBJECTIVES: This study investigates outcomes in children fit with electric-acoustic stimulation (EAS) and addresses three main questions: (1) Are outcomes with EAS superior to outcomes with conventional electric-only stimulation in children? (2) Do children with residual hearing benefit from EAS and conventional electric-only stimulation when compared with the preoperative hearing aid (HA) condition? (3) Can children with residual hearing derive benefit from EAS after several years of listening with conventional electric-only stimulation? DESIGN: Sixteen pediatric cochlear implant (CI) recipients between 4 and 16 years of age with an unaided low-frequency pure tone average of 75 dB HL in the implanted ear were included in two study arms. Arm 1 included new recipients, and Arm 2 included children with at least 1 year of CI experience. Using a within-subject design, participants were evaluated unilaterally with the Consonant-Nucleus-Consonant (CNC) word list in quiet and the Baby Bio at a +5 dB SNR using an EAS program and a conventional full electric (FE) program. Arm 1 participants' scores were also compared with preoperative scores. RESULTS: Speech perception outcomes were statistically higher with the EAS program than the FE program. For new recipients, scores were significantly higher with EAS than preoperative HA scores for both the CNC and Baby Bio in noise; however, after 6 months of device use, results in the FE condition were not significantly better than preoperative scores. Long-term FE users benefited from EAS over their FE programs based on CNC word scores. CONCLUSIONS: Whether newly implanted or long-term CI users, children with residual hearing after CI surgery can benefit from EAS. Cochlear implantation with EAS fitting is a viable option for children with HAs who have residual hearing but have insufficient access to high-frequency sounds and poor speech perception.

Residual Cochlear Function in Adults and Children Receiving Cochlear Implants: Correlations With Speech Perception Outcomes.

OBJECTIVES: Variability in speech perception outcomes with cochlear implants remains largely unexplained. Recently, electrocochleography, or measurements of cochlear potentials in response to sound, has been used to assess residual cochlear function at the time of implantation. Our objective was to characterize the potentials recorded preimplantation in subjects of all ages, and evaluate the relationship between the responses, including a subjective estimate of neural activity, and speech perception outcomes. DESIGN: Electrocochleography was recorded in a prospective cohort of 284 candidates for cochlear implant at University of North Carolina (10 months to 88 years of ages). Measurement of residual cochlear function called the "total response" (TR), which is the sum of magnitudes of spectral components in response to tones of different stimulus frequencies, was obtained for each subject. The TR was then related to results on age-appropriate monosyllabic word score tests presented in quiet. In addition to the TR, the electrocochleography results were also assessed for neural activity in the forms of the compound action potential and auditory nerve neurophonic. RESULTS: The TR magnitude ranged from a barely detectable response of about 0.02 µV to more than 100 µV. In adults (18 to 79 years old), the TR accounted for 46% of variability in speech perception outcome by linear regression (r = 0.46; p < 0.001). In children between 6 and 17 years old, the variability accounted for was 36% (p < 0.001). In younger children, the TR accounted for less of the variability, 15% (p = 0.012). Subjects over 80 years old tended to perform worse for a given TR than younger adults at the 6-month testing interval. The subjectively assessed neural activity did not increase the information compared with the TR alone, which is primarily composed of the cochlear microphonic produced by hair cells. CONCLUSIONS: The status of the auditory periphery, particularly of hair cells rather than neural activity, accounts for a large fraction of variability in speech perception outcomes in adults and older children. In younger children, the relationship is weaker, and the elderly differ from other adults. This simple measurement can be applied with high throughput so that peripheral status can be assessed to help manage patient expectations, create individually-tailored treatment plans, and identify subjects performing below expectations based on residual cochlear function.

Early steroid withdrawal results in improved patient and graft survival and lower risk of post-transplant cardiovascular risk profiles: A single-center 10-year experience.

Long-term use of steroids results in predictable secondary effects that can lead to increased morbidity and mortality. In this study, we present 10 years worth of data of early steroid withdrawal (ESW) immunosuppression consisting of mycophenolate, sirolimus, and tacrolimus. From 2003 to 2013, 563 kidney transplant recipients were weaned off steroids prior to discharge. We compared outcomes with that of our 65 historical controls maintained on steroids. We analyzed graft and patient survival and determined the incidence of steroid-related comorbidities such as hypertension, hypercholesterolemia, diabetes, coronary artery disease, and weight gain. Patients on ESW maintenance immunosuppression had improved patient and graft survival compared to controls. (HR: 0.23; P≤.011, 0.57; P=.026). Rates of biopsy-proven acute rejection were not different among both groups (HR: 1.24; P=.610). Incidence of post-transplant diabetes were reduced but not statistically significant (OR: 0.67; P=.138). Additionally, the development of hypertension (OR: 0.86, P≤.01), hypercholesterolemia (RR: 0.82; P=.027), CAD (RR: 0.43; P=.002), and >20 lbs. weight gain (RR: 0.29; P≤.01) was significantly improved over 10 years following initiation of ESW protocols. Early steroid withdrawal in renal transplant recipients results in improved patient and graft survival as well as better rates of post-transplant comorbid conditions.

