Dose Of Spray Research Articles

Significant improvements in SEIzure interVAL (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters.

Intermittent rescue therapy may be used for seizure clusters, which are clinical emergencies that may persist ≥24 h and increase risk of status epilepticus, emergency room visits, and reduced quality of life for patients with epilepsy. Beyond effectiveness for aborting seizure clusters, no data exist on how intermittent rescue therapy may impact the long-term natural course of seizure clusters. This novel analysis explores SEIzure interVAL (SEIVAL; time between seizure clusters) in patients from a long-term safety study of diazepam nasal spray (Valtoco) to assess SEIVAL changes with intermittent rescue therapy across time. Patients were aged 6-65 years. Age- and weight-based doses of diazepam nasal spray were administered during a 12-month treatment period with an optional follow-up period. SEIVAL was evaluated in patients receiving two or more doses of diazepam nasal spray using 90-day periods. Of 163 treated patients, 151 had one or more SEIVALs. One hundred twenty had SEIVALs in Period 1 and one or more other periods. An increase in SEIVAL was noted from Period 1 compared with all subsequent periods (p ≤ .001). A consistent cohort (n=76) had one or more SEIVALs in each of Periods 1-4 (360 days); mean SEIVALs increased significantly (p < .01) from 12.2 days (Period 1) to 25.7 days (Period 4). Similar SEIVAL patterns occurred when repeat doses within a seizure cluster were eliminated and irrespective of age group, treatment duration, and change to concomitant medications. In adults, Quality of Life in Epilepsy scores were maintained with increased SEIVALs. Across 12 months, increases in SEIVAL were demonstrated in patients using diazepam nasal spray for seizure cluster treatment in a phase 3 safety study. Increased time between seizure clusters may reflect a previously unrecognized beneficial effect of intermittent rescue therapy. These results generate a range of biological and behavioral hypotheses and warrant exploration of the impact of intermittent rescue therapy.

Assessment of the effect of two different doses of intranasal nitroglycerine spray on attenuation of haemodynamic stress response to pneumoperitoneum in laparoscopic surgeries: A randomised, double-blinded study.

Background and Aims:The stress response to pneumoperitoneum can be deleterious due to its effects on haemodynamics, thereby increasing the morbidity. We intended to compare different doses of nitroglycerine nasal spray to obtund these responses and to look for any side effects.Methods:After ethical committee clearance and clinical trials registration, 70 patients scheduled for laparoscopic cholecystectomy were recruited. Random allocation was done into two groups by a computer generated randomisation table. Group N4 (n = 35) received 400 μg nitroglycerine and group N8 (n = 35) received 800 μg nitroglycerine with an intranasal spray 2 min prior to pneumoperitoneum. All the haemodynamic parameters were monitored at regular intervals.Results:The heart rate was comparable between the groups except at 6 and 10 min of pneumoperitoneum but showed significant increase from baseline within the groups. Mean arterial pressure (MAP) was statistically significant between the groups, being higher in group N4. Within group N4, MAP was significantly low only at 2 min, 4 min of pneumoperitoneum (101.69 ± 12.34 at baseline versus 93.31 ± 8.07 at 2 min and 97.54 ± 9.07 mm Hg at 4 min) and increased significantly at 30 min of pneumoperitoneum (101.69 ± 12.34 at baseline versus 105.66 ± 12.35 mm Hg) and hence, MAP was observed to be around baseline throughout the rest of intraoperative period. Within group N8, there was a significant decrease in mean, systolic and diastolic blood pressure from baseline at most of the time intervals.Conclusion:800 μg of intranasal nitroglycerine effectively obtunds the hypertensive response associated with pneumoperitoneum as compared to 400 μg without significant side effects.

