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John F Peppin,1,2 Joseph V Pergolizzi Jr,3– 5 Jeffrey Fudin,6– 8 Tricia A Meyer,9 Robert B Raffa3,5,10,11 1Marian University College of Osteopathic Medicine, Indianapolis, IN, USA; 2Pikeville University College of Osteopathic Medicine, Pikeville, KY, USA; 3Enalare Therapeutics Inc., Princeton, NJ, USA; 4NEMA Research Inc., Naples, FL, USA; 5Neumentum Inc., Summit, NJ, USA; 6Western New England College of Pharmacy, Springfield, MA, USA; 7Albany College of Pharmacy & Health Sciences Union University, Albany, NY, USA; 8Remitigate Therapeutics, Delmar, NY, USA; 9Texas A&M College of Medicine, Bryan, TX, USA; 10University of Arizona College of Pharmacy, Tucson, AZ, USA; 11Temple University School of Pharmacy, Philadelphia, PA, USACorrespondence: Robert B Raffa Tel +1 610-291-7019Email robert.raffa@temple.eduAbstract: The interest in substances that stimulate respiration has waxed and waned throughout the years, intensifying following the introduction of a new class of drugs that causes respiratory depression, and diminishing when antidotes or better drug alternatives are found. Examples include the opioids––deaths increasing during overprescribing, diminishing with wider availability of the opioid receptor antagonist naloxone, increasing again during COVID-19; the barbiturates––until largely supplanted by the benzodiazepines; propofol; and other central nervous system depressants. Unfortunately, two new troubling phenomena force a reconsideration of the status-quo: (1) overdoses due to highly potent opioids such as fentanyl, and even more-potent licit and illicit fentanyl analogs, and (2) overdose due to polysubstance use (the combination of an opioid plus one or more non-opioid drug, such as a benzodiazepine, sedating antidepressant, skeletal muscle relaxant, or various other agents). Since these now represent the majority of cases, new solutions are again needed. An interest in respiratory stimulants has been revived. This interest can be informed by a short review of the history of this interesting class of medications. We present a short history of the trajectory of advances toward more selective and safer respiratory stimulants.Keywords: overdose, respiratory depression, respiratory stimulant, carotid body, potassium channels

Peer influence has been found to be correlated with a host of harmful health behaviors. However, little research has been conducted investigating the relationship between peer influence and disordered eating. The present study surveyed 6th-, 7th-, and 8th-grade girls and boys using the Eating Disorder Inventory (EDI) and Inventory of Peer Influence (I-PIEC). This study found a significant positive correlation between peer influence and disordered eating. Multiple regression analyses revealed that peer influence was equally present in both males and females. There were no significant differences between males and females and EDI or I-PIEC scores. The likeability construct of peer influence was the most significant predictor of disordered eating in this study. School nurses are in a unique position to educate both male and female students about the dangers of disordered eating behaviors as well as identify students who may be at risk for these behaviors. [ABSTRACT FROM AUTHOR]

The present investigation expanded on an earlier study by Miyamoto, Osberger, Todd, Robbins, Karasek, et al. (1994) who compared the speech perception skills of two groups of children with profound prelingual hearing loss. The first group had received the Nucleus multichannel cochlear implant and was tested longitudinally. The second group, who were not implanted and used conventional hearing aids, was tested at a single point in time. In the present study, speech perception scores were examined over time for both groups of children as a function of communication mode of the child. Separate linear regressions of speech perception scores as a function of age were computed to estimate the rate of improvement in speech perception abilities that might be expected due to maturation for the hearing aid users (n = 58) within each communication mode. The resulting regression lines were used to compare the estimated rate of speech perception growth for each hearing aid group to the observed gains in speech perception made by the children with multichannel cochlear implants. A large number of children using cochlear implants (n = 74) were tested over a long period of implant use (m = 3.5 years) that ranged from zero to 8.5 years. In general, speech perception scores for the children using cochlear implants were higher than those predicted for a group of children with 101-110 dB HL of hearing loss using hearing aids, and they approached the scores predicted for a group of children with 90-100 dB HL of hearing loss using hearing aids. [ABSTRACT FROM AUTHOR]

In the determination of the speech-reception threshold (SRT), spondaic words are assumed to be homogeneous with respect to intelligibility; and the assumption of equal intelligibility requires that the words be comparable for all signal levels. Previous attempts to assess the equal intelligibility assumption using word thresholds as the sole criterion are not an adequate basis for specifying the equality of intelligibility. In the present study, the recorded spondaic words (Tillman recording) were analyzed in an attempt to create a more homogeneous set of spondaic words for future laboratory work. To achieve this goal, the data reported by Young, Dudley, and Gunter (1982) and data collected in our laboratory were fitted to a logistic function (psychometric function) from which a 50% point (threshold) and slope were obtained. To specify their acoustical parameters, the recorded spondaic words were digitized and the RMS level and duration of each syllable and word were calculated. None of the RMS or duration measures were correlated with word thresholds, so no attempt was made to equate level or duration. On the other hand, when the threshold of each word was adjusted to equal the mean threshold of the set (n = 36), the dispersion among word thresholds and slopes was greatly reduced. Further, we recommend that small sets of 'equally intelligible' spondaic words not be used for clinical testing because set size is a strong factor in determining threshold for spondees (Meyer & Bilger, 1997; Punch & Howard, 1985). [ABSTRACT FROM AUTHOR]

A 13-month-old cochlear implant recipient underwent routine device activation. Three months postoperatively, the patient sustained a fall with contact to the area of the implant without immediate complication. Ten months postoperatively, the position of the external coil appeared to have moved and the patient did not seem to be responding as well to sound. Audiological testing could not elicit normal device impedances. AP and lateral plain radiographs of the skull revealed migration of the internal magnet from its position within the internal coil to a position over the receiver/stimulator. This is the first known published case of cochlear implant magnet migration. [ABSTRACT FROM AUTHOR]

