Observational Real-World Study to Assess Clinical Characteristics and Device Satisfaction in Patients with COPD Treated with Glycopyrrolate/eFlow® CS.

Purpose: To assess clinical characteristics and device satisfaction of patients with chronic obstructive pulmonary disease (COPD) treated with glycopyrrolate/eFlow® Closed System (CS) nebulizer (further referred to as eFlow) under real-world conditions. Participants and Methods: Patients with COPD currently using eFlow were identified by the study sponsor. Consenting patients who met study inclusion criteria completed a cross-sectional survey that included a device satisfaction questionnaire. Means, medians, and standard deviations were calculated. Results: Sixty-six patients met inclusion criteria and completed the survey. Participants' mean ± standard deviation age was 64.9 ± 11.9 years and the majority were white (86.4%) and female (59.1%). Almost two-thirds were former smokers. Thirty-nine (59.1%) reported their COPD to be severe/very severe and 38 (57.6%) reported a COPD exacerbation resulting in a hospitalization, ER visit, or medication modification over the past 12 months. Among 55 participants who had previously used another type of nebulizer, 44 (80%) were overall "much more"/"somewhat more" satisfied with the eFlow compared with their previous nebulizer(s). Regardless of prior nebulizer use, 60 (90.9%) participants were "satisfied"/"very satisfied" overall with the eFlow. Assembly and disassembly, operation, and cleaning were perceived as being "easy"/"very easy" by at least 65% of participants. Among all participants, 57 (86.4%) were "confident"/"very confident" of glycopyrrolate administration. On a Likert scale of 1 ("I don't like it") to 7 ("I like it a lot"), mean scores were at least 5.9 for portability, ease of cleaning, size, weight, short administration time, and relative silence of the device. Over 80% of participants said they "probably"/"definitely" would continue to use eFlow. Conclusion: Based on this real-world study, the majority of patients were highly satisfied with, and confident in, using eFlow.

Treatment Patterns, Healthcare Resource Utilization, and Costs Among Medicare Patients with Multiple Sclerosis in Relation to Disease-Modifying Therapy and Corticosteroid Treatment.

INTRODUCTION: Despite the increasing age of the multiple sclerosis (MS) patient population, data are lacking on MS patients in later life. This retrospective study investigated treatment patterns, healthcare resource utilization (HCRU), and healthcare costs (HCCs) for patients enrolled in Medicare, in relation to disease-modifying therapy (DMT) and corticosteroid treatment as a marker for relapse. METHODS: Medical and pharmacy claims between January 1, 2010 and July 31, 2015 identified MS patients. The anchor date was defined as the most recent MS claim. Analyses were performed on claims in the 12-month baseline period before the anchor date. Outcomes were stratified by DMT use and number (0, 1, or ≥ 2) of corticosteroid treatments. RESULTS: Among Medicare MS patients (n = 7072; mean age 57 years), 66% received DMT during the baseline period; 31% had 1 claim and 16% had ≥ 2 claims for corticosteroids. Compared with patients not receiving DMT, patients on DMT were less likely to receive corticosteroids (39% vs 62%) and had fewer all-cause hospitalization episodes and ER visits. DMT use was associated with lower HCRU but higher HCCs in patients both with and without corticosteroid treatment. DMT switching rates were low, both among patients with no corticosteroid (5.6%) and patients with 1 (9.3%) or ≥ 2 (11.1%) corticosteroid treatments. DMT switches were most frequently from an injectable to an oral therapy. CONCLUSION: In Medicare patients with MS, DMT use was associated with higher HCCs but lower HCRU, indicative of better health outcomes; however, low DMT switching rates may be an indicator of possible clinical inertia. FUNDING: Sanofi. Plain language summary available for this article.

Verbal Working Memory in Children With Cochlear Implants.

