Search

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]

Abstract Paroxysmal supraventricular tachycardia (PSVT) is commonly seen in clinical practice and represents a significant burden to the healthcare system and to patients. First-line treatments include calcium channel blockers (CCB), although they are intravenous and require medical supervision. Etripamil is an investigational self-administered intranasal L-type CCB for unsupervised treatment of PSVT. In this podcast, we discuss the RAPID trial (NCT03464019), which was a phase 3 study that evaluated the safety and efficacy of etripamil in terminating PSVT episodes using a repeat-dosing regimen. RAPID was a multicenter, randomized trial that enrolled adults with electrocardiograph (ECG)-documented PSVT episodes lasting ≥ 20 min. Patients who tolerated test doses of etripamil were randomized 1:1 to receive either etripamil or placebo. Upon perceiving PSVT symptoms, patients began ECG monitoring and performed a vagal maneuver. If arrhythmia termination was unsuccessful, they self-administered 70 mg of etripamil or placebo, followed by an optional second dose after 10 min. The primary endpoint was time to conversion of PSVT to sinus rhythm within 30 min of the initial dose and sustained for ≥ 30 s. The safety group included all patients who self-administered the study treatment. Of 692 enrollees, 184 self-administered the study drug (99 etripamil, 85 placebo) for ECG-confirmed PSVT. Conversion of PSVT to sinus rhythm within 30 min was achieved in 64.3% of etripamil-treated subjects versus 31.2% of placebo-treated subjects. A significant threefold reduction in the median time to conversion of 17.2 min was observed in the etripamil group versus 53.5 min in the placebo group. Treatment-emergent adverse events were mild or moderate and primarily included transient nasal discomfort, nasal congestion, and rhinorrhea. If etripamil is approved by the US FDA, it can potentially address a significant unmet need for PSVT treatment outside a clinical setting, reducing the need for intravenous treatments that require medical supervision. Podcast available for this article.

Paroxysmal supraventricular tachycardia (PSVT) is commonly seen in clinical practice and represents a significant burden to the healthcare system and to patients. First-line treatments include calcium channel blockers (CCB), although they are intravenous and require medical supervision. Etripamil is an investigational self-administered intranasal L-type CCB for unsupervised treatment of PSVT. In this podcast, we discuss the RAPID trial (NCT03464019), which was a phase 3 study that evaluated the safety and efficacy of etripamil in terminating PSVT episodes using a repeat-dosing regimen. RAPID was a multicenter, randomized trial that enrolled adults with electrocardiograph (ECG)-documented PSVT episodes lasting ≥ 20 min. Patients who tolerated test doses of etripamil were randomized 1:1 to receive either etripamil or placebo. Upon perceiving PSVT symptoms, patients began ECG monitoring and performed a vagal maneuver. If arrhythmia termination was unsuccessful, they self-administered 70 mg of etripamil or placebo, followed by an optional second dose after 10 min. The primary endpoint was time to conversion of PSVT to sinus rhythm within 30 min of the initial dose and sustained for ≥ 30 s. The safety group included all patients who self-administered the study treatment. Of 692 enrollees, 184 self-administered the study drug (99 etripamil, 85 placebo) for ECG-confirmed PSVT. Conversion of PSVT to sinus rhythm within 30 min was achieved in 64.3% of etripamil-treated subjects versus 31.2% of placebo-treated subjects. A significant threefold reduction in the median time to conversion of 17.2 min was observed in the etripamil group versus 53.5 min in the placebo group. Treatment-emergent adverse events were mild or moderate and primarily included transient nasal discomfort, nasal congestion, and rhinorrhea. If etripamil is approved by the US FDA, it can potentially address a significant unmet need for PSVT treatment outside a clinical setting, reducing the need for intravenous treatments that require medical supervision. Podcast available for this article. 1VEqT_HzS7TNge6AVaxeS- [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine has dose-dependent selectivity for alpha 2 adrenoceptors. It is a good sedative with analgesic characteristics and good haemodynamic stability. Intranasal sedation is a non-invasive medication delivery method that is both safe and well accepted by both children and adults. One of the most common procedures in maxillofacial surgery is transalveolar extraction. In minor oral surgery, a painless transalveolar extraction with little post-operative pain would be ideal. Aim: To examine the effectiveness of intranasal dexmedetomidine spray against intranasal normal saline spray in patients undergoing transalveolar extractions for anxiety relief. Method: We compared sedation effect by Ramsay sedation scale, analgesia by visual analogue scale, monitored BP and pulse rate for anxiety, and spo2 levels for any complication in this prospective double-blinded randomized control study for two groups, A group with intranasal dexmedetomidine spray and the B group of intranasal NS spray for placebo effect at 0 min, 15 min, 30 min, and 45 min until transalveolar extraction. Result: As a result of the intranasal spray of dexmedetomidine, there were no related problems such as respiratory depression. There was a substantial difference in sedation and analgesia between group A and the placebo group, as well as a significant decrease in pulse rate and hypotension in the dexmedetomidine group to reduce anxiety. Conclusion: Intranasal injection of atomized dexmedetomidine (1.5 mcg/kg) for patient sedation having transalveolar extractions or other minor surgical operations in oral and maxillofacial surgery is clinically effective, convenient, lowers anxiety, and safe. Clinical Trial Registration: No. CTRI/2021/07/035181. [ABSTRACT FROM AUTHOR]