A Concise Overview on Recent Advances in Pharmaceutical Aerosols and their Commercial Applications

Background: Localized drug delivery to the respiratory system has become an increasingly successful and essential treatment strategy for several pulmonary diseases, including asthma, chronic abstractive disease, pneumonia, bronchitis, and cystic fibrosis. The rising incidence of respiratory diseases is a significant factor driving the worldwide market for respiratory inhaler devices. Objective: The objective of this article is to present various aspects of pharmaceutical aerosols, including their types, components, fundamentals, in-process and finished product quality control tests based on pharmacopeial standards and specifications, and commercial utility considering the pharmaceutical aerosol dosage forms that have been patented from 2000 to 2020, along with a list of marketed pharmaceutical products. Method: Aerosol, collectively referred to as a pressurized device, operates by triggering an appropriate valve system with a continuous or metered dosage of tiny mist spray. It is used not only in the treatment of asthma and chronic obstructive pulmonary disease but also in the treatment of cancer, diabetes, migraine, angina pectoris, acute lung injury, bone disorders, tuberculosis, and many more. A multitude of different variables, including types and properties of propellants, active substances, containers, valves, actuators, spray patterns, valve crimping efficiency, and particle size of the aerosols, influence the therapeutic effectiveness of pharmaceutical aerosols. Conclusion: Based on the current findings, distinct characteristics such as the elimination of firstpass metabolism, quick drug absorption, ease of therapy termination, as well as a larger surface area have attributed to the success of pharmaceutical aerosols.

Method Development, Validation and Estimation of Relative Response Factor for the Quantitation of Known Impurities in Mometasone Furoate Nasal Spray Dosage form by RP-HPLC with UV/PDA Detector

Method Development, Validation and Estimation of Relative Response Factor for the Quantitation of Known Impurities in Mometasone Furoate Nasal Spray Dosage form by RP-HPLC with UV/PDA Detector

Safety of a Second Dose of Diazepam Nasal Spray Within 4 Hours in Patients With Seizure Clusters: Final Results From a Long-Term, Phase 3, Open-Label, Repeat-Dose Safety Study (P14-8.003)

Safety of a Second Dose of Diazepam Nasal Spray Within 4 Hours in Patients With Seizure Clusters: Final Results From a Long-Term, Phase 3, Open-Label, Repeat-Dose Safety Study (P14-8.003)

Safety of Diazepam Nasal Spray in Children and Adolescents With Epilepsy: Results From a Long-Term Phase 3 Safety Study

BackgroundTo evaluate safety and tolerability of long-term treatment with diazepam nasal spray (Valtoco) for seizure clusters in patients aged six to 17 years. MethodsThe study enrolled patients aged six to 65 years with frequent seizure clusters. Age- and weight-based doses of diazepam nasal spray were administered; second doses were permitted if needed. Safety assessments included treatment-emergent adverse events (TEAEs). ResultsOf 163 treated patients, 45 (27.6%) were aged six to 11 years and 33 (20.2%) were aged 12 to 17 years. Mean doses per month were 2.1 in the 6 to 11 subgroup and 2.4 in the 12 to 17 subgroup. Of 1634 seizure clusters in pediatric patients, 186 (11.4%) required a second dose of diazepam nasal spray within 24 hours of the first dose. Similar proportions of TEAEs and serious TEAEs were reported in 6 to 11 (91.1%, 40.0%) and 12 to 17 subgroups (81.8%, 30.3%), respectively. No serious TEAEs were considered treatment related, and no patients discontinued because of TEAEs. Treatment-related TEAEs were more frequent in the 12 to 17 subgroup; only epistaxis and somnolence occurred in two or more patients overall. TEAE rates were similar across subgroups that received concomitant clobazam (90.0%), received prior diazepam rectal gel (90.9%), and were administered less than two versus greater than or equal to two doses per month (87.2% for both) of diazepam nasal spray. Most survey respondents (88%) were satisfied or very satisfied with treatment. ConclusionsIn this long-term safety analysis in pediatric patients with seizure clusters, repeated doses of diazepam nasal spray demonstrated a safety profile consistent across subgroups. These data support the dosing guidelines for diazepam nasal spray according to age and weight for pediatric patients.