Purpose: Verbal working memory in children with cochlear implants and children with normal hearing was examined. Participants: Ninety-three fourth graders (47 with normal hearing, 46 with cochlear implants) participated, all of whom were in a longitudinal study and had working memory assessed 2 years earlier. Method: A dual-component model of working memory was adopted, and a serial recall task measured storage and processing. Potential predictor variables were phonological awareness, vocabulary knowledge, nonverbal IQ, and several treatment variables. Potential dependent functions were literacy, expressive language, and speech-in-noise recognition. Results: Children with cochlear implants showed deficits in storage and processing, similar in size to those at second grade. Predictors of verbal working memory differed across groups: Phonological awareness explained the most variance in children with normal hearing; vocabulary explained the most variance in children with cochlear implants. Treatment variables explained little of the variance. Where potentially dependent functions were concerned, verbal working memory accounted for little variance once the variance explained by other predictors was removed. Conclusions: The verbal working memory deficits of children with cochlear implants arise due to signal degradation, which limits their abilities to acquire phonological awareness. That hinders their abilities to store items using a phonological code.

Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) Therapy Adherence for Patients with Type 2 Diabetes in a Medicare Population.

INTRODUCTION: Anti-diabetes medication regimen adherence is a clinical challenge in elderly patients with type 2 diabetes (T2D) and other comorbidities associated with aging. Glucagon-like peptide-1 receptor agonists (GLP-1RA) therapies such as exenatide once weekly (QW), exenatide twice daily (BID), and liraglutide once daily (QD) are an increasingly used class of drugs with proven efficacy and tolerability. Real-world evidence on adherence to GLP-1RAs in elderly or disabled patients is limited. To further the understanding of this drug class, the current study examined medication adherence in Medicare patients aged ≥65 years with T2D initiating a GLP-1RA. METHODS: This retrospective cohort study used medical and pharmacy claims between 2010 and 2013 for Medicare members in a United States health plan diagnosed with T2D who were new initiators of either exenatide QW (n = 537), exenatide BID (n = 923), or liraglutide QD (n = 3,673). Included patients were between the ages of 65 and 89 and were continuously enrolled for 6 months pre- and post-index. Medication adherence was examined during the post-index period using proportion of days covered (PDC) ≥80% and ≥90%. RESULTS: A significantly higher percentage of patients receiving exenatide QW had a PDC ≥80% (43.2%) versus exenatide BID (39.0%, P < 0.01) and liraglutide QD (35.0%, P < 0.001). The patients receiving exenatide QW were significantly more likely to reach a PDC of ≥90% (37.2%, P < 0.001) than those initiating exenatide BID (20.6%) or liraglutide QD (23.3%). CONCLUSIONS: While results from this retrospective study suggest room for improvement in adherence to GLP-1RAs, medication adherence rates for patients initiating therapy with exenatide QW were higher than patients initiating therapy with exenatide BID or liraglutide QD. Further research is needed to validate these findings in other T2D patient populations. FUNDING: AstraZeneca Pharmaceuticals.

A Comparison of Health Care Resource Utilization and Costs for Patients with Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal Steroids and Intranasal Antihistamines.

