Safety and Pharmacokinetics of a Ciprofloxacin and Azithromycin Stent for Chronic Rhinosinusitis.

OBJECTIVES: Previously, we developed a novel double-coated sinus stent containing ciprofloxacin (inner layer) and azithromycin (outer layer) (CASS), but released drug concentrations were found to be insufficient for clinical usage. Our objectives are to improve drug release of CASS and assess safety and pharmacokinetics in rabbits. METHODS: Dip coating was used to create the CASS with 2 mg ciprofloxacin and 5 mg azithromycin. A uniformed double coating was assessed with scanning electron microscopy (SEM), and the release patterns of both drugs and lactate dehydrogenase (LDH) assay were evaluated over 14 days in vitro. Safety, tolerability, and pharmacokinetics of the CASS were tested in rabbits through insertion into the maxillary sinus and evaluated with nasal endoscopy, CT scans, histology, blood counts and chemistries, and in vivo drug release. RESULTS: SEM confirmed the uniformity of the dual coating of ciprofloxacin and azithromycin, and thickness (µm) was found to be 14.7 ± 2.4 and 28.1 ± 4.6, respectively. The inner coated ciprofloxacin showed a sustained release over 14 days (release %) when soaked in saline solution (day 7, 86.2 ± 3.4 vs. day 14,99.2 ± 5.1). In vivo analysis showed that after 12 days, 78.92 ± 7.67% of CP and 84.12 ± 0.45% of AZ were released into the sinus. There were no significant differences in body weight, white blood cell counts, and radiographic changes before and after CASS placement. No significant histological changes were observed compared to the contralateral control side. CONCLUSION: Findings suggest that the CASS is an effective method for delivering therapeutic levels of antibiotics. Further studies are needed to validate efficacy in a preclinical sinusitis model. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

Glutathione and bicarbonate nanoparticles improve mucociliary transport in cystic fibrosis epithelia.

INTRODUCTION: Cystic fibrosis (CF) airway disease is characterized by thick mucus and impaired mucociliary transport (MCT). Loss of functional cystic fibrosis transmembrane receptor (CFTR) leads to acidification and oxidation of airway surface mucus. Replacing bicarbonate (HCO3 - ) topically fails due to rapid reabsorption and neutralization, while the scavenging antioxidant, glutathione sulfhydryl (GSH), is also rapidly degraded. The objective of this study is to investigate GSH/NaHCO3 nanoparticles as novel strategy for CF airway disease. METHODS: GSH/NaHCO3 poly (lactic-co-glycolic acid) nanoparticles were tested on primary CF (F508del/F508del) epithelial cultures to evaluate dose-release curves, surface pH, toxicity, and MCT indices using micro-optical coherence tomography. In vivo tests were performed in three rabbits to assess safety and toxicity. After 1 week of daily injections, histopathology, computed tomography (CT), and blood chemistries were performed and compared to three controls. Fluorescent nanoparticles were injected into a rabbit with maxillary sinusitis and explants visualized with confocal microscopy. RESULTS: Sustained release of GSH and HCO3 - with no cellular toxicity was observed over 2 weeks. Apical surface pH gradually increased from 6.54 ± 0.13 (baseline) to 7.07 ± 0.10 (24 h) (p < 0.001) and 6.87 ± 0.05 at 14 days (p < 0.001). MCT, ciliary beat frequency, and periciliary liquid were significantly increased. When injected into the maxillary sinuses of rabbits, there were no changes to histology, CT, or blood chemistries. Nanoparticles penetrated rabbit sinusitis mucus on confocal microscopy. CONCLUSION: Findings suggest that GSH/NaHCO3 - nanoparticles are a promising treatment option for viscous mucus in CF and other respiratory diseases of mucus obstruction such as chronic rhinosinusitis.

The Impact of Referral Source on Voice Therapy.

