The Ototoxicity of Chloroquine and Hydroxychloroquine: A Systematic Review

Abstract Introduction Chloroquine and hydroxychloroquine are antimalarial drugs widely used in the treatment of rheumatic diseases. With the global pandemic caused by the new coronavirus, there was an increase in the prescription of these drugs, which led to a major concern regarding their ototoxic effects. Objectives The objective of the present study was to assess existing scientific evidence about the toxic effects of chloroquine and hydroxychloroquine on the peripheral and/or central auditory system. Data Synthesis A systematic literature review was performed by searching the PubMed (Medline), Scopus, Web of Science, LILACS, and SciELO electronic databases, in a search of articles that fullfiled the predefined inclusion and exclusion criteria. The review was conducted in three phases and, in all of them, analyses were performed by two independent researchers. Disagreements were discussed with a third researcher until a consensus was reached. A total of 437 articles were found and 8 were included in this review. Seven of the included studies reported hearing loss in their samples and presented a diagnostic hypothesis of ototoxicity induced by chloroquine or hydroxychloroquine. The most common type of hearing loss was sensorineural, with varying laterality and degrees of severity. The most frequently used audiological test was pure tone audiometry, and only two studies assessed brainstem evoked responses. Conclusion The scientific evidence compiled in this research showed that chloroquine and hydroxychloroquine have an ototoxic effect in the peripheral auditory system. These drugs can cause cochlear damage, including changes in the stria vascularis and lesions in sensory hair cells.

Effects of subchronic inhalation exposure to an organophosphorus insecticide compound containing dichlorvos on wistar rats' otoacoustic emissions / Efeitos da exposição inalatória subcrônica a um inseticida organofosforado contendo diclorvos nas emissões otoacústicas de ratos Wistar

Abstract Introduction Considering that previous studies suggest that pesticides may cause hearing disorders in humans, as well as the lack of studies proving the specific mechanisms of injury and the difficulty of separating concomitant etiological factors of the hearing damage, such as noise and vibration, it is important to develop studies using animal models to elucidate the effects of exposure to those substances isolated from other hearing damage etiologies. Objective To evaluate if the exposure to a dichlorvos based organophosphorus insecticide may induce ototoxicity. Methods 36 male Wistar rats were assigned to 3 groups (12 rats/group): control (exposed to water), positive control (treated with cisplatin to induce hearing damage) and experimental (exposed to dichlorvos based organophosphorus insecticide). The amplitude of distortion product otoacoustic emissions in the frequencies of 4, 6, 8, 10 and 12 kHz was evaluated before and after exposure, as well as systemic toxicity signs, body mass gain and plasma cholinesterase. Open field and plus maze tests were performed in 24 rats: experimental (n = 8), control (n = 8) and positive control group (n = 8 introduced new rats to induce anxiolytic activity) to evaluate the locomotor activity and anxiety, respectively. Results There was no significant change in body mass gain and plasma cholinesterase in the dichlorvos based organophosphorus insecticide group, however, the animals showed transient piloerection, depression and dyspnea during exposure. The behavior was not affected in any group. The frequencies of 8 and 10 kHz were significantly affected bilaterally in the insecticide group, which also showed a significant difference of the control in 10 kHz on the right and 8 and 10 kHz on the left ear. Conclusion Subchronic inhalation exposure to dichlorvos based organophosphorus insecticide induced ototoxicity in the cochlear function of rats without relevant systemic toxicity.

Resumo Introdução Considerando que estudos anteriores sugerem que pesticidas podem causar distúrbios auditivos em humanos, além da falta de estudos que comprovem os mecanismos específicos de lesão e a dificuldade em separar fatores etiológicos concomitantes dos danos auditivos, como ruído e vibração, é importante desenvolver estudos que usem modelos animais para elucidar os efeitos da exposição a substâncias isoladas de outras etiologias de danos auditivos. Objetivo Avaliar se a exposição a um inseticida organofosforado baseado em diclorvos pode induzir ototoxicidade. Método Foram divididos em 3 grupos 36 ratos Wistar machos (12 ratos/grupo): controle (exposto à água), controle positivo (tratado com cisplatina para induzir dano auditivo) e experimental (exposto ao inseticida). A amplitude das emissões otoacústicas por produto de distorção nas frequências de 4, 6, 8, 10 e 12 kHz foi avaliada antes e após a exposição, bem como sinais de toxicidade sistêmica, ganho de massa corporal e colinesterase plasmática. Os testes Open Field e Plus Maze foram feitos em 24 ratos: experimental (n = 8), controle (n = 8) e grupo controle positivo (n = 8, introduziu novos ratos para induzir atividade ansiolítica) para avaliar a atividade locomotora e a ansiedade, respectivamente. Resultados Não houve alteração significativa no ganho de massa corporal e colinesterase plasmática no grupo experimental; entretanto, os animais apresentaram piloereção transitória, depressão e dispneia durante a exposição. O comportamento não foi afetado em qualquer grupo. As frequências de 8 e 10 kHz foram significativamente afetadas bilateralmente no grupo exposto ao inseticida, o qual também mostrou uma diferença significativa do controle em 10 kHz na orelha direita e 8 e 10 kHz na orelha esquerda. Conclusão A exposição subcrônica inalatória de inseticida organofosforado baseado em diclorvos induziu ototoxicidade na função coclear de ratos sem toxicidade sistêmica relevante.

The Ototoxicity of Chloroquine and Hydroxychloroquine: A Systematic Review.

Introduction Chloroquine and hydroxychloroquine are antimalarial drugs widely used in the treatment of rheumatic diseases. With the global pandemic caused by the new coronavirus, there was an increase in the prescription of these drugs, which led to a major concern regarding their ototoxic effects. Objectives The objective of the present study was to assess existing scientific evidence about the toxic effects of chloroquine and hydroxychloroquine on the peripheral and/or central auditory system. Data Synthesis A systematic literature review was performed by searching the PubMed (Medline), Scopus, Web of Science, LILACS, and SciELO electronic databases, in a search of articles that fullfiled the predefined inclusion and exclusion criteria. The review was conducted in three phases and, in all of them, analyses were performed by two independent researchers. Disagreements were discussed with a third researcher until a consensus was reached. A total of 437 articles were found and 8 were included in this review. Seven of the included studies reported hearing loss in their samples and presented a diagnostic hypothesis of ototoxicity induced by chloroquine or hydroxychloroquine. The most common type of hearing loss was sensorineural, with varying laterality and degrees of severity. The most frequently used audiological test was pure tone audiometry, and only two studies assessed brainstem evoked responses. Conclusion The scientific evidence compiled in this research showed that chloroquine and hydroxychloroquine have an ototoxic effect in the peripheral auditory system. These drugs can cause cochlear damage, including changes in the stria vascularis and lesions in sensory hair cells.

