Neuromodulation for Treatment of Tinnitus: A Systematic Review and Meta-Analysis.

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.

Delays Starting Postoperative Radiotherapy Among Head and Neck Cancer Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL. REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures was performed on nonoverlapping datasets to examine the pooled frequency of PORT delays and time-to-PORT. RESULTS: Thirty-six studies were included in the systematic review and 14 in the meta-analysis. Most studies utilized single-institution (n = 17; 47.2%) or cancer registry (n = 16; 44.4%) data. Twenty-five studies (69.4%) defined PORT delay as >6 weeks after surgery (the definition utilized by the CoC and National Comprehensive Cancer Network Guidelines), whereas 4 (11.1%) defined PORT delay as a time interval other than >6 weeks, and 7 (19.4%) characterized time-to-PORT without defining delay. Meta-analysis revealed that 48.6% (95% confidence interval [CI], 41.4-55.9) of patients started PORT > 6 weeks after surgery. Median and mean time-to-PORT were 45.8 (95% CI, 42.4-51.4 days) and 47.4 days (95% CI, 43.4-51.4 days), respectively. CONCLUSION: Delays in initiating guideline-adherent PORT occur in approximately half of patients with HNSCC. These meta-analytic data can be used to set national benchmarks and assess progress in reducing delays.

Hyperbaric oxygen therapy in malignant otitis externa: A systematic review of the literature.

OBJECTIVE: To review the role of adjuvant hyperbaric oxygen therapy (HBOT) in the treatment of malignant otitis externa (MOE). DATA SOURCES: PubMed, Scopus, Web of Science, Science Direct, and Cochrane Library were searched for the following concepts: "hyperbaric oxygen" and "malignant or necrotizing otitis externa." METHODS: Studies were included if they contained (1) patients with reported evidence of MOE, (2) employment of adjuvant HBOT, (3) details on patients' medical condition, and (4) documented survival outcomes. Extracted information included patient demographics, underlying medical conditions, infectious etiology, signs and symptoms, medical and surgical treatments, duration of medical treatment, mean follow up time, HBOT setting, number of HBOT sessions, complications, survival rate, and all-cause mortality. RESULTS: A total of 16 studies comprising 58 patients (mean age 68.0 years) were included. Diabetes was present in 94.7% of cases and Pseudomonas spp (64.3%) was the most common infectious agent. Cranial nerve VII was involved in 55.2% of cases. Overall, the disease cure rate with adjuvant HBOT was 91.4% and all-cause mortality was 8.6%. Among those who had cranial nerve VII involvement, 72.0% had return of function and 93.8% of them survived. CONCLUSION: HBOT may be an effective treatment option for refractory or advanced MOE but its efficacy remains unproven due to lack of strong scientific evidence. However, its therapeutic value should not be underestimated given good results and few adverse events reported in this study.

Review of the use of nasal and oral antiseptics during a global pandemic.

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine®, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3-4 log10 in 15-30 s in vitro. In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.

Hearing Outcomes of Treatment for Acute Noise-induced Hearing Loss: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the efficacy of various treatment modalities used for acute noise-induced hearing loss (aNIHL) from acute acoustic trauma (AAT) via a systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane, and Scopus databases. STUDY SELECTION: The scientific literature was searched up to October 2018 for articles evaluating hearing outcomes after treatment of aNIHL. DATA EXTRACTION: The following were extracted: Oxford level of evidence, number of patients, mean age, time to presentation, source of noise exposure, method of treatment/intervention, baseline hearing threshold, posttreatment hearing threshold, hearing gain, proportion of patients with no recovery, partial recovery, or complete recovery, and treatment complications. DATA SYNTHESIS: Sixteen studies with 932 patients met inclusion criteria for systematic review and four studies with 187 patients were included in the meta-analysis. CONCLUSIONS: Treatment modalities identified were steroids, vascular agents, nootropics, antioxidants, vitamins, cell apoptosis inhibitors, and hyperbaric oxygen therapy. Meta-analysis demonstrated significant improvement in mean hearing threshold for patients with high-frequency hearing loss, those treated within 48 hours, and those receiving treatment with a nootropic agent. Significant heterogeneity was present in experimental design among included studies and many were of lower levels of evidence. More prospective, large scale, randomized, double-blinded, placebo-controlled clinical trials are required to determine optimal treatment regimens for patients suffering from aNIHL caused by AAT.

