Efficient symptomatic treatment and viral load reduction for children with influenza virus infection by nasal-spraying Bacillus spore probiotics.

Influenza virus is a main cause of acute respiratory tract infections (ARTIs) in children. This is the first double-blind, randomized, and controlled clinical trial examining the efficacy of nasal-spraying probiotic LiveSpo Navax, which contains 5 billion of Bacillus subtilis and B. clausii spores in 5 mL, in supporting treatment of influenza viral infection in pediatric patients. We found that the nasal-spraying Bacillus spores significantly shortened the recovery period and overall treatment by 2 days and increased treatment effectiveness by 58% in resolving all ARTIs' symptoms. At day 2, the concentrations of influenza virus and co-infected bacteria were reduced by 417 and 1152 folds. Additionally, the levels of pro-inflammatory cytokines IL-8, TNF-α, and IL-6 in nasopharyngeal samples were reduced by 1.1, 3.7, and 53.9 folds, respectively. Compared to the standard control group, treatment regimen with LiveSpo Navax demonstrated significantly greater effectiveness, resulting in 26-fold reduction in viral load, 65-fold reduction in bacterial concentration, and 1.1-9.5-fold decrease in cytokine levels. Overall, nasal-spraying Bacillus spores can support the symptomatic treatment of influenza virus-induced ARTIs quickly, efficiently and could be used as a cost-effective supportive treatment for respiratory viral infection in general.Clinical trial registration no: NCT05378022 on 17/05/2022.

In situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nose-to-brain delivery: development, characterization and deposition studies in a 3D-printed human nasal cavity model.

The nasal route has been investigated as a promising alternative for drug delivery to the central nervous system, avoiding passage through the blood-brain barrier and improving bioavailability. In this sense, it is necessary to develop and test the effectiveness of new formulations proposed for the management of neurological disorders. Thereby, the aim of this work was to develop and characterize an ion sensitive in situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nasal delivery in the treatment of epilepsy. Physical characterization of the developed formulations was performed and included the evaluation of rheological features, particle size, polydispersity index (PDI) and zeta potential (ZP) of an in situ hydrogel containing DZP-NLC. Afterwards, in vitro drug release, in vitro mucoadhesion and biocompatibility studies with RPMI 2650 nasal cells were performed. The in situ hydrogel containing DZP-NLC was aerosolized with a nasal spray device specifically designed for nose-to-brain delivery (VP7 multidose spray pump with a 232 N2B actuator) and characterized for droplet size distribution and spray cone angle. Finally, the deposition pattern of this hydrogel was evaluated in a 3D-printed human nasal cavity model. The developed in situ hydrogel containing DZP-NLC presented adequate characteristics for nasal administration, including good gelling ability, mucoadhesiveness and prolonged drug release. In addition, after inclusion in the hydrogel net, the particle size (81.79 ± 0.53 nm), PDI (0.21 ± 0.10) and ZP (-30.90 ± 0.10 mV), of the DZP-NLC remained appropriate for nose-to-brain delivery. Upon aerosolization in a nasal spray device, a suitable spray cone angle (22.5 ± 0.2°) and adequate droplet size distribution (Dv (90) of 317.77 ± 44.12 µm) were observed. Biocompatibility studies have shown that the developed formulation is safe towards RPMI 2650 cells in concentrations up to 100 µg/mL. Deposition studies on a 3D-printed human nasal cavity model revealed that the best nasal deposition profile was obtained upon formulation administration without airflow and at an angle from horizontal plane of 75°, resulting in 47% of administered dose deposited in the olfactory region and 89% recovery. The results of this study suggested that the intranasal administration of the developed in situ hydrogel containing DZP-NLC could be a promising alternative to the conventional treatments for epilepsy.

Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.

BACKGROUND: The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed. RESULTS: Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration. CONCLUSION: Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.

Determination of heavy metals and essential elements in nasal sprays and drops (Saline/Sea Water) and evaluation in terms of toxicity.

