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Report the incidence of and treatment patterns for facial nerve palsy after skull base fracture.Retrospective cohort study.IBM MarketScan Commercial Database (2006-2019).Human subjects with skull base fracture, per International Classification of Diseases-9th and 10th Revisions-Clinical Modification diagnosis codes.The primary outcomes were the incidence and median time to facial nerve palsy diagnosis within 30 days of skull base fracture. Secondary outcomes were treatments (corticosteroids, antivirals, facial nerve decompression, botulinum toxin, and facial reanimation), demographics, and rates of hearing loss, vertigo, tympanic membrane rupture, cerebrospinal fluid leak, comorbidities, and loss of consciousness.The 30-day incidence of facial nerve palsy after skull base trauma was 1.0% (738 of 72,273 patients). The median (95% confidence interval [CI]) time to diagnosis was 6 (6-7) days, and only 22.9% were diagnosed within 1 day. There were significantly higher rates (risk difference, 95% CI) of hearing loss (26%, 22-29%), tympanic membrane rupture (6.3%, 4.5-8.1%), cerebrospinal fluid leak (6.4%, 4.5-8.3%), comorbidity (14%, 10.4-17.6%), and loss of consciousness (24.3%, 20.7-27.9%). Loss of consciousness was associated with longer median (95% CI) time to facial nerve palsy diagnosis: 10 (9-10) days. Corticosteroids were the most common treatment but only reported for less than one-third of patients. Only eight patients underwent facial nerve decompression.Facial nerve palsy after skull base fracture is associated with higher comorbidity, and the diagnosis is often delayed. Few patients were treated with surgery, and there are inconsistencies in the types and timing of treatments.

1) To determine the relationship of electrocochleography (ECochG) responses measured on the promontory with responses measured at the round window (RW) and various intracochlear sites. 2) To evaluate if promontory ECochG responses correlate with postoperative speech-perception performance using the cochlear implant (CI).Prospective cohort study.Tertiary referral center.Ninety-six adult CI recipients with no cochlear malformations or previous otologic surgery.Acoustically evoked ECochG responses were measured intraoperatively at both extracochlear and intracochlear locations. ECochG total response (ECochG-TR), a measure of residual cochlear function, was calculated by summing the fast Fourier transformation amplitudes in response to 250-Hz to 2-kHz acoustic stimuli. Speech-perception performance was measured at 3 months.There were strong linear correlations for promontory ECochG-TR with the ECochG-TRs measured at the RW ( r = 0.95), just inside scala tympani ( r = 0.91), and after full insertion ( r = 0.83). For an individual subject, the morphology of the ECochG response was similar in character across all positions; however, the response amplitude increased from promontory to RW (~1.6-fold) to just inside scala tympani (~2.6-fold), with the largest response at full insertion (~13.1-fold). Promontory ECochG-TR independently explained 51.8% of the variability ( r2 ) in consonant-nucleus-consonant at 3 months.Promontory ECochG recordings are strongly correlated with responses previously recorded at extracochlear and intracochlear sites and explain a substantial portion of the variability in CI performance. These findings are a critical step in supporting translation of transtympanic ECochG into the clinic preoperatively to help predict postoperative CI performance.

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Purpose:Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)–unrelated HNSCC.Patients and Methods:Neoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (Results:Thirty-six patients enrolled. After neoadjuvant pembrolizumab, serious (grades 3–4) adverse events and unexpected surgical delays/complications did not occur. pTR-2 occurred in eight patients (22%), and pTR-1 in eight other patients (22%). One-year relapse rate among 18 patients with high-risk pathology was 16.7% (95% confidence interval, 3.6%–41.4%). pTR ≥10% correlated with baseline tumor PD-L1, immune infiltrate, and IFNγ activity. Matched samples showed upregulation of inhibitory checkpoints in patients with pTR-0 and confirmed clonal loss in some patients.Conclusions:Among patients with locally advanced, HPV-unrelated HNSCC, pembrolizumab was safe, and any pathologic response was observed in 44% of patients with 0% pathologic complete responses. The 1-year relapse rate in patients with high-risk pathology was lower than historical.

