array:23 [ "pii" => "S0001651920300406" "issn" => "00016519" "doi" => "10.1016/j.otorri.2019.12.003" "estado" => "S300" "fechaPublicacion" => "2020-11-01" "aid" => "983" "copyright" => "Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Acta Otorrinolaringol Esp. 2020;71:349-57" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S000165192030039X" "issn" => "00016519" "doi" => "10.1016/j.otorri.2019.12.002" "estado" => "S300" "fechaPublicacion" => "2020-11-01" "aid" => "982" "copyright" => "Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Acta Otorrinolaringol Esp. 2020;71:358-66" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo original</span>" "titulo" => "Expresión de E-cadherina y β-catenina en carcinomas de células escamosas de laringe e hipofaringe" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "358" "paginaFinal" => "366" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Expression of E-cadherin and β-catenin in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 828 "Ancho" => 1800 "Tamanyo" => 369727 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">(x400), (A)tinción positiva de E-cadherina en el epitelio normal, (B) tinción negativa de E-cadherina en carcinoma, (C) tinción negativa de β-catenina en carcinoma, (D) tinción positiva de E-cadherina en carcinoma, (E) tinción positiva de β-catenina de membrana en carcinoma y (F) tinción positiva de β-catenina nuclear.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Patricia García-Cabo, Juana María García-Pedrero, M. Ángeles Villaronga, Francisco Hermida-Prado, Rocío Granda-Díaz, Eva Allonca, Fernando López, Juan Pablo Rodrigo" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Patricia" "apellidos" => "García-Cabo" ] 1 => array:2 [ "nombre" => "Juana María" "apellidos" => "García-Pedrero" ] 2 => array:2 [ "nombre" => "M. Ángeles" "apellidos" => "Villaronga" ] 3 => array:2 [ "nombre" => "Francisco" "apellidos" => "Hermida-Prado" ] 4 => array:2 [ "nombre" => "Rocío" "apellidos" => "Granda-Díaz" ] 5 => array:2 [ "nombre" => "Eva" "apellidos" => "Allonca" ] 6 => array:2 [ "nombre" => "Fernando" "apellidos" => "López" ] 7 => array:2 [ "nombre" => "Juan Pablo" "apellidos" => "Rodrigo" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173573520301034" "doi" => "10.1016/j.otoeng.2019.12.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573520301034?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000165192030039X?idApp=UINPBA00004N" "url" => "/00016519/0000007100000006/v1_202011120632/S000165192030039X/v1_202011120632/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0001651920300443" "issn" => "00016519" "doi" => "10.1016/j.otorri.2019.11.007" "estado" => "S300" "fechaPublicacion" => "2020-11-01" "aid" => "987" "copyright" => "Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Acta Otorrinolaringol Esp. 2020;71:343-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Fine-needle aspiration cytology in the diagnosis of salivary gland lesions. The role of the Milan system for reporting cytopathology" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "343" "paginaFinal" => "348" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Citología por aspiración con aguja fina en el diagnóstico de las lesiones de las glándulas salivales. El papel del sistema Milán en citopatología" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "José-Fernando Val-Bernal, María Martino, Sara Marcos, Elena Yllera, Belén García-Montesinos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "José-Fernando" "apellidos" => "Val-Bernal" ] 1 => array:2 [ "nombre" => "María" "apellidos" => "Martino" ] 2 => array:2 [ "nombre" => "Sara" "apellidos" => "Marcos" ] 3 => array:2 [ "nombre" => "Elena" "apellidos" => "Yllera" ] 4 => array:2 [ "nombre" => "Belén" "apellidos" => "García-Montesinos" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001651920300443?idApp=UINPBA00004N" "url" => "/00016519/0000007100000006/v1_202011120632/S0001651920300443/v1_202011120632/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "The impact of medical interventions for reducing ototoxicity during treatment for multi-drug resistant tuberculosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "349" "paginaFinal" => "357" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Katijah Khoza-Shangase, Lineo Lecheko, Liepollo Ntlhakana" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Katijah" "apellidos" => "Khoza-Shangase" "email" => array:1 [ 0 => "katijah.khoza@wits.ac.za" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Lineo" "apellidos" => "Lecheko" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Liepollo" "apellidos" => "Ntlhakana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Speech Pathology and Audiology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa – PhD in Audiology (University of the Witwatersrand), South Africa" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Speech Pathology and Audiology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa – Master's in Audiology (University of the Witwatersrand), South Africa" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Impacto de las intervenciones médicas para reducir la ototoxicidad durante el tratamiento de la tuberculosis multirresistente a los fármacos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2044 "Ancho" => 2454 "Tamanyo" => 391485 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Mean thresholds of monthly pure tone audiometry results of the control group.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The World Health Organisation<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> now estimates that about 6.1% of the world population is living with disabling hearing loss. There are various and wide-ranging causes for hearing loss, including the use of ototoxic drugs. Certain drugs, namely aminoglycosides and certain anti-malarial medications, are known to cause hearing loss,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">2</span></a> but are however usually reserved for treating life threatening conditions such as tuberculosis (TB),<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> as in the current study. Ototoxic medications such as aminoglycosides continue to present controversy in the medical world, as they remain considerably toxic to the inner ear<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">4,5</span></a>; and significantly impact the affected individual's quality of life.