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.

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).

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.

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.

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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ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia.

SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) in vitro models mimicking the in vivo human airway epithelium.IMPORTANCE Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the in vitro airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our in vitro data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.

Cannabinoids in glioblastoma multiforme-hype or hope?

Cannabis and its derivatives are being used increasingly by patients with cancer, including patients with glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy. Despite promising preclinical data suggesting potential anti-cancer effects for cannabinoids in GBM, clinical and safety data are lacking. This editorial will discuss a recent Phase 1b trial of nabiximols oromucosal spray in combination with dose-intense temozolomide in patients with recurrent GBM in the context of other relevant findings in this field.

A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma.

BACKGROUND: Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM. METHODS: Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored. RESULTS: The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK. CONCLUSIONS: With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: Part 1- NCT01812603; Part 2- NCT01812616.

Carrageenan-containing over-the-counter nasal and oral sprays inhibit SARS-CoV-2 infection of airway epithelial cultures.

Pharmaceutical interventions are urgently needed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission. As SARS-CoV-2 infects and spreads via the nasopharyngeal airways, we analyzed the antiviral effect of selected nasal and oral sprays on virus infection in vitro. Two nose sprays showed virucidal activity but were cytotoxic precluding further analysis in cell culture. One nasal and one mouth spray suppressed SARS-CoV-2 infection of TMPRSS2-expressing Vero E6 cells and primary differentiated human airway epithelial cultures. The antiviral activity in both sprays could be attributed to polyanionic ι- and κ-carrageenans. Thus, application of carrageenan-containing nasal and mouth sprays may reduce the risk of acquiring SARS-CoV-2 infection and may limit viral spread, warranting further clinical evaluation.

Effects of an Indomethacin Oral Spray on Pain Due to Oral Mucositis in Cancer Patients Treated With Radiotherapy and Chemotherapy: A Double-Blind, Randomized, Placebo-Controlled Trial (JORTC-PAL04).

CONTEXT: Oral mucositis (OM) pain due to anticancer chemo- and radiotherapy has a very negative impact on patient quality of life. However, no high-quality studies have been performed regarding the analgesic efficacy of indomethacin (IM) oral spray for OM pain. OBJECTIVES: This randomized, placebo-controlled, double-blind trial aimed to evaluate the analgesic efficacy of IM oral spray for OM pain due to anticancer chemo- and radiotherapy. METHODS: From July 2015 to December 2016, we enrolled adult cancer patients with OM pain that was due to anticancer chemo- or radiotherapy and was rated 4 or higher on Brief Pain Inventory (BPI) Item 5. Patients were randomly assigned in a 1:1 ratio to receive either IM oral spray or placebo. The primary endpoint was the change in the BPI Item 6 ("current pain") score from before to 30 minutes after treatment. Secondary endpoints were the areas under the curves of BPI Item 6 at 15, 60, 120, 180, and 240 minutes after treatment; five items related to meals and conversation from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, Head and Neck Module 35; the Clinical Global Impressions-Improvement (CGI-I) scale; and adverse events. RESULTS: A total of 60 patients were assigned to receive IM oral spray (n = 33) or placebo spray (n = 27). The average change in the BPI item 6 score from before to 30 minutes after treatment was -1.85 (95% confidence interval: -2.37 to -1.32) in the IM spray group and -0.59 (-1.02 to -0.16) in the placebo group, indicating a significant difference (-1.26, -1.94 to -0.57, P < 0.01). The pain improvement persisted for 180 minutes. The intergroup differences in ability to drink liquids, ease in conversing, and CGI-I were all significant (P = 0.03, P = 0.02, and P < 0.01, respectively). No serious adverse events were reported. CONCLUSION: IM oral spray alleviated short-term OM pain due to anticancer chemo- and radiotherapy, and may reduce the difficulty in eating meals.