PDF file - 486KB, Figure S1 (A) Average statistics for depth of coverage at 20X, 30X and 40X of all MOC lines. Robust reads were obtained in all samples with a range of 97-98 percent for 20X, 93-95 percent for 30X and 88-92 percent for 40X. (B) Putative SNVs, nsSNVs (Table S1 and S2) and Indels (Table S4) of all MOC lines. Figure S2 Oncoprints from cBio of AKAP9, MED12L, THSD7A, MUC5B, MYH6, LAMA1, LRP2, and 3 RAS (Table S6) genes representing other candidate tumor promoters as compared to the 3 RAS genes. Note that for AKAPs and MED components, we found 9 AKAP family member mutations in 20.4 percent of tumors, with AKAP9 changes in 7 percent (Fig. 1D). Six components of the mediator complex were mutated in 14.7% of cases, with MED12L changes in 5% (Fig. 1E). Figure S3 Number of nsSNV's per node negative (N0) and node positive (N+) tumor in (A) all TCGA OSCC (note that patient TCGA-D6-6516 (N0) with 1463 mutations is not included in this graph) and (B) TCGA OSCC patients who had smoking history reported. There was no significant difference in the average number of mutations between N0 (3272 nsSNVs) and N+ (3097 nsSNVs) patients regardless of smoking status (Tables S8, S9). This analysis showed 17 genes commonly mutated in mouse indolent and human N0 tumors and 55 common genes mutated in mouse aggressive and human N+ tumors (Supplementary Table S10). However, none of these common genes were mutated at high frequency in the human N0 or N+ datasets (Supplementary Table S11 and 12). Finally, comparing N0 and N+ tumors from human TCGA data also showed that specific mutations occur infrequently in both the metastatic and non-metastatic tumors (data not shown). Figure S4 SAM plotsheet of MOC line microarray data with estimated miss rates for delta=4.68 Figure S5 (A) GSEA data of OCAMP-A on UW/FHCRC data with (B) first condensation of enriched genes. (C) GSEA data of OCAMP-A on MDA data with (D) first condensation of enriched genes. (E) GSEA data of OCAMP-A on TCGA data with (F) first condensation of enriched genes. Figure S6 (A) Disease specific survival (DSS) after weighted voting classification of OCAMP-B signature on the MD Anderson dataset shows worse outcome for those with aggressive classification (p=0.028). Figure S7 (A) Disease specific survival (DSS) and (B) overall survival (OS) after weighted voting classification of OCAMP-B signature on the UW/FHCRC dataset shows worse outcome for those with aggressive classification (p

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Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance.Experimental Design: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan–Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy.Results: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L, and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy.Conclusions: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873–84. ©2014 AACR.

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XLS file - 6534KB, S1 SNVs indolent lines. S2 SNVs aggressive lines. S3 Distribution of nucleotide changes. S4 MOC line mutations have similarity to 32 most common HNSCC TCGA mutations. S5 MOC line conservation with human OSCC drivers and novel mutations. S6 Indels all MOC lines. S7 Comparison of predicted changes between aggressive and indolent lines. S8 MOC line common mutations. S9 Unique aggressive MOC line mutations. S10 Comparison of MOC line mutations with TCGA N0 and N+ mutations. S11 TCGA mutation burden per tumor in N0 and N+ specimens. S12 MOC line and TCGA common mutations. S13 Rate of alterations of aggressive MOC/TCGA N+ mutations from Table S10. S14 Rate of alterations of indolent MOC/TCGA N0 mutations from Table S10. S15 SAM analysis of aggressive versus indolent expression data. S16 Compiled rank metric scores of OCAMP-A genes across three human datasets. S17 Cross tabulation and multivariable analysis of OCAMP-B on MD dataset. S18 Weighted voting classification with OCAMP-B on independent UPENN dataset. S19 SVM output data for training and test sets. S20 OCAMP-A comparison to three published signatures.

