A systematic review and meta-analysis of neuromodulators to treat chronic airway hypersensitivity.

OBJECTIVES: Chronic laryngitis can present with numerous symptoms, including chronic cough. Patients who do not respond to standard treatment are sometimes diagnosed with chronic airway hypersensitivity (CAH). In many centers, neuromodulators are prescribed off-label despite limited evidence of efficacy. A previous meta-analysis suggested neuromodulator therapy improved cough-related quality-of-life (QoL). This current updated and expanded meta-analysis examined whether neuromodulators reduced cough frequency, reduced cough severity, and/or improved QoL in CAH patients. DATA SOURCES: PubMed, Embase, Medline, Cochrane Review, and publication bibliographies were searched from 01/01/2000 to 07/31/2021 using MESH terms. REVIEW METHODS: PRISMA guidelines were followed. 999 abstracts were identified/screened, 28 studies were fully reviewed, and 3 met inclusion criteria. Only randomized controlled trials (RCT) investigating CAH patients with comparable cough-related outcomes were included. Three authors reviewed potentially eligible papers. Fixed-effect models and calculated pooled estimates using the Inverse-Variance method were used. RESULTS: The estimated difference in change in log coughs per hour (from baseline to intervention end) between treatment and control groups was -0.46, 95%CI [-0.97; 0.05]. Estimated change-from-baseline in VAS scores was -12.24, 95 % CI [-17.84; -6.65] lower for patients who received treatment vs placebo. Estimated change-from-baseline for LCQ scores was 2.15, 95 % CI [1.49-2.80] higher for patients who receive treatment vs placebo. Only change in LCQ score was clinically significant. CONCLUSIONS: This study tentatively suggests that neuromodulators have the potential to reduce cough symptoms associated with CAH. However, high-quality evidence is lacking. This could be due to limited treatment effect or significant limitations in the design and comparability of existing trials. A well-designed and properly powered RCT is needed to authoritatively test the efficacy of neuromodulators for the treatment of CAH. LEVEL OF EVIDENCE: Level I, evidence from a systematic review or meta-analysis of all relevant RCTs (randomized controlled trial) or evidence-based clinical practice guidelines based on systematic reviews of RCTs or three or more RCTs of good quality that have similar results.

Evaluating the use of baclofen as adjunct treatment for muscle tension dysphonia.

OBJECTIVE: To explore whether use of baclofen as adjunct treatment to voice therapy (VT) led to improvement in subjective throat symptoms in patients with primary muscle tension dysphonia (MTD). MTD is associated with excessive paralaryngeal muscle contraction, and baclofen is a muscle relaxant. STUDY DESIGN: Cross-sectional, questionnaire-based study. METHODS: An initial pool of patients, who were diagnosed with primary MTD and received 1+ VT session(s) at a single tertiary-care center from 2015 to 2019, were placed into either a baclofen group (prescribed 10 mg baclofen t.i.d. PRN along with VT) based on symptomatology or non-baclofen group (VT alone). They were administered questionnaires via postage mail or phone that included the Voice Handicap Index-10 (VHI-10), Reflux Symptom Index (RSI), and other survey elements. A retrospective chart review collected demographic and other clinical data from recruited participants. RESULTS: A total of 314 non-baclofen and 63 baclofen patients met the inclusion criteria of this study, with 37 non-baclofen patients (mean age = 47.5 years, 62.2% female) and 15 baclofen patients (mean age = 45.5 years, 73.3% female) recruited. There was no significant difference in mean [SD] VHI-10 scores (11.30 [8.20] vs. 12.60 [10.75]; p = 0.638) and RSI scores (13.46 [10.44] vs. 16.20 [10.65]; p = 0.398) between non-baclofen and baclofen groups, respectively. CONCLUSION: There was no significant difference in voice psychometric outcomes between non-baclofen and baclofen groups, measured primarily by the VHI-10 and RSI questionnaire components. Further studies are warranted to assess the efficacy and safety of baclofen as a therapeutic option for MTD.

The use of vitamin D in preventing post-thyroidectomy hypocalcemia: An endocrinologist survey study.