Effects of subchronic inhalation exposure to an organophosphorus insecticide compound containing dichlorvos on wistar rats' otoacoustic emissions.

INTRODUCTION: Considering that previous studies suggest that pesticides may cause hearing disorders in humans, as well as the lack of studies proving the specific mechanisms of injury and the difficulty of separating concomitant etiological factors of the hearing damage, such as noise and vibration, it is important to develop studies using animal models to elucidate the effects of exposure to those substances isolated from other hearing damage etiologies. OBJECTIVE: To evaluate if the exposure to a dichlorvos based organophosphorus insecticide may induce ototoxicity. METHODS: 36 male Wistar rats were assigned to 3 groups (12 rats/group): control (exposed to water), positive control (treated with cisplatin to induce hearing damage) and experimental (exposed to dichlorvos based organophosphorus insecticide). The amplitude of distortion product otoacoustic emissions in the frequencies of 4, 6, 8, 10 and 12kHz was evaluated before and after exposure, as well as systemic toxicity signs, body mass gain and plasma cholinesterase. Open field and plus maze tests were performed in 24 rats: experimental (n=8), control (n=8) and positive control group (n=8 introduced new rats to induce anxiolytic activity) to evaluate the locomotor activity and anxiety, respectively. RESULTS: There was no significant change in body mass gain and plasma cholinesterase in the dichlorvos based organophosphorus insecticide group, however, the animals showed transient piloerection, depression and dyspnea during exposure. The behavior was not affected in any group. The frequencies of 8 and 10kHz were significantly affected bilaterally in the insecticide group, which also showed a significant difference of the control in 10kHz on the right and 8 and 10kHz on the left ear. CONCLUSION: Subchronic inhalation exposure to dichlorvos based organophosphorus insecticide induced ototoxicity in the cochlear function of rats without relevant systemic toxicity.

Ototoxicity of an association of insecticides compounds containing dichlorvos and cypermethrin in Wistar rats

ABSTRACT Purpose: to evaluate possible ototoxicity secondary to exposure to a combination of pesticides (dichlorvos and cypermethrin based insecticides). Methods: the Wistar rats were divided into 3 groups (12 animals per group): control (water), positive control for hearing damage (cisplatin) and experimental (exposed to dichlorvos and cypermethrin). The amplitude of distortion product otoacoustic emissions was assessed before and after the exposure. Systemic toxicity signs were also evaluated (clinical signs, weight gain and plasma cholinesterase). Wilcoxon test analyzed the post-exposure amplitudes compared to pre-exposure and Kruskal Wallis following Dunn's post hoc tests analyzed the amplitudes' variation. Normally distributed variables were evaluated by Student's t test. Results: body weight and plasma cholinesterase values were similar comparing the pre and post exposure in the experimental group. The control group did not manifest significant amplitude reduction of otoacoustic emissions between the pre and post evaluation. In the group exposed to cisplatin there was a significant reduction in amplitudes at 12 kHz on the right (p = 0.006; Wilcoxon) and 4 kHz on the left (p = 0.032; Wilcoxon). In the group exposed to pesticides, there was a significant reduction in the right ear at 4 kHz (p = 0.034; Wilcoxon) and 8 kHz (p = 0.019; Wilcoxon) and in the left ear at 4 kHz (p = 0.007; Wilcoxon), 6 kHz (p = 0.023; Wilcoxon), 8 kHz (p = 0.045; Wilcoxon) and 12 kHz (p = 0.028; Wilcoxon). Conclusion: there was ototoxicity in the experimental group, without a relevant systemic toxicity.

Morphometric Evaluation of the Recurrent Laryngeal Nerve of Wistar Rats Exposed to Pesticides.

The literature has been shown that exposition by inhalation to chemical compounds can cause vocal disorders and dysphagia in humans, in addition to other symptoms that are manifested according to the type, concentration and duration of exposure to the substance. Cypermethrin and dichlorvos are pesticides widely used in agriculture, public health, veterinary, and home environments. Despite the scientific evidence that cypermethrin and dichlorvos can cause neurodegenerative damage and motor alterations, there are no studies evaluating the toxic effects of these pesticides on the morphology of structures responsible for vocal mobility, especially to the Recurrent Laryngeal Nerve (RLN). Considering the association between vocal disorders in humans and variations in RLN and morphometry, the aim of this study was to evaluate the possible alterations in the microstructure of RLN secondary to subchronic exposure to cypermethrin (pyrethroid) and dichlorvos (organophosphate) in Wistar rats. The experimental protocol (approved by CEUA-UFCSPA: 321/15 and 323/15) consisted of 15 male Wistar rats, allocated in 3 groups: Control (n = 5, exposed to water), Cypermethrin (n = 5, exposed to cypermethrin - 1/10 of the inhalation median lethal concentration [LC50] - 0.25 mg/L) and dichlorvos (n = 5, exposed to dichlorvos - 1/10 of the LC50 - 1.5 mg/L). Inhalation exposure was performed for 4 hours, 5 times per week, for 6 weeks. The nerves were collected, histologically processed and analyzed using morphometric parameters measured using ZEN 2.6 (Zeiss - Germany). The cypermethrin and dichlorvos groups showed significant changes (P < 0.001, ANOVA) in the g-ratio and in the thickness of the myelin sheath of the RLN when compared to the control animals, however, none of the other parameters evaluated showed statistically significant differences. These findings indicate that repeated inhalation exposure to commercial products of cypermethrin and dichlorvos is able to modify the structure of the RLN and possibly generating vocal changes and / or dysphagia.