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Anxiety and depression have demonstrated a positive correlation with vocal handicap among patients with benign causes of dysphonia. Our objective is to explore differences in initial Vocal Handicap Index-10 (VHI-10) scores between patients with a mental health history of anxiety or depression and those without.Retrospective cohort study.Demographic data, diagnoses, and initial VHI-10 scores were collected for patients presenting with dysphonia to 2 tertiary laryngology clinics.A Kruskal-Wallis test and subsequent Mann-WhitneyA total of 620 cases of benign dysphonia were analyzed. Forty-two percent of the patient cohort had a preexisting diagnosis of anxiety (n = 121, 20%), depression (n = 64, 10%), or anxiety and depression (n = 74, 12%). VHI-10 scores were higher in patients with depression than in those without anxiety or depression (median difference, 4 [95% CI, 1-8];Patients with a history of depression who presented with dysphonia had worse vocal handicap than those without anxiety/depression history. Future studies may clarify how optimization of anxiety and depression can affect patient-reported vocal handicap.

Introduction: Though severe illness due to COVID-19 is uncommon in children, there is an urgent need to better determine the risk factors for disease severity in youth. This study aims to determine the impact a preexisting endocrine diagnosis has on severity of COVID-19 presentation in youth. Methods: The cross-sectional chart review study included all patients less than 25 years old with a positive SARS-CoV-2 PCR at St. Louis Children’s Hospital between March 2020 and February 2021. Electronic medical record data for analysis included patient demographics, BMI percentile, inpatient hospitalization or admission to the pediatric intensive care unit (PICU), and the presence of a preexisting endocrine diagnosis such as diabetes mellitus (type 1 and type 2), adrenal insufficiency, and hypothyroidism. Two outcome measures were analyzed in multivariate analysis: inpatient admission and PICU admission. Adjusted odds ratios with a 95% CI were calculated using binary logistic regression, along with p values after Wald χ2 analysis. Results: 390 patients were included in the study. Mean age was 123.1 (±82.2) months old. 50.3% of patients were hospitalized, and 12.1% of patients were admitted to intensive care. Preexisting diagnoses of diabetes mellitus, obesity, and hypothyroidism were associated with an increased risk of hospital and ICU admission, independent of socioeconomic status. Discussion/Conclusion: This study provides evidence that unvaccinated youth with a preexisting diagnosis of obesity, hypothyroidism, or diabetes mellitus infected with COVID-19 are more likely to have a more severe clinical presentation requiring inpatient hospital admission and/or intensive care.

Importance: Time to surgical intervention is an oft-investigated potentially modifiable risk factor for complications after mandible fracture. Objective: To identify novel risk factors for malunion/nonunion after mandible fracture and determine the impact of treatment delay on malunion and nonunion after open reduction of mandible fractures. Design: Retrospective cohort. Setting and Participants: Encounter billing records from the New York State Inpatient Databases, State Emergency Department Databases, and State Ambulatory Surgery Databases. Patients aged 18 years and older with isolated mandible fracture in the emergency department or inpatient setting from January 1, 2006 to September 30, 2015. Main Outcomes and Measures: Mandibular Malunion/Nonunion. Results: A total of 19,152 adults were diagnosed with isolated mandible fracture. After fracture, 247 patients (1.3%) developed mandibular malunion or nonunion. In multivariable analysis, patients with open fractures (odds ratio [OR] 1.93, confidence interval [95% CI] 1.40–2.65), body fractures (OR 2.00, 1.50–2.65), alcohol abuse (OR 1.61, 1.22–2.11), diabetes mellitus (OR 1.57, 1.02–2.42), and Medicaid insurance (OR 1.46, 1.03–2.07) had increased risk, whereas patients with subcondylar fractures had reduced risk (OR 0.45, 0.28–0.72) of mandibular malunion/nonunion. The risk of mandibular malunion/nonunion after open reduction increased with treatment delay until 6–7 days after presentation (OR 1.84, 1.11–3.06). Conclusion and Relevance: Although treatment delay is often unavoidable, these findings suggest that physicians should consider early intervention in patients requiring open reduction of mandible fractures when able.

