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Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides' pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.
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Biguanidas/química , Biguanidas/farmacologia , Ácidos e Sais Biliares/química , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanomedicina Teranóstica , Doença Crônica/tratamento farmacológico , Desenvolvimento de Medicamentos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Metformina/administração & dosagem , Metformina/farmacocinética , Nanomedicina Teranóstica/métodosRESUMO
OBJECTIVES: To explore the factors influencing the uptake of cochlear implants in adults, determine the impact of each factor, and to conceptualize the journey to implantation from a multistakeholder perspective. DESIGN: Concept mapping was used to integrate input from multiple stakeholders, each with their own experience and expertise. This mixed participatory method collects qualitative and quantitative data collection and enables further quantitative analysis. There were two participant cohorts: clients (cochlear implant recipients, candidates, and family members) and professionals (cochlear implant audiologists, ear, nose, and throat surgeons, administration staff, managers. and manufacturer representatives). A total of 93 people participated in the study: client cohort (n = 60, M age = 66.60 years) and professional cohort (n = 33, M age = 45.24 years). Participants brainstormed statements in response to the question "What influences people's decision to get/not get a cochlear implant?" They subsequently grouped the statements and named each group. They rated each statement as to its impact on the decision and prioritized the need for each to be changed/improved using a five-point Likert scale. Multidimensional scaling was used to produce a visual representation of the ideas and their relationship in the form of concepts. Further analysis was conducted to determine the differences between the cohorts, subcohorts, and concepts. RESULTS: One hundred ten unique statements were generated and grouped into six concepts which either directly affected the client or their environment. These concepts were: external influences (awareness and attitude of non-implant professionals about uptake, cost, logistics, the referral pathway, public awareness); uncertainties, beliefs, and fears (fears, negative effect of word of mouth, unsuccessful previous ear surgery, cosmetics of the device, misunderstanding of how a cochlear implant functions, eligibility for an implant and outcomes after implantation); health problems (mental and physical health); hearing difficulties (social, emotional, and communication impacts of hearing loss, severity of hearing loss, benefit from and experience with hearing aids); implant professionals (implant team's attitude, knowledge and relationship with clients, quality of overall service); and goals and support (clients 'hearing desires and goals, motivation, positive impact of word of mouth, family support, having a cochlear implant mentor. The six concepts fell into two overarching domains: the client-driven domain with four concepts and the external domain with two concepts. The mean rating of concepts in terms of impact on a client's decision to get an implant ranged from 2.24 (external influences, the main barrier) to 4.45 (goals and support, the main driver). Ratings significantly differed between the client and professional cohorts. CONCLUSIONS: This study increases our understanding of the factors, which influence a client's decision choose a cochlear implant as a hearing treatment. It also provides new information on the influence of the other stakeholders on the client journey. The magnitude of the generated statements in the client-driven domain highlights the pivotal role of individualized care in clinical settings in influencing a client's decision and the need for the professionals to understand a client's needs and expectations. A client's persistent hearing difficulties, goals, and support network were identified as drivers to the uptake of cochlear implants. However, the barriers identified highlight the need for a collaborative multi- and interdisciplinary approach to raise awareness in and educate non-implant hearing professionals about the cochlear implant process, as well as providing information to empower clients to make educated decisions and consider a cochlear implant as a hearing management option.
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Implante Coclear , Implantes Cocleares , Surdez , Auxiliares de Audição , Perda Auditiva , Adulto , Idoso , Surdez/cirurgia , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Globally, about 50 million people were living with dementia in 2015, with this number projected to triple by 2050. With no cure or effective treatment currently insight, it is vital that factors are identified which will help prevent or delay both age-related and pathological cognitive decline and dementia. Observational data have suggested that hearing loss is a potentially modifiable risk factor for dementia, but no conclusive evidence from randomised controlled trials is currently available. METHODS: The HearCog trial is a 24-month, randomised, controlled clinical trial aimed at determining whether a hearing loss intervention can delay or arrest the cognitive decline. We will randomise 180 older adults with hearing loss and mild cognitive impairment to a hearing aid or control group to determine if the fitting of hearing aids decreases the 12-month rate of cognitive decline compared with the control group. In addition, we will also determine if the expected clinical gains achieved after 12 months can be sustained over an additional 12 months and if losses experienced through the non-correction of hearing loss can be reversed with the fitting of hearing aids after 12 months. DISCUSSION: The trial will also explore the cost-effectiveness of the intervention compared to the control arm and the impact of hearing aids on anxiety, depression, physical health and quality of life. The results of this trial will clarify whether the systematic correction of hearing loss benefits cognition in older adults at risk of cognitive decline. We anticipate that our findings will have implications for clinical practice and health policy development. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ANZCTR: 12618001278224 ), registered on 30.07.2018.