Can a Nasal/Oral/Ocular Spray Inactivate and Prevent SARS-CoV-2 infection? A hypothesis / ¿Puede un Spray Nasal/Oral/Ocular Inactivar y Prevenir la Infección por SARS-CoV-2?: Una hipótesis

ABSTRACT: The COVID-19 pandemic has created challenges that have been dealt with adopting measures such as prolonged or intermittent social distancing, which may even be necessary until 2022. Furthermore, it has been described that a SARS-CoV-2 contagion route corresponds to the inhalation of the virus. Medications via nasal/eye spray and inhalers, therefore, could fulfill the function of inactivating SARS-CoV-2. Due to the abovementioned reasons, we suggest the following hypothesis: The use of Ocular/Nasal/Oral sprays could prevent the infection and the further spread of SARS-CoV-2.

RESUMEN: La pandemia de COVID-19 propone desafíos que han sido manejados con medidas como distanciamiento social prologado o intermitente, el cual podría ser necesario hasta 2022. Se ha descrito que la ruta de contagio de SARS-CoV-2 corresponde a la inhalación del virus. La medicación a través de un spray nasal/ocular podría cumplir la función de inactivar SARS-CoV-2. Por las razones antes presentadas, los autores sugerimos la siguiente hipótesis: El uso de un spray ocultar/nasal/oral previene la infección y replicación de SARS-CoV-2.

Derivation of cancer no significant risk levels and screening safety assessment for 2-nitropropane in spray products.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 µg/day and 32 µg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.

Estudo randomizado duplo-cego e placebo controlado do substituto salivar com sistema enzimático para xerostomia em pacientes irradiados em região de cabeça e pescoço / Randomized double-blind, placebo-controlled study of salivary substitute with enzymatic system for xerostomia in patients irradiated in the head and neck region

Xerostomia e/ou hipossalivação é uma das mais frequentes complicações orais em pacientes irradiados em região de cabeça e pescoço, com importante impacto na qualidade de vida ao longo do tempo. O objetivo do estudo, foi avaliar a eficácia do Bioxtra Spray® na redução da intensidade de xerostomia e seu impacto na qualidade de vida em pacientes que foram irradiados em região de cabeça e pescoço pela técnica de Radioterapia de Intensidade Modulada (IMRT) ou Radioterapia Conformada Tridimensional (RTC3D), em um período de 8 a 9 meses após o término do tratamento. Foi realizado um estudo prospectivo, randomizado, duplo cego e placebo controlado, com um total de 40 pacientes alocados no Grupo Placebo (n=19) ou Bioxtra Spray® (n=21). Os pacientes utilizaram ambos os produtos três vezes ao dia durante 30 dias. Para as análises, foram realizadas a avaliação da intensidade da xerostomia, avaliação da taxa de fluxo salivar não estimulada e estimulada através da sialometria e a avaliação da qualidade de vida através do Questionário de Qualidade de Vida da Universidade de Washington, validado em português (QQV-UW) em 2 fases: Fase 1 (antes do uso de ambos os produtos); Fase 2 (após 30 dias de uso dos produtos). Em relação à intensidade da xerostomia, não foram observadas melhoras significativas da queixa de boca seca após 30 dias de uso do Bioxtra Spray®( p>0,05). Analisando os exames de sialometria, foi observado que, após 30 dias de uso, o Grupo Bioxtra Spray® apresentou saliva não estimulada e estimulada significativamente maior quando comparado ao Grupo Placebo (p<0,05). Em relação à qualidade de vida, de maneira geral o Grupo Placebo apresentou melhores escores gerais dos domínios do QQV-UW quando comparados ao Grupo Bioxtra Spray® nas duas fases do estudo (p<0,05). Não foram observadas diferenças significativas em relação ao domínio saliva do QQV-UW entre os grupos nas duas fases do estudo. Interessante observar que os pacientes de ambos os Grupos que foram submetidos à técnica IMRT apresentaram índices tanto na taxa de fluxo salivar quanto na qualidade de vida significativamente melhores em ambas as fases do estudo quando comparados à técnica RTC3D. Por fim, concluímos que o Bioxtra Spray®, na metodologia estudada, não apresentou resultados positivos na lubrificação oral e na qualidade de vida dos pacientes. Contudo, estudos em longo prazo que avaliam seu efeito enzimático na proteção dos tecidos orais são recomendados

