Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

[Efficacy of Sildenafil oral spray for the treatment of erectile dysfunction in patients with type 2 diabetes mellitus and prediabetes].

AIM: To evaluate the results of using Sildenafil in the form of an oral spray (Gent) for the treatment of erectile dysfunction (ED) in men with type 2 diabetes mellitus (DM) and prediabetes. MATERIAL AND METHODS: A total of 60 patients were divided into two groups of 30 people. The group 1 included patients with prediabetes, while group 2 consisted of patients with type 2 DM. All men had proven ED. The severity of ED was assessed using the International Index of Erectile Function (IIEF-5). To assess the state of penile blood flow, all patients underwent Doppler ultrasound before and after treatment. Patients with prediabetes used Sildenafil in the form of oral spray (Gent) 25 mg (2 doses) 1 time per day for 1 month, patients with type 2 diabetes received 50 mg (4 injections) every other day for 1 month. In addition, most of the subjects took metformin and followed diet therapy. RESULTS: In patients of both groups, the administration of Sildenafil oral spray led to a decrease in body weight, waist circumference, a decrease in insulin and Hemoglobin A1C level without changing of hypoglycemic therapy in those with type 2 DM. In men with prediabetes, a decrease in fasting insulin levels was found. During treatment, half of the persons with impaired glucose metabolism had an increase in the testosterone level. According to IIEF-5, a decrease in the severity of ED in both groups of patients was seen. In men with prediabetes, the average IIEF-5 score increased from 15.98 to 21.57 points (p<0.05), while in patients with type 2 DM it improved from 12.18 to 18.44 points (p<0.05). Doppler ultrasound indicated a significant increase in the maximum systolic blood flow velocity and arterial resistivity index after treatment with Sildenafil oral spray in patients with both prediabetes and type 2 diabetes. CONCLUSION: Sildenafil oral spray can be effectively used for the treatment of ED in men with type 2 DM and prediabetes.

A Prospective Study of AFree Oral Spray as an Adjuvant Therapy for Mild and Moderate COVID-19 in Community Health Stations: Clinical Progression and Viral Clearance Outcomes.

BACKGROUND/AIM: The aim of this study was to evaluate the safety and efficacy of AFree oral spray, in combination with Standard of Care, in treating mild to moderate COVID-19 patients. This was an open-label, single-blinded, and controlled randomized clinical trial. PATIENTS AND METHODS: The study involved 1,252 patients, who were randomly assigned to either the control or study group, with 626 patients in each group. Patients in the control group were treated with Standard of Care recommended by the Ministry of Health of Vietnam, while patients in the study group received AFree oral spray in addition to Standard of Care for a period of 10 days. The clinical progression and outcomes of both groups were compared. RESULTS: The results showed that the proportion of patients with clinical symptoms on the 5th, 7th and 10th days were significantly lower in the study group (45.05%, 3.19% and 0%, respectively) compared to the control group (86.10%, 67.73% and 22.84%, respectively). Additionally, the rate of Real-time PCR test positivity for COVID-19 was significantly lower in the study group compared to the control group on the 4th, 7th, and 10th days (82.75% vs. 98.72%, 9.27% vs. 92.97%, and 1.12% vs. 50.48%, respectively). Furthermore, no side effects or complications related to AFree oral spray were recorded in the study group. CONCLUSION: The use of AFree oral spray resulted in significant improvements in clinical symptoms, recovery time, and viral clearance in COVID-19 patients with mild to moderate symptoms. This therapy has been shown to be safe and can be used as an adjuvant treatment for COVID-19 as well as other respiratory viral infections.

Therapeutic Efficacy of AFree Oral Spray on the Symptoms and Course of Moderate and Severe COVID-19 in the Field Hospital.

