Simultaneous determination of tramadol in earwax and urine samples: effects of age, duration time and sex.

Background: This study aims to determine the concentrations of tramadol in earwax (µg/g) and urine (µg/ml) samples taken from postoperative patients, to evaluate the sensitivity of earwax (cerumen) as an alternative analyte and compare it with the findings in urine samples. Results: The results indicated that tramadol concentrations in earwax samples were averaged 45.08 µg/g (range: 13.5-107.7 µg/g), whereas tramadol concentrations in urine samples were averaged 4.97 µg/ml (range: 1.57-10.11 µg/ml). There were significant differences when comparing age groups, duration and sex between earwax and urine samples (p < 0.05). Conclusion: Despite the significant differences between earwax and urine samples, earwax can be used as a bioindicator of tramadol detection.

Cancer evaluation in dogs using cerumen as a source for volatile biomarker prospection.

Cancer is one of the deadliest diseases in humans and dogs. Nevertheless, most tumor types spread faster in canines, and early cancer detection methods are necessary to enhance animal survival. Here, cerumen (earwax) was tested as a source of potential biomarkers for cancer evaluation in dogs. Earwax samples from dogs were collected from tumor-bearing and clinically healthy dogs, followed by Headspace/Gas Chromatography-Mass Spectrometry (HS/GC-MS) analyses and multivariate statistical workflow. An evolutionary-based multivariate algorithm selected 18 out of 128 volatile metabolites as a potential cancer biomarker panel in dogs. The candidate biomarkers showed a full discrimination pattern between tumor-bearing dogs and cancer-free canines with high accuracy in the test dataset: an accuracy of 95.0% (75.1-99.9), and sensitivity and specificity of 100.0% and 92.9%, respectively. In summary, this work raises a new perspective on cancer diagnosis in dogs, being carried out painlessly and non-invasive, facilitating sample collection and periodic application in a veterinary routine.

Molecular strategy for the direct detection and identification of the most common fungal community in cerumen specimens by multiplex PCR.

Introduction. Otomycosis is a superficial fungal infection that is responsible for approximately 9-27 % of otitis externa. However, fungal communities in otomycosis are varied, but Aspergillus spp. and Candida spp. are the most common causes of this infection.Hypothesis Statement. The multiplex PCR assay is postulated to be able to directly detect more than one fungal genus in cerumen specimens.Aim. This study aimed to develop and evaluate the role of the multiplex PCR assay in detecting the most common genus of fungi that cause otomycosis directly from the cerumen specimens.Methodology. To detect Candida and Aspergillus/Penicillium genera, three pairs of primers, including pan-fungal, pan-Candida, and pan-Aspergillus/Penicillium, were used in a multiplex PCR. In order to evaluate the performance and reproducibility of the multiplex PCR. the cerumen of 140 patients suspected of otomycosis were investigated.Results. Pan-Candida and pan-Aspergillus/Penicillium primers were designed to amplify the ITS1-5.8S-ITS2 region and the ß-tubulin gene, respectively. In the multiplex PCR assay, 64 (47.40 %) and 118 (87.40 %) specimens were positive with pan-Candida and pan-Aspergillus/Penicillium primers, respectively. Double amplicon bands of Candida and Aspergillus were obtained in 51 (37.77 %) specimens. In the culture method, yeast (n=18, 13.33 %) and mould (n=117, 86.66 %) were isolated from 135 cerumen specimens. The sensitivity, specificity, and positive and negative predictive values of the multiplex PCR assays using culture method results as the gold standard were determined to be 94, 33, 97, and 22 %, respectively.Conclusion. In our study, multiplex PCR assays enabled simultaneous detection of two common genera of the causative agent of otomycosis in a cerumen specimen. Regarding the high sensitivity of the first step of the multiplex PCR assay, this assay may be used for the direct detection of Candida and Aspergillus genera in other clinical specimens.

"Do-It-Yourself" Ear Canal Care.

There are a large variety of over-the-counter home remedies and devices for cerumen impaction available in the United States. It is a challenge for clinicians to maintain awareness of the safety and efficacy of these tools, as they are not considered "medical devices" and frequently have no requirement for demonstrating safety or efficacy. This article provides a broad overview of the products being advertised to patients and discusses considerations when recommending home cerumen maintenance.