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Disfunção Cognitiva , Demência , Auxiliares de Audição , Idoso , Austrália , Protocolos Clínicos , Cognição , Disfunção Cognitiva/prevenção & controle , Demência/diagnóstico , Humanos , Nova Zelândia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Objective: Recent changes to cochlear implant (CI) candidacy criteria have led to the inclusion of candidates with greater levels of hearing in the contralateral and/or implanted ear. This study assessed the impact of various hearing loss configurations on CI uptake rates (those assessed as eligible for CI, who proceed to CI).Design: Retrospective cohort study.Study sample: Post-lingually deaf adult CI candidates (n = 619) seen at a Western Australian cochlear implant clinic.Results: An overall CI uptake rate of 44% was observed. Hearing loss configuration significantly impacted uptake rates. Uptake rates of 62% for symmetrical hearing loss, 48% for asymmetrical hearing loss (four-frequency average hearing loss (4FAHL) asymmetry ≤60 dB), 25% for highly asymmetrical hearing loss (4FAHL asymmetry >60 dB), 38% for hearing losses eligible for electric-acoustic stimulation, and 22% for individuals with single-sided hearing loss were observed. Hearing loss configuration and age were both significant factors in relation to CI uptake although the impact of age was limited.Conclusion: CI clinics who apply or are considering applying expanded CI candidacy criteria within their practice should be aware that candidates with greater levels of residual hearing in at least the contralateral ear are less likely to proceed to CI.
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Implante Coclear , Implantes Cocleares , Perda Auditiva , Percepção da Fala , Adulto , Austrália , Perda Auditiva/diagnóstico , Perda Auditiva/cirurgia , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify which preoperative patient characteristics influence sequential bilateral cochlear implantation performance and to create a statistical model that predicts benefit. DESIGN: Multicentre retrospective cohort study. SETTING: All patients were operated in four academic teaching hospitals in Perth, Australia, and followed up by audiologists of the Ear Science Institute Australia. PARTICIPANTS: A total of 92 postlingually deafened adult patients who had undergone sequential cochlear implantations between 19 June 1990 and 14 March 2016 were included. Patients were excluded if the 12-month follow-up consonant-nucleus-consonant (CNC) phoneme score was missing. MAIN OUTCOME MEASURE: The effect of 18 preoperative factors on the CNC phoneme score in quiet (at 65 dB SPL) with the second cochlear implant (CI2) one year after implantation. RESULTS: Two factors were positively correlated to speech understanding with CI2: Wearing a hearing aid (HA) before receiving CI2 (r = 0.46, P = 0.00) and the maximum CNC phoneme score with the first CI (CI1) (r = 0.21, P = 0.05). Two factors were negatively correlated: the length of hearing loss before CI2 in the second implanted ear (r = -0.25, P = 0.02) and preoperative pure tone average (PTA) (0.5, 1, 2 kHz) before CI2 in the second implanted ear (r = -0.27, P = 0.01). The following model could be created: predicted CNC phoneme score with CI2 (%) = 16 + (44 * HA use before CI2 (yes)) - (0.22 * length of hearing loss before CI2 (years)) + (0.23 * CNC phoneme score with CI1 (%)). Because the effect of HA use before implantation played such a major role, we also created a model after exclusion of the HA factor: Predicted CNC phoneme score with CI2 (%) = 82 - (0.17 * length of hearing loss before CI2 (years)) - (0.27 * PTA in second implanted ear before CI2 (0.5, 1, 2 kHz)) + (0.20 * CNC phoneme score with CI1 (%)). CONCLUSION: Advanced age or a long interval between implantations does not necessarily lead to poor CI2 results. Patients who are successful HA users before CI2, who have a low PTA before CI2, a high CNC phoneme score with CI1 and a limited length of hearing loss before CI2, are likely to be successful CI2 recipients.