Oral Spray – A Review on Promising Drug Delivery System for Oral Cavity

Aim: This review aims to compile information related to marketed oral spray preparation along with their formulation and clinical application.&#x0D; Objective: The main objective of this overview is to study the marketed oral spray dosage form for treatment of different diseases and learn about its advantages over the other oral dosage forms e.g. tablet, capsule, patches etc.&#x0D; Description: Oral spray with Mucoadhesive polymers forms small droplets that quickly adheres to the mucosal surface and let the drug permeate into the blood circulation easily. The oral mucosa has shown promising results for the systemic absorption of many drugs owing to the highly permeable nature of the mucosal membrane. Oral sprays are very fast, the most effective and easy way to get daily dose vitamins, minerals, and other nutrients ingredients. Due to this advantage oral sprays have emerged as an effective alternative for bypassing extensive first pass effect.&#x0D; Conclusion: It has been a very well known fact that the oral route of administration is the most popular route of drug administration. However the drwabacks like extensive first pass metabolism and drug degradation in stomach makes this route not suitable for all drugs and thus an alternative oral drug delivery systems are necessary to explaoint benefits of oral route. Many researchers are working to develop oral spray formulations for drugs which need quick permeation followed by quick onset of action and also provide an effective alternative of conventional oral drug delivery systems.

Lack of clinically relevant differences in safety and pharmacokinetics after second‐dose administration of intranasal diazepam within 4 h for acute treatment of seizure clusters: A population analysis

ObjectiveCurrent diazepam nasal spray labeling requires waiting 4 h before administering a second dose. The objective of the current analyses was to examine safety and pharmacokinetic profiles of second doses of diazepam nasal spray given 0−4 h after the first dose.MethodsTwo datasets were analyzed. The first, a long‐term, repeat‐dose safety study of diazepam nasal spray, compared rates of treatment‐emergent adverse events (TEAEs), serious TEAEs, and treatment‐related TEAEs for patients receiving ≥1 second dose ≤4 h versus all second doses >4 h after the first. The second was a population pharmacokinetic analysis using data from three phase 1 studies to model drug exposure when a second dose of diazepam nasal spray was administered across multiple time points (1 min−4 h) following the first dose.ResultsIn the repeat‐dose safety study, a second dose of diazepam nasal spray was administered ≤24 h after the first to treat 485 seizure clusters in 79 patients. Rates of TEAEs were similar between patients receiving ≥1 second dose in ≤4 h (89.5%, n = 38) compared with >4–24 h only (80.5%, n = 41). The most common treatment‐related TEAEs were associated with nasal discomfort, which was mild or moderate and transient. There were no reports of respiratory or cardiac depression. The pharmacokinetic simulations of second doses predicted comparable elevations of plasma diazepam concentrations with administrations across a range of intervals after the first dose (1 min−4 h).SignificanceThese data indicate that the safety and pharmacokinetic profiles of a second dose of diazepam nasal spray administered within 4 h of the first dose are consistent with those associated with current labeling. This is potentially important for patients with seizure clusters who have a recurrent seizure within 4 h of first treatment and might benefit from immediate retreatment to reduce the risk of progression to status epilepticus.

Safety, Tolerability, and Pharmacokinetic Study of 101BHG-D01 Nasal Spray, a Novel Long-Acting and Selective Cholinergic M Receptor Antagonist, in Healthy Chinese Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Single-Dose Escalation, First-In-Human Study.

101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects. A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t), the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), the maximum plasma concentration (Cmax), the time to maximum plasma concentration (Tmax), and the elimination half-life (t1/2). Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), anterior rhinoscopy, ophthalmic examination, and ambulatory ECG monitoring. Following single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median Tmax of 0.34-0.50 h and eliminated slowly with a mean t1/2 ranging from 4.29 to 46.76 h for different dose groups. The Cmax and AUC of 101BHG-D01 increased linearly across the examined dose range of 40-960 µg. 101BHG-D01 nasal spray was well tolerated, all AEs were mild, and no serious adverse events occurred during the study. 101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean Cmax and AUC increased proportionally to the studied dose. The pharmacokinetic, safety, and tolerability profiles of 101BHG-D01 nasal spray indicate that it is a good candidate for further development as a treatment for rhinorrhea in rhinitis.