Follow the Wax: The Natural Protection of the Ear Canal and Its Biome.

The external canal is a unique environment that has an elaborate mechanism for self-cleaning and protection. The fundamental basis of this is the epithelial migration of the desquamating layers of the keratinizing epithelium that lines the entire canal and ear drum. This migratory movement results in a "conveyor belt" effect where the dead skin is moved out of the bony ear canal to the cartilaginous portion, where it is lifted off with the help of glandular skin secretions and the hairs of the canal to form what we call "ear wax." The ear wax has numerous protective properties and is essential to the health of the external ear. The protective properties are due to chemical properties of the wax, in addition to intrinsic chemical secretions by the sebaceous and cerumen apocrine glands. The protection also comes from a diverse population of organisms that exist in the external ear that are usually saprophytic, commensal, and symbiotic, but in some cases, they can become parasitic and pathologic. Detection and quantification of the members of this biome has been difficult, and their overall role in the normal biome of the ear and their transition into pathogens remain an area of active research and investigation.

Determination of cannabinoids in human cerumen samples by use of UPLC-MS/MS as a potential biomarker for drug use.

A quantitative analytical procedure was developed and validated by the use of Ultra- Performance Liquid Chromatography tandem Mass Spectrometry (UPLC-MS/MS) for the determination of Cannabidiol (CBD), Cannabinol (CBN), Δ9-Tetrahydrocannabinol (Δ9-THC), Cannabichromene (CBC), Cannabigerol (CBG) and 11-Nor- 9- Carboxy- Tetrahydrocannabinol (THC-COOH) in an unconventional biological matrix, cerumen. All the investigated calibration curves were characterized by high correlation values (R2 ≥ 0.9965). The LODs and LOQs ranged from 0.004 to 0.009 µg g-1 and 0.012-0.029 µg g-1, respectively. Intra-assay and inter-assay precision were found to be 0.6-2.5%, and 0.8-2.2%, respectively. All recovery values of cannabinoids, with the use of the optimum cotton swab, at low (0.008 µg g-1 of cerumen), medium (0.037 µg g-1of cerumen) and high (0.16 µg g-1 of cerumen) control levels, were estimated to be above 86%. The method developed here permitted the analysis of real cerumen samples obtained from fourteen cannabis users. In twelve out of fourteen cases, Δ9-THC was found to be positive, while in six cases, three major cannabinoids, CBN, CBG and Δ9-THC were quantified at concentrations 0.02-0.21 µg g-1, 0.01-0.24 µg g-1 and 0.01-4.86 µg g-1, respectively. Subject #8 has the highest amount of the detected substances in both left and right ear, with Δ9-THC at a concentration of 1.85 and 4.86 µg g-1, CBG 0.06 and 0.24 µg g-1, CBN 0.10 and 0.21 µg g-1, respectively. In addition, a detection window for the substances Δ9-Tetrahydrocannabinol, Cannabinol and Cannabigerol, in cerumen, was defined with success. In this case, Δ9-THC reached a maximum detection frame of up to fifteen days after smoking 0.5 g of marijuana cigarette. ANOVA-one-way analysis also indicated that the average earwax production of non-cannabis users differs significantly from the one of cannabis users (p = 0.048, <0.05). On the other hand, no significant difference was noticed between male and female users as the p value exceeded 0.05. In addition, no significant effect was observed on earwax production in regard to age, frequency and the last time of use (p > 0.05). These last three factors proved to have a significant impact on cannabinoids concentrations, since p values were less than 0.05.

Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of 25 psychoactive drugs in cerumen and its application to real postmortem samples.