Ototoxicity of cypermethrin in Wistar rats / Ototoxicidade da cipermetrina em ratos Wistar

Abstract Introduction: This study presents the effect of cypermethrin on the cochlear function in Wistar rats post-subchronic inhalation exposure. Worldwide several pesticides are described as causing health disorders. Cypermethrin is currently one of the most commonly used, however, little is known about its harmful effects, especially related to hearing. Human studies have associated pesticides with hearing disorders, but they present limited conclusions due to the multiple factors to which the population is exposed, such as noise. Objective: Mimic human exposure to cypermethrin and to verify the effects on cochlear function. Methods: It is a subchronic inhalation animal study (6 weeks, 4 hours/day), using 36 male Wistar aged 60 day. Rats were randomly assigned into three groups: Control (12 rats exposed to inhalation of water); Positive Control for auditory lesion (12 rats administrated with 24 mg/kg intraperitoneal cisplatin); Experimental (12 rats exposed to inhalation of cypermethrin - 0.25 mg/L). Animals were evaluated by distortion product otoacoustic emissions pre- and post-exposure. Results: The frequencies of 8, 10 and 12 kHz in both ears (right p = 0.003; 0.004; 0.008 and left 0.003; 0.016; 0.005 respectively) and at frequencies 4 and 6 in the right ear (p = 0.007 and 0.015, respectively) in the animals exposed to cypermethrin resulted in reduction. Conclusion: Subchronic inhalation exposure to cypermethrin provided ototoxicity in rats.

Resumo Introdução: Este estudo apresenta o efeito da cipermetrina sobre a função coclear em ratos Wistar após exposição por inalação subcrônica. Em todo o mundo, vários pesticidas são descritos como causadores de distúrbios de saúde. A cipermetrina é atualmente um dos mais utilizados, porém pouco se conhece sobre seus efeitos deletérios, principalmente relacionados à audição. Estudos em humanos associaram pesticidas a alterações auditivas, mas apresentaram conclusões limitadas devido aos múltiplos fatores aos quais a população está exposta, como, por exemplo, o ruído. Objetivo: Mimetizar a exposição humana à cipermetrina e verificar os seus efeitos na função coclear. Método: Estudo de inalação subcrônica em animais (6 semanas, 4 horas/dia), 36 ratos machos Wistar com 60 dias. Os ratos foram distribuídos aleatoriamente em três grupos: controle (12 ratos expostos à inalação de água); controle positivo para lesão auditiva (12 ratos com administração de 24 mg/kg de cisplatina intraperitoneal); e experimental (12 ratos expostos a inalação de cipermetrina - 0,25 mg/L). Os animais foram avaliados por emissões otoacústicas por produto de distorção, pré e pós-exposição. Resultados: As frequências de 8, 10 e 12 kHz em ambas as orelhas (direita p = 0,003; 0,004; 0,008 e esquerda 0,003; 0,016; 0,005 respectivamente) e frequências 4 e 6 na orelha direita (p = 0,007 e 0,015, respectivamente) apresentaram redução nos animais expostos à cipermetrina. Conclusão: A exposição subcrônica por inalação à cipermetrina resultou em ototoxicidade em ratos.

Central auditory processing in teenagers with non-cholesteatomatous chronic otitis media / Processamento auditivo central em adolescentes com otite média crônica não colesteatomatosa

Abstract Introduction: Evidences of possible effects of early age otitis media with effusion in the central auditory processing, emphasize the need to consider such effects also in subjects with chronic otitis media. Aim: To investigate and analyze the impact of non-cholesteatomatous chronic otitis media on central auditory processing in teenagers. Methods: This is a study in which 68 teenagers were recruited, 34 with a diagnosis of non-cholesteatomatous chronic otitis media (study group) and 34 without otological disease history (control group). The evaluation of the subjects consisted of: anamnesis, pure-tone threshold audiometry, speech audiometry and a behavioral test battery for assessment of central auditory processing. Results: A statistically significant difference was found between the means observed in the study and control groups in all tests performed. An association was found between the control group and subgroups of the study group with unilateral alterations in all tests. An association was shown between the results for the control group and study group for family income, with a greater impact on subjects with a lower income. Conclusions: Non-cholesteatomatous chronic otitis media affects the central auditory processing in teenagers suffering from the disorder, and monaural low-redundancy hearing is the most affected auditory mechanism. Unilateral conductive changes cause more damage than bilateral ones, and lower family income seems to lead to more changes to the central auditory processing of subjects with non-cholesteatomatous chronic otitis media.

Resumo Introdução: As evidências de prováveis efeitos de otite média com efusão precoce no proces-samento auditivo central, ressaltam a necessidade de se considerar tais efeitos também em sujeitos com otite média crônica. Objetivo: Investigar e analisar o impacto da otite média crônica não colesteatomatosa no processamento auditivo central em adolescentes. Método: Estudo para o qual foram recrutados 68 adolescentes, 34 com diagnóstico de otite média crônica não colesteatomatosa (grupo de estudo) e 34 sem história otológica (grupo controle). A avaliação dos indivíduos consistiu de: anamnese, audiometria do limiar auditivo para tons puros, audiometria vocal e bateria de testes comportamentais para avaliação do processamento auditivo central. Resultados: Foi encontrada uma diferença estatisticamente significante entre as médias observadas nos grupos de estudo e controle em todos os testes. Foi encontrada uma associação entre o grupo controle e os subgrupos do grupo de estudo com alterações unilaterais em todos os testes. Houve associação entre os resultados dos grupos controle e de estudo para a renda familiar, com maior impacto nos indivíduos com menor renda. Conclusões: A otite média crônica não colesteatomatosa afeta o processamento auditivo central em adolescentes, a audição monoaural de baixa redundância é o mecanismo auditivo mais afetado. Alterações condutivas unilaterais causam mais danos do que as bilaterais e a menor renda familiar parece conduzir a mais alterações no processamento auditivo central de indivíduos com otite média crônica não colesteatomatosa.

