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Objective Background Methods Results Conclusion To compare the rate and extent of absorption of zavegepant 10 mg (therapeutic dose) or 20 mg (supratherapeutic dose) nasal spray during a migraine attack versus non‐migraine period, assess safety, and explore efficacy and the relationship between zavegepant concentration and therapeutic response.Physiologic changes occurring during a migraine attack could affect the pharmacokinetics of treatments for migraine.This was a Phase 1, multicenter, open‐label, randomized, single‐dose, two‐period, fixed‐sequence, comparative bioavailability study. Participants with a history of 2–8 migraine attacks per month of moderate or severe pain intensity were randomized to a single dose of zavegepant 10 or 20 mg, administered intranasally during a migraine attack (Period 1) and in a non‐migraine period (Period 2). Blood samples were collected pre‐dose and at pre‐specified intervals up to 24 h post‐dose for plasma zavegepant concentration measurement. Safety was monitored throughout, and efficacy (migraine pain intensity score, nausea, photophobia, phonophobia, aura, and functional disability) assessed during Period 1. Plasma zavegepant pharmacokinetic parameters were calculated by standard noncompartmental methods, including maximum plasma concentration (Cmax), area under plasma concentration–time curve from time zero to infinity (AUC0–inf), and time of Cmax (Tmax).A total of 37 participants were evaluable for pharmacokinetics. Following administration of zavegepant 10 mg, geometric mean ratios for Period 1/Period 2 were 82.8% (90% confidence interval [CI] 60.5–113.2) for Cmax and 90.1% (90% CI 70.2–115.5) for AUC0–inf. Following administration of zavegepant 20 mg, geometric mean ratios for Period 1/Period 2 were 72.5% (90% CI 57.9–90.8) for Cmax and 73.4% (90% CI 58.8–91.7) for AUC0–inf. Averaging over the study period, geometric mean ratios for zavegepant 20 mg/10 mg were 142.5% (90% CI 118.6–171.4) for Cmax and 157.0% (90% CI 133.6–184.5) for AUC0–inf. Median Tmax was 0.5 h for both doses regardless of Period. Zavegepant was well tolerated in both study periods and effective during Period 1 at both dose levels. There was no apparent correlation between concentration at 0.5 h or 2 h post‐dose and efficacy outcomes.Zavegepant exposure was comparable during a migraine attack and a non‐migraine period, particularly at the therapeutic dose of 10 mg. When averaging over migraine and non‐migraine periods, there was a less‐than‐dose proportional increase in zavegepant exposure when the dose was doubled from 10 to 20 mg. The median Tmax was 0.5 h regardless of migraine attack or dose. Zavegepant 10 and 20 mg exhibited favorable safety profiles during migraine attacks and non‐migraine periods, and were effective to relieve pain, associated symptoms, and functional disability during migraine attacks, with no apparent correlation between zavegepant concentration and efficacy outcomes. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusion The potential for drug–drug interaction of multiple‐dose intranasal zavegepant on the single‐dose oral contraceptive ethinyl estradiol and levonorgestrel (EE‐LNG) was evaluated.Zavegepant (as a nasal spray) is a calcitonin gene‐related peptide receptor antagonist approved in the United States for treatment of acute migraine in adults.This single‐center, Phase 1, open‐label, fixed‐sequence study included healthy, nonsmoking females (18–45 years old). In treatment Period 1, a single oral dose of EE‐LNG 0.02–0.10 mg was administered on Day 1. In treatment Period 2, intranasal zavegepant (20 mg daily; 10 mg per nostril separated by 1 h) was administered on Days 1–5; 1 oral dose of EE‐LNG 0.02–0.10 mg was administered immediately after first 10 mg intranasal zavegepant dose on Day 2. Blood samples for EE‐LNG concentrations were collected on Day 1, treatment Period 1, and Day 2, treatment Period 2, and zavegepant concentrations on Day 2, treatment Period 2. Noncompartmental pharmacokinetic parameters included maximum observed concentration (Cmax), area under the concentration‐time curve (AUC) from Time 0 to last non‐zero concentration (AUC0‐t), and AUC from Time 0 to infinity (AUC0‐inf). The safety and pharmacokinetic sample sizes were 26 and 23, respectively.Statistical comparisons of pharmacokinetic exposure parameters after co‐administration of zavegepant and EE‐LNG versus EE‐LNG alone showed small, but statistically insignificant, changes in either EE or LNG exposure. EE comparison ratios (90% confidence intervals [CIs]) were 109.9% (105.3%, 114.8%) for AUC0‐inf and 110.2% (104.6%, 116.1%) for Cmax. LNG comparison ratios (90% CIs) were 107.0% (100.2%, 114.3%) for AUC0‐inf and 108.8% (99.9%, 118.4%) for Cmax. Frequently reported treatment‐emergent adverse events included dysgeusia (n = 25, 96%), throat irritation (n = 11, 42%), headache (n = 10, 39%), nasal discomfort (n = 7, 27%), pharyngeal paresthesia (n = 5, 19%), and nausea (n = 4, 15%).Co‐administration of zavegepant nasal spray with a single dose of an oral contraceptive resulted in no clinically meaningful changes (<12% increase) in EE‐LNG exposure. [ABSTRACT FROM AUTHOR]

Purpose: Antibody therapy for chronic rhinosinusitis with nasal polyps (CRSwNP) has been established in Germany since 2019. With limited long-term data on biologic treatment for CRSwNP, we conducted a comprehensive evaluation of our 4-year data. This monocentric study aims to assess the real-world effects of this treatment on clinical course, quality of life, treatment adherence, biologic switching, dual therapy, and comorbidities. Methods: We retrospectively analysed biologic therapy data in patients with severe chronic rhinosinusitis with nasal polyps. 191 patients with CRSwNP treated with Dupilumab, Mepolizumab, or Omalizumab were observed for up to 4 years in a real-life setting. Results: We observed clear symptom improvements with few side effects. No loss of efficacy or tolerability was noted during the 4-year period. Patients reported high satisfaction compared to previous therapies, with overall improved quality of life. Revision surgery or oral steroid use during biologic therapy was rare. Some patients prolonged injection intervals or discontinued steroid nasal spray. Biologic switching occurred infrequently due to side effects or inadequate response and was generally well tolerated. Many patients reported additional positive effects such as asthma or allergy symptom improvement and reduced medication intake. Conclusion: In summary, this study confirms the potency and tolerability of biologics for CRSwNP treatment, with sustained efficacy over 4 years. Biologic switching is a viable option for inadequate response or intolerable side effects. Therapy positively impacts Th2 comorbidities, corticosteroid requirements, surgery need, and overall compliance remains high. Clinical trial registration: Project No.: 22–0802. Registry name: Biologika bei Patient*innen mit chronischer Sinusitis mit Nasenpolypen. [ABSTRACT FROM AUTHOR]

The blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA. [ABSTRACT FROM AUTHOR]