Heavy metals are toxic to human health and their concentrations in drinking water are sometimes above the limits recommended by the World Health Organization (WHO). In addition to drinking water, a possible source for the intake of heavy metals is nasal sprays, which are frequently used to combat upper respiratory tract infections, especially in young children. Different types of nasal sprays are sold in pharmacies, such as saline solutions prepared from NaCl, sea water, or ocean water. In this work, Al, Sb, As, B, Cd, Cr, Co, Cu, Fe, Mn, Ni, Si, and Zn analyzes were performed on 22 saline samples with ICP-MS to determine their toxicity levels. For some samples, the toxic element concentrations were above the drinking water limits. Because nasal sprays are administered to the region close to the brain, the potential risk should be considered more fully. The accuracy of the results was tested by the standard addition method and certified reference material (CRM) analysis, which obtained recovery values for the elements of 83%-115% and 82%-108% for standard addition and CRM analysis, respectively. This is the first study to consider the risk of heavy metals in nasal sprays.

Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study.

BACKGROUND: Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK plus oral antidepressant (AD) after a relapse in SUSTAIN-1. METHODS: Patients aged 18-64 years who achieved stable remission or response with ESK and subsequently relapsed after randomization to continue ESK or switch to placebo nasal spray (PBO) in SUSTAIN-1 and entered the IND phase of SUSTAIN-3 were included in this interim analysis. Response (≥50% improvement in total score from baseline for Montgomery-Åsberg Depression Rating Scale [MADRS] and Patient Health Questionnaire 9-item [PHQ-9]), remission (MADRS score ≤12; PHQ-9 total score <5), changes in depression rating scores (measured as mean change from baseline), and safety were evaluated (incidence of treatment-emergent and serious adverse events [AE]). RESULTS: Of the 96 eligible patients who entered IND in SUSTAIN-3, 32 (33.3%) were taking ESK+AD at the time of relapse in SUSTAIN-1 and 64 (66.7%) were taking AD+PBO. Substantial improvements in depressive symptoms were observed over the second IND phase in both groups and were maintained over the optimization/maintenance (OP/M) phase. MADRS response rates following a second IND were 71.9% and 73.4% for previously relapsed (PR) ESK+AD and PR-AD+PBO, respectively; remission rates were 62.5% and 60.9%, respectively. During the IND and OP/M phases, 58.3% and 83.3% of patients experienced a treatment-emergent AE, respectively. No patients discontinued due to an AE during the second IND. CONCLUSIONS: Patients with TRD benefitted from receiving a second IND and maintenance treatment with ESK and no new safety signals were identified.

[A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea].

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.

Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment.

BACKGROUND AND OBJECTIVES: Nasal esketamine is indicated for the treatment of adults with treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Primary objectives of this study were to evaluate the effect of nasal decongestant pretreatment in patients with allergic rhinitis and the impact of daily nasal corticosteroid administration by healthy subjects on nasal esketamine pharmacokinetics. METHODS: Patients with allergic rhinitis self-administered 56 mg of nasal esketamine after pretreatment with nasal oxymetazoline (0.05%) at 1 h before esketamine and without oxymetazoline pretreatment. They were exposed to grass pollen in an allergen challenge chamber to induce allergic rhinitis symptoms at approximately 2 h before each esketamine administration until 1 h after. Healthy subjects self-administered esketamine (56 mg) before and after administration for 16 consecutive days of mometasone (200 µg), with the second esketamine dose administered 1 h after the last mometasone dose. The plasma pharmacokinetics of esketamine and noresketamine were assessed after each esketamine administration. The tolerability of esketamine, including effects on dissociative and potential psychotomimetic symptoms and level of sedation and suicidal ideation and behavior, was evaluated. RESULTS: The rate of esketamine absorption was slightly greater in patients exhibiting symptoms of allergic rhinitis (decrease in median tmax from 32 min to 22 min). Increases in esketamine Cmax and AUC were also small (mean, ≤ 21%). The pharmacokinetics of esketamine was not affected by oxymetazoline or mometasone pretreatment. Esketamine was well tolerated when it was administered with or without pretreatment of oxymetazoline or mometasone. CONCLUSIONS: Patients exhibiting symptoms of rhinitis may receive nasal esketamine spray without dose adjustment. In addition, esketamine may be administered 1 h after using a nasal decongestant or corticosteroid. TRIAL REGISTRATION: The study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014-000534-38) registries.

Access and real-world use patterns of esketamine nasal spray among patients with treatment-resistant depression covered by private or public insurance.

