Comparing Hearing Loss in Children with Adults Living with Sickle Cell Disease and Sickle Cell Traits.

BACKGROUND: Hearing loss is a neurological sequelae associated with sickle cell disease (SCD) and probably sickle cell trait (SCT) in children and adults but remains understudied. AIM: This study aimed to compare the hearing impairment among children and adults living with SCD or SCT. METHODS: A comparative cross-sectional study conducted in four departments with SCD outpatient clinic in a tertiary hospital in Nigeria. Participants with Sickle cell disease (HbSS) and Sickle cell trait (HbAS) (cohort) and HbAA (control) had comprehensive ear and hearing assessments for sensorineural hearing loss. Audiometric results were categorized according to WHO classifications and data analysed with Statistical Analysis System (SAS 9.4). RESULTS: A total of 212 participants (106 cohort and control, respectively), aged 6 months to 55 years, were enrolled. Of these, 35% of children with SCD and 25% with SCT had hearing impairment, while 30% of adults with SCD, 36.1% with SCT, and 11% with HbAA had hearing impairment. There was asymmetry in the hearing impairment, with the left ear more affected in children and the right ear in adults. The odds ratio (OD) of hearing impairment was higher in HbSS (2.48 (95% confidence interval (CI):1.51-4.14); P = 0.0004) and HbAS (2.28 (95% CI: 1.1-4.58); P = 0.02) participants compared with HbAA but was not statistically significant when adjusted for frequency of hospitalization, crises, blood transfusion and routine drugs in HbAS (P = 0.49) unlike HbSS (P = 0.03). CONCLUSION: The prevalence of hearing loss among children and adults with SCD is higher than in those with HbA genotype. The frequency of hospitalization, crises, blood transfusion and taking routine drugs may influence hearing impairment in SCT but may not in SCD.

Scoping Review of Predisposing Factors Associated with Sensorineural Hearing Loss in Sickle Cell Disease.

PURPOSE: Sickle cell disease (SCD) is a genetically inherited red blood cell disorder that affects people all over the world but is more common among blacks of African ancestry than other races. The condition is linked to sensorineural hearing loss (SNHL). This scoping review aims to evaluate studies that reported SNHL in SCD patients and to identify demographic and contextual risk factors for SNHL in SCD patients. METHODS: We conducted scoping searches for relevant studies in PubMed, Embase, Web of Science, and Google Scholar. All articles were evaluated independently by two authors. The checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was used. SNHL was detected at hearing levels above 20 decibels. RESULTS: In terms of methodology, the studies reviewed were diverse, with 15 being prospective and four being retrospective. Fourteen of the 19 articles chosen from 18,937 search engine results were case-control studies. Sex, age, foetal haemoglobin (HbF), SCD type, painful vaso-occlusive crisis (PVO), blood parameters, flow-mediated vasodilation (FMV), and hydroxyurea use were all extracted. Few studies investigated SNHL risk factors with noticeable knowledge gaps. Age, PVO, and certain blood parameters appear to predispose to SNHL, whereas decreased FMV, the presence of HbF, and the use of hydroxyurea appear to have an inverse relationship with the development of SNHL in SCD. CONCLUSION: There is a clear gap in the existing literature regarding the knowledge of demographic and contextual risk factors that is required for the prevention and management of SNHL in SCD.