Objective: This review sought to answer the following research question: What are the characteristics of pediatric necrotizing otitis externa (NOE)? Moreover, we wanted to highlight the clinical importance of the current limitations in the literature., Methods: A scoping review was performed to determine what is known about NOE in the pediatric population. Four databases (COCHRANE Library, CINAHL, PubMed, and Scopus) were queried for articles published in English between 1976 to 2022. Variables extracted included comorbidities, demographics, outcomes, and treatment., Results: A total of 20 studies (N = 439) reported sufficient measures to be included in the review. Patients with NOE had a mean age of 10.0 years (range 2 months to 14 years) with a male-to-female gender ratio of 1.1:1. Mean length of hospital stay was 2.9 days (95%CI: 2.7-3.0). Demographics included 45.4% Caucasian, 6.0% African American, and 2.7% Asian/Pacific Islander. Less than 5% of patients had diabetes, while other reported comorbidities included neutropenia (n = 6), anemia (n = 5), dehydration/malnutrition (n = 4), Stevens Johnson Syndrome (n = 2), some form of immunosuppression/organ transplantation (n = 2), thrombocytopenia (n = 2), and leukopenia (n = 2). There have been no reported deaths from NOE in children., Conclusions: In the adult population NOE most commonly affects patients with diabetes, but our review reveals that diabetes does not appear to play as big a role in children. The disease seems to commonly affect patients with immunosuppression or severe health conditions. Complications such as cranial nerve palsies appear to be more common in the pediatric population. Specifically, the role of biopsy and culture in the treatment of pediatric NOE is stressed as they are important in treatment decisions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: COVID-19 has led to delays in providing healthcare in both emergency and non-emergency settings, especially in surgical subspecialties which rely heavily on referrals and in-person visits. Without an established telehealth infrastructure, many otorhinolaryngological departments experienced decreases in consultations. Telemedicine has attempted to bridge the gap between pre- and post-pandemic periods by creating a safe avenue of communication between otorhinolaryngologists and patients. This review hopes to address the accuracy of telemedicine in patient diagnosis and management., Methods: Searches were conducted since study conception until June 30, 2022, on multiple databases including PubMed, SCOPUS, and CINAHL for this systematic review and meta-analysis. Diagnostic accuracy, management accuracy, kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were meta-analyzed by comparing virtual visits to in-person visits (gold standard)., Results: Nineteen studies were included in this review. A total of 1518 patients were included across all studies. When comparing virtual visits against in-person visits, accurate diagnosis was made in 86.2% [82.1,89.9, I 2  = 73.5%, P  < 0.0001] of patients and management accuracy was 91.5% [86.1,95.7, I 2  = 81.8%, P  < 0.0001] when treating patients. Kappa value determining interrater reliability was 0.8 [0.7,0.9, I 2  = 81.8%, P  < 0.0001]., Conclusion: Our data suggest that diagnostic and management concordance is above 80% when comparing diagnosis and management strategies in patients who underwent both telehealth and in-person visits with an otorhinolaryngologist. In uncomplicated patients, telehealth might be a reliable source for diagnosis and management however, in-person consultation is likely still required for pathologies in which physical exam, imaging or procedural elements represent a vital component of the work-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To systematically review polysomnographic and cephalometric data in obstructive sleep apnea (OSA) patients with obesity (body mass index [BMI] ≥30 kg/m 2 ) treated with maxillomandibular advancement (MMA)., Data Sources: Scopus, PubMed, CINAHL, and The COCHRANE Library., Review Methods: A search was performed from inception until April 3, 2024, in each database., Results: A total of 14 studies (143 subjects) were included. The mean age was 44.3 years (range: 17-69), 80.2% males (95% CI: 72.5-86.5), mean BMI of 35.3 (95% CI: 33.1-37.5), and mean duration to follow-up post-MMA was 13.7 months (95% CI: 10.1-17.3). All objective outcomes improved significantly; overall, apnea-hypopnea index (AHI) decreased by -57.3 ([95% CI: -71.5 to -43.2], p < 0.0001) lowest oxygen saturation (LSAT) increased by 14.1% ([95% CI: 9.9 to 18.3], p < 0.0001), and Epworth Sleepiness Scale (ESS) decreased by -9.4 ([95% CI: -13.5 to -5.2], p < 0.0001). Surgical cure was 39.2% (95% CI: 20.3-60.0), and surgical success was 85.6% (95% CI: 77.8-91.5). Comparing percent reduction in class 3 obesity (-92.9%) as compared to class 1 (-85.5%) and class 2 (-83.6%) exhibited a significant difference (1 vs 3 p = 0.0012, 2 vs 3 p = 0.015)., Conclusions: Our findings suggest that MMA significantly improves subjective and objective outcomes in OSA amongst patients with obesity with results comparable to the overall population. Success rates remained above 80% in studies with the highest mean BMI. In addition, patients with class 3 obesity yielded a significantly increased benefit based on percent reduction in AHI compared with class 1 and 2., Level of Evidence: 1 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To comprehensively examine the characteristics and prognosis of bilateral sudden sensorineural hearing loss (BSSHL) and its subtypes compared to unilateral sudden sensorineural hearing loss (USSHL)., Data Sources: PubMed, Scopus, and CINAHL., Review Methods: Databases were searched from inception to December 5, 2023, for studies reporting patient characteristics and audiometric outcomes for BSSHL and its simultaneous (Si-BSSHL) and sequential (Se-BSSHL) subtypes. Meta-analysis of continuous measures, proportions (%), mean differences (Δ), and odds ratio (OR) were performed., Results: Eleven studies were included, consisting of 368 patients with BSSHL and 2,705 patients with USSHL. The pooled prevalence among all SSHL cases was 88.1% (95% CI: 81.2%-93.6%) for USSHL and 11.9% (95% CI: 6.4% to 18.8%) for BSSHL. PTA improvement following treatment with steroids was significantly worse in patients with BSSHL (Δ15.3 dB; 95% CI: 14.6 to 15.9; p < 0.0001) compared to patients with USSHL. There was no significant difference in post-treatment PTA improvement between the BSSHL subtypes. Patients with Si-BSSHL were significantly less likely to have an idiopathic etiology (OR: 0.4; 95% CI: 0.2 to 0.8; p = 0.01) and significantly more likely to have an autoimmune disease etiology (OR: 27.4; 95% CI: 2.2 to 336.1; p = 0.01), comorbid cardiovascular disease (OR: 2.3; 95% CI: 1.1 to 5.1; p = 0.03), and comorbid hypertension (OR: 2.5; 95% CI: 1.6 to 3.8; p < 0.0001) compared to patients with USSHL., Conclusions: BSSHL is a considerably rarer form of SSHL with worse prognosis compared to USSHL. BSSHL, and Si-BSSHL in particular, has significantly greater associations with systemic pathologies compared to USSHL. Laryngoscope, 134:3883-3891, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Use of permanent hair dyes causes unintended oxidative damage during the short time frame of the dyeing process that leads to perceivable changes in the feel, manageability and appearance of hair. Moreover, after hair has been dyed, regular exposure to the sun as a key environmental stressor continues to stimulate additional oxidative damage and to induce newly developed hair colours to fade prematurely or undergo changes in colour quality., Objective: To document the utility of acetyl zingerone methyl ether (MAZ) as a newly designed haircare ingredient to afford extra protection against oxidative damage and safeguard the integrity of hair colour., Results: We demonstrate that MAZ is compatible chemically with the high alkaline conditions required for the colouring process and from theoretical calculations preferentially binds Fe and Cu ions relative to Ca or Zn ions. In model Fenton reactions MAZ effectively chelated active redox metals (Fe and Cu ions) in the presence of excess Ca +2 ions to inhibit the production of hydroxyl radicals, and in separate studies, MAZ neutralized singlet oxygen with greater efficiency than α-tocopherol by a factor of 2.5. When mixed into permanent dyes prior to hair tress application, MAZ significantly reduced combing forces, and SEM images led to substantial reductions in visual signs of surface damage. In a 28-day clinical study, relative to controls, mixing MAZ into hair dyes prior to application interfered neither with colour development nor with ability to cover grey hair and led to significant improvements in perceived attributes associated with hair's condition immediately following the dyeing process. Over a 28-day maintenance phase, especially between Day 14 and Day 28, continued use of shampoo and conditioner containing MAZ significantly preserved gloss measurements and hair colour in terms of longevity and colour quality as remaining desired and fresh compared to use of control shampoo and conditioner., Conclusion: This work establishes MAZ as a next-generation hair care ingredient for use in permanent dyes to attenuate oxidative damage and in shampoos and conditioners to promote longevity of hair colour and to maintain overall health and appearance of hair on a daily basis., (© 2024 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Objective: To characterize the pattern of hearing loss in Charcot-Marie-Tooth (CMT) disease to help guide clinical management., Databases Reviewed: CINAHL, PubMed, and Scopus., Methods: Two independent investigators selected studies on CMT patients with pure-tone average (PTA) and auditory brainstem response (ABR) data. Case reports, case series <5 patients, and data that overlapped with another study were excluded. Investigators performed data extraction, quality rating, and risk-of-bias assessment using the Newcastle-Ottawa Scale. Meta-analysis of mean difference using fixed/random effects models was used. Also, data were analyzed using a weighted one-way analysis of variance, with post-hoc Tukey's test for comparison., Results: Ultimately, 6 prospective studies (N = 197) were included. The most common demyelinating subtype (CMT1A) had significantly prolonged ABR latency values across wave III (0.20 ms, 95% confidence interval [CI]: 0.05-0.35), wave V (0.20 ms, 95% CI: 0.01-0.39), waves I-III (0.20 ms, 95% CI: 0.01-0.39), and waves I-V (0.20 ms, 95% CI: 0.01-0.39) when compared to matched controls. The autosomal recessive demyelinating subtype (CMT4C) had significantly worse PTA when compared to the most common subtype (CMT1A) (Δ 28.93 dB, 95% CI 18.34-39.52) and nondemyelinating subtype (CMT2A) (Δ 28.3 dB, 95% CI: 15.98-40.62)., Conclusions: Patients with CMT can present with a variety of phenotypes depending on the causative mutation. The ABR interpeak latency values for the most common demyelinating form of CMT are delayed when compared to matched controls. Most subtypes have normal hearing thresholds, apart from CMT4C, which presents with mild hearing loss on average., Competing Interests: The authors disclose no conflicts of interest. There was no external funding source for this project., (Copyright © 2024, Otology & Neurotology, Inc.)

Objective: To determine if librarian collaboration was associated with improved database search quality, search reproducibility, and systematic review reporting in otolaryngology systematic reviews and meta-analyses., Methods: In this retrospective cross-sectional study, PubMed was queried for systematic reviews and meta-analyses published in otolaryngology journals in 2010, 2015, and 2021. Two researchers independently extracted data. Two librarians independently rated search strategy reproducibility and quality for each article. The main outcomes include association of librarian involvement with study reporting quality, search quality, and publication metrics in otolaryngology systematic reviews and meta-analyses. Categorical data were compared with Chi-Squared tests or Fisher's Exact tests. Continuous variables were compared via Mann Whitney U Tests for two groups, and Kruskal-Wallis Tests for three or more groups., Results: Of 559 articles retrieved, 505 were analyzed. More studies indicated librarian involvement in 2021 (n=72, 20.7%) compared to 2015 (n=14, 10.4%) and 2010 (n=2, 9.0%) (p=0.04). 2021 studies showed improvements in properly using a reporting tool (p<0.001), number of databases queried (p<0.001), describing date of database searches (p<0.001), and including a flow diagram (p<0.001). Librarian involvement was associated with using reporting tools (p<0.001), increased number of databases queried (p<0.001), describing date of database search (p=0.002), mentioning search peer reviewer (p=0.02), and reproducibility of search strategies (p<0.001). For search strategy quality, librarian involvement was associated with greater use of "Boolean & proximity operators" (p=0.004), "subject headings" (p<0.001), "text word searching" (p<0.001), and "spelling/syntax/line numbers" (p<0.001). Studies with librarian involvement were associated with publication in journals with higher impact factors for 2015 (p=0.003) and 2021 (p<0.001)., Conclusion: Librarian involvement was associated with improved reporting quality and search strategy quality. Our study supports the inclusion of librarians in review teams, and journal editing and peer reviewing teams., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Rachel Whitney, Michael C. Shih, Tamar Gordis, Shaun A. Nguyen, Ted A. Meyer, Emily A. Brennan.)