OBJECTIVE: To describe access and real-world use patterns of esketamine nasal spray among adults with treatment-resistant depression (TRD) with private or public insurance. METHODS: Adults with ≥1 claim for esketamine nasal spray were selected from Clarivate's Real World Data product (January 2016-March 2021). Patients with evidence of TRD initiating esketamine (index date) after 05 March 2019 were included. Esketamine access, as measured by pharmacy claim approval rate for each treatment session, and use patterns were described post-index (follow-up period). RESULTS: Among 535 patients with pharmacy claims for esketamine nasal spray (mean age 49.1 years; 65.4% females), 534 had the first esketamine claim being a pharmacy claim, of which 34.6% were approved, 46.3% were rejected, and 19.1% were abandoned. Main reasons for rejection included "claim not covered by plan" (57.1%), "claim errors" (52.6%), and "prior authorization required" (22.7%). The approval rate increased to 85.2% by the second esketamine treatment session. A total of 273 patients initiated esketamine (mean age 49.3 years; 66.3% females). Patients had a mean ± standard deviation (SD) of 11.8 ± 13.3 esketamine sessions over a mean ± SD of 11.8 ± 6.4 months; 47.6% of patients completed ≥8 sessions (i.e. the number of sessions in induction phase) over a mean ± SD of 80.1 ± 71.9 days (per label, 28 days); 48 (17.6%) patients completed induction per label, and among them 93.8% continued treatment. CONCLUSIONS: Initial access to esketamine nasal spray may be hindered by prior authorization or claim filing errors. Among patients who initiated esketamine, treatment compliance generally deviates from label recommendations; yet, most of those who received induction per label successfully transition to maintenance with esketamine.

Esketamine nasal spray is a novel therapy for treatment-resistant depression (TRD). In the United States, insurance plans often regulate access to esketamine. Additionally, for patients, it may be challenging to comply to the treatment schedule, because patients must receive esketamine in a certified treatment center, be monitored for 2 h for potential side effects, and they cannot drive until the next day. This real-world study used insurance claims data and found that patients with TRD had difficulties accessing esketamine. Among those with access, esketamine use patterns were suboptimal.

Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study.

Pediatric developmental epileptic encephalopathies are often refractory to treatment despite stable antiseizure therapy. The safety profile of diazepam nasal spray (Valtoco) as rescue therapy for seizure clusters was described in a long-term safety study. This post hoc analysis assessed safety and effectiveness within a subpopulation of patients with developmental epileptic encephalopathies. Of 163 treated patients, 64 were diagnosed with ≥1 pediatric developmental epileptic encephalopathy. Among the most common developmental epileptic encephalopathies were Rett syndrome (n = 16), Lennox-Gastaut syndrome (n = 9), and Dravet syndrome (n = 7). In the broad pediatric developmental epileptic encephalopathy group, 10.6% of seizure clusters were treated with a second dose, with similar proportions in the 3 individual encephalopathies. Across groups, treatment-emergent adverse event rates ranged from 66.7% to 100%. Only epistaxis (n = 2) was treatment-related and reported in >1 patient. In this long-term safety analysis in patients with developmental epileptic encephalopathies, diazepam nasal spray demonstrated a consistent safety profile, supporting its use in these hard-to-treat patients (ClinicalTrials.gov NCT02721069).

The efficacy and safety of varenicline nasal spray for the management of dry eye signs: a systematic review and meta-analysis.

BACKGROUND: Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment. METHODS: The Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials. RESULTS: Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs. CONCLUSION: VNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.

Effect of phthalocyanine oral and nasal antiseptic solutions on the infectivity of SARS-CoV-2 in patients with COVID-19: a randomized controlled trial.