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Implante Coclear/métodos , Surdez/cirurgia , Audição/fisiologia , Percepção da Fala/fisiologia , Adulto , Surdez/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This systematic review of the literature reveals which pre-operative factors affect sequential cochlear implantation outcomes in adults. The findings can help health care prof-essionals provide evidence-based advice on the expected benefits from a second cochlear implant (CI). We searched PubMed, EMBASE, and the Cochrane database from November 1977 to August 26, 2017, using the terms "sequential cochlear implantation"; the most frequently cited predictors for unilateral cochlear implantation performance and other potential predictors for sequential implantation outcome; and "speech perception," "localization" as well as synonyms of all of the above. Ten studies were included. The effects of age, duration of hearing loss, time between implantations, preoperative hearing, etiology of hearing loss, hearing aid use and duration of follow-up on sequential cochlear implantation performance were studied. The literature has shown that duration of deafness, age at onset of deafness, etiology of hearing loss, and preoperative speech perception score are (inversely) related to unilateral cochlear implantation outcome in adults. One would expect that these factors would also affect sequential bilateral implantation outcome. However, the best available evidence to date shows that advanced age, a long duration of deafness, or a long interval between implantations should not be considered negative factors when considering sequential bilateral cochlear implantation.
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OBJECTIVE: Examine the accuracy of automated audiometry in a clinically heterogeneous population of adults using the KUDUwave automated audiometer. DESIGN: Prospective accuracy study. Manual audiometry was performed in a sound-treated room and automated audiometry was not conducted in a sound-treated environment. STUDY SAMPLE: 42 consecutively recruited participants from a tertiary otolaryngology department in Western Australia. RESULTS: Absolute mean differences ranged between 5.12-9.68 dB (air-conduction) and 8.26-15 dB (bone-conduction). A total of 86.5% of manual and automated 4FAs were within 10 dB (i.e. ±5 dB); 94.8% were within 15 dB. However, there were significant (p < 0.05) differences between automated and manual audiometry at 250, 500, 1000, and 2000 Hz (air-conduction) and 500 and 1000 Hz (bone-conduction). The effect of age (≥55 years) on accuracy (p = 0.014) was not significant on linear regression (p > 0.05; R(2) =( ) 0.11). The presence of a hearing loss (better ear ≥26 dB) did not significantly affect accuracy (p = 0.604; air-conduction), (p = 0.218; bone-conduction). CONCLUSIONS: This study provides clinical validation of automated audiometry using the KUDUwave in a clinically heterogeneous population, without the use of a sound-treated environment. Whilst threshold variations were statistically significant, future research is needed to ascertain the clinical significance of such variation.
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Audiometria/métodos , Monitoramento Ambiental/métodos , Perda Auditiva/diagnóstico , Audição , Estimulação Acústica , Adulto , Idoso , Idoso de 80 Anos ou mais , Limiar Auditivo , Automação , Condução Óssea , Feminino , Perda Auditiva/etiologia , Perda Auditiva/fisiopatologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Austrália Ocidental , Adulto JovemRESUMO
OBJECTIVES: The purpose of this study was to establish a statistical definition for stability in cochlear implant maps. Once defined, this study aimed to compare the duration taken to achieve a stable map in first and second implants in patients who underwent sequential bilateral cochlear implantation. This article also sought to evaluate a number of factors that potentially affect map stability. DESIGN: A retrospective cohort study of 33 patients with sensorineural hearing loss who received sequential bilateral cochlear implantation (Cochlear, Sydney, Australia), performed by the senior author. Psychophysical parameters of hearing threshold scores, comfort scores, and the dynamic range were measured for the apical, medial, and basal portions of the cochlear implant electrode at a range of intervals postimplantation. Stability was defined statistically as a less than 10% difference in threshold, comfort, and dynamic range scores over three consecutive mapping sessions. A senior cochlear implant audiologist, blinded to implant order and the statistical results, separately analyzed these psychophysical map parameters using current assessment methods. First and second implants were compared for duration to achieve stability, age, gender, the duration of deafness, etiology of deafness, time between the insertion of the first and second implant, and the presence or absence of preoperative hearing aids were evaluated and its relationship to stability. Statistical analysis included performing a two-tailed Student's t tests and least squares regression analysis, with a statistical significance set at p ≤ 0.05. RESULTS: There was a significant positive correlation between the devised statistical definition and the current audiology methods for assessing stability, with a Pearson correlation coefficient r = 0.36 and a least squares regression slope (b) of 0.41, df(58), 95% confidence interval 0.07 to 0.55 (p = 0.004). The average duration from device switch on to stability in the first implant was 87 days using current audiology methods and 81 days using the statistical definition, with no statistically significant difference between assessment methods (p = 0.2). The duration to achieve stability in the second implant was 51 days using current audiology methods and 60 days using the statistical method, and again no difference between the two assessment methods (p = 0.13). There was a significant reduction in the time to achieve stability in second implants for both audiology and statistical methods (p < 0.001 and p = 0.02, respectively). There was a difference in duration to achieve stability based on electrode array region, with basal portions taking longer to stabilize than apical in the first implant (p = 0.02) and both apical and medial segments in second implants (p = 0.004 and p = 0.01, respectively). No factors that were evaluated in this study, including gender, age, etiology of deafness, duration of deafness, time between implant insertion, and the preoperative hearing aid status, were correlated with stability duration in either stability assessment method. CONCLUSIONS: Our statistical definition can accurately predict cochlear implant map stability when compared with current audiology practices. Cochlear implants that are implanted second tend to stabilize sooner than the first, which has a significant impact on counseling before a second implant. No factors evaluated affected the duration required to achieve stability in this study.