PURPOSE: In the present study, a method for the detection of 25 psychoactive substances in cerumen was developed and validated. This method targets opiates, cocaine, antidepressants, benzodiazepines, antipsychotics and antiparkinsons. METHODS: Analysis was performed on a SCIEX Triple Quad 6500+ system after liquid-liquid extraction. Methanol with 1% acetic acid was chosen as the extraction solvent. After the addition of the solvent, samples were vortexed, sonicated, centrifuged and directly injected into the liquid chromatography-tandem mass spectrometry system. RESULTS: The method was found to be selective and sensitive (limit of detection: 0.017 ng-0.33 ng/mg), the assay was linear for all analytes with linear regression coefficient ranging 0.9911-1.00. The values for intra-assay precision was between 4.34 and 14.6% and inter-assay precision between 5.81 and 17.7%, with accuracy within the acceptable criteria for all analytes. All analytes in cerumen specimens were stable for 48 h at 4 °C and 72 h at - 20 °C, whilst no significant matrix effect or carryover was observed. Applicability was proven by analyzing cerumen samples from 25 deceased with a history of drug abuse. All analytes were detected in real samples, thus confirming the sensitivity of the developed method. CONCLUSIONS: According to our knowledge, it is the first time that a method for the simultaneous detection of 25 psychoactive drugs in cerumen was developed, fully validated and finally applied to 25 postmortem samples.

Trends in Billing and Medicare Reimbursement for In-Office Cerumen Removal by Otolaryngologists and Other Providers.

OBJECTIVES: To analyze trends in billing patterns, Medicare reimbursement, and practice-setting for otolaryngologists (ORLs) and other provider types performing in-office cerumen removal. METHODS: This retrospective study included data on Medicare-billing providers from the Medicare Part B: Provider Utilization and Payment Datafiles (2012-2018). Number of providers performing in-office cerumen removal, total sums and medians for Medicare reimbursements and services, and services per patient were gathered along with geographic distributions. RESULTS: There have been near linear declines in number of general physicians and other provider types performing cerumen extractions with 42.6% and 40.7% declines, respectively, and near linear growth in number of ORLs and advanced practice providers (APPs) with 9.7% and 51.1% growth, respectively. At the median, general physicians, APPs, and other provider types have been billing for a similar and constant number of cerumen extractions per provider, while ORLs have seen a 10.6% increase. Total Medicare reimbursement to general physicians and other provider types has fallen 45.0% and 32.5%, respectively, and to ORLs and APPs has grown 16.9% and 103.4%, respectively. Compared to non-ORLs, ORLs tend to bill for cerumen extraction out of an urban setting rather than a rural setting (P < .001). CONCLUSIONS: General physicians and other provider types are increasingly referring cerumen disimpaction patients to ORL physicians and allowing APPs to perform these procedures, indicating a change in landscape of medical practice among these providers. General physicians may be filling a need in the rural setting, where there are fewer ORLs practicing.

Determination of fentanyl and norfentanyl in cerumen in the setting of postmortem investigation.

Cerumen is an emerging alternative biological matrix in the field of forensic toxicology. An ultra-high-pressure liquid chromatography-mass spectrometry/mass spectrometry [UHPLC-MS/MS] method for the determination of fentanyl and norfentanyl in cerumen was developed and applied in a mixed drug toxicity fatal case. The method was found to be selective and sensitive (LOQ: 0.05 ng/mg for fentanyl and 0.02 ng/mg for norfentanyl), while validation included recovery, carryover, short-term stability, matrix effect, accuracy, and precision (RSD%). Accuracy ranged from 83.1% to 103.5%, while intra- and inter-day precision ranged from 8.6% to 13.1% and from 8.3% to 15.8%, respectively. Matrix effect experiments showed that matrix did not significantly affect signal intensity (82.3%-96.8%). Short-term stability concerning sample extracts was found satisfactory. Fentanyl and norfentanyl were detected in cerumen at a concentration of 1.17 and 0.36 ng/mg respectively. The findings in cerumen corroborate the cause of death and suggest that cerumen is a potential specimen for detecting drugs of abuse in forensic cases.

The Outcome of Cerumen Removal in the Pediatric Emergency Department.