Introduction: Nasal and sinus surgery, especially using endoscopy, relies upon adequate haemostasis to be safe and effective. Often other haemostatic methods, such as cautery are not viable, and other methods must be employed. This study examines the effectiveness of dexmedetomidine in controlled hypotension and for surgical field visibility in endoscopic sinus surgery and other nasal surgeries., Review Methods: A literature search was conducted in PubMed, Scopus, CINAHL and Central for randomised controlled trials using dexmedetomidine for controlled hypotension in adult patients undergoing endoscopic sinus surgery or other nasal surgery. Meta-analysis of mean differences and single means were performed., Results: Of 935 identified studies, 31 met the inclusion criteria. A statistically significant difference in Fromme-Boezaart surgical field visibility scores was found comparing dexmedetomidine to placebo (p < 0.00001) and propofol (p < 0.0001), but not other agents. A significant difference in intraoperative blood loss volume was found compared with placebo (51.5mL, p < 0.00001) and propofol (13.6mL, p < 0.0001), but not other agents., Conclusion: Dexmedetomidine demonstrated significantly improved surgical field visibility and blood loss volume compared with placebo and propofol, but not other agents. Dexmedetomidine is viable and useful for controlled hypotension in nasal surgery. Choice of controlled hypotension agent should follow patient and procedure-specific considerations., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objective: To develop a convolutional neural network-based computer vision model to recognize and track 2 mastoidectomy surgical instruments-the drill and the suction-irrigator-from intraoperative video recordings of mastoidectomies., Study Design: Technological development and model validation., Setting: Academic center., Methods: Ten 1-minute videos of mastoidectomies done for cochlear implantation by varying levels of resident surgeons were collected. For each video, containing 900 frames, an open-access computer vision annotation tool was used to annotate the drill and suction-irrigator class images with bounding boxes. A mastoidectomy instrument tracking module, which extracts the center coordinates of bounding boxes, was developed using a feature pyramid network and layered with DETECTRON, an open-access faster-region-based convolutional neural network. Eight videos were used to train the model, and 2 videos were used for testing. Outcome measures included Intersection over Union (IoU) ratio, accuracy, and average precision., Results: For an IoU of 0.5, the mean average precision for the drill was 99% and 86% for the suction-irrigator. The model proved capable of generating maps of drill and suction-irrigator stroke direction and distance for the entirety of each video., Conclusions: This computer vision model can identify and track the drill and suction-irrigator from videos of intraoperative mastoidectomies performed by residents with excellent precision. It can now be employed to retrospectively study objective mastoidectomy measures of expert and resident surgeons, such as drill and suction-irrigator stroke concentration, economy of motion, speed, and coordination, setting the stage for characterization of objective expectations for safe and efficient mastoidectomies., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: To evaluate the treatment efficacy of neuromodulation versus sham for the treatment of tinnitus., Data Sources: Cochrane Library, CINAHL, PubMed, Scopus., Review Methods: The Cochrane Library, CINAHL, PubMed, and Scopus were searched from inception through May 2023 for English language articles documenting "neuromodulation" and "tinnitus" stratified by sham-controlled randomized control trials with 40 or more patients. Data collected included Beck Anxiety Inventory, Beck Depression Inventory (BDI), Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire, and Visual Analog Scale. A Meta-analysis of continuous measures (mean) and proportions (%) were conducted., Results: A total of 19 randomized control trials (N = 1186) were included. The mean age was 48.4 ± 5.3 (range: 19-74), mean duration of tinnitus was 3.8 ± 3.4 years, 61% [56.2-65.7] male, and 55.7% [46-65] with unilateral tinnitus. The short-term effect of transcutaneous electrical nerve stimulation and transcranial direct current stimulation on THI score is -16.2 [-23.1 to -9.3] and -19 [-30.1 to -7.8], respectively. The long-term effect of repetitive transcranial magnetic stimulation on THI score is -8.6 [-11.5 to -5.7]. Transcranial direct current stimulation decreases BDI score by -11.8 [-13.3 to -10.3]., Conclusion: As measured by the Tinnitus Handicap Index, our findings suggest the effects of transcutaneous electrical nerve stimulation and transcranial direct current stimulation reach significant benefit in the short term, whereas repetitive transcranial magnetic stimulation reaches significant benefit in the long term. Based on the BDI, transcranial direct current stimulation significantly reduces comorbid depression in patients with tinnitus., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: The aim was to analyze the global impact of the COVID-19 pandemic and national lockdowns on the incidence of otitis media (OM), a common otolaryngologic disease., Data Sources: PubMed, Scopus, and CINAHL., Review Methods: A systematic review and meta-analysis were performed using PRISMA reporting guidelines. OM incidence (measured as newly diagnosed OM cases over total patients seen over a time period), OM antibiotic prescriptions (OM cases for which antibiotics were prescribed over total OM cases), and tympanostomy tube surgeries (all tympanostomy tube surgeries over total surgical cases) were extracted. Meta-analysis of proportions and comparison of proportions were performed., Results: Of 1004 studies screened, 26 studies in 11 countries met inclusion criteria. The percentages of OM cases pre- and during-lockdown were 6.67%, 95% CI [4.68%, 8.99%], and 2.63% [2.02%, 3.31%], respectively, with an OR of 0.31 favoring during-lockdown [0.25, 0.39] (p < 0.00001). Antibiotic prescriptions per all OM episodes pre- and during-lockdown were 1.61% [0.17%, 8.46%] and 0.62% [0.07%, 3.32%], with an OR of 0.37 favoring during-lockdown ([0.35, 0.40], p < 0.00001). Tympanostomy tube surgery proportions pre- and during-lockdown were 31.64% [6.85%, 64.26%] and 29.99% [4.14%, 66.55%], with an OR of 0.94 favoring neither during- nor pre-lockdown [0.45, 2.00] (p = 0.88)., Conclusion: The incidence of OM decreased significantly following international lockdowns due to the COVID-19 pandemic, with antibiotic prescriptions for OM episodes showing a corresponding decrease. Despite these reductions, numbers of tympanostomy tube procedures did not change significantly. These reductions are likely due to social distancing, decreased exposure through high transmission facilities such as day cares, decreased health care utilization, and even possibly decreased air pollution. Laryngoscope, 134:2028-2037, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To characterize the short-term outcomes of patients undergoing surgical repair of lateral skull base cerebrospinal fluid (CSF) leaks followed by a shortened length of stay (LOS) protocol., Study Design: Retrospective study., Setting: Tertiary medical center., Methods: A total of 156 adult patients from July 2016 to December 2022 who underwent repair of CSF leaks via transmastoid (TM), middle cranial fossa (MCF), or combined (TM/MCF) approaches were included. Data collected included: LOS, presentation to the emergency department (ED), need for readmission, major neurologic complications (stroke, seizure, and meningitis), and CSF leak recurrence., Results: Approximately half of patients underwent a TM repair (49.4%), whereas the other half underwent either an MCF (3.8%) or combined TM/MCF repair (46.8%). No peri-/postoperative lumbar drains were used and only 2 (1.3%) patients were admitted to the intensive care unit after surgery. Mean LOS for the cohort was 1.1 ± 0.7 days and was longer for surgeries involving MCF (1.3 ± 0.6) compared to TM (0.8 ± 0.7). Ninety-two percent of TM cases were discharged within 24 hours (32% on the same day) while for cases involving an MCF approach, 72.2% of patients were discharged within 24 hours. Of the patients in the study, 6 (3.8%) presented to an ED for minor complications and no patient required readmission. Revision surgery was required for 3 (1.9%) patients for recurrent CSF leak., Conclusion: Our findings suggest that short LOS after surgical repair of lateral skull base defects in the treatment of CSF leak is safe and effective., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: To characterize the opioid prescribing patterns for and requirements of patients undergoing repair of spontaneous cerebrospinal fluid (sCSF) leaks of the lateral skull base., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: Adults with lateral skull base sCSF leaks who underwent repairs between September 1, 2014, and December 31, 2020., Main Outcome Measure: Mean morphine milligram equivalents (MMEs) of opioids dispensed to inpatients and prescribed at discharge, additional pain control medications dispensed, and outpatient additional opioid requests were compared between groups., Results: Of 78 patients included, 46 (59%) underwent repair via a transmastoid (TM), 6 (7.7%) via a middle cranial fossa (MCF), and 26 (33.3%) via a combined TM-MCF approach. Inpatients received a mean of 21.3, 31.4, and 37.6 MMEs per day during admission for the TM, MCF, and combined TM-MCF approaches, respectively ( p = 0.019, ηp 2 = 0.101). Upon discharge, nearly all patients (n = 74, 94.9%) received opioids; 27.3, 32.5, and 37.6 MMEs per day were prescribed after the TM, MCF, and TM-MCF approaches, respectively ( p = 0.015, ηp 2 = 0.093). Five (6.4%) patients requested additional outpatient pain medication, after which three were prescribed 36.7 MMEs per day. Patients with idiopathic intracranial hypertension required significantly more inpatient MMEs than those without (41.5 versus 25.2, p = 0.02, d = 0.689), as did patients with a history of headaches (39.6 versus 23.6, p = 0.042, d = 0.684)., Conclusions: Patients undergoing sCSF leak repair via the MCF or TM-MCF approaches are prescribed more opioids postoperatively than patients undergoing the TM approach. Patients with a history of headaches or idiopathic intracranial hypertension might require more opioids postoperatively., Competing Interests: Conflicts of Interest: None., (Copyright © 2024, Otology & Neurotology, Inc.)

