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Research in Social & Administrative... Aug 2022Aminoglycosides are widely used, broad-spectrum antibiotics with significant potential for ototoxicity. Global efforts to prevent ototoxicity must account for... (Review)
Review
BACKGROUND
Aminoglycosides are widely used, broad-spectrum antibiotics with significant potential for ototoxicity. Global efforts to prevent ototoxicity must account for aminoglycoside overuse and non-prescription use.
OBJECTIVES
The goals of this study were to a) estimate the prevalence of aminoglycoside overuse by synthesizing evidence on self-medication, over the counter (OTC) availability, and household antibiotic storage for later use, and to report the specific aminoglycosides used and the predictors of overuse, and b) leverage this information to comment on potential risk of ototoxicity.
METHODS
Two systematic search strings were conducted to extract peer-reviewed articles published from 2005 to 2020. The first focused on overuse of aminoglycoside antibiotics. The second focused on potentially ototoxic effects of aminoglycosides related to drug overuse.
RESULTS
A total of 26 articles were included (first search string: n = 21; second search string: n = 5). The prevalence of aminoglycoside self-medication was high and household storage and OTC availability of aminoglycosides was common. Gentamicin was the most commonly overused aminoglycoside. No studies provided information on antibiotic dosing or resultant toxicities, including ototoxicity.
CONCLUSIONS
The limited available evidence indicates that antibiotic overuse (self-medication, home storage, and non-prescription availability) is relatively common, especially in low resource settings, and that aminoglycoside antibiotics comprise a variable, but concerning, proportion of non-prescribed antibiotics. Additional evidence is needed to evaluate the relationship between these dispensing patterns and ototoxicity.
Topics: Aminoglycosides; Anti-Bacterial Agents; Humans; Ototoxicity; Prescription Drug Overuse
PubMed: 34711521
DOI: 10.1016/j.sapharm.2021.10.004 -
The International Tinnitus Journal Mar 2021Prevalence of tinnitus range from 7.1% to 14.6% (National Center for Health Statistics, 2016), but the mechanisms responsible for the development of this abnormal...
INTRODUCTION
Prevalence of tinnitus range from 7.1% to 14.6% (National Center for Health Statistics, 2016), but the mechanisms responsible for the development of this abnormal sensory state remain poorly understood.
OBJECTIVES
To determine the evidence for different etiologies and pathophysiology of tinnitus identified by clinical diagnostic tests in the adult population.
STUDY DESIGN
Systematic literature review.
METHODS
Review of data base using PRISMA guidelines: Google Scholar, Medline, Springer Link, Pubmed. In addition, manual reference search of identified papers. Randomized controlled trials, case control study, prospective cohort studies, and retrospective reviews of consecutive patients in which clear data were reported with respect to etiology and pathophysiology of tinnitus.
RESULTS
Sixty seven articles met the inclusion criteria. The papers searched recent studies from 2004 to 2018 for different etiologies such as noise exposure, age, ototoxic drugs, hearing loss among patients with tinnitus. Multiple pathophysiology were identified, including inner ear pathology, auditory nerve synchronisation, central nervous system anomalies and limbic and autonomous nervous system problems. The group of papers evaluated tinnitus patients with specific diagnostic tests such as pure tone audiometry, Immitance audiometry, otoacoustic emission, Auditory brainstem response and diagnostic imaging of fMRI, MRI and PET study.
CONCLUSIONS
The results indicate a high level of heterogeneity between the studies for all the assessed areas. These results support the need for greater stratification of the tinnitus population and the importance of a standardized Puretone audiometry with extended high frequency, OAE, ABR and diagnostic imaging (fMRI, MRI & PET) method to make comparisons between studies possible. Diagnostic imaging is an important useful method for identification of intracranial pathology that can present with tinnitus as a primary symptom. Establishment of a direct causal link between tinnitus and these etiologies and pathophysiology remains elusive.
Topics: Adult; Audiometry, Pure-Tone; Case-Control Studies; Humans; Prospective Studies; Retrospective Studies; Tinnitus
PubMed: 34410084
DOI: 10.5935/0946-5448.20210015 -
JAMA Network Open Aug 2021Platinum-induced ototoxic effects are a significant issue because platinum-based chemotherapy is one of the most commonly used therapeutic medications. Sodium... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Platinum-induced ototoxic effects are a significant issue because platinum-based chemotherapy is one of the most commonly used therapeutic medications. Sodium thiosulfate (STS) is considered a potential otoprotectant for the prevention of platinum-induced ototoxic effects that functions by binding the platinum-based agent, but its administration raises concerns regarding the substantial attenuation of the antineoplastic outcome associated with platinum.