Xerostomia and/or hyposalivation are common oral complication in patients irradiated in the head and neck region with an important impact on quality of life over time. The aim of this study was to evaluate the effectiveness of Bioxtra Spray® in reducing xerostomia intensity and its impact on the quality of life of patients who were irradiated in the head and neck region by the Intensity Modulated Radiation Therapy (IMRT) or Three Dimensional Conformal Radiotherapy (RTC3D) over a period of 6 months to 1 year after the end of treatment. A prospective, randomized, double-blind, placebo-controlled study was performed, with a total of 40 patients allocated to the Placebo Arm (n= 19) or Bioxtra Spray® (n = 21). Patients used both products three times a day for 30 days and for the analyzes, the evaluation of xerostomia grade, evaluation of the unstimulated and stimulated salivary flow rate through sialometry and the evaluation of quality of life through the University of Washington Quality of Life Questionnaire, validated in Portuguese (UW-QoL) were performed in 2 phases: Phase 1 (before the use of both products); Phase 2 (after 30 days of using both products). Regarding xerostomia grade, no significant improvement in dry mouth complaints was observed after 30 days of use (p> 0.05). Analyzing the sialometry exams, it was observed that after 30 days of use, the Bioxtra Spray® Group showed unstimulated and stimulated salivary flow rate significantly higher when compared to the Placebo Arm (p <0.05). Regarding quality of life, in general, the Placebo Arm had better overall scores than in the UW-QoL domains when compared to the Bioxtra Spray® Group in the two phases of the study (p <0.05). No significant differences were observed in relation to the UW-QoL saliva domain between the groups in the two phases of the study. It is interesting to note that patients from both Groups who underwent the IMRT technique showed significantly better rates of salivary flow and quality of life in both phases of the study when compared to the RTC3D technique. In conclusion, we observed that Bioxtra Spray® did not present positive results in oral lubrication and in patients' quality of life. However, studies evaluating its enzymatic effect in protecting oral tissues are recommended

Radiotherapy-induced xerostomia: a randomised, double-blind, controlled trial of Visco-ease™ oral spray compared with placebo in patients with cancer of the head and neck.

Radiotherapy-induced xerostomia (RIX) is a common and untreatable side effect of radiotherapy to the head and neck. Visco-ease™ mouth spray (Lamellar Biomedical Ltd), a new product that is made from lamellar body mimetics, reduces the viscosity of saliva ex vivo. The purpose of this study was to evaluate its safety and effectiveness in the treatment of RIX in 43 patients with cancer of the head and neck. They were randomised into the Visco-ease™ or placebo groups, and asked to complete the Groningen radiotherapy-induced xerostomia (GRIX) questionnaire each week. The primary endpoint was a change in GRIX score from baseline to end of treatment. There was no difference in scores between the two groups, and none of the patients had device-related serious adverse events. Visco-ease™ oral spray was safe and tolerable but no better than placebo in reducing RIX in this group of patients.

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial.

CONTEXT: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. OBJECTIVES: We examined the effect of two doses of prophylactic FSS on exertional dyspnea. METHODS: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%-45% (high dose) or 15%-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. RESULTS: Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected. CONCLUSION: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.

A study on factors determining dose of topical lignocaine during broncho-alveolar lavage by spray-as-you-go technique: A single centre observational study.