OBJECTIVE: To evaluate the use of preoperative vitamin D levels and postoperative vitamin D supplementation among endocrinologists for the prevention of post-thyroidectomy hypocalcaemia. METHODS: Endocrinologist members of the American Thyroid Association (ATA) were contacted via email to complete a 21-question survey, which included both questions about demographic information, and preventing and managing postoperative hypocalcaemia after thyroidectomy. Univariate and multivariate analysis was performed to determine the respondents' use of preoperative vitamin D levels, dose and duration of preoperative vitamin D repletion, decision to delay surgery for low vitamin D levels in the case of a benign or malignant disease, and routine prescription of postoperative calcium or vitamin D supplementation. RESULTS: 225 endocrinologists who were ATA members responded to the questionnaire. When compared to endocrinologists practicing in other countries, those that practice in the United States were 2.5 times more likely to check preoperative vitamin D levels (95% CI[1.404, 4.535], P = .002), significantly more likely to replete vitamin D deficient patients with high-dose vitamin D (ie ≥50K IU/week), 4.458 times more likely to prescribe prophylactic supplemental calcium (95% CI[2.446, 8.126]; P < .0001) and 3.48 more likely to prescribe supplemental vitamin D (95% CI [1.906, 6.355]; P < .0001). Endocrinologists who have been in practice for >10 years were also 1.915 times more likely to prescribe supplemental vitamin D (95% CI (1.080, 3.395); P = .0263). Physicians that treat >50 thyroidectomy cases/year were 2.083 more likely to recommend a vitamin D repletion duration of >1 month than those that treat ≤50 cases/year ([1.036, 4.190], P = .0395). Lastly, if the patient has low preoperative vitamin D levels, 47.05% of respondents chose to delay surgery in a benign disease, while only 11.61% of respondents would do so in a case of malignant disease. CONCLUSIONS: Approximately one-half of surveyed endocrinologists reported using preoperative vitamin D levels to assess a patient's risk for post-thyroidectomy hypocalcaemia. Endocrinologists practicing in the United States, compared to those practicing in other countries, were more likely to both test for preoperative vitamin D levels and to recommend prophylactic post-thyroidectomy calcium and vitamin D supplementation.

Randomized double blind trial of amitriptyline versus placebo in treatment of chronic laryngopharyngeal neuropathy.

OBJECTIVE: A neuropathic etiology has been suggested for patients with chronic laryngopharyngitis symptoms without visible structural pathology. Prior studies have shown that treatment with neuro-modulating medications is beneficial, but it is unknown if this was due to placebo effect. Our objective was to compare the efficacy of amitriptyline versus placebo in treating chronic laryngopharyngeal neuropathy. STUDY DESIGN: Prospective, randomized placebo-controlled trial. METHODS: Patients were randomized to receive placebo or amitriptyline for 8weeks. Primary outcome was change in modified Reflux Symptom Index (mRSI) score. Secondary outcomes were change in Voice Handicap Index-10 (VHI) scores, rates of adverse effects, and overall symptom severity. RESULTS: Eighteen patients completed the study. The average difference in mRSI and VHI-10 scores after treatment were not significantly different between study arms. However, more subjects taking amitriptyline felt their symptoms had subjectively improved (6 out of 9, 67%), while the remainder noted no change. In the placebo group, only 4 out of 9 subjects (44%) felt their symptoms were better and 2 felt worse. Subjects took an average of 25mg of amitriptyline or placebo daily by the end of the 8-week treatment period. No serious adverse effects were noted. CONCLUSION: Although there was a trend toward greater subjective improvement in overall symptoms with amitriptyline, interpretation is limited due to the small sample size. Larger randomized controlled trials to determine the efficacy of neuro-modulating agents in the treatment of chronic laryngopharyngeal neuropathy, as well as better metrics to characterize this disorder, are warranted.

Endoscopic Assessment of Swallowing After Prolonged Intubation in the ICU Setting.