The nasopharynx, at the back of the nose, constitutes the dominant initial viral infection trigger zone along the upper respiratory tract. However, as per the standard recommended usage protocol (“Current Use”, or CU) for intranasal sprays, the nozzle should enter the nose almost vertically, resulting in sub-optimal nasopharyngeal drug deposition. Through the Large Eddy Simulation technique, this study has replicated airflow under standard breathing conditions with 15 and 30 L/min inhalation rates, passing through medical scan-based anatomically accurate human airway cavities. The small-scale airflow fluctuations were resolved through use of a sub-grid scale Kinetic Energy Transport Model. Intranasally sprayed droplet trajectories for different spray axis placement and orientation conditions were subsequently tracked via Lagrangian-based inert discrete phase simulations against the ambient inhaled airflow field. Finally, this study verified the computational projections for the upper airway drug deposition trends against representative physical experiments on sprayed delivery performed in a 3D-printed anatomic replica. The model-based exercise has revealed a new “Improved Use” (or, IU) spray usage protocol for viral infections. It entails pointing the spray bottle at a shallower angle (with an almost horizontal placement at the nostril), aiming slightly toward the cheeks. From the conically injected spray droplet simulations, we have summarily derived the following inferences: (a) droplets sized between 7–17 μm are relatively more efficient at directly reaching the nasopharynx via inhaled transport; and (b) with realistic droplet size distributions, as found in current over-the-counter spray products, the targeted drug delivery through the IU protocol outperforms CU by a remarkable 2 orders-of-magnitude.

Abstract Background Air pollution may induce or reinforce nasal inflammation regardless of allergy status. There is limited direct clinical evidence informing the treatment of airborne pollution-related rhinitis. Objective To assess the effectiveness of intranasal budesonide in adults with self-reported rhinitis symptoms triggered/worsened by airborne pollution. Methods Adults in northern China with self-reported rhinitis symptoms triggered or worsened by airborne pollution were randomized to budesonide 256 µg/day or placebo for 10 days in pollution season (October 2019 to February 2020). The primary endpoint was the mean change from baseline in 24-h reflective total nasal symptom score (rTNSS) averaged over 10 days. The secondary endpoints were subject-assessed Global Impression of Change (SGIC), mean change from baseline in individual nasal symptom severity, and mean change from baseline in individual non-nasal symptoms of cough and postnasal drip severity. One-sided P

Background: Air pollution may induce or reinforce nasal inflammation regardless of allergy status. There is limited direct clinical evidence informing the treatment of airborne pollution-related rhinitis. Objective: To assess the effectiveness of intranasal budesonide in adults with self-reported rhinitis symptoms triggered/worsened by airborne pollution. Methods: Adults in northern China with self-reported rhinitis symptoms triggered or worsened by airborne pollution were randomized to budesonide 256 µg/day or placebo for 10 days in pollution season (October 2019 to February 2020). The primary endpoint was the mean change from baseline in 24-h reflective total nasal symptom score (rTNSS) averaged over 10 days. The secondary endpoints were subject-assessed Global Impression of Change (SGIC), mean change from baseline in individual nasal symptom severity, and mean change from baseline in individual non-nasal symptoms of cough and postnasal drip severity. One-sided P < 0.0125 was considered statistically significant. Results: After an interruption by COVID-19, an interim analysis showed that the study could be ended for efficacy with n = 206 participants (103/group) since the primary efficacy endpoint demonstrated significant results. The final efficacy results showed that the 10-day-averaged rTNSS change in the budesonide group was greater than with placebo (− 2.20 vs − 1.72, P = 0.0107). Budesonide also significantly improved 10-day-averaged itching/sneezing change (− 0.75 vs − 0.51, P = 0.0009). Results for SGIC and all other individual symptoms did not show significant differences between the two groups. Conclusions: Intranasal budesonide 256 µg once daily improved the total nasal symptoms and itching/sneezing over 10 days in adults with rhinitis triggered/worsened by airborne pollution. [ABSTRACT FROM AUTHOR]