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Due to high numbers of patients currently on long term treatment for tuberculosis, it is said that South Africa is “…potentially facing the risk of a significant proportion of the population acquiring aminoglycoside-induced permanent hearing loss”.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">6</span></a> In 2017, it was reported in a News24 article by Singh, that 123 TB patients in Kwa Zulu Natal had gone deaf following TB treatment. In this article the reason cited for the patients going deaf was negligence by the department of health, “… as their TB treatment was not properly monitored causing a complete loss of hearing”.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">7</span></a> It is for such reasons that ototoxicity monitoring during long term treatment with aminoglycosides is critical.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8–10</span></a> If identified early and followed up with medical intervention, it may be possible to reduce further deterioration of hearing function to the point of affecting lower frequencies that are important for speech understanding.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">9,11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The World Health Organization,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> in line with preventive audiology that advocates for early detection and intervention of hearing impairment, highlights the importance of active surveillance for known adverse effects of MDR-TB treatment through close monitoring programmes. Should adverse effects be detected early, WHO<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> provides intervention strategies. These intervention strategies, as far as ototoxicity is concerned, recommend the following:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1.</span><p id="par0020" class="elsevierStylePara elsevierViewall">Document hearing and compare to a baseline audiogram</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2.</span><p id="par0025" class="elsevierStylePara elsevierViewall">If early signs of ototoxicity are noted<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">a.</span><p id="par0030" class="elsevierStylePara elsevierViewall">Increase the dose interval from e.g. daily to thrice weekly,</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">b.</span><p id="par0035" class="elsevierStylePara elsevierViewall">Consider using capreomycin if an aminoglycoside was the prior injectable in the regimen</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">3.</span><p id="par0040" class="elsevierStylePara elsevierViewall">If hearing loss continues despite the dose adjustment discontinue the injectable agent and add additional drugs to reinforce the regimen of the drug.</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">In the revised protocol, less ototoxic drugs such as bedaquiline and linezolid are prioritized as the first drugs of choice, i.e. in group A, whilst a known ototoxin such as amikacin is in group C, only to be considered when drugs from groups A and B cannot be used.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The revised treatment protocol for MDR-TB, although approved by the WHO,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> has not been adopted at a national level by many countries due to the exorbitant costs involved with the new treatment,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">12</span></a> as well as due to reported multiple barriers to programmatic introduction such as “…technical expertise and guidance, confusion about pharmacovigilance requirements, challenges with registration and import and difficulties obtaining the other medications needed for successful treatment outcomes”.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">13</span></a> South Africa is leading the way as the only country in the world to have adopted the revised treatment protocol for MDR-TB within its national TB treatment policy, and as such bedaquiline is registered in the country and available nationally, including at sub-district levels such as where hospitals A and B where the current study was conducted are situated.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1,12–14</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">To evaluate the effectiveness of the applied WHO medical intervention strategies, prior to the national roll-out of bedaquiline as the first line treatment in South Africa, Hospital A which is situated in the province of Kwa-Zulu Natal, and Hospital B situated in the Eastern Cape, both classified as rural hospitals, formed the study data collection sites. The difference between the two hospitals was that, at the time of the current study, Hospital B implemented medical intervention strategies according to WHO,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> as well as counselling and aural rehabilitation at the point of detection of ototoxicity; whilst Hospital A continued with treatment unchanged, and only implemented counselling and aural rehabilitation to those affected. This difference in the two hospitals made the current study aimed at investigating the impact of early medical interventions to reduce ototoxicity of aminoglycosides for the treatment of MDR-TB possible, as audiological comparison could be done without refusing patients treatment. Determining the impact of interventions aimed at reducing the overall disabling impact of ototoxicity within this context could significantly influence audiological practice, while improving the patients’ quality of life.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Aim of the study</span><p id="par0060" class="elsevierStylePara elsevierViewall">The main aim of the study was to investigate the impact of early medical interventions aimed at reducing the ototoxic effects of long-term use of aminoglycosides for the treatment of MDR-TB in a group of adult patients at a rural hospital in the Eastern Cape, South Africa. The specific sub-aims included:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">1.