OBJECTIVES: The purpose of this study was to identify the frequency of swallowing dysfunction after extubation in a sample of patients with no preexisting dysphagia. METHODS: Mechanically ventilated patients in the ICU with no prior history of dysphagia received a flexible endoscopic evaluation of swallowing (FEES) exam within 72 hours after extubation. The FEES was then analyzed for variables related to swallowing patterns and laryngeal pathology. Univariate analyses were performed to identify relationships between variables. RESULTS: Fifty-nine patients were included in this study. After extubation, 21 (35.6%) penetrated and 13 (22.0%) aspirated. The mean days intubated was 9.4 ± 6.1. Various forms of laryngeal injury were associated with worse swallowing scores, and delayed onset of the swallow was a common finding in all patients post extubation. Of the 44 participants evaluated ≤ 24 hours post extubation, 56.8% penetrated/aspirated. Of the 15 patients evaluated >24 hours post extubation, 60.0% penetrated/aspirated. CONCLUSIONS: This study found a high frequency of dysphagia after prolonged intubation in patients with no preexisting dysphagia. Important variables leading to dysphagia are often overlooked, such as swallowing delay and laryngeal pathology. The timing of swallowing assessments did not reveal any difference in dysphagia frequency, suggesting that it might not be necessary to wait to perform dysphagia screens or evaluations.

Impact of Insurer on Papillary Thyroid Carcinoma Outcomes, Stage, and Treatment Modalities.

BACKGROUND: While the impact of insurance has been described for thyroid cancer as a whole, we sought to further characterize this relationship for the papillary sub-group (PTC). METHODS: Those patients with primary site thyroid tumors from 2007 to 2016 with histology-confirmed PTC were extracted from the SEER database. These parameters yielded 103 219 participants for demographic, extent of disease, and treatment parameter study and 103 025 for outcome studies. RESULTS: Compared to their counterparts, those with Medicaid were more likely to have stage T3 or greater (<.0001) disease at presentation. Those with Medicare/private insurance were more likely to have No staging at diagnosis (P < .0001). Similarly, those with Medicaid exhibited poorer overall (98.0%, 90.9%, 81.6% vs 98.9%, 95.0%, 90.0%; P < .0001) and cause-specific (99.3%, 98.0%, 95.8% vs 99.7%, 99.1%, 98.4%; P < .0001) survival after 1, 5, and 9 years respectively. CONCLUSION: Insurer has a significant impact on the stage at diagnosis of papillary thyroid carcinoma while having limited effect on the treatment modalities offered. Statistically significant overall and cause-specific mortality differences were appreciated but are likely clinical insignificant. Further work to elucidate the social factors likely affecting these patients is warranted.

The Relationship Between Pitch Discrimination and Fundamental Frequency Variation: Effects of Singing Status and Vocal Hyperfunction.

PURPOSE: The purpose of this study was to investigate the relationship between pitch discrimination and fundamental frequency (fo) variation in running speech, with consideration of factors such as singing status and vocal hyperfunction (VH). METHOD: Female speakers (18-69 years) with typical voices (26 non-singers; 27 singers) and speakers with VH (22 non-singers; 30 singers) completed a pitch discrimination task and read the Rainbow Passage. The pitch discrimination task was a two-alternative forced choice procedure, in which participants determined whether tokens were the same or different. Tokens were a prerecorded sustained /ɑ/ of the participant's own voice and a pitch-shifted version of their sustained /ɑ/, such that the difference in fo was adaptively modified. Pitch discrimination and Rainbow Passage fo variation were calculated for each participant and compared via Pearson's correlations for each group. RESULTS: A significant strong correlation was found between pitch discrimination and fo variation for non-singers with typical voices. No significant correlations were found for the other three groups, with notable restrictions in the ranges of discrimination for both singer-groups and in the range of fo variation values for non-singers with VH. CONCLUSIONS: Speakers with worse pitch discrimination may increase their fo variation to produce self-salient intonational changes, which is in contrast to previous findings from articulatory investigations. The erosion of this relationship in groups with singing training and/or with VH may be explained by the known influence of musical training on pitch discrimination or the biomechanical changes associated with VH restricting speakers' abilities to change their fo.

A mini-invasive approach is feasible in patients with primary hyperparathyroidism and discordant or negative localisation studies.