Objective: This review sought to determine the characteristics of adults diagnosed with new onset laryngomalacia including airway symptoms, laryngoscopic findings, treatments, and outcomes. Moreover, we wanted to highlight suspected limitations in the literature., Data Sources: Studies were identified through CINAHL, Cochrane Review, PubMed, and Scopus published between 1966 and 2023., Review Methods: The search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews checklist by 2 independent investigators. A meta-analysis of proportions and continuous measures was conducted., Results: Of the 1121 abstracts identified, 33 articles pertaining to laryngomalacia in the adult population were included. The most common presenting symptoms were stridor at rest (78.3%, 65.1-88.3) and dyspnea with exertion (83.8%, 64.8-96.3). The most suspected etiology was exercise-induced (86.0%, 69.4-95.5), and the most common description of laryngomalacia on visualization was collapse of supraglottic structures during exercise (93.3%, 79.0-99.1). Nonsurgical options were attempted in 87.0% (54.0-99.1), which included oral appliances, respiratory retraining, breathing techniques, and working with a speech pathologist. Surgical options were ultimately performed in 84.2% (75.0-91.0). Complete resolution of symptoms following therapy was seen in 61.9% (48.0-74.6)., Conclusion: Adult onset laryngomalacia is difficult to characterize. It typically presents in patients during exercise, with neurological injury, or idiopathically. Surgical management can lead to improvement or complete resolution of symptoms. The need for a universal nomenclature is highlighted in this review, as it is inconsistently classified., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment., Data Sources: CINAHL, PubMed, and Scopus were searched for articles from conception to October 2022. MESH and key terms such as "tinnitus," "placebo," and "medication" were used to find randomized, placebo-controlled trials. The search was limited to articles in English., Methods: Randomized controlled trials with adult subjects evaluating tinnitus pretreatment and posttreatment with an oral or intratympanic medication versus a placebo arm were included. Crossover studies, studies involving middle/inner ear operations or devices, and studies that exclusively included nonidiopathic etiologies of tinnitus were excluded. Mean tinnitus symptom survey scores for the Tinnitus Handicap Inventory (THI), Tinnitus Severity Index, Tinnitus Functional Index, Tinnitus Handicap Questionnaire, and Visual Analog Scales for tinnitus Intensity/Loudness (VAS-L), Annoyance (VAS-An), and Awareness (VAS-Aw) were extracted for both placebo and experimental groups., Results: 953 studies were screened with 23 studies being included in the final analysis. Meta-analysis of mean difference (MD) was calculated using RevMan 5.4. MD between pretreatment and posttreatment THI scores of the placebo arms was 5.6 (95% confidence interval, 3.3-8.0; p < 0.001). MD between pretreatment and posttreatment VAS scores of the placebo groups for Loudness, Annoyance, and Awareness were 0.8 (0.0 to 1.6, p = 0.05), 0.2 (-0.2 to 0.5, p = 0.34), and 0.3 (-0.0 to 0.7, p = 0.08), respectively., Conclusions: Placebo treatment has shown effectiveness in improving patient-reported evaluations of tinnitus when using some standardized metrics such as THI and VAS-L; however, the improvement is not as substantial as nonplacebo treatment., Competing Interests: The authors received no financial support for the research, authorship, and/or publication of this article. The authors declare that there are no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Purpose: Meniere's Disease is a condition known for its recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. Previous studies have demonstrated significant influence of placebo treatments. Our objective was to quantify the magnitude of the placebo effect in randomized controlled trials for Meniere's Disease., Materials and Methods: A systematic review was performed by searching PubMed, SCOPUS, CINAHL, and Cochrane databases from inception through September 27, 2022. Data extraction, quality rating, and risk of bias assessment were performed by two independent reviewers. A meta-analysis of mean differences with 95 % confidence interval, weighted summary proportions, and proportion differences were calculated using random and fixed effects models., Results: A total of 15 studies (N = 892) were included in the review. Significant improvement was seen in the functional level scores of the pooled placebo groups, with a mean difference of -0.6 points, (95%CI: -1.2 to -0.1). There was no difference in pure tone audiometry, speech discrimination score, or vertigo frequency at 1 and 3 months for the placebo group. Patient-reported vertigo episodes were improved in 52.5 % (95%CI: 39.2 to 65.5) of the placebo group and was significantly less than the pooled experimental group (90.1 %, 95%CI: 39.2 to 65.5, p < 0.001)., Conclusions: The placebo effect in Meniere's Disease trials is associated with some symptomatic improvement in subjective outcomes, such as patient reported vertigo episodes. However, the clinical significance is questionable across other outcomes measures, especially when analyzing objective data. The extent and strength of the placebo effect continues to be a hurdle in the search for better treatment options., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare quality of life (QOL) outcomes of percutaneous and transcutaneous bone conduction devices (pBCD and tBCD, respectively)., Databases Reviewed: Pubmed, Scopus, CINAHL., Methods: A systematic review was performed searching for English language articles from inception to March 15, 2023. Studies reporting QOL outcomes measured using a validated tool following implantation of either pBCDs or tBCDs were considered for inclusion. QOL outcomes included scores for Glasgow Benefit Inventory, Glasgow Children's Benefit Inventory, Abbreviated Profile of Hearing Aid Benefit, and the Speech, Spatial, and Qualities of Hearing Scale. A meta-analysis of continuous measures was performed., Results: A total of 52 articles with 1,469 patients were included. Six hundred eighty-nine patients were implanted with pBCDs, and the remaining 780 were implanted with tBCDs. Average Glasgow Benefit Inventory scores for the tBCD group (33.0, 95% confidence interval [22.7-43.3]) were significantly higher than the pBCD group (30.9 [25.2-36.6]) (Δ2.1 [1.4-2.8], p < 0.0001). Mean Glasgow Children's Benefit Inventory scores (Δ3.9 [2.0-5.8], p = 0.0001) and mean gain in Abbreviated Profile of Hearing Aid Benefit scores (Δ5.6 [4.8-6.4], p < 0.0001) were significantly higher among patients implanted with tBCDs than those implanted with pBCDs. Patients implanted with tBCDs also had significantly higher gains on the Speech (Δ1.1 [0.9-1.3], p < 0.0001), Spatial (Δ0.8 [0.7-0.9], p < 0.0001), and Qualities of Hearing (Δ1.2 [1.1-1.3], p < 0.0001) portions of the Speech, Spatial, and Qualities of Hearing Scale than those implanted with pBCDs., Conclusions: Patients implanted with transcutaneous devices had better QOL outcomes than those implanted with percutaneous devices., Competing Interests: Conflicts of interest: The authors report no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Despite uncertain efficacy, cannabinoids and derived products are becoming increasingly used in the field of palliative care for oncologic patients. Cannabinoids chiefly include psychoactive tetrahydrocannabinol (THC) and nonpsychoactive cannabidiol (CBD). Use of and research interest in THC, CBD, and combination THC/CBD products have increased in recent years, particularly after the Agriculture Improvement Act of 2018 made cannabis plants with <0.3% THC no longer controlled substances, and many states recently legalized THC use altogether. To provide an updated review of this topic, we reviewed randomized controlled trials with >50 patients studying cannabinoid use in cancer patients. We found that THC products, including THC and THC/CBD combination products, are helpful for treating chemotherapy-induced nausea/vomiting. CBD products were not helpful for this indication. For most other studied indications (anorexia/cachexia, mood, general global symptoms), there was no convincing evidence to support widespread cannabinoid use in cancer symptom management. The evidence for treating cancer-related pain with THC/CBD products is somewhat conflicting. We conclude that, apart from using THC products to treat chemotherapy-induced nausea/vomiting, cannabinoid products should not be routinely recommended for cancer supportive care. Further research in the form of large randomized controlled trials is warranted in this area., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2024 Baylor University Medical Center.)