The establishment of a porcine rheumatoid arthritis model: Collagen induced arthritis minipig model.

Rheumatoid arthritis (RA) research has been largely dependent on collagen induced arthritis (CIA) rodent models, however, they may not translate well to humans due to innate differences in the size, physiology and lifespan. The present study aimed to establish a CIA porcine model with the physical, hematological, histopathological and etiological properties closer to their human equivalent in an attempt to better meet the needs of RA research. Three month old minipigs were administered of bovine type II collagen (CII) emulsified with complete Freund's adjuvants on Day 1 and incomplete Freund's adjuvants on Day 22, via an intradermal or intra-articular route. The clinical, radiological and hematological assessments of immunized animals were made periodically until Day 43, during which period the onset and progression of arthritis was recorded and characterized. In addition, the histopathological and micro-tomographic assessments of the cartilage degradation with regard to mononuclear cell infiltration, and joint deformity indicated a higher severity in the intradermal injection group over the intra-articular group. With confirmation of the susceptibility to heterogeneous CII for arthritis induction in minipig, the potential suitability of this test system as a large animal model for RA has been demonstrated.

Acoustically evoked auditory change complex in children with auditory neuropathy spectrum disorder: a potential objective tool for identifying cochlear implant candidates.

OBJECTIVES: The overall aim of the study was to evaluate the feasibility of using electrophysiological measures of the auditory change complex (ACC) to identify candidates for cochlear implantation in children with auditory neuropathy spectrum disorder (ANSD). To achieve this overall aim, this study (1) assessed the feasibility of measuring the ACC evoked by temporal gaps in a group of children with ANSD across a wide age range and (2) investigated the association between gap detection thresholds (GDTs) measured by the ACC recordings and open-set speech-perception performance in these subjects. DESIGN: Nineteen children with bilateral ANSD ranging in age between 1.9 and 14.9 years (mean: 7.8 years) participated in this study. Electrophysiological recordings of the auditory event-related potential (ERP), including the onset ERP response and the ACC, were completed in all subjects and open-set speech perception was evaluated for a subgroup of 16 subjects. For the ERP recordings, the stimulus was a Gaussian noise presented through ER-3A insert earphones to the test ear. Two stimulation conditions were used. In the "control condition," the stimulus was an 800-msec Gaussian noise. In the "gapped condition," the stimuli were two noise segments, each being 400 msec in duration, separated by one of five gaps (i.e., 5, 10, 20, 50, or 100 msec). The interstimulation interval was 1200 msec. The aided open-set speech perception ability was assessed using the Phonetically Balanced Kindergarten (PBK) word lists presented at 60 dB SPL using recorded testing material in a sound booth. For speech perception tests, subjects wore their hearing aids at the settings recommended by their clinical audiologists. For a subgroup of five subjects, psychophysical GDTs for the Gaussian noise were also assessed using a three-interval, three-alternative forced-choice procedure. RESULTS: Responses evoked by the onset of the Gaussian noise (i.e., onset responses) were recorded in all stimulation conditions from all subjects tested in this study. The presence/absence, peak latency and amplitude, and response width of the onset response did not correlate with aided PBK word scores. The objective GDTs measured with the ACC recordings from 17 subjects ranged from 10 to 100 msec. The ACC was not recorded from two subjects for any gap durations tested in this study. There was a robust negative correlation between objective GDTs and aided PBK word scores. In general, subjects with prolonged objective GDTs showed low-aided PBK word scores. GDTs measured using electrophysiological recordings of the ACC correlated well with those measured using psychophysical procedures in four of five subjects who were evaluated using both procedures. CONCLUSIONS: The clinical application of the onset response in predicting open-set speech-perception ability is relatively limited in children with ANSD. The ACC recordings can be used to objectively evaluate temporal resolution abilities in children with ANSD having no severe comorbidities, and who are older than 1.9 years. The ACC can potentially be used as an objective tool to identify poor performers among children with ANSD using properly fit amplification, and who are thus, cochlear implant candidates.

Improving adherence to national recommendations for zoster vaccination through simple interventions.