BACKGROUND/AIM: A prospective randomized, open-label, single-blinded clinical trial was conducted to evaluate the efficacy of AFree on the symptoms and course of moderate and severe COVID-19 in the field hospital. PATIENTS AND METHODS: Two hundred hospitalized patients diagnosed with COVID-19 were enrolled. The patients were randomized into 100 patients in the interventional AFree group and 100 in the control group. The AFree group patients were treated with AFree oral spray in conjunction with the standard COVID-19 treatment protocol, while the control group of patients were treated with only standard care. RESULTS: Patients of the AFree group demonstrated a remarkedly faster improvement in all COVID-19-related symptoms, resulting in a shorter time for complete recovery than the control group. More importantly, they showed a shorter time for complete viral clearance. Adding AFree to the standard of care protocol also significantly improved the restoration of taste and smell and reduced lung infiltration. Additionally, the patients in the AFree group also exhibited fewer adverse effects related to treatment. CONCLUSION: AFree oral spray is a simple-to-use, safe, and effective adjunctive treatment for moderate and severe COVID-19 cases. AFree oral spray was demonstrated to potentially be effective for COVID-19 prevention.

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial.

BACKGROUND: The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT). METHODS: Prior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions. RESULTS: In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05). CONCLUSIONS: The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

Efficacy of a Flavored Lubricating Oral Spray on Medication Swallowing in Older Individuals.

Background Difficulty swallowing occurs in up to 35% of patients 50 years of age or older and can contribute to medication nonadherence and other alterations. The use of a flavored lubricating spray, available over-the-counter and found to be helpful in children to swallow oral solid medications, is not well studied in older adults. Objective To evaluate the effect of a flavored lubricating spray on the ability to swallow oral solid medication in older people. Methods A randomized, open-label, crossover study included community-dwelling individuals 65 to 88 years of age who took at least one solid oral medication daily and were not diagnosed with dysphagia, Parkinson's disease, or esophageal tumor. Participants were randomized to the strawberry-flavored lubricating spray or usual care and then crossed over to the alternate option. The median rating for swallowing difficulty for their regular medications was compared using a Likert scale, from 1 (very difficult) to 5 (very easy). To provide a degree of standardization between participants, all participants were also instructed to swallow a vitamin C (1,000 mg) tablet both with and without the flavored spray and rate their difficulty swallowing the tablet using the same Likert scale. Results There were 39 (90.7%) participants who completed the study. The median rating for swallowing difficultly was 5 (very easy) with the spray vs. 4 (easy) with usual care (P < 0.0001). For the 66.7% who took the vitamin C tablets, the median rating for swallowing difficulty was 5 (very easy) with the spray vs. 3.5 (between neutral and easy) without (P < 0.0001). There were 94.8% of participants who found the spray easy/ very easy to use, and 89.7% reported it tasted okay to delicious. Conclusion The use of a flavored lubricating spray provided an effective and easy-to-use tool to make medication swallowing easier in community-dwelling older adults without a diagnosis associated with difficulty swallowing.

Investigating the applicability of polar fabric phase sorptive extraction for the HPLC quantitation of salivary vitamin B12 following administration of sublingual tablets and oral sprays.

In this study, a simple and rapid fabric phase sorptive extraction (FPSE) protocol combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) was developed for the monitoring of salivary vitamin B12 levels. Different sol-gel coated cellulose and polyester membranes were evaluated and sol-gel Carbowax 20 M coated polyester membranes were chosen for the selective extraction of the target analyte from saliva samples. Face-centered central composite design (FC-CCD) was employed for the investigation and optimization of sample volume, extraction time and stirring rate, while the other experimental factors were investigated using the classical one-factor-at-a- time" (OFAT) method. Validation of the FPSE-HPLC-UV method was conducted according to the FDA guidelines for bioanalytical methodologies. The lower limit of quantification for vitamin B12 was 0.10 µg mL-1 and the linear range was 0.10-10.0 µg mL-1. The relative recoveries for intra-day and inter-day studies were 87.5-113.8% and 88.2-119.2%, respectively. The relative standard deviation was better than 8.2% in all cases, demonstrating good method precision. The sol-gel Carbowax 20 M coated FPSE membranes were found to be reusable for up to 25 times. Finally, the proposed scheme was successfully employed for the quantitation of salivary vitamin B12 at different time points following the administration of sublingual tablets and oral sprays.

Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Previous clinical and in vitro investigations have supported the efficacy of a glycerol throat spray containing cold-adapted cod trypsin (ColdZyme) against respiratory viruses causing the common cold bycreating a protective mucosal barrier shown to deactivate common cold virus in vitro and decrease pharyngeal rhinovirus load. METHODS AND FINDINGS: This was a double-blind, randomized, parallel-group, placebo-controlled study conducted at 10 German sites to evaluate the efficacy of the medical device ColdZyme, a glycerol mouth spray containing cold-adapted cod trypsin for a naturally occurring common cold versus placebo spray. Adults experiencing a minimum of three common colds during the previous year, but otherwise healthy, were enrolled to begin treatment with the mouth spray or placebo six times daily at first sign of a common cold. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) quality of life (QoL) domain and a sore throat scale were recorded daily by subjects, as well as any use of allowed rescue treatment. Between January and April 2019, 701 subjects were enrolled and randomly assigned to the ColdZyme group (n = 351) or the placebo group (n = 350). Of the 701 subjects, 438 (62.5%) subjects developed symptoms typical of common cold, and all 438 started study treatment (n = 220 in the ColdZyme group and n = 218 in the placebo group). The demographic profile of the treatment groups were comparable with 68.1% female and almost all subjects being Caucasian (98.4%). The age ranged between 18 and 70 years with a mean age of 41.3 (±14.4) years. There were no differences between the groups in primary and major secondary endpoints, however, the assessment using the WURSS-21 QoL domain and Jackson score suggests a slightly faster recovery with ColdZyme as symptoms and complaints affecting the quality of life were shortened by about 1 day. The beneficial effect of ColdZyme was particularly noticeable on the fifth day of the common cold. A positive difference between treatment groups was also seen for the subjects' assessments of global efficacy of the investigational product A robust safety profile for ColdZyme was demonstrated throughout the study. CONCLUSION: The safety and tolerability of ColdZyme have been confirmed in a large study population and further establishes evidence of a faster recovery from common cold symptoms. Early self-diagnosis and early use of ColdZyme mouth spray is a safe alternative for treatment of naturally occurring colds.

Evaluation the efficacy and safety of N-acetylcysteine inhalation spray in controlling the symptoms of patients with COVID-19: An open-label randomized controlled clinical trial.

The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n = 250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 h, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs. 3.2%, p < 0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs. 7.8, p < 0.001), hemoglobin (12.3 vs. 13.3, p = 0.002), C-reactive protein (CRP: 6 vs. 11.5, p < 0.0001) and aspartate aminotransferase (AST: 32 vs. 25.5, p < 0.0001). No differences were seen for hospital length of stay (11.98 ± 3.61 vs. 11.81 ± 3.52, p = 0.814) or the requirement for intensive care unit (ICU) admission (7.2% vs. 11.2%, p = 0.274). NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for Severe Acute Respiratory Syndrome Coronavirus-2 is limited and further research is required.

Randomized, Double-Blind, Placebo-Controlled Trial of a Throat Spray with Selected Lactobacilli in COVID-19 Outpatients.

