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Journal of Audiology & Otology Apr 2024Chloroquine and its analog hydroxychloroquine are derivatives of 4-aminoquinoline and are regularly used in the treatment of malaria and autoimmune diseases. Among the...
BACKGROUND AND OBJECTIVES
Chloroquine and its analog hydroxychloroquine are derivatives of 4-aminoquinoline and are regularly used in the treatment of malaria and autoimmune diseases. Among the side effects of these drugs, alterations associated with the auditory system are frequently mentioned. Thus, the aim of this systematic review is to systematically review publications on hearing disorders and chloroquine or hydroxychloroquine use.
MATERIALS AND METHODS
Inclusion criteria were observational or interventional studies on audiological assessment in participants who were using chloroquine or hydroxychloroquine. The methodological quality was independently assessed by two reviewers using the Meta-Analysis of Statistics: assessment and review Instrument. The certainty of the evidence was assessed using the GRADE tool.
RESULTS
A total of 1,372 non-duplicate papers were screened, out of which 17 were included in the final qualitative synthesis, and 5 studies in the meta-analysis. The odds ratio for the two subgroups evaluated did not show significance with no heterogeneity between the effects observed between the different diseases (I2=0%) and obtaining the global estimate of 0.76 (95% confidence interval [CI]=0.41-1.39; p>0.05). Despite the inclusion of papers with different disease samples, the heterogeneity observed in the analysis was low (I2= 0%) and prediction interval (95% PI=0.32-1.80; p>0.05) remained close to that estimated by the CI (95% CI=0.41-1.39; p>0.05). The certainty of the evidence assessed by the GRADE tool was considered very low due to the risk of bias, indirect evidence, and imprecision.
CONCLUSIONS
The findings of this study suggest that the use of chloroquine/hydroxychloroquine is not associated with hearing disorders.
PubMed: 38382520
DOI: 10.7874/jao.2023.00157 -
Frontiers in Psychology 2023Congenital toxoplasmosis (CT) occurs mainly by primary maternal infection during pregnancy. It is estimated that the incidence of vertical transmission to the fetus is...
BACKGROUND
Congenital toxoplasmosis (CT) occurs mainly by primary maternal infection during pregnancy. It is estimated that the incidence of vertical transmission to the fetus is 20% and that infected women are more likely to have a premature birth or low birth weight neonate since there is an association between CT and the rate of premature birth and low birth weight. In addition to severe neurological and ophthalmic consequences, hearing disorders such as hearing loss are also among the clinical manifestations seen in children with CT. Given the above, the objective of this study is to verify what are the auditory disorders seen in children with CT.
METHODS
This literature review was structured according to the PRISMA statement and based on the terms of Study Target Population, Intervention, Comparison, Outcomes, and Study Types (PICOS). To obtain the studies, the following electronic databases were consulted: PubMed, Web of Science, Scopus, and Lilacs. The combined terms used for the search were: ("auditory evoked potentials" OR "hearing" OR "hearing loss") AND ("congenital toxoplasmosis"). The selection of articles was carried out independently, blindly, by two of the authors, to minimize risk of bias.
RESULTS
The search in the databases identified 172 articles, after excluding duplicate articles, 105 studies were identified. From the selection made by reading the titles and abstracts, 11 studies were selected for full-text reading. A total of 94 studies were excluded. An article was selected from the list of references. Therefore, 12 studies were included in the final analysis. It was observed that a significant percentage of studies sought to study the peripheral auditory pathway, verifying the occurrence or association between hearing loss and the presence of congenital infection. Only two studies evaluated the central auditory pathway, using the Brainstem Auditory Evoked Potential (BAEP) and the Frequency Following Response (FFR).