Objective: To compare audiometric outcomes, complications, and revisions required for percutaneous (pBCD) versus transcutaneous (tBCD) implantable bone-conduction devices for the treatment of hearing loss associated with congenital aural atresia (CAA).Databases Reviewed.PubMed, Scopus, CINAHL., Methods: A systematic review was performed searching for English language articles from inception to December 14, 2022. Studies reporting audiometric outcomes or complications for either pBCDs or tBCDs for the treatment of CAA were selected for inclusion. A meta-analysis of single means and meta-analysis of proportions with comparison (Δ) of weighted proportions was conducted., Results: A total of 56 articles with 756 patients were selected for inclusion. One hundred ninety patients were implanted with pBCDs, whereas the remaining 566 were implanted with tBCDs. Mean pure-tone audiometry improvement in the pBCD group (39.1 ± 1.1 dB) was significantly higher than in the tBCD group (34.6 ± 1.6 dB; Δ4.5 dB; 95% confidence interval, 4.2-4.7 dB; p < 0.0001). The average improvement in speech reception threshold was 38.6 ± 2.5 dB in the percutaneous group as compared with 32.7 ± 1.6 dB in the transcutaneous group (Δ5.9 dB [5.3-6.5 dB], p < 0.0001). Overall complication rates for patients implanted with pBCDs and tBCDs were 29.0% (15.7-44.4%) and 9.4% (6.5%-13.0%), respectively (Δ19.6% [12.0-27.7%], p < 0.0001)., Conclusions: Patients with CAA implanted with pBCDs had significantly better audiometric outcomes than those implanted with tBCDs. However, complication rates were significantly higher among the pBCD group., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

This article's objective is to present the latest evidence and information on the management of postoperative nausea and vomiting (PONV). PONV continues to affect 30% of the surgical population causing patient dissatisfaction, extending length of stay, and increasing overall costs. This review includes the introduction of 2 new intravenous formulations of antiemetics (amisulpride, aprepitant), updates on nontraditional therapies, suggestions for combination prophylaxis, emerging data on rescue treatment, and considerations for special populations and settings. Both of the new antiemetics provide promising options for pharmacologic interventions for PONV with favorable safety profiles., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To perform a systematic review of otolaryngologic presentation rates to emergency department settings before and after lockdown due to the COVID-19 pandemic., Sources: PubMed, Scopus, and CINAHL., Methods: A systematic search was conducted following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses) for studies describing otolaryngologic presentations to emergency department and rapid access clinic settings both in the before-lockdown and after-lockdown periods. The start of after-lockdown period varied based on initiation of lockdown, ranging from March 1st to June 1st of 2020 across general emergency department studies., Results: A total of 14 studies were included in this review. About 10 were general emergency departments, 3 were specifically pediatric emergency departments, and 1 study focused on the geriatric population (>65 years). A total of 13 790 patients were included, with 9446 in the before-lockdown period (68.5%) and 4344 in the after-lockdown period (31.5%). Meta-analysis of proportions for otolaryngologic presentations across general emergency departments was performed. Comparison of weighted proportions found significant differences between before-lockdown and after-lockdown presentation rates for infectious etiologies, tonsillitis specifically, foreign bodies, non-infectious airway issues, and epistaxis among these studies., Conclusions: The increased proportions of various non-infectious presentations (eg, epistaxis, foreign bodies, and airway issues) following lockdown might be associated with proportional decreases in infectious pathologies, given decreased social contact to prevent SARS-CoV-2 transmission. Overall, it is important for otolaryngologists to recognize what presentations might more commonly be seen and require evaluation and potential intervention in light of a global pandemic.