INTRODUCTION: Adherence to voice therapy is essential in achieving successful voice outcomes. Previous studies within the field of voice therapy have suggested that shorter wait times and utilization of an interprofessional practice (IPP) model of care have a positive effect on voice therapy completion rates. While the implementation of IPP has gained popularity, especially at academic voice centers, the majority of speech-language pathologists (SLP) practice in a traditional (T) setting where they are unaffiliated with the referring otolaryngologist. PURPOSE: This study aims to further examine how SLP practice models (interprofessional vs traditional) affect voice therapy initiation and completion rates. The secondary aim is to determine if voice therapy attendance rates have changed since the authors' initial investigations over 10 years ago. METHODS: A retrospective chart review of 452 patients was conducted. Data was collected on patient demographics (sex, age), diagnosis, severity of dysphonia (CAPE-V), quality of life impact (V-RQOL raw score), practice setting (IPP vs T), date of referral, date of voice therapy initial evaluation, number of therapy sessions completed, and attendance to therapy sessions defined as completion or dropout. RESULTS/CONCLUSIONS: Initiation of voice therapy treatment was the point in the referral process that was most impacted by practice model. Over half (53%) of referrals to voice therapy in a traditional practice model did not lead to initiation of treatment, while only 23% of the referrals taking place in an IPP model failed to initiate (P < 0.001). This study also demonstrated an improving, but continued rate of noninitiation and dropout from voice therapy when compared to data that was collected 10 years prior.

Postoperative Opioid Use in Rhinoplasty Procedures: A Standardized Regimen.

The objective of this study was to create a standardized regimen for preoperative and postoperative analgesic prescribing patterns in rhinoplasty. A prospective study including patients (n = 35) undergoing rhinoplasty by a single surgeon at a tertiary hospital was conducted. Patients were enrolled in this study from August 2018 to November 2019. Patients then completed a diary documenting pain scores and analgesic use for 14 days postoperatively. Patient demographics, complications, rhinoplasty technique performed, and medical history were noted. At the second postoperative clinic visit, the diaries were submitted and pill counts were conducted to ensure accuracy. A total of 23 patients completed this study. The average age of the cohort was 39.07 ± 15.01 years, and 48% were females. The mean number of opioids consumed was 6.15 ± 4.85 pills (range: 0-18). Females consumed an average of 7.2 ± 5.2 pills and males consumed 4.5 ± 3.96 pills. The mean number of acetaminophen and ibuprofen tablets consumed were 7.48 ± 8.52 pills (range: 0-36) and 10.83 ± 10.99 pills (range 0-39), respectively. No postoperative nosebleeds were reported. Males had significantly higher pain scores than females on postoperative days 1 to 8. The mean pain score for postoperative days 8 to 14 was less than 1. Linear regression analysis showed that there was no association between the rhinoplasty technique used and the number of opioids consumed. Rhinoplasty is typically associated with mild pain even when osteotomies are included with the procedure. Our results suggest that surgeons can limit rhinoplasty opioid prescriptions to around seven pills and achieve sufficient pain control in most patients. Preoperative counseling suggesting a low postoperative pain level and the encouragement of nonsteroidal anti-inflammatory drug use will help reduce the risk and misuse of opioid prescriptions.

Development of smart anti-glycan reagents using immunized lampreys.

Studies on the expression of cellular glycans are limited by a lack of sensitive tools that can discriminate specific structural features. Here we describe the development of a robust platform using immunized lampreys (Petromyzon marinus), which secrete variable lymphocyte receptors called VLRBs as antibodies, for generating libraries of anti-glycan reagents. We identified a wide variety of glycan-specific VLRBs detectable in lamprey plasma after immunization with whole fixed cells, tissue homogenates, and human milk. The cDNAs from lamprey lymphocytes were cloned into yeast surface display (YSD) libraries for enrichment by multiple methods. We generated VLRB-Ig chimeras, termed smart anti-glycan reagents (SAGRs), whose specificities were defined by microarray analysis and immunohistochemistry. 15 VLRB antibodies were discovered that discriminated between linkages, functional groups and unique presentations of the terminal glycan motif. The development of SAGRs will enhance future studies on glycan expression by providing sequenced, defined antibodies for a variety of research applications.

Does Medicaid expansion improve access to care for the first-time shoulder dislocator?

