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The Cochrane Database of Systematic... Jan 2020Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Topical antibiotics, the most common treatment for CSOM, act to kill or inhibit the growth of micro-organisms that may be responsible for the infection. Antibiotics can be used alone or in addition to other treatments for CSOM, such as antiseptics or ear cleaning (aural toileting).
OBJECTIVES
To assess the effects of topical antibiotics (without steroids) for people with CSOM.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with at least a one-week follow-up involving participants (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. The interventions were any single, or combination of, topical antibiotic agent(s) of any class, applied directly into the ear canal as ear drops, powders or irrigations, or as part of an aural toileting procedure. The two main comparisons were topical antibiotic compared to a) placebo or no intervention and b) another topical antibiotic (e.g. topical antibiotic A versus topical antibiotic B). Within each comparison we separated studies where both groups of participants had received topical antibiotic a) alone or with aural toileting and b) on top of background treatment (such as systemic antibiotics).
DATA COLLECTION AND ANALYSIS
We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks and after four weeks; health-related quality of life using a validated instrument; ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways.
MAIN RESULTS
We included 17 studies with a total of 2198 participants. Twelve studies reported the sample size in terms of participants (not ears); these had a total of 1797 participants. The remaining five studies reported both the number of participants and ears, representing 401 participants, or 510 ears. A: Topical antibiotics versus placebo or no treatment (with aural toilet in both arms and no other background treatment) One small study compared a topical antibiotic (ciprofloxacin) with placebo (saline). All participants received aural toilet. Although ciprofloxacin was better than saline in terms of resolution of discharge at one to two weeks: 84% versus 12% (risk ratio (RR) 6.74, 95% confidence interval (CI) 1.82 to 24.99; 35 participants, very low-certainty evidence), the very low certainty of the evidence means that it is very uncertain whether or not one intervention is better or worse than the other. The study authors reported that "no medical side-effects and worsening of audiological measurements related to this topical medication were detected" (very low-certainty evidence). B: Topical antibiotics versus placebo or no treatment (with use of oral antibiotics in both arms) Four studies compared topical ciprofloxacin to no treatment (three studies; 190 participants) or topical ceftizoxime to no treatment (one study; 248 participants). In each study all participants received the same antibiotic systemically (oral ciprofloxacin, injected ceftizoxime). In at least one study all participants received aural toilet. Useable data were only available from the first three studies; ciprofloxacin was better than no treatment, resolution of discharge occurring in 88.2% versus 60% at one to two weeks (RR 1.47, 95% CI 1.20 to 1.80; 2 studies, 150 participants; low-certainty evidence). None of the studies reported ear pain or discomfort/local irritation. C: Comparisons of different topical antibiotics The certainty of evidence for all outcomes in these comparisons is very low. Quinolones versus aminoglycosides Seven studies compared an aminoglycoside (gentamicin, neomycin or tobramycin) with ciprofloxacin (734 participants) or ofloxacin (214 participants). Whilst resolution of discharge at one to two weeks was higher in the quinolones group the very low certainty of the evidence means that it is very uncertain whether or not one intervention is better or worse than the other (RR 1.95, 95% CI 0.88 to 4.29; 6 studies, 694 participants). One study measured ear pain and reported no difference between the groups. Quinolones versus aminoglycosides/polymyxin B combination ±gramicidin We identified three studies but data on our primary outcome were only available in one study. Comparing ciprofloxacin to a neomycin/polymyxin B/gramicidin combination, for an unknown treatment duration (likely four weeks), ciprofloxacin was better (RR 1.12, 95% CI 1.03 to 1.22, 186 participants). A "few" patients experienced local irritation upon the first instillation of topical treatment (numbers/groups not stated). Others Other studies examined topical gentamicin versus a trimethoprim/sulphacetamide/polymixin B combination (91 participants) and rifampicin versus chloramphenicol (160 participants). Limited data were available and the findings were very uncertain.
AUTHORS' CONCLUSIONS
We are uncertain about the effectiveness of topical antibiotics in improving resolution of ear discharge in patients with CSOM because of the limited amount of low-quality evidence available. However, amongst this uncertainty there is some evidence to suggest that the use of topical antibiotics may be effective when compared to placebo, or when used in addition to a systemic antibiotic. There is also uncertainty about the relative effectiveness of different types of antibiotics; it is not possible to determine with any certainty whether or not quinolones are better or worse than aminoglycosides. These two groups of compounds have different adverse effect profiles, but there is insufficient evidence from the included studies to make any comment about these. In general, adverse effects were poorly reported.