Basic bronchoscopic diagnostic procedures like Broncho-alveolar lavage (BAL) are often performed without sedation, using lignocaine administered via the working channel of bronchoscope (spray-as-you-go technique) and other routes. Our aim was to evaluate the factors responsible for variation in the total dose of lignocaine administered in individual subjects. We prospectively included consecutive subjects undergoing BAL in an outpatient setting from August 2016 to November 2017 at our centre. The subjects were administered lignocaine via nebulization, nasal gel, oropharyngeal spray before and during bronchoscopy ("spray-as-you-go") as per a predefined protocol. The demographic details, high resolution computerized tomography (HRCT) characteristics, procedural details, doses of lignocaine administered and a visual analogue scale (VAS) for satisfaction with the procedure were recorded. Using lignocaine dose as outcome, variables were assessed for effect by univariate and multivariate regression analysis. 96 subjects were included with a mean age of 40 years and male predominance (60.4%). Cough was the most common presenting symptom (64.6%). Predisposing factors included tuberculosis (47.9%) and smoking (23.2%). Maximum variation in lignocaine dose occurred prior to intubating vocal cords using "spray-as-you-go", which was significantly related to history of past tuberculosis (p = 0.031), obstructive airway disease (p = 0.009), fibrotic sequelae (p = 0.011) and bronchiectasis (p = 0.049). Obstructive airway disease and fibrotic sequelae were also significant on multivariate analysis (p = 0.01 and 0.005 respectively). Obstructive airway disease and architectural distortion due to fibrotic sequelae leads to higher dose requirement for lignocaine during BAL by fibre-optic bronchoscopy. Caution must be maintained during bronchoscopic procedures to avoid exceeding recommended maximum doses in such patients.

Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a oral spray for children with recurrent streptococcal pharyngotonsillitis: a randomized placebo-controlled clinical study.

PURPOSE: Group A beta-hemolytic Streptococcus (GABHS) causes a recurrent acute pharyngotonsillitis (RAPT) in children. Moreover, the repeated use of antibiotics contributes to its resistance. However, S. Salivarius 24SMB and S. oralis 89a were effective probiotics in other infections. Thus, we decided to evaluate this combination efficacy compared to placebo in RAPT. METHODS: Patients with microbiologically confirmed GABHS were enrolled in this randomized, placebo-controlled trial. They received the aforementioned combination or placebo as an oral spray. We investigated episodes of frequency and duration, need for antibiotics, school days lost, the treatment impact on life quality, treatment compliance and side effects during a 90-day treatment and a 6-month follow-up. RESULTS: We included 41 patients in each group. The mean number of GABHS infection was significantly lower during both study periods for the two groups. However, our treatment group showed a lower rate. Moreover, the probiotic group had a lower mean number and a shorter median duration of GABHS episodes during both study periods than controls. Furthermore, the mean duration of antibiotic treatment was lower in the probiotic group during the 90-day and 6-month follow-up periods. Similarly, patients in the probiotic group showed a significantly lower mean number of absence days from school but higher EQ-VAS score. Indeed, all patients included were compliant to treatment. CONCLUSIONS: We identified potential probiotics, possessing desirable features against GABHS pharyngotonsillitis. Our findings represent the first evidence which throws the light on using these probiotics that can reduce antibiotics use which did not have efficient results regarding recurrence.

Treatment of symptomatic oral mucositis with sodium hyaluronate and synthetic amino acid precursors of collagen in patients undergoing haematopoietic stem cell transplantation.