OBJECTIF: La drépanocytose est une maladie héréditaire des globules rouges qui touche des personnes partout dans le monde, mais qui est plus fréquente chez les Noirs d'ascendance africaine que dans les autres races. Cette maladie est liée à la perte auditive neurosensorielle (SNHL). L'objectif de cette revue est d'évaluer les études qui rapportent une perte auditive neurosensorielle chez les patients atteints de DICS et d'identifier les facteurs de risque démographiques et contextuels de cette perte auditive chez les patients atteints de DICS. MÉTHODES: Nous avons effectué des recherches pour trouver des études pertinentes dans PubMed, Embase, Web of Science, et Google Scholar. Tous les articles ont été évalués indépendamment par deux auteurs. La liste de contrôle Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) a été utilisée. Le SNHL a été détecté à des niveaux d'audition supérieurs à 20 décibels. RÉSULTATS: En termes de méthodologie, les études examinées étaient diverses, 15 étant prospectives et quatre rétrospectives. Quatorze des 19 articles choisis parmi les 18 937 résultats du moteur de recherche étaient des études cas-témoins. Le sexe, l'âge, l'hémoglobine fœtale (HbF), le type de DICS, la crise vaso-occlusive douloureuse (PVO), les paramètres sanguins, la vasodilatation médiée par le flux (FMV) et l'utilisation de l'hydroxyurée ont tous été extraits. Peu d'études se sont penchées sur les facteurs de risque du SNHL, avec des lacunes notables dans les connaissances. L'âge, la PVO et certains paramètres sanguins semblent prédisposer au SNHL, tandis qu'une diminution de la FMV, la présence d'HbF et l'utilisation d'hydroxyurée semblent avoir une relation inverse avec le développement du SNHL chez les patients atteints de DICS. CONCLUSION: Il existe une lacune évidente dans la littérature existante en ce qui concerne la connaissance des facteurs de risque démographiques et contextuels qui sont nécessaires pour aider à la prévention et à la gestion du SNHL dans la DICS. Mots Clés: Perte auditive sensoriell; drépanocytose.

Promoter region variation in NFE2L2 influences susceptibility to ototoxicity in patients exposed to high cumulative doses of cisplatin.

Ototoxicity is a disabling reaction to cisplatin chemotherapy. Much of the inter-individual variability in the development of hearing impairment among cisplatin-receiving patients has not been fully accounted for. In particular, little is known about the pharmacogenomics of cisplatin-induced ototoxicity. This study sought to investigate the role of variation in five candidate genes in a cohort of South African cancer patients. Five variants within the candidate genes were genotyped in 214 patients, of which SLC22A2 rs316019 and NFE2L2 rs6721961 associated with reduced rates of ototoxicity. In the patients who were exposed to cumulative cisplatin doses ⩾200 mg m-2 (n=113), the variant rs6721961 associated with ototoxicity according to three different grading scales of hearing loss (ASHA, P=0.005; Chang, P=0.028; CTCAE, P=0.004). The NFE2L2 promotor variant rs6721961 may therefore be protective against hearing loss in cisplatin-receiving cancer patients.

Patients' costs associated with seeking and accessing treatment for drug-resistant tuberculosis in South Africa.

SETTING: South Africa is one of the world's 22 high tuberculosis (TB) burden countries, with the second highest number of notified rifampicin-resistant TB (R(R)-TB) and multidrug-resistant TB (MDR-TB) cases. OBJECTIVE: To estimate patient costs associated with the diagnosis and treatment of R(R)-TB/MDR-TB in South Africa. DESIGN: Patients diagnosed with R(R)-TB/MDR-TB and accessing care at government health care facilities were surveyed using a structured questionnaire. Direct and indirect costs associated with accessing R(R)-TB/MDR-TB care were estimated at different treatment durations for each patient. RESULTS: A total of 134 patients were surveyed: 84 in the intensive phase and 50 in the continuation phase of treatment, 82 in-patients and 52 out-patients. The mean monthly patient costs associated with the diagnosis and treatment of R(R)-TB/MDR-TB were higher during the intensive phase than the continuation phase (US$235 vs. US$188) and among in-patients than among out-patients (US$269 vs. US$122). Patients in the continuation phase and those accessing care as out-patients reported higher out-of-pocket costs than other patients. Most patients did not access social protection for costs associated with R(R)-TB/MDR-TB illness. CONCLUSION: Despite free health care, patients bear high costs when accessing diagnosis and treatment services for R(R)-TB/MDR-TB; appropriate social protection mechanisms should be provided to assist them in coping with these costs.