Central giant cell granuloma is an uncommon, benign, proliferative lesion of unknown etiology, most commonly affecting anterior mandible of younger age group. Early diagnosis may be of benefit to the patient as conservative treatment modalities may be used as compared to radical surgical treatment. Calcitonin as a therapy for central giant cell granuloma of the jaws is a promising alternative to surgical curettage, particularly for larger lesions. We report a case of central giant cell granuloma of mandible in a 14-year-old female patient, who is being treated solely with intranasal spray of salmon calcitonin for 14 months showing greater results.

The aim of this study is to compare the delivery site of topical drugs using the short nozzle and the long nozzle. Fourteen fresh frozen cadaver heads were obtained. All cadaver specimens underwent bilateral endoscopic wide maxillary antrostomy, frontal sinusotomy, and complete sphenoethmoidectomy. The right nasal cavity of each cadaver was sprayed with radiolabeled saline using the short nozzle (short nozzle group), while the left nasal cavity was sprayed using the long nozzle (long nozzle group). The distribution of radioactive saline within the sinus cavities was determined using single-photon emission computed tomography/computed tomography. The distribution of the radiolabeled saline in reference with the maxillary line, vestibule, maxillary, ethmoid, sphenoid, and frontal sinus was compared between the 2 groups using Fisher exact test. The number of specimens that demonstrated radioactivity above the maxillary line is higher in the long nozzle group (14 cadavers, 100%) compared to short nozzle group (9 cadavers, 64.3%; p =.02). There are fewer specimens that demonstrated deposition of radioactive saline in the vestibule in the long nozzle group (6 cadavers, 42.86%) compared to short nozzle group (13 cadavers, 92.86%; P =.006). Compared to short nozzle group, there are more specimens demonstrating radioactivity in the maxillary, ethmoid, sphenoid, and frontal sinus in the long nozzle group, but the differences were not statistically significant (p = 0.241, 0.347, 0.126, 0.5). Compared to short nozzle, long nozzle more frequently delivers intranasal drugs beyond the maxillary line and less frequently in the vestibule. These findings support the hypothesis that the use of long and narrow nozzle, instead of the conventional short nozzle, can improve sinonasal drug delivery in post-endoscopic sinus surgery nose. [ABSTRACT FROM AUTHOR]

Background and Aims: Preoperative anxiety in children leading to postoperative negative changes and long-term behavioral problems needs better preanesthetic sedation. Across the world, midazolam is the most commonly used premedicant in pediatric patients. The fact that no single route has achieved universal acceptance for its administration suggests that each route has its own merits and demerits. This study compares oral midazolam syrup and intranasal midazolam spray as painless and needleless systems of drug administration for preanesthetic sedation in children. Material and Methods: With randomization, Group O (30 children): Received oral midazolam syrup 0.5 mg/kg and Group IN (30 children): Received intranasal midazolam spray 0.2 mg/kg. Every child was observed for acceptance of drug, response to drug administration, sedation scale, separation score, acceptance to mask, recovery score and side effects of drug. Data were analyzed using Student's t-test, standard error of the difference between two means and Chi-square test. Results: In Group O and IN, 15/30 children (50%) and 7/30 children (23%) accepted drug easily (P < 0.05); 4/22 children (18%) in Group O and 11/20 children (55%) in Group IN cried after drug administration (P < 0.05). In both the groups, sedation at 20 min after premedication (Group O [80%] 24/30 vs. Group IN [77%] 23/30), parental separation and acceptance to mask were comparable (P > 0.05); 12/30 children (40%) in Group IN showed transient nasal irritation. Conclusion: Oral midazolam and intranasal midazolam spray produce similar anxiolysis and sedation, but acceptance of drug and response to drug administration is better with oral route.