Background: In individuals with coronavirus disease (COVID-19), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL) plays an important role in infectivity. Objectives: This study aimed to evaluate the reduction in the VL and infectivity induced by phthalocyanine mouthwash and nasal spray in patients with COVID-19. Methods: Patients with mild COVID-19 were recruited to participate in a triple-blinded randomized controlled trial. Participants were assigned to one of three groups: Group 1, non-active mouthwash and saline nasal spray (SNS); Group 2, phthalocyanine mouthwash and SNS; and Group 3 phthalocyanine mouthwash and phthalocyanine nasal spray. VL was assessed in nasopharyngeal and oropharyngeal swabs collected at the time of clinical diagnosis at baseline as well as 24 and 72 hours after starting the rinsing protocols. Findings: Forty-six participants were included in the analysis: 15, 16, and 15 in Groups 1, 2, and 3, respectively. After 72 hours, the reduction in VL was significantly higher in Group 3 (mean cycle threshold (Ct) decrease: 11.21) than in Group 1 (mean Ct decrease: 5.53). Additionally, only the mean VL in Group 3 was reduced to a non-contagious level after 72 hours. Main conclusions: Use of phthalocyanine mouthwash and nasal spray is effective at reducing SARS-CoV-2 infectivity.

Determining the clinical and cost-effectiveness of nasal sprays and a physical activity and stress management intervention to reduce respiratory tract infections in primary care: A protocol for the 'Immune Defence' randomised controlled trial.

BACKGROUND: Most adults in the UK experience at least one viral respiratory tract infection (RTI) per year. Individuals with comorbidities and those with recurrent RTIs are at higher risk of infections. This can lead to more severe illness, worse quality of life and more days off work. There is promising evidence that using common nasal sprays or improving immune function through increasing physical activity and managing stress, may reduce the incidence and severity of RTIs. METHODS AND DESIGN: Immune Defence is an open, parallel group, randomised controlled trial. Up to 15000 adults from UK general practices, with a comorbidity or risk factor for infection and/or recurrent infections (3 or more infections per year) will be randomly allocated to i) a gel-based nasal spray designed to inhibit viral respiratory infections; ii) a saline nasal spray, iii) a digital intervention promoting physical activity and stress management, or iv) usual care with brief advice for managing infections, for 12 months. Participants will complete monthly questionnaires online. The primary outcome is the total number of days of illness due to RTIs over 6 months. Key secondary outcomes include: days with symptoms moderately bad or worse; days where work/normal activities were impaired; incidence of RTI; incidence of COVID-19; health service contacts; antibiotic usage; beliefs about antibiotics; intention to consult; number of days of illness in total due to respiratory tract infections over 12 months. Economic evaluation from an NHS perspective will compare the interventions, expressed as incremental cost effectiveness ratios. A nested mixed methods process evaluation will examine uptake and engagement with the interventions and trial procedures. TRIAL STATUS: Recruitment commenced in December 2020 and the last participant is expected to complete the trial in April 2024. DISCUSSION: Common nasal sprays and digital interventions to promote physical activity and stress management are low cost, accessible interventions applicable to primary care. If effective, they have the potential to reduce the individual and societal impact of RTIs. TRIAL REGISTRATION: Prospectively registered with ISRCTN registry (17936080) on 30/10/2020. SPONSOR: This RCT is sponsored by University of Southampton. The sponsors had no role in the study design, decision to publish, or preparation of the manuscript.

New Nasal Spray for Migraine Headaches.

Zavegepant (Zavzpret), a nasal spray, is approved to treat adults with acute migraine with or without aura. It should not be used as a preventative.The most common adverse effects of zavegepant are taste disorders, nausea, nasal discomfort, and vomiting. Hypersensitivity reactions are also possible.Patients should avoid coadministration with intranasal decongestants, as these can decrease zavegepant absorption.

Etripamil Nasal Spray: Therapeutic Potential for Treating Paroxysmal Supraventricular Tachycardia.

Patients with arrythmias are at an increased risk of heart-related comorbidities and complications. Specifically, patients with paroxysmal supraventricular tachycardia (PSVT), a type of arrythmia, are at increased risk of lightheadedness or shortness of breath, due to the increased rate of the heartbeat. Most patients are prescribed oral medications to control their heart rates and maintain a normal heart rhythm. Researchers have been tasked with discovering alternative treatment options with new delivery methods to treat arrythmias such as PSVT. A nasal spray was subsequently designed and is currently undergoing clinical studies. This review aims to present and discuss the current clinical and scientific evidence pertaining to etripamil.

Clinical effectiveness of fluticasone furoate nasal spray for perennial allergic rhinitis in children: a comprehensive review.