ImportanceThe number of olfactory dysfunction cases has increased dramatically because of the COVID-19 pandemic. Identifying therapies that aid and accelerate recovery is essential.ObjectiveTo determine the efficacy of bimodal visual-olfactory training and patient-preferred scents vs unimodal olfactory training and physician-assigned scents in COVID-19 olfactory loss.Design, Setting, and ParticipantsThis was a randomized, single-blinded trial with a 2-by-2 factorial design (bimodal, patient preferred; unimodal, physician assigned; bimodal, physician assigned; unimodal, patient preferred) and an independent control group. Enrollment occurred from February 1 to May 27, 2021. Participants were adults 18 to 71 years old with current olfactory loss defined as University of Pennsylvania Smell Identification Test (UPSIT) score less than 34 for men and less than 35 for women and duration of 3 months or longer. Olfactory loss was initially diagnosed within 2 weeks of COVID-19 infection.InterventionsParticipants sniffed 4 essential oils for 15 seconds with a 30-second rest in between odors for 3 months. Participants in the physician-assigned odor arms trained with rose, lemon, eucalyptus, and clove. Participants randomized to the patient-preferred arms chose 4 of 24 available scents. If assigned to the bimodal arm, participants were shown digital images of the essential oil they were smelling.Main Outcomes and MeasuresThe primary end point was postintervention change in UPSIT score from baseline; measures used were the UPSIT (validated, objective psychometric test of olfaction), Clinical Global Impressions Impression–Improvement (CGI-I; self-report improvement scale), and Olfactory Dysfunction Outcomes Rating (ODOR; olfaction-related quality-of-life questionnaire).ResultsAmong the 275 enrolled participants, the mean (SD) age was 41 (12) years, and 236 (86%) were female. The change in UPSIT scores preintervention to postintervention was similar between the study arms. The marginal mean difference for change in UPSIT scores preintervention to postintervention between participants randomized to patient-preferred vs physician-assigned olfactory training was 0.73 (95% CI, −1.10 to 2.56), and between participants randomized to bimodal vs unimodal olfactory training was 1.10 (95% CI, −2.92 to 0.74). Five (24%) participants in the control arm had clinically important improvement on UPSIT compared with 18 (53%) in the bimodal, patient-preferred arm for a difference of 29% (95% CI, 4%-54%). Four (19%) participants in the control group self-reported improvement on CGI-I compared with 12 (35%) in the bimodal, patient-preferred arm for a difference of 16% (95% CI, −7% to 39%). The mean change in ODOR score preintervention to postintervention was 11.6 points (95% CI, 9.2-13.9), which was not deemed clinically important nor significantly different between arms.Conclusions and RelevanceBased on the change in UPSIT scores, this randomized clinical trial did not show any difference between intervention arms, but when exploring within-patient change in UPSIT as well as self-reported impression of improvement, active interventions were associated with larger improvement than controls with a potential advantage of bimodal intervention. While not definitive, these results suggest that patients with COVID-19 olfactory loss may benefit from bimodal visual-olfactory training with patient-preferred scents.Trial RegistrationClinicalTrials.gov Identifier: NCT04710394

A growing body of research suggests that standard group-based models might provide little insight regarding individuals. In the current study, we sought to compare group-based and individual predictors of bothersome tinnitus, illustrating how researchers can use dynamic structural equation modeling (DSEM) for intensive longitudinal data to examine whether findings from analyses of the group apply to individuals. A total of 43 subjects with bothersome tinnitus responded to up to 200 surveys each. In multilevel DSEM, survey items loaded on three factors (tinnitus bother, cognitive symptoms, and anxiety), and results indicated a reciprocal relationship between tinnitus bother and anxiety. In fully idiographic models, the three-factor model fit poorly for two individuals, and the multilevel model did not generalize to most individuals, possibly because of limited power. Research examining heterogeneous conditions, such as tinnitus bother, may benefit from methods such as DSEM that allow researchers to model dynamic relationships.