OBJECTIVE: In 2011, 15.8% of eligible patients in the United States were vaccinated against herpes zoster (HZ). To increase the usage of the HZ vaccine by studying physicians' knowledge, attitudes, practices, and perceived obstacles after interventions to overcome barriers. METHODS: General internal medicine physicians were surveyed with a cross-sectional internet survey from October to December 2011 before interventions to increase the use of the HZ vaccine and 1 year later. Interventions included education, increasing availability at the medical center pharmacy, and electronic medical record reminders. Outcome measures included changes in knowledge, attitudes, and practices, and perceived barriers. McNemar chi-square tests were used to compare the changes from the baseline survey for physicians who completed the follow-up survey. RESULTS: Response rate for the baseline study was 33.5% (89/266) and for the follow-up was 29.8% (75/252). Fifty-five completed both surveys. There was a decrease from 57% at baseline to 40% at follow-up in the proportion of physicians who reported that less than 10% of their patients were vaccinated. They were more likely to know the HZ annual incidence (30% baseline; 70% follow-up; P=0.02), and report having educational information for physicians (7% baseline; 27% follow-up; P=0.003). The top helpful intervention was nursing administration of the vaccine. Average monthly HZ vaccine usage in the affiliated outpatient pharmacy increased in 10 months between surveys by 156% compared with the 3 months before the baseline survey. CONCLUSIONS: Interventions implemented during the study led to an increase in physicians' basic knowledge of the HZ vaccine and an increase in usage at the affiliated pharmacy.

Long-Term Perceived Benefit of Pediatric Cochlear Implant Users with Unilateral Hearing Loss.

OBJECTIVE: To assess the perceived benefit of cochlear implant (CI) use for children with unilateral hearing loss (UHL) and evaluate whether perceived abilities are associated with performance on measures of speech recognition and spatial hearing. METHOD: Nineteen children with moderate-to-profound UHL underwent cochlear implantation. The Speech Spatial and Qualities of Hearing Questionnaire modified for children (SSQ-C) were completed by parental proxy pre-operatively and at 3, 6, 9, 12, 18, and 24 months post-activation. Linear mixed models evaluated perceived benefits over the study period. Pearson correlations assessed the association between subjective report and performance on measures of word recognition with the CI alone and spatial hearing (speech recognition in spatially-separated noise and sound source localization) in the combined condition (CI plus contralateral ear). RESULTS: For the SSQ-C, parents reported significant improvements with CI use as compared to pre-operative perceptions (p < 0.001); improved perceptions were either maintained or continued to improve over the 2-year post-activation period. Perceived benefit did not significantly correlate with word recognition with the CI alone or spatial hearing outcomes in the combined condition. CONCLUSION: Families of children with UHL observed benefits of CI use early after cochlear implantation that was maintained with long-term device use. Responses to subjective measures may broaden our understanding of the experiences of pediatric CI users with UHL in addition to outcomes on typical measures of CI performance. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:919-925, 2024.

Effect of Age and Unaided Acoustic Hearing on Pediatric Cochlear Implant Users' Ability to Distinguish Yes/No Statements and Questions.

PURPOSE: The purpose of this study was to evaluate the ability to discriminate yes/no questions from statements in three groups of children: bilateral cochlear implant (CI) users, nontraditional CI users with aidable hearing preoperatively in the ear to be implanted, and controls with normal hearing. Half of the nontraditional CI users had sufficient postoperative acoustic hearing in the implanted ear to use electric-acoustic stimulation, and half used a CI alone. METHOD: Participants heard recorded sentences that were produced either as yes/no questions or as statements by three male and three female talkers. Three raters scored each participant response as either a question or a statement. Bilateral CI users (n = 40, 4-12 years old) and normal-hearing controls (n = 10, 4-12 years old) were tested binaurally in the free field. Nontraditional CI recipients (n = 22, 6-17 years old) were tested with direct audio input to the study ear. RESULTS: For the bilateral CI users, performance was predicted by age but not by 125-Hz acoustic thresholds; just under half (n = 17) of the participants in this group had measurable 125-Hz thresholds in their better ear. For nontraditional CI recipients, better performance was predicted by lower 125-Hz acoustic thresholds in the test ear, and there was no association with participant age. Performance approached that of the normal-hearing controls for some participants in each group. CONCLUSIONS: Results suggest that a 125-Hz acoustic hearing supports discrimination of yes/no questions and statements in pediatric CI users. Bilateral CI users with little or no acoustic hearing at 125 Hz develop the ability to perform this task, but that ability emerges later than for children with better acoustic hearing. These results underscore the importance of preserving acoustic hearing for pediatric CI users when possible.

Factors that influence performance in pediatric cochlear implant recipients with cochlear nerve deficiency.