Impact of reduced hospitalisation on the cost of treatment for drug-resistant tuberculosis in South Africa.

SETTING: The cost of multidrug-resistant tuberculosis (MDR-TB) treatment is a major barrier to treatment scale-up in South Africa. OBJECTIVE: To estimate and compare the cost of treatment for rifampicin-resistant tuberculosis (RR-TB) in South Africa in different models of care in different settings. DESIGN: We estimated the costs of different models of care with varying levels of hospitalisation. These costs were used to calculate the total cost of treating all diagnosed cases of RR-TB in South Africa, and to estimate the budget impact of adopting a fully or partially decentralised model vs. a fully hospitalised model. RESULTS: The fully hospitalised model was 42% more costly than the fully decentralised model (US$13,432 vs. US$7753 per patient). A much shorter hospital stay in the decentralised models of care (44-57 days), compared to 128 days of hospitalisation in the fully hospitalised model, was the key contributor to the reduced cost of treatment. The annual total cost of treating all diagnosed cases ranged from US$110 million in the fully decentralised model to US$190 million in the fully hospitalised model. CONCLUSION: Following a more decentralised approach for treating RR-TB patients could potentially improve the affordability of RR-TB treatment in South Africa.

High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa.

BACKGROUND: Cisplatin is administered as the first-line treatment of soft-tissue cancers. It has a reported cure rate of up to 85%, but is associated with a high incidence of ototoxicity, characterised by irreversible bilateral hearing loss and affecting 23 - 50% of adults who receive the drug. OBJECTIVES: To determine the incidence of cisplatin-induced ototoxicity at Groote Schuur Hospital (GSH), Cape Town, South Africa. METHODS: retrospective cross-sectional study of cisplatin-receiving cancer patients attending GSH between January 2006 and August 2011. RESULTS: A total of 377 patients were recorded as receiving cisplatin therapy during the study period. A 300% increase in new cisplatin-receiving patients receiving audiological monitoring was observed between 2006 and 2010. However, only patients with all clinical data as well as baseline and follow-up audiometric analyses were investigated. One hundred and seven such patients were identified, 55.1% of whom developed cisplatin-induced ototoxicity while receiving high-dose (> or = 60 mg/m2) cisplatin treatment. Higher cumulative cisplatin dosages were associated with development of significant hearing loss (p = 0.027). The odds of developing cisplatin-induced hearing loss were elevated for patients with head and neck tumours and lymphoma (p = 0.0465 and p = 0.0563, respectively) and were significantly lower for those with reproductive cancers (p = 0.0371). CONCLUSION: Comprehensive audiological monitoring should be available for every patient during cisplatin treatment to minimise the development of disabling hearing loss.

Potential roles of stem cells in the management of sensorineural hearing loss.

BACKGROUND: In the management of sensorineural hearing loss, effective therapy for degenerated hair cells, third order neurons, ganglions, dendrites and synaptic areas of the vestibulo-cochleo-cerebral pathway remains an enigma. Transplantation of stem and progenitor cells appears to be an emerging potential solution, and is the focus of this review. AIM: To review recent developments in the management of sensorineural hearing loss in the field of stem cell research. MATERIALS AND METHOD: A systematic review of the English language literature included all experimental and non-experimental studies with a Jadad score of three or more, published between 2000 and 2010 and included in the following databases: Cochrane Library Ear, Nose and Throat Disorders; Medline; Google Scholar; Hinari; and the Online Library of Toronto University. RESULTS: Of the 455 and 29 600 articles identified from Medline and Google Scholar, respectively, 48 met the inclusion criteria. These were independently reviewed and jointly analysed. CONCLUSION: Although there is not yet any evidence from successful human studies, stem cell and 'alternative stem cell' technology seems to represent the future of sensorineural hearing loss management.