OBJECTIVE
To evaluate the association between concurrent STS and reduced risk of ototoxic effects among patients undergoing platinum-based chemotherapy and to evaluate outcomes, including event-free survival, overall survival, and adverse outcomes.
DATA SOURCES
From inception through November 7, 2020, databases, including the Cochrane Library, PubMed, Embase, Web of Science, and Scopus, were searched.
STUDY SELECTION
Studies enrolling patients with cancer who were undergoing platinum-based chemotherapy that compared ototoxic effects development between patients who received STS and patients who did not and provided adequate information for meta-analysis were regarded as eligible. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
DATA EXTRACTION AND SYNTHESIS
The data were extracted by 2 reviewers independently. A random-effects model was used to explore objectives.
MAIN OUTCOMES AND MEASURES
Relative risks (RRs) for ototoxic effects development and hemopoietic event development comparing the experimental group and the control group were estimated. Secondary outcomes were hazard ratios (HRs) for event-free survival and overall survival. Sensitivity analysis and trial sequential analysis were conducted to further consolidate pooled results.
RESULTS
Among 4 eligible studies that were included, there were 3 randomized clinical trials and 1 controlled study. A total of 278 patients were allocated to the experimental group (ie, platinum-based chemotherapy plus STS; 158 patients, including 13 patients using contralatral ears of the control group as samples) or the control group (ie, chemotherapy; 133 patients, including 13 patients using contralateral ears of the experimental group as samples). Overall, patients who received STS had a statistically significantly decreased risk of ototoxic effects during the course of platinum-based chemotherapy (RR, 0.61; 95% CI, 0.49-0.77; P < .001; I2 = 5.0%) without a statistically significant increase in the risk of poor event-free survival (HR, 1.13; 95% CI, 0.70-1.82; P = .61; I2 = 0%) or overall survival (HR, 1.90; 95% CI, 0.90-4.03; P = .09; I2 = 0%). In the trial sequential analysis of event-free survival (z = -0.52) and overall survival (z = -1.68), although the cumulative z curves did not surpass the traditional significance boundary (-1.96 to 1.96 for both) or sequential monitoring boundary (event-free survival: -8.0 to 8.0; overall survival boundary not renderable in the analysis because the information size was too small) of the adjusted CI, they did not reach the required information size.
CONCLUSIONS AND RELEVANCE
This meta-analysis found that concurrent STS delivery was associated with a decreased risk of platinum-induced ototoxic effects among patients treated with platinum-induced chemotherapy. These findings suggest that concurrent STS for protection against ototoxic effects should be considered for patients indicated for platinum-based chemotherapy.
Topics: Adolescent; Adult; Antineoplastic Agents; Child; Clinical Trials as Topic; Female; Humans; Male; Ototoxicity; Platinum Compounds; Protective Agents; Thiosulfates; Young Adult
PubMed: 34338793
DOI: 10.1001/jamanetworkopen.2021.18895 -
Stem Cells International 2021A systematic review was conducted to compare the effectiveness and safety of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) for regeneration of the... (Review)
Review
OBJECTIVE
A systematic review was conducted to compare the effectiveness and safety of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF) for regeneration of the tympanic membrane (TM).
METHODS
The PubMed database was searched for relevant studies. Experimental and clinical studies reporting acute and chronic TM perforations in relation to two healing outcomes (success rate and closure time) and complications were selected.
RESULTS
A total of 47 studies were included. Five experimental studies showed closure rates of 55%-100% with FGF2 compared with 10%-62.5% in controls for acute perforations. Five experimental studies showed closure rates of 30.3%-100% with EGF and 3.6%-41% in controls for chronic perforations. Two experimental studies showed closure rates of 31.6% or 85.7% with FGF2 and 15.8% or 100% with EGF. Nine clinical studies of acute large perforations showed closure rates of 91.4%-100% with FGF2 or EGF. Two clinical studies showed similar closure rates between groups treated with FGF2 and EGF. Seven clinical studies showed closure rates of 88.9%-100% within 3 months and 58%-66% within 12 months using FGF2 in repair of chronic perforations, but only one study showed a significantly higher closure rate in the saline group compared with the FGF2 group (71.4% vs. 57.5%, respectively, = 0.547). In addition, three experimental studies showed no ototoxicity associated with FGF2 or EGF. No middle ear cholesteatoma or epithelial pearls were reported, except in one experimental study and one clinical study, respectively.
CONCLUSIONS
FGF2 and EGF showed good effects and reliable safety for the regeneration of TM. In addition, EGF was better for the regeneration of acute perforations, while FGF2 combined with biological scaffolds was superior to EGF for chronic perforations, but was associated with high rates of reperforation over time. Further studies are required to determine whether EGF or FGF2 is better for TM regeneration.