CONCLUSION
Toxoplasmosis affects not only the peripheral areas but central areas as well. Most studies suggest this pathology as a risk factor for both peripheral and central impairment. Research has found a greater association between CT and mild to moderate hearing loss, in addition to alterations in exams such as BAEP and FFR. These data recommend that CT be reported as a global public health problem and can help assess complications and impacts of hearing disorders as a result of CT. There is a gap about studies that retract the co-occurrence between CT and other Risk Indicators for Hearing Loss (RIHL), such as prematurity, permanence in the intensive care unit, and use of ototoxic medications, lack of longitudinal studies, that accompany the development of hearing and language of children with CT, since the consequences of this infection may be late.
PubMed: 38298366
DOI: 10.3389/fpsyg.2023.1286211 -
Preventive Medicine Mar 2024This systematic review explores the multifaceted nature of risk factors contributing to adult-onset HL. The objective was to synthesise the most recent epidemiological... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review explores the multifaceted nature of risk factors contributing to adult-onset HL. The objective was to synthesise the most recent epidemiological evidence to generate pooled proportional incidences for the identified risk factors.
METHODS
We conducted an extensive search of electronic databases (MEDLINE, EMBASE, and psychINFO) for studies providing epidemiological evidence of risk factors associated with hearing loss. Topic modelling using Latent Dirichlet Allocation (LDA) was first conducted to determine how many risk factor themes were available from the papers. Data were analysed by calculating the pooled proportional incidence using a meta-analysis of proportions.
RESULTS
From the 72 studies reviewed, six key risk factor themes emerged through LDA topic modelling. The review identified ototoxicity, primarily caused by cancer treatments and antibiotics, infectious diseases like COVID-19, occupational noise exposure, lifestyle factors, health conditions, biological responses, and age progression as significant risk factors for HL. The highest proportional incidence was found with cancer-related ototoxicity at 55.4% (95%CI: 39.0-70.7), followed closely by ototoxicity from infectious diseases at 50.0% (95%CI: 28.5-71.5). This high proportional incidence suggests the need to explore less destructive therapies and proactively monitor hearing function during treatments.
CONCLUSIONS
The findings of this review, combined with the synthesis of epidemiological evidence, enhance our understanding of hearing loss (HL) pathogenesis and highlight potential areas for intervention, thereby paving the way for more effective prevention and management of adult-onset hearing loss in our ageing global population.
Topics: Adult; Humans; Ototoxicity; Hearing Loss; Risk Factors; Anti-Bacterial Agents; Communicable Diseases
PubMed: 38296002
DOI: 10.1016/j.ypmed.2024.107882 -
The Lancet. Global Health Feb 2024Hearing loss affects approximately 1·6 billion individuals worldwide. Many cases are preventable. We aimed to estimate the annual number of new hearing loss cases that...
BACKGROUND
Hearing loss affects approximately 1·6 billion individuals worldwide. Many cases are preventable. We aimed to estimate the annual number of new hearing loss cases that could be attributed to meningitis, otitis media, congenital rubella syndrome, cytomegalovirus, and ototoxic medications, specifically aminoglycosides, platinum-based chemotherapeutics, and antimalarials.
METHODS
We used a targeted and a rapid systematic literature review to calculate yearly global incidences of each cause of hearing loss. We estimated the prevalence of hearing loss for each presumed cause. For each cause, we calculated the global number of yearly hearing loss cases associated with the exposure by multiplying the estimated exposed population by the prevalence of hearing loss associated with the exposure, accounting for mortality when warranted.
FINDINGS
An estimated 257·3 million people per year are exposed to these preventable causes of hearing loss, leading to an estimated 33·8 million new cases of hearing loss worldwide per year. Most hearing loss cases were among those with exposure to ototoxic medications (19·6 million [range 12·6 million-27·9 million] from short-course aminoglycoside therapy and 12·3 million from antimalarials). We estimated that 818 000 cases of hearing loss were caused by otitis media, 346 000 by meningitis, 114 000 by cytomegalovirus, and 59 000 by congenital rubella syndrome.
INTERPRETATION
The global burden of preventable hearing loss is large. Hearing loss that is attributable to disease sequelae or ototoxic medications contributes substantially to the global burden of hearing loss. Prevention of these conditions should be a global health priority.
FUNDING
The US National Institute on Deafness and Other Communication Disorders and the US National Institute on Aging.