Preoperative localisation of pathological glands in patients with primary hyperparathyroidism (PHP) is the mainstay for mini-invasive parathyroidectomy. Nevertheless, a not negligible number of patients presents discordant or negative neck ultrasound (US) and 99mTc-Sestamibi (MIBI) scan. The aim of this study was to assess if a mini-invasive approach is feasible in this kind of patients. In this retrospective study were included patients that underwent parathyroidectomy for PHP. Patients were divided into two groups according to concordance of US and MIBI scan results. 242 patients were included: 183 had concordant preoperative studies, and 59 had discordant or negative studies. A mini-invasive approach was possible in 42 (72.9%) patients with unclear preoperative studies, whereas 12 (20.3%) additional patients required conversion to BNE. The incidence of persistent PHP was higher in patients with unclear preoperative studies (8.5% vs 2.7%), but this difference did not reach a statistical significance (p = 0.121). In patients with unclear preoperative studies, a negative result of intraoperative PTH allowed to avoid a persistent disease in 12 patients, while in 3 cases led to an unnecessary additional exploration. In patients with discordant preoperative studies a mini-invasive approach is feasible; in this setting, the use of intraoperative PTH is mandatory to reduce the incidence of persistent PHP.

Social determinants of health and treatment decisions in head and neck cancer.

BACKGROUND: This study compares select social determinants of health (SDOH) with treatment modality selection and treatment completion in head and neck cancer (HNC) patients, to better understand disparities in health outcomes. METHODS: A retrospective cohort study of HNC (n = 1428) patients was conducted. Demographic and disease-specific variables were recorded, including treatment modality selection and completion. Data were analyzed using two-sample t tests, chi-square, and Fisher's exact tests. RESULTS: Primary language was significantly associated with treatment choice, where non-English speakers were less likely to choose treatment as recommended by the Tumor Board. Lower mean distance from the hospital (37.38 [48.31] vs. 16.92 [19.10], p < 0.0001) and a county-based higher mean percentage of bachelor degree or higher education (42.16 [8.82] vs. 44.95 [6.19], p < 0.0003) were associated with treatment selection. CONCLUSION: Language, distance from the hospital, and education affected treatment selection in this study and may be useful in understanding how to counsel patients on treatment selection for HNC.

The Role of Vitamin D as a Prognostic Marker in Papillary Thyroid Cancer.

The role of vitamin D in modulating several cancer-related pathways has received an increasing amount of attention in the past several years. Previous literature has found an abundance of evidence of vitamin D exerting an anti-proliferative, anti-inflammatory, and pro-differentiation effect in various types of cancers including breast, colon, prostate, and pancreatic cancer. Although the link between vitamin D and thyroid cancer remains controversial, both biochemical evidence and clinical studies have attempted to establish a link between papillary thyroid carcinoma (PTC) and vitamin D status. Furthermore, the use of vitamin D as a prognostic marker has received increased attention, both in regards to clinical outcomes and cancer staging. In this review, we briefly discuss the metabolism and proposed mechanism of action of vitamin D in the context of PTC, and explore links between modulators in the vitamin D pathway and progression of PTC. We provide evidence from both clinical studies as well as molecular studies of metabolic targets, including vitamin D receptor and activating enzymes exerting an effect on PTC tissue, which indicate that vitamin D may play a significant prognostic role in PTC.

The role of Rapid Intraoperative Parathyroid Hormone (ioPTH) assay in determining outcome of parathyroidectomy in primary hyperparathyroidism: A systematic review and meta-analysis.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder. In the last few decades, the introduction of Rapid Intraoperative Parathyroid Hormone (ioPTH) monitoring has allowed to ensurance of the excision of all hyperfunctioning parathyroid tissues, reducing the risks of persistent and recurrent PHPT. However, the use of ioPTH is still debated among endocrine surgeons. MATERIAL AND METHODS: The objective of this systematic review and meta-analysis was to assess if ioPTH monitoring is able to reduce the incidence of persistent or recurrent PHPT. A systematic literature search was performed using PubMed, Scopus, ISI-Web of Science and Cochrane Library Database. Prospective and retrospective studies addressing the efficacy of ioPTH monitoring were included in the systematic review and meta-analysis. The random-effects model was assumed to account for different sources of variation among studies. The overall effect size was computed through the inverse variance method. Heterogeneity across studies, possible outlier studies, and publication bias were evaluated. RESULTS: A total of 28 studies with 13,323 patients were included in the quantitative analysis. The incidence of operative failure was 3.2% in the case group and 5.8% in the control group. After excluding three outlier studies, the quantitative analysis revealed that ioPTH reduced significantly the incidence of postoperative persistent or recurrent PHPT. (Risk Difference = -0.02; CI = -0.03, -0.01; p < 0.001). There was no evidence of heterogeneity among the studies (Q = 19.92, p = 0.70; I2 = 0%). The analysis of several continuous moderators revealed that the effectiveness of ioPTH was larger in studies with lower preoperative serum calcium values and higher incidences of multiple gland disease. CONCLUSION: ioPTH monitoring is effective in reducing the incidence of persistent and recurrent PHPT. Its routine use should be suggested in the next guidelines regarding management of PHPT.