</span><p id="par0065" class="elsevierStylePara elsevierViewall">To review data on the audiological function of adult patients on treatment for MDR-TB that had preventative medical intervention strategies applied in response to early signs of ototoxicity.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">2.</span><p id="par0070" class="elsevierStylePara elsevierViewall">To compare hearing function in the group of adults where preventative medical intervention strategies were implemented (intervention group) to a group where preventative medical intervention strategies were not implemented (control group).</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">3.</span><p id="par0075" class="elsevierStylePara elsevierViewall">To determine the impact of preventative medical intervention strategies on ototoxicity during long-term treatment for MDR-TB.</p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">The medical interventions were those in line with the WHO<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> guidelines as detailed below:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">1.</span><p id="par0085" class="elsevierStylePara elsevierViewall">If early signs of ototoxicity are noted<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">a.</span><p id="par0090" class="elsevierStylePara elsevierViewall">Increase the dose interval from e.g. daily to thrice weekly,</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">b.</span><p id="par0095" class="elsevierStylePara elsevierViewall">Consider using capreomycin if an aminoglycoside was the prior injectable in the regimen</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">2.</span><p id="par0100" class="elsevierStylePara elsevierViewall">If hearing loss continues despite the dose adjustment discontinue the injectable agent and add additional drugs to reinforce the regimen of the drug.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">3.</span><p id="par0105" class="elsevierStylePara elsevierViewall">In the revised protocol, less ototoxic drugs such as bedaquiline and linezolid are prioritized as the first drugs of choice.</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Research design and methods</span><p id="par0110" class="elsevierStylePara elsevierViewall">A retrospective record review with a control group design was used for the current study; where existing hard copy audiological and medical records of adult participants diagnosed and treated for MDR-TB at a hospital in the Eastern Cape, in the period June 2014 to June 2016 for the intervention group were reviewed alongside those of a control group, comprising of similar patient records at a provincial hospital in Kwa-Zulu Natal South Africa. The audiological record review of the study included baseline and subsequent monthly audiological evaluations of all participants. The medical record reviews involved exploring medical intervention strategies applied when signs of ototoxicity were identified in an attempt to prevent further ototoxic hearing loss for the intervention group. This element was not investigated in the control group as such preventative medical strategies were not applied at the time of data collection.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The sample in this study was restricted to a part of the population that was infected and on treatment for MDR-TB. All the participants were diagnosed with MDR-TB, and 62 (72%) participants presented with previous history of tuberculosis. Of the 62 participants presenting with a history of TB, 41 (66%) were found to have completed their treatment whilst 21 (34%) did not complete treatment. All the records were reviewed, and the researchers selected participants that met the inclusion criteria purposely for the benefit of extracting the most valid and reliable data for the study. The same inclusion and exclusion criteria were applied for both the intervention and control groups, with the exception that participant records of patients for the intervention group were drawn from a research site where ototoxicity preventative medical intervention strategies were applied.<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">•</span><p id="par0120" class="elsevierStylePara elsevierViewall">The intervention group comprised a total of 32 participant files, and the control group 54. Participant records that were included in the study met the following inclusion criteria:</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">•</span><p id="par0125" class="elsevierStylePara elsevierViewall">MDR-TB diagnoses and long-term treatment of 6 months with injectable aminoglycosides<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a>; due to their documented effects.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">6,15</span></a></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">•</span><p id="par0130" class="elsevierStylePara elsevierViewall">Adults between 18 and 49.11 years of age to control for age effects on susceptibility to ototoxicity.</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">•</span><p id="par0135" class="elsevierStylePara elsevierViewall">Participant records with baseline hearing evaluation prior to treatment administration or within 72<span class="elsevierStyleHsp" style=""></span>hours of treatment initiation, but no longer than two weeks of treatment initiation.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">8,16</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">•</span><p id="par0140" class="elsevierStylePara elsevierViewall">Participant records containing baseline and subsequent monthly evaluations reflecting data which includes: case history, otoscopic examination, tympanometry conventional and ultra-high frequency air conduction audiometry, as well as at least five months of audiological monitoring over the intensive phase of MDR-TB treatment.</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">•</span><p id="par0145" class="elsevierStylePara elsevierViewall">Participant history including a history of co-occurrence with HIV, significant noise exposure, past use of ototoxic medication, history of otitis media in childhood, or other potential causes for hearing loss was recorded.