Aim: The aim of this study is to analyze the effect of intranasal anesthetic spray for maxillary anterior teeth. Objective: The objective of this study is to determine and assess the effect of intranasal anesthetic spray for maxillary anterior teeth. Materials and Methods: Thirty patients having mild-to-moderate endodontic pain were selected, of which 15 patients receiving intranasal (IN) anesthetic spray and the next 15 receiving infiltration. Baseline pain level was noted before the spray was given and pain level was noted 30 min after administration of the spray. Result: From this study, it was evident that there is a significant difference in the visual analog scale score infiltration and IN anesthetic spray. Conclusion: The pilot clinical study shows that the post-operative effects of IN lignocaine can be used as an adjuvant for performing maxillary anterior root canal therapy. [ABSTRACT FROM AUTHOR]

Background: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments.Methods: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam. Each treatment was given as 10 separate IN sprays, self-administered 5 min apart. The study was stopped early due to poor tolerability after five treatment-resistant depressed participants were included. Feasibility, safety (acute and cumulative), cognitive and efficacy outcomes were assessed. Plasma ketamine and norketamine concentrations were assayed after the first treatment.Results: Significant acute cardiovascular, psychotomimetic and neurological side effects occurred at doses < 100 mg ketamine. No participants were able to self-administer all 10 ketamine sprays due to incoordination; treatment time occasionally had to be extended (>45 min) due to acute side effects. No hepatic, cognitive or urinary changes were observed after the treatment course in either group. There was an approximately two-fold variation in ketamine and norketamine plasma concentrations between ketamine participants. At course end, one participant had remitted in each of the ketamine and midazolam groups.Conclusions: IN ketamine, with the drug formulation and delivery device used, was not a useful treatment approach in this study. Absorption was variable between individuals and acute tolerability was poor, requiring prolonged treatment administration time in some individuals. The drug formulation, the delivery device, the insufflation technique and individual patient factors play an important role in tolerability and efficacy when using IN ketamine for TRD. [ABSTRACT FROM AUTHOR]

Introduction & Objective: Induction of anesthesia in children can be a challenge for anesthetist. A stormy induction may increase the personality & behavioral changes. Therefore, it is desirable that they enter the operating room sedated. Many drugs are used for preanesthetic medication and there are many routes for administration. One route of administration is nasal mucous. In this study we compared the effect and side effect of three drugs (midazolam, ketamin and fentanyle) after intra nasal administration. Materials & Methods: This is a double blind clinical trial. In this study we selected 60 patients (20 patients for every group A, B or C.) We used 3 mg/kg ketamin or 3µg/kg fentanyle or 0.3 mg/kg midazolam by intranasal spray. After administration and in 5, 10 and 15 minutes, we observed the SPO2, PR and RR. After 15 min’s we separated children from parents and brought them to the operating room and controlled the acceptance of separation, depth of sedation with Ramsay score, acceptance of mask and tolerance of IV canulation. The data were then analyzed using K2 and kruskal-wallis test. Results: In our study we found that in SPO2 fentanyle had the highest rate of reduction even though none of the children had SPO2 lower than 90%. There were no differences between drugs in RR. In fentanyle group, we had the lowest rate and in ketamin group the highest rate. Midazolam had the medium rate. The rate of sedation for acceptance of separation from parents had no difference between the groups and all drugs with this dosage were effective for this aim. However, in Ramsay score, acceptance of mask and tolerance of IV canulation, the midazolam was more effective than the others. Conclusion: Intranasal administration of midazolam is a safe route for sedation in children in the pre-anesthetic time.

Background and Aims: Preoperative anxiety in children leading to postoperative negative changes and long-term behavioral problems needs better preanesthetic sedation. Across the world, midazolam is the most commonly used premedicant in pediatric patients. The fact that no single route has achieved universal acceptance for its administration suggests that each route has its own merits and demerits. This study compares oral midazolam syrup and intranasal midazolam spray as painless and needleless systems of drug administration for preanesthetic sedation in children. Material and Methods: With randomization, Group O (30 children): Received oral midazolam syrup 0.5 mg/kg and Group IN (30 children): Received intranasal midazolam spray 0.2 mg/kg. Every child was observed for acceptance of drug, response to drug administration, sedation scale, separation score, acceptance to mask, recovery score and side effects of drug. Data were analyzed using Student's t-test, standard error of the difference between two means and Chi-square test. Results: In Group O and IN, 15/30 children (50%) and 7/30 children (23%) accepted drug easily (P < 0.05); 4/22 children (18%) in Group O and 11/20 children (55%) in Group IN cried after drug administration (P < 0.05). In both the groups, sedation at 20 min after premedication (Group O [80%] 24/30 vs. Group IN [77%] 23/30), parental separation and acceptance to mask were comparable (P > 0.05); 12/30 children (40%) in Group IN showed transient nasal irritation. Conclusion: Oral midazolam and intranasal midazolam spray produce similar anxiolysis and sedation, but acceptance of drug and response to drug administration is better with oral route. [ABSTRACT FROM AUTHOR]