OBJECTIVE: To assess the clinical effectiveness of fluticasone furoate nasal spray (FFNS) versus placebo on nasal symptoms and safety in children with perennial allergic rhinitis (AR). METHODS: A comprehensive review was conducted with data obtained from Medline and Embase databases up to April 2023. The population of interest was patients aged 2-12 years with perennial AR. The selection was limited to randomized controlled trials (RCTs), comparing FFNS with placebo. Outcomes of interest included the reflective total nasal symptoms scores (rTNSS) and safety. To assess the minimal clinically important difference for rTNSS, the Cohen's guideline was used. If the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceeded the threshold of -0.20, effects were considered clinically significant. RESULTS: Three RCTs (959 pediatric patients) were selected. One study evaluated the short-term use of FFNS, another evaluated the long-term use of FFNS, and another evaluated both the short-term and long-term use of FFNS. FFNS produced a statistically significant reduction over placebo in rTNSS (SMD -0.18; 95 percent CI -0.35 to -0.01, p = 0.03) in long-term treatment studies, but not in short-term treatment studies. However, since the mean reduction did not reach the minimum clinically important difference (SMD -0.20), these results were considered clinically not relevant. Safety outcomes with FFNS were similar to placebo. CONCLUSIONS: The currently available evidence suggests that FFNS, 110 µg once daily, compared to placebo, does not produce a meaningful clinical effect on nasal symptom in children with perennial AR.

The Efficacy and Safety of Etripamil Nasal Spray for Acute Paroxysmal Supraventricular Tachycardia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) treatment requires medically supervised intervention. Etripamil is a novel short-acting calcium channel blocker. Its intranasal spray formulation has a rapid onset of action and shows promise for the unsupervised treatment of PSVT. OBJECTIVE: We aimed to evaluate the efficacy and safety of etripamil nasal spray for the acute conversion of PSVT. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching the PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane databases through to 1 December 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI). RESULTS: Three RCTs with a total of 496 participants were included in our analysis. Etripamil was effective for PSVT conversion at 15 min (RR 1.84, 95% CI 1.37-2.48), 30 min (RR 1.86, 95% CI 1.42-2.44), and 60 min (RR 1.25, 95% CI 1.05-1.50) after drug administration; decreasing medical intervention-seeking (RR 0.58, 95% CI 0.37-0.90); and decreasing emergency room (ER) visits (RR 0.61, 95% CI 0.38-0.97). However, there was no difference at 300 min (RR 1.10, 95% CI 0.97-1.25) and it was associated with higher rates of adverse events (RR 3.17, 95% CI 2.15-4.69). CONCLUSION: Etripamil nasal spray was effective and well tolerated to induce PSVT termination for up to 60 min. Therefore, etripamil nasal spray constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

[Observation of the long-term clinical efficacy of "Fuyang Guben" acupuncture-moxibustion therapy on perennial allergic rhinitis and its effects on the total IgE and IL-4 in the serum].

OBJECTIVE: To investigate the long-term clinical efficacy and safety of "Fuyang Guben" (supporting yang and consolidating root) acupuncture-moxibustion therapy on perennial allergic rhinitis (PAR), and to explore its functioning mechanism. METHODS: The patients with PAR were randomly divided into acupuncture + western medicine group (n=30) and western medicine group (n=30). In the western medicine group, fluticasone propionate nasal spray was administered, one spray in each nostril in one treatment, once a day, for 6 weeks. On the basis of the western medicine group, fuyangguben acupuncture-moxibustion therapy was supplemented. Acupuncture was applied to Shangxing (GV23), Yintang (GV24+), and bilateral Yingxiang (LI20), Shangyingxiang (EX-HN8), Sibai (ST2), Hegu (LI4) and Chize (LU5); warm needling was applied at Dazhui (GV14). The patients of this group received 30 min of acupuncture-moxibustion therapy 3 times weekly during the first 4 weeks and twice a week in the last 2 weeks, totally for 6 weeks. Before treatment, after treatment, in week 10, 18 and 30 of follow-up visits, the reflective total nasal symptom score (rTNSS), the total non-nasal symptom score (TNNSS), the total ophthalmic symptom score (TOSS), and the score of the rhinitis quality of life (RQLQ) scale were compared in the patients of the two groups separately. Using ELISA, the serum concentrations of total immunoglobulin E (IgE) and interleukin-4 (IL-4) were detected before and after treatment. RESULTS: After treatment, the rTNSS, TNNSS, TOSS, as well as RQLQ score were lower in comparison with those before treatment in each group (P<0.05).The rTNSS, TNNSS, TOSS and the score of RQLQ in the week 10, 18 and 30 of follow-up visits were reduced when compared with those before treatment in each group (P<0.05), and these scores in the acupuncture + western medicine group were remarkably lower than those of the western medicine group (P<0.05). After treatment, the serum contents of total IgE and IL-4 were significantly decreased when compared with those before treatment in the acupuncture + western medicine group (P<0.05), and these indicators in the acupuncture + western medicine group were lower than those of the western medicine group (P<0.05). CONCLUSION: On the base of treatment with fluticasone propionate nasal spray, "Fuyang Guben" acupuncture-moxibustion therapy is safe and effective on PAR, presenting a remarkably long-term efficacy. The functioning mechanism may be related to the down-regulation of total IgE and IL-4 in serum.