</p></li></ul></p><p id="par0150" class="elsevierStylePara elsevierViewall">Participant records meeting the following criteria were excluded from inclusion in the study:<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">•</span></span><p id="par0155" class="elsevierStylePara elsevierViewall">Records of participants aged 50 and above were excluded to control for presbycusis influence.</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">•</span></span><p id="par0160" class="elsevierStylePara elsevierViewall">Participant records that indicated conductive and/or mixed hearing loss at any stage during the six-month monitoring period were excluded for possible influence on reliability of findings in an ototoxicity monitoring programme.</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel"><span class="elsevierStyleBold">•</span></span><p id="par0165" class="elsevierStylePara elsevierViewall">Participant files that showed inconsistent monthly monitoring of more than three months were also excluded to ensure consistent long-term data, for better coherency during analysis.</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Materials and procedures</span><p id="par0170" class="elsevierStylePara elsevierViewall">Data collection commenced following ethical approval from the relevant supervisory authority at the University's Ethical Committee (Medical) (protocol number: M160708) as well as from the relevant hospitals’ authorities. Once approval was secured, participant records meeting the inclusion criteria were reviewed. A data capturing sheet was designed and used to capture all relevant data including age, gender, MDR-TB Treatment regimen, audiological results, early medical intervention strategies applied to prevent ototoxicity in the intervention group, and audiological management including information counselling, aural rehabilitation, hearing aid evaluation and/or fitting of hearing aids. All data collected were then analyzed in accordance with the research aims. All ethical considerations were observed. Ethical considerations were based on the Nuremberg Code of Ethics, the World Medical Associations (WMA) Declaration of Helsinki and the Belmont Report on ethical treatment of research participants.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Both data collection sites utilized the standard audiological protocol for ototoxicity monitoring that was in accordance with the “Guidelines for the audiologic management of individuals treated with cochleotoxic drug therapy” as established by ASHA.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> Pure tone audiometry assessments included the conventional frequency range (250–8000<span class="elsevierStyleHsp" style=""></span>Hz) as well as the ultra-high frequencies up to 11,200<span class="elsevierStyleHsp" style=""></span>Hz for the intervention group. Normal hearing was clinically classified as hearing that is within 0–25<span class="elsevierStyleHsp" style=""></span>dB pure tone thresholds for adults, with hearing loss categorized accordingly.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a> The criteria used to define ototoxicity in this study was that by ASHA.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Data analysis and statistical procedures</span><p id="par0180" class="elsevierStylePara elsevierViewall">The study made use of both descriptive and inferential statistics.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">15</span></a> Data on the audiological function of adult patients on treatment for MDR-TB that had preventative medical intervention strategies applied in response to early signs of ototoxicity, were analyzed using descriptive statistics. Paired-<span class="elsevierStyleItalic">t</span> test analysis and logistical regression analysis, set at a significance level of 0.05 (<span class="elsevierStyleItalic">p</span>-value), were applied to determine the effect of independent variables (treatment regimen, medical intervention strategies) on a dependent variable (ototoxicity). An acknowledged limitation in the study was that the groups were not paired, and so potential disparities between groups in terms of possible confounding variables such as the diagnosis of diabetes could not be controlled for. Fortunately, the final samples did not present with significant confounding variables other than those included in the analysis.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Reliability and validity</span><p id="par0185" class="elsevierStylePara elsevierViewall">Reliability was ensured by safeguarding that all participant records were well documented, that equipment used during assessments was calibrated, and that assessment tools used were valid and in accordance with practice standards. All files were collected by the researcher to further ensure consistency in the study for both the intervention and control groups. Validity was safeguarded by ensuring that the tests performed were appropriate and followed established protocols for the monitoring of patients on MDR-TB, and this includes assessment of frequencies<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>8000<span class="elsevierStyleHsp" style=""></span>Hz.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The current study was a retrospective record review study, which may raise questions of bias and inaccuracies of the existing data, as the testing procedures were conducted at a different time and often by a different person, therefore raising questions about reliability and validity of the existing data. The fact that all assessments were conducted by qualified registered audiologists mitigates this challenge.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results of the total sample at baseline</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Description of participants</span><p id="par0195" class="elsevierStylePara elsevierViewall">The total sample from both the intervention and the control groups comprised of a total of <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>86 patient files with the age range between 18 and 49 years, with a mean age of 33.3 years. Both groups had more males than females, the control group had more participants with HIV (47%) as well as more participants with a previous history of TB (45%) than the intervention group; where only 27% had HIV and 27% had a previous history of TB.