Introduction: Treatment resistant depression (TRD) affects approximately 10-- 30% of patients with major depressive disorder, and most patients with TRD do not respond to real-world treatments (RWT). Treatment with esketamine nasal spray (NS) plus a selective serotonin or serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) has significant long-term clinical benefit over RWT in patients with TRD. However, the impact on patient-reported function remains to be determined. Methods: The ICEBERG analysis was an indirect treatment comparison performed using data from two studies of patients with TRD: SUSTAIN-2 (esketamine NS; NCT02497287) and the European Observational TRD Cohort (EOTC; RWT; NCT03373253; clinicaltrials.gov). Here, patient--reported functional remission, assessed using the Sheehan Disability Scale (SDS), was defined as SDS ≤6 at Month 6. Analyses were conducted using propensity score re--weighting and multivariable models based on 18 covariates. Results: At Month 6, the probability of functional remission in esketamine NS --treated patients from SUSTAIN-2 (n=512) was 25.6% (95% confidence interval [CI] 21.8-29.4), while the adjusted probability for RWT patients from the EOTC (n=184) was 11.5% (95% CI 6.9-16.1; relative risk: 2.226 [95% CI 1.451-3.416]; p=0.0003). In the total combined population (N=696), patients who did not achieve clinical response or remission had a low probability of achieving functional remission (5.84% and 8.76%, respectively). However, for patients who did achieve clinical response or remission, the probability of achieving functional remission was greater (43.38% and 54.15%, respectively), although many still did not achieve this status. Conclusions: For patients with TRD, esketamine NS had a significant functional benefit versus RWT after 6 months of treatment. Irrespective of treatment, achievement of clinical response or remission was insufficient to attain functional remission. Nevertheless, clinical remission increased the likelihood of achieving functional remission, further supporting an important role for clinical remission in for the path towards functional recovery. [ABSTRACT FROM AUTHOR]

Background: Cocaine may be applied to decongest the nasal mucosa before nasotracheal intubation, but patients risk a criminal offence if cocaine is detected when patients drive a car shortly after surgery. We aimed to evaluate whether benzoylecgonine levels in saliva exceeded the cut‐off point 24 h after administration in patients undergoing nasotracheal intubation and whether cocaine would be detectable above the Danish legal fixed limit in blood samples 1 and 24 h after surgery. Methods: We conducted a prospective study following approval from the local research ethics committee and the national medicine agency. Written informed consent was obtained from all patients. We included patients scheduled for surgery under general anaesthesia with nasotracheal intubation. They received 80 mg cocaine as a nasal spray 5 min before induction and nasotracheal intubation. The primary outcome was a dichotomous assessment of benzoylecgonine levels in saliva samples measured 24 h after administration of nasal cocaine with a cut‐off limit of 200 ng/mL. Secondary outcomes were dichotomous assessments of cocaine in whole blood samples measured 1 and 24 h after administration of nasal cocaine with a cut‐off limit of 0.01 mg/kg. Results: Overall, 70 patients had valid saliva samples and 75 had valid blood samples 24 h after cocaine administration. Benzoylecgonine in saliva was traceable above the cut‐off in 9/70 patients (13%; CI95%: 6% to 23%), and cocaine in blood was detected above the cut‐off in 2/75 patients (3%; CI95%: 0.3% to 9%). Conclusion: We found benzoylecgonine traceable in saliva in 13% of patients and cocaine traceable in blood in 3% of patients 24 h after administration of 80 mg nasal cocaine. Patients should be informed when receiving cocaine and advised not to drive for at least 24 h. [ABSTRACT FROM AUTHOR]

Zavegepant, a high‐affinity, selective, small‐molecule calcitonin gene‐related peptide receptor antagonist, is approved as a nasal spray for acute treatment of migraine in adults. This phase I, open‐label, single‐center, single‐period, nonrandomized study in six healthy male subjects assessed mass balance recovery after a single 15‐min intravenous (IV) infusion dose of carbon‐14 ([14C])‐zavegepant. Blood, urine, and fecal samples were collected over 192 h for analysis of zavegepant in plasma and urine; total radioactivity (TR) in plasma, whole blood, urine, and feces; and zavegepant metabolite profiling and structural identification in plasma, urine, and feces. An average of 96.6% of radioactivity administered was recovered in excreta. Most TR (mean 84.9%) was recovered in the feces, indicating that biliary/fecal elimination was the main route. Volume of distribution of zavegepant based on the terminal phase (129 L) was higher than total body water (42 L), indicating substantial distribution into tissue. Total plasma clearance of zavegepant (220 mL/min) is identical to whole blood clearance given the blood/plasma partition ratio of 1, lower than typical hepatic blood flow (1450 mL/min). The observed plasma terminal half‐life of zavegepant was 6.8 h. Exposure to zavegepant accounted for ~90% of circulating plasma TR, suggesting that very low levels of uncharacterized circulating metabolites were present. Metabolite profiling did not identify any metabolites representing ≥10% of radioactivity in plasma, urine, or feces. A single IV infusion of 5 mg [14C]‐zavegepant was well tolerated in healthy male subjects. Disposition findings of IV [14C]‐zavegepant are applicable to the disposition of the approved zavegepant nasal spray. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion Nasal anaesthetic‐decongestant sprays are commonly used prior to nasal instrumentation, such as flexible and rigid nasal endoscopy. Co‐phenylcaine (lignocaine 5%, phenylephrine 0.5%, ENT Technologies Pty Ltd., Melbourne, VIC, Australia) is a combination spray commonly used for this purpose. However, lignocaine is less potent than other local anaesthetics, and both active constituents of Co‐phenylcaine have a bitter taste. It was hypothesised that a combination spray containing tetracaine and oxymetazoline would both offer more potent topical anaesthesia and have a better taste.Four anaesthetic‐decongestant nasal sprays were tested in 10 healthy participants (Co‐phenylcaine, and tetracaine 0.5%, 1% and 2% with oxymetazoline 0.05%). Sensory thresholds were sequentially measured at the head of the inferior turbinate using Semmes‐Weinstein monofilaments over the following hour. Participants also rated taste on a Likert‐style scale, and reported whether they experienced subjective numbness of the maxillary teeth.A median peak sensory threshold of 60 g (the maximum tested) was observed with Co‐phenylcaine, but this threshold was exceeded by all the tetracaine‐based sprays. Tetracaine 2% with oxymetazoline 0.05% had a significantly more rapid onset than Co‐phenylcaine (4 min vs. 6 min, p < 0.05) and a longer duration of action. Eight participants reported dental numbness after administration of tetracaine 2% with oxymetazoline 0.05%, but only one participant after Co‐phenylcaine. Tetracaine‐based sprays were generally perceived to taste less unpleasant than Co‐phenylcaine.Tetracaine 2% with oxymetazoline 0.05% is a more potent and rapidly acting anaesthetic‐decongestant spray than Co‐phenylcaine, with a longer duration of action. [ABSTRACT FROM AUTHOR]

COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays—low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusion\nKEY POINTSESKALE is a French, multicentre, observational study of adults with treatment-resistant depression (TRD) treated with esketamine. This interim analysis describes baseline demographic and clinical characteristic evolution in patients included and treated from early access program to post-marketing launch.Data were collected from medical records and included patient characteristics, disease history at esketamine initiation, use of neurostimulation, the patient’s care pathway, and the number of antidepressant treatment lines prescribed prior to esketamine initiation. Descriptive statistics were used for each cohort: the early access program ‘Temporary Authorisation for Use’ (ATU), post-ATU, and post-launch cohorts.The overall ESKALE cohort (N = 160 included; n = 157 treated with esketamine; average age 49.0 years; 66.2% female) demonstrated moderate-to-severe depression according to clinical assessment and a mean Montgomery-Åsberg Depression Rating Scale score of 32.6 (8.0); however, severity, subtype, and comorbidities were heterogeneous across the cohorts. Earlier use of esketamine and prior to alternative treatments occurred during the later cohorts.These findings demonstrated a high burden of TRD in these patients and that esketamine is used in TRD treatment regardless of their disease severity, subtype, or existing comorbidities. These results also suggest that esketamine is potentially a clinically useful alternative treatment, particularly with healthcare professionals gaining greater familiarity with and easier access to esketamine.ESKALE is a long-term, French, multicentre, observational study based on secondary data in adult patients with treatment-resistant depression (TRD) who initiated esketamine treatment in one of three mutually exclusive cohorts: the Temporary Authorisation for Use (ATU), post-ATU, and post-launch cohorts.ESKALE is one of the largest European real-world studies investigating the profiles of more than 150 patients and their treatment with esketamine before and after marketing authorisation.A majority of patients had moderate to severe TRD, with multiple treatment failures with medications and/or neurostimulation prior to esketamine initiation.Esketamine nasal spray administration was undertaken more frequently in an outpatient setting, with the post-administration period monitoring being undertaken mostly by nurses.Esketamine was used in patients with TRD in real-world conditions regardless of their disease severity and subtype or existing comorbidities.These results highlight both the need for an effective treatment for TRD and the adoption of esketamine by multidisciplinary teams that are involved in esketamine prescription and administration.ESKALE is a long-term, French, multicentre, observational study based on secondary data in adult patients with treatment-resistant depression (TRD) who initiated esketamine treatment in one of three mutually exclusive cohorts: the Temporary Authorisation for Use (ATU), post-ATU, and post-launch cohorts.ESKALE is one of the largest European real-world studies investigating the profiles of more than 150 patients and their treatment with esketamine before and after marketing authorisation.A majority of patients had moderate to severe TRD, with multiple treatment failures with medications and/or neurostimulation prior to esketamine initiation.Esketamine nasal spray administration was undertaken more frequently in an outpatient setting, with the post-administration period monitoring being undertaken mostly by nurses.Esketamine was used in patients with TRD in real-world conditions regardless of their disease severity and subtype or existing comorbidities.These results highlight both the need for an effective treatment for TRD and the adoption of esketamine by multidisciplinary teams that are involved in esketamine prescription and administration. [ABSTRACT FROM AUTHOR]

Background: Intranasal corticosteroids were recommended as first‐line drugs for the treatment of allergic rhinitis (AR) children. A variety of corticosteroids were available for clinical choice; however, which could relieve the clinical symptoms of patients to the greatest extent was currently unknown. Thus, we performed a network meta‐analysis (NMA) to systematically evaluate the effectiveness and safety of different corticosteroids in treating children with AR, which might provide a basis for more rational clinical treatment decisions. Methods: Seven electronic databases were searched, and the retrieval time range was the time from their inception to November 2023. The literature screening, data extraction, and assessment of the risk of bias of included studies were completed independently by two reviewers. A frequentist NMA was performed with Stata17.0 software. Results: A total of 43 RCTs covering 10,897 participants were included. In the improvement of reflective total nasal symptom score (rTNSS) and instantaneous total nasal symptom score (iTNSS), fluticasone furoate nasal spray (FFNS) and beclomethasone dipropionate (BDP) nasal aerosol presented the best efficacy. Regarding the incidence of adverse reactions, mometasone furoate aqueous nasal spray (MFANS) and BDP showed a good safety profile. In terms of the influence of cortisol (urinary free cortisol, plasma cortisol) and growth, no significant difference was observed between the different groups. Conclusion: The results showed that BDP nasal aerosol and FFNS had best efficacy; MFANS and BDP had the best safety profile. However, this conclusion was less convincing because of the limited numbers of patients/controls and study quality. [ABSTRACT FROM AUTHOR]

Background/Objectives: Dendrimer-based astodrimer sodium nasal spray was assessed for its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe illness for vulnerable groups. Methods: This was a randomised, double-blind, placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray in reducing SARS-CoV-2 viral burden in the nasopharynx of outpatients with COVID-19. Non-hospitalised adults with SARS-CoV-2 infection were randomised 1:1 to astodrimer or placebo four times daily from Day 1 to Day 7. Nasopharyngeal swabs for SARS-CoV-2 load determination were self-obtained daily from Day 1 to Day 8. The primary endpoint was an area under the curve of SARS-CoV-2 RNA copies/mL through Day 8 (vAUCd1–8). The primary analysis population was the modified intent-to-treat population (mITT: all randomised participants exposed to the study treatment who had at least one post-baseline viral load determination). Safety analyses included all randomised participants exposed to the study treatment. Study registration: ISRCTN70449927; Results: 231 participants were recruited between 9 January and 20 September 2023. The safety population comprised 109 and 113 participants randomised to astodrimer and placebo, respectively, with 96 and 101 participants in the mITT. Astodrimer sodium nasal spray reduced the SARS-CoV-2 burden (vAUCd1–8) vs. placebo in non-hospitalised COVID-19 patients aged 16 years and over (−1.2 log10 copies/mL × Day). The reduction in SARS-CoV-2 load was statistically significant in those aged 45 years and older (−3.7, p = 0.017) and the effect increased in older age groups, including in those aged 65 years and older (−7.3, p = 0.005). Astodrimer sodium nasal spray increased the rate of viral clearance and helped alleviate some COVID-19 symptoms, especially loss of sense of smell. Overall, 31 participants (14%) had ≥1 adverse event (AE). Four AEs were deemed possibly related to treatment. Most AEs were of mild severity and occurred at similar rates in both treatment arms. Conclusions: Astodrimer nasal spray reduces viral burden and accelerates viral clearance, especially in older populations, and is well tolerated. [ABSTRACT FROM AUTHOR]

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The nasal cavity possesses a unique set of anatomical characteristics for delivering active pharmaceutical ingredients, but there are several limitations that recent research in the field of the intranasal administration of APIs aims to overcome. For the effective delivery of nasal preparations, active pharmaceutical ingredients are incorporated into various micro- and nanosystems. Some of the most commonly encountered API delivery systems in the scientific literature include liposomal systems, polymer particles with mucoadhesive properties, in situ gels, nano- and microemulsions, and solid lipid particles. This article provides a review of research on the development of nasal preparations for treating local nasal cavity diseases (in particular, for antibiotic delivery), systemic diseases (analgesics, drugs for cardiovascular diseases, antiviral and antiemetic drugs), CNS disorders (Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, depression), and vaccine delivery. The literature data show that active research is underway to reformulate drugs of various pharmacotherapeutic groups into a nasal form. [ABSTRACT FROM AUTHOR]

This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18–65 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy. [ABSTRACT FROM AUTHOR]