Topics: Humans; Rubella Syndrome, Congenital; Antimalarials; Hearing Loss; Meningitis; Otitis Media
PubMed: 38245112
DOI: 10.1016/S2214-109X(23)00514-4 -
Increased risk of hearing loss associated with macrolide use: a systematic review and meta-analysis.Scientific Reports Jan 2024The increased risk of hearing loss with macrolides remains controversial. We aimed to systematically review and meta-analyze data on the clinical risk of hearing loss,... (Meta-Analysis)
Meta-Analysis
The increased risk of hearing loss with macrolides remains controversial. We aimed to systematically review and meta-analyze data on the clinical risk of hearing loss, tinnitus, and ototoxicity following macrolide use. A systematic search was conducted across PubMed, MEDLINE, Cochrane, and Embase databases from database inception to May 2023. Medical Subject Heading (MeSH) terms and text keywords were utilized, without any language restrictions. In addition to the electronic databases, two authors manually and independently searched for relevant studies in the US and European clinical trial registries and Google Scholar. Studies that involved (1) patients who had hearing loss, tinnitus, or ototoxicity after macrolide use, (2) intervention of use of macrolides such as azithromycin, clarithromycin, erythromycin, fidaxomicin, roxithromycin, spiramycin, and/or telithromycin, (3) comparisons with specified placebos or other antibiotics, (4) outcomes measured as odds ratio (OR), relative risk (RR), hazard ratio (HR), and mean difference for ototoxicity symptoms using randomized control trial (RCT)s and observational studies (case-control, cross-section, and cohort studies) were included. Data extraction was performed independently by two extractors, and a crosscheck was performed to identify any errors. ORs along with their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines for RCTs and Meta-Analysis of Observational Studies in Epidemiology guidelines for observational studies were followed. We assessed the hearing loss risk after macrolide use versus controls (placebos and other antibiotics). Based on data from 13 studies including 1,142,021 patients (n = 267,546 for macrolide and n = 875,089 for controls), the overall pooled OR was 1.25 (95% CI 1.07-1.47). In subgroup analysis by study design, the ORs were 1.37 (95% CI 1.08-1.73) for RCTs and 1.33 (95% CI 1.24-1.43) for case-control studies, indicating that RCT and case-control study designs showed a statistically significant higher risk of hearing loss. The group with underlying diseases such as multiple infectious etiologies (OR, 1.16 [95% CI 0.96-1.41]) had a statistically significant lower risk than the group without (OR, 1.53 [95% CI 1.38-1.70] P = .013). The findings from this systematic review and meta-analysis suggest that macrolide antibiotics increase the risk of hearing loss and that healthcare professionals should carefully consider this factor while prescribing macrolides.
Topics: Humans; Macrolides; Tinnitus; Ototoxicity; Anti-Bacterial Agents; Hearing Loss; Deafness
PubMed: 38167873
DOI: 10.1038/s41598-023-50774-1 -
International Journal of Molecular... Oct 2023With more than 466 million people affected, hearing loss represents the most common sensory pathology worldwide. Despite its widespread occurrence, much remains to be... (Review)
Review
With more than 466 million people affected, hearing loss represents the most common sensory pathology worldwide. Despite its widespread occurrence, much remains to be explored, particularly concerning the intricate pathogenic mechanisms underlying its diverse phenotypes. In this context, metabolomics emerges as a promising approach. Indeed, lying downstream from molecular biology's central dogma, the metabolome reflects both genetic traits and environmental influences. Furthermore, its dynamic nature facilitates well-defined changes during disease states, making metabolomic analysis a unique lens into the mechanisms underpinning various hearing impairment forms. Hence, these investigations may pave the way for improved diagnostic strategies, personalized interventions and targeted treatments, ultimately enhancing the clinical management of affected individuals. In this comprehensive review, we discuss findings from 20 original articles, including human and animal studies. Existing literature highlights specific metabolic changes associated with hearing loss and ototoxicity of certain compounds. Nevertheless, numerous critical issues have emerged from the study of the current state of the art, with the lack of standardization of methods, significant heterogeneity in the studies and often small sample sizes being the main limiting factors for the reliability of these findings. Therefore, these results should serve as a stepping stone for future research aimed at addressing the aforementioned challenges.