Relação entre os achados audiológicos e de consciência fonológica em um grupo de crianças com fissura labial e/ou palatina / Relationship between audiological and phonological awareness findings in a group of children with cleft lip and / or palate / Relación entre hallazgos audiológicos y conciencia fonológica en un grupo de niños con labio leporino y/o paladar hendido

Introdução: Crianças com perdas auditivas podem apresentar comprometimento na fala e, consequentemente, desvantagens no desenvolvimento das competências linguísticas, como a consciência fonológica. Indivíduos com fissura labial e/ou palatina apresentam predisposição para perda auditiva e dificuldades de consciência fonológica, no entanto, há poucos estudos que demonstrem correlatos sobre esta inter-relação. Objetivo: Analisar os achados audiológicos e de consciência fonológica em um grupo de crianças com fissura labial e/ou palatina. Métodos: Estudo observacional transversal aprovado pelo Comitê de Ética em Pesquisa (1.974.629), realizado com um grupo de 36 crianças com fissura labial e/ou palatina. Critérios de inclusão: crianças com fissuras labiais e/ou palatinas com idades entre 4 e 12 anos, de ambos os gêneros, sem diagnóstico de síndromes associadas. Para investigar o histórico de otite média foi aplicado um recordatório junto aos responsáveis pelas crianças. A consciência fonológica foi avaliada com o Instrumento de Avaliação Sequencial - CONFIAS. Para averiguar a acuidade auditiva, as crianças realizaram a Audiometria Tonal Liminar. Resultados: A amostra foi composta por 13 crianças, com idades entre 4 e 8 anos. Todas apresentaram prejuízos nos escores do CONFIAS, sendo 92,3% no nível da sílaba e 84,6% no do fonema. Verificou-se que 69,2% tinham histórico de otite média. Na audiometria, 77% apresentaram perda auditiva condutiva. Não houve correlação entre os resultados de consciência fonológica com os achados audiológicos. Conclusão: As crianças com fissura labial e/ou palatina demonstraram dificuldades de consciência fonológica, mesmo não havendo correlação com os achados audiológicos, não se descartou a hipótese de uma inter-relação entre as variáveis.

Introduction: Children with hearing loss may present speech impairment, consequently disadvantages in the development of language skills, such as phonological awareness. Individuals with cleft lip and / or palate are predisposed to hearing loss and difficulties in phonological awareness; however, there are few studies that demonstrate correlation of this interrelation. Objective: Analyze the audiological and phonological awareness findings in a group of children with cleft lip and palate. Methods: Observational cross-sectional study approved by the Ethical Committee in Research under the number 1.974.629, held with a group of 36 children. Inclusion criteria: children with cleft lip and / or palate aged between 4 and 12 years, of both genders, without a diagnosis of associated syndromes. To investigate the history of otitis media, a reminder was applied to those responsible for the children. The Sequential Evaluation Instrument - CONFIAS was used to analyze phonological awareness. To verify the auditory acuity, the children performed the pure tone audiometry. Results: The sample consisted of 13 children, aged between 4 and 8 years. All of them presented losses in the CONFIAS scores, 92.3% in the syllable level and 84.6% in the phoneme level. It was found that 69.2% had a history of otitis media. In audiometry, 77% presented conductive hearing loss. There was no correlation between phonological awareness and auditory findings. Conclusion: Children with cleft lip and palate presented phonological awareness difficulties, even though there was no correlation with the audiological findings, the hypothesis of an interrelationship between the variables.

Introducción:Los niños con pérdida auditiva pueden presentar problemas del habla y, en consecuencia, desventajas en el desarrollo de las habilidades del lenguaje, como la conciencia fonológica. Las personas con labio leporino y/o paladar hendido están predispuestas a pérdida de audición y dificultades en la conciencia fonológica, sin embargo, hay pocos estudios que demuestren correlatos sobre esta interrelación. Objectivo: Analizar los hallazgos audiológica y de la conciencia fonológica en un grupo de niños con hendidura del labio y/o paladar hendido. Métodos: Estudio observacional transversal aprobado por el Comité de ética de la investigación (1.974.629), realizado con un grupo de 36 niños con hendidura del labio y/o paladar hendido. Criterios de inclusión: niños con labio leporino y/o paladar hendido entre 4 y 12 años, de ambos sexos, sin diagnóstico de síndromes asociados. Para investigar el historial de otitis media, se aplicó una recordatória a los responsables de los niños.La conciencia fonológica se evaluó utilizando el Instrumento de evaluación secuencial - CONFIAS. Para comprobar la agudeza auditiva, los niños realizan la medida cautelar de la audiometría tonal. Resultados: La muestra consistió en 13 niños, con edades entre 4 y 8 años. Todos presentaron pérdidas en los puntajes de CONFIAS, 92.3% en nivel de sílabas y 84.6% en nivel de fonemas. Se encontró que 69.2% tenía antecedentes de otitis media. En audiometría, 77% tenía pérdida auditiva conductiva. No hubo correlación entre conciencia fonológica y los resultados de las audiometrias. Conclusión: Los niños con labio leporino y/o paladar hendido demostraron dificultades en conciencia fonológica, incluso con ninguna correlación con los hallazgos audiológicos, no si descartó la posibilidad de una relación entre las variables.

Ototoxicity of cypermethrin in Wistar rats.

INTRODUCTION: This study presents the effect of cypermethrin on the cochlear function in Wistar rats post-subchronic inhalation exposure. Worldwide several pesticides are described as causing health disorders. Cypermethrin is currently one of the most commonly used, however, little is known about its harmful effects, especially related to hearing. Human studies have associated pesticides with hearing disorders, but they present limited conclusions due to the multiple factors to which the population is exposed, such as noise. OBJECTIVE: Mimic human exposure to cypermethrin and to verify the effects on cochlear function. METHODS: It is a subchronic inhalation animal study (6 weeks, 4hours/day), using 36 male Wistar aged 60 day. Rats were randomly assigned into three groups: Control (12 rats exposed to inhalation of water); Positive Control for auditory lesion (12 rats administrated with 24mg/kg intraperitoneal cisplatin); Experimental (12 rats exposed to inhalation of cypermethrin - 0.25mg/L). Animals were evaluated by distortion product otoacoustic emissions pre- and post-exposure. RESULTS: The frequencies of 8, 10 and 12kHz in both ears (right p=0.003; 0.004; 0.008 and left 0.003; 0.016; 0.005 respectively) and at frequencies 4 and 6 in the right ear (p=0.007 and 0.015, respectively) in the animals exposed to cypermethrin resulted in reduction. CONCLUSION: Subchronic inhalation exposure to cypermethrin provided ototoxicity in rats.

Central auditory processing in teenagers with non-cholesteatomatous chronic otitis media.