Levosulpiride (LSP) has been studied for its wide medicinal potential. One of its uses is in the treatment of schizophrenia. LSP has limited oral bioavailability because of its low permeability, dissolvability, and P-Glycoprotein (Pgp) efflux effect. Contrary to conventional methods, the intranasal route provides safe and effective treatment as well as targeted action. It can also prevent the P-gp efflux effect and increase brain bioavailability. In this research, we aimed to develop LSP-loaded Phospholipid Magnesomes (PMs), a novel vesicular nanosystem, recently fabricated for brain targeting by the Ultra-sonication method with materials including Phospholipon 90G, the combination of Propylene glycol and ethanol, magnesium sulphate (MgSO4) and water. The Box-Behnken design was utilized with 29 runs to optimize the LSP-PMs formulation. The formulation was confirmed and evaluated by the FTIR, DSC, PXRD, and TEM study. The formulation was investigated in vitro at pH 6.4, and the results showed that the formulation had improved drug release. The optimized LSP-PMs formula had a vesicle sizing of 85.035 ± 2.77 nm, a PDI of 0.392 ± 0.69, and a %EE of 76.024 %. Spherical and multilamellar morphology of LSP-PMs were visible by the TEM. The optimized LSP-PMs had the quickest medication diffusing profile, achieving 100% in one hour. The LSP-PMs formulation was stable at room temperature for 50 days when screened for the stability study. Thus, to sum up, the nano-vesicular system of LSP-PMs demonstrated to be a promising formulation for enhancing drug release of the poorly water-soluble and permeable LSP. Further investigation to analyze nasal transport to the brain, pharmacokinetic and pharmacodynamic effects, local safety, and the behavior of the developed carrier will require additional research. [ABSTRACT FROM AUTHOR]

Objectives: In the United States (US), prescription drug coverage is subject to prior authorization (PA) criteria, which may vary between health plans and may exceed drug label requirements. This study aimed to characterize profiles and treatment history of patients with treatment-resistant depression (TRD) who initiated esketamine nasal spray, by stringency of their health plans' PA criteria relative to the esketamine label. Methods: Adults with evidence of TRD (≥2 antidepressant courses of adequate dose and duration) prior to initiating esketamine were identified using US insurance claims data (03/2016–02/2022). Based on health plan PA criteria for esketamine obtained from Managed Markets Insight & Technology data (05/2020–02/2022), patients were grouped into stringent (PA criteria exceeds label) and non-stringent (PA criteria less stringent or equal to label) cohorts. Patient treatment history before esketamine initiation was compared using Wilcoxon rank sum and Fisher's exact tests. Results: The stringent cohort included 168 patients (mean age: 45 years, 63% female) and the non-stringent cohort included 400 patients (mean age: 45 years, 70% female). During the ongoing major depressive episode before esketamine initiation, the stringent versus non-stringent cohort completed 3.9 versus 3.8 antidepressant treatment courses, on average (p = 0.217); 94.6% versus 96.8% used augmentation therapy (p = 0.240), including 59.3% versus 58.1% with an antipsychotic (p = 0.844), respectively. Conclusions: Regardless of health plan stringency, on average, patients exceeded US label-mandated number of antidepressant trials before esketamine initiation, which questions the need for health insurance plans PA criteria above label. [ABSTRACT FROM AUTHOR]

Key points: PVP‐I is a widely used antiseptic but only recently proposed for intranasal use.The extent of iodine absorption from available PVP‐I nasal products is unknown.Iodine absorption from use of Nasodine (0.5% PVP‐I nasal spray) is not clinically significant. [ABSTRACT FROM AUTHOR]

Treatment-Resistant Depression (TRD) affects almost 30 % of patients with Major Depressive Disorder (MDD). Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD in combination with a Serotonin Specific Reuptake Inhibitor/SSRI or a Serotonin-Norepinephrine Reuptake Inhibitor/SNRI. There is a lack of studies investigating the effectiveness and safety of ESK-NS in combination with other oral antidepressants. To assess the efficacy of Vortioxetine plus ESK-NS in mitigating depressive symptoms and emotional blunting, as well as its tolerability in TRD subjects, compared to the standard-of-care of SSRI/SNRI plus ESK-NS. We conducted a post-hoc analysis of the REAL-ESK study. The study included twenty TRD patients, ten subjects taking Vortioxetine as the main oral antidepressant with ESK-NS, and ten subjects taking SSRI or SNRI with ESK-NS. Psychometric assessments (Montgomery-Åsberg Depression Rating Scale/MADRS, Brief Psychiatric Rating Scale/BPRS) were conducted at baseline(T0), one month(T1), and three months after the treatment initiation(T2). The combination of Vortioxetine and ESK-NS was as effective as the standard-of-care in reducing depressive symptoms, with a higher effect size in reducing emotional blunting at T2. The safety and tolerability profile of the Vortioxetine+ESK-NS combination appeared to be better, with a lower rate of treatment-emergent adverse events. The combination of Vortioxetine and ESK-NS may be a valuable alternative to the standard-of-care SSRI/SNRI plus ESK-NS in TRD patients, particularly regarding the reduction of emotional blunting and potentially a better safety and tolerability profile. Further randomized controlled trials with larger sample sizes and prospective designs are needed to confirm these findings. • Esketamine nasal spray (ESK-NS) is a new treatment for TRD. • Standard-of-care combines ESK-NS with SSRIs or SNRIs. • We compared the effectiveness of Vortioxetine + ESK-NS vs. SSRI/SNRI + ESK-NS. • We found similar antidepressant effect with a better safety profile for Vortioxetine. • Vortioxetine + ESK-NS was more effective against emotional blunting. [ABSTRACT FROM AUTHOR]

Naloxone nasal spray is recommended for patients with risk factors for opioid overdose. However, cancer patients' perceptions and beliefs regarding naloxone prescriptions and their self-perceived risks for overdose are understudied. To determine the proportion of cancer patients at risk for overdose who perceived naloxone as beneficial. Between July 2020 and April 2022, we surveyed 150 adult patients from the supportive care ambulatory clinic at a tertiary cancer center in the United States who received a co-prescription of naloxone nasal spray. We measured patients' knowledge of overdose risk-factors, attitudes, beliefs, and education received on naloxone. Risk-factors between beneficial vs. nonbeneficial groups were analyzed. The survey was administered on paper or via a telephone interview. Of the 150 patients, 55% were male, 70% were white, and 81% had advanced cancer. The majority of patients believed naloxone was beneficial (100/150, 67%). When compared to the nonbeneficial group, more patients from the beneficial group agreed that the concurrent use of alcohol (100% vs. 90%; P = 0.004) or sedating drugs (96% vs. 85%; P = 0.04) with opioids could result in overdoses and felt safe having naloxone at home (95% vs. 60%; P <0.0001). More patients from the nonbeneficial group associated naloxone prescription with being suspected of misusing opioids (12/50 vs. 8/100; P = 0.01), and fewer had confidence in their caregivers' ability to administer naloxone (69% vs. 95%; P < 0.0001). Most patients understood the benefits of naloxone and felt safe having one at home. More research is needed to identify knowledge gaps and develop educational strategies for those who find it nonbeneficial. [ABSTRACT FROM AUTHOR]