To evaluate the impact of different open set sentence recognition tests in quiet, +10 dB signal to noise ratio (SNR), and +5 dB SNR in adult cochlear implant (CI) recipients above and below 65 years of age.Multi-institution, prospective, non-randomized, single-subject repeated measures design.Ninety six adults more than or equal to 18 years old with postlingual bilateral sensorineural hearing loss.Participants received a CI532 in one ear. Speech perception measures were evaluated before and 6-months after activation.Subjects completed consonant-nucleus-constant (CNC) words in quiet and AzBio sentences in noise using +10 and +5 dB SNR, and Montreal Cognitive Assessment (MOCA).Ninety six adult patients were enrolled (n = 70 older [≥65 yr], n = 26 younger [65 yr]). There was no difference in CNC scores (CI alone 58.4% versus 67.5%, p = 0.0857; best aided 66.7% versus 76.1%, p = 0.3357). Older adults performed worse on AzBio +10 dB SNR compared with younger patients (CI alone 37.4% versus 56.9%, p = 0.0006; best aided 51.4% versus 68.2%; p = 0.01), and in AzBio +5 dB SNR (CI alone 7.7% versus 11.2%, p = 0.0002; best aided 15.3% versus 22.3%, p = 0.0005). The magnitude of change in AzBio +10 dB SNR was significantly less in older adults in CI alone (15.3% versus 22.3%; p = 0.0493) but not best aided (21.5% versus 31.3%; p = 0.105). The magnitude of change was drastically worse in AzBio +5 dB SNR for older adults (CI alone 6.7% versus 22.1%, p = 0.0014; best aided 9.5% versus 21.5%; p = 0.0142). There was no significant difference in MOCA between the two age groups.While both older and younger patients have similar outcomes with respect to CNC word scores in quiet, the addition of noise disproportionally impacts older patients. Caution should be exercised testing the elderly in noise; testing in noise may disproportionally impact performance expectations and should be more carefully considered when used for candidacy criteria and counseling. Future studies need to further investigate the disproportionate effect of noise on candidacy testing and its impact on how elderly patients are qualified.

To examine long-term speech and cognition outcomes in older adult cochlear implant (CI) recipients. First, by evaluating if CI performance was maintained over an extended follow-up period regardless of preoperative cognitive status. Secondly, by evaluating if there was a difference in the rate of cognitive decline between preoperative mild and normal cognition following CI over an extended period of time.Retrospective cohort study.CI recipients ≥65 years of age implanted between 2009 and 2014 with 4+ years follow up. Pre- and postoperative audiometric and speech outcome assessments were collected. Cognitive status was measured using the mini mental status examination (MMSE) at numerous time points.Fifty-three patients met inclusion. Patients were divided into two groups based on preoperative MMSE with scores considered normal (28-30) and those with mildly impaired cognition (MIC, scores 25-27). Audiometric and speech performance improved significantly at one-year post implantation and this was maintained without significant change at 4+ years, regardless of cognitive status. Mixed modeling analysis controlling for age demonstrated no significant difference in the rate of cognitive decline at 4+ years post implantation between the normal cognition cohort (1.74; 95%CI 0.89-2.6) and MIC (2.9; 95%1.91-3.88).Speech performance was significantly improved and sustained after CI in both normal cognition and MIC patients. The rate of cognitive decline in older adult CI patients appears to be similar regardless of preoperative cognitive status. Although results demonstrate rates of cognitive decline following CI did not differ between cognition groups over 4+ years, future studies will need to further investigate this over extended time periods with a more comprehensive cognitive testing battery.Level 4 Laryngoscope, 2022.

ImportanceEffect size quantifies the magnitude of the difference or the strength of the association between variables. In clinical research it is important to calculate and report the effect size and the confidence interval (CI) because it is needed for sample size calculation, meaningful interpretation of results, and meta-analyses.ObservationsThere are many different effect size measures that can be organized into 2 families or groups—d family and r family. The d family includes measures that quantify the differences between groups. The r family includes measures that quantify the strength of the association. Effect sizes that are presented in the same units as the characteristic being measured and compared are known as nonstandardized or simple effect sizes. The nonstandardized effect sizes have the advantage of being more informative, easier to interpret, and easier to evaluate in the light of clinical significance or practical relevance. Standardized effect sizes are unit-less and are helpful for combining and comparing effects of different outcome measures or across different studies (ie, meta-analysis).Conclusions and RelevanceThe choice of the correct effect size measure depends on the research question, study design, targeted audience, and the statistical assumptions being made. For a complete and meaningful interpretation of results from a clinical research study, the investigator should make clear the type of effect size being reported, its magnitude and direction, degree of uncertainty of the effect size estimate as presented by the CIs, and whether the results are compatible with a clinically meaningful effect.