Primary care urgently needs treatments for coronavirus disease 2019 (COVID-19) patients because current options are limited, while these patients who do not require hospitalization encompass more than 90% of the people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a throat spray containing three Lactobacillaceae strains with broad antiviral properties in a randomized, double-blind, placebo-controlled trial. Before the availability of vaccines, 78 eligible COVID-19 patients were randomized to verum (n = 41) and placebo (n = 37) within 96 h of a positive PCR-based SARS-CoV-2 diagnosis, and a per-protocol analysis was performed. Symptoms and severity were reported daily via an online diary. Combined nose-throat swabs and dried blood spots were collected at regular time points in the study for microbiome, viral load, and antibody analyses. The daily reported symptoms were highly variable, with no added benefit for symptom resolution in the verum group. However, based on 16S V4 amplicon sequencing, the acute symptom score (fever, diarrhea, chills, and muscle pain) was significantly negatively associated with the relative abundance of amplicon sequence variants (ASVs) that included the applied lactobacilli (P < 0.05). Furthermore, specific monitoring of these applied lactobacilli strains showed that they were detectable via quantitative PCR (qPCR) analysis in 82% of the patients in the verum group. At the end of the trial, a trend toward lower test positivity for SARS-CoV-2 was observed for the verum group (2/30; 6.7% positive) than for the placebo group (7/27; 26% positive) (P = 0.07). These data indicate that the throat spray with selected antiviral lactobacilli could have the potential to reduce nasopharyngeal viral loads and acute symptoms but should be applied earlier in the viral infection process and substantiated in larger trials. IMPORTANCE Viral respiratory tract infections result in significant health and economic burdens, as highlighted by the COVID-19 pandemic. Primary care patients represent 90% of those infected with SARS-CoV-2, yet their treatment options are limited to analgesics and antiphlogistics, and few broadly acting antiviral strategies are available. Microbiome or probiotic therapy is a promising emerging treatment option because it is based on the multifactorial action of beneficial bacteria against respiratory viral disease. In this study, an innovative topical throat spray with select beneficial lactobacilli was administered to primary COVID-19 patients. A remote study setup (reducing the burden on hospitals and general practitioners) was successfully implemented using online questionnaires and longitudinal self-sampling. Our results point toward the potential mechanisms of action associated with spray administration at the levels of viral loads and microbiome modulation in the upper respiratory tract and pave the way for future clinical applications of beneficial bacteria against viral diseases.

NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia (NACTOPAISD): Clinical trial protocol.

Up to 80 % nursing home residents with dementia experiences chronic pain. Contextually, 97 % presents fluctuant neuropsychiatric symptoms (NPS). Among the most challenging is agitation, connected with undertreated pain and managed through neuroleptics doubling death risk. Evidence is accumulating in favor of the involvement of the endocannabinoid system in nociception and NPS. This double-blind, placebo-controlled, randomized trial (NAbiximols Clinical Translation To the treatment of Pain and Agitation In Severe Dementia [NACTOPAISD]) aims at investigating efficacy and safety of oral spray nabiximols, containing Δ9-tetrahydrocannabinol and cannabidiol (Sativex®), for pain and agitation treatment in severe dementia patients (Mini-Mental State Examination ≤ 12) over 65. The coprimary endpoints are efficacy on pain and agitation, assessed through the recently validated Italian Mobilization-Observation-Behavior-Intensity-Dementia and the Cohen-Mansfield Agitation Inventory. The secondary endpoint is the evaluation of efficacy duration after wash-out and the assessment of quality of life through the DEMQOL. Any adverse events will be reported. The results undergo statistical analysis plan. NACTOPAISD might provide rationale for a translational safer pain and agitation treatment in severe dementia. It is approved by Calabria Region Ethics Committee and follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and the Consolidated Standards of Reporting Trials (CONSORT) statements.

The effects of a combination oral spray (Mucosamin®) for the prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation: a double blind randomized clinical trial.