Key points The original manufacturer of azelastine‒fluticasone (AZ‒FL) prevented generic availability until 2020 via patent enforcement. Following generic availability of AZ‒FL, Medicare utilization increased and spending decreased. Retail prices for generic AZ‒FL remain high due to markup by manufacturers and pharmacies. [ABSTRACT FROM AUTHOR]

Background: Zavegepant is the first small molecule calcitonin gene-related peptide receptor antagonist for intranasal administration for the acute treatment of migraine. The objective of this study was to evaluate the safety and tolerability of zavegepant in the acute treatment of migraine under repeated, as-needed dosing for up to one year. Methods: This phase 2/3, one-year open-label safety study of zavegepant 10 mg nasal spray for the acute treatment of migraine enrolled adults aged ≥18 years with a history of two to eight moderate to severe monthly migraine attacks. Participants used one dose of zavegepant as needed to self-treat migraine attacks of any severity, up to eight times per month, for 52 weeks. Results: Participants were enrolled between 29 June and 4 December 2020. Of the 608 participants entering long-term treatment, 603 were treated with study drug. Participants administered a mean (SD) of 3.1 (1.55) zavegepant doses per month. There were no deaths. Of the seven serious adverse events reported, none was considered related to treatment. Altogether, 6.8% (41/603) of treated participants had an adverse event leading to study drug discontinuation. The most frequent adverse event leading to discontinuation was dysgeusia (1.5% [9/603]). The most common treatment-emergent adverse events (≥5% of participants) were dysgeusia (39.1% [236/603]); nasal discomfort (10.3% [62/603]); COVID-19 (7.5% [45/603]); nausea (6.1% [37/603]); nasal congestion and throat irritation (5.5% [33/603] each); and back pain (5.3% [32/603]). Aminotransferases >3x the upper limit of normal occurred in 2.6% [16/603] of participants; none had concurrent elevations in bilirubin >2x upper limit of normal. Conclusions: One year of zavegepant 10 mg nasal spray up to eight times per month was safe and well tolerated. Trial registration: Clinicaltrials.gov: NCT04408794 [ABSTRACT FROM AUTHOR]

Objective: Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment. Study Design: This is the protocol of an observational, prospective study. Methods: We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks (“induction phase”), then once a week for 4 additional weeks (“maintenance phase”). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders. Expected results: An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized. Conclusion: Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD. [ABSTRACT FROM AUTHOR]

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD. [ABSTRACT FROM AUTHOR]

The deposition, residence time, and dissolution profile of nasal suspensions containing corticosteroids play a key role in their in vivo efficacy after administration. However, the conventional methods available to characterize nasal products appear to be unsuitable to exhaustively cover these aspects. The work aims to investigate technological aspects of Ryaltris (mometasone furoate and olopatadine hydrochloride nasal spray) compared to other commercial anti-allergic nasal products, namely, Dymista (azelastine hydrochloride and fluticasone propionate), Nasonex (mometasone furoate), and Avamys (fluticasone furoate). Innovative characterization methods were combined with more traditional approaches to investigate the anti-allergic nasal sprays. These methods applied together allowed to differentiate between the different products and provided a clear picture of the nasal product behavior in terms of drug dissolution and deposition. In particular, the dissolution tests were performed exploiting the Respicell® apparatus, an innovative technique that allows for the investigation of inhalation products. Then, formulation viscosities were considered along with a formulation flow test on an inclined plane. Finally, the intranasal deposition profile of the commercial formulations was determined using a silicon nasal cast. The results highlight in vitro significant differences in terms of viscosity as well as dissolution rate of the nasal products, with Ryaltris showing a higher viscosity and lower flow compared to other products, which, along with a corticosteroid faster dissolution rate than Dymista, suggest a potential advantage in terms of clinical behavior. [ABSTRACT FROM AUTHOR]

While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this pre-registered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (inert). After the first session, participants were randomized to two groups and underwent functional MRI. One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief. Our results revealed that nasal sprays with a side effect lead to lower pain than inert nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. Functional MRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects. In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Ptosis associated with rhinosinusitis may indicate orbital or cavernous sinus involvement, typically accompanied by various other symptoms. However, isolated ptosis is a rare occurrence. This explains the diverse treatment approaches found in this literature review, ranging from conservative management to surgery. Imaging plays a crucial role in diagnosis and treatment planning. Isolated upper lid ptosis is a rare manifestation of acute rhinosinusitis, typically occurring without other neuro‐ophthalmological or orbital signs. This report presents a case of unilateral isolated ptosis in an adult male with acute rhinosinusitis. A 30‐year‐old male with asthma and bipolar disorder, and recent intranasal drug use, presented with nasal congestion, facial pressure, headache, and left eye droopiness. Neurological examination found left ptosis as the only abnormality. Lab results were normal, and COVID‐19 PCR was negative. Imaging showed pansinusitis without complications. The patient received IV antibiotics and steroids, followed by oral antibiotics and steroids. Ptosis resolved within 3 days and did not recur at three‐month follow‐up. Only seven cases of isolated ptosis with rhinosinusitis have been reported, all in males, most recovering with medical therapy alone. This is the first case treated with high‐dose steroids in addition to antibiotics. Isolated ptosis may be due to inflammation of the oculomotor nerve's distal branch or related muscular structures. Isolated ptosis in rhinosinusitis has a favorable prognosis. Imaging is crucial to exclude severe complications. The role of steroids needs further evaluation, and the timing for considering surgery remains to be defined. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a common childhood disease. Although various drugs have been used to treat allergic rhinitis, including nasal corticosteroids, antileukotrienes, and antihistamines, there is still controversy about the optimal dose and the best combination with the highest efficacy. Higher doses of antihistamines are recommended for better control of urticaria, but there is insufficient evidence regarding the efficacy of increased doses of antihistamines in allergic rhinitis. The aim of the study was to evaluate the effectiveness of different drug combinations in the treatment of children with allergic rhinitis. Sixty-four children with persistent moderate to severe allergic rhinitis were enrolled and randomly divided into 4 groups. All children received mometasone furoate nasal spray once daily. In addition to mometasone, each group received one of the following drugs or drug combinations: daily desloratadine, twice daily desloratadine, montelukast, or a combination of desloratadine and montelukast. The severity of symptoms before and after the intervention was evaluated based on the total nasal symptoms score, including sneezing, nasal congestion, nasal itching, and rhinorrhea. Sixty patients completed the study. The reduction of nasal congestion score and total nasal symptoms score in the groups receiving desloratadine twice a day and desloratadine plus montelukast was superior to the daily desloratadine group and daily montelukast groups. According to this work, the treatment of allergic rhinitis with mometasone nasal spray with desloratadine twice a day or with the combination of desloratadine and montelukast was more effective than other treatment regimens. [ABSTRACT FROM AUTHOR]