OBJECTIVE: Cerumen obstructs the visualization of the tympanic membrane (TM) in up to 40% of children, sometimes posing a challenge to rule out the diagnosis of acute otitis media (AOM) as the source of otalgia (for verbal children), irritability, fever, and febrile seizures. We aim to determine the rate at which removing the cerumen from blocking the view of the TM could change the management of these patients in the pediatric emergency department (PED). METHODS: We retrospectively investigated all medical records of patients who underwent cerumen removal in the PED at a tertiary children's hospital from 2018 to 2019. We analyzed the effect of the procedure on the subsequent workup during their PED visit. RESULTS: Of 482 children who presented to the PED with otalgia, irritability, fever, and/or febrile seizures and who were referred to an otolaryngologist for subsequent treatment after preliminary evaluation in the PED, 176 were included in the study group after having the cerumen removed from one or both ears. Seventy-three of them were given a diagnosis of AOM, 93 had a normal-appearing TM, and 10 had external otitis. Twenty-one percent of those with AOM and 46% of those with a normal TM ( P = 0.008) had blood drawn as part of their workup in their PED visit. The rate of chest x-rays was also significantly less for the AOM group (16% vs 30%, P = 0.03), and they also underwent fewer urine tests ( P = NS). CONCLUSION: Cerumen removal changes the management of children in the PED who present with a possible diagnosis of an ear infection. Cerumen removal could avoid unnecessary laboratory and imaging studies, which could save time, costs, and suffering.

Otoscopy and tympanometry outcomes from the National Health and Nutrition Examination Survey (NHANES).

PURPOSE: The purpose of the study was to estimate the prevalence of conductive pathologies based on tympanometric and otoscopic findings in adults in the U.S. and examine relationships between abnormal findings and audiometrically defined or reported perceived hearing loss and tinnitus. MATERIALS AND METHODS: Data from 3409 individuals aged 20-69 years from the 1999-2000 and 2000-2002 cycles of the National Health and Nutrition Examination Survey (NHANES) were analyzed. Outcomes included report of ear tubes, self-perceived hearing loss, and tinnitus (yes or no). Otoscopy involved screening for presence of cerumen (ear wax) and physical abnormality for each ear. Ear-specific tympanometry included measures of middle ear pressure, external ear volume, tympanometric width, and admittance/compliance for each ear. Mean and prevalence estimates are provided applying sample weights. A multivariate ordinal regression model adjusting for age, sex, race/ethnicity, and education was used to examine relationships between otoscopy or tympanometry measures with hearing loss and tinnitus. RESULTS: Approximately 12% of the sample showed evidence of abnormal tympanometry and 12% showed evidence of abnormal otoscopy in at least one ear. Measured hearing loss was consistently related to tympanometry outcomes, in both univariate and adjusted models, but perceived hearing loss and tinnitus were not related to abnormal tympanometry or otoscopy. The most common reason for abnormal otoscopy was presence of excessive or impacted cerumen, representing an estimated 10% of the population. CONCLUSIONS: With 1 out of 10 adults having excessive cerumen, adults considering over-the-counter (OTC) hearings aids may benefit from an ear examination prior to purchase.

Quality Improvement in Otolaryngology-Head and Neck Surgery: Developing Registry-Enabled Quality Measures From Guidelines for Cerumen Impaction and Allergic Rhinitis Through a Transparent and Systematic Process.

BACKGROUND AND SIGNIFICANCE: Quality measurement can drive improvement in clinical care and allow for easy reporting of quality care by clinicians, but creating quality measures is a time-consuming and costly process. ECRI (formerly Emergency Care Research Institute) has pioneered a process to support systematic translation of clinical practice guidelines into electronic quality measures using a transparent and reproducible pathway. This process could be used to augment or support the development of electronic quality measures of the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) and others as the Centers for Medicare and Medicaid Services transitions from the Merit-Based Incentive Payment System (MIPS) to the MIPS Value Pathways for quality reporting. METHODS: We used a transparent and reproducible process to create electronic quality measures based on recommendations from 2 AAO-HNSF clinical practice guidelines (cerumen impaction and allergic rhinitis). Steps of this process include source material review, electronic content extraction, logic development, implementation barrier analysis, content encoding and structuring, and measure formalization. Proposed measures then go through the standard publication process for AAO-HNSF measures. RESULTS: The 2 guidelines contained 29 recommendation statements, of which 7 were translated into electronic quality measures and published. Intermediate products of the guideline conversion process facilitated development and were retained to support review, updating, and transparency. Of the 7 initially published quality measures, 6 were approved as 2018 MIPS measures, and 2 continued to demonstrate a gap in care after a year of data collection. CONCLUSION: Developing high-quality, registry-enabled measures from guidelines via a rigorous reproducible process is feasible. The streamlined process was effective in producing quality measures for publication in a timely fashion. Efforts to better identify gaps in care and more quickly recognize recommendations that would not translate well into quality measures could further streamline this process.