PURPOSE: Oral mucositis (OM) is a frequent complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Damage to the nuclear and non-nuclear materials of the mucosal cells by the production of Reactive Oxygen Species (ROS) and proinflammatory cytokines could result to development and progression of OM. Previous studies have shown the effectiveness of Mucosamin® oral spray in the management of pain and acceleration of OM healing. The aims of the current study were to evaluate prophylactic effects of Mucosamin® oral spray in reducing the incidence and severity of OM in pediatric patients undergoing allogeneic HSCT. METHOD: The current study was designed as a double-blind, placebo-controlled randomized clinical trial. Sixty patients were enrolled in the study and received placebo or Mucosamin® spray. Patients in both groups used sprays 4 times daily. Product application was begun at the time of initiation of conditioning regimen and was continued for 14 days. RESULTS: Mucosamin® significantly reduced incidence and severity of OM compared to the placebo (P values: 0.027 and 0.035, respectively). This product could also decrease OM duration and delay OM onset (P values: 0.007 and 0.006, respectively). CONCLUSION: Mucosamin® could effectively reduce incidence, severity, and duration of OM and delay OM onset in pediatric patients undergoing allogeneic HSCT. TRIAL REGISTRATION: The study protocol was registered in the Iranian Registry of Clinical Trials under the registry number IRCT20190917044805N1.

In vitro effect of an oral spray and mouthrinses on dual species cariogenic bacteria biofilm.

PURPOSE: To determine the efficacy of an oral spray and oral rinses to inhibit oral cariogenic dual species biofilm formation on hydroxyapatite (HA) discs. METHODS: The Streptococcus mutans (NCTC 10449, ATCC), Lactobacilli casei (NCIB 8820, ATCC) dual species biofilm formation and inhibition on HA disc was tested using five antimicrobial products, i.e., oral spray (Oral Shield), Mouthrinse (Listerine Ultra Clean, Listerine Cool Mint, Crest Pro-Health, ACT Restoring). An untreated group served as control. The established biofilm on the surface of each disc was treated or untreated with oral spray and mouthrinse for 2 minutes after 24 or 48 hours. The dual species biofilm formation and inhibition on HA discs was determined using the spread plate method and colonies were counted and expressed as colony forming units (CFU/mL). Further, the HA disc was subjected to confocal laser scanning microscope (CLSM) examination to determine the viability of cells using live-dead staining and a scanning electron microscope (SEM) to examine the effect on bacteria biofilm and morphology. The cytotoxic effect of test spray and mouthrinse was tested on OKF6/TERT-2 cells using the MTT method. RESULTS: At each time point, 24- or 48-hours, S. mutans and L. casei mixed biofilm on HA discs had a significantly (P> 0.001) fewer number of bacteria in the treated groups than the untreated one. The oral spray and mouthrinses had a detrimental effect on bacteria biofilm, morphology and cell wall, whereas no significant changes were observed in the untreated group. Cytotoxic assay revealed that the oral spray was safe for human oral keratinocyte cells. CLINICAL SIGNIFICANCE: The tested oral spray could offer potential to inhibit the cariogenic bacteria and protect the tooth enamel from cariogenic bacterial biofilm.

¿Desechan correctamente los pacientes sus dispositivos de inhalación? Proyecto AIRE / Do patients deliver inhalers correctly? The AIRE project

Objetivos: Conocer las actitudes y conocimientos de los usuarios respecto a cómo y dónde se desechan los inhaladores tras finalizar su uso, y describir su opinión sobre el uso de inhaladores recargables. Métodos: Estudio transversal, multicéntrico y de opinión, diseñado para conocer el comportamiento y actitudes respecto al circuito de desecho de los inhaladores y a la utilización de inhaladores recargables. La información se obtuvo mediante la aplicación de un cuestionario ad hoc de conocimientos y actitudes, conteniendo datos de uso y reciclado de inhaladores. Resultados: Se incluyeron 303 sujetos (57,5 ± 19,9 años; tiempo de empleo de inhaladores 9,6±9,8 años; asma/EPOC: 46,2/25,7%). El inhalador más empleado fue el aerosol presurizado en suspensión (30,5%). La mayoría otorgaban una elevada importancia al reciclado de inhaladores (7,75±2,76, sobre 10), y a disponer cada seis meses del mismo inhalador recargable mensualmente (7,77±2,79, sobre 10). El 33% refería haber sido informado alguna vez sobre dónde depositar el inhalador. En cuanto al reciclado, el 42,9% lo hacía en el punto SIGRE de la farmacia. Respecto al destino final de los inhaladores, el 43,6% creía que los dispositivos entregados se reciclaban o destruían y un 35,3% desconocía qué ocurre con los inhaladores después de depositarlos en el punto SIGRE. Conclusiones: A pesar de que los usuarios consideran importante el reciclado de inhaladores y disponer de inhaladores recargables, un porcentaje significativo no los deposita en el punto SIGRE, no han sido informados sobre el lugar correcto de depósito, y desconocen qué ocurre con los inhaladores desechados. Son necesarias campañas de información (AU)