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Audiological function of adult patients on treatment for MDR-TB</span><p id="par0200" class="elsevierStylePara elsevierViewall">The results obtained revealed a difference in mean pure tone thresholds in both groups when <span class="elsevierStyleItalic">monthly pure tone audiometry results were compared</span> as visually depicted in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Difference in hearing function between the two groups</span><p id="par0205" class="elsevierStylePara elsevierViewall">Results, as depicted in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>, revealed overall gradual progression of hearing loss in both ears for both groups. The intervention group's results revealed a gradual progression of hearing loss from normal hearing across the frequency range (250–11,200<span class="elsevierStyleHsp" style=""></span>Hz) at baseline, to a mild hearing loss (31.33–40.45<span class="elsevierStyleHsp" style=""></span>dB) in the final session of assessment in the frequency range of 4000–11,200<span class="elsevierStyleHsp" style=""></span>Hz, with normal hearing in the lower frequencies. The control group results also revealed progressive hearing loss. From baseline, hearing progressed from normal across the conventional frequency range (250–8000<span class="elsevierStyleHsp" style=""></span>Hz), to a mild hearing loss (35.22<span class="elsevierStyleHsp" style=""></span>dB at 8000<span class="elsevierStyleHsp" style=""></span>Hz) in the final session of assessment. The ultra-high frequencies (10,000<span class="elsevierStyleHsp" style=""></span>Hz and 12,500<span class="elsevierStyleHsp" style=""></span>Hz), however, revealed a mild to moderate hearing loss (39.25–51.73<span class="elsevierStyleHsp" style=""></span>dB) at baseline to a moderately severe to severe hearing loss (65.42–71.96<span class="elsevierStyleHsp" style=""></span>dB) at the final session of assessment.</p><p id="par0210" class="elsevierStylePara elsevierViewall">The results reveal clear progression of hearing loss over this time period in both groups. In the intervention group, hearing loss, on average, progressed from normal hearing at baseline, except at 11,200 (27.32<span class="elsevierStyleHsp" style=""></span>dB), to a mild to moderate hearing loss in the final session of assessment. Additionally, results revealed the severest average increase in hearing thresholds to have occurred in the high and ultra-high frequency ranges of 4000<span class="elsevierStyleHsp" style=""></span>Hz to 11,200<span class="elsevierStyleHsp" style=""></span>Hz (33–44.39<span class="elsevierStyleHsp" style=""></span>dB). The control group's mean pure tone thresholds at baseline, however, revealed a moderate ultra-high frequency hearing loss with normal hearing in the conventional frequency range. A clear progression in hearing loss is also revealed for the control group, as hearing loss progressed to mild to moderate in the final session of assessment, affecting conventional frequencies from 6000<span class="elsevierStyleHsp" style=""></span>Hz to 12,500<span class="elsevierStyleHsp" style=""></span>Hz (36.78–71.74<span class="elsevierStyleHsp" style=""></span>dB). Thus, results of the control group revealed the severest average increase in hearing thresholds occurred in the high and ultra-high frequency range of 6000–12,500<span class="elsevierStyleHsp" style=""></span>Hz.</p><p id="par0215" class="elsevierStylePara elsevierViewall">The difference in the progression of hearing loss in both groups was clinically significant when using the Silman and Silverman<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a> system of classification of hearing loss, as the intervention group presented with a mild to moderate high frequency hearing loss, whilst the control group presented with a moderate to moderately severe high frequency hearing loss. Overall, the results reveal clinically significant better hearing sensitivity in the intervention group when compared to the control group; thus, suggesting that early medical preventative strategies implemented had a positive impact in the hearing function of participants in the intervention group.</p><p id="par0220" class="elsevierStylePara elsevierViewall">The patients’ audiological function tracked using pure-tone audiometry results from 250<span class="elsevierStyleHsp" style=""></span>Hz to 11,200<span class="elsevierStyleHsp" style=""></span>Hz, for both ears for the intervention and control groups, revealed differences in mean pure-tone thresholds across frequencies; differences that were statistically significant on calculation of significance levels with the <span class="elsevierStyleItalic">t</span>-test at 0.05 for each session. All the <span class="elsevierStyleItalic">p</span>-values obtained were statistically significant.</p><p id="par0225" class="elsevierStylePara elsevierViewall">Overall the results revealed that although hearing loss developed in both groups and progressively worsened with each subsequent assessment session; in the group where medical intervention strategies were implemented, hearing loss developed at a much slower rate when compared to the group where such strategies were not implemented. Furthermore, the degree of the hearing loss in the intervention group was less severe when compared to that in the control group at the last follow up session.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">The impact of the interventions on the hearing thresholds</span><p id="par0230" class="elsevierStylePara elsevierViewall">Medical intervention strategies, which were only implemented in the intervention group when hearing loss was first detected included ‘reduce dosage and review in two weeks with audiology first’ for 56% of the intervention group; and ‘continue treatment and monitor closely’ for the rest.