Topics: Animals; Humans; Reproducibility of Results; Hearing Loss; Deafness; Metabolomics; Metabolome
PubMed: 37894867
DOI: 10.3390/ijms242015188 -
Brazilian Journal of Otorhinolaryngology 2023To determinate the otoprotective efficacy of melatonin.in experimental models of rodents through a systematic review of the literature. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determinate the otoprotective efficacy of melatonin.in experimental models of rodents through a systematic review of the literature.
METHODS
Altogether, 154 articles were found in four databases. The PICOS strategy (Population, Intervention, Comparison, and Outcome) was used to define the eligibility criteria. Studies that met the inclusion criteria for the second step were included in a qualitative synthesis. Each study type was analyzed with the CAMARADES quality of assessment's checklist and the SYRCLE RoBS risk of bias.
RESULTS
Seven articles were selected, and four were included in the meta-analysis. It was possible to obtain seven outcomes according to the standard auditory frequencies presented among the studies, considering a minimum of three standard frequencies. The outcomes analyzed were for the frequencies of 1500, 2000, 3000, 4000, 5000, 6000, and 8000 Hz.
CONCLUSION
Melatonin can provide protection against the ototoxic effects of cisplatin and aminoglycosides at 5000 Hz, 6000 Hz, and 8000 Hz, thereby minimizing the reduction in Otoacustic Emissions (OAE) amplitude. The same effect was not observed in the lower frequencies. Despite the limited number of studies that were evaluated, the results appeared consistent in higher frequencies. However, the methodology of the available studies did not meet the necessary methodological rigor that promotes the safe replicability of these studies.
Topics: Animals; Melatonin; Rodentia; Cisplatin
PubMed: 37451174
DOI: 10.1016/j.bjorl.2023.101288 -
Radiation Oncology (London, England) Jun 2023The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have...
BACKGROUND
The risk of ototoxicity, characterized by hearing impairment, tinnitus, or middle ear inflammation, is elevated in both child and adult cancer survivors who have undergone head-neck or brain radiation, or a combination of the two. To provide optimal care for these cancer survivors and minimize subsequent complications, it is crucial to comprehend the relationship between radiotherapy and ototoxicity.
METHODS
A comprehensive search of databases, including the Cochrane Library, PubMed, Embase, and Web of Science, was conducted from the inception of the knowledge base up until January 2023. The metafor-package was employed to compare ototoxicity rates in individuals receiving radiotherapy. Two independent assessors extracted data and analyzed targets using a random-effects model.
RESULTS
Out of the 28 randomized controlled trials (RCTs) included in the analysis, 25 were prospective RCTs. Subgroup analysis revealed that mean cochlear radiation dose, primary tumor location, radiotherapy modality, and patient age significantly influenced total hearing impairment. Intensity-modulated radiotherapy was associated with less ototoxicity than 2D conventional radiotherapy (OR, 0.53; 95% CI, 0.47-0.60; P = 0.73; I = 0%). Stereotactic radiotherapy appeared to be a superior option for hearing preservation compared to radiosurgery (OR, 1.44; 95% CI, 1.00-2.07; P = 0.69; I = 0%). Children demonstrated a higher risk of hearing impairment than adults. More than 50% of patients with vestibular neuroadenoma experienced hearing impairment following radiation therapy. A strong association was observed between the average cochlear radiation dose and hearing impairment. Increased cochlear radiation doses may result in a heightened risk of hearing impairment.
CONCLUSION
Several risk factors for radiation-induced hearing impairment were identified in this study. High cochlear radiation doses were found to exacerbate the risk of hearing impairment resulting from radiation therapy.