Olopatadine hydrochloride nasal spray 0.6% (OLO) and azelastine nasal spray 137 micrograms (AZE) are effective in treating allergic rhinitis and AZE is indicated for nonallergic vasomotor rhinitis (VMR). This study evaluates the relative safety and efficacy of OLO and AZE in patients with VMR. This randomized, double-blind, parallel-group, multicenter study compared OLO (an investigational use) with AZE over 14 days in patients (n = 129) ≥12 years of age with chronic VMR. Efficacy included the severity of nasal symptom scores. Safety included adverse events (AEs) and nasal examinations. Patient perceptions of treatment satisfaction and changes in allergy condition were determined using the Treatment Satisfaction Questionnaire for Medication and Patient Global Assessment scores. In the OLO and AZE groups, reflective scores for individual nasal symptoms (nasal congestion, rhinorrhea, postnasal drip, and sneezing) and total nasal VMR symptom scores decreased significantly from baseline to day 14 (p < 0.05). No significant between-group differences were observed (p > 0.05). No serious AEs were reported in either group. Overall, 22 and 20 AEs were reported in the OLO and AZE groups, respectively. The most common AE was taste disturbance, reported by three (5.3%) and six (10.3%) patients in the OLO and AZE groups, respectively. Patients in both groups reported similar treatment satisfaction scores and a majority of patients in both groups perceived an overall improvement in their rhinitis condition. OLO has a similar efficacy and safety profile to AZE for the management of VMR in patients ≥12 years of age. [ABSTRACT FROM AUTHOR]

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of intranasal, an intravenous infusion, and intramuscular glucagon has been studied in 5 healthy subjects and 11 patients with insulin-dependent diabetes mellitus. After infusion the elimination half-life was significantly longer in diabetics (11.9 vs 6.6 min) and the apparent volume of distribution was twice as high in diabetics (0.19 vs 0.37 l·kg). The metabolic clearance rates were the same in the two groups (18.9 and 21.3 ml·min·kg in controls and in diabetics) and were about twice those previously reported. After 1 mg intranasally the C of immunoractive glucagon (IRG) was similar in diabetic and in healthy subjects. Administration of a higher dose (2 mg) to diabetic patients produced a higher plasma level, although not proportionately so. The AUC after 1 mg was also similar in controls and in diabetics. The elimination half-life in both groups was similar to the value found after IV infusion; it was significantly shorter in controls (5.5 min) than in diabetics (13.8 min). In both groups, mean C was significantly lower than after IM glucagon, the relative bioavailability of 1 mg intranasally vs IM injection being less than 30%. After IM administration, the C and AUC of IRG in controls and in diabetic patients, were identical. The apparent elimination half-life was also similar in the two groups, and was three- to four-times longer (28.6 and 31.4 min) than after infusion or intranasal administration, possibly because estimation of the t was affected by slow release of the hormone from the site of injection. [ABSTRACT FROM AUTHOR]

Desmopressin acetate (1-desamino-8-Darginine vasopressin, DDAVP) has mostly been given by the parenteral route for the treatment of mild hemophilia A and von Willebrand's disease type I. In the present study the hemostatic effects of desmopressin acetate administered intranasally by spray in a dose of 300 µg and intravenously 0.3-0.4 µg/kg were assessed and compared in 8 patients with hemophilia A and 22 patients with von Willebrand's disease type I. A bioequivalent response to intravenous and intranasal desmopressin acetate was found in Factor VIII coagulant activity (VIII:C) in the hemophilia patients. In the von Willebrand patients, an equivalent shortening of the bleeding time was seen after the two modes of administration, even though intravenous injection gave a higher increase in plasma levels of VIII:C and vWF:Ag. In five patients with von Willebrand's disease the duration of the spray effect on VIII:C and vWF:Ag was followed for 24 h. After 12 h the mean level of VIII : C was 1.4, and of vWF:Ag 1.5, times the basal level. The findings suggest that the spray can be recommended for home or prophylactic treatment of patients with mild hemophilia A and von Willebrand's disease. [ABSTRACT FROM AUTHOR]