Панавир® в комплексной профилактике реактивации герпесвирусных инфекций у детей с рецидивирующими инфекциями органов респираторного тракта

Background: the importance of developing therapeutic options for the prevention of herpesvirus infection (HVI) reactivation in children is underpinned by a high prevalence of recurring diseases. Such recurrences with clinical manifestations are reported within 3 — 6 months after the clinically effective courses of antiviral therapy including direct-acting antivirals. Aim: analysis of clinical and virological efficacy of complex therapy which includes Panavir® Inlight spray for prevention of ARI in children with HVI reactivation. Patients and Methods: within the follow-up program, the clinical assessment was performed in 76 patients, comprising 35 (46.1%) girls and 41 (53.9%) boys, 0 — 14 years old, with a median age of 5 (IQR 2–8) years. The follow-up period was 3 months. The treatment group consisted of 49 children who received Panavir® Inlight Spray as a part of the combination therapy. The control group consisted of 27 children to whom Panavir® Inlight Spray was not administered. Panavir® Inlight Spray dosage regimen: 1 or 2 sprays in the throat after meals, 3 treatment courses, 14 days each, spaced 14 days apart. Clinical examinations and laboratory tests were performed for all patients over multiple time points. Serological and PCR methods were used for HHV diagnosing. The viral DNA load was evaluated for human herpes virus (HHV) 6А/В, cytomegalovirus, and Epstein-Barr virus in the oropharyngeal smears during the treatment. Results: 38 (77.6%) patients of the treatment group and 15 (55.6%) children of the control group reported that the subjective symptoms (monthly ARI, subfebrile fever, prolonged nasal congestion, etc.) disappeared or decreased. At the time of initiating therapy, DNA of one or more herpesviruses was isolated in the oropharyngeal smears of all patients from the compared groups. After the therapy completion, the viral DNA was not isolated in the oropharyngeal smears of 37 (75.5%) patients of the treatment group and in 16 (59.3%) patients of the control group. Median HHV 6А/В load in the oropharynx decreased from 645.0 (IQR 399.00–1600.00) copies/ml to 399.00 (IQR 0.00–775.00) copies/ml. Based on the results of complex assessment of patients, a reduction of HHV activity was found in 27 (55.1%) patients receiving Panavir® Inlight Spray and in 10 (37.0%) control group patients. Amid the administered therapy, the rate of HHV reactivation was significantly lower in the treatment group — in 3 (6.1%) patients than in the comparison group — in 10 (37.0%) patients (р&lt;0,001). Conclusion: the use of Panavir® Inlight Spray in combination with other drugs for preventing HHV reactivation in children with recurring respiratory infections helps to improve the general sense of well-being and to preserve HHV latency after the treatment course containing direct antivirals. A decrease in the viral DNA load in the oropharyngeal smears (the most pronounced for HHV 6А/В) was reported in patients receiving Panavir® Inlight Spray. KEYWORDS: children, recurring respiratory infections, herpesvirus infections, Panavir Inlight Spray. FOR CITATION: Melekhina E.V., Muzyka A.D., Soldatova E.Yu., Shalbarova T.V. Panavir® in combination with other drugs for the prevention of herpesvirus infection reactivation in children with recurring respiratory infections. Russian Medical Inquiry. 2022;6(11):618–625 (in Russ.). DOI: 10.32364/2587-6821-2022-6-11-618-625.