The purpose of the study is to evaluate the clinical effects of Mucosamin® (a spray preparation containing sodium hyaluronate combined with a pool of amino acids of precursor collagen, including L-Proline, L-Leucine, L-Lysine and glycine) on wound healing and pain management of oral mucositis after hematopoietic stem cell transplantation. The importance of professional dental hygiene by dental hygienist in reducing the severity of oral mucositis as unique therapy or in addition to therapy with Mucosamin® was also evaluated. One hundred thirty-seven patients undergoing hematopoietic stem cell transplantation were recruited in a case-control study and divided into 4 groups: Group A: professional oral hygiene + Mucosamin®; Group B: professional oral hygiene + standard treatment with chlorhexidine 0.20%;; Group C: only Mucosamin®; Group D: only standard treatment with chlorhexidine 0.20%. The following evaluations were made: WHO mucositis scale, OMAS mucositis scale, VAS, periodontal recording, days of mucositis. Comparing the groups at the onset of OM on WHO scale, it was observed that Group A grade 1 occurrence was more statistically significant than Group B (p= 0.03*); comparison between Group A and D showed a statistically significant difference in favour of Group A (p= 0.0002*). Also OMAS scale showed a statistically significant difference between groups who assumed Mucosamin, who developed lower OM grade (p = 0.001*). There was a statistically significant difference between group A compared with group B over the overall duration of OM (p = 0.02*), as well as between group A and group D (p=0.03*). According to the present study the combination of a careful debridement, correct oral hygiene during hospitalization and the use of Mucosamin® exponentially reduces the severity and duration of mucositis and consequently the discomfort of the patient. Moreover, it can be stated that the use of Mucosamin® also results in a reduction in the extent of chemotherapy lesions. Hyaluronic acid and amino acid-based sprays can be a valuable therapeutic aid in the treatment of mucositis.

[The Collaboration between Clinical Therapy and Academic Study to Benefit Patients].

　Cancer chemotherapy-induced stomatitis may spread throughout a patient's entire oral cavity and decrease the patient's QOL. The therapy for stomatitis at Iwate Medical University Hospital (IMUH) includes dental treatment before chemotherapy, in addition to oral rinses or cryotherapy as a preventative measure. However, in our survey of doctors and nurses, the responses of patients "satisfied" with the present approach for stomatitis treatment reached only 5.1%. Therefore, we attempted treatment using an indomethacin spray, prepared as a hospital preparation, with pre-approval of the ethics committee and based on a previous report of its positive effect on patients at another hospital. We observed that the indomethacin spray succeeded in decreasing chemotherapy-induced oral pain, and its effect was maintained for 2 h in patients at IMUH. The ratio of female patients who rated indomethacin spray as good was higher than that of males. Comments from some patients included a complaint that the nozzle of the injection tip was too short; thus we increased the length of the nozzle from 2 to 7 cm. At present, indomethacin spray is being used to treat stomatitis patients at IMUH. Indeed, the indomethacin spray has been used since October 2011. It was used on 34 patients in 2016. In this review, we describe the collaboration between IMUH and the basic application of studies in our university laboratory.

[Evaluation of the Stability of Indomethacin Oral Spray in Two Different Formulation Conditions].

　Indomethacin (IM) oral spray is a hospital preparation that is used to reduce pain from oral mucositis induced by radiotherapy and chemotherapy. IM oral spray consists of IM (0.25%) dissolved in KH2PO4-NaOH buffer (Formulation A) or Formulation A containing xylitol (Xyl) and glycerin (Gly) (Formulation B). To clarify the stability of IM oral spray in two different formulation conditions, we evaluated the residual rates of IM in these formulations to determine the optimal storage temperature and shelf-life. IM oral spray was stored at freezer temperature (-20°C), refrigerator temperature (4°C) and room temperature (25°C) for up to 16 weeks after preparation. The residual rate of IM was determined by using HPLC. The residual rates of IM in Formulation A and Formulation B after storage for 16 weeks at freezer temperature were ≥95%. When stored at refrigerator temperature, the residual rate of IM in Formulation A was 96.1% after 12 weeks, and the residual rates of IM in Formulation B were 95.8% after 2 weeks, 90.1% after 4 weeks and 72.7% after 12 weeks. These results suggested that Formulation A is stable for at least 12 weeks when stored at 4°C. However, degradation of IM seemed to be accelerated in the formulation containing Xyl and Gly, suggesting that the expiration date should be shortened to 2 weeks at 4°C. In addition, both formulations were stable for at least 16 weeks in a freezer, indicating that long-term preservation is possible.