New Alzheimer Disease Drugs, Long COVID and the Central Nervous System, and a Nasal Spray for Migraines-Highlights From the 2023 American Academy of Neurology Conference.

This Medical News article discusses research presented at the recent American Academy of Neurology Conference.

Overcoming barriers to the management of seizure clusters: ease of use and time to administration of rescue medications.

INTRODUCTION: Patients with epilepsy can experience seizure clusters (acute repetitive seizures), defined as intermittent, stereotypic episodes of frequent seizure activity that are distinct from typical seizure patterns. There are three FDA-approved rescue medications, diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray, that can be administered to abort a seizure cluster in a nonmedical, community setting. Despite their effectiveness and safety, rescue medications are underutilized, and patient/caregiver experiences and perceptions of ease of use may constitute a substantial barrier to greater utilization. AREAS COVERED: The literature on rescue medications for seizure clusters is reviewed, including the effectiveness and safety, with an emphasis on ease and timing of treatment and associated outcomes. Barriers to greater utilization of rescue medication and the role of seizure action plans are discussed. EXPERT OPINION: Intranasal rescue medications are easier to use and can be administered more rapidly than other routes (rectal, intravenous). Importantly, rapid administration of intranasal rescue medications has been associated with shorter durations of seizure activity as compared with rectal/intravenous routes. Intranasal rescue medications are also easy to use and socially acceptable. These factors potentially remove or reduce barriers to use and optimize the management of seizure clusters.

Post-exposure prophylaxis with SA58 (anti-SARS-COV-2 monoclonal antibody) nasal spray for the prevention of symptomatic COVID-19 in healthy adult workers: a randomized, single-blind, placebo-controlled clinical study.

Monoclonal antibodies (mAbs) and the post-exposure prophylaxis (PEP) with mAbs represent a very important public health strategy against coronavirus disease 2019 (COVID-19). This study has assessed a new Anti-SARS-COV-2 mAb (SA58) Nasal Spray for PEP against COVID-19 in healthy adults aged 18 years and older within three days of exposure to a SARS-CoV-2 infected individual. Recruited participants were randomized in a ratio of 3:1 to receive SA58 or placebo. Primary endpoints were laboratory-confirmed symptomatic COVID-19 within the study period. A total of 1222 participants were randomized and dosed (SA58, n = 901; placebo, n = 321). Median of follow-up was 2.25 and 2.79 days for SA58 and placebo, respectively. Adverse events occurred in 221 of 901 (25%) and 72 of 321 (22%) participants with SA58 and placebo, respectively. All adverse events were mild in severity. Laboratory-confirmed symptomatic COVID-19 developed in 7 of 824 participants (0.22 per 100 person-days) in the SA58 group vs. 14 of 299 (1.17 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 80.82% (95%CI 52.41%-92.27%). There were 32 SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positives (1.04 per 100 person-days) in the SA58 group vs. 32 (2.80 per 100 person-days) in the placebo group, resulting in an estimated efficacy of 61.83% (95%CI 37.50%-76.69%). A total of 21 RT-PCR positive samples were sequenced and all were the Omicron variant BF.7. In conclusion, SA58 Nasal Spray showed favourable efficacy and safety in preventing symptomatic COVID-19 or SARS-CoV-2 infection in adults who had exposure to SARS-CoV-2 within 72 h.