Development and comprehensive greenness assessment for MEKC and HPTLC methods for simultaneous estimation of sertaconazole with two co-formulated preservatives in pharmaceutical dosage forms

Four greenness assessment tools: National Environmental Methods Index (NEMI), Ecoscale Assessment (ESA), Green Analytical Procedure Index (GAPI) and the most recent Analytical GREEness metric (AGREE) were tested to evaluate two proposed MEKC and HPTLC methods for the simultaneous determination of the antifungal drug sertaconazole (SER) and two co-formulated preservatives methyl paraben (MEP) and sorbic acid (SOR). Method I was micellar electrokinetic capillary chromatography (MEKC). Electrophoretic conditions were optimized to improve separation, sensitivity, and rapidity. The proposed method used a fused silica capillary (50 cm × 50 μm id), and the background electrolyte was 50 mM acetate buffer pH 4.6 containing 15 mM SDS with 17 s injection time. The applied voltage was 30 kV. The diode array detector (DAD) was set at 210 nm for measurement of SER and 254 nm for both MEP and SOR. The Three compounds were resolved in less than 6 min with migration times 3.07, 4.29, and 5.97 min for SER, MEP, and SOR respectively. The described method was linear over the range of 5–100 μg/mL for SER, MEP and SOR with correlation coefficients >0.9995. For method II: high-performance thin-layer chromatography (HPTLC) analysis was carried out on aluminum-backed sheet of silica gel using chloroform-ethyl acetate (3:7) as mobile phase. Retardation factors were 0.20, 0.71, and 0.88 for SER, MEP, and SOR respectively. Quantification was achieved with UV densitometry at 210 nm for SER and 254 nm for MEP and SOR. The linearity ranges were 0.1–1 μg/spot for the three drugs with correlation coefficients >0.9998. The analytical performance of both methods was thoroughly validated according to International Conference on Harmonization (ICH) guidelines with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The proposed MEKC and HPTLC methods were successfully applied for estimation of the studied drugs in laboratory prepared mixtures and in the cream and spray dosage forms.

In Vitro Ciliotoxicity and Cytotoxicity Testing of Repeated Chronic Exposure to Topical Nasal Formulations for Safety Studies.

Certain active drugs and excipients of nasal formulations may impair ciliary function and mucociliary clearance. The ciliary beat frequency (CBF) is a key parameter for determining mucociliary clearance rate, and in vitro assessments of CBF have proven to be accurate and reproducible. Since topical nasal formulations are applied with repeated doses, it is essential to elucidate their chronic, as opposed to acute, effect on mucociliary clearance and nasal mucosa. The aim of this study was to assess for the first time the ciliotoxicity and cytotoxicity of nasal sprays intended for chronic treatment (with repeated doses) using a previously designed set-up for CBF measurements. For 2 weeks, the 3D nasal MucilAir™ in vitro models were treated daily with undiluted or clinically relevant doses of mometasone nasal spray, placebo nasal spray, culture medium, or they were untreated. We demonstrated a dose-dependent and time-dependent (cumulative) effect of the nasal sprays on ciliary activity and cytotoxicity using CBF measurements and ultrastructural analysis, respectively. Our results indicate that repeated administration of clinically relevant doses of mometasone nasal spray is safe for in vivo use, which is in good agreement with a previous clinical study. Overall, our study suggests that such in vitro assays have great potential for topical nasal drug screening.

Diabetes insipidus as the first manifestation of granulomatosis with polyangiitis: A case report

Background: Granulomatosis with Polyangiitis (GPA) is a necrotizing granulomatosis vasculitis that may influence most organs, but posterior pituitary involvement as the first manifestation is unusual. However, there are some case reports in this regard. Case presentation: A 49-year-old menopausal woman presented with polyuria, polydipsia and weight loss over time headache, purulent nasal discharge, malaise, ear pain developed. After right myringotomy due to secretory otitis media and nasal cavity biopsy, the symptoms exacerbated. Diabetes insipidus was documented by Deprivation test. Thus, 20 microgram nasal spray DDAVP was prescribed. Pituitary MRI +/- Gad demonstrated pituitary involvement. Pituitary axis hormone evaluation was consistent with menopausal state. Chest spiral CT scan showed speculated border soft tissue mass lesion. GPA confirmed with ACR criteria and C-ANCA positive. Therefore, corticosteroid and rituximab were started. Symptoms of DI responded well to the treatment and the spray dosage was decreased. Conclusion: DI can be the first manifestation of GPA; although it is rare, it is worth to be diagnosed early and serious treatment of vasculitis should be started to prevent irreversible damage to the hypophysis cell and unnecessary procedure. Keywords: GPA; granalomatosis vasculitis; diabetes insipidus.