</p><p id="par0235" class="elsevierStylePara elsevierViewall">Upon review at the initial two-week follow-up, a variety of additional medical interventions were implemented. The most common medical intervention strategies employed were to reduce the dosage of the ototoxic drug in 61% of the sample, with the daily dosage reduced to 800<span class="elsevierStyleHsp" style=""></span>mg in 39% of participants; while the administration of the drug was reduced from daily to thrice weekly in 22% of participants, and the rest of the participants that did not show signs of ototoxicity continued treatment under close medical and audiological monitoring; as reflected in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>. Treatment with the ototoxic drug was stopped in seven (28%) of the participants, five were initiated on bedaquiline, one commenced continuation phase treatment, whilst another was initiated on pre-XDR treatment, due to overall treatment failure.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Discussion of results</span><p id="par0240" class="elsevierStylePara elsevierViewall">The study comprised of 86 participants (32 intervention group and 54 in the control group). The sample included 48 males and 38 females, between the ages of 18 and 49 with a mean age of 33 years. The unequal number of participants between the control and the intervention groups could present as a challenge to the generalization of the current results, however this could not be controlled for as data was collected in accordance with the convenience sampling method, and as such all available participants that met the inclusion criteria were included in the study.</p><p id="par0245" class="elsevierStylePara elsevierViewall">Current findings in both groups revealed progressive hearing loss. In both groups, the development and progression of hearing loss was more aggressive in the high and ultra-high frequencies. Extensive literature exists supporting high frequency hearing loss as a result of ototoxic medication. The prominence of high frequency hearing loss in the current study concurs with findings from Apanna et al.,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">18</span></a> and Duggal and Sarkar's,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">11</span></a> where high frequencies were also found to be most affected bilaterally. Current findings thus support the use of highly sensitive and specific measures, such as ultra-high frequency audiometry, for early identification and intervention of high frequency hearing loss in this population.</p><p id="par0250" class="elsevierStylePara elsevierViewall">With regards to the comparison of hearing function between the two groups, the results reveal that the rate at which hearing loss progressed was significantly more aggressive in the control group than in the intervention group. In terms of degree of hearing loss, the hearing loss in the final session of assessment was mild to moderate in the intervention group, and mild to moderately severe for the control group. These results indicate that in the group where medical intervention strategies were implemented, hearing loss appears to have progressed at a slower rate than in the control group, where intervention strategies were not implemented. These findings are in agreement with a recent study by Maluleka et al.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> which found hearing loss to progress at a slower rate in patients where medical intervention strategies were implemented. Such findings provide support for implementation of medical intervention strategies as they clearly illustrate a positive benefit for the patient in regard to the severity of hearing loss; with consequent preservation of the patients’ quality of life at the same time as preservation of the quantity of life.</p><p id="par0255" class="elsevierStylePara elsevierViewall">Medical intervention strategies implemented in the intervention group upon diagnoses of ototoxicity in line with the ASHA<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">8</span></a> criteria for ototoxic hearing loss, were consistent with the WHO<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> guidelines for the programmatic management of adverse reactions to MDR-TB treatment. The common intervention strategies employed were ‘to reduce the dosage of the ototoxic drug, by either reducing the daily dosage or reducing the administration of the drug to thrice weekly’ and ‘to change the ototoxic drug to a less ototoxic drug, i.e. bedaquiline’. These intervention strategies are not unusual. A South African study investigating the effectiveness of medical interventions implemented during ototoxicity monitoring to prevent further deterioration of hearing thresholds, also found the most common types of medical interventions to be ‘change frequency of drug administration’ in 46% and ‘stop treatment’ in 19% of the sample.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> Therefore, current findings support the adjustment of ototoxic treatment dosage and administration thereof, as well as the changing of ototoxic treatment to less ototoxic drugs whenever possible in order to prevent further hearing loss in patients. More research investigating the impact or effectiveness of such intervention strategies is greatly needed, however, current findings raise implications for the practice of audiology and ototoxicity monitoring of MDR-TB patients, as results reveal that a potential to slow down the progression of hearing as a result of ototoxic MDR-TB medication may exist.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0260" class="elsevierStylePara elsevierViewall">The main aim of the study was to investigate the impact of early medical intervention aimed at reducing the ototoxic effects of long-term use of aminoglycosides for the treatment of MDR-TB in a group of adult patients at a rural hospital in the Eastern Cape, South Africa. Current findings provide evidence supporting careful use of preventive medical intervention measures to conserve hearing function in patients on ototoxic medications. Commonly applied medical intervention strategies including reducing dosage of the ototoxic drug by reducing daily dosing as well as by reducing the administration of the drug from daily to thrice weekly; as well as stopping the ototoxic drug and replacing it with less toxic drugs (bedaquiline) were found in the current study. Such contextually relevant findings have the potential to contribute towards audiological care by way of provision of evidence to advocate for early identification and monitoring of ototoxicity; with efficacious implementation of recommended intervention/preventative measures in light of the fact that a window of opportunity to reduce further hearing loss may exist.