A small amount of evidence suggests that nasal sprays, or physical activity and stress management, could shorten the duration of respiratory infections. This study aimed to assess the effect of nasal sprays or a behavioural intervention promoting physical activity and stress management on respiratory illnesses, compared with usual care. This randomised, controlled, open-label, parallel-group trial was done at 332 general practitioner practices in the UK. Eligible adults (aged ≥18 years) had at least one comorbidity or risk factor increasing their risk of adverse outcomes due to respiratory illness (eg, immune compromise due to serious illness or medication; heart disease; asthma or lung disease; diabetes; mild hepatic impairment; stroke or severe neurological problem; obesity [BMI ≥30 kg/m2]; or age ≥65 years) or at least three self-reported respiratory tract infections in a normal year (ie, any year before the COVID-19 pandemic). Participants were randomly assigned (1:1:1:1) using a computerised system to: usual care (brief advice about managing illness); gel-based spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); saline spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); or a brief behavioural intervention in which participants were given access to a website promoting physical activity and stress management. The study was partially masked: neither investigators nor medical staff were aware of treatment allocation, and investigators who did the statistical analysis were unaware of treatment allocation. The sprays were relabelled to maintain participant masking. Outcomes were assessed using data from participants' completed monthly surveys and a survey at 6 months. The primary outcome was total number of days of illness due to self-reported respiratory tract illnesses (coughs, colds, sore throat, sinus or ear infections, influenza, or COVID-19) in the previous 6 months, assessed in the modified intention-to-treat population, which included all randomly assigned participants who had primary outcome data available. Key secondary outcomes were possible harms, including headache or facial pain, and antibiotic use, assessed in all randomly assigned participants. This trial was registered with ISRCTN, 17936080, and is closed to recruitment. Between Dec 12, 2020, and April 7, 2023, of 19 475 individuals screened for eligibility, 13 799 participants were randomly assigned to usual care (n=3451), gel-based nasal spray (n=3448), saline nasal spray (n=3450), or the digital intervention promoting physical activity and stress management (n=3450). 11 612 participants had complete data for the primary outcome and were included in the primary outcome analysis (usual care group, n=2983; gel-based spray group, n=2935; saline spray group, n=2967; behavioural website group, n=2727). Compared with participants in the usual care group, who had a mean of 8·2 (SD 16·1) days of illness, the number of days of illness was significantly lower in the gel-based spray group (mean 6·5 days [SD 12·8]; adjusted incidence rate ratio [IRR] 0·82 [99% CI 0·76–0·90]; p<0·0001) and the saline spray group (6·4 days [12·4]; 0·81 [0·74–0·88]; p<0·0001), but not in the group allocated to the behavioural website (7·4 days [14·7]; 0·97 [0·89–1·06]; p=0·46). The most common adverse event was headache or sinus pain in the gel-based group: 123 (4·8%) of 2556 participants in the usual care group; 199 (7·8%) of 2498 participants in the gel-based group (risk ratio 1·61 [95% CI 1·30–1·99]; p<0·0001); 101 (4·5%) of 2377 participants in the saline group (0·81 [0·63–1·05]; p=0·11); and 101 (4·5%) of 2091 participants in the behavioural intervention group (0·95 [0·74–1·22]; p=0·69). Compared with usual care, antibiotic use was lower for all interventions: IRR 0·65 (95% CI 0·50–0·84; p=0·001) for the gel-based spray group; 0·69 (0·45–0·88; p=0·003) for the saline spray group; and 0·74 (0·57–0·94; p=0·02) for the behavioural website group. Advice to use either nasal spray reduced illness duration and both sprays and the behavioural website reduced antibiotic use. Future research should aim to address the impact of the widespread implementation of these simple interventions. National Institute for Health and Care Research. [ABSTRACT FROM AUTHOR]

Dysfunction of the hypothalamus is associated with endocrine imbalances, growth abnormalities, and reproductive disorders. However, there is a lack of targeted treatment strategies focused on the hypothalamus. In this study, we constructed a multifunctional nanocarrier system (S@ANP) to directly target the hypothalamic neurokinin receptor 3 (NK3R) via an intranasal delivery strategy. This system could overcome the primary obstacles in drug delivery for hypothalamus‐related diseases. Under the guidance of a modified (Trp7, β‐Ala8)‐neurokinin A (4‐10) peptide with cysteine, nanoparticles encapsulated with SB222200, an NK3R inhibitor, were found to readily penetrate hypothalamic cells with substantial loading capacity, encapsulation efficiency, and sustained release in vitro. Moreover, intranasal delivery represents an optimal delivery strategy that allows for a significant reduction in oral dosage and enables nanoparticles to bypass the blood‒brain barrier and target relevant parts of the brain. The mucolytic agent N‐acetyl‐L‐cysteine (NAC) was loaded into the nanoparticles (S@ANP + NAC) to increase mucosal solubility and intranasal delivery efficiency. In vivo evaluations showed that S@ANP + NAC could effectively target the hypothalamus and modulate NK3R‐regulated hypothalamic functions in mice. Due to its high hypothalamic targeting efficiency and low toxicity, this intranasal nanoparticle drug delivery system may serve as a potential strategy for precision therapy of hypothalamic disorders. [ABSTRACT FROM AUTHOR]

Diazepam is a cornerstone immediate‐use antiseizure rescue therapy that may extend the duration between seizure clusters in people living with epilepsy. However, our mechanistic understanding of intermittent rescue therapy on disease progression is limited by the lack of suitable preclinical models. Specifically, the pharmacokinetics of diazepam varies widely between humans and laboratory animals. Here, we developed a novel repeat rescue therapy dosing paradigm in rats to maintain prolonged therapeutic concentrations seen in humans. Rats received three diazepam doses separated by 1 h (0.75, 1.5, or 3 mg/kg, intraperitoneal); plasma and brains were collected at 10 min and 1, 3, or 6 h following the last dose. Plasma and brain concentrations followed a dose‐dependent increase with peak concentrations following the repeat 3 mg/kg paradigm (180 ng/mL) being equivalent to plasma levels observed in human studies with diazepam nasal spray. Increased brain‐to‐plasma ratios in this paradigm indicate that diazepam accumulation in the brain may be long‐acting at the site of action. Overall, our repeat diazepam dosing paradigm mimics drug concentrations and accumulation seen in humans, offering a preclinical tool to study the impact of benzodiazepine rescue therapy on seizure‐cluster biology in rodent models of epilepsy. Plain language summary: There is more to learn about how diazepam works in the brains of people who use it only when they have two or more seizures in 24 h (this is called a seizure cluster). Ethical studies in animals can be used to learn more about medicines in the body. In this study, we showed that three doses of diazepam in rats give about the same amount of the drug as one dose for a person. We can now test rats with epilepsy to see how the drug might work in people who take it when needed for seizure clusters. [ABSTRACT FROM AUTHOR]

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms "fentanyl" AND "overdose" AND "children". The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures. [ABSTRACT FROM AUTHOR]