OBJECTIVES: Children with cochlear nerve deficiency (CND) have wide variability in outcomes with cochlear implant (CI) use. The current study aims to report a large cohort of pediatric CI recipients with CND and to evaluate for factors that may predict improved performance. METHODS: The current study is a retrospective review of pediatric CI recipients with CND at a tertiary academic hospital. Variables including cochlear nerve status (hypoplasia vs aplasia), age at implantation, cochleovestibular malformation, bony cochlear nerve aperture, internal auditory canal aperture, and cognitive delay were evaluated for predictors of postoperative performance. A stepwise multinomial regression analysis was performed. RESULTS: Forty-seven CI recipients (54 ears) were included in the analysis. A majority (59%) showed auditory capabilities with their CI. Twenty percent of recipients achieved some level of open-set speech perception with their CI. The regression analysis identified cochlear nerve status and cognitive delay as predictors of performance. CI recipients with cochlear nerve hypoplasia had significantly improved performance compared to those with aplasia (p = 0.003). Recipients with cognitive delay had more limited benefit than those without cognitive delay (p = 0.033). CONCLUSIONS: Children with CND can benefit from CI use, with outcomes spanning from non-use to development of spoken language. Predictive factors for improved performance include a lack of cognitive delay and cochlear hypoplasia rather than aplasia. These can be important considerations for parent counseling and decision making.

Manhattan Vision Screening and Follow-up Study (NYC-SIGHT): Vision and refractive error results.

CLINICAL RELEVANCE: Optometrists can play a key role in providing access to eye care in underserved populations by organising community-based eye health screenings that include optometric exams to detect vision impairment and uncorrected refractive error. BACKGROUND: Community-based eye health screenings and optometric exams were conducted in the NYC-SIGHT Study. METHODS: A sub-analysis of vision impairment and refractive error results within a 5-year prospective, cluster-randomised clinical trial. Eligible individuals (age ≥40 years) were recruited from 10 affordable housing developments in Upper Manhattan. Developments were randomised into usual care (received glasses prescription only) and intervention (free glasses) groups. Participants with 6/12 visual acuity or worse, intraocular pressure 23-29 mmHg, or an unreadable fundus image were scheduled with the study optometrist for refraction and a non-dilated exam. Visual improvement data were obtained by comparing the presenting acuity at screening compared to the best corrected acuity after refraction by the optometrist. Chi-square, two-sample t-tests, and a stepwise multivariate logistic regression model were used to determined factors associated with improvable visual impairment. RESULTS: Seven hundred and eight participants completed screening, 308 received an optometric exam. Those with improvable vision impairment (n = 251), mean age: 69.8 years, 70.5% female, 53% African American, 39.8% Hispanic, >95% had health insurance. Refractive error diagnosed in 87.8% of the participants; lines of improvement: 2 lines (n = 59), 3 to 5 lines (n = 120), and ≥6 lines (n = 72). Stepwise multivariate logistic regression analysis showed that participants with visual acuity 6/12 or worse (odds ratio 16.041, 95% confidence interval 6.009 to 42.822, p = 0.000) or a normal fundus image (odds ratio 2.783, 95% confidence interval 1.001 to 7.740, p = 0.05) had significantly higher odds of improvable vision impairment. CONCLUSION: This innovative, targeted community-based study included an optometrist who detected high rates of refractive error and improvable vision impairment in an underserved population living in New York City.

Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT): Subanalysis of Referral to Ophthalmology.

PURPOSE: The Manhattan Vision Screening and Follow-up Study aims to provide access to eye care for underserved populations, detect native rates of ocular pathology, and refer participants with eye disease to ophthalmology. This subanalysis describes the reasons for referral to ophthalmology and identifies risk factors associated with being referred. METHODS: Enrolled participants were aged ≥40 years, living independently in public housing developments and able to provide consent for eye health screenings. Those with habitual visual acuity 20/40 or worse, intraocular pressure (IOP) 23-29 mmHg, or an unreadable fundus image failed and were scheduled with the on-site optometrist. The optometric exam determined whether further referral to ophthalmology for a clinic exam was warranted. Those with an abnormal image or IOP ≥30 mmHg were referred directly to ophthalmology. Main outcome was factors associated with referral to ophthalmology. RESULTS: A total of 708 individuals completed the eye health screening over 15 months. A total of 468 participants were referred to ophthalmology (250 had an abnormal image and 218 were referred by the optometrist). Those referred were predominantly older adults (mean age 70.0 ± 11.4 years), female (66.7%), African American (55.1%) and Hispanic (39.5%). Seventy percent of participants had not had a recent eye exam. Stepwise multivariate logistic regression analysis showed that participants with pre-existing glaucoma (OR 3.14, 95% CI 1.62 to 6.08, p = 0.001), an IOP ≥23 mmHg (OR 5.04, 95% 1.91 to 13.28, p = 0.001), or vision impairment (mild) (OR 2.51, 95% CI 1.68 to 3.77, p = 0.001) had significantly higher odds of being referred to ophthalmology. CONCLUSION: This targeted community-based study in Upper Manhattan provided access to eye care and detected a significant amount of ocular pathology requiring referral to ophthalmology in this high-risk population.