</p><p id="par0265" class="elsevierStylePara elsevierViewall">Current results, however, need to be considered in relation to the methodological weaknesses identified in the methodology. These included the lack of total control over confounding variables due to the nature of the population being studied, and the nature of the disease; the retrospective nature of the study; as well as the small sample sizes in both groups. Nonetheless, current findings reveal valuable information about the role audiologists in South Africa need to play in the development and maintenance of ototoxicity monitoring programmes. This includes ensuring that ototoxicity monitoring does not happen in isolation from medical intervention preventative measures. Regardless of the fact that a new treatment regimen for MDR-TB treatment that prioritizes the use of drugs that are less ototoxic, such as bedaquiline, has been released by the WHO, access to these drugs is not universal with expense being the biggest limiting factor especially in developing countries. South Africa remains the only country that has adopted this new treatment regimen at a national level. In countries where bedaquiline is not available nationally, the current results indicate that close monitoring with medical interventions when ototoxicity is diagnosed may play an important role in reducing or curbing further hearing loss during MDR-TB treatment.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Authors’ contribution</span><p id="par0270" class="elsevierStylePara elsevierViewall">Authors K.K.-S. and L.L. co-conceptualised the idea for the research as well as the design and methodology adopted. L.L. collected the data for the study and analyzed the data with assistance from K.K.-S. and L.N., under whose supervision she worked. All three authors were involved in writing up of the manuscript for publication. All authors read and approved the final manuscript.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Novelty of the work</span><p id="par0275" class="elsevierStylePara elsevierViewall">Preventive audiology is a field that is growing within low and middle income countries where reliance on evidence from high income countries has been the norm despite significant contextual factors differences. Some focus has been placed on establishing contextually relevant evidence around establishing ototoxicity of certain drugs, but limited research has been conducted on preventive measures for ototoxicity. This study fills this gap and has contextual relevance in that limited “safe” alternative drugs are often available. Findings from this study have important implications for TB management in the South African context, which is amongst countries with the highest incidence of TB.</p><p id="par0280" class="elsevierStylePara elsevierViewall">We look forward to your response, and thank you so much for considering it for publication in the journal.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflict interests</span><p id="par0285" class="elsevierStylePara elsevierViewall">The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1412493" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1292654" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1412492" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1292655" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Aim of the study" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Research design and methods" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Materials and procedures" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Data analysis and statistical procedures" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Reliability and validity" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0045" "titulo" => "Results of the total sample at baseline" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Description of participants" ] ] ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Audiological function of adult patients on treatment for MDR-TB" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Difference in hearing function between the two groups" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "The impact of the interventions on the hearing thresholds" ] ] ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion of results" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors’ contribution" ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Novelty of the work" ] 11 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict interests" ] 12 => array:2 [ "identificador" => "xack491829" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-09-17" "fechaAceptado" => "2019-12-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1292654" "palabras" => array:4 [ 0 => "Aminoglycosides" 1 => "Medical intervention strategies" 2 => "Multi-drug resistant tuberculosis" 3 => "Ototoxicity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1292655" "palabras" => array:4 [ 0 => "Aminoglucósidos" 1 => "Estrategias de intervención médica" 2 => "Tuberculosis multirresistente a los fármacos" 3 => "Ototoxicidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The impact of medical interventions for reducing ototoxicity requires focus in contexts where safe non-ototoxic alternative drugs are not yet available.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The goal was to investigate the impact of medical intervention strategies for reducing the ototoxic effects of long-term use of aminoglycosides for the treatment of Multi-Drug Resistant Tuberculosis (MDR-TB) in adults at a rural hospital in the Eastern Cape, South Africa.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A retrospective record review with a control group design was used, with audiological and medical record reviews of all participants’ files over a six-month period. A total of 86 participants (intervention group <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>32 and control group <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>54) were included. Descriptive and inferential statistics were used to analyze the data.