Spray volume, dose and time of day of glyphosate application in the control of Urochloa brizantha

In order to optimize machinery use, the application of herbicides has been performed at different times of the day and night. Therefore, knowledge about the pesticide that will be used and how the spray volume and time of application affect the effectiveness of the product is very important. Thus, the objective of this work was to study the influence of spray volume and different time of application on the control of Urochloa brizantha by different doses of glyphosate. The treatments were arranged in a 5 x 3 x 2 factorial scheme in a randomized block design with four replications. Five doses of glyphosate (0; 1080; 1440; 1800 and 2160 g∙ha-1∙a.e.), three times of application (morning, afternoon and evening) and two spray volumes (50 and 100 L·ha-1) were evaluated. A control assessment was performed at 21 days after application, in addition to the accumulation of dry matter and the leaf area index on the regrowth. A satisfactory control of the grass was obtained for applications performed in the morning and afternoon, without interference of the volume applied and the doses tested. Evening application reduces the effectiveness of glyphosate in Urochloa brizantha burndown.

Effect of 1 puff of sublingual nitroglycerin spray versus 1 puff of normal saline spray in attenuating pressor response to extubation

Ideal agent to attenuate hemodynamic response to extubation should be readily available, easy to administer, cost effective with fast onset of action and peak with minimal side effects. Nitroglycerin is one of the most widely used drug to control intra-operative rise in blood pressure. Nitroglycerin is potent vasodilator, predominantly acting on venules than arterioles by generating nitric oxide (NO) in vascular smooth muscle. A thorough pre-anaesthetic evaluation was done on day before surgery. Detailed medical history was elicited and detailed physical examination was carried out. Patients were kept nil per orally for 8 hours prior to surgery. Preoperatively investigations like CBC, RBS and Sr. Creatinine were done. ECG and CXR were done if patient was more than 40 years of age. In our study patient received 1 puff (0.4mg) which resulted in a small although insignificant increase in BP till 3 minutes. It may be possible to attenuate this small increase in BP by using higher dose of NTG spray instead of 0.4mg and requires further evaluation. It was observed that there was tachycardia as Injection Glycopyrrolate was given just before intervention since, both the groups received the same drug it will not act as bias.

Pemanfaatan Minyak Atsiri Daun Sirih (Piper Betle Linn) Sebagai Anti Nyamuk

Betel leaf (Piper betle Linn) is a plant that is widely known by the people of Indonesia, contains phenolic compounds and their derivatives which reaches 30% in extracts and essential oils, and at a concentration of 100 ppm it can kill mosquito larvae based on insecticidal activity. This study aims to utilize betel leaf essential oil, which was obtained by steam distillation method in the form of a spray dosage form and to find out at what concentration the betel leaf essential oil can be used as an insect repellent. This research is a laboratory experiment, there are 3 formulas of mosquito repellent spray (F1, F2 and F3) with a concentration of 13%, 15%, and 17%. The tests carried out on the anti-mosquito spray preparation were organoleptic tests and tests the effectiveness of the preparations against ten adult mosquitoes. Anti-mosquito spray preparation with a concentration of 17% betel leaf essential oil which is more effective at repelling and killing mosquitoes. Further research can develop the use of betel leaf essential oil with variations in different concentrations, or in combination with other active ingredients as mosquito repellent

Sativex\xae (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience

BackgroundThis retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications.MethodsOf 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months.ResultsMean 0–10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks’ range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile.ConclusionsMore than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.