BACKGROUND: The purpose of this study was to assess the effect of individual state Medicaid expansion status on access to care for shoulder instability. METHODS: Four pairs of Medicaid expanded (Louisiana, Kentucky, Iowa, and Nevada) and unexpanded (Alabama, Virginia, Wisconsin, and Utah) states in similar geographic locations were chosen for the study. Twelve practices from each state were randomly selected from the American Orthopedic Society for Sports Medicine directory, resulting in a sample size of 96 independent sports medicine offices. Each office was called twice to request an appointment for a fictitious 16-year-old first-time shoulder dislocator with either in-state Medicaid insurance or Blue Cross Blue Shield (BCBS) private insurance. RESULTS: A total of 91 physician offices in 8 states were contacted by telephone. An appointment was obtained at 36 (39.6%) offices when calling with Medicaid and at 74 (81.3%) offices when calling with BCBS (P < .001). Thirty-five (38.5%) offices were able to make appointments for both types of insurance, 39 (42.9%) for only BCBS, 1 (1.1%) for only Medicaid, and 16 (17.5%) for neither. For Medicaid patients, an appointment was booked in 13 (27.7%) clinics from Medicaid expanded states and in 23 (52.3%) clinics from unexpanded states (P = .016). CONCLUSION: For a first-time shoulder dislocator, access to care is more difficult with Medicaid insurance compared with private insurance. Within Medicaid insurance, access to care is more difficult in Medicaid expanded states compared with unexpanded states. Medicaid patients in unexpanded states are twice as likely as those in expanded states to obtain an appointment.

Prevalence of chronic rhinosinusitis in bronchiectasis patients suspected of ciliary dyskinesia.

BACKGROUND: Mucociliary clearance is a main defense mechanism of the airway and is impaired in ciliary dyskinesia. The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia. METHODS: Bronchiectasis patients referred to a rhinology clinic for nasal brush biopsy (NBB) were included in this study. NBB was performed using a curettage technique whereby ciliated epithelial cells were obtained from the surface of the inferior nasal turbinate. Results of transmission electron microscopy findings, primary ciliary dyskinesia (PCD) gene (35 genes) analyses (Invitae), and sinus computed tomography (CT) scans were reviewed. RESULTS: Twenty-three patients (age, 54 ± 2.9 years) were referred for NBB between 2015 and 2018. Thirteen patients (56.5%) met the criteria for diagnosis of CRS. Nineteen patients had ciliary ultrastructural defects. The most common finding was compound cilia (n = 11, 47.8%). Five patients (21.7%) had central microtubule defects (CMD) with higher forced expiratory volume in 1 second (FEV1 ) at the time of referral than those without CMD (CMD+ , 91 ± 3.7%; CMD- , 73.5 ± 5.7%; p = 0.023). Of 15 subjects with a PCD gene panel, 67% (9 of 15) carried at least 1 gene associated with PCD. Only 1 patient reached diagnosis of PCD. Approximately 50% of non-PCD carriers had a smoking history (p < 0.05). Lund-Mackay scores did not significantly differ between PCD and non-PCD carriers (p = 0.72). CONCLUSION: Nearly half of bronchiectasis patients referred for NBB had concurrent CRS. The presence of ciliary abnormalities was not amplified in bronchiectasis patients with CRS compared to those without CRS. Extrinsic factors may be related to ciliary structural abnormalities in non-PCD gene carriers.

Using nudges to reduce waste? The case of Toronto's plastic bag levy.

The overuse of disposable plastic bags is a major environmental problem across the globe. In recent years, numerous jurisdictions have sought to curb disposable bag use by implementing a levy or fee at the point of purchase. These levies are typically small and symbolic (around $0.05 per bag), but serve as a highly-visible and continuous reminder to consumers. As such, they are consistent with nudging policies that seek to encourage broad changes in behaviour through small, non-coercive measures that influence people's thinking about an issue. While existing empirical evidence suggests that nudges are highly effective in reducing disposable bag use, we argue that many of these studies are flawed because they lack adequate temporal and geographic controls. We use longitudinal data from four waves of a major Canadian survey to analyze the effect of a disposable bag levy in the City of Toronto. Controlling for demographics and changes in social norms over time, we find that the levy increased the use of reusable shopping bags by 3.4 percentage points. Moreover, we find that the impact of the policy was highly variable across behavioural and demographic groups. The levy was highly effective in encouraging people who already used reusable bags to use them more frequently, while having no effect on infrequent users. We also find that the effects are limited to households with high socio-economic status (as measured by income, educational attainment, and housing situation). This suggests important limitations for nudging policy more generally, as people with lower socio-economic status appear to have been unaffected by this behavioural prompt.