Topics: Administration, Topical; Anti-Bacterial Agents; Chronic Disease; Humans; Otitis Media, Suppurative; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31896168
DOI: 10.1002/14651858.CD013051.pub2 -
The International Journal of... Jan 2021The use of injectable antibiotics to treat multidrug-resistant TB (MDR-TB) is associated with substantial morbidity due to long-term hearing loss. This systematic... (Meta-Analysis)
Meta-Analysis
The use of injectable antibiotics to treat multidrug-resistant TB (MDR-TB) is associated with substantial morbidity due to long-term hearing loss. This systematic review evaluates the incidence of ototoxicity among patients treated for MDR-TB, and the evidence for routine audiometric monitoring to mitigate its severity. Studies of ototoxicity among patients with MDR-TB were identified from six databases: PubMed, MEDLINE, Web of Science, Embase, SCOPUS and the Cochrane Library. Meta-analyses were performed to determine the overall incidence of hearing loss, tinnitus and vertigo. The incidence of hearing loss was further stratified by country income status and the injectable agent used during treatment. Among 64 studies from 25 countries including 12 793 patients, 28.3% (95%CI 23.4-33.1) of patients treated with injectables reported hearing loss. Tinnitus and vertigo were experienced by respectively 14.5% (95%CI 10.3-18.7) and 8.1% (95%CI 4.7-11.6) of patients. The incidence of hearing loss was highest among patients treated with amikacin (33.4%, 95%CI 18.2-48.6), and lowest among those treated with capreomycin (2.0%, 95%CI 0-5.5). We found that audiometry was widely used as a method of evaluating hearing loss, and was feasible in a wide range of settings. Injectable antibiotics contribute to significant morbidity in patients with MDR-TB. In settings where they are used, routine audiometric monitoring is recommended to prevent irreversible damage.
Topics: Amikacin; Antitubercular Agents; Capreomycin; Humans; Ototoxicity; Tuberculosis, Multidrug-Resistant
PubMed: 33384041
DOI: 10.5588/ijtld.20.0217 -
Journal of Cancer Survivorship :... Feb 2023A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate... (Review)
Review
PURPOSE
A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer.
METHODS
This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review.
CONCLUSIONS
All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents.
IMPLICATIONS FOR CANCER SURVIVORS
Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care.
Topics: Child; Humans; Adult; Antineoplastic Agents; Prognosis; Ototoxicity; Quality of Life; Cancer Survivors; Neoplasms
PubMed: 36729346
DOI: 10.1007/s11764-022-01315-8 -
The Journal of International Advanced... Mar 2022Nowadays, immunosuppressant drugs are widely used to prevent rejection in organ transplantation and to treat autoimmune diseases. Ototoxicity related to...
BACKGROUND
Nowadays, immunosuppressant drugs are widely used to prevent rejection in organ transplantation and to treat autoimmune diseases. Ototoxicity related to immunosuppressant drugs has been anecdotally reported but scarcely investigated. The aim of this investigation was to systematically review the available data on ototoxicity due to immunosuppressant therapy for transplantation or autoimmune disease.
METHODS
A search of electronic databases (PubMed, Web of Science, and Scopus) was performed in order to identify studies concerning otovestibular toxicity due to immunosuppressant therapy for transplantation or autoimmune disease between January 1980 and November 2020.
RESULTS
Eighteen articles were considered eligible for the review. Totally 131 patients experienced ototoxicity related to immunosuppressive treatment. Hearing loss was the most common clinical manifestation (128 cases) and was mainly bilateral. Tinnitus was reported in 52 cases and vertigo in 2. The immunosuppressant drugs most frequently involved in ototoxic manifestations were calcineurin inhibitors (cyclosporine and tacrolimus), often related to their high serum levels.
CONCLUSION
Immunosuppressant-related ototoxicity is clinically relevant in uncommon but definitely challenging situations. Clinicians should be aware of this and inquire about hearing impairment symptoms during therapy and refer symptomatic patients to an otolaryngologist/audiologist. Further large-scale, prospective investigations are necessary to better characterize the ototoxicity of each class of immunosuppressants.
Topics: Autoimmune Diseases; Hearing Loss; Humans; Immunosuppressive Agents; Ototoxicity; Prospective Studies
PubMed: 35418366
DOI: 10.5152/iao.2022.21416 -
Therapeutic Drug Monitoring Dec 2023Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic...