PubMed: 34306094
DOI: 10.1155/2021/2366291 -
International Journal of Particle... 2021To evaluate the clinical outcomes and treatment related toxicities of charged particle-based re-irradiation (reRT; protons and carbon ions) for the definitive management...
PURPOSE
To evaluate the clinical outcomes and treatment related toxicities of charged particle-based re-irradiation (reRT; protons and carbon ions) for the definitive management of recurrent or second primary skull base and head and neck tumors.
MATERIALS AND METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied for the conduct of this systematic review. Published work in English language evaluating the role of definitive charged particle therapies in the clinical setting of reRT for recurrent or second primary skull base and head and neck tumors were eligible for this analysis.
RESULTS
A total of 26 original studies (15 protons, 10 carbon ions, and 1 helium/neon studies) involving a total of 1,118 patients (437 with protons, 670 with carbon ions, and 11 with helium/neon) treated with curative-intent charged particle reRT were included in this systematic review. All studies were retrospective in nature, and the majority of them (n=23, 88 %) were reported as single institution experiences (87% for protons, and 90% for carbon ion-based studies). The median proton therapy reRT dose was 64.5 Gy (RBE 1.1) (range, 50.0 - 75.6 Gy ), while the median carbon ion reRT dose was 53.8 Gy (RBE 2.5 - 3.0) (range, 44.8 - 60 Gy ). Induction and/or concurrent chemotherapy was administered to 232 (53%) of the patients that received a course of proton reRT, and 122 (18%) for carbon ion reRT patients. ReRT with protons achieved 2-year local control rates ranging from 50% to 86%, and 41% to 92% for carbon ion reRT. The 2-year overall survival rates for proton and carbon ion reRT ranged from 33% to 80%, and 50% to 86% respectively. Late ≥ G3 toxicities ranged from 0% to 37%, with brain necrosis, ototoxicity, visual deficits, and bleeding as the most common complications. Grade 5 toxicities for all treated patients occurred in 1.4% (n= 16/1118) with fatal bleeding as the leading cause.
CONCLUSIONS
Based on current data, curative intent skull base and head and neck reRT with charged particle radiotherapy is feasible and safe in well-selected cases, associated with comparable or potentially improved local control and toxicity rates compared to historical reRT studies using photon radiotherapy. Prospective multi-institutional studies reporting oncologic outcomes, toxicity, and dosimetric treatment planning data are warranted to further validate these findings and to improve the understanding of the clinical benefits of charged particle radiotherapy in the reRT setting.
PubMed: 34285942
DOI: 10.14338/IJPT-20-00064.1 -
Revista Da Associacao Medica Brasileira... 2021To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine...
OBJECTIVE
To present scientific evidence based on a systematic review of the literature (PRISMA), aiming to systematize evidence of the ototoxic effects of hydroxychloroquine (HCQ).
METHODS
The studies were selected using a combination based on the Medical Subject Headings (MeSH). The databases searched were MEDLINE (PubMed), LILACS, SciELO, and BIREME, encompassing articles from January 2010 to May 2020, with no restrictions of language and place of publication.
RESULTS
A total of 148 articles with the potential to be included were retrieved. Of these, two answered the research question, which consisted of seeking evidence of the ototoxic effects of hydroxychloroquine. These studies scored 11 in their quality assessment with the modified protocol by Pithon et al.13.
CONCLUSIONS
The studies reported possible ototoxicity of HCQ. Audiovestibular changes, such as hearing loss, peripheral vestibular syndrome, and tinnitus were evidenced in patients submitted to HCQ. The improvement in the audiological examinations and the regression in the vestibular syndrome after stopping the treatment with HCQ are strong arguments in favor of the ototoxicity caused by this medication. However, there are still divergences about the relationship between ototoxic effects and the use of HCQ.
Topics: Hearing Loss; Humans; Hydroxychloroquine; Ototoxicity
PubMed: 34259762
DOI: 10.1590/1806-9282.67.Suppl1.20200677 -
The Journal of Laryngology and Otology Aug 2021Sodium 2-mercaptoethanesulfonate (Mesna) has been proposed as a chemical aid in any surgical procedure, including cholesteatoma surgery. This review investigated the...
OBJECTIVE
Sodium 2-mercaptoethanesulfonate (Mesna) has been proposed as a chemical aid in any surgical procedure, including cholesteatoma surgery. This review investigated the benefits and safety of Mesna during surgical management of cholesteatoma and adhesive otitis media.
METHOD
A systematic literature review was performed to identify clinical studies evaluating topical Mesna application during ear surgery (cholesteatoma or atelectasis). A qualitative analysis based on data extracted was conducted.