IMPORTANCE: Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic. OBJECTIVE: To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19–related OD. DESIGN, SETTING, AND PARTICIPANTS: This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021. INTERVENTIONS: Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19–related questions. RESULTS: A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, −13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, −1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, −2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, −4% to 52%) in favor of theophylline. CONCLUSIONS AND RELEVANCE: This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19–related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04789499

This case series aims to determine the maximum tolerable dose of theophylline delivered via high-volume, low-pressure nasal saline irrigation for treatment of postviral olfactory dysfunction.

ImportancePrevalence of post-viral olfactory loss has increased dramatically due to the frequency and severity of olfactory dysfunction associated with infection by the SARS-CoV-2 virus.ObjectiveTo determine the trajectory of COVID-19 olfactory loss over a six-month period. A key secondary objective is to assess predictive factors associated with the recovery of olfaction.DesignLongitudinal repeated-measures study that enrolled from May 5, 2020 to February 2, 2021, with the last date of data collection on June 15, 2021.SettingBarnes-Jewish HealthCare/Washington University School of Medicine facilities (Saint Louis, Missouri, USA).ParticipantsIndividuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction on nasopharyngeal swab and indicated olfactory loss on COVID-19 screening questionnaire. Individuals were excluded if they had previously diagnosed history of olfactory loss, neurodegenerative disorders, less than 18 years of age, admitted to hospital service, unable to read, write, and understand English, or lacked computer or internet access.Interventions/ExposuresWatch and wait for spontaneous recovery.Main Outcome(s) and Measure(s)Participants completed olfactory assessments every 30 days for six months. Each assessment consisted of the University of Pennsylvania Smell Identification Test (UPSIT), an objective “scratch-and-sniff” test, and Clinical Global Impressions (CGI), a subjective Likert rating scale.ResultsThe mean age was 41 years old (SD = 16). 39 (80%) were female and 42 (86%) white. At baseline assessment of objective olfaction, 18 (36%) participants had anosmia or severe hyposmia. Subjective, complete recovery at six months was 81% (95% CI 74% to 88%). Likelihood of recovery was associated with age less than 50 years (aHR = 8.1 (95% CI 1.1 to 64.1)) and mild olfactory loss at baseline (UPSIT = 30-33 for males and 31-34 for females) (aHR 6.2 (95% CI 1.2 to 33.0)).Conclusions and RelevanceThe trajectory of olfactory recovery among adults with COVID-19 olfactory loss illustrated rapid recovery within 2-3 weeks of infection, and by six months 81% had recovered based on self-report. Age less than 50 years old and mild severity of olfactory loss at baseline were associated with increased likelihood of recovery of olfaction. These findings can be used to inform shared decision-making with patients.

OBJECTIVE: This is the first database study to assess the effectiveness of prophylactic preoperative antibiotics (PPAs) in mandible fracture repair. STUDY DESIGN: Retrospective cohort SETTING: Database study using United States inpatient and outpatient insurance claims submitted from July 2006 to March 2015 METHODS: The IBM® MarketScan® Commercial database was queried for adults aged 18 to 64 years old who had undergone first time mandible fracture repair using CPT codes for open and closed repair. Primary outcomes included (1) surgical revision, (2) local infection, and (3) osteomyelitis. Rates were compared between cohorts based on whether or not patients had filled antibiotic prescriptions during the pre-operative period alone. The effects of drug abuse and type of mandible repair (i.e. open versus closed) were explored. Multivariate Poisson regression models were used to calculate adjusted relative risk (aRR) estimates. 95% confidence intervals (CI) were used to determine statistically significant differences. RESULTS: A total of 2676 patients were included with 847 (31.7%) filling PPAs, and 1829 (68.3%) filling no antibiotics. The rates of revision, local infection, and osteomyelitis were 38.9%, 5.8%, and 2.1%, respectively. After multivariate analysis, exposure to PPAs was not associated [aRR; 95% CI] with surgical revision [1.04; 0.94–1.15], local infection [1.16; 0.82–1.64], or osteomyelitis [1.21; 0.68–2.14]. Patients were more likely to fill PPAs if they underwent open (35.3%), versus closed (26.6%) repair (proportion difference [PD]: 8.7%; 5.2–12.2%), but exposure to antibiotics did not predict outcomes on subgroup analysis. CONCLUSION: PPAs do not improve mandible repair outcomes, regardless of repair type.