Objectives: To assess users’ attitudes and knowledge of users about how and where inhalers are removed after finalizing their use, and to describe their opinion about utilizing re-usable inhalers. Methods: Cross-sectional, multi-center, and opinion survey, conducted to assess behavior and attitudes regarding the disposal of inhalers recycling and the use of re-usable inhalers, through the application of an ad hoc questionnaire about the knowledge and attitudes, with data about the use and recycling of inhalers. Results: A total of 303 subjects (57.5±19.9 years; time of inhalers’ use 9.6±9.8 years; asthma/COPD: 46.2%/25.7%) were included. Pressurized metered-dose inhalers were the most commonly used inhalers (30.5%). Most users considered the recycling of inhalers to be very important (7.75±2.76, out of 10), and rated highly the availability of having a monthly rechargeable inhaler every 6 months (7.77±2.79, out of 10). Only 33% of users had been informed by their healthcare professionals about the place of delivering the inhaler. With respect to recycling, 42.9% of all users recycled in the SIGRE point of the pharmacy. Regarding the final destination of inhalers, 43.6% thought that the removed inhalers were recycled or destroyed, but 35.3% did not know what would happen to the inhalers after placing in the SIGRE point. Conclusions: Despite users considered the importance of inhalers recycling and the availability of re-usable inhalers, a significant proportion does not recycle in the SIGRE point, has not been informed about the appropriate place of delivering the inhaler and ignores what happens to inhalers. Information campaigns are warranted (AU)

Comment on Huijghebaert et al. Does Trypsin Oral Spray (Viruprotect®/ColdZyme®) Protect against COVID-19 and Common Colds or Induce Mutation? Caveats in Medical Device Regulations in the European Union. Int. J. Environ. Res. Public Health 2021, 18, 5066.

I read with interest the recent paper of Huijghebaert et al. published recently in this journal [...].

Reply to Davison, G. Comment on "Huijghebaert et al. Does Trypsin Oral Spray (Viruprotect®/ColdZyme®) Protect against COVID-19 and Common Colds or Induce Mutation? Caveats in Medical Device Regulations in the European Union. Int. J. Environ. Res. Public Health 2021, 18, 5066".

We have read the comment from Davison with great interest [...].

A randomised clinical trial on the effect of oral antimicrobial sprays in institutionalised elders.

OBJECTIVE: To compare the effectiveness of chlorine dioxide, chlorhexidine and placebo sprays in improving oral hygiene among institutionalised elders. BACKGROUND: Available evidence suggests that oral sprays may be an effective alternative delivery method for plaque control; however, few studies have evaluated antimicrobial agents other than chlorhexidine. MATERIALS AND METHODS: A total of 228 elders across 11 nursing homes in Hong Kong were recruited into the clinical trial. Participants were randomly allocated into one of the following groups: 0.1% pH-balanced chlorine dioxide spray, 0.2% chlorhexidine spray or sterile water spray (placebo control), once daily. Dental plaque, gingival bleeding and other clinical oral health outcomes were assessed at baseline, 3 and 6 months. Participant acceptability of the interventions was assessed at the end of the clinical trial. RESULTS: Review assessments were conducted for 135 elders at 6 months. Significantly greater reductions in plaque index scores were observed with the chlorhexidine spray (0.4) and chlorine dioxide spray (0.3) than the placebo spray (0.1). While significant reductions in gingival bleeding scores were observed within the chlorhexidine (7.4), chlorine dioxide (7.5) and placebo (5.3) sprays after 6 months, change scores were not significantly different between groups. Significantly greater increases in the levels of staining were observed in the chlorhexidine spray group (-0.1) than the chlorine dioxide (0.0) and placebo spray (0.0) groups. CONCLUSION: Antimicrobial sprays were shown to be effective among institutionalised elders. Chlorine dioxide spray showed equivalent effects on dental plaque and gingival bleeding relative to the chlorhexidine spray over a 6-month period.