Objective: To compare the presentation and outcomes of patients with and without obstructive eustachian tube dysfunction (oETD) undergoing repair of lateral skull base spontaneous cerebrospinal fluid (sCSF) leaks., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: Adults with lateral skull base sCSF leaks who underwent repairs from January 1, 2011, to December 31, 2020, were collected., Main Outcome Measure: Comparative statistics and effect sizes were used to compare clinical features, operative findings, and outcomes between groups., Results: Of 92 ears from 89 patients included, 51.1% (n = 47) had oETD. There were no differences in demographics between patients with and without oETD. Mean age was 60.7 ± 13.1 versus 58.5 ± 12.8 years ( d = -0.17 [-0.58 to 0.24]), mean body mass index was 33.8 ± 8.5 versus 36.0 ± 8.0 kg/m 2 ( d = 0.27 [-0.14 to 0.68]), and female sex preponderance was 59.6% (n = 28) versus 68.8% (n = 31; Φ = -0.09), respectively. There were no differences in the radiologic number, size, and locations of defects. Patients with oETD had less pneumatized mastoids than those without oETD ( p = 0.001; Φ = 0.43). Mean change from preoperative to postoperative air pure-tone average for those with and without oETD was -1.1 ± 12.6 versus 0.1 ± 17.2 dB ( d = 0.09 [-0.04 to 0.58]), respectively. Six ears (6.5%; three with and three without oETD) underwent revisions for rhinorrhea/otorrhea between 5 and 28 months postoperatively, during which four leaks were found, the two patients without leaks had oETD., Conclusions: The presentation of sCSF leaks and outcomes of repairs in patients with oETD do not differ from those without oETD. Although postoperative otorrhea might represent an inflammatory or infectious process in patients with oETD, reexploration is warranted if patients do not improve with conservative treatment., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: To compare audiometric outcomes, complications, and revisions required for implantable bone-conduction devices (BCDs) versus atresia surgery for the treatment of hearing loss associated with congenital aural atresia., Databases Reviewed: PubMed, Scopus, CINAHL., Methods: Databases were searched for English articles from inception to July 1, 2022, for studies reporting audiometric outcomes or complications for either BCDs or atresia surgery for the treatment of congenital aural atresia. Main outcome measures included pure-tone audiometry, air-bone gap, speech reception threshold, associated complications, and rates of revision for each treatment option., Results: We identified 973 abstracts, of which 89 were selected for data extraction and analysis. A total of 2,611 patients were included, 1,901 in the atresia surgery group and 710 in the BCDs group. A meta-analysis of single means was conducted for age and audiometric outcomes, and a meta-analysis of proportions was conducted for complications and revisions. The average short-term improvement in pure-tone audiometry for the BCDs group was 34.4 ± 1.6 dB compared with 22.4 ± 1.5 dB for the atresia surgery group, representing a significant difference (12.0 dB; 95% confidence interval, 11.9-12.2; p < 0.0001). A smaller proportion of complications were reported in the devices group (16.9%) compared with the atresia surgery group (45.7%). In addition, a smaller proportion of cases in the devices group required some degree of revision (17.8%) compared with the atresia surgery group (23.0%)., Conclusions: This study demonstrates that implantable BCDs have significantly better audiometric outcomes as well as a lower rate of complications and revisions required compared with atresia surgery., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Despite the availability of several classes of antiemetics, postoperative nausea and vomiting (PONV) remains a substantial burden for patients following surgery, resulting in patient dissatisfaction and prolonged stays in post-anesthesia care units and ultimately increasing the cost of care. Enhanced recovery protocols and PONV management guidelines are now centered on the assessment of the individual patient's risk for developing PONV, as well as multimodal prophylaxis using antiemetics targeting different mechanisms of action. Over the last two decades, the neurokinin-1 receptor (NK1R) has emerged as a therapeutic target for the management of PONV. This review of the literature explains the role of the NK1R and its ligand-substance P-in vomiting, describes the pharmacologic and pharmacokinetic properties of NK1R antagonists (NK1RAs) and summarizes the clinical evidence supporting NK1RAs for PONV prophylaxis in patients undergoing surgery. In particular, we discuss the therapeutic application of NK1RA in PONV prophylaxis protocols owing to their advantages over other antiemetic classes in efficacy, duration of efficacy, safety, pharmacology, and ease of administration. Future studies will be aimed at further investigating the efficacy and safety of NK1RA-based multimodal combinations, particularly among vulnerable populations (e.g., children and elderly)., (© 2023 Heron Therapeutics. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Objective: The process of cochlear implantation (CI) and subsequent post-cochlear implant care is extensive and can be difficult to navigate for patients considered medically frail. This study investigates potential impact of patient frailty on speech recognition and quality of life outcomes after CI., Study Design: Retrospective review of a prospectively maintained database., Setting: Tertiary cochlear implant center., Patients: Three hundred seventy adults undergoing CI for traditional bilateral hearing loss indication., Interventions: None., Main Outcome Measures: Comparison of pre-CI to 12-month post-CI change in consonant-nucleus-consonant phoneme/words, AzBio sentences in quiet/+10SNR, and Cochlear Implant Quality of Life (CIQOL)-35 Profile domain and global scores based on degree of patient frailty as assessed using the five-factor modified frailty index and Charlson Comorbidity Index., Results: The average age at implantation was 65.4 years (±SD, 15.7; 19-94 years). Overall, there were minimal to absent and nonsignificant differences in speech recognition outcomes (consonant-nucleus-consonant phoneme/words, and AzBio sentences +10SNR) based on pre-CI patient frailty. The exception was less improvement in AzBio quiet sentence score in patients noted to be severely frail based on Charlson Comorbidity Index (57.1% vs. 35.2%, d = 0.7 [0.3, 1]). Similar findings were observed for CIQOL-35 Profile domain and global scores where no associations were found other than decreased improvement in the social domain in patients noted to be severely frail (21.7 vs. -0.3, d = 1 [0.4, 1.7])., Conclusions: Although some differences in outcomes were noted based on cochlear implant user frailty, these were small and isolated to only a few outcome measures. Therefore, assuming the patient is medically safe for surgery, preoperative frailty should not dissuade clinicians from recommending CI., Competing Interests: Conflicts of Interest and Source of Funding: None., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: To determine if body mass index (BMI) increases the risk of cerebrospinal fluid (CSF) leak after lateral skull base surgery., Data Sources: CINAHL, PubMed, and Scopus were searched from January 2010 to September 2022 for articles published in English., Study Selection: Articles that reported BMI or obesity with and without CSF leaks after lateral skull base surgery were included., Data Extraction: Two reviewers (F.G.D. and B.K.W.) independently performed study screening, data extraction, and risk of bias assessment., Data Synthesis: A total of 11 studies and 9,132 patients met inclusion criteria. Meta-analysis of mean difference (MD), odds ratio (OR), proportions, and risk ratio (RR) were calculated using RevMan 5.4 and MedCalc 20.110. BMI for patients with CSF leak after lateral skull base surgery (29.39 kg/m 2 , 95% confidence interval [CI] = 27.75 to 31.04) was significantly greater than BMI for patients without CSF leak after lateral skull base surgery (27.09 kg/m 2 , 95% CI = 26.16 to 28.01) with an MD of 2.21 kg/m 2 (95% CI = 1.09 to 3.34, p = 0.0001). The proportion of patients with BMI ≥ 30 kg/m 2 that had a CSF leak was 12.7%, and the proportion of patients with BMI < 30 kg/m 2 (control) that had a CSF leak was 7.9%. The OR for CSF leak after lateral skull base surgery in patients with BMI ≥ 30 kg/m 2 was 1.94 (95% CI = 1.40 to 2.68, p < 0.0001), and the RR was 1.82 (95% CI = 1.36 to 2.43, p < 0.0001)., Conclusion: Elevated BMI increases the risk of CSF leak after lateral skull base surgery., Level of Evidence: IIa., Competing Interests: Conflicts of interest and financial disclosure: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: To determine if simultaneous administration of acoustic vibration and oscillating expiratory pressure affects the severity of facial pain among patients with complaint of "sinus headache"., Methods: This is a prospective single-arm observational study performed at a tertiary care medical center. Subjects with complaint of sinus headache without evidence of chronic rhinosinusitis on exam or computed tomography participated in a clinical study applying simultaneous acoustic vibrations and positive expiratory pressure to the nasal cavity twice daily over 4 weeks. Efficacy was assessed using three validated pain metrics-pain visual analog scale (VAS), brief pain inventory-short form (BPI-SF), and McGill pain questionnaire-short form (MPQ-SF). Device safety and patient satisfaction were also assessed using questionnaires., Results: Twenty-nine patients (mean age 49 years, 55% female) completed the study without any major adverse events. At the 4 week follow-up, facial pain VAS improved from mean ± SD of 59.6 ± 15.7 to 34.6 ± 21.7 ( p  < .001), BPI mean pain (mean ± standard deviation) improved from 4.4 ± 2.0 to 2.9 ± 1.9 ( p  = .007), and MPQ-SF total improved from 12.2 ± 6.5 to 6.5 ± 5.2 ( p  < .001) with approximately 70% of patients achieving a minimal clinically important difference (MCID) across all metrics. Additionally, pain VAS was assessed 5 min after a single use at baseline with significant improvement ( p  < .001). Eighty-six percent of subjects would both use device again and recommend it to others., Conclusions: Simultaneous administration of acoustic vibration and oscillating expiratory pressure appears to be a safe treatment for sinus headaches in patients without objective evidence of chronic sinusitis. Results from this initial study are promising with regard to efficacy in treatment of sinus headaches but will require further study., Level of Evidence: 2c., Competing Interests: None., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Microsurgical operations such as middle ear surgery rely heavily on visibility of the surgical field. Anesthetic techniques such as controlled hypotension have been developed to improve surgical field visibility by attempting to decrease bleeding. Many agents have been utilized to achieve controlled hypotension intraoperatively. Dexmedetomidine is a relatively newer agent which works on alpha-2 receptors to decrease sympathetic tone. This paper sought to determine the efficacy of dexmedetomidine for optimizing surgical field visibility in MES., Methods: A comprehensive search strategy was used in PubMed, SCOPUS, CINAHL, and CENTRAL through August 9, 2022 for this systematic review and meta-analysis., Inclusion Criteria: adult patients undergoing middle ear surgery with dexmedetomidine used for controlled hypotension to improve surgical field visibility. Risk of bias was assessed via Cochrane RoB 2. Meta-analysis of mean difference for surgical field scores and risk ratios for positive surgical field scores were used to compare dexmedetomidine with placebo or other agents., Results: Fourteen studies were included in this review. Statistically significant mean difference was found to favor dexmedetomidine over placebo for Fromme-Boezaart surgical field scores. Statistically significant results were also demonstrated favoring dexmedetomidine over other agents in risk ratio for receiving positive surgical field scores, as well as surgeon and patient satisfaction scores., Conclusions: Controlled hypotension is an invaluable tool for surgical field visibility. Improved surgical field visibility was observed with dexmedetomidine compared with placebo and various other agents. Risk of sub-optimal bleeding scores was significantly lower with dexmedetomidine. Dexmedetomidine is effective at improving surgical field visibility in middle ear surgery., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Xylose is the second most abundant monomeric sugar in plant biomass. Consequently, xylose catabolism is an ecologically important trait for saprotrophic organisms, as well as a fundamentally important trait for industries that hope to convert plant mass to renewable fuels and other bioproducts using microbial metabolism. Although common across fungi, xylose catabolism is rare within Saccharomycotina, the subphylum that contains most industrially relevant fermentative yeast species. The genomes of several yeasts unable to consume xylose have been previously reported to contain the full set of genes in the XYL pathway, suggesting the absence of a gene-trait correlation for xylose metabolism. Here, we measured growth on xylose and systematically identified XYL pathway orthologs across the genomes of 332 budding yeast species. Although the XYL pathway coevolved with xylose metabolism, we found that pathway presence only predicted xylose catabolism about half of the time, demonstrating that a complete XYL pathway is necessary, but not sufficient, for xylose catabolism. We also found that XYL1 copy number was positively correlated, after phylogenetic correction, with xylose utilization. We then quantified codon usage bias of XYL genes and found that XYL3 codon optimization was significantly higher, after phylogenetic correction, in species able to consume xylose. Finally, we showed that codon optimization of XYL2 was positively correlated, after phylogenetic correction, with growth rates in xylose medium. We conclude that gene content alone is a weak predictor of xylose metabolism and that using codon optimization enhances the prediction of xylose metabolism from yeast genome sequence data., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The cumulative damage skin sustains from exposure to environmental stressors throughout life exerts significant effects on skin aging and cancer development. One of the main ways by which environmental stressors mediate their effects within skin is through induction of reactive oxygen species (ROS). In this review, we chronicle the multiple properties by which acetyl zingerone (AZ) as a skincare ingredient can benefit skin (1) by helping manage overproduction of ROS through multiple routes as an antioxidant, physical quencher and selective chelator, (2) by fortifying protection after UV exposure ends to prevent the type of epidermal DNA damage that correlates with development of skin cancer, (3) by modulating matrisome activity and nurturing the integrity of the extracellular matrix (ECM) within the dermis and (4) through its proficient ability to neutralize singlet oxygen, by stabilizing the ascorbic acid precursor tetrahexyldecyl ascorbate (THDC) in the dermal microenvironment. This activity improves THDC bioavailability and may blunt pro-inflammatory effects of THDC, such as activation of type I interferon signaling. Moreover, AZ is photostable and can sustain its properties during UV exposure, in contrast to α-tocopherol. All these properties of AZ translate into measurable clinical benefits to improve the visual appearance of photoaged facial skin and to strengthen the skin's own defenses against sun damage.