To evaluate the effectiveness of cognitive training in improving tinnitus bother and to identify predictors of patient response.Prospective open-label randomized controlled trial.Online.Participants were adults with subjective idiopathic nonpulsatile tinnitus causing significant tinnitus-related distress. The intervention group trained by using auditory-intensive exercises for 20 minutes per day, 5 days per week, for 8 weeks. The active control group trained on the same schedule with non-auditory intensive games. Surveys were completed at baseline, 8 weeks, and 12 weeks.A total of 64 participants completed the study. The median age was 63 years (range, 25-69) in the intervention group and 61 years (34-68) in the control group. Mixed model analysis revealed that within-subject change in Tinnitus Functional Index in the intervention group was not different than the control group, with marginal mean differences (95% CI): 0.24 (-11.20 to 10.7) and 2.17 (-8.50 to 12.83) at 8 weeks and 2.33 (-8.6 to 13.3) and 3.36 (-7.91 to 14.6) at 12 weeks, respectively. When the 2 study groups were compared, the control group had higher Tinnitus Functional Index scores than the intervention group by 10.5 points at baseline (95% CI, -0.92 to 29.89), 8.1 at 8 weeks (95% CI, -3.27 to 19.42), and 9.4 at 12 weeks (95% CI, -2.45 to 21.34).Auditory-intensive cognitive training was not associated with changes in self-reported tinnitus bother. Given the potential for neuroplasticity to affect tinnitus, we believe that future studies on cognitive training for tinnitus remain relevant.

ImportancePatient-reported outcome measures (PROMs) allow clinicians and researchers to assess health-related information from a patient’s perspective. These measures have been used more frequently over the last several decades, but an associated minimal clinically important difference (MCID) is needed to optimize their utility. This narrative review identified the top 100 most-cited otolaryngology-related PROM development and validation publications and assessed the presence and characteristics of the PROMs’ associated MCID.ObservationsIn this narrative review, a literature search in Scopus and Web of Science was conducted on June 29, 2022, using keywords related to PROM development and validation studies in otolaryngology and reference lists. Studies that met the definition of a PROM and assessed an otolaryngologic disorder or study population were included for full-text review. After full-text review of 188 articles, the top 100 most-cited PROM development and validation publications, resulting in 106 total PROMs, were chosen for review. A total of 39 (37%) of the identified PROMs had an associated MCID. Of those reporting an MCID, 14 (35.9%) used an anchor-based method, 12 (30.8%) used a distribution-based method, 10 (25.6%) used both, and 3 (7.7%) did not specify or used neither method. Rhinology had the greatest number of PROMs with an associated MCID (16 of 24, 66%), and pediatrics had the fewest (1 of 13, 7.7%). The median number of citations of PROMs with an MCID was higher than those without an MCID.Conclusions and RelevanceThe majority of the most-cited PROMs in otolaryngology lack an associated MCID. These data indicated that there are a multitude of PROMs that have been cited hundreds of times and used for decades without the ability to identify whether a particular change in score on the instrument is clinically meaningful. There is a need to determine and validate MCIDs for commonly used PROMs to aid clinical research and trial interpretation.

