Intranasal Atomized Dexmedetomidine in Combination with Intranasal Atomized Butorphanol for dressing change sedation and analgesia in adult burn patients: A Randomized Clinical Trial.

We aimed to evaluate the efficacy of the Intranasal Atomized Dexmedetomidine (IAD)+Intranasal Atomized Butorphanol (IAB) combination therapy on adult burn patients undergoing dressing changes. Herein, 46 adult burn patients were enrolled and randomly divided into two groups: Dexmedetomidine-Butorphanol (DB) and Saline-Butorphanol (SB), treated with atomized dexmedetomidine+butorphanol and saline +butorphanol, respectively. The primary outcomes were the Ramsay Sedation Scale (RSS) and the Visual Analog Scale (VAS) scores. The secondary outcomes were Mean Blood Pressure (MBP), Heart Rate (HR), Respiratory Rate (RR), peripheral blood oxygen saturation (SpO2), total butorphanol consumption, and Adverse Effects (AEs). The two groups were comparable in age, sex, weight, and Total Burn Surface Area (TBSA). During dressing changes, the DB group exhibited significantly lower RSS levels (P<0.05). Besides, the two groups showed no significant differences in VAS scores across all measurement time points. Notably, the DB group exhibited decreased MBP at the beginning of the operation (P<0.0001), 10 min after (P<0.0001), and 20 min after (P=0.0205). HR decreased significantly at the beginning (P=0.0005) and 10 min after (P=0.0088) in the DB group. Furthermore, the two groups showed no significant differences in RR and SpO2 levels. Additionally, the rescue butorphanol dose was lower in the DB group (P<0.001). Finally, dizziness and nausea incidences were significantly lower in the DB group (P<0.05). In conclusion, besides its hemodynamic adverse reactions, the IAD+IAB combination therapy exerted a better sedation effect in adult burn patients than IAB treatment alone.

Overcoming treatment-resistant depression with machine-learning based tools: a study protocol combining EEG and clinical data to personalize glutamatergic and brain stimulation interventions (SelecTool Project).

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens.

Pharmacovigilance of esketamine nasal spray: an analysis of the FDA adverse event reporting system database.

Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the Food and Drug Administration (FDA) adverse event reporting system (FAERS) database between 2019 Q1 and 2023 Q4. Reporting odds ratio (ROR), proportional reporting ratio (PRR), and multi-item gamma Poisson shrinker (MGPS) were performed to detect risk signals from the FAERS data to identify potential ESK-NS-AEs associations. A total of 14,606 reports on AEs with ESK-NS as the primary suspected drug were analyzed. A total of 518 preferred terms signals and 25 system organ classes mainly concentrated in psychiatric disorders (33.20%), nervous system disorders (16.67%), general disorders and administration site conditions (14.21%), and others were obtained. Notably, dissociation (n = 1,093, ROR 2,257.80, PRR 899.64, EBGM 876.86) exhibited highest occurrence rates and signal intensity. Moreover, uncommon but significantly strong AEs signals, such as hand-eye coordination impaired, feeling guilty, and feelings of worthlessness, were observed. Additionally, dissociative disorder (n = 57, ROR 510.92, PRR 506.70, EBGM 386.60) and sedation (n = 688, ROR 172.68, PRR 155.53, and EBGM 142.05) both presented strong AE signals, and the former is not recorded in the Summary of Product Characteristics (SmPC). In clinical applications, close attention should be paid to the psychiatric disorders and nervous system disorders, especially dissociation. Meanwhile, clinical professionals should be alert for the occurrence of AEs signals not mentioned in the SmPC and take preventive measures to ensure the safety of clinical use.

Whole-Genome Deep Sequencing of the Healthy Adult Nasal Microbiome.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the "gateway microbiomes". Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18-48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

Onset-of-Efficacy of Azelastine HCl 0.15% Nasal Spray for allergic rhinitis in an environmental exposure chamber.