BACKGROUND: Allergic rhinitis (AR) is a common condition that can be treated with a number of different therapies. Treatments such as intranasal antihistamines (INAs) and intranasal steroids (INSs) are widely used by AR patients. For some allergy sufferers, a combination of therapies, specifically an INA and an INS, is required to address their symptoms. A new treatment, the formulation of azelastine hydrochloride and fluticasone pro-pionate used as a single spray (MP-AzeFlu), has become available for AR patients who need both types of treatment. In this regard, the comparison with the alternative concomitant use of INAs and INSs is of interest. The current study examines the health care resource utilization and costs for each cohort. OBJECTIVE: To examine the resource utilization and costs associated with AR for patients treated with MP-AzeFlu or concurrent therapy with single-ingredient INA and INS sprays (free-combination therapy). METHODS: A retrospective administrative claims study for commercially insured patients from a large U.S. health plan was performed. Patients with an AR diagnosis and a prescription claim for MP-AzeFlu or free-combination therapy between September 1, 2012, and September 30, 2013, were identified. Patients were aged at least 12 years at index date (first prescription fill for intranasal therapy) and were required to have 12 months pre-index and 6 months post-index of continuous enrollment. Health care resource utilization and costs were assessed for the post-index period. The cohorts were adjusted on baseline demographic and clinical characteristics using inverse propensity treatment weights. Other covariates, prescriber specialty, product switching during the post-index period, and pre-index total costs were included in the regression models measuring outcomes. One clinical characteristic of interest was the presence of asthma as comorbidity. A subset analysis of AR patients with asthma was also performed. RESULTS: All-cause-related pharmacy fills as well as pharmacy, medical, and total costs were significantly reduced by using MP-AzeFlu (N = 810) instead of the free combination of drugs (N = 726). For AR-related health care resource utilization, the MP-AzeFlu cohort had significantly fewer pharmacy fills than the free-combination cohort (1.01 and 1.17, respectively; P < 0.001) with no significant difference in outpatient services and specialist visits (P = 0.139 and P = 0.117, respectively). Six-month AR-related pharmacy and total costs were significantly lower (P < 0.001 and P = 0.001) for the MP-AzeFlu cohort ($128 and $334, respectively) than the free-combination cohort ($268 and $458, respectively). There was no statistically significant difference in AR-related medical costs between the 2 cohorts (P = 0.454). For the subcohort of AR patients with asthma, the MP-AzeFlu cohort had lower 6-month asthma resource utilization and costs than the free-combination cohort. CONCLUSIONS: These findings suggest that, for AR patients needing INAs and INSs, the single-spray formulation MP-AzeFlu had better economic outcomes than for patients who rely on the free combination of these agents. MP-AzeFlu also appears to keep asthma-related utilization and costs down for those AR patients who also suffer from asthma. Potential explanations for these findings are explored. DISCLOSURES: This study was funded by Meda Pharmaceuticals. Authors were either employed by Meda Pharmaceuticals or received consulting fees from Meda Pharmaceuticals. Comprehensive Health Insights and Sedaghat received funding from Meda Pharmaceuticals as a consultant to participate in this study. Dufour and Caldwell-Tarr are employees of Comprehensive Health Insights. Harrow is currently employed by TESARO. This study was conceived by Harrow, Dufour, and Caldwell-Tarr. All authors contributed to the design of the study. Dufour took the lead in data collection, along with Caldwell-Tarr, and data interpretion was performed by Harrow, along with the other authors. Analyses were performed by Dufour. The manuscript was written and revised by all authors.

Nonword repetition in children with cochlear implants: a potential clinical marker of poor language acquisition.

PURPOSE: Cochlear implants (CIs) can facilitate the acquisition of spoken language for deaf children, but challenges remain. Language skills dependent on phonological sensitivity are most at risk for these children, so having an effective way to diagnose problems at this level would be of value for school speech-language pathologists. The goal of this study was to assess whether a nonword repetition (NWR) task could serve that purpose. METHOD: Participants were 104 second graders: 49 with normal hearing (NH) and 55 with CIs. In addition to NWR, children were tested on 10 measures involving phonological awareness and processing, serial recall of words, vocabulary, reading, and grammar. RESULTS: Children with CIs performed more poorly than children with NH on NWR, and sensitivity to phonological structure alone explained that performance for children in both groups. For children with CIs, 2 audiological factors positively influenced outcomes on NWR: being identified with hearing loss at a younger age and having experience with wearing a hearing aid on the unimplanted ear at the time of receiving a 1st CI. NWR scores were better able to rule out than to rule in such language deficits. CONCLUSIONS: Well-designed NWR tasks could have clinical utility in assessments of language acquisition for school-age children with CIs.

Perceptual weighting strategies of children with cochlear implants and normal hearing.

PURPOSE: This study compared perceptual weighting strategies of children with cochlear implants (CIs) and children with normal hearing (NH), and asked if strategies are explained solely by degraded spectral representations, or if diminished language experience accounts for some of the effect. Relationships between weighting strategies and other language skills were examined. METHOD: One hundred 8-year-olds (49 with NH and 51 with CIs) were tested on four measures: (1) labeling of cop-cob and sa-sha stimuli; (2) discrimination of the acoustic cues to the cop-cob decision; (3) phonemic awareness; and (4) word recognition. RESULTS: No differences in weighting of cues to the cop-cob decision were observed between children with CIs and NH, suggesting that language experience was sufficient for the children with CIs. Differences in weighting of cues to the sa-sha decision were found, but were not entirely explained by auditory sensitivity. Weighting strategies were related to phonemic awareness and word recognition. CONCLUSIONS: More salient cues facilitate stronger weighting of those cues. Nonetheless, individuals differ in how salient cues need to be to capture perceptual attention. Familiarity with stimuli also affects how reliably children attend to acoustic cues. Training should help children with CIs learn to categorize speech sounds with less-salient cues. LEARNING OUTCOMES: After reading this article, the learner should be able to: (1) recognize methods and motivations for studying perceptual weighting strategies in speech perception; (2) explain how signal quality and language experience affect the development of weighting strategies for children with cochlear implants and children with normal hearing; and (3) summarize the importance of perceptual weighting strategies for other aspects of language functioning.