Desmopressin (1-desamino-8-D-arginine vasopressin), an established hemostatic agent for the treatment of bleeding in mild hemophilia A, von Willebrand's disease, or platelet disorders, has mostly been given parenterally as intravenous or subcutaneous injections. Intranasal administration by spray has been shown to yield significant and highly reproducible increases in the plasma concentrations of factor VIII and von Willebrand factor and platelet adhesiveness, and to be suitable for self-administration at home, as it is easy to handle and does not involve the use of needles. This paper presents data from a questionnaire answered by 78 patients with mild hemophilia A, von Willebrand's disease, or platelet disorders, who had used the spray at home to treat bleeding symptoms. The patients experienced decreased blood loss and shortened duration of epistaxis, menorrhagia, tissue bleeding, and bleeding in connection with minor surgery or tooth extraction. The use of factor VIII concentrates was diminished, as were the number of visits to outpatient care and absence from school or work. [ABSTRACT FROM AUTHOR]

Over the last few years, oxytocin (OT) administration to investigate the role of the oxytocinergic system in the social behavior of dogs has become of more and more interest. To date, the most common OT administration method for dogs is the intranasal spray commonly used for humans. Due to the different nasal conformation of dogs and the unpleasantness of the procedure, most dogs need to be restrained to allow administration. This has 2 main drawbacks—it may hinder reliable administration, which might lead to tremendous variance in the uptake of OT across individuals and it is likely to be stressful for the dogs. Alternatively, a vaporizer mask can be used to administer aerolized OT and dogs can be trained to voluntarily enter the mask, which might enable a more reliable administration without having to restrain the dogs. The aim of this study was to compare the efficacy of these 2 methods to identify a reliable non-invasive method for exogenous OT administration, thereby assisting future research on the role of OT in canines. We administered OT to pet dogs using either an intranasal spray bottle or a vaporizer mask and assessed urinary OT concentrations as a measure of OT uptake. We found that only when administered using a vaporizer mask, OT significantly increased in all subjects, while using a spray bottle led to considerable variance in OT uptake and an inconsistent increase in urinary OT concentrations across individuals. These results suggest that using a vaporizer mask should be preferred over using an intranasal spray bottle for OT administration in dogs. If not available, experimenters should at least monitor OT uptake after administration using spray bottles, to evaluate the success of the method. • OT can be reliably administered to dogs using a vaporizer mask. • Urinary OT levels increase consistently following aerolized OT administration. • Spray bottle OT administration leads to considerable variance in OT uptake. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a debilitating illness with significant morbidity and mortality, leading to attempted and completed suicides. It affects interpersonal relationships and also contributes to decreased productivity, causing financial burden to individuals and society. Patients often fail to respond to various antidepressant medication trials resulting in treatment-resistant depression (TRD). Current antidepressant medications work by modulating the monoaminergic systems and takes several weeks to establish a clinical response. Ketamine has been used extensively as an anesthetic agent since the 1970s, and more recent research has shown its rapid and robust effectiveness in TRD the subject of this review. Ketamine is a racemic mixture comprised of two enantiomers (R)-ketamine and (S)-ketamine and acts as an NMDA receptor antagonist. Most research studies have explored its antidepressant and antisuicidal effects by using it as an intravenous infusion or via the intranasal route due to increased bioavailability. Recently an intranasal esketamine spray was approved by the United States Food and Drug Administration (FDA) for TRD as an adjunct to standard antidepressant treatment in a supervised setting. Regarding its safety profile, multiple research studies have established the short-term safety and efficacy of ketamine in TRD. The cardiorespiratory and neuropsychiatric adverse events observed in these studies were mostly transient. However, ketamine is a scheduled agent with abuse potential, making its long-term use challenging and mandating further research., Competing Interests: Conflict of interest Syed Z. Iqbal MD: The author does have any disclosure. Sanjay J. Mathew MD: Dr. Mathew has served as a consultant to Janssen, the manufacturer of esketamine nasal spray. He has also served as a consultant to several companies who are developing ketamine or related compounds for psychiatric indications., (© 2020 Elsevier Inc. All rights reserved.)