BACKGROUND: Azelastine nasal spray is effective in relieving symptoms of seasonal and perennial allergic rhinitis. OBJECTIVE: The objective of this single center, double-blinded, placebo-controlled, crossover study was to evaluate the time to onset of efficacy of azelastine HCl 0.15% vs placebo in participants with seasonal allergic rhinitis. METHODS: 110 participants aged 18 to 65 years were randomized to receive azelastine HCl 0.15% two sprays per nostril vs placebo nasal spray after being continuously exposed to ragweed pollen in an environmental exposure chamber (EEC). Symptoms were evaluated subjectively by the total nasal symptom score (TNSS) scale. The primary efficacy parameter was the time to onset of efficacy of azelastine as measured by the change from baseline in TNSS 15, 30, 45, 60, 90, 120, 180, and 240-minute post-dose. RESULTS: The azelastine nasal spray group had statistically significant improvement in TNSS compared with placebo 30 minutes post-dose (p=0.0002), and the effect was sustainable throughout the EEC session for all subsequent time points (p<0.0001). Adverse events were mild, including bitter taste, nasal discomfort, epistaxis, sinusitis, and nausea. No major adverse events were reported during the study. CONCLUSION: Azelastine HCl 0.15% nasal spray relieves nasal symptoms associated with allergic rhinitis and has a fast onset of action within 30 minutes. The overall safety profile of azelastine has also been proven to be safe. These results, along with prior findings on efficacy and improved quality of life for people suffering from allergic rhinitis, establish the important clinical role of azelastine HCl 0.15%.

Effect of Olfactory Rehabilitation on the Recovery of Post-Coronavirus Disease Olfactory Dysfunction: A Randomized Controlled Trial.

Introduction Persistent olfactory dysfunction was seen in many patients upon coronavirus disease 2019 (COVID-19) infection recovery. However, research on its management was very limited, especially among the Southeast Asian population. Objectives We aim to investigate the role of olfactory rehabilitation and topical corticosteroids among post-COVID-19 olfactory dysfunction patients in Malaysia, and at the same time to determine factors leading to olfactory recovery post-COVID-19 infection. Methods Adult Malaysians with persistent olfactory dysfunction one month post-COVID-19 recovery were recruited. Thirty-one patients were randomly assigned into three groups with 10 patients being given olfactory training (Group 1), another 10 being given mometasone furoate nasal spray/olfactory training (Group 2), and 11 patients being assigned to the control group (Group 3). All groups were followed up for an average duration of six months. Olfactory function was evaluated by Top International Biotech Smell Identification Test (TIBSIT) scores and Olfactory Disorder Questionnaire (eODQ) prior to randomization, at three and six months after recruitment. Results The baseline characteristics of patients were similar in all groups. Generally, patients of all three groups showed a statistically significant improvement in the TIBSIT scores after six months. The TIBSIT scores for Group 2 were statistically significantly higher than the control at three months but not at six months. As for Group 1, no statistically significant differences in TIBSIT scores at both three and six months were noted when compared to control. Statistically significant improvements were seen in the eODQ scores in all three groups. Conclusion No superiority of intervention for post-COVID-19 olfactory dysfunction was seen compared to control.

Efficacy of 0.1% Xylometazoline-Hydrochloride Nasal Decongestant Spray in Postoperative Sign/Symptom Relief Following Septoplasty: A Randomized Control Trial.

Objective:This study evaluated the efficacy of 0.1% xylometazoline-hydrochloride nasal decongestant spray compared to 0.9% saline nasal spray in relieving post-septoplasty clinical nasal findings and symptoms. Methods: This triple-blinded randomized-clinical-trial was conducted in 2 tertiary-care hospitals in Karachi-Pakistan. A total of 120 septoplasty patients were recruited from June 20, 2022, to June 20, 2023. Randomly equally-assigned participants received either 0.9% isotonic-saline (control group) or 0.1% xylometazoline-hydrochloride (intervention group) nasal sprays. Participants were instructed to use nasal sprays for 1 week, twice daily, with a 12 hour interval between the 2 doses as a single spray per nostril. Follow-up assessments were conducted on days 3 and 7 after surgery. Postoperative symptoms, nasal-endoscopic findings, adverse-effects, and patient satisfaction were compared using Chi-square test and a P value of <.05 was considered significant. Results: Of 120 participants, 106 were analyzed with 53 participants in each group. By the end of third postoperative day, intervention group exhibited significantly lower rates of self-reported symptoms, including bleeding (7.5%:54.7%), nasal obstruction (3.8%:45.3%), headache (1.9%:30.2%), pain (3.8%:7.5%), as well as clinical nasal findings, including nasal edema (1.9%:58.5%), crusting (11.3%:58.5%), nasal discharge (9.4%:22.6%), and nonhealed scarring (18.9%:58.5%), compared to control group (P value < .001). On the seventh day, intervention group exhibited absence of self-reported symptoms and clinical nasal findings, whereas control group still experienced moderate symptoms (P value < .001). Intervention group had significantly higher patient satisfaction (P value < .001). Conclusions: Xylometazoline spray is highly effective in relieving post-septoplasty clinical nasal findings and symptoms, without adverse effects, indicating potential for wider clinical utilization.Trial Registration: UMIN Clinical-trial-registry: UMIN000052217. (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000059598).

Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions.

Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy's development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of α and ß adrenergic receptors, which are the key components of epinephrine's mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis.

In Situ Gelling Behavior and Biopharmaceutical Characterization of Nano-Silver-Loaded Poloxamer Matrices Designed for Nasal Drug Delivery.

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine-silver nanoparticles conjugates (SN-CX). Optimization of the formulation was carried out by applying varying ratios of P407 and HPMC in the presence and absence of SN-CX so that gelation would occur in the temperature range of the nasal cavity (30-34 °C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature (Tg), whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way while leading to an even further decrease in Tg. SN-CX-loaded nasal formulations composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study.

The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle's insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentially increasing drug wastes and dosimetry variability. To address this issue, we designed a new spray pump that separated the nozzle from the actuator and connected them with a flexible tube, thereby eliminating nozzle retraction during application. The objective of this study is to test the new device's performance in comparison to the conventional nasal pump in terms of spray generation, plume development, and dosimetry distribution. For both devices, the spray droplet size distribution was measured using a laser diffraction particle analyzer. Plume development was recorded with a high-definition camera. Nasal dosimetry was characterized in two transparent nasal cavity casts (normal and decongested) under two breathing conditions (breath-holding and constant inhalation). The nasal formulation was a 0.25% w/v methyl cellulose aqueous solution with a fluorescent dye. For each test case, the temporospatial spray translocation in the nasal cavity was recorded, and the final delivered doses were quantified in five nasal regions. The results indicate minor differences in droplet size distribution between the two devices. The nasal plume from the new device presents a narrower plume angle. The head orientation, the depth at which the nozzle is inserted into the nostril, and the administration angle play crucial roles in determining the initial deposition of nasal sprays as well as the subsequent translocation of the liquid film/droplets. Quantitative measurements of deposition distributions in the nasal models were augmented with visualization recordings to evaluate the delivery enhancements introduced by the new device. With an extension tube, the modified device produced a lower spray output and delivered lower doses in the front, middle, and back turbinate than the conventional nasal pump. However, sprays from the new device were observed to penetrate deeper into the nasal passages, predominantly through the middle-upper meatus. This resulted in consistently enhanced dosing in the middle-upper turbinate regions while at the cost of higher drug loss to the pharynx.

Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

AIMS: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. METHODS: Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5 mg dose of nalbuphine nasal spray vs. 10 mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. RESULTS: Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6 = 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset = 0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia = 5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. CONCLUSION: Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

Comparative study of nasal cavity drug delivery efficiency with different nozzles in a 3D printed model.

Background: Nasal sprays are widely used in treating nasal and sinus diseases; however, there are very few studies on the drug delivery efficiency of nasal sprays. In this study, the drug delivery efficiency of three different nasal spray devices was evaluated in vitro using a 3D printed cast model of nasal cavity. Methods: Three nasal spray devices with different nozzles and angles of administration were used in the 3D model of the nasal cavity and paranasal sinuses. The spraying area (SA), maximal spraying distance (MSD), and spraying distribution scores on the nasal septum and lateral nasal wall were recorded. Results: Different nasal spray devices have their own characteristics, including volume of each spray, SA, and plume angle. The SA of the three nozzles on the nasal septum increased with an increasing angle of administration. When the angle of administration was 50°, each nozzle reached the maximal SA. There was no statistically significant difference in MSD among the three nozzles at the three angles. The total scores for each nozzle using the three different spraying angles were as follows: nozzle A, 40° > 30° > 50°; nozzle B, 30° > 40° > 50°; and nozzle C, 30° > 40° > 50°. The total scores for different nozzles using the same angle were statistically significantly different and the scores for nozzle C were the highest. Nozzle C had the minimum plume angle. None of the three nozzles could effectively delivered drugs into the middle meatus at any angle in this model. Conclusions: The design of the nozzle affects drug delivery efficiency of nasal spray devices. The ideal angle of administration is 50°. The nozzle with smaller plume angle has higher drug delivery efficiency. Current nasal spray devices can easily deliver drugs to most areas of the nasal cavity, such as the turbinate, nasal septum, olfactory fissure, and nasopharynx, but not the middle meatus. These findings are meaningful for nozzle selection and device improvements.

Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Åsberg Depression Rating Scale and the 9-item Patient Health Questionnaire.

OBJECTIVE: To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery-Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD). METHODS: Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models. RESULTS: In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (-12.8 [0.46] vs -10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044). CONCLUSIONS: In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

AM-301, a barrier-forming nasal spray, versus saline spray in seasonal allergic rhinitis: A randomized clinical trial.

RATIONALE: Saline nasal sprays are frequently used in the management of seasonal allergic rhinitis (SAR) for the cleansing and clearing of aeroallergens from the nasal cavity. Also using a drug-free approach, AM-301 nasal spray is forming a thin film barrier on the nasal mucosa to prevent contact with allergens, trap them, and facilitate their discharge. A clinical trial compared the efficacy, safety, and tolerability of AM-301 and saline spray in SAR. METHODS: A total of 100 patients were randomized 1:1 to self-administer AM-301 or saline 3 × daily for 2 weeks. Primary efficacy endpoint: reduction in mean daily reflective Total Nasal Symptom Score (rTNSS). Secondary efficacy endpoints: reduction in mean instantaneous TNSS and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), global impression of efficacy. Safety and tolerability: adverse events, relief medication use, symptom-free days, global impression of tolerability. RESULTS: AM-301-treated patients achieved a significantly lower rTNSS than the saline group (LS square means difference -1.1, 95% CI -1.959 to -0.241, p = .013) with improvement observed across all individual nasal symptoms. Likewise, all secondary endpoints showed statistical significance in favor of AM-301; for example, quality of life was significantly improved overall (p < .001) as well as for each individual RQLQ domain. Both treatments showed similarly good safety and tolerability. With AM-301, fewer patients used relief medication and more enjoyed symptom-free days compared to saline treatment. CONCLUSIONS: AM-301 was more effective than saline in improving SAR nasal symptoms and related quality of life while offering similar tolerability, demonstrating the benefits of a barrier approach.

The Efficacy of Elonide Nasal Corticosteroids in Managing Allergic Rhinitis: A Randomized, Double-Blinded Trial.

Background: Mometasone furoate nasal spray is efficacious in relieving allergic rhinitis symptoms. The objectives of this study were, firstly, to compare the efficacy of Elonide to Nasonex® and a placebo and secondly, to investigate the side effects of Elonide. Method: This was a prospective, single-centered, double blinded, randomized, placebo-controlled, non-inferiority trial. A total of 163 participants from the Otorhinolaryngology Clinic, Hospital Canselor Tuanku Muhriz (HCTM), were randomized into three treatment groups receiving Elonide (n = 56), Nasonex® (n = 54), and placebo (n = 53) nasal sprays using an online randomizer (Random.org). Treatment was administered for 4 weeks. The primary outcome measure was the Total Nasal Resistance (TNR), and the secondary outcomes were the Visual Analogue Score (VAS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ) score. Side effects were recorded. Results: There were significant improvements for all groups from baseline. The Elonide group had the greatest mean difference for all primary and secondary outcomes compared to Nasonex® and the placebo (0.77 ± 2.44 vs. 0.35 ± 1.16, p = 1.00 vs. 0.17 ± 0.82, p = 0.01). Elonide is non-inferior to Nasonex (p = 1.00) and superior to the placebo (p < 0.05). The highest side effects reported were for Nasonex (n = 14, 26%), followed by the placebo (n = 8, 16%) and Elonide (n = 6, 12%); headaches (n = 9, 17%) and sore throat (n = 9, 17%) were the most common. Conclusions: Elonide has similar efficacy to Nasonex® when compared to a placebo in the treatment of AR in adults. Elonide is safe and tolerable, with fewer side effects and no adverse side effects.

Dihydroergotamine mesylate nasal spray: an acute treatment option for migraine in adults.