BACKGROUND
Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.
METHODS
An updated systematic review was conducted on behalf of the Canadian Pharmacogenomics Network for Drug Safety, based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 statement. Pharmacogenomic studies that reported associations between genetic variation and cisplatin-induced ototoxicity were included. The evidence on genetic associations was summarized and evaluated, and knowledge gaps that can be used to inform future pharmacogenomic studies identified.
RESULTS
Overall, 40 evaluated reports, considering 47 independent patient populations, captured associations involving 24 genes. Considering GRADE criteria, genetic variants in 2 genes were strongly (ie, odds ratios ≥3) and consistently (ie, replication in ≥3 independent populations) predictive of cisplatin-induced ototoxicity. Specifically, an ACYP2 variant has been associated with ototoxicity in both children and adults, whereas TPMT variants are relevant in children. Encouraging evidence for associations involving several other genes also exists; however, further research is necessary to determine potential clinical relevance.
CONCLUSIONS
Genetic variation in ACYP2 and TPMT may be helpful in predicting patients at the highest risk of developing cisplatin-induced ototoxicity. Further research (including replication studies considering diverse pediatric and adult patient populations) is required to determine whether genetic variation in additional genes may help further identify patients most at risk.
Topics: Adult; Humans; Child; Cisplatin; Antineoplastic Agents; Pharmacogenetics; Ototoxicity; Canada; Acylphosphatase
PubMed: 37726872
DOI: 10.1097/FTD.0000000000001113 -
Otolaryngology--head and Neck Surgery :... Apr 2023To raise awareness of the growing list of non-platinum-based chemo- and immunotherapeutic agents that have been associated with ototoxicity and to introduce the possible...
OBJECTIVE
To raise awareness of the growing list of non-platinum-based chemo- and immunotherapeutic agents that have been associated with ototoxicity and to introduce the possible mechanism of ototoxicity of these agents.
DATA SOURCES
PubMed, Embase, and Web of Science.
REVIEW METHODS
A systematic review was performed following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). PubMed, Embase, and Web of Science databases were searched for published reports of ototoxicity from non-platinum-based chemo- and immunotherapeutic agents in adult and pediatric patients. Therapies that utilized any platinum-based agent were excluded.
CONCLUSIONS
Ototoxicity from non-platinum-based chemo- and immunotherapies is an evolving problem. There were 54 reports-39 case reports and 15 cohort studies-documenting ototoxicity from 7 agents/combination therapies. Of these reports, 37 (69%) were published within the last 15 years (after 2005). No recovery of hearing was documented in 21 of 56 cases (38%). Pretreatment audiograms were uncommon (19/54 studies, 35%), despite documented ototoxic associations.
IMPLICATIONS FOR PRACTICE
There is a growing number of novel, ototoxic, non-platinum-based chemo- and immunotherapeutic agents with various potential mechanisms of action. Otolaryngologists will need to prioritize awareness of these agents. This growing list of agents, many of which have reversible effects, suggest a need for standardized ototoxicity monitor protocols so that appropriate and timely management options can be implemented.
Topics: Adult; Child; Humans; Antineoplastic Agents; Cisplatin; Hearing Loss; Ototoxicity; Immunotherapy
PubMed: 35439087
DOI: 10.1177/01945998221094457 -
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 -
Journal of the Association For Research... Feb 2023Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Identifying risk factors for tinnitus could facilitate not only the recommendations for prevention measures, but also identifying potential pathways for new interventions. This study reports the first comprehensive systematic review of analytical observational studies able to provide information about causality (i.e., case-control and cohort designs).
METHODS
A literature search of four electronic databases identified epidemiological studies published on tinnitus and different exposures. Independent raters screened all studies, extracted data, and evaluated study quality using the Newcastle-Ottawa Scale. Reported relative risks (RR), hazard ratios (HR), odds ratios (OR), and prevalence ratios (PR) with 95% confidence intervals (CI) were used to compute crude estimates of RR for tinnitus risk factors.