Objectives: To examine patterns of change and plateau in speech recognition scores in postlingually hearing impaired adult cochlear implant recipients. The study also examines variations in change patterns for different speech materials and testing conditions., Study Design: Used systematic review with meta-analysis., Methods: Articles in English reporting speech recognition scores of adults with postlingual hearing loss at pre-implantation and at least two post-implantation time points were included. Statistically significant changes were determined by meta-analysis and the 95% confidence interval., Results: A total of 22 articles representing 1954 patients were included. Meta-analysis of mean difference demonstrated significant improvements in speech recognition score for words in quiet (37.4%; 95% confidence interval [34.7%, 40.7%]), sentences in quiet (49.4%; 95% confidence interval [44.9%, 53.9%]), and sentences in noise (30.8%; 95% confidence interval [25.2%, 36.4%]) from pre-op to 3 months. Scores continued to increase from 3 to 12 months but did not reach significance. Similarly, significant improvements from pre-op to 3 months were observed for consonant nucleus consonant (CNC) words in quiet (37.1%; 95% confidence interval [33.8%, 40.4%]), hearing in noise test (HINT) sentences in quiet (46.5%; 95% confidence interval [37.0%, 56.0%]), AzBio sentences in quiet (45.9%; 95% confidence interval [44.2%, 47.5%]), and AzBio sentences in noise (26.4%; 95% confidence interval [18.6%, 34.2%]). HINT sentences in noise demonstrated improvement from pre-op to 3 months (35.1%; 95% confidence interval [30.0%, 40.3%]) and from 3 to 12 months (15.5%; 95% confidence interval [7.2%, 23.8%])., Conclusions: Mean speech recognition scores demonstrate significant improvement within the first 3 months, with no further statistically significant improvement after 3 months. However, large individual variation should be expected and future research is needed to explain the sources of these individual differences. Laryngoscope, 133:1014-1024, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To determine if exfoliation syndrome (XFS) is associated with hearing loss (HL) or vestibular dysfunction., Data Sources: PubMed, Scopus, CINAHL, and Cochrane Library through April 1, 2022., Review Methods: Two reviewers independently screened abstracts, selected articles for inclusion, and extracted data. Studies included for qualitative analysis conducted audiometric, tympanometric, or vestibular evaluations on all subjects., Results: Twenty-one publications (1148 patients with XFS and 1212 controls) were included in the systematic review, and 16 publications (968 patients with XFS and 1147 controls) in the meta-analysis. Greater severity of HL was seen for patients with XFS compared to controls across all frequencies (odds ratio [OR] 8.8 [7.3-10.2]). Patients with XFS were more likely to have moderate to profound sensorineural HL (OR 1.8 [1.3-2.5]), and less likely to have none to mild HL (OR 0.34 [0.17-0.67]) or no HL (OR 0.37 [0.28-0.50]). Three studies found patients with XFS had lower tympanometric peaks. Two studies found that abnormal vestibular testing results could be more common for patients with XFS., Conclusions: HL is associated with XFS. A sensorineural component to HL is confirmed, and mixed HL is possible. Given the high prevalence and infrequent diagnosis of XFS, the authors hypothesize that the current understandings of presbycusis might be improved by further investigation in XFS. Laryngoscope, 133:1025-1035, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To determine the prevalence of polypharmacy in patients presenting with dizziness to a tertiary neurotology clinic and analyze the association between polypharmacy and clinical characteristics., Design: Retrospective, cross-sectional review. Demographics, symptoms, diagnoses, medications, audiometry, dizziness handicap index (DHI) scores, and cognitive failure questionnaire (CFQ) scores were extracted from charts of patients seen as new patients from September 1, 2019, to March 31, 2020, with a primary complaint of dizziness., Results: A total of 382 patients were included. More than two-thirds of the patients (n = 265, 69.4%) met criteria for polypharmacy (≥5 medications), of which most (n = 249, 94.0%) were prescribed a potentially ototoxic drug. Approximately 10% of patients were taking five or more ototoxic medications (oto-polypharmacy). Polypharmacy was correlated to age and was more common for patients with diabetes, hypertension, other cardiovascular comorbidities, and depression (odds ratio [OR], 3.73-6.67; p < 0.05). Polypharmacy was twice as likely in patients with mild to moderate hearing loss (OR 2.02 [1.24-3.29] and OR 2.13 [1.06-4.27], respectively; p < 0.05) and ~1.5× more likely in patients who had moderate to severe DHI scores (OR 1.65 [1.05-2.59] and OR 1.63 [1.00-2.65], respectively; p < 0.05). Patients with polypharmacy also had higher CFQ scores compared to those without polypharmacy (CFQ 32.5 [19.0-48.0] versus CFQ 25.0 [13.0-40.0]; p = 0.002. Oto-polypharmacy was more common for patients with lightheadedness as a dizziness descriptor (OR 3.16 [1.56-6.41]; p < 0.01). However, oto-polypharmacy was only more common for patients with mild to moderate hearing loss (OR 2.69 [1.33-5.45] and OR 2.86 [1.31-6.20], respectively; p < 0.01) and severe DHI scores (2.31 [1.12-4.77], p = 0.02)., Conclusions: The prevalence of polypharmacy in patients with vestibular disorders is high. Some of the medications that patients are on are also potentially ototoxic at variable degrees. Polypharmacy is more common when lightheadedness is one of the dizziness descriptors and seems to be associated with worse scores on patient-reported outcome measures (DHI, CFQ). Medication reconciliation and multidisciplinary involvement could help to better address polypharmacy in this patient population. However, further investigation is needed to elucidate polypharmacy's role in symptom presentation, vestibular testing results, and therapeutic strategies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To provide an updated comparison of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), respiratory disturbance index (RDI), oxygen saturation (O 2 sat), and lowest oxyhemoglobin saturation (LSAT) measured by portable sleep study devices (PSSDs) compared to polysomnography (PSG)., Data Sources: Primary studies were identified through PubMed, Scopus, CINAHL, and Cochrane., Review Methods: A systematic review was performed by searching databases from inception through August 2021. Only studies examining simultaneous monitoring of a PSSD and PSG were included.  Respiratory indices AHI, ODI, RDI, O 2 sat, and LSAT was collected Meta-correlations and meta-regressions were conducted to compare sleep variable measurements between PSSD and PSG., Results: A total of 24 studies (N = 1644 patients) were included. The mean age was 49.5 ± 12.0 (range = 13-92), mean body mass index (BMI) was 30.4 ± 5.7 (range = 17-87), and 69.4% were male. Meta-correlation showed significant associations between PSSD and PSG for AHI (n = 655, r = .888; p < .001), ODI (n = 241, r = .942; p < .001), RDI (n = 313, r = .832; p < .001), O 2 sat (n = 171, r = .858; p < .001), and LSAT (n = 197, r = .930; p < .001). Meta-regressions indicated significant predictive correlations for AHI (n = 655; r = .96; p < .001), ODI (n = 740; r = .75; p = .031), RDI (n = 197; r = .99; p = .005), and LSAT (n = 197; r = .85; p = .030), but not for O 2 sat (n = 171; r = .31; p = .692)., Conclusions: Respiratory indices correlate strongly between PSSD and PSG, which is further supported by meta-regressions results. PSSD might be a valuable cost and time-saving OSA screening tool., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Importance: Many cochlear implant centers screen patients for cognitive impairment as part of the evaluation process, but the utility of these scores in predicting cochlear implant outcomes is unknown., Objective: To determine whether there is an association between cognitive impairment screening scores and cochlear implant outcomes., Design, Setting, and Participants: Retrospective case series of adult cochlear implant recipients who underwent preoperative cognitive impairment screening with the Montreal Cognitive Assessment (MoCA) from 2018 to 2020 with 1-year follow-up at a single tertiary cochlear implant center. Data analysis was performed on data from January 2018 through December 2021., Exposures: Cochlear implantation., Main Outcomes and Measures: Preoperative MoCA scores and mean (SD) improvement (aided preoperative to 12-month postoperative) in Consonant-Nucleus-Consonant phonemes (CNCp) and words (CNCw), AzBio sentences in quiet (AzBio Quiet), and Cochlear Implant Quality of Life-35 (CIQOL-35) Profile domain and global scores., Results: A total of 52 patients were included, 27 (52%) of whom were male and 46 (88%) were White; mean (SD) age at implantation was 68.2 (13.3) years. Twenty-three (44%) had MoCA scores suggesting mild and 1 (2%) had scores suggesting moderate cognitive impairment. None had been previously diagnosed with cognitive impairment. There were small to medium effects of the association between 12-month postoperative improvement in speech recognition measures and screening positive or not for cognitive impairment (CNCw mean [SD]: 48.4 [21.9] vs 38.5 [26.6] [d = -0.43 (95% CI, -1.02 to 0.16)]; AzBio Quiet mean [SD]: 47.5 [34.3] vs 44.7 [33.1] [d = -0.08 (95% CI, -0.64 to 0.47)]). Similarly, small to large effects of the associations between 12-month postoperative change in CIQOL-35 scores and screening positive or not for cognitive impairment were found (global: d = 0.32 [95% CI, -0.59 to 1.23]; communication: d = 0.62 [95% CI, -0.31 to 1.54]; emotional: d = 0.26 [95% CI, -0.66 to 1.16]; entertainment: d = -0.005 [95% CI, -0.91 to 0.9]; environmental: d = -0.92 [95% CI, -1.86 to 0.46]; listening effort: d = -0.79 [95% CI, -1.65 to 0.22]; social: d = -0.51 [95% CI, -1.43 to 0.42])., Conclusions and Relevance: In this case series, screening scores were not associated with the degree of improvement of speech recognition or patient-reported outcome measures after cochlear implantation. Given the prevalence of screening positive for cognitive impairment before cochlear implantation, preoperative screening can be useful for early identification of potential cognitive decline. These findings support that screening scores may have a limited role in preoperative counseling of outcomes and should not be used to limit candidacy.