Language structures used by kindergartners with cochlear implants: relationship to phonological awareness, lexical knowledge and hearing loss.

OBJECTIVES: Listeners use their knowledge of how language is structured to aid speech recognition in everyday communication. When it comes to children with congenital hearing loss severe enough to warrant cochlear implants (CIs), the question arises of whether these children can acquire the language knowledge needed to aid speech recognition, in spite of only having spectrally degraded signals available to them. That question was addressed in the present study. Specifically, there were three goals: (1) to compare the language structures used by children with CIs to those of children with normal hearing (NH); (2) to assess the amount of variance in the language measures explained by phonological awareness and lexical knowledge; and (3) to assess the amount of variance in the language measures explained by factors related to the hearing loss itself and subsequent treatment. DESIGN: Language samples were obtained and transcribed for 40 children who had just completed kindergarten: 19 with NH and 21 with CIs. Five measures were derived from Systematic Analysis of Language Transcripts: (1) mean length of utterance in morphemes, (2) number of conjunctions, excluding and, (3) number of personal pronouns, (4) number of bound morphemes, and (5) number of different words. Measures were also collected on phonological awareness and lexical knowledge. Statistics examined group differences, as well as the amount of variance in the language measures explained by phonological awareness, lexical knowledge, and factors related to hearing loss and its treatment for children with CIs. RESULTS: Mean scores of children with CIs were roughly one standard deviation below those of children with NH on all language measures, including lexical knowledge, matching outcomes of other studies. Mean scores of children with CIs were closer to two standard deviations below those of children with NH on two out of three measures of phonological awareness (specifically those related to phonemic structure). Lexical knowledge explained significant amounts of variance on three language measures, but only one measure of phonological awareness (sensitivity to word-final phonemic structure) explained any significant amount of unique variance beyond that, and on only one language measure (number of bound morphemes). Age at first implant, but no other factors related to hearing loss or its treatment, explained significant amounts of variance on the language measures, as well. CONCLUSIONS: In spite of early intervention and advances in implant technology, children with CIs are still delayed in learning language, but grammatical knowledge is less affected than phonological awareness. Because there was little contribution to language development measured for phonological awareness independent of lexical knowledge, it was concluded that children with CIs could benefit from intervention focused specifically on helping them learn language structures, in spite of the likely phonological deficits they experience as a consequence of having degraded inputs.

Do adults with cochlear implants rely on different acoustic cues for phoneme perception than adults with normal hearing?

PURPOSE Several acoustic cues specify any single phonemic contrast. Nonetheless, adult, native speakers of a language share weighting strategies, showing preferential attention to some properties over others. Cochlear implant (CI) signal processing disrupts the salience of some cues: In general, amplitude structure remains readily available, but spectral structure less so. This study asked how well speech recognition is supported if CI users shift attention to salient cues not weighted strongly by native speakers. METHOD Twenty adults with CIs participated. The /bɑ/-/wɑ/ contrast was used because spectral and amplitude structure varies in correlated fashion for this contrast. Adults with normal hearing weight the spectral cue strongly but the amplitude cue negligibly. Three measurements were made: labeling decisions, spectral and amplitude discrimination, and word recognition. RESULTS Outcomes varied across listeners: Some weighted the spectral cue strongly, some weighted the amplitude cue, and some weighted neither. Spectral discrimination predicted spectral weighting. Spectral weighting explained the most variance in word recognition. Age of onset of hearing loss predicted spectral weighting but not unique variance in word recognition. CONCLUSION The weighting strategies of listeners with normal hearing likely support speech recognition best, so efforts in implant design, fitting, and training should focus on developing those strategies.

Low-frequency signals support perceptual organization of implant-simulated speech for adults and children.