RESULTS
From 27 articles, 5 retrospective studies were selected for a full analysis for a total of 607 patients (aged 5 to 72 years). Three studies evaluated cholesteatoma recidivism after Mesna application during cholesteatoma surgery, one study evaluated the surgical success rate of Mesna application for the treatment of atelectatic ears and adhesive otitis media, and one study evaluated potential ototoxicity of Mesna during cholesteatoma surgery. All the studies showed overall improvement in recurrence and residual cholesteatoma disease after Mesna application during surgery. Sensorineural hearing loss was not encountered after Mesna application.
CONCLUSION
Mesna application in cholesteatoma surgery could represent a valid and safe support tool during surgical treatment carried out both with microscopy and endoscopy. More studies are required to confirm these promising results.
Topics: Cholesteatoma, Middle Ear; Ear, Middle; Humans; Mesna; Otitis Media; Protective Agents
PubMed: 34219630
DOI: 10.1017/S0022215121001535 -
International Journal of... 2021To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs...
To describe the audio-vestibular disorders related to the newly SARS-CoV-2 infection, including the possible ototoxicity side-effects related to the use of drugs included in the SARS-CoV-2 treatment protocols. A systematic review was performed according to the PRISMA protocol. The Medline and Embase databases were searched from March 1, 2020 to April 9, 2021. Initially the search yielded 400 manuscripts, which were reduced to 15, upon the application of inclusion criteria. Sensorineural hearing loss (SNHL) is the most frequent audio-vestibular symptom described, occurring alone or in association with tinnitus and vertigo. The etiopathogenesis of the inner ear disorders related to COVID-19 infection is still poorly understood. The number of reports of COVID-19 infections associated to audio-vestibular disorders is increasing; even if the quality of the studies available is often insufficient, audio-vestibular disorders should be considered as possible manifestations to be included among the symptoms of this infection.
Topics: COVID-19; Hearing Loss, Sensorineural; Humans; Ototoxicity; SARS-CoV-2; Vestibular Diseases
PubMed: 34142589
DOI: 10.1177/20587384211027373 -
Travel Medicine and Infectious Disease 2021Drugs used in curative and prophylactic antimalarial treatment may be ototoxic and lead to permanent hearing loss, but there is no consensus regarding prevalence and... (Review)
Review
BACKGROUND
Drugs used in curative and prophylactic antimalarial treatment may be ototoxic and lead to permanent hearing loss, but there is no consensus regarding prevalence and permanence of ototoxic hearing loss caused by antimalarials. The purpose of this systematic narrative review was to synthesize current evidence on antimalarial ototoxicity in human populations.
METHOD
Studies published between 2005 and 2018 that reported prevalence of post-treatment hearing loss in individuals treated for malaria were included.
RESULTS
Twenty-two studies including data from 21 countries were included. Primary themes of the included studies were to evaluate drug safety and/or efficacy (n = 13) or ototoxic effects of drugs (n = 9). Hearing data were measured objectively in 9 studies. Five studies focused on quinine (or derivates), 10 focused on artemisinin combination therapies, and 7 considered multiple drug combinations. There is a paucity of evidence that thoroughly reports potentially permanent ototoxic effects of antimalarials.
CONCLUSIONS
Antimalarial drugs may be ototoxic in some cases. More research in human populations is needed to describe ototoxicity of current antimalarials and of future drugs that will be used/developed in response to antimalarial resistance. It is recommended that randomized trials evaluating drug safety objectively measure and report ototoxic hearing loss as an adverse event.
Topics: Antimalarials; Hearing Loss; Humans; Malaria; Quinine
PubMed: 34129960
DOI: 10.1016/j.tmaid.2021.102117 -
Clinical Pharmacology and Therapeutics Feb 2022Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity)....
Aminoglycosides are widely used antibiotics with notable side effects, such as nephrotoxicity, vestibulotoxicity, and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is the mitochondrial homologue of the prokaryotic 16s rRNA. Some MT-RNR1 variants (i.e., m.1095T>C; m.1494C>T; m.1555A>G) more closely resemble the bacterial 16s rRNA subunit and result in increased risk of aminoglycoside-induced hearing loss. Use of aminoglycosides should be avoided in individuals with an MT-RNR1 variant associated with an increased risk of aminoglycoside-induced hearing loss unless the high risk of permanent hearing loss is outweighed by the severity of infection and safe or effective alternative therapies are not available. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of aminoglycosides based on MT-RNR1 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).
Topics: Aminoglycosides; Anti-Bacterial Agents; Clinical Decision-Making; Genotype; Hearing Loss, Sensorineural; Humans; Ototoxicity; Patient Safety; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Predictive Value of Tests; RNA, Ribosomal; Risk Assessment; Risk Factors
PubMed: 34032273
DOI: 10.1002/cpt.2309