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as amajor 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, hereinwe 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. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aimed to address acceptance and long-term adherence to Continuous Positive Airway Pressure (CPAP) treatment among non-responder patients to ImThera THN system who initially declined this therapy. Material and methods: We employed a structured outpatient approach to communicate THN study results, categorize initial CPAP nonadherence reasons, and encourage CPAP trials through tailored appointments. Recorded follow-ups addressed individual concerns, providing medical guidance and acknowledging person-specific challenges. Adherence data were collected using CPAP hour meters at predetermined intervals, following Belgium's social security stipulations. Results: Between July 2014 and October 2016, eleven participants, including one woman, with prior CPAP experience (average 2months) were enrolled. Initial non-adherence was linked to ENT or psychological factors. Ten patients agreed to CPAP trials, where interventions included changing CPAP brand, pressure adjustments, mask changes, and additional measures like cognitive-behavioral therapy and nasal spray. After 1 year, mean adherence was 6.3 ± 2 h/day, and average CPAP usage duration was 8.67 ± 2.13 years. As of November 2023, eight out of eleven patients were still actively using CPAP. Conclusion: In this investigation, we challenged the concept of CPAP non-adherence, highlighting evolving adherence and the significance of continuous monitoring and personalized interventions. Our findings underscore ongoing patient education, multidisciplinary support, and dynamic intervention adaptation for enhanced adherence in challenging patient populations. The results provide insights applicable to non-adherent patients with obstructive sleep apnea, emphasizing the importance of individualized care and sustained engagement for improved CPAP acceptance. [ABSTRACT FROM AUTHOR]

Background. The efficacy and safety of esketamine nasal spray (ESK) were established in registration trials in patients with treatment‐resistant depression (TRD). This French real‐world study aimed to describe the treatment patterns, effectiveness, and safety of ESK in TRD patients over a 12‐month follow‐up. Materials and Methods. This study used secondary data from patient files of hospital‐based psychiatrists and started during the first French patient early access to ESK. The response and remission rates with ESK were analyzed using the total score of the Montgomery–Åsberg Depression Rating Scale (MADRS). The time to first treatment response and work resumption were described (Kaplan–Meier method). Adverse events (AEs) were analyzed. Results. Prior to ESK initiation, the 157 analyzed patients (age ≤ 65 years, 82.8%; female, 66.2%) had depression for 10.5 years (median, IQR, 4.2–21.2) and received a median of 6 (3–8) previous treatment lines. At ESK initiation, the mean ± SD total MADRS score was 32.1 ± 7.7. At that time, ESK was combined with antidepressants (93.6% of patients; SNRI, 65.0%; SSRI, 57.3%) and/or other potentiation strategy (63.1%; atypical antipsychotics, 36.3%; lithium, 25.6%; antiepileptics, 21.7%). During the 12‐month follow‐up, 125 patients (79.6%) discontinued ESK. The median duration of ESK treatment was 19.4 weeks (IQR, 4.4–40.1). At 1 month after ESK initiation, 40.2% of still treated patients met criteria for clinical response and 19.7% for remission (median time to response, 5.7 weeks; 95% CI (4.1–8.4)). 82.6% of active patients were on sick leave at ESK initiation; the work resumption rate was 24% (13%–40%) 12 weeks later. AEs were reported in 68.6% of patients, serious AEs in 17.2%, and AEs leading to ESK discontinuation in 14.6%. Conclusion. These real‐world effectiveness and safety data were consistent with findings from previous clinical trials, describing the real‐life clinical experience of patients receiving ESK and confirming that ESK has its place in therapy for the treatment of TRD. [ABSTRACT FROM AUTHOR]

Background: Postoperative sleep disturbance has a potentially detrimental effect on postoperative recovery. Perioperative patients are affected by several factors. General anesthesia induces a non-physiological state that does not resemble natural sleep. Exposure to propofol/sevoflurane can lead to desynchronization of the circadian rhythm, which may result in postoperative sleep disturbance characterized by mid-cycle advancement of sleep and daytime sleepiness. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with a unique sedative effect that facilitates the transition from sleep to wakefulness. Basic research has shown that dexmedetomidine induces deep sedation, similar to physical sleep, and helps maintain forebrain connectivity, which is likely to reduce delirium after surgery. The aim of this study is to evaluate the influence of exposure to the mono-anesthetic propofol on the development of postoperative sleep disturbance in young and middle-aged female patients undergoing hysteroscopy and whether prophylactic administration of dexmedetomidine influences reducing postoperative sleep disturbance. Methods: This prospective randomized controlled trial (RCT) will include 150 patients undergoing hysteroscopy at the First Affiliated Hospital of Xiamen University. Participants will be randomly assigned to three groups in a 1:1:1 ratio. The dexmedetomidine group will have two subgroups and will receive a nasal spray of 0.2 µg/kg or 0.5 µg/kg 25 min before surgery, while the control group will receive a saline nasal spray. Three groups will undergo hysteroscopy with propofol-based TIVA according to the same scheme. Sleep quality will be measured using a wearable device and double-blind sleep assessments will be performed before surgery and 1, 3, and 7 days after surgery. SPSS 2.0 is used for statistical analysis. A χ2 test is used to compare groups, and t-test is used to determine statistical the significance of continuous variables. Discussion: The purpose of this study is to investigate the incidence of propofol-associated sleep disorders and to test a combination of dexmedetomidine anesthesia regimen for the prevention of postoperative sleep disorders. This study will help to improve patients' postoperative satisfaction and provide a new strategy for comfortable perioperative medical treatment. Trial registration: ClinicalTrials.gov NCT06281561. Registered on February 24, 2024. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsTo investigate the clinical efficacy and safety of Loratadine combined with Glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis.A total of 100 pediatric patients with moderate to severe bronchial asthma and seasonal allergic rhinitis admitted to our hospital between January 2020 and January 2023 were included in this study. All patients met the complete inclusion and exclusion criteria. Based on different treatment interventions, they were divided into the control group (n = 50) and the observation group (n = 50). Patients in the control group received treatment with glucocorticoid nasal spray, while patients in the observation group received combined intervention with Loratadine in addition to the treatment received by the control group. The clinical treatment outcomes, incidence of adverse reactions, as well as the scores of nasal symptoms, asthma control, and peak expiratory flow rates at different treatment time points (baseline, T1: 30 days after treatment, T2: 60 days after treatment, T3: 90 days after treatment) were compared between the two groups. The combined treatment of Loratadine with Glucocorticoid nasal spray demonstrates significant clinical efficacy in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. It further promotes the recovery of peak expiratory flow rates, improves symptoms of rhinitis and asthma in pediatric patients. Importantly, the application of this combined treatment does not increase the risk of adverse reactions in pediatric patients, indicating its high safety profile. This treatment approach is worthy of clinical application and further promotion. [ABSTRACT FROM AUTHOR]