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Results revealed progressive hearing loss in both groups, with worsening of thresholds at each subsequent assessment session. The progression of the hearing loss, however, was much slower in the intervention group, with degree of hearing loss being more severe in the control group in the final session of assessment (36.78–71.74<span class="elsevierStyleHsp" style=""></span>dB), when compared to the intervention group (33–44.39<span class="elsevierStyleHsp" style=""></span>dB). Furthermore, the hearing loss in the intervention group remained in the high frequencies while that in the control group progressed to involve the lower frequencies on the audiogram. The most common medical intervention strategies employed in the current study were to reduce the dosage of the ototoxic drug (61%), with the daily dosage reduced to 800<span class="elsevierStyleHsp" style=""></span>mg in 39% of participants, while the administration of the drug was reduced from daily to thrice weekly in 22% of participants.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The results reveal better hearing sensitivity over the treatment period in the intervention group when compared to the control group; thus suggesting that early medical strategies implemented had a significant preventive impact. Current findings are relevant to the audiological, medical and pharmaceutical fields, particularly within the South African context where resource constraints are a consideration in all treatment measures.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El impacto de las intervenciones médicas para reducir la ototoxicidad requiere concentrarse en los contextos en los que no se dispone de fármacos alternativos no ototóxicos seguros.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo fue investigar el impacto de las intervenciones médicas para reducir los efectos ototóxicos del uso prolongado de aminoglucósidos para el tratamiento de la tuberculosis multirresistente a los fármacos (MDR-TB) en adultos, en un hospital rural en Cabo Oriental, Sudáfrica.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Métodos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se realizó una revisión retrospectiva de historias con grupo control de las revisiones audiológicas y médicas de todos los participantes durante un periodo de 6 meses, incluyéndose a un total de 86 participantes (grupo intervención n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>32 y grupo control n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>54). Se utilizaron estadísticas descriptivas e inferenciales para analizar los datos.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los resultados revelaron hipoacusia progresiva en ambos grupos, con empeoramiento de los umbrales en cada examen sucesivo. Sin embargo, la progresión de la hipoacusia fue menor en el grupo intervención, siendo más severo el grado de pérdida auditiva en el grupo control en el examen final de evaluación (36,78-71,74<span class="elsevierStyleHsp" style=""></span>dB), en comparación con el grupo intervención (33-44,39<span class="elsevierStyleHsp" style=""></span>dB). Además, la hipoacusia se mantuvo en frecuencias altas en el grupo intervención, mientras que en el grupo control experimentó una progresión, incluyendo las frecuencias bajas en el audiograma. Las intervenciones médicas más comunes utilizadas en el presente estudio fueron la reducción de la dosis de fármacos ototóxicos (61%), reduciéndose la dosis diaria a 800<span class="elsevierStyleHsp" style=""></span>mg en el 39% de los participantes, mientras que la administración del fármaco se redujo de una a tres veces por semana en el 22% de los participantes.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los resultados revelan mejor sensibilidad auditiva a lo largo del periodo de tratamiento en el grupo intervención, en comparación con el grupo control, lo cual sugiere que las estrategias médicas tempranas implementadas tuvieron un impacto preventivo significativo. Los hallazgos actuales son relevantes para los campos audiológico, médico y farmacéutico, particularmente en el contexto de Sudáfrica, donde las limitaciones de recursos son dignas de consideración en todas las medidas de tratamiento.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1605 "Ancho" => 2600 "Tamanyo" => 349425 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Mean thresholds of monthly pure tone audiometry results of the intervention group.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2044 "Ancho" => 2454 "Tamanyo" => 391485 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Mean thresholds of monthly pure tone audiometry results of the control group.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1362 "Ancho" => 2167 "Tamanyo" => 227305 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Medical intervention strategies applied at first follow-up review subsequent to the detection of ototoxicity in the intervention group.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0100" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization. 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The authors would also like to acknowledge the National Institute for the Humanities and Social Sciences (NIHSS) for funding towards time out for writing fees.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/00016519/0000007100000006/v1_202011120632/S0001651920300406/v1_202011120632/en/main.assets" "Apartado" => array:4 [ "identificador" => "5852" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Artículos originales" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00016519/0000007100000006/v1_202011120632/S0001651920300406/v1_202011120632/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001651920300406?idApp=UINPBA00004N" ]
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Original article
The impact of medical interventions for reducing ototoxicity during treatment for multi-drug resistant tuberculosis
Impacto de las intervenciones médicas para reducir la ototoxicidad durante el tratamiento de la tuberculosis multirresistente a los fármacos
a Department of Speech Pathology and Audiology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa – PhD in Audiology (University of the Witwatersrand), South Africa
b Department of Speech Pathology and Audiology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa – Master's in Audiology (University of the Witwatersrand), South Africa