Comparison of the Cerumenolytic Activities of New and Currently Used Agents.

OBJECTIVES: This study compared the cerumen dissolution activities of 7.5% sodium bicarbonate, 5% potassium hydroxide, 10% lactic acid, 3% salicylic acid, 10% glycolic acid, and distilled water. METHODS: An in vitro study was conducted with 36 cerumen samples. The cerumenolytic activities of the 6 agents were assessed by recording the degree of cerumen disintegration using digital photography at 15 minutes, 30 minutes, 1 hour, 2 hours, and 12 hours. The undissolved cerumen that remained after 12 hours was removed from the solutions and weighed after drying. RESULTS: Potassium hydroxide showed the fastest cerumenolytic activity, dissolving a moderate amount of cerumen at 30 minutes, while glycolic acid and salicylic acid caused no visible changes in the cerumen samples. Samples treated with potassium hydroxide and sodium bicarbonate exhibited higher degrees of disintegration compared to samples treated with distilled water (odds ratio and 95% CI: 273.237 [0.203-367 470.4] and 1.129 [0.002-850.341], respectively). The greatest reduction in cerumen weight was associated with the use of sodium bicarbonate; however, this result did not reach statistical significance. CONCLUSIONS: Among the solutions tested, 5% potassium hydroxide showed the fastest dissolution activity, yielding moderate disintegration within only 30 minutes. In terms of residual cerumen weight within 12 hours, all solutions exhibited equivalent effectiveness in the disintegration of cerumen.

Association Between Earwax-Determinant Genotypes and Acquired Middle Ear Cholesteatoma in a Japanese Population.

OBJECTIVE: A single-nucleotide polymorphism 538G>A in the human ABCC11 gene is a determinant of the earwax morphotype. ABCC11 538GG and GA correspond to wet earwax and 538AA to dry earwax. Despite a putative positive correlation between the frequency of the 538G allele and the prevalence of cholesteatoma, minimal clinical information is currently available. We aimed to evaluate this association between the ABCC11 genotypes and acquired middle ear cholesteatoma. STUDY DESIGN: Case-control study. SETTING: Single-center academic hospital. METHODS: We recruited 67 Japanese patients with acquired middle ear cholesteatoma (cholesteatoma group) and 100 Japanese controls with no history of middle ear cholesteatoma. We assessed the ABCC11 genotypes for all participants. Clinical information was collected from the cholesteatoma group. The genotype data of 104 Japanese people from the 1000 Genomes Project who represent the general population were used. RESULTS: The proportion of participants with ABCC11 538GG or GA was significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). The ABCC11 538G allele frequency was also significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). Multivariate logistic regression analyses revealed a significant association between the ABCC11 genotype and acquired middle ear cholesteatoma (odds ratio, 5.49; 95% CI, 2.61-11.5; P < .001). CONCLUSION: Our results suggest that the ABCC11 genotypes could be associated with the development of acquired middle ear cholesteatoma among Japanese people.

The role of the mother habit to clean the ears against incidence of cerumen obturans in children.

OBJECTIVE: This study aims to describe the role of the mother habit against incidence of cerumen obturans in children. METHODS: This study is an observational analysis with a cross-sectional design. This study was conducted on 119 elementary students and their mother habits at SD Kera-Kera, Makassar, Indonesia. The aged samples between 6 and 13 years, an otoscopic examination was performed to determine cerumen obturans and an interview method to know ear cleaning habits. RESULTS: In this study, it was found that 84.9% of the samples experienced obtaining cerumen in one or both ears, especially in children aged ≤10 years (71%), where 82.4% of the ear cleaning were made by their mother, using a cotton bud or cerumen hooks with the main complaints of the children is discomfort or impairment of hearing where these habits are not recognized by the level of education or the main activities of mothers. CONCLUSIONS: The mother's habit of cleaning the ears ear plays a major role in the incidence of cerumen obturans in children. The habit of cleaning the ears not seeing the people who do it or the frequency affects the high incidence of cerumen obturans found in children, especially elementary school students under ten years old.