Risk factors of permanent hypoparathyroidism after total thyroidectomy Retrospective analysis of 285 consecutive patients.

AIM: Permanent hypoparathyroidism is the most common long-term complication after total thyroidectomy. The aim of the present study was to investigate the risk factors of this complication. MATERIAL AND METHODS: Patients undergoing thyroidectomy in our Unit between January 2017 and February 2018 were retrospectively analysed. They were divided into 2 groups: those with normal parathyroid function in the long term were included in Group A, those who developed permanent hypoparathyroidism in Group B. RESULTS: Two hundred and eighty-five patients were included in this study: 271 in Group A and 14 in Group B. No statistically significant difference was found in terms of sex, age, extent of surgery, rate of retrosternal goiter, postoperative stay and histopathological findings between the 2 groups. On the contrary, mean operative time, rate of patients with PTH values < 6.3 pg/mL on postoperative day 1 and mean thyroid weight were significantly greater in Group B than in Group A (P = 0.049, P < 0.001, P = 0.014; respectively). CONCLUSIONS: Long operative times, PTH levels < 6.3 pg/mL on postoperative day 1 and high thyroid weight have proved to be strong risk factors of permanent hypoparathyroidism after total thyroidectomy. Thus, in these cases a careful follow-up is highly recommended. KEY WORDS: Permanent hypoparathyroidism, Risk factors, Total thyroidectomy.

Survival characteristics of injected human cartilage slurry in a nude mouse model: a preliminary study.

We conducted a study to examine the viability, host response, and volume retention characteristics of drilled human septal cartilage slurry when injected into an athymic nude mouse model. We injected 0.2 ml of the slurry into the hind limbs of 6 mice. The mice were sequentially sacrificed over a period of 180 days. Histologic reviews of the hind limbs were performed to determine the viability of injected chondrocytes, host response, and volume retention. Specimens were obtained and histomorphologic analysis was performed at 1, 30, 90, and 180 days after injection. We identified viable cartilage throughout the study. Cartilage injection was well tolerated, and minimal inflammatory reaction occurred without significant adverse effects. The injected bolus of cartilage was found to have progressively dispersed throughout the muscle over time. Our findings warrant further investigation with a larger cohort of nude mice or possibly human subjects.

Singing voice handicap and videostrobolaryngoscopy in healthy professional singers.

OBJECTIVES: This study correlates the Singing Voice Handicap Index (SVHI) scores with videostrobolaryngoscopy in healthy professional singers as a measure of self-perceived vocal health versus actual pathology seen on examination. The objective was to measure the strength of self-assessment among professional singers and determine if there is a benefit of combining SVHI and videostrobolaryngoscopy for routine assessment of singers without an obvious singing voice problem. STUDY DESIGN: Prospective cross-sectional study. METHODS: Forty-seven singers were included in the study. Singers produced spoken and sung pitches during videostrobolaryngoscopy. Examinations were blindly rated by two independent fellowship-trained laryngologists who assessed vocal fold appearance and function. The correlation between SVHI scores and total pathologic findings seen on videostrobolaryngoscopy was analyzed using linear regression and serial t tests. RESULTS: SVHI scores (mean of 22.45/144) were as expected for healthy singers. However, although all singers self-identified as healthy, laryngeal abnormalities were relatively common. The interrater reliability of total pathologic findings between two laryngologists was 71% (P = 0.006). Linear regression found no significant correlation (P = 0.9602) between SVHI scores and videostrobolaryngoscopy findings. CONCLUSION: Greater than expected laryngeal pathology was seen in these professional singers, who identified themselves as healthy, which possibly indicates a minimal impact on their singing voice and/or perception of vocal health. These findings demonstrate that laryngeal appearance alone does not dictate nor fully explain the sound or apparent health of a professional singer. Sustaining good vocal health is complex, and even experienced singers may not reliably assess the presence of pathology.