Topics: Adult; Child; Humans; Hearing; Hearing Loss; Ototoxicity; Radiosurgery; Radiotherapy; Radiotherapy, Intensity-Modulated
PubMed: 37270526
DOI: 10.1186/s13014-023-02268-7 -
Advances in Radiation Oncology 2023The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB)... (Review)
Review
PURPOSE
The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into superior clinical outcomes (including survival and toxicities) compared with traditional photon-based techniques.
METHODS AND MATERIALS
We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles reporting on clinical outcomes of pediatric and/or adult patients with MB treated with proton radiotherapy were included. Evidence quality was assessed using a modified Newcastle Ottawa scale and GRADE score.
RESULTS
Thirty-five studies were included, with a total of 2059 patients reported (representing an estimated 630-654 unique patients). None of the studies were randomized, 12 were comparative, 9 were prospective, 3 were mixed, and 22 were retrospective. Average mean/median follow-up was 5.0 years (range, 4 weeks to 12.6 years). The majority of studies (n = 19) reported on treatment with passive scatter proton beams exclusively. Average study quality was 6.0 out of 9 (median, 6; standard deviation, 1.6). Nine studies scored ≥8 out of 9 on the modified Newcastle Ottawa Scale; an overall "moderate" GRADE score was assigned. Well-designed comparative cohort studies with adequate follow-up demonstrate superior neurocognitive outcomes, lower incidence of hypothyroidism (23% vs 69%), sex hormone deficiency (3% vs 19%), greater heights, and reduced acute toxicities in patients treated with protons compared to photons. Overall survival (up to 10 years), progression-free survival (up to 10 years), brain stem injury, and other endocrine outcomes were similar to those reported for photon radiation. There was insufficient evidence to make conclusions on endpoints of quality of life, ototoxicity, secondary malignancy, alopecia, scoliosis, cavernomas, and cerebral vasculopathy.
CONCLUSIONS
Moderate-grade evidence supports proton radiotherapy as a preferred treatment for craniospinal irradiation of MB based on equivalent disease control and comparable-to-improved toxicity versus photon beam radiation therapy.
PubMed: 37008255
DOI: 10.1016/j.adro.2023.101189 -
BMC Cancer Dec 2022Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often...
BACKGROUND
Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often experience long-term toxicities. The main objective of this systematic review is to provide an overview of the discovery of novel associations of germline polymorphisms with treatment response and/or chemotherapy-induced toxicities in osteosarcoma. METHODS: MEDLINE and Embase were systematically searched (2010-July 2022). Genetic association studies were included if they assessed > 10 germline genetic variants in > 5 genes in relevant drug pathways or if they used a genotyping array or other large-scale genetic analysis. Quality was assessed using adjusted STrengthening the REporting of Genetic Association studies (STREGA)-guidelines. To find additional evidence for the identified associations, literature was searched to identify replication studies.
RESULTS
After screening 1999 articles, twenty articles met our inclusion criteria. These range from studies focusing on genes in relevant pharmacokinetic pathways to whole genome sequencing. Eleven articles reported on doxorubicin-induced cardiomyopathy. For seven genetic variants in CELF4, GPR35, HAS3, RARG, SLC22A17, SLC22A7 and SLC28A3, replication studies were performed, however without consistent results. Ototoxicity was investigated in one study. Five small studies reported on mucosistis or bone marrow, nephro- and/or hepatotoxicity. Six studies included analysis for treatment efficacy. Genetic variants in ABCC3, ABCC5, FasL, GLDC, GSTP1 were replicated in studies using heterogeneous efficacy outcomes.
CONCLUSIONS
Despite that results are promising, the majority of associations were poorly reproducible due to small patient cohorts. For the future, hypothesis-generating studies in large patient cohorts will be necessary, especially for cisplatin-induced ototoxicity as these are largely lacking. In order to form large patient cohorts, national and international collaboration will be essential.
Topics: Child; Adolescent; Humans; Pharmacogenetics; Ototoxicity; Osteosarcoma; Cisplatin; Bone Neoplasms
PubMed: 36536332
DOI: 10.1186/s12885-022-10434-5