RESULTS
From 2389 records identified, a total of 374 articles were read as full text (24 reviews, 301 cross-sectional studies, 42 cohort studies, and 7 case-control studies). However, from 49 case-control and cohort studies, only 25 adequately reported risk ratios. Using the findings from these studies, positive causal associations were found for various hearing-related factors (i.e., unspecified hearing loss, sensorineural hearing loss, occupational noise exposure, ototoxic platinum therapy, and otitis media). Evidence was also found for a number of non-otological risk factors including temporo-mandibular joint disorder, depression, chronic obstructive pulmonary disease, and hyperlipidemia. Negative associations indicating preventative effects were found for diabetes and high alcohol consumption. No associations were found for low alcohol consumption, body mass index, head injury, heart failure, hypertension, leisure noise exposure, migraine, rheumatoid arthritis, sex, smoking, stroke, and whiplash. However, with the exception of unspecified hearing loss, these findings resulted from pooling no more than 4 studies, illustrating that the vast majority of the associations still remain inconclusive.
CONCLUSIONS
These systematic review and meta-analysis confirm a number of otological and non-otological risk factors for tinnitus. By highlighting major gaps in knowledge, our synthesis can help provide direction for future research that will shed light on the pathophysiology, improve management strategies, and inform more effective preventions.
Topics: Humans; Tinnitus; Cross-Sectional Studies; Hearing Loss; Risk Factors; Hearing Loss, Sensorineural; Observational Studies as Topic
PubMed: 36380120
DOI: 10.1007/s10162-022-00874-y -
Thorax Nov 2015Ototoxicity is a severe side effect of aminoglycoside antibiotics. Aminoglycosides are recommended for the treatment of multidrug-resistant TB (MDR-TB). N-Acetylcysteine... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB.
BACKGROUND
Ototoxicity is a severe side effect of aminoglycoside antibiotics. Aminoglycosides are recommended for the treatment of multidrug-resistant TB (MDR-TB). N-Acetylcysteine (NAC) appears to protect against drug- and noise-induced hearing loss. This review aimed to determine if coadministering NAC with aminoglycoside affected ototoxicity development, and to assess the safety and tolerability of prolonged NAC administration.
METHODS
Eligible studies reported on the efficacy of concomitant NAC and aminoglycoside administration for ototoxicity prevention or long-term (≥ 6 weeks) administration of NAC regardless of indication. Pooled estimates were calculated using a fixed-effects model. Heterogeneity was assessed using the I(2) statistic.
RESULTS
Three studies reported that NAC reduced ototoxicity in 146 patients with end-stage renal failure receiving aminoglycosides. Pooled relative risk for otoprotection at 4-6 weeks was 0.14 (95% CI 0.05 to 0.45), and the risk difference was -33.3% (95% CI 45.5% to 21.2%). Eighty-three studies (N=9988) described the administration of NAC for >6 weeks. Abdominal pain, nausea and vomiting, diarrhoea and arthralgia were increased 1.4-2.2 times.
DISCUSSION
This review provides evidence for the safety and otoprotective effect of NAC when coadministered with aminoglycoside. It represents a strong justification for a clinical trial to investigate the effect of concomitant NAC treatment in patients receiving aminoglycosides as part of MDR-TB treatment.
Topics: Acetylcysteine; Aminoglycosides; Ear Diseases; Free Radical Scavengers; Humans; Tuberculosis, Multidrug-Resistant
PubMed: 26347391
DOI: 10.1136/thoraxjnl-2015-207245 -
Cadernos de Saude Publica Jul 2012Mercury is neurotoxic, and numerous studies have confirmed its ototoxic effect. However, the diagnosis and follow-up of mercury exposure require understanding the... (Review)
Review
Mercury is neurotoxic, and numerous studies have confirmed its ototoxic effect. However, the diagnosis and follow-up of mercury exposure require understanding the pathophysiology of the chemical substance. Based on a systematic literature review, this study aimed to demonstrate whether mercury is ototoxic and to analyze its mechanism of action on the peripheral and central auditory system, in order to contribute to the diagnosis and follow-up of exposure. This was a systematic review of studies published on the effects of mercury exposure on the auditory system. The full text of the studies and their methodological quality were analyzed. The review identified 108 studies published on the theme, of which 28 met the inclusion criteria. All the articles in the analysis showed that mercury exposure is ototoxic and produces peripheral and/or central damage. Acute and long-term exposure produces irreversible damage to the central auditory system. Biomarkers were unable to predict the relationship between degree of mercury poisoning and degree of lesion in the auditory system.
Topics: Ear Diseases; Environmental Exposure; Hearing Loss; Humans; Mercury; Severity of Illness Index; Time Factors
PubMed: 22729255
DOI: 10.1590/s0102-311x2012000700003