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Implante Coclear/métodos , Perda Auditiva Bilateral/reabilitação , Perda Auditiva Neurossensorial/reabilitação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Audiologia , Limiar Auditivo , Criança , Pré-Escolar , Implantes Cocleares , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Psicofísica , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Tympanic membrane perforations are common and represent a management challenge to clinicians. Current treatments for chronic perforations involve a graft surgery and require general anaesthesia, including associated costs and morbidities. Bioactive molecules (e.g. growth factors, cytokines) play an important role in promoting TM wound healing following perforation and the use of growth factors as a topical treatment for tympanic membrane perforations has been suggested as an alternative to surgery. However, the choice of bioactive molecules best suited to promote wound healing has yet to be identified. We investigated the effects of hyaluronic acid, vitronectin, TGF-α, IL-24 and their combinations on migration, proliferation and adhesion of cultured human tympanic membrane-derived keratinocytes (hTM), in addition to their possible mechanisms of action. We found that TGF-α, TGF-α/HA and TGF-α/IL-24 promoted wound healing by significantly increasing both migration and proliferation. TGF-α and/or HA treated cells showed comparable cell-cell adhesion whilst maintaining an epithelial cell phenotype. With the use of receptor binding inhibitors for ErbB1 (AG1478) and CD44 (BRIC235), we revealed that the activation of ErbB1 is required for TGF-α/HA-mediated migration and proliferation. These results suggest factors that may be incorporated into a tissue-engineered membrane or directly as topical treatment for tympanic membrane perforations and hence reduce the need for a surgery.
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Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Ácido Hialurônico/farmacologia , Queratinócitos/citologia , Fator de Crescimento Transformador alfa/farmacologia , Membrana Timpânica/citologia , Caderinas/genética , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Ensaios de Migração Celular , Células Cultivadas , Células Epiteliais/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , Receptores de Hialuronatos/metabolismo , Interleucinas/farmacologia , Queratinócitos/efeitos dos fármacos , Fenótipo , Quinazolinas/farmacologia , Membrana Timpânica/efeitos dos fármacos , Membrana Timpânica/metabolismo , Tirfostinas/farmacologia , Vitronectina/farmacologiaRESUMO
Usher syndrome (USH) is the most common cause of inherited deaf-blindness. Here, we produced the LEIi020-A and LEIi020-B induced pluripotent stem cell (iPSC) lines from dermal fibroblasts derived from a patient with USH1B caused by inheritance of homozygous c.496del variants in MYO7A using episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, LIN28, mir302/367 microRNA and shRNA for TP53. Both iPSC lines expressed pluripotency markers, demonstrated trilineage differentiation potential and displayed a 46,XY karyotype. These cell lines represent a valuable resource for the production of retinal and otic tissues to support research into the pathogenesis and treatment of USH1B.