Objective: To describe cases and timing of pediatric post-tonsillectomy hemorrhage (PTH), to evaluate predictors of PTH, and to determine the optimal amount of postoperative care unit (PACU) monitoring time. Study Design: Using the Pediatric Health Information System (PHIS) database and electronic medical records, a matched case-control study from 2005 to 2015 was performed. Setting: A single, tertiary-care institution. Subjects and Methods: Each case of PTH was matched with 1 to 4 controls for the following factors: age, sex, surgeon, and time of year. A total of 124 cases of PTH and 479 tonsillectomy controls were included. The rate and timing of postoperative bleeding were assessed, and matched pair analysis was performed using conditional logistic regression. Results: Our institutional PTH rate of 1.9% (130 of 6949) included 124 patients; 15% (19) were primary (≤24 hours), with 50% (9) occurring within 5 hours. Twenty-one percent (4 of 19) of primary PTH patients received operative intervention. Eighty-five percent (105 of 124) of all cases were secondary PTH, and 47% (49) of those patients received operative intervention. Cold steel (OR 1.9, 95% CI 1.1-3.3) and Coblation (OR 1.9, 95% CI 1.2-3.1) techniques and tonsillectomy alone (OR 3.7, 95% CI 1.9-7.2) increased odds of PTH. Patients who developed PTH had 4 times the odds of having a preceding postoperative respiratory event than controls (OR 4.0, 95% CI 1.6-10.0). Conclusion: We conducted a rigorous case-control study for PTH, finding that PTH was associated with use of cold steel and Coblation techniques and with tonsillectomy alone. Patients with a postoperative respiratory event may be more likely to develop a PTH and should be counseled accordingly. A PACU monitoring time of 4 hours is sufficient for outpatient tonsillectomy.

OBJECTIVE Hearing loss remains a significant morbidity for patients with vestibular schwannomas (VS). A growing number of reports suggest audibility with cochlear implantation following VS resection; however, there is little consensus on preferred timing and cochlear implant (CI) performance. DATA SOURCES A systematic literature search of the Ovid Medline, Embase, Scopus, and clinicaltrails.gov databases was performed on 9/7/2018. PRISMA reporting guidelines were followed. STUDY SELECTION Included studies reported CI outcomes in an ear that underwent a VS resection. Untreated VSs, radiated VSs, and CIs in the contralateral ear were excluded. DATA EXTRACTION Primary outcomes were daily CI use and attainment of open-set speech. Baseline tumor and patient characteristics were recorded. Subjects were divided into two groups: simultaneous CI placement with VS resection (Group 1) versus delayed CI placement after VS resection (Group 2). DATA SYNTHESIS Twenty-nine articles with 93 patients met inclusion criteria. Most studies were poor quality due to their small, retrospective design. Group 1 had 46 patients, of whom 80.4% used their CI on a daily basis and 50.0% achieved open-set speech. Group 2 had 47 patients, of whom 87.2% used their CI on a daily basis and 59.6% achieved open-set speech. Group 2 had more NF2 patients and larger tumors. CI timing did not significantly impact outcomes. CONCLUSIONS Audibility with CI after VS resection is feasible. Timing of CI placement (simultaneous versus delayed) did not significantly affect performance. Overall, 83.9% used their CI on a daily basis and 54.8% achieved open-set speech.

Background There is no consensus regarding the best route of intranasal delivery of corticosteroids in the treatment of chronic rhinosinusitis (CRS). The study objective of this work was to compare the impact of mometasone furoate nasal spray (MFNS) vs mometasone nasal irrigation in the management of CRS patients who have not undergone sinus surgery. Methods A double-blind, placebo-controlled, randomized clinical trial was conducted in adults with CRS. Individuals with nasal polyps and/or history of sinus surgery were excluded. Patients were randomized to receive 8 weeks of either MFNS or mometasone nasal irrigation. The primary outcome measure was change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score between the 2 groups. Secondary outcome measures included patient global response to treatment and Lund-Kennedy endoscopy scores. Results A total of 43 participants completed the study (n = 22, MFNS; n = 21,mometasone nasal irrigation). Fourteen (64%) participants in the MFNS group and 17 (81%) in the mometasone lavage group had a clinically meaningful improvement in SNOT-22 scores with a proportion difference of 17% (95% confidence interval [CI], -9% to 44%). The least-squares (LS) mean difference between the 2 groups for SNOT-22 was -8.6 (95% CI, -17.7 to 0.58; p = 0.07), whereas the LS mean difference between the 2 groups for Lund-Kennedy endoscopy scores was 0.16 (95% CI, -0.84 to 1.15; p = 0.75). No adverse events were associated with the study. Conclusion Both MFNS and mometasone nasal irrigations are beneficial in symptom management of CRS. Our study suggests that patients who perform mometasone lavage do better in a clinically meaningful way, but our results are not definitive and further studies are warranted.