INTRODUCTION: Evidences of possible effects of early age otitis media with effusion in the central auditory processing, emphasize the need to consider such effects also in subjects with chronic otitis media. AIM: To investigate and analyze the impact of non-cholesteatomatous chronic otitis media on central auditory processing in teenagers. METHODS: This is a study in which 68 teenagers were recruited, 34 with a diagnosis of non-cholesteatomatous chronic otitis media (study group) and 34 without otological disease history (control group). The evaluation of the subjects consisted of: anamnesis, pure-tone threshold audiometry, speech audiometry and a behavioral test battery for assessment of central auditory processing. RESULTS: A statistically significant difference was found between the means observed in the study and control groups in all tests performed. An association was found between the control group and subgroups of the study group with unilateral alterations in all tests. An association was shown between the results for the control group and study group for family income, with a greater impact on subjects with a lower income. CONCLUSIONS: Non-cholesteatomatous chronic otitis media affects the central auditory processing in teenagers suffering from the disorder, and monaural low-redundancy hearing is the most affected auditory mechanism. Unilateral conductive changes cause more damage than bilateral ones, and lower family income seems to lead to more changes to the central auditory processing of subjects with non-cholesteatomatous chronic otitis media.

Alterações funcionais e estruturais do complexo craniofacial na síndrome branquio-óculo-facial: relato de caso / Functional and structural alterations of the craniofacial complex in the branchio-oculo-facial syndrome: case report / Alteraciones funcionales y estructurales del complejo craneofacial en el síndrome branquio-óculo-facial: relato de caso

Objetivo: Descrever características clínicas, alterações funcionais e estruturais de complexo craniofacial de sujeito com síndrome branquio-óculo-facial. Método: Paciente de 13 anos e 3 meses, respiradora oral com perda auditiva condutiva de grau moderadamente severo em ambas as orelhas, diagnosticada com síndrome branquio-óculo-facial, apresentou: fissura labiopalatina transforame bilateral completa corrigida por labioplastia e palatoplastia primárias, assimetria facial, fístula em região anterior de palato duro, atresia maxilar transversa, dentinogênese imperfeita, trespasse horizontal negativo, oclusão Classe I de Angle e mordida aberta anterior e lateral bilateralmente, desvio severo da linha média superior para a esquerda, incisivo lateral superior permanente semi-erupcionado por vestibular do canino superior decíduo do lado esquerdo, retenção prolongada do segundo molar inferior decíduo direito, apinhamento dentário inferior, hipotonia e posicionamento inadequado de língua, ausência de vedamento labial em repouso, deglutição adaptada, alteração na mobilidade de lábios, bochechas e palato mole com escape de ar nasal na fala, caracterizando disfunção velofaríngea. Sujeitos com fissura lábiopalatina podem apresentar grande variedade de alterações na produção dos fones. Paciente apresenta crescimento deficiente da maxila que, como relatado na literatura, pode alterar o desenvolvimento do terço médio da face com repercussão na oclusão dentária, fala e formato do nariz. Conclusão: As alterações clínicas funcionais e estruturais relatadas são na maioria do complexo craniofacial, demonstrando a importância da otorrinolaringologia, fonoaudiologia e odontologia na terapêutica interdisciplinar dos pacientes com a síndrome.

Introduction: Branchio-Oculo-Facial Syndrome (BOFS) is a rare autosomal disease with variable expression, dependent on genetic mutations, whose phenotype is characterized by ocular, hearing and craniofacial alterations. Purpose: describe the clinical features, the functional and structural alterations in the craniofacial complex of a subject with branchio-oculo-facial syndrome. Method: A 13-year and 3-month-old girl, with moderately severe conductive bilateral hearing loss diagnosed with BOFS, presented: bilateral cleft lip and palate treated by labioplasty and palatoplasty, facial asymmetry, anterior maxillary fistula, transverse maxillary atresia, imperfect dentinogenesis, negative horizontal trespass, Angle Class I bilateral, anterior and lateral open bite on both sides, severe left superior midline deviation, eruption by vestibular of the superior canine on the left side, prolonged retention of the second inferior molar right deciduous, lower dental crowding, hypotonia and inadequate tongue positioning, absence of labial resting at rest, adapted swallowing, alteration in mobility of lips, cheeks and palate with nasal air exhaust in speech, characterizing velopharyngeal dysfunction. There are few publications of BOFS, given its rarity. Subjects with cleft lip and palate may present a wide variety of changes in the production of headphones. Patient presents deficient growth of the maxilla which, as reported in the literature, may alter the development of the middle third of the face with repercussion in dental occlusion, speech and nose shape. Conclusion: The functional and structural clinical alterations reported are the majority of the craniofacial complex, demonstrating the importance of otorhinolaryngology, speech therapy and orthodontics in the interdisciplinary therapy of patients with BOFS.

Introducción: El síndrome branquio-oculo-facial (BOFS) es una enfermedad autosómica rara con expresión variable, dependiente de las mutaciones genéticas, caracterizada por alteraciones oculares, auriculares y craneofaciales. Propósito: describir características clínicas, alteraciones funcionales y estructurales del complejo craneofacial de un sujeto con BOFS. Método: Niña de 13 años y 3 meses de edad, con pérdida de audición conductiva moderadamente grave bilateralmente diagnosticada con SBOF, presentó: paladar y labio hendido bilateral tratado por labioplastia y palatoplastia primarias, asimetría facial, fístula maxilar anterior, atresia maxilar transversal, dentinogénesis imperfecta, traspaso horizontal negativo, clase I de Angle bilateral, mordida abierta anterior y lateral bilateralmente, desviación severa de la línea media superior izquierda, erupción vestibular del canino superior del lado izquierdo, retención prolongada del segundo molar inferior derecho deciduo, apiñamiento dental, hipotonía e inadecuada colocación de la lengua, ausencia de sello labial en reposo, deglución adaptada, alteración de movilidad de labios, mejillas y velo del paladar con escape de aire nasal y disfunción velofaríngea Hay pocas publicaciones de BOFS, dada su rareza. Los sujetos con labio y paladar hendido pueden presentar una gran variedad de cambios en la producción de auriculares. El paciente presenta crecimiento deficiente del maxilar que, según se informa en la literatura, puede alterar el desarrollo del tercio medio de la cara con repercusión en la oclusión dental, habla y la forma de la nariz. Conclusión: Alteraciones clínicas funcionales y estructurales la mayoría del complejo craniofacial. Eso demuestra la importancia de otorrinolaringología, fonoaudiología y odontología en la terapia interdisciplinaria de pacientes con SBOF.;Introdução: A Síndrome Branquio-Óculo-Facial é uma doença autossômica rara com expressão variável, dependente das mutações genéticas, cujo fenótipo caracteriza-se por alterações oculares, auriculares e craniofaciais.