Transcutaneous Electrical Stimulation Therapy in Obstructive Sleep Apnea: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the treatment efficacy of transcutaneous electrical nerve stimulation (TENS) in patients with obstructive sleep apnea (OSA). DATA SOURCES: Primary studies were identified though PubMed, Scopus, OVID, and Cochrane Library. REVIEW METHODS: Systematic review was conducted by querying databases for articles published through July 2019. The search identified randomized controlled trial, randomized comparison, or observational studies pertaining to TENS treatment for OSA. Meta-analysis was performed on pre- and posttreatment apnea-hypopnea index (AHI), mean oxygen saturation (SaO2), lowest oxygen saturation (LSAT), and arousal index (AI). RESULTS: Literature search identified 10 studies that reported sufficient outcome measures to be considered for analysis. A total of 198 patients were identified with a mean age of 50.9 years with a male to female ratio of 1.6:1. Average body mass index (BMI) of the cohort was 29.8 kg/m2. Treatment with TENS demonstrated reduction in AHI by 12.9 points (95% confidence interval, -22.3 to -3.43; P = .008). The mean differences in SaO2, LSAT, and AI did not reach statistical significance. CONCLUSION: The TENS treatment of upper airway dilator muscles resulted in reduction of AHI in patients with OSA. However, its effects on SaO2, LSAT, and AI were equivocal. Its impact on patients' quality of life could not be assessed due to heterogeneity in outcome measures. Future randomized controlled trials with generalizable standardized outcome measures are needed to assess the efficacy and compliance of TENS.

Transcutaneous Electrical Nerve Stimulation for Treatment of Tinnitus: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the treatment efficacy of transcutaneous electrical nerve stimulation (TENS) in patients with tinnitus. DATA SOURCES: PubMed, Scopus, Web of Science, and Cochrane Library were searched for the following concepts: "Transcutaneous Electric Nerve Stimulation" and "Tinnitus." STUDY SELECTION: Inclusion: 1) double- or single-blinded randomized controlled trials; 2) double- or single-blinded randomized comparison trials; 3) prospective or retrospective observational studies; and 4) case series. Exclusion: Non-English studies, nonhuman studies, case reports (n ≤ 5), and review articles. DATA EXTRACTION: Tinnitus Handicap Inventory (THI), the Visual Analog Scale (VAS), and perceived tinnitus suppression after treatment. Additional data collected included tinnitus laterality, duration of symptoms, location of electrode placement, time to follow-up, etiology of tinnitus, and treatment side effects. DATA SYNTHESIS: The literature search yielded 2941 unique articles. After reviewing 118 full-text articles, 17 studies reporting on 1,215 patients were included for final analysis. Four studies provided data available for meta-analysis of pre- and posttreatment THI and VAS (Cochrane Review Manager). TENS showed significant overall reduction on THI (-7.55 [-10.93 to -4.18], p < 0.0001) and VAS (-0.65 [-0.99 to -0.30], p < 0.0002). Subjective improvement of tinnitus was pooled across 13 studies using meta-analysis of proportions (MedCalc). Tinnitus suppression occurred in 40.0% [28.9-51.7%] patients. Among those who responded, 22.2% [12.2-29.7%] experienced complete suppression and 10.2% [0.2-31.9%] experienced persistent improvement at 3 months. CONCLUSIONS: TENS represents a safe and feasible treatment option for tinnitus and might be a worthy consideration among the spectrum of interventions developed for tinnitus.

Implantation of a defibrillator in a patient with an upper airway stimulation device.