INTRODUCTION: Although the landscape of migraine symptomatic treatment has been enriched by novel effective drugs, it is mandatory to critically reappraise older molecules to ascertain whether they could still represent reliable alternatives in specific endophenotypes of patients or migraine attacks. Among these, dihydroergotamine (DHE) nasal spray has been shown to be effective and is characterized by greater tolerability and manageability than the parenteral DHE formulation. AREAS COVERED: In this narrative review, the authors describe the pharmacodynamic and pharmacokinetic properties of DHE nasal spray and explore the results of the trials which explored its efficacy, safety and tolerability as migraine symptomatic treatment. They also discuss the limitations of the classically used device and the attempts that several companies are carrying out to generate devices warranting a more reproducible drug absorption. EXPERT OPINION: DHE nasal spray could be considered as rescue treatment in patients who have failed other symptomatic therapeutic strategies. Nevertheless, in the perspective of tailored therapy, the intranasal route of administration and the consequent rapid onset of action may represent benefits putatively making DHE a treatment of choice for challenging migraine attacks such as those with nocturnal onset or quickly reaching the climax of both headache and neurovegetative associated symptoms.

Rhinitis Control and Medication Use in a Real-World Sample of Patients With Persistent Rhinitis or Rhinosinusitis: A Community Pharmacy Study.

BACKGROUND: Little is known about rhinitis control in real-life, nor about the contribution of treatment-related and patient-related factors. OBJECTIVE: This study aimed to examine the level of rhinitis control and rhinitis medication utilization in patients with persistent rhinitis and to identify predictors of rhinitis control. METHODS: A cross-sectional observational study was conducted in patients with persistent rhinitis recruited in community pharmacies. Participants completed the Rhinitis Control Assessment Test, a questionnaire on patient/rhinitis characteristics, and rhinitis medication use. A visual analog scale for nasal symptoms was also completed. Pharmacy dispensing data were used to calculate adherence to intranasal glucocorticoids. Nasal spray technique was evaluated using a standardized checklist. Predictors of rhinitis control were explored using a linear regression model. RESULTS: A total of 1,514 patients, recruited in 215 pharmacies, participated in the study (mean age 48.7 y, 62% female). Almost 60% exhibited suboptimal rhinitis control (Rhinitis Control Assessment Test ≤ 21 of 30). A 50-mm cut-off on the visual analog scale yielded 78.1% sensitivity to identify suboptimal rhinitis control. Participants most frequently used intranasal glucocorticoids (55.6%) and intranasal decongestants (47.4%). Only 10.3% of current nasal spray users demonstrated perfect technique. More than half (54.8%) of glucocorticoid users were identified as underadherent. Female sex, self-reported nasal hyperreactivity, active asthma, and use of oral/intranasal decongestants or nasal saline were identified as predictors of worse rhinitis control. CONCLUSIONS: Suboptimal rhinitis control was common in this real-life sample of persistent rhinitis patients. Improving use of rhinitis medication may be key to increase disease control.

Phase II Trial of the Impact 0.5% Povidone-Iodine Nasal Spray (Nasodine®) on Shedding of SARS-CoV-2.

OBJECTIVE: A Phase II trial was conducted to determine if nasal disinfection with a commercial Good Manufacturing Practice-manufactured 0.5% povidone-iodine nasal spray (Nasodine®) may be a useful adjunct in the management of COVID-19 by reducing viral shedding and prevention of transmission of SARS-CoV-2. The aim was to confirm the results from a human single-dose pilot study by assessing repeated and frequent doses on nasal shedding of SARS-CoV-2 from adult subjects with confirmed COVID-19. METHODS: A multicenter, randomized, double-blinded, placebo-controlled Phase II clinical trial involving adults with early COVID-19 symptoms. Baseline nasal swabs were collected to quantify pretreatment SARS-CoV-2 nasal viral load, followed by Nasodine treatment eight times daily over 3 calendar days. Daily nasal swabs were collected post-dose to assess the impact of treatment on nasal viral load, measured by log10 TCID50 in quantitative culture. RESULTS: Nasodine subjects exhibited significantly improved reduction in viral load (log10 TCID50) on Days 2-4 compared to placebo recipients (p = 0.028), rate of nasal clearance of viable virus (p = 0.032), and complete (100%) nasal and throat clearance of the virus by Day 5. No difference was seen in antigen shedding as measured by time transition from Rapid Antigen Test (RAT) positivity to RAT negativity. CONCLUSION: A total of 20 doses of Nasodine® nasal spray administered over 2.5 days significantly reduced the titers of viable SARS-CoV-2 virus in the nasal passages of COVID-19 subjects. This is the first study demonstrating the efficacy of a tolerable intranasal formulation of povidone-iodine on viral shedding in COVID-19 subjects. Nasal disinfection may diminish viral transmission to others. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:3947-3952, 2024.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.