Questionnaires and checklists for central auditory processing screening used in Brazil: a systematic review / Questionários e checklists para triagem do processamento auditivo central utilizados no Brasil: revisão sistemática

Abstract Introduction: The action of listening involves a complex interaction between the peripheral and central auditory systems. Central auditory processing disorder can be described as any problem in one or more auditory abilities. Literature reports that behavioral questionnaires and checklists can be applied to screen individuals at risk for central auditory processing disorder. Objective: To identify and analyze in the national literature questionnaires and checklists for the screening of central auditory processing available in Brazil for the Portuguese language. Methods: The research was carried out in electronic databases and "gray literature". The search strategy was: "questionnaires OR surveys and questionnaires AND auditory OR hearing tests OR auditory perception AND Brazil". The research was carried out between June and August of 2017. Study selection followed inclusion and exclusion criteria. The criteria adopted included Brazilian studies, without date and design restriction, that were carried out, translated, adapted and/or validated to Brazilian Portuguese or European Portuguese, as tools for central auditory processing screening. International studies that were not adapted to the Portuguese language were excluded, as well as the ones that were not available in full. Results: A total of 3664 publications were found and seven articles were selected for this systematic review, according to the established criteria. Conclusions: There is scarce national literature for central auditory processing screening and the only tool validated to Brazilian Portuguese, published as a monograph, is the auditory processing domains questionnaire. It is suggested that new studies with greater methodological stringency related to the processes of tool adaptation and validation be developed and published in the usual scientific databases, aiming at greater diffusion and clinical applicability.

Resumo Introdução: O ato de ouvir envolve uma complexa interação entre os sistemas auditivo periférico e central. O transtorno do processamento auditivo central pode ser descrito como qualquer alteração em uma ou mais habilidades auditivas. A literatura refere que questionários e checklists comportamentais podem ser aplicados para triagem de indivíduos em risco para o transtorno do processamento auditivo central. Objetivo: Identificar na literatura nacional e analisar questionários e checklists para triagem do processamento auditivo central disponíveis no Brasil para a língua portuguesa. Método: Pesquisa realizada em bases de dados eletrônicas e "literatura cinza". A estratégia de busca foi a seguinte: questionnaires OR surveys and questionnaires AND auditory OR hearing tests OR auditory perception AND Brazil. A pesquisa foi realizada de junho a agosto de 2017. A seleção dos estudos seguiu critérios de inclusão e exclusão. Os critérios adotados compreenderam estudos brasileiros, sem restrição de data e delineamento, que tenham sido elaborados, traduzidos, adaptados e/ou validados para o português brasileiro ou europeu, questionários e checklists como instrumentos para triagem do processamento auditivo central. Foram excluídos estudos internacionais não adaptados à língua portuguesa, bem como aqueles não disponíveis na íntegra. Resultados: Foram encontradas 3.664 publicações e sete trabalhos foram selecionados para esta revisão sistemática, conforme os critérios estabelecidos. Conclusões: Há escassa literatura nacional para triagem do processamento auditivo central e o único instrumento validado para o português brasileiro, publicado em formato de monografia, é o Auditory Processing Domains Questionnaire. Sugere-se que novos trabalhos com maior rigor metodológico nos processos de adaptação e validação dos instrumentos sejam desenvolvidos e publicados nas bases científicas usuais, com vistas à maior difusão e aplicabilidade clínica.

Questionnaires and checklists for central auditory processing screening used in Brazil: a systematic review.

INTRODUCTION: The action of listening involves a complex interaction between the peripheral and central auditory systems. Central auditory processing disorder can be described as any problem in one or more auditory abilities. Literature reports that behavioral questionnaires and checklists can be applied to screen individuals at risk for central auditory processing disorder. OBJECTIVE: To identify and analyze in the national literature questionnaires and checklists for the screening of central auditory processing available in Brazil for the Portuguese language. METHODS: The research was carried out in electronic databases and "gray literature". The search strategy was: "questionnaires OR surveys and questionnaires AND auditory OR hearing tests OR auditory perception AND Brazil". The research was carried out between June and August of 2017. Study selection followed inclusion and exclusion criteria. The criteria adopted included Brazilian studies, without date and design restriction, that were carried out, translated, adapted and/or validated to Brazilian Portuguese or European Portuguese, as tools for central auditory processing screening. International studies that were not adapted to the Portuguese language were excluded, as well as the ones that were not available in full. RESULTS: A total of 3664 publications were found and seven articles were selected for this systematic review, according to the established criteria. CONCLUSIONS: There is scarce national literature for central auditory processing screening and the only tool validated to Brazilian Portuguese, published as a monograph, is the auditory processing domains questionnaire. It is suggested that new studies with greater methodological stringency related to the processes of tool adaptation and validation be developed and published in the usual scientific databases, aiming at greater diffusion and clinical applicability.

Alteração auditiva em osteogênese imperfeita: revisão sistemática de literatura / Auditory alteration in osteogenesis imperfecta: systematic literature review

RESUMO Objetivos Analisar as publicações científicas sobre audição em indivíduos com osteogênese imperfeita. Estratégias de pesquisa Trata-se de revisão sistemática de literatura. Foram selecionados os descritores Hearing OR Hearing Loss AND Osteogenesis Imperfecta. Duas revisoras consultaram as bases de dados Cochrane Library, PubMed, LILACS, Scopus e Embase. Critérios de seleção utilizaram-se os Descritores em Ciências da Saúde, não sendo delimitado período de publicação dos estudos. Foram critérios de inclusão estudos de coorte, seguimento, transversais, casos controle e em idioma inglês. Foram critérios de exclusão artigos editoriais, relatos/séries de casos, resumos de eventos e estudos conduzidos em animais. Os estudos selecionados foram analisados pela Iniciativa STROBE e pelo Sistema GRADE. Resultados Dos 652 estudos obtidos, foram selecionados 16. A perda auditiva do tipo condutiva foi o tipo mais comum na população com osteogênese imperfeita (OI) e seu início ocorre por volta da segunda década de vida. A definição e a classificação para aferição de perda auditiva, nas publicações com a população com osteogênese imperfeita, apresentaram discordância entre os estudos. Conclusão Esta revisão respondeu às perguntas a que se propôs, constatando que as alterações audiológicas encontradas em pacientes com OI são do tipo condutivo, neurossensorial e misto. Alterações condutivas são mais comuns em pacientes mais jovens e alterações neurossensoriais, em pacientes mais velhos. A Iniciativa STROBE apontou itens descritos de forma parcial e o Sistema GRADE concluiu que os estudos apresentaram alguma falha metodológica.