The patient is a 62-year-old man with continuous positive airway pressure-intolerant obstructive sleep apnea who was enrolled in a study for a hypoglossal nerve upper airway stimulation device (UAS). Nearly 2.5 years later, he was admitted to the hospital for unstable angina. Diagnostic workup revealed a prior myocardial infarction, an ejection fraction of 30% on maximal medical therapy, and episodes of nonsustained ventricular tachycardia. During hospitalization, the patient received an implantable cardioverter defibrillator (ICD). This is the first reported case of simultaneous use of a UAS and an ICD, and we report no untoward device interference between the two implantable devices.

Upper airway stimulation for obstructive sleep apnea: The surgical learning curve.

OBJECTIVES/HYPOTHESIS: To determine the effect of surgeon experience with an upper airway stimulation (UAS) system on surgical time and complication rates. STUDY DESIGN: Retrospective review. METHODS: Surgical procedure times and complication rates observed in patients implanted at 22 study centers as part of a phase III, multicenter surgical trial of upper airway nerve stimulation therapy for obstructive sleep apnea were reviewed. RESULTS: The study included 126 subjects who were predominantly male (83%), with a mean age of 54.5 years (range = 31-80 years), and the mean body mass index was 28.4 ± 2.6. There were an average of 5.7 (range = 1-22) surgical implants per site, with an average surgical time of 2.52 ± 0.98 hours (range = 1.08-6.0 hours). The surgical implant time decreased significantly with surgeon experience, from 2.98 ± 1.18 hours for a surgeon's first implant (n = 22) to 2.08 ± 0.55 hours for the fifth implant (n = 10, P = .025). Surgical time was inversely correlated with the site implant number (rho = -0.334, P < .001). Procedure-specific complications were uncommon and self-limited and did not decrease appreciably with increasing experience. CONCLUSIONS: Surgical time for implantation of the UAS system decreased significantly after the first five implants and then stabilized. The rate of surgical complications did not decrease with surgeon experience, although this may be attributable to the low overall rate of serious surgical complications and low number of implants at some centers. LEVEL OF EVIDENCE: 4.

Hyperbaric oxygen therapy for the treatment of radiation-induced xerostomia: a systematic review.

OBJECTIVE: Radiation-induced xerostomia is one of the most common morbidities of radiation therapy in patients with head and neck cancer. However, in spite of its high rate of occurrence, there are few effective therapies available for its management. The aim of this study was to assess the efficacy of hyperbaric oxygen on the treatment of radiation-induced xerostomia and xerostomia-related quality of life. STUDY DESIGN: PubMed, Google Scholar, and the Cochrane Library were searched for retrospective or prospective trials assessing subjective xerostomia, objective xerostomia, or xerostomia-related quality of life. To be included, patients had to have received radiation therapy for head and neck cancer, but not hyperbaric oxygen therapy (HBOT). RESULTS: The systematic review initially identified 293 potential articles. Seven studies, comprising 246 patients, qualified for inclusion. Of the included studies, 6 of 7 were prospective in nature, and 1 was a retrospective study; and 2 of the 7 were controlled studies. CONCLUSIONS: HBOT may have utility for treating radiation-induced xerostomia refractory to other therapies. Additionally, HBOT may induce long-term improvement in subjective assessments of xerostomia, whereas other therapies currently available only provide short-term relief. The strength of these conclusions is limited by the lack of randomized controlled clinical trials.

Clinical and quality-of-life outcomes following gland-preserving surgery for chronic sialadenitis.