Objective: The use of computer-based auditory training (CBAT) after cochlear implantation is associated with improved speech recognition and real-world functional abilities. However, patient-related factors associated with CBAT use remain unknown. This study seeks to identify such factors and recognize those at risk for not implementing CBAT., Study Design: Prospective natural experiment., Setting: Tertiary academic center., Patients: A total of 117 new adult cochlear implant (CI) recipients with bilateral moderate-to-profound hearing loss., Interventions/main Outcome Measures: Patient demographic and lifestyle information, preimplantation aided speech recognition scores, Cochlear Implant Quality of Life (CIQOL) domain and global scores, CIQOL-Expectations scores, and CBAT use in the first 3 months after activation. Patient-related variables included age, sex, race, duration of hearing loss before implantation, hours of CI use per day, hearing-aid use before implantation, living arrangements/marital status, annual household income, employment, technology use, and education., Results: Overall, 33 new CI users (28.2%) used CBAT in the first 3 months after activation. On bivariate analysis of the pre-CI CIQOL scores, CIQOL-Expectations score, aided speech recognition scores, and demographic/lifestyle factors examined, regular use of smartphone, tablet, or computer technology was significantly associated with an increased likelihood of CBAT use (odds ratio, 9.354 [1.198-73.020]), whereas higher CIQOL-Expectations emotional domain scores were associated with a lower likelihood of CBAT use (d = -0.69 [-1.34 to -0.05]). However, using multivariable analysis to control for potential confounding factors revealed no significant associations between CBAT use in the first 3 months after cochlear implantation and any examined factor., Conclusions: No associations between patient demographic, lifestyle, or pre-CI speech recognition and patient-reported outcome measures and CBAT use were identified. Therefore, discussions with all patients after implantation on the availability of CBAT and its potential benefits are warranted. In addition, given the limited overall use of CBAT and its association with improved CI outcomes, future studies are needed to investigate facilitators and barriers to CBAT use., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Cyclobutane pyrimidine dimers (CPDs) are ultraviolet radiation (UV)-induced carcinogenic DNA photoproducts that lead to UV signature mutations in melanoma. Previously, we discovered that, in addition to their incident formation (iCPDs), UV exposure induces melanin chemiexcitation (MeCh), where UV generates peroxynitrite (ONOO - ), which oxidizes melanin into melanin-carbonyls (MCs) in their excited triplet state. Chronic MeCh and energy transfer by MCs to DNA generates CPDs for several hours after UV exposure ends (dark CPD, dCPDs). We hypothesized that MeCh and the resulting dCPDs can be inhibited using MeCh inhibitors, and MC and ONOO - scavengers. Here, we investigated the efficacy of Acetyl Zingerone (AZ), a plant-based phenolic alkanone, and its chemical analogs in inhibiting iCPDs and dCPDs in skin fibroblasts, keratinocytes, and isogenic pigmented and albino melanocytes. While AZ and its methoxy analog, 3-(4-Methoxy-benzyl)-Pentane-2,4-dione (MBPD) completely inhibited the dCPDs, MBPD also inhibited ~50% of iCPDs. This suggests the inhibition of ~80% of total CPDs at any time point post UV exposure by MBPD, which is markedly significant. MBPD downregulated melanin synthesis, which is indispensable for dCPD generation, but this did not occur with AZ. Meanwhile, AZ and MBPD both upregulated the expression of nucleotide excision repair (NER) pathways genes including Xpa , Xpc , and Mitf . AZ and its analogs were non-toxic to the skin cells and did not act as photosensitizers. We propose that AZ and MBPD represent "next-generation skin care additives" that are safe and effective for use not only in sunscreens but also in other specialized clinical applications owing to their extremely high efficacy in blocking both iCPDs and dCPDs.

The Martini 3 force field is a full reparametrization of the Martini coarse-grained model for biomolecular simulations. Due to the improved interaction balance, it allows for a more accurate description of condensed phase systems. In the present work, we develop a consistent strategy to parametrize carbohydrate molecules accurately within the framework of Martini 3. In particular, we develop a canonical mapping scheme which decomposes arbitrarily large carbohydrates into a limited number of fragments. Bead types for these fragments have been assigned by matching physicochemical properties of mono- and disaccharides. In addition, guidelines for assigning bonds, angles, and dihedrals were developed. These guidelines enable a more accurate description of carbohydrate conformations than in the Martini 2 force field. We show that models obtained with this approach are able to accurately reproduce osmotic pressures of carbohydrate water solutions. Furthermore, we provide evidence that the model differentiates correctly the solubility of the polyglucoses dextran (water-soluble) and cellulose (water insoluble but soluble in ionic liquids). Finally, we demonstrate that the new building blocks can be applied to glycolipids. We show they are able to reproduce membrane properties and induce binding of peripheral membrane proteins. These test cases demonstrate the validity and transferability of our approach.

Objective: To examine the effectiveness of Eustachian tube procedures for the treatment of baro-challenge Eustachian tube dysfunction., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, databases, including PubMed (National Library of Medicine, National Institutes of Health), Scopus (Elsevier), and CINAHL (EBSCO), were searched for articles examining the effectiveness of Eustachian tube procedures for baro-challenge Eustachian tube dysfunction. Outcome measures included symptom resolution, ability to return to work, equalization problems (EP) scores, Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores, and pressure chamber testing parameters. Pooled meta-analysis was performed for dichotomous measures and ETDQ-7 scores., Results: Eleven articles with 81 patients were included. Seventy-two patients from 10 articles underwent balloon Eustachian tube dilation; nine patients in 1 study underwent laser Eustachian tuboplasty (LET). All 81 patients were preoperatively symptomatic with barometric pressure change, and 26/30 (86.7%) were unable to work due to symptoms. On meta-analysis, after balloon dilation Eustachian tuboplasty (BDET), 82.5% (n = 30 [95% confidence interval: 42%-100%]) had improvement in ability to valsalva, 79.1% (n = 16 [57.9%-94.1%]) in ability to return to work, and 84.3% (n = 69 [69.8%-94.7%]) in any symptom. Of 25 patients with individual ETDQ-7 scores, 79.1% [51.4, 96.9] had improvements after BDET. For four case series with 36 patients, ETDQ-7 scores decreased by 1.2 [0.7, 1.7] (p < 0.00001). Of 20 patients with preoperative ETDQ-7 scores >2.0, there was a mean decrease of 2.1 [1.3, 2.8] (p < 0.00001)., Conclusion: From the available evidence, Eustachian tube procedures appear to be effective at improving symptoms of baro-challenge Eustachian tube dysfunction. However, higher quality evidence is needed to support making definite recommendations for the use of balloon Eustachian tube dilation or LET for these patients. Laryngoscope, 132:2473-2483, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)