ABSTRACT Purpose To analyze scientific publications on the hearing issue of patients with osteogenesis imperfecta. Reserch strategy This study is a systematic literature review. The following descriptors were selected "Hearing" OR "Hearing Loss" AND "Osteogenesis Imperfecta". Two reviewers searched the Cochrane Library, Pubmed, Latin American and Caribbean Health Sciences Literature, Scopus and Embase databases. Selection criteria Descriptors in Health Sciences were used and the publication period of studies was not limited. Inclusion criteria were cohort, follow-up, cross-sectional, and control studies in English language. Exclusion criteria were editorial articles, case reports, case summaries, and animal studies. Selected studies were analyzed by the STROBE Initiative and the GRADE System. Results Of the 652 studies, 16 were selected. Conductive hearing loss is the most common type in the osteogenesis imperfecta (OI) population and its onset is around the second decade of life. Definition and classification for hearing loss measurement in publications with the osteogenesis imperfecta population present disparities among studies. Conclusion This review met the objectives proposed, concluding that audiological alterations found in OI patients are of conductive, sensorineural and mixed types; conductive alterations are more common in younger patients and sensorineural alterations in older ones. The STROBE initiative partially pointed out described items and the GRADE system concluded that studies present some methodological failure.

Parameters for Applying the Brainstem Auditory Evoked Potential with Speech Stimulus: Systematic Review

Abstract Introduction Studies using the Brainstem Auditory Evoked Potential with speech stimulus are increasing in Brazil, and there are divergences between the methodologies used for testing. Objectives To analyze the parameters used in the study of the Brainstem Auditory Evoked Potentials with speech stimulus. Data Synthesis The survey was performed using electronic databases. The search strategy was as follows: "Evoked potentials, auditory" OR "Brain stem" OR "Evoked potentials, auditory, brain stem" AND "Speech." The survey was performed from June to July of 2016. The criteria used for including articles in this study were: being written in Portuguese, English or Spanish; presenting the description of the testing parameters and the description of the sample. In the databases selected, 2,384 articles were found, and 43 articles met all of the inclusion criteria. The predominance of the following parameters was observed to achieve the potential during study: stimulation with the syllable /da/; monaural presentation with greater use of the right ear; intensity of 80 dB SPL; vertical placement of electrodes; use of in-ear headphones; patient seated, distracted in awake state; alternating polarity; use of speech synthesizer software for the elaboration of stimuli; presentation rate of 10.9/s; and sampling rate of 20 kHz. Conclusions The theme addressed in this systematic review is relatively recent. However, the results are significant enough to encourage the use of the procedure in clinical practice and advise clinicians about the most used procedures in each parameter.

Correlation between cognitive functions and central auditory processing in adolescents with non-cholesteatomatous chronic otitis media.

Auditory deprivation associated with early otitis media with effusion has been considered a risk factor for central auditory processing (CAP), as well as for the development of a number of cognitive functions. OBJECTIVE: To study the neuropsychological functions of attention, working memory and executive function in adolescents with and without non-cholesteatomatous chronic otitis media (NCCOM) and analyze their interrelationships with the behavioral evaluation of CAP. METHODS: Sixty-eight adolescents were recruited, 34 were diagnosed with NCCOM (study group - SG), and 34 had no otological history (control group - CG). The Neupsilin Brief Neuropsychological Assessment Instrument was used. CAP was assessed by: Masking Level Difference, Synthetic Sentence Identification, Random Gap Detection Test, Duration Pattern Sequence Test and Dichotic Digits Test. RESULTS: The results of Neupsilin showed lower scores in the study group when compared to the control group on the following tests: digit sequence repetition, ascending digit ordering, auditory sentence span, and phonemic verbal fluency. An association was found between central auditory processing tests and Neupsilin subtests. CONCLUSION: The effects of NCCOM on attention, memory and executive function related to central auditory processing disorder in adolescents seem to be enhanced by the severity of the disease.

A privação auditiva associada à otite média precoce com efusão tem sido considerada um fator de risco para o processamento auditivo central (CAP), bem como para o desenvolvimento de diversas funções cognitivas. OBJETIVO: Estudar as funções neuropsicológicas da atenção, memória de trabalho e função executiva em adolescentes com e sem otite média crônica não-colesteatomatosa (NCCOM) e analisar suas inter-relações com a avaliação comportamental da PAC. MÉTODOS: Sessenta e oito adolescentes foram recrutados, 34 foram diagnosticados com NCCOM (grupo de estudo - GE) e 34 não tinham história otológica (grupo controle - GC). Utilizou-se o Instrumento de Avaliação Neuropsicológica Breve de Neupsilin. O CAP foi avaliado por: Diferença de Nível de Mascaramento, Identificação de Frase Sintética, Teste de Detecção de Intervalo Aleatório, Teste de Sequência de Padrão de Duração e Teste de Dígitos Dicóticos. RESULTADOS: Os resultados de Neupsilin mostraram menores escores no grupo de estudo quando comparados ao grupo controle nos seguintes testes: repetição de sequência de dígitos, ordenação de dígitos ascendentes, extensão de sentenças auditivas e fluência verbal fonêmica. Foi encontrada uma associação entre os testes do processamento auditivo central e os subtestes de Neupsilin. CONCLUSÃO: Os efeitos do NCCOM na atenção, memória e função executiva relacionados ao transtorno do processamento auditivo central em adolescentes parecem ser potencializados pela gravidade da doença.