OBJECTIVES/HYPOTHESIS: Gland-preserving salivary surgery utilizing salivary endoscopy has been proposed as a treatment alternative in the management of chronic sialadenitis. This study seeks to determine medium-term clinical and quality-of-life (QOL) outcomes following a gland-preserving approach for chronic sialadenitis. STUDY DESIGN: Cross-sectional survey with retrospective chart review. METHODS: All patients undergoing attempted gland-preserving salivary surgery with salivary endoscopy for chronic sialadenitis at a tertiary, academic salivary referral center between October 2008 and April 2013 were identified from a quality assurance database. A research database was constructed to examine clinical factors of interest. A clinical outcomes and QOL survey was mailed to all eligible patients in order to obtain long-term follow-up data. RESULTS: A total of 206 of 306 (67%) eligible patients returned the survey. The median length of follow-up was 17 months (3-54 months). The majority of patients (89%) endorsed symptom improvement after gland-preserving therapy. Surgical excision was performed on 8% of affected glands. Patients with chronic sialadenitis due to stones reported a greater incidence of symptom resolution (P = 0.0004) and more favorable QOL outcomes (P = 0.0001) than patients with nonstone etiologies. CONCLUSIONS: Patients undergoing gland-preserving salivary surgery with salivary endoscopy for chronic sialadenitis have favorable long-term symptom improvement and gland retention rates. Although patients with stones demonstrated the best outcomes, improvement was documented for all etiologies of chronic sialadenitis. LEVEL OF EVIDENCE: 4.

Isotonic saline nasal irrigation is an effective adjunctive therapy to intranasal corticosteroid spray in allergic rhinitis.

BACKGROUND: This study was designed to determine if the addition of large-volume, low-positive pressure nasal irrigations delivered with isotonic sodium chloride (hereinafter "saline") added to intranasal corticosteroid therapy improves quality of life and objective measures of nasal breathing in patients with allergic rhinitis when compared with intranasal corticosteroid alone. METHODS: A prospective, unblinded, single-arm pilot study was performed of patients with allergic rhinitis already on intranasal corticosteroid pharmacotherapy. Patients added large-volume low-pressure saline irrigation twice daily for 8 weeks to their ongoing regiment of nasal corticosteroid. Mini-Rhinoconjunctivitis Quality of life Questionnaire (mRQLQ) assessment and nasal peak inspiratory flow (NPIF) were performed at baseline and at 4 and 8 weeks. RESULTS: A total of 40 patients were enrolled. Twice-daily nasal irrigation with isotonic saline significantly (p < 0.001) reduced mRQLQ scores, from 36.7 ± 20.48 (baseline) to 14.9 ± 11.03 (4 weeks) to 10.10 ± 10.65 (8 weeks). No significant changes were seen in NPIF, pattern use of nasal steroid use, or adverse events. CONCLUSION: Large-volume, low-positive pressure nasal irrigation with isotonic saline is an effective adjunctive therapy to improve quality of life in patients with allergic rhinitis already on intranasal corticosteroid therapy. This study was a part of the clinical trial NCT01030146 registered at clinicaltrials.gov.

Preclinical use of longitudinal MRI for screening the efficacy of S-nitrosoglutathione in treating spinal cord injury.

PURPOSE: To evaluate the therapeutic efficacy of S-nitrosoglutathione (GSNO) in spinal cord injury (SCI) using in vivo MRI in combination with neuorobehavioral testing and postmortem tissue analysis. MATERIALS AND METHODS: Sixteen female rats were mildly injured at the vertebral T10 level and randomized into control (n = 8) and GSNO-treatment (n = 8) groups. GSNO was delivered at 0.05 mg/kg dose in saline by means of tail vein at 1 hr postinjury and then given orally on the following days. On postinjury days 1, 3, 7, and 28, the rats were tested behaviorally, then scanned using sagittal T2-weighted MRI for the quantification of lesion, edema, and hemorrhagic regions at the injury site. Excised cords were analyzed using histology and immunohistochemistry. RESULTS: Treatment with GSNO was feasible in rats with SCI. On the average, the GSNO group at each scan day 1, 3, 7, and 28 exhibited better functional recovery as indicated by the behavioral performance of 52%, 33%, 19%, and 18%, and had smaller lesions of -4%, -16%, -20%, and -17% compared with the controls, respectively. Edema trend was parallel to the lesion volumes in both groups. Ex vivo data demonstrated that GSNO plays a role in neuronal tissue preservation and sparing. CONCLUSION: The data collectively provided the preliminary evidence that the injured rats responded favorably to GSNO treatment. Longitudinal MRI provides critical quantitative information regarding the changes in lesion properties, which helps evaluating the efficacy of an exogenous intervention in SCI.