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Homozigoto , Células-Tronco Pluripotentes Induzidas , Fator 4 Semelhante a Kruppel , Miosina VIIa , Síndromes de Usher , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Síndromes de Usher/genética , Síndromes de Usher/patologia , Linhagem Celular , Diferenciação Celular , Masculino , Fibroblastos/metabolismoRESUMO
BACKGROUND: The baby boomer population will become high users of the health-care system in coming years. Self-report of hearing loss at a primary health-care visit may offer timely referrals to audiological services, but there has been no population-based study of self-reported hearing loss in the baby boomer generation. PURPOSE: To determine the clinical value and audiometric correspondence of self-reported hearing loss as a screening tool for the baby boomer population. RESEARCH DESIGN: A population-based study, Busselton Healthy Ageing Study (BHAS), surveying baby boomers born between 1946 and 1964 from the shire of Busselton, Western Australia. STUDY SAMPLE: A randomized sample of noninstitutionalized baby-boomers listed on the electoral roll (n = 6690) and resident in the shire are eligible to participate. This study reports on data from the first 1004 attendees (53.5% female) with a mean age of 56.23 (SD = 5.43). DATA COLLECTION AND ANALYSIS: Data from a self-report question on hearing loss and diagnostic pure tone audiometry was utilized for this study. Analysis included screening performance measures of self-report compared to audiometric cut-offs, receiver operator curve (ROC) to determine optimal level, analysis of variance to compare hearing status to self-report, and binary logistic regression to determine best audiometric predictors. RESULTS: Of the sample, 16% self-reported hearing loss (72.1% males). Logistic regression indicated 4000 Hz as the most important individual frequency related to self-report while the four-frequency average (500, 1000, 2000, and 4000 Hz) >25 dB in the worse ear was the most significant averaged cutoff with 68% sensitivity and 87% specificity. Of those who self-reported a hearing loss, 80% had either a four-frequency average hearing loss >25 dB in the worse ear or a high-frequency average (4000 and 8000 Hz) hearing loss greater than 35 dB in the worse ear. CONCLUSIONS: Baby boomer adults who self-report hearing impairment on direct inquiry are most likely to have a hearing loss. A simple question at a primary health care visit may facilitate a timely referral for audiological services in a baby boomer adult, who may be more amenable to rehabilitation.
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Envelhecimento , Inquéritos Epidemiológicos , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Autorrelato , Idoso , Audiometria de Tons Puros/estatística & dados numéricos , Estudos de Coortes , Coleta de Dados/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Atenção Primária à Saúde/estatística & dados numéricos , Curva ROC , Encaminhamento e Consulta/estatística & dados numéricos , Austrália Ocidental/epidemiologiaRESUMO
Despite significant advances in the development of therapeutics for hearing loss, drug delivery to the middle and inner ear remains a challenge. As conventional oral or intravascular administration are ineffective due to poor bioavailability and impermeability of the blood-labyrinth-barrier, localized delivery is becoming a preferable approach for certain drugs. Even then, localized delivery to the ear precludes continual drug delivery due to the invasive and potentially traumatic procedures required to access the middle and inner ear. To address this, the preclinical development of controlled release therapeutics and drug delivery devices have greatly advanced, with some now showing promise clinically. This review will discuss the existing challenges in drug development for treating the most prevalent and damaging hearing disorders, in particular otitis media, perforation of the tympanic membrane, cholesteatoma and sensorineural hearing loss. We will then address novel developments in drug delivery that address these including novel controlled release therapeutics such as hydrogel and nanotechnology and finally, novel device delivery approaches such as microfluidic systems and cochlear prosthesis-mediated delivery. The aim of this review is to investigate how drugs can reach the middle and inner ear more efficiently and how recent innovations could be applied in aiding drug delivery in certain pathologic contexts.
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Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (µCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using µCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by µCT, before and after contrast staining with osmium tetroxide (OsO4), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that µCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO4 significantly enhanced the visible tissue reaction detected using µCT. Overall, µCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.