OBJECTIVE: Using signals processed to simulate speech received through cochlear implants and low-frequency extended hearing aids, this study examined the proposal that low-frequency signals facilitate the perceptual organization of broader, spectrally degraded signals. DESIGN: In two experiments, words and sentences were presented in diotic and dichotic configurations as four-channel noise-vocoded signals (VOC-only), and as those signals combined with the acoustic signal below 0.25 kHz (LOW-plus). Dependent measures were percent correct recognition, and the difference between scores for the two processing conditions given as proportions of recognition scores for VOC-only. The influence of linguistic context was also examined. STUDY SAMPLE: Participants had normal hearing. In all, 40 adults, 40 seven-year-olds, and 20 five-year-olds participated. RESULTS: Participants of all ages showed benefits of adding the low-frequency signal. The effect was greater for sentences than words, but no effect of diotic versus dichotic presentation was found. The influence of linguistic context was similar across age groups, and did not contribute to the low-frequency effect. Listeners who had poorer VOC-only scores showed greater low-frequency effects. CONCLUSION: The benefit of adding a low-frequency signal to a broader, spectrally degraded signal derives in some part from its facilitative influence on perceptual organization of the sensory input.

Working memory in children with cochlear implants: problems are in storage, not processing.

BACKGROUND: There is growing consensus that hearing loss and consequent amplification likely interact with cognitive systems. A phenomenon often examined in regards to these potential interactions is working memory, modeled as consisting of one component responsible for storage of information and another component responsible for processing of that information. Signal degradation associated with cochlear implants should selectively inhibit storage without affecting processing. This study examined two hypotheses: (1) A single task can be used to measure storage and processing in working memory, with recall accuracy indexing storage and rate of recall indexing processing; (2) Storage is negatively impacted for children with CIs, but not processing. METHOD: Two experiments were conducted. Experiment 1 included adults and children, 8 and 6 years of age, with NH. Procedures tested the prediction that accuracy of recall could index storage and rate of recall could index processing. Both measures were obtained during a serial-recall task using word lists designed to manipulate storage and processing demands independently: non-rhyming nouns were the standard condition; rhyming nouns were predicted to diminish storage capacity; and non-rhyming adjectives were predicted to increase processing load. Experiment 2 included 98 8-year-olds, 48 with NH and 50 with CIs, in the same serial-recall task using the non-rhyming and rhyming nouns. RESULTS: Experiment 1 showed that recall accuracy was poorest for the rhyming nouns and rate of recall was slowest for the non-rhyming adjectives, demonstrating that storage and processing can be indexed separately within a single task. In Experiment 2, children with CIs showed less accurate recall of serial order than children with NH, but rate of recall did not differ. Recall accuracy and rate of recall were not correlated in either experiment, reflecting independence of these mechanisms. CONCLUSIONS: It is possible to measure the operations of storage and processing mechanisms in working memory in a single task, and only storage is impaired for children with CIs. These findings suggest that research and clinical efforts should focus on enhancing the saliency of representation for children with CIs. Direct instruction of syntax and semantics could facilitate storage in real-world working memory tasks.

Improving speech-in-noise recognition for children with hearing loss: potential effects of language abilities, binaural summation, and head shadow.

OBJECTIVE: This study examined speech recognition in noise for children with hearing loss, compared it to recognition for children with normal hearing, and examined mechanisms that might explain variance in children's abilities to recognize speech in noise. DESIGN: Word recognition was measured in two levels of noise, both when the speech and noise were co-located in front and when the noise came separately from one side. Four mechanisms were examined as factors possibly explaining variance: vocabulary knowledge, sensitivity to phonological structure, binaural summation, and head shadow. STUDY SAMPLE: Participants were 113 eight-year-old children. Forty-eight had normal hearing (NH) and 65 had hearing loss: 18 with hearing aids (HAs), 19 with one cochlear implant (CI), and 28 with two CIs. RESULTS: Phonological sensitivity explained a significant amount of between-groups variance in speech-in-noise recognition. Little evidence of binaural summation was found. Head shadow was similar in magnitude for children with NH and with CIs, regardless of whether they wore one or two CIs. Children with HAs showed reduced head shadow effects. CONCLUSION: These outcomes suggest that in order to improve speech-in-noise recognition for children with hearing loss, intervention needs to be comprehensive, focusing on both language abilities and auditory mechanisms.