This study aimed to optimize the formula of aripiprazole nanosuspension for intranasal drug delivery. Response Surface Methodology (RSM) was employed to determine the influence of independent variables, including drug concentration, polymer concentration, and the ratio of polymer combination, on the nanosuspension characteristics. The parameters under investigation were particle size (d mean), polydispersity index, and drug content. Fifteen formulas generated from Box-Behnken Design (BBD) were prepared using the combination of high-shear homogenization--ultrasonication method, and the Design Expert software was applied for optimum formula determination. The result showed significant effects of the independent variables on the nanosuspension characteristics, with particle sizes ranging from 143.6 -- 334.6 nm, PDI values of 0.302 -- 0.649, and drug content of 98.7 -- 102.1%. The predicted optimum formula had a drug concentration of 28 mg/mL in the organic solvent, polymer concentration of 1.5% (w/v), and HPMC to PVP ratio of 1.4 with desirability of 0.94. Additionally, it exhibited desirable characteristics, such as a particle size of 171.2 ± 11.4 nm, a PDI value of 0.317 ± 0.02, and a high drug content of 100.04 ± 0.65%. The optimized formula was also evaluated for its morphology using TEM, in vitro duration of mucoadhesion and physical-chemical stability study. In conclusion, the aripiprazole nanosuspension prepared and optimized using RSM exhibited favorable characteristics, including small particle size, narrow distribution, and high drug content. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective(s): ”Quality by Design” (QbD) is a novel approach to product development that involves understanding the product and process, as well as the relationship between critical quality attributes (CQA) and critical process parameters (CPP). This study aimed to optimize the gabapentin-loaded solid lipid nanoparticle formulation (GP-SLN) using a QbD approach and evaluate in vitro and ex vivo performance. Materials and Methods: The GP-SLN formulation was created using the microemulsion method by combining Gelucire 48/16, Tween 80, and Plurol Oleique CC 497. The Box-Behnken experimental design was adopted to investigate the effects of independent factors on dependent factors. The GPSLN formulation was assessed based on particle size and distribution, zeta potential, morphology, entrapment efficiency, release kinetics, permeation parameters, stability, and nasal toxicity. Results: The nanoparticles had a cubical shape with a particle size of 185.3±45.6 nm, a zeta potential of -24±3.53 mV, and an entrapment efficiency of 82.57±4.02%. The particle size and zeta potential of the GP-SLNs remained consistent for 3 months and followed Weibull kinetics with a significantly higher ex vivo permeability (1.7 fold) than a gabapentin solution (GP-SOL). Histopathology studies showed that intranasal administration of the GP-SLN formulation had no harmful effects. Conclusion: The current study reports the successful development of a GP-SLN formulation using QbD. A sustained release of GP was achieved and its nasal permeability was increased. Solid lipid nanoparticles with optimum particle size and high entrapment efficiency may offer a promising approach for the intranasal delivery of drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The intranasal (IN) route of administration is important for topical drugs and drugs intended to act systemically. More recently, direct nose-to-brain input was considered to bypass the blood-brain barrier. Processes related to IN absorption and nose-to-brain distribution are complex and depend, sometimes in contrasting ways, on chemico-physical and structural parameters of the compounds, and on formulation options. Due to the intricacies of these processes and despite the large number of articles published on many different IN compounds, it appears that absorption after IN dosing is not yet fully understood. In particular, at variance of the understanding and modelling approaches that are available for predicting the pharmacokinetics (PK) following oral administration of xenobiotics, it appears that there is not a similar understanding of the chemico-physical and structural determinants influencing drug absorption and disposition of compounds after IN administration, which represents a missed opportunity for this research field. This is even more true regarding the understanding of the direct nose-to-brain input. Due to this, IN administrations may represent an interesting and open research field for scientists aiming to develop PK property predictions tools, mechanistic PK models describing rate and extent of IN absorption, and translational tools to anticipate the clinical PK following IN dosing based on in vitro and in vivo non clinical experiments. This review intends to provide: i) some basic knowledge related to the physiology of PK after IN dosing, ii) a non-exhaustive list of preclinical and clinical examples related to compounds explored for the potential nose-to-blood and nose-to-brain passage, and iii) the identification of some areas requiring improvements, the understanding of which may facilitate the development of IN drug candidates. [ABSTRACT FROM AUTHOR]

Background: Postnasal drip (PND) syndrome is a prevalent complaint encountered in otolaryngology practices. PND may be refractory to medical therapy, and surgical treatments are complicated by side effects. Objective: While posterior nasal nerve (PNN) ablation has demonstrated efficacy for chronic rhinitis overall, we sought to examine the effect of PNN ablation for patients with PND as their primary complaint. Methods: This is a retrospective case series study of 40 chronic rhinitis (CR) patients with a primary complaint of PND. Included patients had to have failed medical therapy such as anti-cholinergic nasal sprays, reflux treatments, and/or nasal steroids. Primary outcome measures included 22 item Sino-Nasal Outcome Test (SNOT-22) PND component and Total Nasal Symptom Score. Secondary outcome measure was subjective improvement, defined as a > 30% improvement in PND symptoms. Results: Median follow-up was 138 days (interquartile range: 72-193). 72.5% (29/40) of patients reported at least a 30% improvement in PND symptoms. Mean PND SNOT-22 scores were 4.2/5 (SD = 0.8) pre-procedure versus 1.9/5 (SD = 1.3) post-procedure (P =.001). PNN ablation response did not correlate to ipratropium bromide nasal spray response, although younger and non-smoker patients had better response rates. Conclusion: This exploratory study of PNN ablation for the primary symptom of PND demonstrates efficacy as assessed by the PND component of SNOT-22 and subjective improvement. These results can be useful in guiding physician–patient discussions in determining treatment options for medically refractory PND. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In order to carry out mathematical modeling of the drug particles or drop movement in the human respiratory system, an approach to reverse prototyping of the studied areas based on the medical data (computed tomography) results is presented. To adapt the computational grid, a mathematical model of airflow in channels of complex geometry (respiratory system) has been developed. Based on the data obtained, the results of computational experiments for a single-phase system are presented. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited. Methods: We conducted post hoc analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged =6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded. Results: Seizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray. Conclusion: These results suggest that diazepam nasal spray can be effectively administered at any time of day. [ABSTRACT FROM AUTHOR]

Introduction: Allergic rhinoconjunctivitis (AR) is an IgE-mediated inflammation of nasal and ocular mucosa after environmental allergen exposure, mainly by house dust mites (HDM). AR affects more than one third of the population worldwide and it is associated with loss of quality of life (QoL). Aim: To analyse the improvement in the QoL in 50 patients with moderate-persistent AR due to house HDM before and after receiving 1 year of subcutaneous specific aeroallergen immunotherapy treatment (SAIT). Material and methods: A prospective observational study was performed based on clinical practice in 50 patients with moderate-severe persistent AR due to HDM and candidates to SAIT. Forty-one patients completed the study. Patients were evaluated with the ESPRINT short-version QoL questionnaire, a score of medication use and visual analogue scale (VAS) symptom score, prior to and 12 months after SAIT. Results: Forty-one patients (25 women, mean age 26.9 years). Mean ESPRINT values prior to the start SAIT was 3.06 (moderate-severe) and 1 year after starting subcutaneous SAIT the mean value dropped in all patients to 0.88 (mild). The VAS score symptom dropped from 8.26 to 3.68. 97.56% of patients used 3 or more drugs (oral antihistamine, ophthalmic/intranasal antihistamine, intranasal corticosteroid and/or oral antileukotrienes) prior to starting SAIT, and 1 year after it, 58.53% used one on-demand medication to control symptoms, oral antihistamine or nasal spray, and not daily use. Conclusions: Subcutaneous SAIT seems to be a valid treatment in our patients with moderate-persistent AR due to HDM, since it reduces the ESPRINT score, VAS score and the use of medication. An improvement in the quality of life and satisfaction was observed by the patients themselves. [ABSTRACT FROM AUTHOR]