Evaluation of Mucosamin Effect on Treating Radiation Induced Oral Mucositis during and after Radiotherapy amongst Patients with Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Oral mucositis is a serious complication radiation therapy for cancer. This is a major complication during radiation therapy of the head and neck tumors in approximately all patients. Therefore, this study was conducted to evaluate the effect of Mucosamin on treatment of radiation induced oral mucositis during and after radiotherapy amongst patients with oral cavity squamous cell carcinoma. MATERIALS AND METHODS: In this prospective clinical trial, eligible patients who referred to radiation oncology department of Namazi Hospital, Shiraz, Iran from Jan 2018 till Jan 2019 were evaluated. The cases with confirmed pathologic diagnosis of squamous cell carcinoma of the oral cavity underwent 6,000 cGy radiation therapy and were randomly divided into two groups: 1- Intervention group; Mucosamin spray for 3-4 times a day (n = 40); 2 - Control group; standard medications (3 times a day) (n = 40). Oral mucositis was evaluated weekly based on RTOG scoring scale. Grade of mucositis was recorded during treatment and after radiation therapy. RESULTS: A total of 80 patients were divided in two groups of Mucosamin and control. From week 3 until the end of radiotherapy (week 6) and after radiotherapy (week 8), there was a significant difference in the severity of oral mucositis between the Mucosamin and the control groups (P <0.05). CONCLUSION: The results of this study showed that Mucosamin spray was able to significantly improved radiation-induced oral mucositis in patients with oral squamous cell carcinoma.
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Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience.

BACKGROUND: This 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. METHODS: Of 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. RESULTS: Mean 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. CONCLUSIONS: More 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.

Does Trypsin Oral Spray (Viruprotect®/ColdZyme®) Protect against COVID-19 and Common Colds or Induce Mutation? Caveats in Medical Device Regulations in the European Union.

BACKGROUND: nasal or oral sprays are often marketed as medical devices (MDs) in the European Union to prevent common cold (CC), with ColdZyme®/Viruprotect® (trypsin/glycerol) mouth spray claiming to prevent colds and the COVID-19 virus from infecting host cells and to shorten/reduce CC symptoms as an example. We analyzed the published (pre)-clinical evidence. METHODS: preclinical: comparison of in vitro tests with validated host cell models to determine viral infectivity. Clinical: efficacy, proportion of users protected against virus (compared with non-users) and safety associated with trypsin/glycerol. RESULTS: preclinical data showed that exogenous trypsin enhances SARS-CoV-2 infectivity and syncytia formation in host models, while culture passages in trypsin presence induce spike protein mutants. The manufacturer claims >98% SARS-CoV-2 deactivation, although clinically irrelevant as based on a tryptic viral digest, inserting trypsin inactivation before host cells exposure. Efficacy and safety were not adequately addressed in clinical studies or leaflets (no COVID-19 data). Protection was obtained among 9-39% of users, comparable to or lower than placebo-treated or non-users. Several potential safety risks (tissue digestion, bronchoconstriction) were identified. CONCLUSIONS: the current European MD regulations may result in insufficient exploration of (pre)clinical proof of action. Exogenous trypsin exposure even raises concerns (higher SARS-CoV-2 infectivity, mutations), whereas its clinical protective performance against respiratory viruses as published remains poor and substandard.