FDA approves higher dosage of naloxone nasal spray to treat opioid overdose

The U.S. Food and Drug Administration has approved a higher dose naloxone hydrochloride nasal spray product to treat opioid overdose.

An Early Calcium Loading during Cherry Tree Dormancy Improves Fruit Quality Features at Harvest

The possible role of an early calcium application via sprays (0.25, 0.5 and 1M CaCl2) on dormant buds to improve sweet cherry (cv. Ferrovia) fruit quality at harvest was investigated. Fruit quality characteristics were also investigated in response to the age of spurs, the ripening stage, and their interactions. Results indicate that calcium enters the dormant flower buds and the phloem but not to the dormant vegetative buds. At harvest, the levels of Zn, Mn, and Cu were declined in fruits by increasing CaCl2 doses of sprays. Fruit respiratory activity was higher and on–tree fruit cracking was lower in red-colour (unripe) cherries as well as in fruit that was produced by 2-year-old short spurs or by Ca-treated buds. Differences in the sweet cherry skin metabolic profiles were identified. Fruit produced from Ca-exposed spurs exhibited lower levels of ribose and other cell-wall-related sugars and higher sucrose, maltose, and quininic acid levels. Nutrient shift was increased in red cherries, while anthocyanins were boosted in the black ones. PCA analysis was performed between the high dose of calcium spray and a control for mineral element content and cherry quality traits. This study illustrates that the high dose of calcium application during bud dormancy can effectively improve sweet cherry fruit characteristics, in terms of calcium content, cracking incidence, and fruit set. Overall, the present study contributes to a better understanding of the impact of calcium nutrition in fruit crops, which will provide references for alternative nutrient management and quality control in sweet cherry production.

Observational study investigating Ectoin\xae Rhinitis Nasal Spray as natural treatment option of acute rhinosinusitis compared to treatment with Xylometazoline

IntroductionSymptomatic relief of acute rhinosinusitis is commonly achieved with nasal decongestants. The current observational study investigated the efficacy and safety of treatment of acute rhinosinusitis with Ectoin® Rhinitis Spray compared to or in combination with Xylometazoline-containing decongesting nasal spray.MethodsPatients with acute rhinosinusitis applied either Ectoin® Rhinitis Spray, Xylometazoline nasal spray or a combination of both products. Rhinosinusitis symptoms were assessed, and nasal oedema and endonasal redness were determined by rhinoscopy. Patient diaries based on the validated SNOT (Sino Nasal Outcome Test) questionnaire evaluated rhinosinusitis parameters over time and influences of the disease on quality of life. Following treatment, investigators and patients judged the efficacy and tolerability.ResultsEctoin® Rhinitis Spray diminished common rhinosinusitis symptoms such as nasal obstruction, nasal secretion, facial pain/headache, and smell/taste impairment. Upon treatment over 7 days, rhinosinusitis sum scores decreased statistically significantly (p < 0.001) by − 64.25%, which was comparable to that achieved with Xylometazoline-containing decongesting nasal spray (− 67.60%). No side effects were observed during treatment with Ectoin® Rhinitis Spray, whereas treatment with Xylometazoline-containing nasal spray resulted in nasal mucosa dryness. Concomitant treatment with both products diminished the development of nasal dryness and required fewer applications of Xylometazoline-containing nasal spray.ConclusionEctoin® Rhinitis Spray is an effective, natural treatment option for acute rhinosinusitis, which may be used as monotherapy or as add-on treatment with a Xylometazoline-containing nasal spray. The concomitant use of Ectoin® Rhinitis Spray might reduce the needed dose of decongestant nasal spray and counteract bothersome side effects such as dry nasal mucosa.Trial registrationThe current study was registered in the ClinicalTrials.gov database under the identifier: NCT03693976 (date of registration: Oct 3, 2018).