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BACKGROUND: This study aimed to describe available evidence of cochlear implantation delivery arrangements in adults and the outcomes by which these service models are measured. METHODS: Scoping review of English language, primary studies conducted on adults (≥18 years) with ten or more subjects, published between January 2000 and June 2022, which assessed the effects of delivery arrangements of cochlear implantation were included. MEDLINE, EMBASE, CINAHL Plus, AMED, PsycINFO, LILACS, KoreaMed, IndMed, Cochrane CRCT, ISRCTN registry, WHO ICTRP and Web of Science were systematically searched. Included studies had to have a method section explicitly measure at least one of the Cochrane Effective Practice and Organization of Care (EPOC) outcome category. Criteria for systematic reviews and delivery arrangement category based on EPOC taxonomy was included in data extraction. Data was narratively synthesized based on EPOC categories. RESULTS: A total of 8135 abstracts were screened after exclusion of duplicates, of these 357 studies fulfilled the inclusion criteria. Around 40% of the studies investigated how care is delivered, focusing on quality and safety systems. New care pathways to coordinate care and the use of information and communication technology were emerging areas. There was little evidence on continuity, coordination and integration of care, how the workforce is managed, where care is provided and changes in the healthcare environment. The main outcome measure for various delivery arrangements were the health status and performance in a test. CONCLUSION: A substantial body of evidence exists about safety and efficacy of cochlear implantation in adults, predominantly focused on surgical aspects and this area is rapidly growing. There is a lack of evidence on aspects of care delivery that may have more impact on patients' experience such as continuity, coordination and integration of care and should be a focus of future research. This would lead to a better understanding of how patient's view CI experience, associated costs and the value of different care models.
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Implante Coclear , Humanos , Adulto , Revisões Sistemáticas como Assunto , Atenção à Saúde , Custos e Análise de Custo , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Up to 1.5 billion people worldwide suffer from various forms of hearing loss, with an additional 1.1 billion people at risk from various insults such as increased consumption of recreational noise-emitting devices and ageing. The most common type of hearing impairment is sensorineural hearing loss caused by the degeneration or malfunction of cochlear hair cells or spiral ganglion nerves in the inner ear. There is currently no cure for hearing loss. However, emerging frontier technologies such as gene, drug or cell-based therapies offer hope for an effective cure. In this review, we discuss the current therapeutic progress for the treatment of hearing loss. We describe and evaluate the major therapeutic approaches being applied to hearing loss and summarize the key trials and studies.
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PURPOSE: To define the rotational anatomy of the osseous spiral lamina (OSL) at the hook region and along the basal turn of the cochlea and to illustrate the potential utility of high-resolution MRI images to study inner ear ultrastructure. METHODS: Retrospective review of high-resolution temporal bone MRI images in 20 consecutive adult patients referred for imaging unrelated to hearing loss. The main outcome measure utilised images in an oblique sagittal plane to measure the rotation of the OSL relative to the vertical axis in the hook region and along the basal turn of the cochlea. RESULTS: The right OSL is noted to rotate in a clockwise direction as one proceeds anteriorly; over the same distance, the left OSL rotates in an anti-clockwise direction. The average overall rotation for all subjects as measured over a distance of 1-7 mm from the posterior margin of the round window was 25.95°. Inter-subject variability was noted. CONCLUSIONS: Prominent rotation of the OSL was noted in the hook region, this being most pronounced in the proximity to the round window. This concept may have implications for cochleostomy site selection with implant surgery. The study highlights the feasibility of high-resolution MRI to be used to systematically study variations in intra-cochlear anatomy.
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Imageamento por Ressonância Magnética/métodos , Lâmina Espiral/anatomia & histologia , Adulto , Idoso , Cóclea/anatomia & histologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Osso Temporal/anatomia & histologia , Adulto JovemRESUMO
OBJECTIVE: To explore factors influencing postoperative experiences of adult cochlear implant (CI) recipients, determine the impact of each factor, and conceptualize recipients' postoperative journey. STUDY DESIGN: Participatory mixed methods; concept mapping. SETTING: Tertiary care (private and public). PATIENTS: Ninety-three participated in the brainstorming activity. Eighty-nine completed the sorting tasks (96% retention rate): CI recipients (n = 44), significant others (n = 13), CI audiologists (n = 14) and surgeons (n = 5), CI clinics' administration staff (n = 5) and managers (n = 3), and CI manufactures' clinical support staff (n = 5). INTERVENTIONS: Rehabilitative (CIs). MAIN OUTCOME MEASURES: Statements were generated and rated by participants. Similarity of grouping of the statements informed the matrices used for cluster analysis to form concepts. RESULTS: Eighty-seven unique statements described the factors influencing adapting to, use, and maintenance of CIs after implantation. These were grouped, and five concepts were identified: financial considerations, complications, device usability and durability, device programming and adaptation, and patient motivation and supports. Although statements within the concepts financial considerations and complications were negatively rated, statements within the concepts device programming and adaptation, and patient motivation and supports were mostly rated as having positive influence in patients' postoperative journey. The concept device usability and durability contained both negatively and positively rated statements. CONCLUSIONS: Postoperative experience of adult CI recipients is a multifaceted journey with several challenges to address to improve services. Although support from and connection with family and clinicians, and simplicity of using a CI device facilitated the experience, medical and surgical complications, durability, and cost of maintaining the device challenged the postoperative experience.