Parameters for Applying the Brainstem Auditory Evoked Potential with Speech Stimulus: Systematic Review.

Introduction Studies using the Brainstem Auditory Evoked Potential with speech stimulus are increasing in Brazil, and there are divergences between the methodologies used for testing. Objectives To analyze the parameters used in the study of the Brainstem Auditory Evoked Potentials with speech stimulus. Data Synthesis The survey was performed using electronic databases. The search strategy was as follows: "Evoked potentials, auditory" OR "Brain stem" OR "Evoked potentials, auditory, brain stem" AND "Speech." The survey was performed from June to July of 2016. The criteria used for including articles in this study were: being written in Portuguese, English or Spanish; presenting the description of the testing parameters and the description of the sample. In the databases selected, 2,384 articles were found, and 43 articles met all of the inclusion criteria. The predominance of the following parameters was observed to achieve the potential during study: stimulation with the syllable /da/; monaural presentation with greater use of the right ear; intensity of 80 dB SPL; vertical placement of electrodes; use of in-ear headphones; patient seated, distracted in awake state; alternating polarity; use of speech synthesizer software for the elaboration of stimuli; presentation rate of 10.9/s; and sampling rate of 20 kHz. Conclusions The theme addressed in this systematic review is relatively recent. However, the results are significant enough to encourage the use of the procedure in clinical practice and advise clinicians about the most used procedures in each parameter.

Correlation between cognitive functions and central auditory processing in adolescents with non-cholesteatomatous chronic otitis media / Correlação entre funções cognitivas e processamento auditivo central em adolescentes com otite média crônica não colesteatomatosa

Abstract Auditory deprivation associated with early otitis media with effusion has been considered a risk factor for central auditory processing (CAP), as well as for the development of a number of cognitive functions. Objective: To study the neuropsychological functions of attention, working memory and executive function in adolescents with and without non-cholesteatomatous chronic otitis media (NCCOM) and analyze their interrelationships with the behavioral evaluation of CAP. Methods: Sixty-eight adolescents were recruited, 34 were diagnosed with NCCOM (study group - SG), and 34 had no otological history (control group - CG). The Neupsilin Brief Neuropsychological Assessment Instrument was used. CAP was assessed by: Masking Level Difference, Synthetic Sentence Identification, Random Gap Detection Test, Duration Pattern Sequence Test and Dichotic Digits Test. Results: The results of Neupsilin showed lower scores in the study group when compared to the control group on the following tests: digit sequence repetition, ascending digit ordering, auditory sentence span, and phonemic verbal fluency. An association was found between central auditory processing tests and Neupsilin subtests. Conclusion: The effects of NCCOM on attention, memory and executive function related to central auditory processing disorder in adolescents seem to be enhanced by the severity of the disease.

Resumo A privação auditiva associada à otite média precoce com efusão tem sido considerada um fator de risco para o processamento auditivo central (CAP), bem como para o desenvolvimento de diversas funções cognitivas. Objetivo: Estudar as funções neuropsicológicas da atenção, memória de trabalho e função executiva em adolescentes com e sem otite média crônica não-colesteatomatosa (NCCOM) e analisar suas inter-relações com a avaliação comportamental da PAC. Métodos: Sessenta e oito adolescentes foram recrutados, 34 foram diagnosticados com NCCOM (grupo de estudo - GE) e 34 não tinham história otológica (grupo controle - GC). Utilizou-se o Instrumento de Avaliação Neuropsicológica Breve de Neupsilin. O CAP foi avaliado por: Diferença de Nível de Mascaramento, Identificação de Frase Sintética, Teste de Detecção de Intervalo Aleatório, Teste de Sequência de Padrão de Duração e Teste de Dígitos Dicóticos. Resultados: Os resultados de Neupsilin mostraram menores escores no grupo de estudo quando comparados ao grupo controle nos seguintes testes: repetição de sequência de dígitos, ordenação de dígitos ascendentes, extensão de sentenças auditivas e fluência verbal fonêmica. Foi encontrada uma associação entre os testes do processamento auditivo central e os subtestes de Neupsilin. Conclusão: Os efeitos do NCCOM na atenção, memória e função executiva relacionados ao transtorno do processamento auditivo central em adolescentes parecem ser potencializados pela gravidade da doença.

Monitoring of hearing and language in primary health care: project pilot. / Monitoramento da audição e da linguagem na atenção primária à saúde: projeto piloto.

This article analyzes the feasibility of implementing a program that monitors the hearing and language development in the first year of life. It is a prospective longitudinal study, in which 41 community health workers were invited to monitor, on a monthly basis, by means of a questionnaire validated earlier, the hearing and language of children born in their micro areas of expertise. Thirty-nine community health workers agreed to participate, with only two refusals. Five gave up participating. Twenty-six (66.66%) did not perform monitoring, seven (17.94%) monitored improperly and only six (15.38%) monitored properly. Just one child failed the quiz, who was forwarded to the hospital that conducted the auditory screening for retesting. These professionals' high activity demand was considered the main reason for the difficulties encountered in this project. In addition, there is the difficulty to have contact with the Family Health Strategy teams, as well as the impossibility of permanent face-to-face discussions and the influence of the community health agents' supervisors.

Este artigo analisa a viabilidade da implantação de um programa de monitoramento do desenvolvimento auditivo e de linguagem no primeiro ano de vida. Trata-se de um estudo longitudinal prospectivo, no qual quarenta e um agentes comunitários de saúde foram convidados a monitorar mensalmente, por meio de um questionário já validado, a audição e a linguagem de crianças nascidos nas suas microáreas de atuação. Trinta e nove agentes comunitários de saúde aceitaram participar, havendo apenas duas recusas. Cinco desistiram da participação. Vinte e seis (66,66%) não realizaram o monitoramento, sete (17,94%) monitoraram de forma inadequada e apenas seis (15,38%) monitoraram adequadamente. Apenas uma criança falhou no questionário, a qual foi reencaminhada ao hospital em que realizou a triagem auditiva para reteste. Acredita-se que a elevada demanda de atividades destes profissionais foi o principal motivo para as dificuldades observadas neste projeto. Além disso, destaca-se a dificuldade no contato com as equipes de Estratégia Saúde da Família, bem como a inviabilidade de discussões presenciais permanentes e a influência dos supervisores dos agentes comunitários de saúde.