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Implante Coclear , Implantes Cocleares , Adulto , HumanosRESUMO
Recent studies in our laboratories have shown promising effects of bile acids in â drug encapsulation for oral targeted delivery (via capsule stabilization) particularly when encapsulated with Eudragit NM30D® and â viable-cell encapsulation and delivery (via supporting cell viability and biological activities, postencapsulation). Accordingly, this study aimed to investigate applications of bile acid-Eudragit NM30D® capsules in viable-cell encapsulation ready for delivery. Mouse-cloned pancreatic ß-cell line was cultured and cells encapsulated using bile acid-Eudragit NM30D® capsules, and capsules' images, viability, inflammation, and bioenergetics of encapsulated cells assessed. The capsules' thermal and chemical stability assays were also assessed to ascertain an association between capsules' stability and cellular biological activities. Bile acid-Eudragit NM30D® capsules showed improved cell viability (e.g., F1 < F2 & F8; p < 0.05), insulin, inflammatory profile, and bioenergetics as well as thermal and chemical stability, compared with control. These effects were formulation-dependent and suggest, overall, that changes in ratios of bile acids to Eudragit NM30D® can change the microenvironment of the capsules and subsequent cellular biological activities.
Assuntos
Anti-Inflamatórios , Ácidos e Sais Biliares , Células Imobilizadas/metabolismo , Colesterol , Células Secretoras de Insulina/metabolismo , Nanocápsulas , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Colesterol/farmacologia , Camundongos , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologiaRESUMO
Bile acids (BA)s are known surfactants and well-documented to play a major role in food digestion and absorption. Recently, potential endocrinological and formulation-stabilisation effects of BAs have been explored and their pharmacological effects on supporting cell survival and functions have gained wide interest. Hence, this study aimed to explore the hyper-glycaemic dependent dose-effect of the BA chenodeoxycholic acid (CDCA) when encapsulated with pancreatic ß-cells, allowing assessment of CDCA's impacts when encapsulated. Four different concentrations of the BA were prepared, and viable cells were encapsulated and incubated for 2 days. Multiple analyses were carried out including confocal imaging, glucose-induced cellular mitochondrial viability indices, insulin production, inflammatory biomarker analyses and cellular bioenergetics measurements. There was a significant dose-effect with different concentrations of the BA, affecting cellular viability and antioxidant activities, cell functions and insulin release, inflammatory biomarkers, and cellular-bioenergetics at different oxidative stress levels. The results demonstrate that, when encapsulated, the BA CDCA exerts positive pharmacological effects at the cellular level, and such effects are concentration dependent.
RESUMO
OBJECTIVE: Conductive hearing loss (CHL) commonly arises in patients with spontaneous dehiscence of the tegmen of the temporal bone with meningoencephalocele (SME). The aim of this study was to further investigate 1) the potential mechanisms for CHL in this setting; 2) hearing outcomes following surgery to address SME, and 3) the possible causes of persistent CHL following surgery. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS AND INTERVENTION: Seven patients (six female; nine ears) who underwent middle cranial fossa repair of SME and were found to have a tegmen tympani dehiscence from October 2010 to September 2014 were included in the study. MAIN OUTCOME MEASURES: Pre- and postoperative pure-tone audiometry. RESULTS: Eight of nine ears (89%) had audiometric hearing loss at presentation. Seven ears (78%) had an air bone gap of ≥15âdB; all of these had an encephalocele traversing the tegmen tympani defect, four had a middle ear effusion, and three had a simultaneous superior semicircular canal dehiscence (SSCCD). The CHL resolved postoperatively in four of seven ears. Two of the three ears with persistent CHL had SSCCD. Attic ossicular fixation was identified in the other patient and the CHL resolved after ossiculoplasty. CONCLUSIONS: CHL associated with SME can be attributed preoperatively to ossicular chain fixation and synchronous SSCCD as well as the more commonly cited cerebrospinal fluid effusion and prolapse of meningoencephalocele onto the ossicular chain. Persistent postoperative CHL can also occur due to SSCCD and ossicular fixation by adhesions.